Satoshi Hasegawa

Processing of materials by ultrashort laser pulses has evolved significantly over the last decade and is starting to reveal its scientific, technological and industrial potential. In ultrafast laser manufacturing, optical energy of tightly focused femtosecond or picosecond laser pulses can be delivered to precisely defined positions in the bulk of materials via two-/multi-photon excitation on a timescale much faster than thermal energy exchange between photoexcited electrons and lattice ions. Control of photo-ionization and thermal processes with the highest precision, inducing local photomodification in sub-100-nm-sized regions has been achieved. State-of-the-art ultrashort laser processing techniques exploit high 0.1-1 μm spatial resolution and almost unrestricted three-dimensional structuring capability. Adjustable pulse duration, spatiotemporal chirp, phase front tilt and polarization allow control of photomodification via uniquely wide parameter space. Mature opto-electrical/mechanical technologies have enabled laser processing speeds approaching meters-per-second, leading to a fast lab-to-fab transfer. The key aspects and latest achievements are reviewed with an emphasis on the fundamental relation between spatial resolution and total fabrication throughput. Emerging biomedical applications implementing micrometer feature precision over centimeter-scale scaffolds and photonic wire bonding in telecommunications are highlighted.

We have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. We have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-microm diameter tumor was detectable at a depth of 0.5 mm whereas a 1, 800-microm tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.

The water stability of the fast lithium ion conducting glass–ceramic electrolyte, Li1+x+yAlxTi2−xSiyP3−yO12 (LATP), has been examined in distilled water, and aqueous solutions of LiNO3, LiCl, LiOH, and HCl. This glass–ceramics are stable in aqueous LiNO3 and aqueous LiCl, and unstable in aqueous 0.1 M HCl and 1 M LiOH. In distilled water, the electrical conductivity slightly increases as a function of immersion time in water. The Li–Al/Li3−xPO4−yNy/LATP/aqueous 1 M LiCl/Pt cell, where lithium phosphors oxynitrides Li3−xPO4−yNy (LiPON) are used to protect the direct reaction of Li and LATP, shows a stable open circuit voltage (OCV) of 3.64 V at 25 °C, and no cell resistance change for 1 week. Lithium phosphors oxynitride is effectively used as a protective layer to suppress the reaction between the LATP and Li metal. The water-stable Li/LiPON/LATP system can be used in Li/air secondary batteries with the air electrode containing water.

RAS GTPases mediate a wide variety of cellular functions, including cell proliferation, survival, and differentiation. Recent studies have revealed that germline mutations and mosaicism for classical RAS mutations, including those in <i>HRAS</i>, <i>KRAS</i>, and <i>NRAS</i>, cause a wide spectrum of genetic disorders. These include Noonan syndrome and related disorders (RAS/mitogen-activated protein kinase [RAS/MAPK] pathway syndromes, or RASopathies), nevus sebaceous, and Schimmelpenning syndrome. In the present study, we identified a total of nine missense, nonsynonymous mutations in <i>RIT1</i>, encoding a member of the RAS subfamily, in 17 of 180 individuals (9%) with Noonan syndrome or a related condition but with no detectable mutations in known Noonan-related genes. Clinical manifestations in the <i>RIT1</i>-mutation-positive individuals are consistent with those of Noonan syndrome, which is characterized by distinctive facial features, short stature, and congenital heart defects. Seventy percent of mutation-positive individuals presented with hypertrophic cardiomyopathy; this frequency is high relative to the overall 20% incidence in individuals with Noonan syndrome. Luciferase assays in NIH 3T3 cells showed that five RIT1 alterations identified in children with Noonan syndrome enhanced ELK1 transactivation. The introduction of mRNAs of mutant <i>RIT1</i> into 1-cell-stage zebrafish embryos was found to result in a significant increase of embryos with craniofacial abnormalities, incomplete looping, a hypoplastic chamber in the heart, and an elongated yolk sac. These results demonstrate that gain-of-function mutations in <i>RIT1</i> cause Noonan syndrome and show a similar biological effect to mutations in other RASopathy-related genes.

Experimental studies of the collisions of heavy nuclei at relativistic energies have established the properties of the quark–gluon plasma (QGP), a state of hot, dense nuclear matter in which quarks and gluons are not bound into hadrons1–4. In this state, matter behaves as a nearly inviscid fluid5 that efficiently translates initial spatial anisotropies into correlated momentum anisotropies among the particles produced, creating a common velocity field pattern known as collective flow. In recent years, comparable momentum anisotropies have been measured in small-system proton–proton (p+p) and proton–nucleus (p+A) collisions, despite expectations that the volume and lifetime of the medium produced would be too small to form a QGP. Here we report on the observation of elliptic and triangular flow patterns of charged particles produced in proton–gold (p+Au), deuteron–gold (d+Au) and helium–gold (3He+Au) collisions at a nucleon–nucleon centre-of-mass energy $$\sqrt {s_{{\mathrm{NN}}}}$$ = 200 GeV. The unique combination of three distinct initial geometries and two flow patterns provides unprecedented model discrimination. Hydrodynamical models, which include the formation of a short-lived QGP droplet, provide the best simultaneous description of these measurements. A quark–gluon plasma is produced in proton–gold, deuteron–gold and helium–gold collisions. Observing elliptic and triangular flow in this nearly inviscid fluid from these different initial geometries provides a unique benchmark for hydrodynamic models.

Several coronary artery Z score models have been developed. However, a Z score model derived by the lambda-mu-sigma (LMS) method has not been established.Echocardiographic measurements of the proximal right coronary artery, left main coronary artery, proximal left anterior descending coronary artery, and proximal left circumflex artery were prospectively collected in 3,851 healthy children ≤18 years of age and divided into developmental and validation data sets. In the developmental data set, smooth curves were fitted for each coronary artery using linear, logarithmic, square-root, and LMS methods for both sexes. The relative goodness of fit of these models was compared using the Bayesian information criterion. The best-fitting model was tested for reproducibility using the validation data set. The goodness of fit of the selected model was visually compared with that of the previously reported regression models using a Q-Q plot.Because the internal diameter of each coronary artery was not similar between sexes, sex-specific Z score models were developed. The LMS model with body surface area as the independent variable showed the best goodness of fit; therefore, the internal diameter of each coronary artery was transformed into a sex-specific Z score on the basis of body surface area using the LMS method. In the validation data set, a Q-Q plot of each model indicated that the distribution of Z scores in the LMS models was closer to the normal distribution compared with previously reported regression models. Finally, the final models for each coronary artery in both sexes were developed using the developmental and validation data sets. A Microsoft Excel-based Z score calculator was also created, which is freely available online (http://raise.umin.jp/zsp/calculator/).Novel LMS models with which to estimate the sex-specific Z score of each internal coronary artery diameter were generated and validated using a large pediatric population.

Mitchell et al. (1976, 1977) suggested that pica, eating of nonnutritive substances such as kaolin, is an illness-response behavior in rats. In the present study, we first confirmed their suggestion and then examined the effects of antiemetics on emetic-induced pica in rats. Intraperitoneal injection of apomorphine induced dose-dependent kaolin consumption. Pretreatment with domperidone inhibited apomorphine-induced kaolin intake. Oral administration of copper sulfate and intraperitoneal injection of cisplatin also induced dose-dependent kaolin consumption. Pretreatment with ondansetron inhibited cisplatin-induced kaolin intake. These findings suggest that pica in rats was induced through 1) dopamine D2 receptors in the chemoreceptor trigger zone, and 2) the stomach, partly via 5-HT3 receptors in the visceral afferents in the stomach wall. The present findings support the conclusion that pica i rats is analogous to vomiting in other species and suggest that pica in rats is mediated by the same mechanisms as vomiting in humans. Accordingly, we extended the utility of the animal model to pharmacological research of emesis with pica as an analogue to emesis.

A water-stable Li metal anode with water-stable lithium-conducting glass ceramics, (LTAP), and a lithium-conducting polymer electrolyte, , was proposed as the lithium anode for lithium–air batteries with an aqueous solution at the air electrode. LTAP was unstable when in direct contact with Li metal, and the cell resistance of Li∕LTAP∕Li rapidly increased as a function of the contact time. The symmetrical cell showed no change in the total resistance (around at ) over a period of . The membrane served as a protective interlayer to suppress the reaction between the water-stable glass ceramics LTAP and Li metal effectively. The ∕LTAP∕aqueous air cell showed a stable open-circuit voltage of at for . The open-circuit voltage was comparable with that calculated from the cell reaction of . The cell exhibited a favorable discharge and charge performance at and .

It has long been believed that trypsin is normally synthesized only in the pancreas. In the present study, expression of trypsin in human and mouse nonpancreatic tissues was examined. Northern blot analysis of normal human tissues indicated that the trypsin gene is expressed at high levels in the pancreas and spleen and considerably in the small intestine. However, in situ hybridization and immunohistochemistry demonstrated that trypsin is widely expressed in epithelial cells of the skin, esophagus, stomach, small intestine, lung, kidney, liver, and extrahepatic bile duct, as well as splenic and neuronal cells. In the spleen, trypsin message was detected in macrophages, monocytes, and lymphocytes in the white pulp. In the brain, it was detected in the nerve cells of the hippocampus and cerebral cortex. Analysis by gelatin zymography confirmed the presence of a latent or an active form of trypsin in various normal mouse tissues. Reverse transcription-polymerase chain reaction analysis also confirmed the expression of trypsin genes in the spleen, liver, kidney, and brain of normal mice. Such a broad distribution of trypsin suggests its general roles in the maintenance of normal epithelial cell functions, the immune defense system, and the central nervous system.

The lithium ion conducting solid lithium phosphorous nitride (LiPON) has been sputtered on the water-stable NASICON-type lithium ion conducting solid electrolyte Li1+x+yAlxTi2−xP3−ySiyO12 (LATP). The stability and the interface resistance of the Li–Al/LiPON/LATP/LiPON/Li–Al cell have been examined. It is shown that the LiPON film protects LATP from reacting with the Li–Al alloy. The impedance of the Li–Al/LiPON/LATP/LiPON/Li–Al cell has been measured in the temperature range 25–80 °C. The total cell resistance is about 8600 Ω cm2 at room temperature and 360 Ω cm2 at 80 °C. The analysis of the impedance profiles suggests that the Li–Al/LiPON interface resistance is dominant at lower temperatures. The LATP plate immersed in water for 1 month shows only a slight degradation in the conductivity.

Living organisms detect changes in temperature using thermosensory molecules. However, these molecules and/or their mechanisms for sensing temperature differ among organisms. To identify thermosensory molecules in plants, we investigated chloroplast positioning in response to temperature changes and identified a blue-light photoreceptor, phototropin, that is an essential regulator of chloroplast positioning. Based on the biochemical properties of phototropin during the cellular response to light and temperature changes, we found that phototropin perceives temperature based on the temperature-dependent lifetime of the photoactivated chromophore. Our findings indicate that phototropin perceives both blue light and temperature and uses this information to arrange the chloroplasts for optimal photosynthesis. Because the photoactivated chromophore of many photoreceptors has a temperature-dependent lifetime, a similar temperature-sensing mechanism likely exists in other organisms. Thus, photoreceptors may have the potential to function as thermoreceptors.

Production of L-valine under oxygen deprivation conditions by Corynebacterium glutamicum lacking the lactate dehydrogenase gene ldhA and overexpressing the L-valine biosynthesis genes ilvBNCDE was repressed. This was attributed to imbalanced cofactor production and consumption in the overall L-valine synthesis pathway: two moles of NADH was generated and two moles of NADPH was consumed per mole of L-valine produced from one mole of glucose. In order to solve this cofactor imbalance, the coenzyme requirement for L-valine synthesis was converted from NADPH to NADH via modification of acetohydroxy acid isomeroreductase encoded by ilvC and introduction of Lysinibacillus sphaericus leucine dehydrogenase in place of endogenous transaminase B, encoded by ilvE. The intracellular NADH/NAD(+) ratio significantly decreased, and glucose consumption and L-valine production drastically improved. Moreover, L-valine yield increased and succinate formation decreased concomitantly with the decreased intracellular redox state. These observations suggest that the intracellular NADH/NAD(+) ratio, i.e., reoxidation of NADH, is the primary rate-limiting factor for L-valine production under oxygen deprivation conditions. The L-valine productivity and yield were even better and by-products derived from pyruvate further decreased as a result of a feedback resistance-inducing mutation in the acetohydroxy acid synthase encoded by ilvBN. The resultant strain produced 1,470 mM L-valine after 24 h with a yield of 0.63 mol mol of glucose(-1), and the L-valine productivity reached 1,940 mM after 48 h.

Following anterior cruciate ligament (ACL) reconstruction, restricted weight bearing and immobilization results in thigh and calf muscle atrophy and weakness. The purpose of this study was to assess the effect of electrical muscle stimulation (EMS) on prevention of muscle atrophy in patients during the early rehabilitation stage after ACL reconstruction.Twenty patients with acute ACL tears were divided into two groups randomly. The control group (CON group) participated in only the usual rehabilitation program. In addition to this protocol, the electrical muscle stimulation group (EMS group) received EMS training using the wave form of 20 Hz exponential pulse from the 2nd post-operative day to 4 weeks after the surgery.Muscle thickness of vastus lateralis and calf increased significantly 4 weeks after surgery in the EMS group, while it decreased significantly in the CON group. The decline of knee extension strength was significantly less in the EMS group than in the CON group at 4 weeks after the surgery, and the EMS group showed greater recovery of knee extension strength at 3 months after surgery.EMS implemented during the early rehabilitation stage is effective in maintaining and increasing muscle thickness and strength in the operated limb.

We previously demonstrated efficient L-valine production by metabolically engineered Corynebacterium glutamicum under oxygen deprivation. To achieve the high productivity, a NADH/NADPH cofactor imbalance during the synthesis of l-valine was overcome by engineering NAD-preferring mutant acetohydroxy acid isomeroreductase (AHAIR) and using NAD-specific leucine dehydrogenase from Lysinibacillus sphaericus. Lactate as a by-product was largely eliminated by disrupting the lactate dehydrogenase gene ldhA. Nonetheless, a few other by-products, particularly succinate, were still produced and acted to suppress the L-valine yield. Eliminating these by-products therefore was deemed key to improving theL-valine yield. By additionally disrupting the phosphoenolpyruvate carboxylase gene ppc, succinate production was effectively suppressed, but both glucose consumption and L-valine production dropped considerably due to the severely elevated intracellular NADH/NAD(+) ratio. In contrast, this perturbed intracellular redox state was more than compensated for by deletion of three genes associated with NADH-producing acetate synthesis and overexpression of five glycolytic genes, including gapA, encoding NADH-inhibited glyceraldehyde-3-phosphate dehydrogenase. Inserting feedback-resistant mutant acetohydroxy acid synthase and NAD-preferring mutant AHAIR in the chromosome resulted in higher L-valine yield and productivity. Deleting the alanine transaminase gene avtA suppressed alanine production. The resultant strain produced 1,280 mM L-valine at a yield of 88% mol mol of glucose(-1) after 24 h under oxygen deprivation, a vastly improved yield over our previous best.

The energy spacing of the spin-doublet states in the ${}_{\mathrm{\ensuremath{\Lambda}}}^{4}$He hypernucleus indicate a large spin dependent charge symmetry breaking in the $\mathrm{\ensuremath{\Lambda}}\phantom{\rule{0}{0ex}}N$ interaction.

We present a method of rendering aerial and volumetric graphics using femtosecond lasers. A high-intensity laser excites physical matter to emit light at an arbitrary three-dimensional position. Popular applications can thus be explored, especially because plasma induced by a femtosecond laser is less harmful than that generated by a nanosecond laser. There are two methods of rendering graphics with a femtosecond laser in air: producing holograms using spatial light modulation technology and scanning of a laser beam by a galvano mirror. The holograms and workspace of the system proposed here occupy a volume of up to 1 cm 3 ; however, this size is scalable depending on the optical devices and their setup. This article provides details of the principles, system setup, and experimental evaluation, and discusses the scalability, design space, and applications of this system. We tested two laser sources: an adjustable (30--100fs) laser that projects up to 1,000 pulses/s at an energy of up to 7mJ/pulse and a 269fs laser that projects up to 200,000 pulses/s at an energy of up to 50μJ/pulse. We confirmed that the spatiotemporal resolution of volumetric displays implemented using these laser sources is 4,000 and 200,000 dots/s, respectively. Although we focus on laser-induced plasma in air, the discussion presented here is also applicable to other rendering principles such as fluorescence and microbubbles in solid or liquid materials.

A direct measurement of the helicity dependence of the total photoabsorption cross section on the proton was carried out at MAMI (Mainz) in the energy range 200 < E_gamma < 800 MeV. The experiment used a 4$\pi$ detection system, a circularly polarized tagged photon beam and a frozen spin target. The contributions to the Gerasimov-Drell-Hearn sum rule and to the forward spin polarizability $\gamma_0$ determined from the data are 226 \pm 5 (stat)\pm 12(sys) \mu b and -187 \pm 8 (stat)\pm 10(sys)10^{-6} fm^4, respectively, for 200 < E_\gamma < 800 MeV.

With the advent of networking technologies intelligent network elements, such as the digital cross-connect system (DCS), will make it possible to dynamically reconfigure a network for restoration purposes. Both restoration control of DCSs and spare-channel design issues are presented, and how they work together so that a fast and economical SONET self-healing network is obtained. In order to achieve fast restoration, a distributed control mechanism that is applicable to both line and path restoration is proposed. The proposed method allows the shared use of spare channels for various failure scenarios, including multiple failure cases, so that the efficient use of spare channels can be achieved. A linear-programming-based scheme is proposed to obtain spare-channel assignment, where a network-flow technique is used. Through a simulation study, a fast and economical self-healing network is verified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Holographic femtosecond laser processing with multiplexed phase Fresnel lenses for high-speed parallel fabrication of microstructures is proposed. Use of a spatial light modulator (SLM) allows independent tunability of the diffraction peaks, three-dimensional parallelism, and arbitrary, variable features. The diffraction peaks are made uniform by changing the center phase and size of each phase Fresnel lens while taking account of the intensity distribution of the irradiated laser pulse and the spatial frequency response of the SLM.

Here, we report a fluorescent spontaneous bone metastatic model of human prostate cancer developed by surgical orthotopic implantation of green fluorescent protein (GFP)-expressing prostate cancer tissue. Human prostate cancer PC-3 cells were transduced with the pLEIN expression retroviral vector containing the enhanced GFP and neomycin resistance genes. Stable GFP high-expression PC-3 clones were selected in vitro with G418, which were then combined and injected s.c. in nude mice. For metastasis studies, fragments of a single highly fluorescent s.c. growing tumor were implanted by surgical orthotopic implantation in the prostate of a series of nude mice. Subsequent micrometastases and metastases were visualized by GFP fluorescence throughout the skeleton, including the skull, rib, pelvis, femur, and tibia The central nervous system, including the brain and spinal cord, was also involved with tumor, as visualized by GFP fluorescence. Systemic organs, including the lung, plural membrane, liver, kidney, and adrenal gland, also had fluorescent metastases. The metastasis pattern in this model reflects the bone and other metastatic sites of human prostate cancer. Thus, this model should be very useful for the study and development of treatment for metastatic androgen-independent prostate cancer.

Abstract An np tandem dye-sensitized solar cell (np-DSC) comprising a titanium dioxide (TiO2) anode and a nickel oxide (NiO) cathode prepared as porous nanostructured films by a sol–gel method using a triblock copolymer template (P123, HO(OCH2CH2)20(OCH(CH3)CH2)70(OCH2CH2)20OH))CH2 exhibited a high open circuit voltage (Voc) of 0.92 V that surpassed the long time champion data, ≈0.8 V for conventional DSC.

The ability of insulin-like growth factor-I (IGF-I), insulin and GH to promote hypoosmoregulatory ability was examined in juvenile rainbow trout (Oncorhynchus mykiss). Following adaptation to 12 parts per thousand (p.p.t.) seawater for 5 days, fish were given a single injection of hormone or vehicle, then exposed to 29 p.p.t. for 24 h and examined for changes in plasma osmolarity, ions and glucose. Ovine GH (oGH; 0.2 micrograms/g) significantly improved the ability of rainbow trout to maintain plasma osmolarity and sodium levels following transfer to 29 p.p.t. seawater. Recombinant bovine IGF-I (0.01, 0.05 and 0.02 micrograms/g) also improved the hypoosmoregulatory ability of trout; the effect being dose-dependent and greater than that of oGH. Bovine insulin (0.01, 0.05 and 0.2 micrograms/g) had no statistically significant effect on plasma ions. The results indicate that IGF-I is a potential mediator of the action of GH in seawater adaptation of salmonids.

Background— Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. Methods and Results— Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of β-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. Conclusions— Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.

A water-stable multilayer Li-metal electrode consisting of a lithium metal, a composite polymer, and a lithium-conducting glass ceramic (LTAP) was proposed as the lithium anode for aqueous lithium–air secondary batteries. The addition of finely dispersed nanosize in the polymer electrolyte greatly reduced the interfacial resistance between the Li anode and the polymer electrolyte. A electrode showed a total resistance of in a 1 M aqueous LiCl solution at , with no change in the electrode resistance over a month. The 1 M LiCl/Pt air cell had a stable open-circuit voltage of 3.80 V, which was equivalent to that calculated from the cell reaction of . The cell exhibited a stable and reversible discharge/charge performance of at , suggesting excellent reversibility of the lithium oxidation reduction reaction for the electrode.

The cross-body stretch and sleeper stretch are widely used for improving flexibility of the posterior shoulder. These stretching methods were modified by Wilk. However, few quantitative data are available on the new, modified stretching methods. A recent study reported the immediate effects of stretching and soft tissue mobilization on the shoulder range of motion (ROM) and muscle stiffness in subjects with posterior shoulder tightness. However, the long-term effect of stretching for muscle stiffness is unknown. The objective of this study was to examine the effects of 2 stretching methods, the modified cross-body stretch (MCS) and the modified sleeper stretch (MSS), on shoulder ROM and muscle stiffness in baseball players with posterior shoulder tightness.Twenty-four college baseball players with ROM limitations in shoulder internal rotation were randomly assigned to the MCS or MSS group. We measured shoulder internal rotation and horizontal adduction ROM and assessed posterior shoulder muscle stiffness with ultrasonic shear wave elastography before and after a 4-week intervention. Subjects were asked to perform 3 repetitions of the stretching exercises every day, for 30 seconds, with their dominant shoulder.In both groups, shoulder internal rotation and horizontal adduction ROM were significantly increased after the 4-week intervention. Muscle stiffness of the teres minor decreased in the MCS group, and that of the infraspinatus decreased in the MSS group.The MCS and MSS are effective for increasing shoulder internal rotation and horizontal adduction ROM and decreasing muscle stiffness of the infraspinatus or teres minor.

To develop a volumetric display of the kind we see in science fiction movies is a dream of many display researchers, including us. Here, we show a new volumetric display with microbubble voxels. The microbubbles are three-dimensionally generated in liquid by focused femtosecond laser pulses. The use of a high-viscosity liquid, which is a key part of the development of this idea, slows down the movement of the microbubbles, and, as a result, volumetric graphics can be displayed. This volumetric bubble display has a wide-angle view, simple refreshing, and no addressing wires, since the transparent liquid is accessed optically rather than electronically. It achieves full-color graphics composed of light-scattering voxels controlled by illumination light sources. Furthermore, a holographic laser drawing method based on a computer-generated hologram displayed on a liquid-crystal spatial light modulator controls the light intensity of the microbubble voxels with an increase in the number of voxels per unit time and the spatial shaping of the voxels.

For optical fiber systems carrying multiple Gb/s, the failure of a key fiber-optic system can result in huge loss of bandwidth. Failure immunization technology for network service survivability (FITNESS) is proposed method to restore fiber networks in a distributed fashion using broadband digital cross-connect systems (B-DCS) in a synchronous optical network (SONET). With intelligent B-DCS cross-connecting at the synchronous transport signal level 1 (STS-1), level, FITNESS unites this distributed intelligence into a single coherent parallel-processing entity to restore the network in under two seconds. Some performance results are obtained through software emulation using a real LATA model are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

This study investigated the influences of ventricular morphology, hemodynamics and clinical findings on exercise capacity in patients after the Fontan operation.Determinants of exercise capacity after the Fontan operation remain unclear.Peak oxygen uptake (PVo2) was determined in 105 patients by exercise test and compared to hemodynamics and clinical findings. Patients were divided into three groups based on ventricular morphology: those with a right ventricle (group RV), a biventricle (group BV) and a left ventricle (group LV).Ten patients with atrioventricular valve regurgitation (AVVR) or hypoxia exhibited a low PVo2. After excluding these patients, although PVo2 did not correlate with hemodynamics, except ventricular ejection fraction (p < 0.02), it correlated with age at the Fontan operation and exercise test (p < 0.002). The PVo2 was higher in group LV (63+/-9%) than in groups RV (55+/-9%) and BV (55+/-12%) (p < 0.01), while an inverse correlation between PVo2 and age at operation was demonstrated only in group RV (p < 0.05). Groups RV or BV and age at exercise test were associated with a lower PVo2, whereas group LV was an independent predictor of a higher PVo2 (p < 0.01). During 4.2 years of follow-up, a decrease in peak heart rate was related to a decrease in PVo2 (p < 0.05). The PVo2 decreased in group RV (p < 0.01).In addition to AVVR, hypoxia, and heart rate response, ventricular morphology is related to exercise capacity. Early Fontan operation may be beneficial in terms of exercise capacity, especially in the group RV patients.

The helicity dependence of the single pion photoproduction on the proton has been measured in the energy range from 200 to 450 MeV for the first time. The experiment, performed at the Mainz microtron MAMI, used a 4π-detector system, a circularly polarized, tagged photon beam, and a frozen-spin target. The data obtained provide new information for multipole analyses of pion photoproduction and determine the main contributions to the Gerasimov-Drell-Hearn sum rule and the forward spin polarizability γ0.Received 6 January 2000DOI:https://doi.org/10.1103/PhysRevLett.84.5950©2000 American Physical Society

International Journal of CancerVolume 76, Issue 6 p. 812-816 Human CancerFree Access Matrilysin-specific antisense oligonucleotide inhibits liver metastasis of human colon cancer cells in a nude mouse model Satoshi Hasegawa, Satoshi Hasegawa Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, Japan Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorNaohiko Koshikawa, Naohiko Koshikawa Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, JapanSearch for more papers by this authorNobuyoshi Momiyama, Nobuyoshi Momiyama Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorKayano Moriyama, Kayano Moriyama Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, JapanSearch for more papers by this authorYasushi Ichikawa, Yasushi Ichikawa Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorTakashi Ishikawa, Takashi Ishikawa Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorMasato Mitsuhashi, Masato Mitsuhashi Hitachi Chemical Research Center, Irvine, CA, USASearch for more papers by this authorHiroshi Shimada, Hiroshi Shimada Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorKaoru Miyazaki, Corresponding Author Kaoru Miyazaki [email protected] Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, JapanDivision of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Miaoka-cho, Totsuka-ku, Yokohama 244, Japan. Fax: (81) 45-820-1901Search for more papers by this author Satoshi Hasegawa, Satoshi Hasegawa Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, Japan Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorNaohiko Koshikawa, Naohiko Koshikawa Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, JapanSearch for more papers by this authorNobuyoshi Momiyama, Nobuyoshi Momiyama Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorKayano Moriyama, Kayano Moriyama Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, JapanSearch for more papers by this authorYasushi Ichikawa, Yasushi Ichikawa Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorTakashi Ishikawa, Takashi Ishikawa Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorMasato Mitsuhashi, Masato Mitsuhashi Hitachi Chemical Research Center, Irvine, CA, USASearch for more papers by this authorHiroshi Shimada, Hiroshi Shimada Second Department of Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa, JapanSearch for more papers by this authorKaoru Miyazaki, Corresponding Author Kaoru Miyazaki [email protected] Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Kanagawa, JapanDivision of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Miaoka-cho, Totsuka-ku, Yokohama 244, Japan. Fax: (81) 45-820-1901Search for more papers by this author First published: 06 December 1998 https://doi.org/10.1002/(SICI)1097-0215(19980610)76:6<812::AID-IJC8>3.0.CO;2-0Citations: 64AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Human colon cancer frequently develops liver metastasis. Matrilysin (MMP-7), the smallest member of the matrix metalloproteinase (MMP) family, is commonly produced by human colon carcinoma cells and has been suggested to be involved in the progression and metastasis of this type of cancer. In the present study, we tested the effect of a matrilysin-specific antisense phosphorothioate oligonucleotide on liver metastasis of the human colon carcinoma cell line WiDr in nude mice. In culture, the antisense oligonucleotide moderately inhibited the secretion of matrilysin by WiDr cells. Injection of WiDr cells into the spleen of nude mice produced many metastatic tumor nodules in the liver. When the antisense oligonucleotide was injected daily into the mice for 11 days, the formation of the metastatic tumor nodules was strongly inhibited in a dose-dependent manner. An inhibition of liver metastasis of over 70% was obtained at a dose of 120 μg of the oligonucleotide per mouse. The antisense oligonucleotide did not inhibit tumor growth in spleen and in liver. A scrambled control oligonucleotide had no effect on liver metastasis of WiDr cells. Our results demonstrate an important role of matrilysin in liver metastasis of human colon cancer and the therapeutic potential of matrilysin antisense oligonucleotides for the prevention of metastasis. Int. J. Cancer 76:812–816, 1998.© 1998 Wiley-Liss, Inc. References Agarwal, B. B., Schwarz, L., Hogan, M. E. and Rando, R. F., Triple helix-forming oligodeoxyribonucleotides targeted to the human tumor necrosis factor (TNF) gene inhibit TNF production and the TNF-dependent growth of human glioblastoma tumor cells. Cancer Res., 56, 5156–5164 (1996). Agrawal, S., Temsamani, J. and Tang, Y. J., Pharmacokinetics, biodistribution, and stability of oligonucleotide phosphorothioates in mice. Proc. nat. Acad. Sci. (Wash.), 88, 7975–7599 (1991). Basset, P., Bellocq, J. P. and Chambon, P., A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature (Lond.), 348, 699–704 (1990). Finlay, I. G. and McArdle, C. S., Effect of occult hepatic metastasis on survival after curative resection for colorectal carcinoma. Gastroenterology, 85, 596–600 (1983). Heppner, K. J., Matrisian, L. M., Jensen, R. A. and Rodgers, W. H., Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Amer. J. Pathol., 149, 273–282 (1996). Ishikawa, T., Ichikawa, Y., Mitsuhashi, M., Momiyama, N., Chishima, T., Tanaka, K., Yamaoka, H., Miyazaki, K., Nagashima, Y., Akitaya, T. and Shimada, H., Matrilysin is associated with progression of colon tumor. Cancer Lett., 106, 5–10 (1996). Koshikawa, N., Yasumitsu, H., Umeda, M. and Miyazaki, K., Multiple secretion of matrix serine proteinases by human gastric carcinoma cell lines. Cancer Res., 52, 5046–5053 (1992). Leonetti, D. A., Lozupone, F., Valentini, A., Geiser, T., Zon, G., Calabrettera, B., Citro, G. C. and Zupi, G., Antitumor effect of c- myc antisense phosphorothioate oligonucleotides on human melanoma cells in vitro and in mice. J. nat. Cancer Inst., 88, 419–429 (1996). Matrisian, L. M., The matrix-degrading metalloproteinases. Bioassays, 14, 455–463 (1992). McDonnell, S., Navre, M., Coffey, R. J., Jr. and Matrisian, L. M., Expression and localization of the matrix metalloproteinase Pump-1 (MMP-7) in human gastric and colon carcinomas. Mol. Carcinogenesis, 4, 527–533 (1991). Miyazaki, K., Hattori, Y., Umenishi, F., Yasumitsu, H. and Umeda, M., Purification and characterization of extracellular matrix-degrading metalloproteinase, Matrin (PUMP-1), secreted from human rectal carcinoma cell line. Cancer Res., 50, 7758–7764 (1990). Momiyama, N., Koshikawa, N., Ishikawa, T., Ichikawa, Y., Hasegawa, S., Nagashima, Y., Mitsuhashi, M., Miyazaki, K. and Shimada, H., Inhibitory effect of matrilysin antisense phosphorothioate oligonucleotides on human colon cancer cell invasion in vitro. Mol. Carcinogenesis (1998). (In press). Mori, M., Barnard, G. F., Mimori, K., Ueo, H., Akiyoshi, T. and Sugimachi, K., Overexpression of matrix metalloproteinase-7 in human colon carcinomas. Cancer (Suppl.), 75, 1516–1519 (1995). Muller, D., Quantin, B., Gesnel, M. C., Millon-Collard, R., Abecassis, J. and Breathnach, R., The collagenase gene family in humans consists of at least four members. Biochem J., 253, 187–192 (1989). Nagashima, Y., Hasegawa, S., Koshikawa, N., Taki, A., Ichikawa, Y., Kitamura, H., Misugi, K., Kihira, Y., Matsuo, Y., Yasumitsu, H. and Miyazaki, K., Expression of matrilysin in vascular endothelial cell adjacent to matrilysin-producing tumor. Int. J. Cancer, 72, 1–5 (1997). Narayanan, R. and Akhtar, S., Antisense therapy. Curr. Opin. Oncol., 8, 509–515 (1996). Newell, K., Witty, J., Rodgers, W. H. and Matrisian, L. M., Expression and localization of the matrix metalloproteinases during colon carcinogenesis. Mol. Carcinogenesis, 10, 199–206 (1994). Noguchi, P., Wallace, R., Johnson, J., Earley, E. M., O'Brinen, S., Ferrone, S., Pellegrino, M. A., Milstien, J., Needy, C., Browne, W. and Petricciani, J., Characterization of WiDr: a human colon carcinoma cell line. In vitro, 15, 401–408 (1979). Pajouh, M. S., Nagle, R. B., Breathnach, R., Brawer, M. K. and Bowden, G. T., Expression of metalloproteinase genes in human prostate cancer. J. Cancer Res. clin. Oncol., 117, 144–150 (1991). Pisani, P., Parkin, D. M. and Ferlay, J., Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden. Int. J. Cancer, 55, 891–903 (1993). Powell, W. C., Knox, J. D., Navre, M., Grogan, T. M., Kittelson, J., Nagle, R. B. and Bowden, G. T., Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. Cancer Res., 53, 417–422 (1993). Pyke, C., Palfkiaer, M. and Danø, K., Messenger RNA for two type collagenases is located in stromal cells in human colon cancer. Amer. J. Pathol., 142, 359–365 (1993). Saijo, Y., Perlaky, L., Wang, H. and Busch, H., Pharmacokinetics, tissue distribution, and stability of antisense oligonucleotide phosphorothiate ISIS3466 in mice. Oncol. Res., 6, 243–249 (1994). Stein, C. A. and Cheng, Y. C., Antisense oligonucleotides as therapeutic reagents—is the bullet really magical? Science, 261, 1004–1012 (1993). Stetler-Stevenson, W. G., Azanavoorian, S. and Liotta, L. A., Tumor cell interactions with the extracellular matrix during invasion and metastasis. Ann. Rev. Cell Biol., 9, 541–573 (1993). Wang, X., Fu, X., Brown, D. P., Crimmin, J. M. and Hoffman, M. R., Matrix metalloproteinase inhibitor BB-94 (Batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res., 54, 4726–4728 (1994). Wilson, C. L., Heppner, K. J., Labosky, P. A., Hogan, B. L. M. and Matrisian, L. M., Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc. nat. Acad. Sci. (Wash.), 94, 1402–1407 (1997). Wilson, C. L. and Matrisian, L. M., Matrilysin: An epithelial matrix metalloproteinase with potentially novel functions. Int. J. Biochem. Cell Biol., 28, 123–136 (1996). Witty, J. P., McDonnell, S., Newell, J. K., Cannon, P., Navre, M., Tressler, J. R. and Matrisian, L. M., Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicityin vivo. Cancer Res., 54, 4805–4812 (1994). Yamamoto, H., Itoh, F., Hinoda, Y. and Imai, K., Suppression of matrilysin inhibits colon cancer cell invasionin vitro. Int. J. Cancer, 61, 218–222 (1995). Yoshimoto, M., Itoh, F., Yamamoto, H., Hinoda, Y., Imai, K. and Yachi, A., Expression of MMP-7 (pump-1) mRNA in human colorectal cancers. Int. J. Cancer, 54, 614–618 (1993). Citing Literature Volume76, Issue610 June 1998Pages 812-816 ReferencesRelatedInformation

Although the mechanisms of 5-fluorouracil (5-FU)-induced diarrhea remain unclear, accumulating evidence has indicated that changes in the mucosal immune system and aquaporins (AQPs) may play a role in its pathogenesis. Therefore, we investigated the possible changes in the gene expression of inflammatory cytokines and AQPs in the intestines of mice with 5-FU-induced diarrhea. In the present study, the expressions of mRNAs that encode inflammatory cytokines, TNF-α, IL-1β, IL-6, Il-17A and IL-22, were significantly increased throughout the entire colon of mice that exhibited diarrhea following 5-FU administration. In contrast, the gene expression of IFNγ was upregulated only in the distal colon. These increases were significantly reduced by the administration of etanercept. However, 5-FU-induced diarrhea was not recovered by etanercept. On the other hand, the genes for AQPs 4 and 8 were markedly present in the colon, and these expressions in the intestines were significantly decreased by treatment with 5-FU. These decreases were not reversed by etanercept. These findings suggest TNF-α neutralization had no effect on the acutely 5-FU-induced diarrhea and impaired AQPs but reduced dramatically several inflammatory cytokines.

and reflect the initial geometry.Good agreement is observed between the measured

This study aims to evaluate the effects of Capacitive and Resistive electric transfer (CRet) and hotpack (HP) on haemoglobin saturation and tissue temperature.The participants were 13 healthy males (mean age 24.5 ± 3.0). They underwent three interventions on different days: (1) CRet (CRet group), (2) HP (HP group) and (3) CRet without power (sham group). The intervention and measurement were applied at the lower paraspinal muscle. Indiba® active ProRecovery HCR902 was used in the CRet group, and the moist heat method was used in the HP group. Oxygenated, deoxygenated and total haemoglobin (oxy-Hb, deoxy-Hb, total-Hb) counts were measured before and after the 15-min interventions, together with the temperature at the skin surface, and at depths of 10 mm and 20 mm (ST, 10mmDT and 20mmDT, respectively). The haemoglobin saturation and tissue temperature were measured until 30 min after the intervention and were collected at 5-min intervals. Statistical analysis was performed for each index by using the Mann-Whitney U test for comparisons between all groups at each time point.Total-Hb and oxy-Hb were significantly higher in the CRet group than in the HP group continuously for 30 min after the intervention. The 10mmDT and 20mmDT were significantly higher in the CRet group than in the HP group from 10- to 30 min after intervention.The effect on haemoglobin saturation was higher in the CRet group than in the HP group. In addition, the CRet intervention warmed deep tissue more effectively than HP intervention.

Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of two-, four-, and six-particle angular correlations in d+Au collisions at sqrt[s_{NN}]=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrt[s_{NN}]=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.

A new type of functional optical microscope system called three-dimensional (3D) stimulation and imaging-based functional optical microscopy (SIFOM) is proposed, to the best of our knowledge. SIFOM can precisely stimulate user-defined targeted biological cells and can simultaneously record the volumetric fluorescence distribution in a single acquisition. Precise and simultaneous stimulation of fluorescent-labeled biological cells is achieved by multiple 3D spots generated by digital holograms displayed on a phase-mode spatial light modulator. Single-shot 3D acquisition of the fluorescence distribution is accomplished by common-path off-axis incoherent digital holographic microscopy in which a diffraction grating with a focusing lens is displayed on another phase-mode spatial light modulator. The effectiveness of the proposed functional microscope system was verified in experiments using fluorescent microbeads and human lung cancer cells located at various defocused positions. The system can be used for manipulating the states of cells in optogenetics.

Massively parallel femtosecond laser processing with more than 1000 beams was demonstrated. Parallel beams were generated by a computer-generated hologram (CGH) displayed on a spatial light modulator (SLM). The key to this technique is to optimize the CGH in the laser processing system using a scheme called in-system optimization. It was analytically demonstrated that the number of beams is determined by the horizontal number of pixels in the SLM NSLM that is imaged at the pupil plane of an objective lens and a distance parameter pd obtained by dividing the distance between adjacent beams by the diffraction-limited beam diameter. A performance limitation of parallel laser processing in our system was estimated at NSLM of 250 and pd of 7.0. Based on these parameters, the maximum number of beams in a hexagonal close-packed structure was calculated to be 1189 by using an analytical equation.

Elevated neurohumoral activity and an abnormal cardiopulmonary response to exercise are well-established characteristics in patients after the Fontan operation. However, there have been few studies addressing cardiac autonomic nervous activity (CANA) in these patients.We evaluated CANA in 63 post-Fontan patients and 44 controls. Cardiac parasympathetic nervous activity (PSNA) was estimated by heart rate (HR) changes after cholinergic blockade, HR variability, and arterial baroreflex sensitivity. Cardiac sympathetic nervous activity was estimated by the heart to mediastinum [(123)I]metaiodobenzylguanidine activity ratio (H/M) and the HR increase (DeltaHR) after isoproterenol infusion (beta). DeltaHR and peak oxygen uptake (VO(2)) were measured by exercise test. There was no difference in beta between the Fontan group and controls. PSNA and H/M were markedly lower than in controls (P<0.001). PSNA and beta were related to DeltaHR (P<0.05); however, peak VO(2) was not correlated with DeltaHR. Neither PSNA nor H/M was associated with clinical features, including hemodynamics, type of repair, number of surgical procedures, age at Fontan operation, or follow-up period, and administration of an angiotensin-converting enzyme inhibitor did not improve the impaired CANA in these patients.After the Fontan procedure, postsynaptic beta-sensitivity is maintained and is important in DeltaHR during exercise as is PSNA, although DeltaHR does not determine exercise capacity. The lack of a relationship between CANA and clinical features implies that, in addition to surgical damage, the Fontan circulation per se may impair CANA. Angiotensin-converting enzyme inhibitor administration does not change this abnormality.

To verify the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the first time experimentally, we measured the helicity dependent total photoabsorption cross section with circularly polarized real photons and longitudinally polarized nucleons in the photon energy range 0.68-1.82 GeV with the tagged photon facility at ELSA. The experiment was carried out with a 4pi detection system, a circularly polarized tagged photon beam, and a frozen spin polarized proton target. The contribution to the GDH sum rule in this photon energy range is [49.9+/-2.4(stat)+/-2.2(syst)] microb.

Water–gas-shift reactions over Pt–Re/TiO2 and Pd–Re/TiO2 catalysts were studied, using the closed gas circulation system and the fixed-bed flow-type reactor. The activity of Pd–Re/TiO2 catalysts was strongly affected by the Re content, while the activity of Pt–Re/TiO2 catalysts was less dependent on the addition ratio of Re, and more dependent on the temperature of reduction. The formation of certain bimetallic clusters between Pt and Re or Pd and Re was confirmed in the cases of Pt–Re(2:3) and Pd–Re(1:1)/TiO2 catalysts; however a different addition manner was suggested for the later acceleration effect over Pd–Re(1:10)/TiO2 catalysts. The FT-IR analyses of the adsorbed species during the reaction exhibited the enhancement of the adsorbed CO peaks in lower wavenumber region with the increase of Re content. Accordingly, Re is supposed to have some effect on these adsorbed CO, which accelerates the WGS reaction, especially in the case of Pd–Re/TiO2 catalysts.

Matrix metalloproteinases (MMP) are considered to play important roles in angiogenesis. In angiogenic processes, endothelial cells secrete MMP-2 or MMP-1 to dissolve the basement membrane or connective tissue around the vessels. MMP-7 (matrilysin) is secreted from the neovasculars induced by cancer and is a metastatic factor of colorectal cancer. The effect of matrilysin on angiogenesis is still unclear, however. We therefore examined the effect of MMP-7 on the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro. Our results showed that recombinant MMP-7 (rMMP-7) accelerated the proliferation of endothelial cells dose-dependently, and did so for endothelial cells cultured not only on type IV collagen, but also on type I collagen. MMP-7 also upregulated MMP-1, -2 secretion, but did not stimulate vascular endothelial growth factor (VEGF) secretion. From this study, we conclude that MMP-7 directly induces angiogenesis, and that therefore MMP-7 would be a good target of cancer therapy.

To understand the skeletal metastatic pattern of non-small cell lung cancer, we developed a stable high-expression green fluorescent protein (GFP) transductant of human lung cancer cell line H460 (H460-GFP). The GFP-expressing lung cancer was visualized to metastasize widely throughout the skeleton when implanted orthotopically in nude mice. H460 was transduced with the pLEIN retroviral expression vector containing the enhanced GFP and the neomycin (G418) resistance gene. A stable high GFP-expressing clone was selected in vitro using 800 microg/ml G418. Stable high-level expression of GFP was maintained in s.c.-growing tumors formed after injecting H460-GFP cells in nude mice. To use H460-GFP for visualization of metastasis, fragments of s.c.-growing H460-GFP tumors were implanted by surgical orthotopic implantation in the left lung of nude mice. Subsequent micrometastases were visualized by GFP fluorescence in the contralateral lung, plural membrane, and widely throughout the skeletal system including the skull, vertebra, femur, tibia, pelvis, and bone marrow of the femur and tibia. The use of GFP-expressing H460 cells transplanted by surgical orthotopic implantation revealed the extensive metastatic potential of lung cancer in particular to widely disseminated sites throughout the skeleton. This new metastatic model can play a critical role in the study of the mechanism of skeletal and other metastasis in lung cancer and in screening of therapeutics that prevent or reverse this process.

Histamine H1-receptors are involved in the development of the symptoms and signs of motion sickness, including emesis. On provocative motion stimulus, a signal for sensory conflict activates the histaminergic neuron system, and the histaminergic descending impulse stimulates H1-receptors in the emetic center of the brain stem. The histaminergic input to the emetic center through H1-receptors is independent of dopamine D2-receptors in the chemoreceptor trigger zone and serotonin 5HT3-receptors in the visceral afferent, which are also involved in the emetic reflex. Antihistamines block emetic H1-receptors to prevent motion sickness. Acetylcholine muscarinic receptors are involved in the generation of signals for sensory conflict. Anti-cholinergic drugs prevent motion sickness by modifying the neural store to facilitate the acquisition of habituation to provocative motion.

In holographic parallel laser processing, precise control of diffraction peaks is important for fabricating enormous numbers of nanometer-scale structures. Although an optimized hologram has high uniformity of the peaks in a computer reconstruction, in practice, the uniformity is decreased owing to the spatial properties of the optical system. A novel optimization method based on peak intensity measurement is proposed to improve the uniformity. The method automatically incorporates the properties of the optical system into the hologram. Improved holographic femtosecond laser processing with this adaptive optimization is demonstrated.

Holographic femtosecond laser processing performs high-speed parallel processing using a computer-generated hologram (CGH) displayed on a liquid crystal spatial light modulator. A critical issue is to precisely control the intensities of the diffraction peaks of the CGH. We propose a method of compensating for the spatial frequency response in the design of CGH using the optimal-rotation-angle method. By applying the proposed method, the uniformity of the diffraction peaks was improved. We demonstrate holographic femtosecond laser processing with two-dimensional and three-dimensional parallelism.

The fluorinated double-tailed glutarate anionic surfactant, sodium 1,5-bis[(1H,1H,2H,2H-perfluorodecyl)oxy]-1,5-dioxopentane-2-sulfonate (8FG(EO)2), was found to stabilize water-in-supercritical CO2 microemulsions with high water-to-surfactant molar ratios (W0). Studies were carried out here to obtain detailed information on the phase stability and nanostructure of the microemulsions by using a high-pressure UV−vis dye probe and small-angle neutron scattering (SANS) measurements. The UV−vis spectra, with methyl orange as a reporter dye, indicated a maximum attainable W0 of 60 at 45 and 75 °C, and SANS profiles indicated regular droplet swelling with a linear relationship between the water core nanodroplet radius and W0. This represents the highest water solubilization reported to date for any water-in-CO2 microemulsion. Further analysis of the SANS data indicated critical packing parameters for 8FG(EO)2 at the microemulsion interface >1.34, representing approximately 1.1 times the value for common aerosol-OT in water-in-heptane microemulsions under equivalent conditions.

We have carried out an experiment to search for a neutron-rich hypernucleus, $^6_{\Lambda}$H, by the $^6$Li($\pi^-,K^+$) reaction at $p_{\pi^-}$ =1.2 GeV/$c$. The obtained missing mass spectrum with an estimated energy resolution of 3.2 MeV (FWHM) showed no peak structure corresponding to the $^6_{\Lambda}$H hypernucleus neither below nor above the $^4_{\Lambda}$H$+2n$ particle decay threshold. An upper limit of the production cross section for the bound $^6_{\Lambda}$H hypernucleus was estimated to be 1.2 nb/sr at 90% confidence level.

We propose a volumetric display based on holographic parallel optical access and two-photon excitation using a computer-generated hologram displayed on a liquid crystal spatial light modulator and a multilayer fluorescent screen. The holographic parallel optical access increased the number of voxels of the volumetric image per unit time. This approach increased the total input energy to the volumetric display, that is, the total fluorescence power, because the maximum energy incident at a point in the multilayer fluorescent screen is limited by the damage threshold. The multilayer fluorescent screen was newly developed to display colored voxels. The thin layer construction of the multilayer fluorescent screen minimized the axial length of the voxels. A volumetric display with only blue-green voxels and a volumetric display with both blue-green and red voxels were demonstrated.

Background In patients with shoulder disease, kinetic chain exercises including hip or trunk movement are recommended. However, the actual muscle activation and scapular kinematics of these exercises are not known. The purpose of this study was to examine the effect of trunk rotation on shoulder exercises that are devised to improve scapular function. Methods Thirteen healthy young men participated in this study. Scaption, external rotation in the first and second positions, and prone scapular retraction at 45°, 90°, and 145° of shoulder abduction were performed with and without trunk rotation. Electromyography was used to assess the scapular muscle activity of the upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and serratus anterior (SA), and electromagnetic motion capture was used to assess scapular motion. The muscle activity ratio, which is the activity of the UT to the MT, LT, and SA, was calculated. These data were compared between 2 conditions (with and without trunk rotation) for each exercise. Results Adding trunk rotation to scaption, the first external rotation, and the second external rotation significantly increased scapular external rotation and posterior tilt, and all 3 exercises increased LT activation. In addition, trunk rotation with scapular retraction at 90° and 145° of shoulder abduction significantly decreased the UT/LT ratio. Conclusions Our findings suggest that shoulder exercises with trunk rotation in this study may be effective in patients who have difficulty in enhancing LT activity and suppressing excessive activation of the UT or in cases in which a decreased scapular external rotation or posterior tilt is observed. In patients with shoulder disease, kinetic chain exercises including hip or trunk movement are recommended. However, the actual muscle activation and scapular kinematics of these exercises are not known. The purpose of this study was to examine the effect of trunk rotation on shoulder exercises that are devised to improve scapular function. Thirteen healthy young men participated in this study. Scaption, external rotation in the first and second positions, and prone scapular retraction at 45°, 90°, and 145° of shoulder abduction were performed with and without trunk rotation. Electromyography was used to assess the scapular muscle activity of the upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and serratus anterior (SA), and electromagnetic motion capture was used to assess scapular motion. The muscle activity ratio, which is the activity of the UT to the MT, LT, and SA, was calculated. These data were compared between 2 conditions (with and without trunk rotation) for each exercise. Adding trunk rotation to scaption, the first external rotation, and the second external rotation significantly increased scapular external rotation and posterior tilt, and all 3 exercises increased LT activation. In addition, trunk rotation with scapular retraction at 90° and 145° of shoulder abduction significantly decreased the UT/LT ratio. Our findings suggest that shoulder exercises with trunk rotation in this study may be effective in patients who have difficulty in enhancing LT activity and suppressing excessive activation of the UT or in cases in which a decreased scapular external rotation or posterior tilt is observed.

On the basis of our previous studies of microbial L-valine production under oxygen deprivation, we developed isobutanol-producing Corynebacterium glutamicum strains. The artificial isobutanol synthesis pathway was composed of the first three steps of the L-valine synthesis pathway; and the subsequent Ehrlich Pathway: pyruvate was converted to 2-ketoisovalerate in the former reactions; and the 2-keto acid was decarboxylated into isobutyraldehyde, and subsequently reduced into isobutanol in the latter reactions. Although there exists redox cofactor imbalance in the overall reactions, i.e., NADH is generated via glycolysis whereas NADPH is required to synthesize isobutanol, it was resolved by taking advantage of the NAD-preferring mutant acetohydroxy acid isomeroreductase encoded by ilvCTM and the NAD-specific alcohol dehydrogenase encoded by adhA. Each enzyme activity to synthesize isobutanol was finely tuned by using two kinds of lac promoter derivatives. Efficient suppression of succinate by-production and improvement of isobutanol yield resulted from inactivation of pckA, which encodes phosphoenolpyruvate carboxykinase, whereas glucose consumption and isobutanol production rates decreased because of the elevated intracellular NADH/NAD+ ratio. On the other hand, introduction of the exogenous Entner–Doudoroff pathway effectively enhanced glucose consumption and productivity. Overexpression of phosphoenolpyruvate:carbohydrate phosphotransferase system specific to glucose and deletion of ilvE, which encodes branched-chain amino acid transaminase, further suppressed by-products and improved isobutanol productivity. Finally, the produced isobutanol concentration reached 280 mM at a yield of 84% (mol/mol glucose) in 24 h.

We demonstrate feedback control of three-dimensional (3D) parallel focusing for automatic compensation of imperfections in an optical system and long-term stability of parallel focusing. These are realized by a computer-generated hologram (CGH) displayed on a spatial light modulator (SLM), and an iterative calculation based on the observation of the 3D focusing intensities with an image sensor on a programmable linear stage. We demonstrate our parallel laser processing method using 40 parallel beams focused at four different planes, with a maximum uniformity of 0.96, applied to single-shot 3D fabrication in transparent glass.

Neurotropism of pancreatic cancer is one of the hypotheses explaining neural invasion, which is one of the characteristics of pancreatic cancer. In these studies, we immunohistochemically examined neural cell adhesion molecules (NCAM), homophilic adhesion molecules expressed on the nerve cells, as a factor of neurotropism, in 15 pancreatic cancer operatively obtained, especially in neural invasive lesions. We also investigated the role of polysialic acid (PSA), which is attached to NCAM and related to the malignant potential of cancers. NCAM was detected in 66.7% of pancreatic cancers, and in all 9 cases with massive perineural invasion. In neural invasive lesions, however, there were perineurium and endoneurium, which do not express NCAM, between the cancer and nerve cells. PSA was also detected in the pancreatic cancers expressing NCAM. Moreover, PSA expression was stronger in the perineural invasive lesions than in the main tumor and was related to the cancer cell proliferation investigated by Ki-67 staining. It is unlikely therefore, that NCAM plays an important role in neurotropism. However, the NCAM expressed on the pancreatic cancer was attached to PSA, which itself plays an important role in the malignant potential of this disease.

A new frozen-spin target has been developed, that allows the detection of emitted particles in an angular acceptance of almost 4π in the laboratory frame. The central part of this new target represents a 3He/4He dilution refrigerator that is installed horizontally along the beam axis. The refrigerator includes an internal superconducting holding coil to maintain the nucleon polarization in the frozen-spin mode longitudinally to the beam. The design of the dilution refrigerator and the use of an internal holding coil enabled for the first time the measurement of a spin-dependent total cross section in combination with a polarized solid state target. This new frozen-spin target was used successfully to measure the helicity asymmetry of the total photoabsorption cross-section at the Mainz accelerator facility MAMI. This experiment has been performed in order to verify for the first time the GDH sum rule.

Matrilysin is believed to play important roles in tumor progression and metastasis. In the present study, we analyzed matrilysin-producing cells in various human cancer tissues by immunohistochemistry and in situ hybridization. Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional-cell carcinomas of the kidney and small-cell lung carcinomas were frequently positive for matrilysin. In addition, we found that endothelial cells of arterioles and venules adjacent to matrilysin-positive tumors expressed matrilysin mRNA and protein. The endothelial cells adjacent to matrilysin-negative tumors and those in normal tissues were negative for matrilysin. Furthermore, analyses by casein zymography, Western blotting and RT-PCR showed that matrilysin was weakly expressed by cultured human umbilical vein endothelial cells. Our results suggest that the expression of matrilysin in vascular endothelial cells and in tumor cells may be regulated by common soluble factors, and that endothelial cell-derived matrilysin may contribute to tumor angiogenesis and tumor metastasis. Int. J. Cancer 72:441–445, 1997. © 1997 Wiley-Liss, Inc.

For the first time we checked the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the proton experimentally in the photon energy range from 0.2–2.9 GeV with the tagged photon facilities at MAMI (Mainz) and ELSA (Bonn). New data of the doubly polarized total cross section difference are presented in the energy range from 1.6 to 2.9 GeV. The contribution to the GDH integral from 0.2–2.9 GeV yields [254±5(stat)±12(syst)] μb with negative contributions in the Regge regime at photon energies above 2.1 GeV. This trend supports the validity of the GDH sum rule.Received 21 February 2004DOI:https://doi.org/10.1103/PhysRevLett.93.032003©2004 American Physical Society

Previous studies have indicated that human transcription initiation factor TFIID is a large complex that contains a TATA-binding polypeptide (TFIID tau or TBP) and other components that qualitatively alter promoter interactions and are uniquely required for activator-dependent (versus basal) transcription. TFIID tau-specific antibody columns have been employed to identify a number of human TFIID polypeptides that are tightly associated with TFIID tau. These differ in size from polypeptides in known general initiation factors, including the initiator-binding factor (TFII-I) which shares some promoter binding characteristics with TFIID. The largest component (p250) identified in TFIID was shown to interact directly and tightly with TFIID tau, suggesting that it may play a major role in the assembly of the TFIID complex.

The helicity dependence of the γ p → pπ 0 reaction has been measured for the first time in the photon energy range from 550 to 790 MeV.The experiment, performed at the Mainz microtron MAMI, used a 4π-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target.These data are predominantly sensitive to the D13(1520) resonance and are used to determine its parameters.

Point mutations in residues comprising the interrupted direct repeats of TFIID eliminated DNA binding in an electrophoretic mobility shift assay. In contrast, mutations in nonconserved residues within the direct repeat regions or in lysine residues comprising the intervening basic repeat had no effect on DNA binding. However, small spacing changes (addition or deletion of one to three residues) in the basic repeat eliminated DNA binding. These results argue for a bipartite DNA binding domain composed of direct repeats with a strict spacing and orientation. Surprisingly, some direct repeat mutations that inhibited DNA binding failed to show a corresponding inhibition of basal transcription, indicating compensating interactions of TFIID with other general factors. The implications of these and other recent results for TFIID structure, promoter recognition, and interactions with other factors are discussed.

The helicity dependence of the total cross section for the γ→p→→nπ+π0 reaction has been measured for the first time at incident photon energies from 400 to 800 MeV. The measurement was performed with the large acceptance detector DAPHNE at the tagged photon beam facility of the MAMI accelerator in Mainz. This channel is found to be excited predominantly when the photon and proton have a parallel spin orientation, due to the intermediate production of the D13 resonance.

The helicity dependence of the total cross section for the γ→p→→pπ0π0 reaction has been measured for the first time at incident photon energies from 400 to 800 MeV. The measurement, performed at the tagged photon beam facility of the MAMI accelerator in Mainz, used the large acceptance detector DAPHNE and a longitudinally polarized frozen-spin target. This channel is found to be excited predominantly when the photon and proton have a parallel spin orientation, most likely due to the intermediate production of the D13(1520) resonance. However, the contribution of the antiparallel spin configuration, arising from other reaction mechanisms, is also not negligible. This result gives important new information to resolve the existing model discrepancies in the identification of the nucleon resonances contributing to this channel.

For experimental investigations of the thermodynamic effect on a cavitating inducer, it is nesessary to observe the cavitation. However, visualizations of the cavitation are not so easy in cryogenic flow. For this reason, we estimated the cavity region in liquid nitrogen based on measurements of the pressure fluctuation near the blade tip. In the present study, we focused on the length of the tip cavitation as a cavitation indicator. Comparison of the tip cavity length in liquid nitrogen (80K) with that in cold water (296K) allowed us to estimate the strength of the thermodynamic effect. The degree of thermodynamic effect was found to increase with an increase of the cavity length. The temperature depression was estimated from the difference of the cavitation number of corresponding cavity condition (i.e., cavity length) between in liquid nitrogen and in cold water. The estimated temperature depression caused by vaporization increased rapidly when the cavity length extended over the throat. In addition, the estimated temperature inside the bubble nearly reached the temperature of the triple point when the pump performance deteriorated.

We have developed a 4-channel multi-anode MCP-PMT, SL10, which exhibits good performance of the transit time spread, σTTS≃30ps for single photons with a gain of ∼106 and a peak quantum efficiency of 20% under a magnetic field of ⩽1.5T. The cross-talk among anodes has been extensively studied. We have taken two measures to suppress it: one is to configure the SL10 to an effectively independent four small pieces of MCP-PMT's by segmenting an electrode of the second MCP-layer; the other is to use a constant-fraction discriminator. A remarkable improvement has been achieved.

A parallel femtosecond pulse irradiation method using a computer-generated hologram displayed on a spatial light modulator provides the advantages of high throughput and high energy-use efficiency. Polarization control of the femtosecond pulse enables some unique properties, for example, selective excitation of an anisotropic molecule, focusing at a size beyond the diffraction limit owing to the longitudinal vector component of a radially polarized beam focused by a high-numerical-aperture objective lens, and fabrication of periodic nanostructures with femtosecond laser light. In this study, we propose a parallel femtosecond laser irradiation system with arbitrary polarization distribution control using a pair of spatial light modulators. By using the system, the interval between the diffraction spots was the closest yet reported by avoiding mutual interference among their side lobes. The interval was improved to half compared with our previous work. We also demonstrated the parallel fabrication of periodic nanostructures with orientation control, which, to our knowledge, is the first reported demonstration of its kind.

Line-shaped femtosecond pulses are well-suited to large-area machining with high throughput in laser cutting, peeling, and grooving of materials. First, we demonstrated the single-shot fabrication of a line structure in a glass surface using a line-shaped pulse generated by a holographic cylindrical lens displayed on a liquid-crystal spatial light modulator. We found the line structure was uniform and smooth near the ends because of the ability to precisely control the intensity distribution and to achieve single-shot fabrication. Second, we demonstrated a line-shaped beam deformed three-dimensionally for showing the potential of holographic line-shaped beam processing. Third, we demonstrated laser peeling of an indium tin oxide film. We found that little debris around the fabricated area was observed, because the debris was removed by the beam itself. Last, we demonstrated laser grooving of stainless steel. We found the swelling of the surface included upwardly growing nanogratings, although many line-shaped pulse irradiations were given. The swelling was caused by the depositions of the debris on the top of the nanogratings.

We present a new method of rendering aerial haptic images that uses femtosecond-laser light fields and ultrasonic acoustic fields. In conventional research, a single physical quantity has been used to render aerial haptic images. In contrast, our method combines multiple fields (light and acoustic fields) at the same time. While these fields have no direct interference, combining them provides benefits such as multi-resolution haptic images and a synergistic effect on haptic perception. We conducted user studies with laser haptics and ultrasonic haptics separately and tested their superposition. The results showed that the acoustic field affects the tactile perception of the laser haptics. We explored augmented reality/virtual reality (AR/VR) applications such as providing haptic feedback of the combination of these two methods. We believe that the results of this study contribute to the exploration of laser haptic displays and expand the expression of aerial haptic displays based on other principles.

Parallel femtosecond laser processing using a computer-generated hologram (CGH) displayed on a spatial light modulator (SLM), called holographic femtosecond laser processing, provides the advantages of high throughput and high energy-use efficiency. Use of a light wave with spatially controlled polarization fields, called a vector wave, also offers novel properties in various applications. In this study, we demonstrated holographic femtosecond laser processing with a vector wave by using a pair of SLMs. In particular, we performed three-dimensional reconstruction with multifocal radial beams. We also realized simultaneous reconstruction with two different types of vector beams by using a novel design method of a CGH composed of multiple small CGHs. To our knowledge, this is the first demonstration of its kind. The polarization fields of the multifocal vector beams at the sample plane were analyzed from the orientations of periodic nanostructures fabricated with femtosecond laser light.

Two-color side-view probing of light-matter interaction from minute focal volume of a tightly focused fs-laser pump pulse reveals charge dynamics with high 0.9 μm optical resolution and approximately ~45fs temporal resolution defined by pulse duration. Use of two colors is advantageous for probing optically excited plasma regions with different density. Holographical digital focusing and spatial filtering were implemented to obtain the same resolution images for subsequent Fourier analysis. Fast plasma density decay with time constant ~150 fs was resolved and is consistent with self-trapping. Potential applications of an optical control over light-induced defects with deep-sub-wavelength resolution is discussed.

Hamstring muscle strain is one of the most common injuries in sports. Therefore, to investigate the factors influencing hamstring strain, the differences in passive tension applied to the hamstring muscles at the same knee and hip positions as during terminal swing phase would be useful information. In addition, passive tension applied to the hamstrings could change with anterior or posterior tilt of the pelvis. The aims of this study were to investigate the difference in passive tension applied to the individual muscles composing the hamstrings during passive elongation, and to investigate the effect of pelvic position on passive tension. Fifteen healthy men volunteered for this study. The subject lay supine with the angle of the trunk axis to the femur of their dominant leg at 70° and the knee angle of the dominant leg fixed at 30° flexion. In three pelvic positions (“Non-Tilt”, “Anterior-Tilt” and “Posterior-Tilt”), the shear elastic modulus of each muscle composing the hamstrings (semitendinosus, semimembranosus, and biceps femoris) was measured using an ultrasound shear wave elastography. The shear elastic modulus of semimembranosus was significantly higher than the others. Shear elastic modulus of the hamstrings in Anterior-Tilt was significantly higher than in Posterior-Tilt. Passive tension applied to semimembranosus is higher than the other muscles when the hamstring muscle is passively elongated, and passive tension applied to the hamstrings increases with anterior tilt of the pelvis.

PHENIX reports differential cross sections of $\mu\mu$ pairs from semileptonic heavy-flavor decays and the Drell-Yan production mechanism measured in $p$$+$$p$ collisions at $\sqrt{s}=200$ GeV at forward and backward rapidity ($1.2<|\eta|<2.2$). The $\mu\mu$ pairs from $c\bar{c}$, $b\bar{b}$, and Drell-Yan are separated using a template fit to unlike- and like-sign muon pair spectra in mass and $p_T$. The azimuthal opening angle correlation between the muons from $c\bar{c}$ and $b\bar{b}$ decays and the pair-$p_T$ distributions are compared to distributions generated using {\sc pythia} and {\sc powheg} models, which both include next-to-leading order processes. The measured distributions for pairs from $c\bar{c}$ are consistent with {\sc pythia} calculations. The $c\bar{c}$ data presents narrower azimuthal correlations and softer $p_T$ distributions compared to distributions generated from {\sc powheg}. The $b\bar{b}$ data are well described by both models. The extrapolated total cross section for bottom production is $3.75{\pm}0.24({\rm stat}){\pm}^{0.35}_{0.50}({\rm syst}){\pm}0.45({\rm global})$[$\mu$b], which is consistent with previous measurements at the Relativistic Heavy Ion Collider in the same system at the same collision energy, and is approximately a factor of two higher than the central value calculated with theoretical models. The measured Drell-Yan cross section is in good agreement with next-to-leading-order quantum-chromodynamics calculations.

Matrilysin produced by human colon cancer cells may be involved in the progression and metastasis of cancer. In the present study, we investigated the association of matrilysin with angiogenesis. One microgram of recombinant matrilysin is confirmed to have increased [3H]-thymidine uptake in human umbilical vein endothelial cells. Then we used micro encapsulation and a mouse hemoglobin enzyme-linked immunosorbent assay system for in vivo quantitation of angiogenesis with BALB/c nu/nu athymic mice. Hundred micrograms of recombinant matrilysin induced angiogenesis to the same degree as 10 microg of basic fibroblast growth factor (bFGF). Angiogenesis was observed at the site implanted with human colon cancer WiDr cells in agarose micro beads. This was inhibited by subcutaneous injection of matrilysin-specific antisense oligonucleotide significantly by 53%. In conclusion, matrilysin may be associated with angiogenesis of human colon cancer through the direct proliferative action on endothelial cells.

We report here the establishment and metastatic properties of bright, highly stable, green fluorescent protein (GFP) expression transductants of the B16 mouse malignant melanoma cell line and the LOX human melanoma line. The highly fluorescent malignant melanoma cell lines allowed the visualization of skeletal and multiorgan metastases after i.v. injection of B16 cells in C57BL/6 mice and intradermal injection of LOX cells in nude mice. The melanoma cell lines were transduced with the pLEIN expression retroviral vector containing the GFP and neomycin resistance genes. Stable B16F0 and LOX clones expressing high levels of GFP were selected stepwise in vitro in levels of G418 of up to 800 microg/ml. Extensive bone and bone marrow metastases of B16F0 were visualized by GFP expression when the animals were sacrificed 3 weeks after cell implantation. Metastases for both cell lines were visualized in many organs, including the brain, lung, pleural membrane, liver, kidney, adrenal gland, lymph nodes, skeleton, muscle, and skin by GFP fluorescence. This is the first observation of experimental skeletal metastases of melanoma, which was made possible by GFP expression. These models should facilitate future studies of the mechanism and therapy of bone and multiorgan metastasis of melanoma.

The class II MHC genes are expressed on the surfaces of B cells, activated T cells, and macrophages and may be induced in other cell types by IFN-gamma. The control of class II gene expression has been shown to be mediated by a series of conserved cis-acting sequences (W, X1, X2, and Y boxes) located immediately 5' to the genes. Although these sequences are conserved, the bp that are important for transcriptional regulation have yet to be identified. To address this issue with regard to the MHC gene HLA-DRA, a series of single bp substitutions spanning the conserved upstream sequences was created and analyzed for their effects on transcription in both B cells and IFN-gamma-treated fibroblasts. In addition, the effects of X1 and X2 box mutations on DNA/protein interactions were examined and compared to the transcriptional data. The results of these studies show that each of the conserved elements participate in maximal expression in B cells and that W, X1, and X2 boxes are important for IFN-gamma induction and expression in fibroblasts. Interestingly, some of the bp changes that altered B cell expression did not alter expression and IFN-gamma induction in fibroblasts, suggesting that different or altered factors control the expression of these genes in the different cell types. Mutant templates designed to eliminate the binding of X1- and X2-specific DNA binding proteins in vivo suggest that these elements and their factors may interact to promote transcription.

A method of optimizing a computer-generated hologram based on parallel second harmonic generation is proposed for holographic femtosecond laser processing. The method, which we call second harmonic optimization, incorporates the width and spatial profile of the pulse into the hologram design. With this method, we demonstrated parallel laser processing with high quality. Because of the enhanced processing accuracy, smaller structures were processed with a smaller energy than in our previous work. In parallel laser processing with 18 beams on a glass surface, the minimum average diameter of the processed structures was 271 nm when the mean fluence of the beams was 0.88 J/cm(2).

We firstly demonstrate the three-dimensional (3D) measurement of a nanometer-sized sphere held in optical tweezers in water using an in-line digital holographic microscope with a green light emitting diode. Suppressing the movement with optical tweezers enabled us to detect the three-dimensional position of a polystyrene sphere with a diameter of 200&#x2009;nm. The positioning resolutions of the microscope were 3.2&#x2009;nm in the transverse direction and 3.4&#x2009;nm in the axial direction, from the standard deviation of measurements of the 200&#x2009;nm sphere fixed on glass. Changes in the Brownian motion in response to a change in the trapping laser power were measured. We also demonstrated that this holographic measurement is an effective method for determining the threshold power of the optical trapping.

We present measurements of the transverse-momentum dependence of elliptic flow $v_2$ for identified pions and (anti)protons at midrapidity ($|\eta|<0.35$), in 0%--5% central $p$$+$Au and $^3$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. When taken together with previously published measurements in $d$$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, the results cover a broad range of small-collision-system multiplicities and intrinsic initial geometries. We observe a clear mass-dependent splitting of $v_2(p_{T})$ in $d$$+$Au and $^3$He$+$Au collisions, just as in large nucleus-nucleus ($A$$+$$A$) collisions, and a smaller splitting in $p$$+$Au collisions. Both hydrodynamic and transport model calculations successfully describe the data at low $p_T$ ($< 1.5$ GeV/$c$), but fail to describe various features at higher $p_T$. In all systems, the $v_2$ values follow an approximate quark-number scaling as a function of the hadron transverse kinetic energy per constituent quark($KE_T/n_q$), which was also seen previously in $A$$+$$A$ collisions.

A method for optimizing a computer-generated hologram (CGH) for high-stability laser processing is proposed. The CGH is optimized during laser processing; therefore, unpredicted dynamic changes in the laser processing system, in addition to its static imperfections, are automatically compensated for by exploiting the rewritable capability of the spatial light modulator. Consequently, the short-term and long-term stability are improved, which will contribute to the realization of high-speed, high-precision laser processing. A CGH that generated 36 parallel beams was continuously optimized, and the maximum uniformity reached 0.98, which is higher than reported in previous research. To the best of our knowledge, this is the first demonstration of gradual improvement of parallel laser processing with in-process optimization of the CGH. Furthermore, it was also demonstrated that the performance of the laser processing system against unexpected disturbances was improved.

Angiomodulin (AGM/TAF/mac25) is a 30-kDa glycoprotein that was identified as an integrin-independent cell adhesion protein secreted by human bladder carcinoma cells. AGM is highly accumulated in small blood vessels of tumor tissues. In the present study, we attempted to identify the cell surface receptor and the cell-binding site of AGM using ECV-304 human vascular endothelial cells and BALB/c3T3 mouse fibroblasts. Heparin, heparan sulfate, and dextran sulfate, but not chondroitin sulfate, inhibited both adhesion of the two cell lines to AGM-coated plates and binding of AGM to these cells. Treatment of cells with heparinase, but not chondroitinase, inhibited both cell adhesion to AGM and AGM binding to cells. These results strongly suggested that heparan sulfates are the major receptor for AGM. Furthermore, we determined a 20-amino acid sequence within AGM molecule as its major cell-binding site. The synthetic peptide for the cell-binding sequence showed cell adhesion activity comparable to that of AGM, and the activity was inhibited by heparin and heparan sulfate. The peptide competitively inhibited cell adhesion to AGM and the binding of AGM to cells. These results indicated that AGM binds to cells through interaction of the identified cell-binding sequence with heparan sulfates on cell surface. It was also found that the heparan sulfate-binding peptide inhibited the formation of capillary tube-like structures of vascular endothelial cells in culture. J. Cell. Biochem. 75:187–195, 1999. © 1999 Wiley-Liss, Inc.

Human transcription initiation factor TFIID contains the TATA-binding protein (TBP) and several TBP-associated factors (TAFs). To investigate the structural organization and function of TFIID, we have cloned and expressed a cDNA encoding the third largest human TFIID subunit, hTAFII100. Immunoprecipitation studies demonstrate that hTAFII100 is an integral subunit that is associated with all transcriptionally-competent forms of TFIID. They further suggest that at least part of the N-terminal region lies on the surface of TFIID, while a C-terminal region containing conserved WD-40 repeats appears inaccessible. Both in vivo and in vitro assays indicate that hTAFII100 interacts strongly with the histone H4-related hTAFII80 and the histone H3-related hTAFII31, as well as a stable complex comprised of both hTAFII80 and hTAFII31. Apparently weaker interactions of hTAFII100 with TBP, hTAFII250, hTAFII28, and hTAFII20, but not hTAFII55, also have been observed. These results suggest a role for hTAFII100 in stabilizing interactions of TAFs, especially the histone-like TAFs, in TFIID. In addition, functional studies show that anti-hTAFII100 antibodies selectively inhibit basal transcription from a TATA-less initiator-containing promoter, relative to a TATA-containing promoter, suggesting a possible core promoter-specific function for hTAFII100. Human transcription initiation factor TFIID contains the TATA-binding protein (TBP) and several TBP-associated factors (TAFs). To investigate the structural organization and function of TFIID, we have cloned and expressed a cDNA encoding the third largest human TFIID subunit, hTAFII100. Immunoprecipitation studies demonstrate that hTAFII100 is an integral subunit that is associated with all transcriptionally-competent forms of TFIID. They further suggest that at least part of the N-terminal region lies on the surface of TFIID, while a C-terminal region containing conserved WD-40 repeats appears inaccessible. Both in vivo and in vitro assays indicate that hTAFII100 interacts strongly with the histone H4-related hTAFII80 and the histone H3-related hTAFII31, as well as a stable complex comprised of both hTAFII80 and hTAFII31. Apparently weaker interactions of hTAFII100 with TBP, hTAFII250, hTAFII28, and hTAFII20, but not hTAFII55, also have been observed. These results suggest a role for hTAFII100 in stabilizing interactions of TAFs, especially the histone-like TAFs, in TFIID. In addition, functional studies show that anti-hTAFII100 antibodies selectively inhibit basal transcription from a TATA-less initiator-containing promoter, relative to a TATA-containing promoter, suggesting a possible core promoter-specific function for hTAFII100.

The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell-specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)-transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 microg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO-treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO-treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.

Three kinds of neurotransmitters (histamine, acetylcholine, and catecholamine) are thought to be important in the neural processes of motion sickness because antihistaminics, scopolamine, and amphetamine are effective in preventing motion sickness. In this study, we examined the neurochemical and neuropharmacologic features of motion sickness in rats. Based on our results, we propose the following hypotheses for the neurochemical mechanisms of motion sickness: (1) the histaminergic neuron system is involved in the signs and symptoms of motion sickness, including vomiting; (2) the acetylcholinergic neuron system is involved in the processes of habituation to motion sickness, including neural store mechanisms; and (3) the catecholaminergic neuron system in the brain stem is not related to the development of motion sickness.

Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat) +/- 4.5(syst)] microb is extracted.

The present study deals with the immunohistochemical detection of four brain-derived proteins and cytokeratin in the normal olfactory mucosa of humans and guinea pigs. Neurofilament protein immunoreactivity was found in the olfactory vesicles, dendrites, and perikaryon of receptor cells, and in thick nerve bundles located deep in the lamina propria. The antiserum to neuron-specific enolase (NSE) selectively stained olfactory receptor cells throughout the length of the bundles. The NSE immunoreactivity also was recognized in nerve bundles of various sizes throughout the lamina propria. Glia-specific S-100 protein immunoreactivity was present in Bowman's glands as well as in all nerve bundles in the lamina propria, but not in any cellular elements constituting the olfactory epithelium. Immunoreactivity for spot-35 protein, which was considered to be specific for cerebellar Purkinje cells, was found in flasklike cells (microvillar cells) occurring near the free surface of the epithelium. The basal cells in the olfactory and respiratory epithelium were stained positively with a cytokeratin antiserum.

Twenty patients who had disturbance of the sense of smell caused by localized inflammation of the ethmoid sinus were studied to determine the effects of endonasal ethmoidectomy on olfaction. The patients were evaluated pre and post-operatively regarding their subjective olfaction, and with the T&T olfactometry and the Alinamine intravenous administration test, both of which are widely used in Japan. The improvement rate was 70.0% subjectively and 80.0% with T&T olfactometry 6 months after surgery. It is concluded that surgery is worthwhile treatment for olfactory disturbances caused by localized ethmoiditis.

Liquid crystal spatial light modulators, which are widely used as display devices for computer-generated holograms, have modulation characteristics that depend on spatial frequency. We describe a method for displaying a computer-generated hologram on a liquid crystal spatial light modulator with compensation of its spatial frequency response. Using this method, we demonstrate a binary phase grating with smaller dependence on the spatial frequency. We also demonstrate application of the display method to holographic femtosecond laser processing.

Holographic two-photon polymerization is based on a high-speed, low-loss parallel laser irradiation technique inside photosensitive materials using a computer-generated hologram displayed on a liquid crystal spatial light modulator. We demonstrated a sparse exposure technique combining parallel exposure and scanning exposure to improve the fabrication throughput and to achieve simultaneous fabrication of linear structures with different widths. We also demonstrated fabrication of space-variant structures by changing a CGH, as well as parallel fabrication of voxel structures with single femtosecond laser pulse irradiation.

Lipase-catalyzed esterification of lactic acid has thus far achieved only limited success due to high acidity and polarity of lactic acid: acid inactivation of enzymes, and immiscibility of lactic acid with hydrophobic organic solvents that are commonly used for non-aqueous enzyme reactions. Herein, we investigated enzymatic esterification of lactic acid with ethanol by using hydrophobic ethers and ketones as reaction media. Both of the solvents are miscible with lactic acid, and have the basicity to suppress the acid inactivation of enzymes, as well as polar solvents. Nevertheless, these solvents would be less harmful to enzymes rather than polar solvents because of their high hydrophobicity. Using the ethers and ketones, ethyl lactate was successfully synthesized enzymatically even at higher lactic acid concentrations, and the enzyme activity was effectively stabilized even in repeated batch-wise reactions (2.0 M lactic acid, 4 weeks). This effect of some ethers and ketone to stabilize the enzyme was significantly higher than that of polar solvents in the presence of polar alcohols, the other substrate. In addition, more various kinds of lipase could esterify 1.0 M lactic acid in the hydrophobic ether and ketone rather than those in hydrophobic solvents, polar solvents, and a solvent-free system.

Background It has been reported that P19 embryonal carcinoma (EC) cells differentiate into beating cardiomyocytes under the action of oxytocin (OT). It has been suggested that dimethylsulfoxide (DMSO) acts via the oxytocin/oxytocin receptor pathway because an oxytocin receptor antagonist not only blocks oxytocin-induced cardiomyocyte differentiation, but also blocks DMSO-induced differentiation. In this study, the differentiation ability of OT was tested using P19CL6 cells. Methods P19CL6 cells were cultured as a confluent monolayer and aggregated cells. OT was then added to culture media as an inducing agent. The cells treated with 1% DMSO were used as a positive control group. Differentiated cells were evaluated morphologically and immunocytochemically, as well as by RT-PCR. In addition, a stable line of green fluorescent protein (GFP)-expressing P19CL6 cells were differentiated into beating cardiomyocytes by OT. Results Aggregated P19CL6 cells could be differentiated into cardiomyocytes, whereas monolayer cells could not differentiate and express specific cardiac muscle marker genes. In the control group, both aggregates and monolayer cells could be differentiated into cardiomyocytes by DMSO. In addition, GFP-expressing P19CL6 cells differentiated efficiently into beating cardiomyocytes when treated with OT. The results of all evaluations confirmed that the differentiated cells were cardiomyocytes. Conclusions We concluded that embryoid body formation (cell aggregation) is necessary for the differentiation of P19CL6 cells into cardiomyocytes when using OT as an inducer agent. Furthermore, because of the high rate of differentiation efficiency, GFP-expressing cardiomyocytes derived from P19CL6 cells have the potential to be used for regenerative therapies in experimental models.

Trunk rotation often accompanies humeral elevation, during daily activities as well as sports activities. Earlier studies have demonstrated that changes in spinal posture contribute to scapular motion during humeral elevation. However, the effect of trunk rotation on scapular kinematics during humeral elevation has received scant attention. This study aimed to clarify how trunk rotation affects scapular kinematics and muscle activities during humeral elevation. Electromagnetic motion capture and electromyography were used to assess scapular and clavicular motion and muscle activity in the right and left sides of 12 healthy young men. The subjects were seated and instructed to elevate both arms with the trunk in neutral, ipsilaterally rotated, or contralaterally rotated position. Ipsilaterally rotated trunk position decreased the internal rotation (by 5°, relative to neutral trunk position) and increased the upward rotation (by 4°, relative to neutral trunk position) of the scapula. Trunk position did not affect clavicular motion during humeral movement. Electromyography showed that contralaterally rotated trunk position increased the activity of the upper trapezius and serratus anterior muscles and decreased the activity of the lower trapezius. Therapists should consider the importance of trunk rotation, which may be the key to developing more efficient rehabilitation programs.

We present time-resolved studies of the dielectric breakdown using tightly focused femtosecond (fs) laser pulses in glass. Axial evolution of the breakdown and material modifications have been retrieved over the time span from 0 to 1 ns with a 50 fs resolution and ∼ 1 μm spatial resolution using interferometric pump-probe technique. It is shown that even at pulse power slightly above critical Pcr ≃ 1 MW/pulse, the filamentation was limited at tight focusing and the central focal region with resolidified glass was localised axially within ∼ 10 μm; it can be used for the waveguide recording. Mechanisms of light-matter interaction at tight focusing and application potential are discussed. The electron-ion scattering time, τe–i ≃ 1.1 fs, for the glass at electron concentration ne ≃ (4–5)×1020 cm−3 was determined within Drude approximation.

We propose three-dimensional (3D) subpixel estimation in the position measurement of a nanoparticle held in optical tweezers in water by using an in-line, low-coherence digital holographic microscope. The 3D subpixel estimation was performed with the addition of axial subpixel estimation to the lateral subpixel estimation introduced in our previous work [Appl. Opt.50, H183 (2011)]. The axial subpixel estimation allowed the step length in the diffraction calculation of a hologram to be increased to &#x223C;20&#x2009;&#x2009;nm while keeping the axial resolution of &#x223C;3&#x2009;&#x2009;nm. This drastically decreased the computation time of the diffraction calculation to less than 10% of the two-dimensional subpixel estimation.

We propose a new digital holography method using an ultra-broadband light source and a chromatic phase-shifter. The chromatic phase-shifter gives different frequency shifts for respective spectral frequencies so that the spectrum of the light reflected from the object can be measured to reveal the spectral property of the object, and arbitrary selection of signals in the temporal frequency domain enables single- and multi-wavelength measurements with wide dynamic range. A theoretical analysis, computer simulations, and optical experiments were performed to verify the advantages of the proposed method.

Abstract This paper describes a remote control system for a crawler-type mobile robot with passive sub-crawlers. This system has a great advantage because it utilizes an essential compliant mechanism that allows the angle of the sub-crawlers to be adapted to the shape of the road surface. Its operation is extremely simple, and it is only necessary to control the movement direction and driving speed in comparison with the case of controlling active sub-crawlers. However, a robot with passive sub-crawlers cannot recover from a situation in which it is stuck. The operator must select a traversable route for unknown rough terrain using only the information obtained from camera images and some sensor data from the robot. In this study, a remote control system for a crawler robot with passive sub-crawlers was developed based on a warning system. This system evaluates the currently selected route by calculating the stabilization for the robot when falling down in the roll and pitch directions. Experimental results obtained using a prototype crawler robot with passive sub-crawlers demonstrated the effectiveness of the proposed system.

In the multiple-plane phase retrieval method, a tedious-to-fabricate phase diffuser plate is used to increase the axial intensity variation for a nonstagnating iterative reconstruction of a smooth object wavefront. Here we show that a spatial light modulator (SLM) can be used as an easily controllable diffuser for phase retrieval. The polarization modulation at the SLM facilitates independent formation of orthogonally polarized scattered and specularly reflected beams. Through an analyzer, the polarization states are filtered enabling beam interference, thereby efficiently encoding the phase information in the axially diverse speckle intensity measurements. The technique is described using wave propagation and Jones calculus, and demonstrated experimentally on technical and biological samples.