I. J. Watson

Creating a successful small molecule drug is a challenging multiparameter optimization problem in an effectively infinite space of possible molecules. Generative models have emerged as powerful tools for traversing data manifolds composed of images, sounds, and text and offer an opportunity to dramatically improve the drug discovery and design process. To create generative optimization methods that are more useful than brute-force molecular generation and filtering via virtual screening, we propose that four integrated features are necessary: large, quantitative data sets of molecular structure and activity, an invertible vector representation of realistic accessible molecules, smooth and differentiable regressors that quantify uncertainty, and algorithms to simultaneously optimize properties of interest. Over the course of 12 months, Terray Therapeutics has collected a data set of 2 billion quantitative binding measurements of small molecules to therapeutic targets, which directly motivates multiparameter generative optimization of molecules conditioned on these data. To this end, we present contrastive optimization for accelerated therapeutic inference (COATI), a pretrained, multimodal encoder-decoder model of druglike chemical space. COATI is constructed without any human biasing of features, using contrastive learning from text and 3D representations of molecules to allow for downstream use with structural models. We demonstrate that COATI possesses many of the desired properties of universal molecular embedding: fixed-dimension, invertibility, autoencoding, accurate regression, and low computation cost. Finally, we present a novel metadynamics algorithm for generative optimization using a small subset of our proprietary data collected for a model protein, carbonic anhydrase, designing molecules that satisfy the multiparameter optimization task of potency, solubility, and drug likeness. This work sets the stage for fully integrated generative molecular design and optimization for small molecules.

Intermetallic γ-TiAl based alloys of the TNM™ alloy family attain their excellent processing characteristics by a high β-phase content present at hot-working temperatures. Subsequent to hot-working the β-phase content is decreased by a heat treatment step performed at temperatures where the β-phase fraction exhibits a minimum. In this study, in- and ex-situ experiments were conducted on three alloys with different contents of β/β0 stabilizing elements. The course of phase fractions as a function of temperature as well as phase transition temperatures were determined by means of in-situ high-energy X-ray diffraction experiments. Additionally, dynamic scanning calorimetry investigations were performed to obtain complementary data on the transition temperatures. Quantitative metallography was conducted on heat treated and quenched specimens to acquire additional information on the dependence of the phase fractions on temperature. By neutron diffraction experiments the ordering temperatures of the constituent phases were determined. It was shown that the experiments yielded consistent results which differ significantly from ThermoCalc simulations for which a commercial TiAl database was used. The differences between the experimental results and the thermodynamic predictions are discussed.

Abstract In recent times, novel titanium aluminides containing the bcc β ‐phase at high temperatures are being developed for improved hot‐working capabilities, however, predictions of the phase diagrams are merely uncertain. Here we present in‐situ neutron studies, which are particularly sensitive to the atomic disorder in the ordered phases. Complementary laser scanning confocal microscopy is employed for in‐situ microstructural investigations.

Abstract We report TeV gamma-ray observations of the ultra-high-energy source MGRO J1908+06 using data from the High Altitude Water Cherenkov Observatory. This source is one of the highest-energy known gamma-ray sources, with emission extending past 200 TeV. Modeling suggests that the bulk of the TeV gamma-ray emission is leptonic in nature, driven by the energetic radio-faint pulsar PSR J1907+0602. Depending on what assumptions are included in the model, a hadronic component may also be allowed. Using the results of the modeling, we discuss implications for detection prospects by multi-messenger campaigns.

Bioenergy is widely included in energy strategies for its GHG mitigation potential. Bioenergy technologies will likely have to be deployed at scale to meet decarbonisation targets, and consequently biomass will have to be increasingly grown/mobilised. Sustainability risks associated with bioenergy may intensify with increasing deployment and where feedstocks are sourced through international trade. This research applies the Bioeconomy Sustainability Indicator Model (BSIM) to map and analyse the performance of bioenergy across 126 sustainability issues, evaluating 16 bioenergy case studies that reflect the breadth of biomass resources, technologies, energy vectors and bio-products. The research finds common trends in sustainability performance across projects that can inform bioenergy policy and decision making. Potential sustainability benefits are identified for People (jobs, skills, income, energy access); for Development (economy, energy, land utilisation); for Natural Systems (soil, heavy metals), and; for Climate Change (emissions, fuels). Also, consistent trends of sustainability risks where focus is required to ensure the viability of bioenergy projects, including for infrastructure, feedstock mobilisation, techno-economics and carbon stocks. Emission mitigation may be a primary objective for bioenergy, this research finds bioenergy projects can provide potential benefits far beyond emissions - there is an argument for supporting projects based on the ecosystem services and/or economic stimulation they may deliver. Also given the broad dynamics and characteristics of bioenergy projects, a rigid approach of assessing sustainability may be incompatible. Awarding 'credit' across a broader range of sustainability indicators in addition to requiring minimum performances in key areas, may be more effective at ensuring bioenergy sustainability.

Nations use product standards, and manipulate them, for reasons othen than practical use or safety. The Soviets once cultivated standards to isolate themselves. In the United States, codes and standards are often used to favor home industries over external competition, and to favor some producers over others. Krislov compares and contrasts the United States, the EC, the forner Eastern bloc, and Japan, to link standard choice with political styles and to trace growing internationalization based on product efficiency criteria.

The marketing staff of several major banks now include an account manager. His essential task is the successful handling of a relationship with a corporate client over a period of time. He will have a sound technical understanding of banking, well‐developed social skills and an ability to work creatively on his own. Unlike the advertising account manager the emphasis of his work is likely to be placed on conforming to established procedures. He will have to operate on many different levels within his customer's organisation. His role is that of a team leader dependent on a whole cross‐section of his corporate resources for support. Three broad streams of research exist which can contribute to a deeper understanding of managing the corporate customer: research into the selling process itself, research into the marketing of services, and research into the major sale. A model in ten stages is suggested that can be used to describe an account manager's job. At each stage an objective/key task is defined, the particular responsibilities of the account manager, the tangible outcome and the skills needed. A second model comprising four stages in managing communications comprises the ideas “listen”, “champion”, “extract” and “display”.

The decay or annihilation of dark matter particles may produce a steady flux of very-high-energy gamma rays detectable above the diffuse background. Nearby clusters of galaxies provide excellent targets to search for the signatures of particle dark matter interactions. In particular, the Virgo cluster spans several degrees across the sky and can be efficiently probed with a wide field-of-view instrument. The High Altitude Water Cherenkov (HAWC) observatory, due to its wide field of view and sensitivity to gamma rays at an energy scale of 300 GeV–100 TeV is well-suited for this search. Using 2141 days of data, we search for γ-ray emission from the Virgo cluster, assuming well-motivated dark matter substructure models. Our results provide some of the strongest constraints on the decay lifetime of dark matter for masses above 10 TeV.Received 7 September 2023Accepted 5 January 2024DOI:https://doi.org/10.1103/PhysRevD.109.043034Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasGamma ray astronomyParticle dark matterParticles & FieldsGravitation, Cosmology & Astrophysics

The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we have leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole genome approaches to map the physical and genetic interactions of TPL at a repressed locus. We identified SPT4, SPT5 and SPT6 as necessary for repression with the SPT4 subunit acting as a bridge connecting TPL to SPT5 and SPT6. We also discovered the association of multiple additional constituents of the transcriptional preinitiation complex at TPL-repressed promoters, specifically those involved in early transcription initiation events. These findings were validated in yeast and plants through multiple assays, including a novel method to analyze conditional loss of function of essential genes in plants. Our findings support a model where TPL nucleates preassembly of the transcription activation machinery to facilitate rapid onset of transcription once repression is relieved.

A minimal non-thermal dark matter model that can explain both the existence of dark matter and the baryon asymmetry in the universe is studied. It requires two color-triplet, iso-singlet scalars with $\mathcal{O}$(TeV) masses and a singlet Majorana fermion with a mass of $\mathcal{O}$(GeV). The fermion becomes stable and can play the role of the dark matter candidate. We consider the fermion to interact with a top quark via the exchange of QCD-charged scalar fields coupled dominantly to third generation fermions. The signature of a single top quark production associated with a bottom quark and large missing transverse momentum opens up the possibility to search for this type of model at the LHC in a way complementary to existing monotop searches.

Zirconolite glass-ceramics are being developed as potential wasteforms for the disposition of Pu wastes in the UK. Previous studies utilised a variety of surrogates whilst this work uses both cold-press and sinter and hot isostatic press methods to validate the wasteform with PuO2. A cold press and sinter sample was fabricated as part of a validation study for plutonium incorporation in hot isostatically pressed (HIPed) wasteforms. The results confirmed the cold-press and sinter, achieved successful waste incorporation and a microstructure and phase assemblage that was in agreement with those expected of a HIPed equivalent. A HIP sample was fabricated of the same composition and characterised by SEM and XRD. Results were in agreement with the sintered sample and achieved complete waste incorporation into the glass-ceramic wasteform. These samples have demonstrated successful incorporation of PuO2 into glass-ceramic HIPed wasteforms proposed for processing Pu-based waste-streams in the UK.

Currently, newly developed artificial intelligence techniques, in particular convolutional neural networks, are being investigated for use in data-processing and classification of particle physics collider data. One such challenging task is to distinguish quark-initiated jets from gluon-initiated jets. Following previous work, we treat the jet as an image by pixelizing track information and calorimeter deposits as reconstructed by the detector. We test the deep learning paradigm by training several recently developed, state-of-the-art convolutional neural networks on the quark-gluon discrimination task. We compare the results obtained using various network architectures trained for quark-gluon discrimination and also a boosted decision tree (BDT) trained on summary variables.

The Belle II Experiment at the High Energy Accelerator Research Organization (KEK) in Tsukuba, Japan, will explore the asymmetry between matter and antimatter and search for new physics beyond the standard model. 172 double-sided silicon strip detectors are arranged cylindrically in four layers around the collision point to be part of a system which measures the tracks of the collision products of electrons and positrons. A total of 1748 radiation-hard APV25 chips read out 128 silicon strips each and send the analog signals by time-division multiplexing out of the radiation zone to 48 Flash Analog Digital Converter Modules (FADC). Each of them applies processing to the data; for example, it uses a digital finite impulse response filter to compensate line signal distortions, and it extracts the peak timing and amplitude from a set of several data points for each hit, using a neural network. We present an overview of the SVD data readout system, along with front-end electronics, cabling, power supplies and data processing.

The High Altitude Water Cherenkov (HAWC) gamma-ray observatory observes atmospheric showers produced by incident gamma rays and cosmic rays with energy from 300 GeV to more than 100 TeV. A crucial phase in analyzing gamma-ray sources using ground-based gamma-ray detectors like HAWC is to identify the showers produced by gamma rays or hadrons. The HAWC observatory records roughly 25,000 events per second, with hadrons representing the vast majority (>99.9%) of these events. The standard gamma/hadron separation technique in HAWC uses a simple rectangular cut involving only two parameters. This work describes the implementation of more sophisticated gamma/hadron separation techniques, via machine learning methods (boosted decision trees and neural networks), and summarizes the resulting improvements in gamma/hadron separation obtained in HAWC.

Ground-based gamma-ray astronomy is still a rather young field of research, with strong historical connections to particle physics. This is why most observations are conducted by experiments with proprietary data and analysis software, as it is usual in the particle physics field. However in recent years, this paradigm has been slowly shifting towards the development and use of open-source data formats and tools, driven by upcoming observatories such as the Cherenkov Telescope Array (CTA). In this context, a community-driven, shared data format (the gamma-astro-data-format or GADF) and analysis tools such as Gammapy and ctools have been developed. So far these efforts have been led by the IACT community, leaving out other types of ground-based gamma-ray instruments.We aim to show that the data from ground particle arrays, such as the High-Altitude Water Cherenkov (HAWC) observatory, is also compatible with the GADF and can thus be fully analysed using the related tools, in this case Gammapy. We reproduce several published HAWC results using Gammapy and data products compliant with GADF standard. We also illustrate the capabilities of the shared format and tools by producing a joint fit of the Crab spectrum including data from six different gamma-ray experiments. We find excellent agreement with the reference results, a powerful check of both the published results and the tools involved. The data from particle detector arrays such as the HAWC observatory can be adapted to the GADF and thus analysed with Gammapy. A common data format and shared analysis tools allow multi-instrument joint analysis and effective data sharing. Given the complementary nature of pointing and wide-field instruments, this synergy will be distinctly beneficial for the joint scientific exploitation of future observatories such as the Southern Wide-field Gamma-ray Observatory and CTA.

The performance of the High Altitude Water Cherenkov Gamma-ray Observatory (HAWC) is mainly shaped by its event reconstruction methodologies, which take as input only the footprint left on the ground by the air shower.We discuss here the revamped reconstruction algorithms, including noise suppression cleaning, a refined core reconstruction method using simulations to fit hit observation, addressing systematic error sources in direction reconstruction, and a new gamma/hadron separation approach based on a more accurate model.As a result, HAWC's angular resolution and gamma/hadron separation reach an improvement of a factor of 2 and 3, respectively, at the highest energies for highly inclined showers and can now observe the Galactic Center at a significance of over 5.Furthermore, we verify the overall performance improvement by observing the Crab Nebula as a reference source which we observe at 250 using 2434 days of data.

Pulsar Inverse Compton halos (TeV halos) are a new subclass of gamma-ray sources.HAWC detected the first two candidates, Geminga and Monogem.These two candidates are of great interest to the anomalous positron excess observed by PAMELA, Fermi-LAT, and AMS-02.This positron excess has been considered to originate from dark matter annihilation, but pulsars can also explain this excess.The HAWC collaboration presented their analysis of the morphology of these pulsars and derived high electron/positron emission efficiency but a diffusion coefficient lower than the average value by a factor of 2 orders of magnitude.Here we present a more in-depth study of Geminga and Monogem with 2139 days of observations from the HAWC observatory.We apply a 3D template model from diffuse-gamma ray electrons/positron emission inverse Compton interactions as they escape the pulsar.

Creating a successful small molecule drug is a challenging multi-parameter optimization problem in an effectively infinite space of possible molecules. Generative models have emerged as powerful tools for traversing data manifolds comprised of images, sounds, and text, and offer an opportunity to dramatically improve the drug discovery and design process. To create generative optimization methods that are more useful than brute-force molecular generation and filtering via virtual screening, we propose that four integrated features are necessary: large, quantitative datasets of molecular structure and activity, an invertible vector representation of realistic accessible molecules, smooth and differentiable regressors that quantify uncertainty, and algorithms to simultaneously optimize properties of interest. Over the course of 12 months, Terray has collected a dataset of 2 billion quantitative binding measurements, which directly motivates multi-parameter generative optimization of molecules conditioned on this data. To this end, we present COATI, a pre-trained, multi-modal encoder-decoder model of druglike chemical space. COATI is constructed without any human biasing of features, using contrastive learning from text and 3D representations of molecules to allow downstream use with structural models. We demonstrate that COATI possesses many of the desired properties of a universal molecular embedding: fixed-dimension, invertibility, autoencoding, accurate regression, and low computation cost. Finally, we present a novel metadynamics algorithm for generative optimization using a small subset of our proprietary data collected for a model protein, Carbonic Anhydrase, designing molecules that satisfy the multi-parameter optimization task of potency, solubility, and druglikeness. This work sets the stage for fully-integrated generative molecular design and optimization for small molecules.

The decay or annihilation of dark matter particles may produce a steady flux of very-high-energy gamma rays detectable above the diffuse background. Nearby clusters of galaxies provide excellent targets to search for the signatures of particle dark matter interactions. In particular, the Virgo cluster spans several degrees across the sky and can be efficiently probed with a wide field-of-view instrument. The High Altitude Water Cherenkov (HAWC) observatory, due to its wide field of view and sensitivity to gamma rays at an energy scale of 300 GeV--100 TeV is well-suited for this search. Using 2141 days of data, we search for gamma-ray emission from the Virgo cluster, assuming well-motivated dark matter sub-structure models. Our results provide some of the strongest constraints on the decay lifetime of dark matter for masses above 10 TeV.

Deep learning techniques are currently being investigated for high energy physics experiments, to tackle a wide range of problems, with quark and gluon discrimination becoming a benchmark for new algorithms. One weakness is the traditional reliance on Monte Carlo simulations, which may not be well modelled at the detail required by deep learning algorithms. The weakly supervised learning paradigm gives an alternate route to classification, by using samples with different quark-gluon proportions instead of fully labeled samples. This paradigm has, therefore, huge potential for particle physics classification problems as these weakly supervised learning methods can be applied directly to collision data. In this study, we show that realistically simulated samples of dijet and Z+jet events can be used to discriminate between quark and gluon jets by using weakly supervised learning. We implement and compare the performance of weakly supervised learning for quark-gluon jet classification using three different machine learning methods: the jet image-based convolutional neural network, the particle-based recurrent neural network and and the feature-based boosted decision tree.

The Belle II Silicon Vertex Detector comprises four layers of double-sided silicon strip detectors (DSSDs), consisting of ladders with two to five sensors each. All sensors are individually read out by APV25 chips with the Origami chip-on-sensor concept for the central DSSDs of the ladders. The chips sit on flexible circuits that are glued on the top of the sensors. This concept allows a low material budget and an efficient cooling of the chips by a single pipe per ladder. We present the construction of the first SVD ladders and results from precision measurements and electrical tests.

The Belle II experiment at the asymmetric SuperKEKB collider in Japan will operate at an instantaneous luminosity approximately 50 times greater than its predecessor (Belle). The central feature of the experiment is a vertex detector comprising two layers of pixelated silicon detectors (PXD) and four layers of double-sided silicon microstrip detectors (SVD). One of the key measurements for Belle II is CP violation asymmetry in the decays of beauty and charm hadrons, which hinges on a precise charged-track vertex determination and low-momentum track measurement. Towards this goal, a proper assembly of the SVD components with precise alignment ought to be performed and the geometrical tolerances should be checked to fall within the design limits. We present an overview of the assembly procedure that is being followed, which includes the precision gluing of the SVD module components, wire-bonding of the various electrical components, and precision 3D coordinate measurements of the final SVD modules. Finally, some results from the latest test-beam are reported.

The Belle II experiment at the SuperKEKB collider in Japan is designed to indirectly probe new physics using approximately 50 times the data recorded by its predecessor. An accurate determination of the decay-point position of subatomic particles such as beauty and charm hadrons as well as a precise measurement of low-momentum charged particles will play a key role in this pursuit. These will be accomplished by an inner tracking device comprising two layers of pixelated silicon detector and four layers of silicon vertex detector based on double-sided microstrip sensors. We describe herein the design, prototyping and construction efforts of the Belle-II silicon vertex detector.

Abstract Microquasars with high-mass companion stars are promising very high energy (VHE; 0.1–100 TeV) gamma-ray emitters, but their behaviors above 10 TeV are poorly known. Using the High Altitude Water Cerenkov (HAWC) observatory, we search for excess gamma-ray emission coincident with the positions of known high-mass microquasars (HMMQs). No significant emission is observed for LS 5039, Cyg X-1, Cyg X-3, and SS 433 with 1523 days of HAWC data. We set the most stringent limit above 10 TeV obtained to date on each individual source. Under the assumption that HMMQs produce gamma rays via a common mechanism, we have performed source-stacking searches, considering two different scenarios: (I) gamma-ray luminosity is a fraction ϵ γ of the microquasar jet luminosity, and (II) VHE gamma rays are produced by relativistic electrons upscattering the radiation field of the companion star in a magnetic field B . We obtain ϵ γ < 5.4 × 10 −6 for scenario I, which tightly constrains models that suggest observable high-energy neutrino emission by HMMQs. In the case of scenario II, the nondetection of VHE gamma rays yields a strong magnetic field, which challenges synchrotron radiation as the dominant mechanism of the microquasar emission between 10 keV and 10 MeV.

After the Phase-2 high-luminosity upgrade to the Large Hadron Collider (LHC), the collision rate and therefore the background rate will significantly increase, particularly in the high $\eta$ region. To improve both the tracking and triggering of muons, the Compact Muon Solenoid (CMS) Collaboration plans to install triple-layer Gas Electron Multiplier (GEM) detectors in the CMS muon endcaps. Demonstrator GEM detectors were installed in CMS during 2017 to gain operational experience and perform a preliminary investigation of detector performance. We present the results of triple-GEM detector performance studies performed in situ during normal CMS and LHC operations in 2018. The distribution of cluster size and the efficiency to reconstruct high $p_T$ muons in proton--proton collisions are presented as well as the measurement of the environmental background rate to produce hits in the GEM detector.

A 69-year-old woman with a history of relapsed acute lymphocytic leukemia presented for evaluation of a diffuse, asymptomatic scaly rash appearing 15 days after initiating inotuzumab ozogamicin 0.5 mg/m2 infusions and ponatinib 45 mg daily, which were started 2 months previously. Review of systems, including pruritus and flu-like symptoms, was negative. The patient received prednisone 20 mg daily and triamcinolone 1% topical treatment without improvement of the rash. The rash only improved upon cessation of ponatinib, while inotuzumab ozogamicin was continued. Examination revealed thick plate-like sheets of desquamation to the scalp, upper portion of the chest, dorsal aspect of the forearms, and distal parts of both legs (Fig 1). Punch biopsies of the upper portion of the chest and lateral aspect of the shin were performed (Figs 2 and 3).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: Based on the clinical presentation and histopathologic findings, what is the most likely diagnosis?A.Acquired ichthyosisB.Pityriasis rotundaC.Eczema craquelé (asteatotic eczema)D.Progressive symmetric erythrokeratoderma (PSEK)E.Atopic dermatitis Answers:A.Acquired ichthyosis – Correct. This is a drug-induced acquired ichthyosis secondary to ponatinib therapy. Acquired ichthyosis is a rare condition with onset in adulthood and can be associated with underlying malignancies, infections, inflammatory disorders, or medications. Ichthyotic scaling commonly presents on the trunks, limbs, and scalp. Scales can be white, brown, or gray and vary in size from 1 mm to 1 cm.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google Scholar, 2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google Scholar, 3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar It has been reported that third-generation tyrosine kinase inhibitors, such as ponatinib, are associated with ichthyosiform eruptions.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google Scholar, 3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar, 4Eber A.E. Rosen A. Oberlin K.E. Giubellino A. Romanelli P. Ichthyosiform pityriasis rubra pilaris-like eruption secondary to ponatinib therapy: case report and literature review.Drug Saf Case Rep. 2017; 4: 19https://doi.org/10.1007/s40800-017-0055-yCrossref PubMed Google Scholar Histopathology, which is nonspecific, may show compact ortho- and/or parakeratotic hyperkeratosis and inflammatory infiltrate in the papillary dermis. The granular layer may be absent (similar to ichthyosis vulgaris), normal, or thickened.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google Scholar, 2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google Scholar, 3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google ScholarB.Pityriasis rotunda – Incorrect. Pityriasis rotunda is characterized by hypopigmented or hyperpigmened, well-demarcated, scaly, round patches or thick plaques, often 10 cm in size. Microscopic features resemble ichthyosis vulgaris with a diminished granular cell layer along with hyperkeratosis and no parakeratosis.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google ScholarC.Eczema craquelé (asteatotic eczema) – Incorrect. Xerosis is the predisposing factor for eczema craquelé and has an indolent course over years. Eczema craquelé is characterized by pruritic skin with fine scale and interconnected fissures.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google ScholarD.PSEK – Incorrect. Also known as Darier-Gottron syndrome, PSEK presents during infancy, extending into puberty but rarely into adulthood. PSEK is characterized by symmetric, well-demarcated, fixed, erythematous, hyperkeratotic plaques involving the cheeks, the extensor surfaces of the upper and lower extremities, and the buttocks. Histopathology demonstrates acanthosis, basket-weave and patchy parakeratotic hyperkeratosis, and a prominent granular layer.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google ScholarE.Atopic dermatitis – Incorrect. Atopic dermatitis is a relapsing, pruritic condition commonly affecting infants and children. It is characterized by scaly, erythematous papules and plaques involving flexural areas with lichenification in chronic cases.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google Scholar Question 2: Which of the following eruptions is not a cutaneous adverse reaction associated with ponatinib therapy?A.Pityriasis rubra pilaris-likeB.SeborrheicC.Lichen planopilaris-likeD.FolliculocentricE.Psoriasiform Answers:A.Pityriasis rubra pilaris-like – Incorrect. Reported pityriasis rubra pilaris-like cases describe asymptomatic, red-orange papules coalescing to plaques with islands of sparing progressively developing over 2 to 12 weeks after ponatinib initiation.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google Scholar, 3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar, 4Eber A.E. Rosen A. Oberlin K.E. Giubellino A. Romanelli P. Ichthyosiform pityriasis rubra pilaris-like eruption secondary to ponatinib therapy: case report and literature review.Drug Saf Case Rep. 2017; 4: 19https://doi.org/10.1007/s40800-017-0055-yCrossref PubMed Google ScholarB.Seborrheic – Incorrect. A case of ponatinib-induced seborrheic eruption has been reported presenting with follicular prominence with hyperkeratotic spicules over the beard area and eyebrows with lateral eyebrow alopecia 10 days after drug initiation.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google ScholarC.Lichen planopilaris-like – Incorrect. Few cases of lichen planopilaris-like eruptions associated with ponatinib have been reported. These have been characterized by follicular erythematous papules with perifollicular scale and loss of hair follicles along the scalp. Additionally, erythematous papules of the eyebrows with nonscarring alopecia were present.5Patel A.B. Solomon A.R. Mauro M.J. Ehst B.D. Unique cutaneous reaction to second- and third-generation tyrosine kinase inhibitors for chronic myeloid leukemia.Dermatology. 2016; 232: 122-125https://doi.org/10.1159/000437383Crossref PubMed Scopus (28) Google ScholarD.Folliculocentric – Incorrect. There are reported cases of ponatinib causing a folliculocentric eruption presenting as asymptomatic perifollicular erythema with prominent follicular hyperkeratotic spicules and dyskeratosis over the chest and abdomen.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google ScholarE.Psoriasiform – Correct. BCR-ABL inhibitors, including imatinib and nilotinib, angiogenesis inhibitors, immune checkpoint inhibitors, and anti-CD20 monoclonal antibodies are anticancer therapies associated with psoriasis hyperkeratotic reactions. There are no reports thus far of ponatinib causing psoriasiform eruptions.3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar Question 3: What is the reported appropriate next step in management for these refractory lesions?A.Topical retinoidB.Systemic retinoidC.Ammonium lactateD.Mycophenolate mofetilE.Urea Answers:A.Topical retinoid – Incorrect. Traditionally, topical retinoid therapy has been used as first-line agents along with topical steroids and anti-seborrheic agents in mild cases.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google Scholar, 3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar, 4Eber A.E. Rosen A. Oberlin K.E. Giubellino A. Romanelli P. Ichthyosiform pityriasis rubra pilaris-like eruption secondary to ponatinib therapy: case report and literature review.Drug Saf Case Rep. 2017; 4: 19https://doi.org/10.1007/s40800-017-0055-yCrossref PubMed Google ScholarB.Systemic retinoid – Correct. Refractory cases have been treated successfully with oral acitretin 10 mg daily. Systemic retinoids should be considered with caution, as liver enzyme abnormalities can occur. The mechanism behind retinoids as effective therapy is unknown. One proposed theory involves retinoids causing upregulation of heparin-binding epidermal growth factor-like growth factor leading to local chemotherapeutic resistance in keratinocytes. Another theory describes the role of retinoids in aiding to terminally differentiate epidermal cells leading to reduced uptake of chemotherapy within keratinocytes.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google Scholar, 3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar, 4Eber A.E. Rosen A. Oberlin K.E. Giubellino A. Romanelli P. Ichthyosiform pityriasis rubra pilaris-like eruption secondary to ponatinib therapy: case report and literature review.Drug Saf Case Rep. 2017; 4: 19https://doi.org/10.1007/s40800-017-0055-yCrossref PubMed Google ScholarC.Ammonium lactate – Incorrect. Ammonium lactate is not used for severe, refractory cases. It has previously been used for mild-to-moderate hyperkeratotic lesions secondary to ponatinib.2Alloo A. Sheu J. Butrynski J.E. et al.Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities.Br J Dermatol. 2015; 173: 574-577https://doi.org/10.1111/bjd.13692Crossref PubMed Scopus (25) Google ScholarD.Mycophenolate mofetil – Incorrect. Mycophenolate mofetil can be considered as a steroid-sparing agent for psoriasiform and erythrodermic eruptions secondary to tyrosine kinase inhibitors; however, it is contraindicated in the setting of this patient’s leukemia.1Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Saunders/Elsevier, 2017Google ScholarE.Urea – Incorrect. Keratolytics, such as urea, have been used as initial therapy for mild-to-moderate ponatinib-induced rashes alongside high-potency topical steroids. Urea has not been used as a first-line agent in severe, refractory cases.3Vastarella M. Fabbrocini G. Sibaud V. Hyperkeratotic skin adverse events induced by anticancer treatments: a comprehensive review.Drug Saf. 2020; 43: 395-408https://doi.org/10.1007/s40264-020-00907-6Crossref PubMed Scopus (9) Google Scholar None disclosed. The authors thank Dr Alun Wang and Dr Garrett Vick for providing the histology images for this manuscript.

Profiles the clearing banks' decision to introduce an apparently new managerial discipline (marketing) into their operations and how this may be regarded historically. Examines the organisational consequences, associated problems and levels of satisfaction with the introduction of marketing as perceived by the senior management of the UK clearing banks. Posits that, following the visits of senior executives to the USA in the early 1960s, banks became involved with marketing. States that there were early problems of acceptance by practising bankers, and this only resolved itself when academies in particular encouraged the study of services marketing. Gives details of the research study that involved the seven English clearing banks and says that this refers to the first phase only of the two phases. Predicts that if marketing is to contribute to the long‐term objectives of the banks and the mutual welfare of both banks and their customers, then it is imperative that its importance is understood and employed.

The Belle II VerteX Detector (VXD) is a 6 layers silicon tracker device that will cope with an unprecedented luminosity of 8×1035 cm−2s−1 achievable by the new SuperKEKB e+e− collider, at the KEK laboratory (Tsukuba, Japan). All environment parameters such as temperature, humidity and radiation levels, must be constantly monitored and under certain conditions action must be promptly taken, such as interlocking the power supply or delivering an abort signal to the SuperKEKB collider. In this contribution we describe the Belle II VXD monitoring system. We also present the first results of the temperature and humidity system commissioned in a Beam Test at DESY in April 2016 and the preliminary results of the radiation monitoring achieved with a prototype system during the first SuperKEKB commissioning phase at KEK in February-June 2016.

The Belle II Silicon Vertex Detector (SVD) was installed recently and has been prepared for physics run at SuperKEKB factory, Tsukuba, Japan. For a reliable operation and data taking of the SVD, a sophisticated and robust run and slow control system has been implemented, which utilizes the Experimental Physics and Industrial Control System (EPICS) framework. EPICS uses client/server and publish/subscribe techniques to communicate between the various sub-systems and computers. The information exchange between the different pieces of software and computers is done by process variables (PVs). These PVs are provided by input/output controllers (IOCs), which communicate and interface with the hardware components. The Belle II SVD slow and run control comprises five groups of subsystems, which are SVD DAQ controller, Flash ADC controller, environmental monitors and interlocks, power supplies and EPICS infrastructure services. In this paper we describe the tasks and the implementation of the individual sub-systems, the interaction between them and the global Belle II run and slow control as well as the first experience from commissioning and initial operation of the SuperKEKB accelerator.

In high-energy particle physics events, it can be advantageous to find the jets associated with the decays of intermediate states, for example, the three jets produced by the hadronic decay of the top quark. Typically, a goodness-of-association measure, such as a $\chi^2$ related to the mass of the associated jets, is constructed, and the best jet combination is found by optimizing this measure. As this process suffers from a combinatorial explosion with the number of jets, the number of permutations is limited by using only the $n$ highest $p_T$ jets. The self-attention block is a neural network unit used for the neural machine translation problem, which can highlight relationships between any number of inputs in a single iteration without permutations. In this paper, we introduce the Self-Attention for Jet Assignment (SaJa) network. SaJa can take any number of jets for input and outputs probabilities of jet-parton assignment for all jets in a single step. We apply SaJa to find jet-parton assignments of fully-hadronic $t\bar{t}$ events to evaluate the performance. We show that SaJa achieves better performance than a likelihood-based approach.

The Belle II experiment at the SuperKEKB asymmetric energy e+e− collider in KEK, Japan will operate at an instantaneous luminosity 40 times larger than that of its predecessor, Belle. It is built with an aim of collecting a huge amount of data (50 ab−1 by 2025) for precise CP violation measurements and new physics search. Thus, we need an accurate vertex determination and reconstruction of low momentum tracks which will be achieved with the help of vertex detector (VXD). The Belle II VXD consists of two layers of DEPFET pixels (`Pixel Detector') and four layers of double-sided silicon microstrip sensors (`Silicon Vertex Detector'), assembled over carbon fibre ribs. In this paper, we discuss about the Belle II Silicon Vertex Detector, especially its design and key features; we also present its module (`ladder') assembly and testing procedures.

The Belle-II VerteX Detector (VXD) has been designed to improve the performances with respect to Belle and to cope with an unprecedented luminosity of 8×1035cm−2s−1 achievable by the SuperKEKB. Special care is needed to monitor both the radiation dose accumulated throughout the life of the experiment and the instantaneous radiation rate, in order to be able to promptly react to sudden spikes for the purpose of protecting the detectors. A radiation monitoring and beam abort system based on single-crystal diamond sensors is now under an active development for the VXD. The sensors will be placed in several key positions in the vicinity of the interaction region. The severe space limitations require a challenging remote readout of the sensors.

The upgrade of the Belle II experiment plans to use a vertex detector based on two different technologies, DEPFET pixel (PXD) technology and double side silicon microstrip (SVD) technology. The vertex electronics are characterized by the topology of SVD bias that forces to design a sophisticated grounding because of the floating power scheme. The complex topology of the PXD power cable bundle may introduce some noise inside the vertex area. This paper presents a general overview of the EMC issues present in the vertex system, based on EMC tests on an SVD prototype and a study of noise propagation in the PXD cable bundle based on Multi-conductor transmission line theory.

Bioenergy is widely included in energy strategies for its GHG mitigation potential. Bioenergy technologies will likely have to be deployed at scale to meet decarbonisation targets, and consequently biomass will have to be increasingly grown/mobilised. Sustainability risks associated with bioenergy may intensify with increasing deployment and where feedstocks are sourced through international trade. This research applies the Bioeconomy Sustainability Indicator Model (BSIM) to map and analyse the performance of bioenergy across 126 sustainability issues, evaluating 16 bioenergy case studies that reflect the breadth of biomass resources, technologies, energy vectors and bio-products. The research finds common trends in sustainability performance across projects that can inform bioenergy policy and decision making. Potential sustainability benefits are identified for People (jobs, skills, income, energy access); for Development (economy, energy, land utilisation); for Natural Systems (soil, heavy metals), and; for Climate Change (emissions, fuels). Also, consistent trends of sustainability risks where focus is required to ensure the viability of bioenergy projects, including for infrastructure, feedstock mobilisation, techno-economics and carbon stocks. Emission mitigation may be a primary objective for bioenergy, this research finds bioenergy projects can provide potential benefits far beyond emissions - there is an argument for supporting/promoting/replicating projects based on the ecosystem services and/or economic stimulation they may deliver. Also given the broad dynamics and characteristics of bioenergy projects, a rigid approach of assessing sustainability may be incompatible. Awarding ‘credit’ across a broader range of sustainability indicators in addition to requiring minimum performances in key areas, may be more effective at ensuring bioenergy sustainability.

There is an increasing interest in the use of the thermal energy within abandoned, flooded coal mines within the UK, which offers a potential seen as a low-carbon source that could support the decarbonizing of heating and contribute to the nation’s 2050 net-zero emission goal. With about 78% of UK dwellings currently using natural gas to fuel central heating, residential and commercial heating is responsible for 23% of the countries carbon emissions. Whilst all the underground coal mines are now closed, about 25% of the population still live above legacy mine workings, a proportion of which remains in deprived rural mining areas and is prone to be affected by energy poverty. Using an open-loop heat pump mine-water heating system, heat could be harnessed from the 12-20°C mine-water filling the underground mining voids to provide an economic low carbon heat resource that could directly benefit the local population, provided that the heat extracted does not exceed the heat in place.Whilst the potential of flooded mine workings to provide sustainable heat energy has been extensively investigated, only a limited number of mine-water heating system are currently operating worldwide, such as Heerlen in the Netherlands. In order to aid the development of the resource in the UK, a better understanding of the sustainability and thermal footprint of heat extraction is required. However, generating an optimal production scenario through numerical modelling requires a thorough understanding of the geometry of mine workings. This is generally highly complex and subject to numerous uncertainties, due to the long history of mining, poor documentation of the mine workings and the inability to characterize the current state of the workings. Hence, no standard modelling approach to quantify the potential thermal resource of abandoned mine workings has yet been developed. In order to develop such a tool, it is essential to quantify the effects and uncertainties linked to the choice of a modelling approach, to the mine geometry or to the values of rock properties.  Here, we focus the analysis on the relative importance of geometrical features in controlling the dynamic heat recharge and extraction rate from pillar-and-stall and longwall mines, using different modelling approaches. We show that the volume of the mining zone and the permeability contrasts between the caved and fracture zone are key controls on the thermal output and that equivalent porous models can reasonably reproduce the power output of more detailed models. A combination of georeferenced mining data, monitoring temperature, hydraulic data, and a range of typical rock property values for the coal measures is then used to develop a conceptual model of the Bilston Glen mine in the UK and provide a first assessment of its static heat potential, accounting for the uncertainty in the mined volume. Calibrated numerical models are finally developed and compared to the analytical solutions to get insights into the dynamic heat recharge of the system in the long-term, and support the development of a generic conceptual tool for the assessment of sustainable rate of heat extraction from mine workings.

21 Moorfields is an over-station commercial office development, located above Moorgate underground station in the heart of the City of London. The multistorey office building spans 55m between supports using an innovative combination of arches coupled with launching trusses and mega-trusses along the east and west facades. Due to the nature and location of the development, the project brief imposed tight robustness requirements, including designing for dynamic forces derived both from multiple permutations of member-removal and event-specific scenarios. This article discusses a performance-based approach to robustness assessment which was implemented on the project, in which the intent of the relevant building regulations was explicitly checked through realistic physics-based simulations.

High energy γ-ray observations are an essential probe of cosmic-ray acceleration mechanisms.The detection of the highest energy γ rays and the shortest timescales of variability are the key to improve our understanding of the acceleration processes and the environment of the cosmic accelerators.The High Altitude Water Cherenkov (HAWC) experiment is a large fieldof-view, multi-TeV, γ-ray observatory continuously operating at 4100 m a.s.l.since March, 2015.The HAWC observatory has an order of magnitude better sensitivity, angular resolution, and background rejection than the previous generation of water-Cherenkov arrays.The improved performance allows us to discover new TeV sources, to detect transient events, to study the Galactic diffuse emission at TeV energies, to measure or constrain the TeV spectra of GeV γ-ray sources, to search for Galactic Pevatrons, and to improve the upper limits on indirect searches for dark matter and the constrains on Lorentz invariance violation.In this contribution I summarize the most recent results from the HAWC observatory using the latest reconstruction algorithm (Pass 5 production) and I discuss their implications for cosmic-ray acceleration and propagation.

We present an update of the survey of Active Galaxies with the High Altitude Water Cherenkov (HAWC) gamma-ray observatory.This work adds 567 days of HAWC data to the previously published survey, providing a refined analysis of an updated total exposure of 2090 days.The sample includes 138 nearby AGNs from the 3FHL catalog.We fit a modified power-law to their very high energy spectra, including the exponential attenuation caused by the Extragalactic Background Light.We found four sources with significant detections (above 5): the radio galaxy M87 and the BL Lac objects Mkn 421, Mkn 501 and 1ES 1215+303.We also report eight sources with a marginal detection (between 3 and 5) of which seven are classified as BL Lac objects and one as a radio galaxy.

TeV halos are a new class of -ray sources recently observed around some middle-aged pulsars.They are extended -ray emission regions with a size bigger than the Pulsar Wind Nebulae but smaller than a Supernova Remnant.Several studies indicate that a TeV halo may be a general signature around a middle-aged pulsar, but this is still an open question.Some recent results suggest TeV halos are significantly contributing to the TeV emission of our Galaxy, and models have been proposed to reproduce the observed population of TeV halos in the Milky Way.In this work, we analyze the emission at TeV energies of the Andromeda galaxy (M31), the closest spiral galaxy to Earth.M31 has also been observed to have a GeV excess similar to the observed in the Galactic Center of our Galaxy.The aim of this work is to model the -ray emission at TeV energies in M31 assuming both the Milky Way and M31 share similar properties.Using 6.5 years of HAWC observations, we compute the flux upper limits in the region of M31 at TeV energies.

In 2020, the HAWC Collaboration presented the first catalog of gamma-ray sources emitting above 56 TeV and 100 TeV.With nine sources detected, this was the highest-energy source catalog to date.Here, we present the results of re-analysis of the old data, along with additional data acquired since then.We use a new version of the reconstruction software with better pointing accuracy and improved gamma/hadron separation.We now see more than 25 sources above 56 TeV, with most sources being located in the Galactic plane.The vast majority of these seem to be leptonic pulsar wind nebulae, but some have been shown to have hadronic emission.We will show spectra and discuss possible emission mechanisms of some of the most interesting sources, including the ones the HAWC Collaboration considers PeVatron candidates.

We present a comparison of the flux normalization using two versions of the official data reconstruction used for HAWC analyses. Pass4 has been used so far for most of the results published by HAWC, in particular we are focusing in the Daily Monitoring of blazars that used 17 months of data. The most recent reconstruction version, Pass5 will be used in future analyses and comes with better pointing accuracy and improved gamma/hadron separation. The aim of this work is to do a comparison of the light curves obtained with both Pass4 and Pass5 and show that the results are consistent for both P4 and P5 withing statistical uncertainties.

We present the results of applying a transformer-based deep learning neural network to the data from the HAWC Gamma-Ray Observatory.HAWC observes the extensive air showers produced by very high energy gamma rays, and registers the Cherenkov radiation produced by the shower by photo-multiplier tubes (PMTs) instrumented in 300 large water Cherenkov detectors.The current HAWC method uses a staged parameterized fitting of the PMT information to find the shower center and incoming angular direction of the initiating gamma-ray, and produces variables which can be used for separating showers produced by gamma rays versus the overwhelming cosmic-ray background.The deep learning model, on the other hand, takes the charge and relative timing information of the PMTs as input and directly outputs an estimate of the incoming direction of the initiating gamma ray and a gamma-hadron discriminator.Both tasks are vital for source analysis.Better angular reconstruction allows for better source localization.Improved cosmic-ray rejection improves the signal-to-noise ratio.The deep learning network is found to perform better in simulation than the current methods at lower energies (around several hundred GeV gamma rays) where fewer PMTs are turned on by the shower, and therefore less information is available.

The High Altitude Water Cherenkov (HAWC) Gamma-ray Observatory, located in the mountains of Mexico, has been performing an unbiased survey of the Northern sky at energies above 300 GeV since becoming fully operational in 2015.HAWC's wide field-of-view enables indirect searches for TeV-scale dark matter from diverse targets including galaxy clusters, dwarf spheroidal galaxies, the Milky Way galactic halo and the Sun.Beyond dark matter, sensitivity to transient bursts of gamma-rays provides a window into the early universe through searches for evaporating primordial black holes and its high energy reach enables searches for violations of the Lorentz symmetry.I will present an overview of beyond-the-Standard-Model searches with HAWC and present some of the world's strongest constraints on these processes at the TeV scale.

Axion-like particles could be potential dark matter candidates, whose conversion from gamma rays could have an impact on the spectra of extremely powerful astronomical gamma-ray sources.For galactic sources, the overall result of this coupling may be reflected as an attenuation of the gamma-ray spectrum at energies above several tens of TeV.Therefore, multi-TeV observatories like the High Altitude Water Cherenkov (HAWC) Observatory would have a unique opportunity to investigate the parameters of ALPs candidates in the mass range from fractions of a neV up to tens of eV.In this study, we present a preliminary study of the spectrum observed of the TeV gamma-ray source eHWC J1908+63, constraining the ALP coupling to better than 10 -12 GeV -1

LHAASO J1849-0003 is one of the twelve gamma-ray sources that can emit photons above 100 TeV reported by LHAASO in 2021.It is spatially coincident with HESS J1849-000, which may be powered by PSR J1849-0001.The High Altitude Water Cherenkov (HAWC) observatory has also observed a possible counterpart source named eHWC J1850+001 above 56 TeV.In this work, we use the most up-to-date HAWC dataset with 2398 days of data to perform dedicated multi-source modeling of the region around eHWC J1850+001.We present the spectrum and morphology of eHWC J1850+001 and other nearby sources identified during a systematic source search.We anticipate the HAWC observational results to determine a potential connection between HESS J1849-000 and LHAASO J1849-0003, providing a more complete TeV spectral study of this energetic source.

Blazars are the most abundant type of extragalactic gamma-ray source, usually presenting high variability across the electromagnetic spectrum. Their Very High Energy (VHE, above 0.1 TeV) emission has been studied in detail using Air Cherenkov Telescopes, with observations biased to flaring periods while their average activity has not been properly characterized. In this work, we report the results of 2090 days of quasi-continuous observations of the blazars 1ES 1215+303 and VER J0521+211, carried out with the High Altitude Water Cherenkov (HAWC) gamma-ray observatory. Fitting a power-law attenuated by photon-photon interaction with the extragalactic background light, we obtained a 6.2 $\sigma$ level detection for 1ES 1215+303 and a 4.3 $\sigma$ marginal detection for VER J0521+211. With the inclusion of the HAWC TeV spectrum, we built quasi-simultaneous multiwavelength spectral distributions and fitted a leptonic emission model to the observed data.

Microquasars are one of the classes of powerful Galactic particle accelerators that emit gamma rays beyond multi-TeV energies. Recently, gamma-ray emission above tens of TeV has been detected from some of these objects. The High Altitude Water Cherenkov (HAWC) observatory has previously reported gamma-ray emission with a median energy of 25 TeV from the microquasar SS 433, suggesting that gamma-ray binaries can accelerate particles to above 100 TeV inside the jets. With 2,321 days of data and better reconstruction algorithms, theHAWC observatory detected emissions above 20 TeV from two other binaries, V4641 Sagittarii and LS 5039. The V4641 Sgr is detected with a significance great than 9 sigma. It’s a low-mass X-ray binary(LMXB) that has been observed with a small-scale jet-like structure in the radio wavelength. In this talk, I will present the preliminary results from V4641 Sgr and discuss possible scenarios for gamma-ray production. We will also present future plans to search for additional X-ray binaries with HAWC.

Located in the southern field of view of the High Altitude Water Cherenkov (HAWC) observatory, the eHWC J1825-134 region is one of the most complicated gamma-ray emission sites on the galactic plane. The region contains a few PeVatron candidates that can accelerate particles up to PeV energies. Disentangling the overlapping gamma-ray emission and associating it with accelerators is crucial to understand the mechanism of cosmic-ray acceleration and gamma-ray production near the accelerators. In this talk, I will present each of the gamma-ray sources resolved in this region using 1910 days of HAWC data, including their spectra. Also, we have studied their potential association with astrophysical accelerators, the binary system LS 5039, two pulsar wind nebulae, and a young star cluster.

The number of observed Fast Radio Burst (FRB) events has grown rapidly over the last few years, but their origin remains unknown. Multiwavelength follow-ups have been encouraged by radio astronomers but the transient nature of the events makes targeted follow-ups difficult unless a source is known to repeat. A wide field-of-view instrument, such as HAWC can overcome this limitation using archival data. In this study we search for very high energy (VHE) gamma rays from FRB source locations over the largest population studied at this energy. Using data from the HAWC Observatory we look at over 200 FRB events from 141 unique locations and search for persistent emission and transient activity in 600 s surrounding the burst time. The results are then placed in context of available models and maximum gamma-ray emission levels from FRBs.

The High Altitude Water Cherenkov (HAWC) observatory is highly suitable for large-scale survey work. The high duty time (95%), large instantaneous FoV (2 sr), and sensitivity over the 300 GeV to more than 100 TeV energy range make it ideal for creating a catalog of very high energy (VHE) sources. Over the lifetime of the HAWC observatory, 4 catalogs have been produced 3 of which were constructed utilizing the full HAWC energy range while another used a restricted (>56 TeV) range. This talk will focus on the status of the planned 4HWC (full energy range) catalog including the newly developed Multi-Source Fit algorithm inspired by the Fermi Extended Source search method for the galactic plane. Using at least an additional 1000 days of data, improved event reconstruction algorithms using HAWC’s newly completed fifth pass through its dataset, and the improved search algorithm we expect to see a major improvement in the sensitivity and accuracy compared to previous catalogs. Additionally, this talk will present preliminary results from tests of the algorithm in “Benchmark” regions in HAWC data, including but not limited to, the Crab Nebula and The Cygnus Cocoon

The Cygnus Cocoon region is a complex region that contains an OB star cluster that is prominent in the TeV energy range.First observed by HEGRA as the unassociated TeV source TeV J2032+4130, follow-up observations with the High-Altitude Water Cherenkov (HAWC) observatory revealed additional complexity in the region.Previous work has found two sources: 3HWC J2031+415 and 3HWC J2020+403.3HWC J2031+415 is a significant TeV gamma-ray source whose emission is a composition of 2 sources: HAWC J2030+409, associated with the Fermi-LAT Cocoon and HAWC J2031+415, a pulsar wind nebula (PWN) possibly associated with PSR J2032+4127.3HWC J2020+403 is a single source and is associated with the supernova remnant Gamma Cygni.Using a multi-source fitting algorithm in The Multi-Mission Maximum Likelihood framework, an investigation of the TeV spectrum and very-high-energy morphology of HAWC J2031+415 is presented in this work.Additionally, X-ray observations from Suzaku are used to constrain the leptonic production of gamma rays by the PWN.

The High Altitude Water Cherenkov (HAWC) Observatory detected significant TeV gamma-ray emission from the jets of a microquasar, SS 433, in 2018. The gamma-ray emission from the powerful jets can reach up to a few tens of TeV, but the spectral studies at these energies have not been carried out. Compared to the east jet lobe, the west jet lobe is more challenging to analyze due to a higher level of contamination from nearby MGRO J1908+06 and the Galactic plane. With the most up-to-date HAWC data, the west jet lobe has over 8 sigma pre-trial significance. In this work, we use $\sim1,922$ days of HAWC data to model the source confused region around the SS 433 west jet lobe and study its spectrum between 1 and over 200 TeV.

Supernova remnant (SNR) G106.3+2.7, home to the Boomerang pulsar wind nebula (PWN), has long been thought to be a cosmic-ray PeVatron. However, its close proximity to the Boomerang PWN and the lack of gamma-ray (GR) observations above 30 TeV have made it difficult to model the nature of the emission mechanism. Recently, both the head (containing the PWN) and the tail (containing diffuse ejecta from the SN event) of the SNR have been separated by the MAGIC and Fermi-LAT observatories, giving us a glimpse into the very-high-energy (VHE) GR regime for both regions. With >6$\sigma$ detections for both the head and tail regions, the HAWC observatory is now able to extend these energy ranges past 50 TeV using new reconstruction algorithms on more than 2000 days of data. We present the multi-wavelength modeling of both the head and the tail regions, which supports a leptonic nature for the head and a lepto-hadronic nature for the tail, as well as possible sources for CR acceleration.

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations.

The perceptual complexity of intransitive adverbials, truncated passives and full passives was investigated in two experiments using rapid visual processing tasks. Both forms of passive were found to be more complex than the intransitive adverbials, presumably because of the lack of correspondence of surface and base orders. However, deletion of the logical subject in truncated passives did not increase their complexity relative to full passives.

A Dissertation submitted to the Graduate School — New Brunswick Rutgers, The State University of New Jersey in partial fulfillment of the requirements for the degree of Doctor of Philosophy

The “chip-on-sensor” concept of this detector minimizes the distance of the signal propagation from the double-sided silicon detector strips to the readout chips and thus reduces noise from strip capacitance. One half of the detector is built, the second half is being assembled at the time of writing. Prototypes have been tested in several test beams as well as in the so-called Phase 2 setup inside the detector structure. First results from a commissioning run of the Belle-II prototype SVD detector are presented. The measured signal-to-noise and timing performance are found to be according to design specifications.

This paper shows the hardware and the procedure utilized to test all components of the readout system (cables, FADC boards, junction boards) of the Belle II Silicon Vertex Detector after the series production. For the FADC board special testing hardware and firmware were designed and created to check all digital and analog inputs and outputs as well as all data interconnections on the board. The main FPGA on the FADC board generates digital signals which are converted to periodic analog differential alternating voltages up to 40 MHz on the FADC board tester, which then are fed into the analog inputs of the FADC board. Histograms and scans of the samples are recorded by using random equivalent-time sampling or sequential equivalent-time sampling, allowing to characterize the behavior of the system with a much higher bandwidth than the ADCs could do with conventional measurements. Small changes of parameters of the assembly (like using a cable of different length) lead to significant changes of the measured values, creating a sensitive testing instrument. The shapes of the distributions are analyzed and compared to references by software which then decides if a test is passed or not. The commissioning setup of the whole readout chain, with all the final components including the final detector, has been tested in three phases. The respective graphs of the signal-to-noise ratios of the strips of a detector module and histograms of the noise development of the whole detector show very high consistency of the SVD readout system.

As the use of immune checkpoint inhibitors (ICI) in cancer treatment regimens continues to rise, so has the incidence of immune-related cutaneous adverse events (irCAEs). Among irCAEs, ICI-induced scleroderma and systemic sclerosis (SSc) are rare and poorly understood. We present a case of progressive and debilitating scleroderma-like changes in a 78-year-old female being treated with durvalumab (anti-PD-L1) for squamous cell carcinoma of the lung. After 12 treatments, the patient started to develop painful skin thickening, fibrosis, and erosions of the hands, ankles, feet, and ankles that subsequently worsened after treatment completion. A full-thickness biopsy confirmed the diagnosis of fibrosing dermatitis. Laboratory values were significant for a positive homogenous ANA (1:320) and an elevated C-reactive protein. The patient’s scleroderma proceeded to involve most of her trunks, arms, and legs despite treatment with hydroxychloroquine, systemic corticosteroids, mycophenolate mofetil, intravenous immunoglobulin, and apremilast. There have been less than 10 cases of limited cutaneous and diffuse cutaneous sclerosis reported in the literature following treatment with anti-PD-1 agents. To our knowledge, this is the first case of scleroderma following anti-PD-L1 therapy. As in this patient, ICI-induced scleroderma can be recalcitrant and can significantly impact quality of life. Patients on ICIs should be carefully examined for scleroderma-like changes as early recognition and treatment initiation could reduce disease severity and lead to improved tolerance to ICIs.

An act of faith.

Microquasars with high-mass companion stars are promising very-high-energy (VHE; 0.1-100 TeV) gamma-ray emitters, but their behaviors above 10 TeV are poorly known. Using the High Altitude Water Cherenkov (HAWC) observatory, we search for excess gamma-ray emission coincident with the positions of known high-mass microquasars (HMMQs). No significant emission is observed for LS 5039, Cygnus X-1, Cygnus X-3, and SS 433 with 1,523 days of HAWC data. We set the most stringent limit above 10 TeV obtained to date on each individual source. Under the assumption that HMMQs produce gamma rays via a common mechanism, we have performed source-stacking searches, considering two different scenarios: I) gamma-ray luminosity is a fraction $\epsilon_\gamma$ of the microquasar jet luminosity, and II) very-high-energy gamma rays are produced by relativistic electrons up-scattering the radiation field of the companion star in a magnetic field $B$. We obtain $\epsilon_\gamma < 5.4\times 10^{-6}$ for scenario I, which tightly constrains models that suggest observable high-energy neutrino emission by HMMQs. In the case of scenario II, the non-detection of VHE gamma rays yields a strong magnetic field, which challenges synchrotron radiation as the dominant mechanism of the microquasar emission between 10 keV and 10 MeV.

An estimate of environmental background hit rate on triple-GEM chambers is performed using Monte Carlo (MC) simulation and compared to data taken by test chambers installed in the CMS experiment (GE1/1) during Run-2 at the Large Hadron Collider (LHC). The hit rate is measured using data collected with proton-proton collisions at 13 TeV and a luminosity of 1.5$\times10^{34}$ cm$^{-2}$ s$^{-1}$. The simulation framework uses a combination of the FLUKA and Geant4 packages to obtain the hit rate. FLUKA provides the radiation environment around the GE1/1 chambers, which is comprised of the particle flux with momentum direction and energy spectra ranging from $10^{-11}$ to $10^{4}$ MeV for neutrons, $10^{-3}$ to $10^{4}$ MeV for $\gamma$'s, $10^{-2}$ to $10^{4}$ MeV for $e^{\pm}$, and $10^{-1}$ to $10^{4}$ MeV for charged hadrons. Geant4 provides an estimate of detector response (sensitivity) based on an accurate description of detector geometry, material composition and interaction of particles with the various detector layers. The MC simulated hit rate is estimated as a function of the perpendicular distance from the beam line and agrees with data within the assigned uncertainties of 10-14.5%. This simulation framework can be used to obtain a reliable estimate of background rates expected at the High Luminosity LHC.

A major task in ground-based gamma-ray astrophysics analyses is to separate events caused by gamma rays from the overwhelming hadronic cosmic-ray background.In this talk we are interested in improving the gamma ray regime below 1 TeV, where the gamma and cosmic-ray separation becomes more difficult.Traditionally, the separation has been done in particle sampling arrays by selections on summary variables which distinguish features between the gamma and cosmic-ray air showers, though the distributions become more similar with lower energies.The structure of the HAWC observatory, however, makes it natural to interpret the charge deposition collected by the detectors as pixels in an image, which makes it an ideal case for the use of modern deep learning techniques, allowing for good performance classifers produced directly from low-level detector information.

The top quark is the most massive fundamental particle of the Standard Model of particle physics, and as the only quark to decay before hadronising gives a unique opportunity for studying QCD, the theory of the strong interaction. In this thesis, we study the tt production cross-section as a function of several variables related to the produced top quarks. This thesis presents variables defined after the hadronisation of the top quark, and so are mostly independent of its theoretical description, unlike previous results which are corrected to the partonic variables. Using the ATLAS detector at the LHC, the measurements are performed for √s = 7 TeV proton–proton collisions. The measurements are sensitive to various parameters entering the description of top quark production, including the Parton Distribution Functions, and so have good potential to be used in furthering our understanding of proton collision physics and for future tunings of the models used in describing the physics.

The Belle II experiment at the SuperKEKB asymmetric e+e− collider in Japan will operate at a luminosity approximately 50 times larger than its predecessor (Belle). At its heart lies a six-layer vertex detector comprising two layers of pixelated silicon detectors (PXD) and four layers of double-sided silicon microstrip detectors (SVD). One of the key measurements for Belle II is time-dependent CP violation asymmetry, which hinges on a precise charged-track vertex determination. Towards this goal, a proper assembly of the SVD components with precise alignment ought to be performed and the geometrical tolerances should be checked to fall within the design limits. We present an overview of the assembly procedure that is being followed, which includes the precision gluing of the SVD module components, wire-bonding of the various electrical components, and precision three dimensional coordinate measurements of the jigs used in assembly as well as of the final SVD modules.

A cosmic ride.

The Borderland organisation is based in rural north-eastern Poland, some five hours' drive from Warsaw. The organisation's mission is to harness the arts as a medium that addresses issues of cultural, national, and ethnic difference. It promotes multi-cultural education and understanding through a variety of proposals, including theatre, oral history collection, filmmaking, publishing, and conflict resolution strategies developed in response to the ethno-national animosity still very much alive in the contested region of Poland where it is located. The organisation's strategies have proven so successful that, with the support of organisations such as the EU and Ford Foundation, they have been exported to places such as the Caucuses, Bosnia and Aceh, Indonesia. Focusing on the Borderland's theatre work and its publishing division, the article explores how the organisation exploits the slippage that blurs the binary between education and training in order to achieve its goal of humanising the other. In doing so, it teases apart the differences between the two as well as draws upon the notion of experiential education championed by the educational researcher and theorist, David Kolb.

A silicon vertex detector (SVD) for the Belle-II experiment comprises four layers of double-sided silicon strip detectors (DSSDs), assembled in a ladder-like structure. Each ladder module of the outermost SVD layer has four rectangular and one trapezoidal DSSDs supported by two carbon-fiber ribs. In order to achieve a good signal-to-noise ratio and minimize material budget, a novel chip-on-sensor “Origami” method has been employed for the three rectangular sensors that are sandwiched between the backward rectangular and forward (slanted) trapezoidal sensors. This paper describes the bonding procedures developed for making electrical connections between sensors and signal fan-out flex circuits (i.e., pitch adapters), and between pitch adapters and readout chips as well as the results in terms of the achieved bonding quality and pull force.

The price of exploration.

# Outcomes and opportunities for improvement in self-inflicted blunt and penetrating trauma {#article-title-2} Self-inflicted trauma (SIT) is a public health issue ranking 4th as leading cause of death and disability in young adults. Retrospective descriptive analysis of patients admitted to a

he mandate of the Upgrade Layout Task Force was to develop a benchmark layout proposal for the ATLAS Phase-2 Upgrade Letter of Intent (LOI), due in late 2012. The work described in this note has evolved from simulation and design studies made using an earlier UTOPIA upgrade tracker layout, and experience gained from the current ATLAS Inner Detector during the first years of data taking. The layout described in this document, called the LoI-layout, will be used as a benchmark layout for the LoI and will be used for simulation and engineering studies described in the LoI.

Over the years software engineering researchers have suggested numerous techniques for estimating development effort. These techniques have been classified mainly as algorithmic, machine learning and expert judgement. Several studies have compared the prediction accuracy of those techniques, with emphasis placed on linear regression, stepwise regression, and Case-based Reasoning (CBR). To date no converging results have been obtained and we believe they may be influenced by the use of the same CBR configuration.The objective of this paper is twofold. First, to describe the application of case-based reasoning for estimating the effort for developing Web hypermedia applications. Second, comparing the prediction accuracy of different CBR configurations, using two Web hypermedia datasets.Results show that for both datasets the best estimations were obtained with weighted Euclidean distance, using either one analogy (dataset 1) or 3 analogies (dataset 2). We suggest therefore that case-based reasoning is a candidate technique for effort estimation and, with the aid of an automated environment, can be applied to Web hypermedia development effort prediction.

In order to stimulate UK based marine energy technology developers, the UK Government launched the Marine Renewables Proving Fund (MRPF) in 2009. This instrument was designed to bridge the gap between early-stage research funding and the recently-criticised Marine Renewables Deployment Fund (MRDF). This paper develops an analysis framework for policy instruments designed to support technology development. The framework is applied to the community of wave and tidal energy developers and their technical progress recorded on a scale of technology readiness levels. Ten UK public sector funding instruments are analysed within this framework, and a rationale developed for the lack of uptake of the MRDF and the likely demand for the MRPF.

Deep thoughts.

The Silicon Vertex Detector of Belle II will be fundamental not only for the reconstruction of B meson vertices, but also for the reconstruction of neutral particles like K shorts, and the tracking of low-pt particles like slow pions associated with the decays of the abundant D* mesons. As a consequence great importance is given to the performance of the software that deals with the simulation and reconstruction of the SVD events. The Belle II experiment is the successor to Belle, one of the two experiments that first observed CP violation in the decay of B mesons. The SuperKEKB collider will deliver 40 times more luminosity than its predecessor KEKB, which requires major upgrades to the detector hardware. This also poses new challenges not only for the data collection and storage, but also for the software framework which is used to process and analyse the experimental data. In this article we present in detail the SVD software framework together with its development for the test of the Vertex Detector system, which took place at DESY in April 2016 using an electron beam.