gebhart/patrepeval huggingface dataset:
Development of the 1/5 scale model of articulated boom system for in-vessel remote maintenance of Fusion Experimental Reactor (2002)

Positioning accuracy is essential in remote maintenance of in-vessel components. To develop an accurate control system, mechanical analysis with the finite element method and dynamic simulation have been carried out. Furthermore, a 1/5 scale prototype model of the boom system has been constructed to develop its control method and to verify the appropriate analysis models. The deflection and the vibration of the boom were measured actually in experiments and were compared with the results of FEM analysis. When the stiffness of joints was defined as a spring element and bolted parts of the boom were simulated in the FEM models, the results of the analysis were quite similar to that of experiments. This indicates the FEM model is appropriate. We have also performed dynamic simulations taking into account the servo control of the boom. Through these comparison, it is proved that this kind of analysis models can be applied to the full scale articulated boom system.
A Ratiometric Fluorescent Probe for Imaging of the Activity of Methionine Sulfoxide Reductase A in Cells (2016)

Methionine sulfoxide reductase A (MsrA) is an enzyme involved in redox balance and signaling, and its aberrant activity is implicated in a number of diseases (for example, Alzheimer's disease and cancer). Since there is no simple small molecule tool to monitor MsrA activity in real time in vivo, we aimed at developing one. We have designed a BODIPY-based probe called (S)-Sulfox-1, which is equipped with a reactive sulfoxide moiety. Upon reduction with a model MsrA (E. coli), it exhibits a bathochromic shift in the fluorescence maximum. This feature was utilized for the real-time ratiometric fluorescent imaging of MsrA activity in E. coli cells. Significantly, our probe is capable of capturing natural variations of the enzyme activity in vivo.
Philosophical Views: The Changing Complexion of America's Academic Research Enterprise (2002)

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Banking on iPSC- Is it Doable and is it Worthwhile (2014)

The discovery of induced pluripotent stem cells (iPSCs) and concurrent development of protocols for their cell-type specific differentiation have revolutionized studies of diseases and raised the possibility that personalized medicine may be achievable. Realizing the full potential of iPSC will require addressing the challenges inherent in obtaining appropriate cells for millions of individuals while meeting the regulatory requirements of delivering therapy and keeping costs affordable. Critical to making PSC based cell therapy widely accessible is determining which mode of cell collection, storage and distribution, will work. In this manuscript we suggest that moderate sized bank where a diverse set of lines carrying different combinations of commonly present HLA alleles are banked and differentiated cells are made available to matched recipients as need dictates may be a solution. We discuss the issues related to developing such a bank and how it could be constructed and propose a bank of selected HLA phenotypes from carefully screened healthy individuals as a solution to delivering personalized medicine.
Creating a better journey of care for patients with heart valve disease (2021)

Heart valve disease has been described as 'the next cardiac epidemic', with prevalence expected to double by 2040 and triple by 2060 due to the ageing of the population. Yet until now, it has been characterized by scarce data, limited research, and low general awareness compared with other cardiovascular diseases. Effective treatment options exist for heart valve disease, and early detection and treatment can dramatically change disease progression, improve quality of life, and reduce mortality. Unfortunately, in too many patients, heart valve disease is undetected, undiagnosed, untreated, or treated too late, leading to avoidable deaths and costs, and significant compromises to people's quality of life. These gaps in the patient pathway can be remedied through appropriate policy action, with a focus on: early detection and diagnosis; timely intervention; patient-centred follow-up care; patient engagement and empowerment; psychological support; and better data to guide practice. Ensuring all patients have access to appropriate diagnosis and care without delays is imperative as we look towards rebuilding stronger and more resilient health systems, and 'build back better' after the coronavirus disease-19 pandemic.
Self-Starting Harmonic Combs in THz Quantum Cascade Lasers (2021)

We report on high temperature, self-starting THz Quantum Cascade Laser harmonic frequency combs. Their coherence is assessed by electrical beatnote measurements and a self-mixing technique and their beatnote can be injection-locked to a RF source.
Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain (2023)

Abstract Pioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously defined the modalities of DNA interactions for the pioneer factor Pax7, we have now used natural isoforms of this pioneer as well as deletion and replacement mutants to investigate the Pax7 structural requirements for chromatin interaction and opening. We show that the GL+ natural isoform of Pax7 that has two extra amino acids within the DNA binding paired domain is unable to activate the melanotrope transcriptome and to fully activate a large subset of melanotrope-specific enhancers targeted for Pax7 pioneer action. This enhancer subset remains in the primed state rather than being fully activated, despite the GL+ isoform having similar intrinsic transcriptional activity as the GL-isoform. C-terminal deletions of Pax7 lead to the same loss of pioneer ability, with similar reduced recruitments of the cooperating TF Tpit and of the co-regulators Ash2 and BRG1. This suggests complex interrelations between the DNA binding and C-terminal domains of Pax7 that are crucial for its chromatin opening pioneer ability.
Abstract 9672: Antiplatelet Therapy and Covid-19 Outcomes in Patients With Stable Coronary Artery Disease (2021)

Introduction: Severe COVID-19 can cause acute respiratory distress syndrome (ARDS), with pulmonary pathology composed of platelet microthrombi. Antiplatelet agents have been investigated as a treatment in ARDS, but without clear evidence of benefit. The decision on antiplatelet use in patients with COVID-19 and coronary artery disease (CAD) is key. Hypothesis: We assessed the hypothesis that increased use of antiplatelet therapy was associated with no worse clinical outcomes in COVID-19 among adults with stable CAD. Methods: We performed a retrospective cohort study of patients who presented with COVID-19 to two New York City hospitals from March 3 to May 15, 2020. Patients were separated into groups based on antiplatelet use, including no outpatient antiplatelet use, monotherapy, and dual antiplatelet therapy (DAPT). Outcomes and complications were compared among the groups, using propensity scoring with inverse probability of treatment weighting. Results: This study included 315 patients with stable CAD and COVID-19. Patients on no outpatient antiplatelet therapy were significantly older and more likely to be taking anticoagulation, while patients on DAPT had the highest rates of diabetes and chronic kidney disease. The most prescribed antiplatelet in the cohort was aspirin (72.1%) followed by clopidogrel (22.5%). There was no difference in COVID-19 admission mortality between the DAPT and monotherapy groups (DAPT 27.9%, monotherapy 27.2%, p=NS). Patients on DAPT had decreased rates of venous thromboembolism compared to monotherapy (DAPT 0.0%, monotherapy 6.4%, p=0.01), and bleeding rates were similar. The rate of home monotherapy continuation in hospital was 79.9%, with the most common reasons for discontinuation being hemorrhage, anemia, and thrombocytopenia. No outpatient antiplatelet use was a high-risk group, with the highest rates of intensive care admissions, intubations and mortality. Conclusions: In conclusion, we found no difference in COVID-19 outcomes for CAD patients on DAPT compared to those on monotherapy. There were decreased clotting complications in patients on more antiplatelet therapy, while bleeding rates were similar. No outpatient antiplatelet use was found to be a high-risk group in COVID-19.
A SEM and non‐contact surface white light profilometry <i>in vivo</i> study of the effect of a crème containing CPP‐ACP and fluoride on young etched enamel (2013)

The aim of this in vivo study was to evaluate the short and a longer term effect on enamel of the application of a crème containing 10% CPP-ACP and 900 ppm fluoride, in orthodontically planned, high caries-risk patients. Epoxy resin replicas of upper lateral incisors were obtained from polyvinyl siloxane (PVS) impressions, before and after etching. The right incisors were left untreated in order to control saliva remineralizing potential. The upper left surfaces were coated with a pea-size amount of the crème. Replicas were obtained at 3 weeks and 6 months and analyzed by SEM and non-contact surface white light profilometry. In the treated sample the profilometric roughness parameters at 3 weeks were statistically significantly lower than the control group values (p < 0.05). At 3 weeks SEM images of the enamel surface showed fewer irregularities. After 6 months, differences between test and control groups were not present on SEM images and profilometric values. CPP-ACP and fluoride crème had positive in vivo effects on enamel surfaces. Significant differences in surface roughness existed after a 3-week period of crème use.
Current injection for field decay compensation in NMR spectrometer magnets (2002)

Current injection is a method to compensate for field drift in persistent nuclear magnetic resonance spectrometer magnets by the direct introduction of incremental current into the magnet through leads attached across a portion of the windings. An applied current ramp will distribute among the sections of the windings defined by the placement of the leads according to the inductance of the circuit. As a result, a current ramp trough leads placed across an inner coil will flow primarily in that coil. The field created by the injection current may be used to cancel a quasi-persistent field decay. The injection current required for the field decay compensation is determined as a function of magnet parameters and decay rate. The drift in field uniformity that results with current injection is found to be proportional to the field decay that is compensated, the drift and the decay being related by a quantity termed the dynamic uniformity; The field uniformity drift is quantified for an example magnet design; showing that the drift in field uniformity can be significant in the context of high resolution spectroscopy. Methods that facilitate shimming, such as gradient shimming, are identified as a natural compliment to current injection.
Enabling Fair Pricing on High Performance Computer Systems with Node Sharing (2014)

Co-location, where multiple jobs share compute nodes in large-scale HPC systems, has been shown to increase aggregate throughput and energy efficiency by 10–20%. However, system operators disallow co-location due to fair-pricing concerns, i.e., a pricing mechanism that considers performance interference from co-running jobs. In the current pricing model, application execution time determines the price, which results in unfair prices paid by the minority of users whose jobs suffer from co-location. This paper presents POPPA, a runtime system that enables fair pricing by delivering precise online interference detection and facilitates the adoption of supercomputers with co-locations. POPPA leverages a novel shutter mechanism – a cyclic, fine-grained interference sampling mechanism to accurately deduce the interference between co-runners – to provide unbiased pricing of jobs that share nodes. POPPA is able to quantify inter-application interference within 4% mean absolute error on a variety of co-located benchmark and real scientific workloads.
3D light sheet fluorescence microscopy of lungs to dissect local host immune - <i>Aspergillus fumigatus</i> interactions (2019)

ABSTRACT Aspergillus fumigatus is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment and progression are highly complex and depend on both fungal attributes and the immune status of the host. Therefore, preclinical animal models are paramount to investigate and gain better insight into the infection process. Yet, despite their extensive use, commonly employed murine models of invasive pulmonary aspergillosis are not well understood due to analytical limitations. Here we present quantitative light sheet fluorescence microscopy (LSFM) to describe fungal growth and the local immune response in whole lungs at cellular resolution within its anatomical context. We analyzed three very common murine models of pulmonary aspergillosis based on immunosuppression with corticosteroids, chemotherapy-induced leukopenia or myeloablative irradiation. LSFM uncovered distinct architectures of fungal growth and degrees of tissue invasion in each model. Furthermore, LSFM revealed the spatial distribution, interaction and activation of two key immune cell populations in antifungal defense: alveolar macrophages and polymorphonuclear neutrophils. Interestingly, the patterns of fungal growth correlated with the detected effects of the immunosuppressive regimens on the local immune cell populations. Moreover, LSFM demonstrates that the commonly used intranasal route of spore administration did not result in the desired intra-alveolar deposition, as more than 60% of fungal growth occurred outside of the alveolar space. Hence, LSFM allows for more rigorous characterization of murine models of invasive pulmonary aspergillosis and pinpointing their strengths and limitations. IMPORTANCE The use of animal models of infection is essential to advance our understanding of complex host-pathogen interactions that take place during Aspergillus fumigatus lung infections. As in the case of humans, mice need to be immunosuppressed to become susceptible to invasive pulmonary aspergillosis, the most serious infection caused by A. fumigatus . There are several immunosuppressive regimens that are routinely used to investigate fungal growth and/or immune responses in murine models of invasive pulmonary aspergillosis (IPA). However, the precise consequences that each immunosuppressive model has on the local immune populations and for fungal growth are not completely understood. Here we employed light sheet fluorescence microscopy (LSFM) to analyze whole lungs at cellular resolution, to pin down the scenario commonly used IPA models. Our results will be valuable to optimize and refine animal models to maximize their use in future research. VISUAL ABSTRACT Quantitative light sheet fluorescence microscopy to dissect local host-pathogen interactions in the lung after A. fumigatus airway infection.
B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models (2020)

Animal models of human antigen-specific B cell receptors (BCRs) generally depend on "inferred germline" sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three BCR knockin mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs). The germline-targeting HIV immunogen eOD-GT8 60mer is currently in clinical trial as a candidate bnAb vaccine priming immunogen. To attempt to model human immune responses to the eOD-GT8 60mer, we tested each authentic naive human VRC01-class BCR mouse model under rare human physiological B cell precursor frequency conditions. B cells with high (HuGL18<sup>HL</sup>) or medium (HuGL17<sup>HL</sup>) affinity BCRs were primed, recruited to germinal centers, and they affinity matured, and formed memory B cells. Precursor frequency and affinity interdependently influenced responses. Taken together, these experiments utilizing authentic naive human VRC01-class BCRs validate a central tenet of germline-targeting vaccine design and extend the overall concept of the reverse vaccinology approach to vaccine development.
Synthetic studies targeted at the cytotoxic 8,9-seco-ent-kaurene diterpenes. Concise complementary stereocontrolled construction of the bridgehead olefin core (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic studies targeted at the cytotoxic 8,9-seco-ent-kaurene diterpenes. Concise complementary stereocontrolled construction of the bridgehead olefin coreLeo A. Paquette and Gaetan LadouceurCite this: J. Org. Chem. 1989, 54, 18, 4278–4279Publication Date (Print):September 1, 1989Publication History Published online1 May 2002Published inissue 1 September 1989https://pubs.acs.org/doi/10.1021/jo00279a010https://doi.org/10.1021/jo00279a010research-articleACS PublicationsRequest reuse permissionsArticle Views656Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Loss of heterozygosity of essential genes represents a widespread class of potential cancer vulnerabilities (2020)

Alterations in non-driver genes represent an emerging class of potential therapeutic targets in cancer. Hundreds to thousands of non-driver genes undergo loss of heterozygosity (LOH) events per tumor, generating discrete differences between tumor and normal cells. Here we interrogate LOH of polymorphisms in essential genes as a novel class of therapeutic targets. We hypothesized that monoallelic inactivation of the allele retained in tumors can selectively kill cancer cells but not somatic cells, which retain both alleles. We identified 5664 variants in 1278 essential genes that undergo LOH in cancer and evaluated the potential for each to be targeted using allele-specific gene-editing, RNAi, or small-molecule approaches. We further show that allele-specific inactivation of either of two essential genes (PRIM1 and EXOSC8) reduces growth of cells harboring that allele, while cells harboring the non-targeted allele remain intact. We conclude that LOH of essential genes represents a rich class of non-driver cancer vulnerabilities.
Leader Election and Shape Formation with Self-Organizing Programmable\n Matter (2015)

We consider programmable matter consisting of simple computational elements,\ncalled particles, that can establish and release bonds and can actively move in\na self-organized way, and we investigate the feasibility of solving fundamental\nproblems relevant for programmable matter. As a suitable model for such\nself-organizing particle systems, we will use a generalization of the geometric\namoebot model first proposed in SPAA 2014. Based on the geometric model, we\npresent efficient local-control algorithms for leader election and line\nformation requiring only particles with constant size memory, and we also\ndiscuss the limitations of solving these problems within the general amoebot\nmodel.\n
Hydrolysis in 2′-chloro-2′-deoxy nucleosides, -nucleotides and -polynucleotides to a rabinose-derivatives (1975)

The rate of hydrolysis of 2'-chloro-2'-deoxycytidine and -uridine, and their 5'-phosphates, -diphosphates and polymers to the corresponding arabinocytidine and arabinouridine derivatives in the presence of Tris-HCL pH 8.9 is determined. This rate is highest for the nucleosides, less for the 5'-phosphates and 5'-diphosphates and even less for the polynucleotides. In the the 2'-chloro-2'-deoxyuridine series the O2, 2'-cyclonucleoside was formed in addition to the arabinonucleoside.
Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis (2009)

Although the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identification and isolation of SC from normal and malignant colon. Accordingly, aldehyde dehydrogenase 1 (ALDH1) was investigated as a possible marker for identifying colonic SC and for tracking them during cancer progression. Immunostaining showed that ALDH1(+) cells are sparse and limited to the normal crypt bottom, where SCs reside. During progression from normal epithelium to mutant (APC) epithelium to adenoma, ALDH1(+) cells increased in number and became distributed farther up the crypt. CD133(+) and CD44(+) cells, which are more numerous and broadly distributed in normal crypts, showed similar changes during tumorigenesis. Flow cytometric isolation of cancer cells based on enzymatic activity of ALDH (Aldefluor assay) and implantation of these cells in nonobese diabetic-severe combined immunodeficient mice (a) generated xenograft tumors (Aldefluor(-) cells did not), (b) generated them after implanting as few as 25 cells, and (c) generated them dose dependently. Further isolation of cancer cells using a second marker (CD44(+) or CD133(+) serially) only modestly increased enrichment based on tumor-initiating ability. Thus, ALDH1 seems to be a specific marker for identifying, isolating, and tracking human colonic SC during CRC development. These findings also support our original hypothesis, derived previously from mathematical modeling of crypt dynamics, that progressive colonic SC overpopulation occurs during colon tumorigenesis and drives CRC development.
Energy Efficiency of a Quadruped Robot with Neuro-Inspired Control in Complex Environments (2021)

This paper proposes an analysis of the energy efficiency of a small quadruped robotic structure, designed based on the MIT Mini Cheetah, controlled using a central pattern generator based on the FitzHugh–Nagumo neuron. The robot’s performance evaluated on structurally complex terrain in a dynamic simulation environment is compared with other robotic structures on wheels and with hybrid architectures. The energy cost involved in carrying out an assigned task involving the need to traverse uneven terrain is calculated as a relevant index to be taken into account. In particular, simple control strategies impacting the leg trajectories are taken into account as the main factors affecting the energy efficiency in different terrain configurations. The adaptation of the leg trajectories is evaluated depending on the terrain characteristics, improving the locomotion performance.