gebhart/patrepeval huggingface dataset:
P45 Is it important to identify an isolated right aortic arch in fetal life? (2016)

<h3>Background</h3> Isolated right aortic arch (RAA) is felt to be a rare finding, present in around 0.1%. The 3 vessel and tracheal view has been part of the fetal medicine departmental screening since 1998 and has now been incorporated into the national screening guidelines. The objective is to define the prenatal associations and postnatal outcomes of fetuses diagnosed with a RAA in utero. <h3>Methods</h3> Retrospective analysis of fetuses diagnosed with an isolated RAA diagnosed at the Harris Birthright Centre for Fetal Medicine between 2000 and 2014. Prenatal and postnatal findings were ascertained from clinical records. Diagnosis of RAA was made in the transverse three-vessel/tracheal view where the aortic arch was demonstrated passing in front of the trachea.(Figure 1) Prenatal data were combined with outcomes obtained from medical records and telephone interviews with patients. <h3>Results</h3> 100 cases of isolated right aortic arch were identified in fetal life at a median gestation of 21weeks (range:11–36). The nuchal translucency (NT) was elevated in 10/64 (16%) where the measurement was known and an extracardiac abnormality detected in 23/100 cases of whom 2 had a raised NT. Genetic abnormalities were confirmed in 13/58 (21%) tested cases comprising: 22q11.2 microdeletion (n = 5), trisomy 21 (n = 2), combined 22q11 microdeletion with mosaicism of 45XO (n = 1), unbalanced translocation (n = 1), balanced translocation (n = 1), duplication of chromosome 16p13 with a recessive disorder of lymphogenesis (n = 1) and other syndromes (n = 3). Of those with abnormal genetics 4/13 had no other abnormal fetal sonographic markers. An aberrant left subclavian artery (ALSCA) was identified in 39/98 (40%), the arterial duct was left sided in 67/75 (89%). In the postnatal period, 3 cases were diagnosed with a double aortic arch. Spontaneous intrauterine death occurred in 6 cases and termination of pregnancy in 9 cases. There were 80 live births and one neonatal death. Five children presented with symptoms of airway obstruction at a median age of 2.9 years (range 1–8). Pulsatile airway compression was identified in all and surgical division of the vascular ring was performed at median age: 2.9years (range: 1–8). Within the past two years, three asymptomatic infants (with RAA, ALSCA, left arterial duct) have been shown by bronchoscopy and cross-sectional imaging to have significant airways compression. Thus, we are currently considering whether all infants with RAA, ALSCA and left duct merit investigation irrespective of symptoms. <h3>Conclusions</h3> Significant genetic abnormalities were identified of which some had no other abnormal fetal sonographic findings. Many patients were discharged after their first postnatal review, but despite this 8 children have required surgical relief of a vascular ring as a result of pulsatile compression of the trachea. Lack of symptoms does not exclude significant airways compression and the true incidence of airway compromise may be underestimated.
Do, or should, all human decisions conform to the norms of a consumer-oriented culture? (1994)

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P4‐023: CLINICAL TRIAL DESIGN FOR A PHASE II, RANDOMIZED, PLACEBO‐CONTROLLED TRIAL OF AMX0035 IN ALZHEIMER'S DISEASE (2019)

Amylyx has developed a novel therapeutic, AMX0035, for the treatment of neurodegenerative disease. AMX0035 is a proprietary combination of two small molecule compounds, Sodium Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), designed to promote neuronal viability through simultaneous inhibition of ER stress and mitochondrial stress. PB and TUDCA have been evaluated separately in in vitro and in vivo models of Alzheimer's disease (AD), and clinical trials in amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. Amylyx discovered a synergy between these two compounds when administered together in a particular range of ratios across multiple preclinical models. Recruitment for the clinical trial began in late 2018. The study will evaluate safety, tolerability, and biomarkers of molecular target engagement, AD pathology, neurodegeneration and neurophysiology that indicate AMX0035 target engagement and neurobiological effects over 24 weeks. This will be a 6-month, parallel-group, randomized, double-blind, placebo-controlled study of people with late mild cognitive impairment (MCI) or early to moderate dementia due to AD. Participants in the active treatment arm will receive 3g of PB and 1g TUDCA administered orally twice daily. Participants will be evaluated at baseline and at week 24 with multi-sequence structural and functional MRI to assess changes in regional brain volumes (T1), cerebral perfusion (ASL), functional connectivity (BOLD) and cerebrovascular pathology (FLAIR, SWI). Lumbar punctures will be performed at baseline and 24 weeks for selected CSF biomarkers including: amyloid-β1-42, tau, neurofilament light chain (NfL), and markers of mitochondrial redox, HDAC activity, neuronal injury, and neuroinflammation. Patients will be evaluated at weeks 1, 6, 12, 18, and 24 for safety, tolerability, and changes in symptoms, as measured with the ADAS-Cog 13, ADCS-ADL, and NPI. This early phase trial is designed to evince target engagement, neurobiological effects, safety and tolerability of AMX0035 with multiple objective endpoints including, standard clinical assessments and both established and novel biomarkers associated with neurocognitive impairment. Data will help determine whether to advance AMX0035 to a larger study to establish efficacy and safety and inform choices in study design, patient characteristics and outcome measures.
Application of antihelix antibodies in protein structure determination (2019)

Antibodies are indispensable tools in protein engineering and structural biology. Antibodies suitable for structural studies should recognize the 3-dimensional (3D) conformations of target proteins. Generating such antibodies and characterizing their complexes with antigens take a significant amount of time and effort. Here, we show that we can expand the application of well-characterized antibodies by "transplanting" the epitopes that they recognize to proteins with completely different structures and sequences. Previously, several antibodies have been shown to recognize the alpha-helical conformation of antigenic peptides. We demonstrate that these antibodies can be made to bind to a variety of unrelated "off-target" proteins by modifying amino acids in the preexisting alpha helices of such proteins. Using X-ray crystallography, we determined the structures of the engineered protein-antibody complexes. All of the antibodies bound to the epitope-transplanted proteins, forming accurately predictable structures. Furthermore, we showed that binding of these antihelix antibodies to the engineered target proteins can modulate their catalytic activities by trapping them in selected functional states. Our method is simple and efficient, and it will have applications in protein X-ray crystallography, electron microscopy, and nanotechnology.
Assessment of the performance of laser-based lateral-crystallization technology via analysis and modeling of polysilicon thin-film-transistor mobility (2003)

In this work, we present a comprehensive set of mobility data for poly-Si thin-film-transistors (TFTs), laser-crystallized by sequential-lateral-solidification. We studied the effect of film thickness and device orientation and employed mobility measurements over a wide temperature range to evaluate how the crystal quality of laterally-crystallized (LC) poly-Si films is affected by various process-related factors. Based on this evaluation, we proposed a simple mobility model introducing crystal-defect scattering as an additional scattering mechanism affecting the TFT mobility. The sub-boundary spacing was used as a measure of the crystal quality of the LC poly-Si material and as the main variable for the purposes of modeling crystal-defect scattering. The model was found to account correctly for the experimentally observed mobility variation and yield a reasonable agreement with a wide variety of independent data. Observed inconsistencies between model predictions and some literature data were discussed in terms of an additional factor that was assumed to be laser-process specific. This factor was speculated to relate to the heating/cooling rate of the film, which drives the material propensity for defect generation. In that sense, excimer-laser-based lateral crystallization appears to enable more control over the poly-Si material crystal quality, hence, seems most effective in producing the highest performance LP poly-Si TFTs, with the most uniform characteristics.
Review of The Princeton Dante Project (2.0) (2011)

Founded by Dr. Robert Hollander, The Princeton Dante Project (2.0) (PDP) is a well-funded project that has received internal funding from Princeton University and external support from the Andrew W. Mellon Foundation, the Gladys Krieble Delmas Foundation, the Edward T. Cone Foundation, and The Clover Foundation. The PDP has also benefited from two generous gifts from Princeton alumni George Castell and Paul Gridley.
Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program (2015)

Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.
Ω-Gate Nanowire Transistors Realized by Sidewall Image Transfer Patterning: 35nm Channel Pitch and Opportunities for Stacked-Nanowires Architectures (2015)

2015 International Conference on Solid State Devices and Materials,Ω-Gate Nanowire Transistors Realized by Sidewall Image Transfer Patterning: 35nm Channel Pitch and Opportunities for Stacked-Nanowires Architectures
Seeing shapes in clouds: On the performance-cost trade-off for heterogeneous infrastructure-as-a-service (2015)

In the near future FPGAs will be available by the hour, however this new Infrastructure as a Service (IaaS) usage mode presents both an opportunity and a challenge: The opportunity is that programmers can potentially trade resources for performance on a much larger scale, for much shorter periods of time than before. The challenge is in finding and traversing the trade-off for heterogeneous IaaS that guarantees increased resources result in the greatest possible increased performance. Such a trade-off is Pareto optimal. The Pareto optimal trade-off for clusters of heterogeneous resources can be found by solving multiple, multi-objective optimisation problems, resulting in an optimal allocation of tasks to the available platforms. Solving these optimisation programs can be done using simple heuristic approaches or formal Mixed Integer Linear Programming (MILP) techniques. When pricing 128 financial options using a Monte Carlo algorithm upon a heterogeneous cluster of Multicore CPU, GPU and FPGA platforms, the MILP approach produces a trade-off that is up to 110% faster than a heuristic approach, and over 50% cheaper. These results suggest that high quality performance-resource trade-offs of heterogeneous IaaS are best realised through a formal optimisation approach.
Ga+ focused ion beam lithography as a viable alternative for multiple fin field effect transistor prototyping (2016)

A novel method for fast and flexible fin field effect transistor (FinFET) prototyping using a Ga+ focused ion beam is presented. The fin width and height control is explored, aiming for the successful fabrication of prototypes. This method results in fins with negligible Ga incorporation, when compared to traditional focused ion beam milling techniques. Our method for multiple fin FinFET prototyping enables advanced device fabrication and great flexibility regarding both the number of fins and fin width. Working FinFET prototypes have been fabricated using the proposed fin definition method, and the electrical characterization is discussed.
ChAsE: chromatin analysis and exploration tool (2016)

Software, source code (MIT License), data and video tutorials available at http://chase.cs.univie.ac.at CONTACT: : mkarimi@brc.ubc.ca or torsten.moeller@univie.ac.atSupplementary information: Supplementary data are available at Bioinformatics online.
Effects of cardiac tamponade on colonic hemodynamics and oxygen uptake (1983)

The local hemodynamic response of the innervated but vascularly isolated colon to decreased systemic perfusion induced by cardiac tamponade was studied in anesthesized dogs as a model of nonocclusive mesenteric ischemia. Increasing levels of pericardial pressure caused progressive decreases in colonic blood flow associated with substantial increases in colonic vascular resistance. These increases in local colonic resistance were proportionately larger than concurrent increases in systemic resistance. The disproportionate response of the colonic resistance vessels was not diminished by colonic (sympathetic) denervation. Reductions of blood flow to 30 ml . min-1 . 100 g-1 resulted in compensatory increases in colonic oxygen extraction such that colonic oxygen consumption remained constant (flow independent) at about 1.5 ml . min-1 . 100 g-1. At blood flows below 30 ml . min-1 . 100 g-1 colonic oxygen consumption was markedly dependent on blood flow. This fundamental relation of colonic oxygen consumption to blood flow was the same whether ischemia was induced by cardiac tamponade, partial mechanical arterial occlusion, or vasoconstrictor (norepinephrine or digoxin) infusion. Furthermore, this relationship was not altered by vasodilation with isoproterenol after the induction of ischemia by any of the above means.
A Low-frequency Passive Seismic Survey in Libya (2009)

Low frequency (~1-6Hz) microtremor signals have been measured at the surface in many locations around the world over hydrocarbon reservoirs (multiphase fluid systems in porous media). These low frequency microtremors are observable as modifications of the frequency domain character of passive seismic records. The anomalies in the data spectra possess remarkably similar characteristics, pointing to a common source mechanism, even though depth, hydrocarbon type and matrix rock vary across the complete geological spectrum. Herein we describe observations from a low frequency passive seismic survey over a shallow reservoir in Libya. Specific conditions of the ambient wave field are discussed in detail. In this data set we observe that the magnitude of the hydrocarbon signal can be proportional to the diurnal variations in the total energy of the seismic background.
Evaluation of in vitro hematotoxicity of c-1311, mitoxantrone and oxaliplatin to FU-GM committed neutrophil-monocyte progenitors from human and rat. (2004)

2110 C-1311 is a member of the relatively large and as yet underutilized imidazoacridinone anticancer drug family. Its structure is closely related to mitoxantrone (Novantrone) and losoxantrone (DuP-941). Xanthus Life Sciences Inc. has advanced C-1311 to phase I clinical trials in solid tumor patients. This study characterizes the in vitro sensitivity of committed neutrophil progenitors from rat and human bone marrow (named CFU-GM) to the toxic effects of continuous exposure C-1311. Human and rat CFU-GM exhibited equivalent susceptibility to C-1311 toxicity: IC 90 ±SD for human CFU-GM was 7.8±1.5 ng/mL and for rat 5.8±0.3 ng/mL (p=0.12). Toxicity of two positive control compounds was also evaluated: mitoxantrone as a positive control for C-1311’s therapeutic class and oxaliplatin (Eloxatin) as a positive control for a successful cytotoxic drug for colon carcinoma in man. Mitoxantrone showed greater toxicity to human than rat CFU-GM than was expected from MTD differentials, which may indicate higher plasma protein binding in man than rat. The IC 90 ±SD for human CFU-GM was 0.23±0.05 ng/mL and for rat 1.69±0.023 ng/mL (p=0.00080). Human CFU-GM tolerated higher concentrations of oxaliplatin than rat CFU-GM, which explains its surprisingly good clinical effectiveness: IC 90 ±SD for human CFU-GM was 2332±269 ng/mL and for rat 211±9 ng/mL (p=0.0052). Mitoxantrone and oxaliplatin are FDA approved drugs, proving that differential sensitivity between human and animal CFU-GM is not the sole determinant of clinical success or failure. In the past, the CFU-GM assay has consistently identified cytotoxic anticancer agents that are more toxic in man than mouse. Equivalent susceptibility of human and rat CFU-GM to C-1311 toxicity indicates that the structural modifications made in the anthracenedione pharmacophore to generate C-1311 improved CFU-GM tolerability more in man than rat and eliminated the species difference in tolerance seen with mitoxantrone. CFU-GM testing predicts a clinical MTD for C-1311 of 81 mg/m 2 /d qdx5 (range 20–320, given ±4-fold accuracy of the model), assuming neutropenia will be dose-limiting in both species; C-1311, not a biologically active metabolite, will be the marrow toxicant; and plasma protein binding will be equivalent in rat and man. If neutropenia is not dose-limiting in man, then the predicted human MTD from the in vitro data will become the upper limit on human tolerability. Recent studies demonstrating that C-1311 has superior efficacy over oxaliplatin in preclinical models suggest C-1311 might fare well in head-to-head clinical trials in colorectal carcinoma, where oxaliplatin doses would be higher than in rodent models, but C-1311 doses would likely not be any higher.
CMOS image sensor camera with focal plane edge detection (2002)

We present a simple, yet robust, VLSI implementation of sampled-method edge detection. Our technique adopts the well-known correlated double sampling (CDS), usually used for fixed pattern noise (FPN) reduction, to perform a sampled differentiation of the captured image to detect visual edges. This circuit is usually an integral part of most CMOS image sensors; therefore no additional area is required to include the proposed edge detection functionality in the image sensor. The imager array was implemented using active pixel sensor (APS) technology with dual mode of operation: a logarithmic (continuous) mode with wide optical dynamic range and a linear (integrating) mode with higher image quality. The real-time edge detection was demonstrated in the both modes of operation. This technique can be easily extended to perform temporal differentiation, providing a simple method for motion detection. The prototype chip was fabricated using standard 0.5 /spl mu/m CMOS process with an array of 64/spl times/64 pixels and pixel size of 30/spl times/30 /spl mu/m. The fill factor is /spl sim/60% and the system working voltage is 3.3 V. Results indicate that the proposed architecture is suitable for applications such as security, and industrial inspection, where integrated functionalities are advantageous.
Prioritization of technical content and impact assessment for changes to performance assessment at the Waste Isolation Pilot Plant (WIPP). (2008)

Waste Isolation Pilot Plant (WIPP) performance assessment consists of twenty-four conceptual models that are used to describe repository performance during the 10,000 year regulatory time period following closure of the facility. Following the recertification of the repository in March of 2006, Sandia National Laboratories and the U. S. Department of Energy (DOE) began a set of activities to identify which models could be improved and updated by inclusion of data from recent repository investigations. Sandia initiated this process by conducting a review of the performance assessment models to determine which models should be updated. Sandia provided the DOE with a list of recommendations, and after discussions with the DOE, Sandia proceeded with a set of scoping calculations to identify the impacts of these changes on modeling repository performance. This paper describes the methodology that Sandia used to determine which changes should be proposed and the impact of some of these changes on estimates of radionuclide releases that could occur in the event of inadvertent human intrusion into the repository. This paper is the first in a series of papers about the proposed changes. The other papers detail the specific changes and the justification for those changes to the models and parameters.
Irradiated and Activated Autologous PBMCs Induce Expansion of Highly Cytotoxic Human NK Cells In Vitro (2013)

Adoptive cell transfer of ex vivo-activated natural killer (NK) cells is a promising therapy for cancer treatment. Because of inhibitory signaling through killer immunoglobulin-like receptor (KIR)-KIR ligands, KIR-mismatched allogeneic NK cell transfer is considered to be a more effective strategy than is autologous transfer. However, purified NK cells do not expand well enough in vitro with good manufacturing practice-compliant components for clinical use. Some investigators have developed selective expansion of NK cells from peripheral blood mononuclear cells, but these cells have the risk of graft-versus-host disease in allogeneic settings because of T cells contamination. In this study, we developed a novel method for NK cell activation and expansion. Using only good manufacturing practice-compliant components and autologous feeder cells, once purified NK cells were effectively expanded (2500-fold at day 17). The expanded cells were highly purified NK cells, and the use of these cells is suitable for allogeneic transfer without the risk of graft-versus-host disease induction. Importantly, the expanded NK cells also showed enhanced cytotoxicity compared with NK cells conventionally expanded by recombinant human interleukin 2. Finally, induction of NKG2D ligand expression on feeder cells implies that the NKG2D-NKG2DL interaction may play a role in NK cell expansion. In conclusion, this method can be used to obtain NK cells for more successful allogeneic NK cell adoptive transfer for use in antitumor immune therapy.
Genetic Improvement of Software: A Comprehensive Survey (2017)

Genetic improvement (GI) uses automated search to find improved versions of existing software. We present a comprehensive survey of this nascent field of research with a focus on the core papers in the area published between 1995 and 2015. We identified core publications including empirical studies, 96% of which use evolutionary algorithms (genetic programming in particular). Although we can trace the foundations of GI back to the origins of computer science itself, our analysis reveals a significant upsurge in activity since 2012. GI has resulted in dramatic performance improvements for a diverse set of properties such as execution time, energy and memory consumption, as well as results for fixing and extending existing system functionality. Moreover, we present examples of research work that lies on the boundary between GI and other areas, such as program transformation, approximate computing, and software repair, with the intention of encouraging further exchange of ideas between researchers in these fields.