gebhart/patrepeval huggingface dataset:
Genotype-Guided Statin Therapy (2010)

One of the promises of the Human Genome Project is individualization of patient care based on highly heterogeneous innate metabolic factors determined by DNA typing of gene polymorphisms. Translation of such gene polymorphisms into clinical decision support for personalized healthcare is the basis for DNA guided medicine. Pharmacogenetics serves as the foundation for the most clinically advanced application of DNA-guided medicine. Statin responsiveness is an area of high research interest given the success of the drug class in the treatment of hypercholesterolemia and in primary and secondary prevention of cardiovascular disease. Ongoing genetic inquiry into response variability indicates probable multigenic determinants for statin efficacy and safety. It is the vision that knowledge of the patient’s genetic status for a number of common variants will soon guide hyperlipidemic intervention.
Perceptual learning can modify blur discrimination mechanisms directly and generalize to improvement of visual acuity. (2022)

Perceptual learning (PL) can improve visual functions, including vision sharpness, in adults with poor vision due to abnormal development (amblyopia) or blurred input due to uncorrected refractive error (presbyopia, myopia). The ability of the brain to perform "de-blurring" of highly blurred images following PL is not fully understood. One hypothesis is that improved blur discrimination is the result of improved contrast discrimination. However, there may be separate mechanisms for blur and contrast discrimination (Morgan 2017), therefore improved contrast discrimination may not fully underlie improved and blur discrimination. This study explored the effect of PL on blur discrimination without contrast cues. The participants (n=9, median age 24) were corrected-to-normal or uncorrected myopes. Participants were asked to discriminate between two Gaussian blurred circles using a temporal 2IFC paradigm. One interval (the reference) had a constant blur standard deviation (6 arcmin) and the other (the test) interval had one of 11 different blur levels; 5 increments, 5 decrements and one equal to the reference. Contrast jitter was applied to both reference and test intervals to minimize any contrast cues. All blur levels were intermixed. Training sessions (6-8) lasting about 20 minutes, consisted of 40 trials per condition (total 440). Participants were pre- and post-tested on both higher and lower reference blur levels and on visual acuity. Blur discrimination thresholds improved in the trained eye and transferred to the untrained eye. The improved blur discrimination also transferred to both higher (8 arcmin) and lower (4.5 arcmin) reference blur levels, and visual acuity improved by, on average, 1.2 lines. Participants with uncorrected or not fully corrected myopia showed improvement in blur discrimination thresholds and improved visual acuity following blur training. Our results show that improved blur discrimination without contrast cues transferred to improved visual acuity, suggesting that PL can modify blur discrimination mechanisms directly.
Mitigation of voltage collapse through active dynamic buffers (2006)

Power electronics continues to grow as an element of electrical loads. Most such loads, including motor drives, computer power supplies, and compact fluorescent lighting, serve to 'isolate' the load dynamics from the utility grid. The unfortunate effect is that these loads enforce local constant power behaviour. This tends to destabilise the supply system, resulting in voltage collapse. In this work, the power buffering technique is examined to mitigate the effects of constant power loads. A power buffer is a device that enforces dynamic isolation to bestow beneficial dynamic characteristics upon the grid. A review of constant-power load dynamics and weak power systems is presented. Through simulations, the generalised power buffer concept is shown to stabilise several examples of power systems. Various techniques and topologies for power buffers are then covered and related to the voltage collapse problem, including critical control methods and parameters. Finally, three experiments are presented that demonstrate the stabilising effects of buffers.
Bryostatins : The Asymmetric Synthesis of the C17-C27Fragment (1994)

Disconnection at C20-C21 leads to two fragments. The C21-C27 fragment is constructed from D-isoburyl lactate via chelationcontrolled allylation. The C17-C20 fragment is obtained from D-pantolactone.
Reduction of residual dipolar interaction in cartilage by spin‐lock technique (2004)

The influence of radiofrequency (RF) spin-lock pulse on the laminar appearance of articular cartilage in MR images was investigated. Spin-lock MRI experiments were performed on bovine cartilage plugs on a 4.7 Tesla small-bore MRI scanner, and on human knee cartilage in vivo on a 1.5 Tesla clinical scanner. When the normal to the surface of cartilage was parallel to B0, a typical laminar appearance was exhibited in T2-weighted images of cartilage plugs, but was absent in T1rho-weighted images of the same plugs. At the "magic angle" orientation (when the normal to the surface of cartilage was 54.7 degrees with respect to B0), neither the T2 nor the T1rho images demonstrated laminae. At the same time, T1rho values were greater than T2 at both orientations throughout the cartilage. T1rho dispersion (i.e., the dependence of the relaxation rate on the spin-lock frequency omega1) was observed, which reached a steady-state value of close to 2 kHz in both parallel and magic-angle orientations. These results suggest that residual dipolar interaction from motionally-restricted water and relaxation processes, such as chemical exchange, contribute to T1rho dispersion in cartilage. Further, one can reduce the laminar appearance in human articular cartilage by applying spin-lock RF pulses, which may lead to a more accurate diagnosis of degenerative changes in cartilage.
A Creative Game Design and Programming App (2019)

We present a game creation app for tablets that builds on the popularity of video games while focusing attention on creativity and problem solving. With our app, users design and build a game by first drawing characters and objects on paper with markers and crayons, and then automatically integrate them with our app. An event-based visual programming language allows to program the game logic. In the spirit of creative play, users can jump at any point between the design, programming and test phases in order to realize their imagination. We evaluate our app with a user study to understand how gender and the use of self-made drawings influence the type of games users create and their state of flow during the process. Our results show that letting users draw their own game elements can lead to higher engagement. We also show that girls tend to spend more time programming and less time testing compared to boys, and that our app can help girls gain self-confidence.
Structural study of the type II 3-dehydroquinate dehydratase fromActinobacillus pleuropneumoniae (2004)

The structure of the type II dehydroquinate dehydratase (DHQase) from Actinobacillus pleuropneumoniae, the third enzyme of the shikimate pathway, has been determined. Crystals diffracting to 1.7 A were obtained in space and on earth using the counter-diffusion technique. The structure was solved using molecular replacement and refined to high resolution. The overall structure of the dodecameric enzyme is described and compared with structures of DHQases from other bacteria. DHQases contain a flexible loop that presumably closes over the active site upon substrate binding. The enzyme can exist in an open or closed conformation. The present structure displays the open conformation, with a sulfate anion bound in the active site. The availability of this structure opens a route to structure-based antibiotics targetting this pathogenic bacterium.
Multi-task additive models with shared transfer functions based on\n dictionary learning (2015)

Additive models form a widely popular class of regression models which\nrepresent the relation between covariates and response variables as the sum of\nlow-dimensional transfer functions. Besides flexibility and accuracy, a key\nbenefit of these models is their interpretability: the transfer functions\nprovide visual means for inspecting the models and identifying domain-specific\nrelations between inputs and outputs. However, in large-scale problems\ninvolving the prediction of many related tasks, learning independently additive\nmodels results in a loss of model interpretability, and can cause overfitting\nwhen training data is scarce. We introduce a novel multi-task learning approach\nwhich provides a corpus of accurate and interpretable additive models for a\nlarge number of related forecasting tasks. Our key idea is to share transfer\nfunctions across models in order to reduce the model complexity and ease the\nexploration of the corpus. We establish a connection with sparse dictionary\nlearning and propose a new efficient fitting algorithm which alternates between\nsparse coding and transfer function updates. The former step is solved via an\nextension of Orthogonal Matching Pursuit, whose properties are analyzed using a\nnovel recovery condition which extends existing results in the literature. The\nlatter step is addressed using a traditional dictionary update rule.\nExperiments on real-world data demonstrate that our approach compares favorably\nto baseline methods while yielding an interpretable corpus of models, revealing\nstructure among the individual tasks and being more robust when training data\nis scarce. Our framework therefore extends the well-known benefits of additive\nmodels to common regression settings possibly involving thousands of tasks.\n
Bilateral Fetal Striatal Grafts in the 3-Nitropropionic Acid-Induced Hypoactive Model of Huntington's Disease (1998)

We investigated the 3-nitropropionic acid (3-NP)–induced hypoactive model of Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can ameliorate behavioral deficits associated with a more advanced stage of HD. Twelve-week-old Sprague–Dawley rats were introduced to the 3-NP dosing regimen (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested for general spontaneous locomotor activity in the Digiscan locomotor apparatus. All rats displayed significant hypoactivity compared to their pre-3-NP injection locomotor activity. Randomly selected rats then received bilateral intrastriatal solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from embryonic day 14 rat fetuses. Approximately 1/3 of each LGE in hibernation medium was infused into each lesioned host striatum. In control rats, medium alone was infused intrastriatally. A 3-mo posttransplant maturation period was allowed prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited a significant increase in locomotor activity compared to their post-3-NP injection activity or to the controls’ posttransplant activity. Surviving striatal grafts were noted in functionally recovered animals. This observation supports the use of fetal striatal transplants to correct the akinetic stage of HD. To the best of our knowledge, this is the first study that has investigated the effects of fetal striatal transplantation in a hypoactive model of HD.
Introductory overview of research instruments for recording the electrical activity of neurons in the human brain (1998)

Scientific advancement is often spurred by the development of new instruments for investigation. Over the last several decades, many new instruments have been produced to further our understanding of the physiology of the human brain. We present a partial overview of some of these instruments, paying particular attention to those which record the electrical activity of the human brain. We preface the review with a brief primer on neuroanatomy and physiology, followed by a discussion of the latest types of apparatus used to investigate various properties of the central nervous system. A special focus is on microelectrode investigations that employ both intracellular and extracellular methods of recording the electrical activity of single neurons; another is on the modern electroencephalographic, electrocorticographic, and magnetoencephalographic methods used to study the spontaneous and evoked field potentials of the brain. Some examples of clinical applications are included, where appropriate.
1001. Metabolic Biotinylation of Cell Surface Receptors for In Vivo Imaging (2006)

A versatile, potent technique for imaging cells in culture and in vivo has been achieved by expressing a metabolically biotinylated reporter protein on the cell surface and visualizing this transgene product with labeled streptavidin moieties. The recombinant reporter protein incorporates the prokaryotic Propionibacterium shermanii 1.3S transcarboxylase domain biotin acceptor peptide (BAP) between an N-terminal signal sequence and the PDGF receptor transmembrane domain (TM,Fig. 1). Western blot analysis of cell homogenates, immunocytochemistry of non-permeablized cells and FACS analysis demonstrated that this BAP-TM reporter protein is efficiently biotinylated by endogenous biotin ligase in mammalian cells with the biotin displayed on the cell surface. Magnetic resonance and fluorescence tomographic imaging in vivo showed significant decrease in the spin-spin relaxation time T2 and over 15-fold increase in fluorescence in BAP-TM-reporter-expressing tumors as compared to control tumors following intravascular injection of streptavidin- magnetic nanoparticles or streptavidin-Alexa680 conjugates, respectively. This reporter proved to be more efficient for magnetic resonance imaging than an engineered transferrin receptor reporter previously developed in our laboratory. Moreover, intravascular injection of streptavidin-horseradish peroxidase conjugates, in conjunction with a gadolinium-based magnetic resonance agent sensitive to peroxidase activity, selectively enhanced BAP-TM- reporter expressing tumors. This BAP-TM reporter allows for non- invasive real time imaging of any cell type transduced to express it in culture or in vivo, and should be compatible with use in humans since streptavidin-biotin system and paramagnetic nanoparticles are being used in clinical trials.
The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality from COVID-19 (2020)

Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and preclinical data suggest alpha-1 adrenergic receptor antagonists (α<sub>1</sub>-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of α<sub>1</sub>-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any α<sub>1</sub>-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63 to 0.85; p ≤ 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65 to 0.84; p ≤ 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03 to 0.94; p = 0.028) compared to matched controls not on any α<sub>1</sub>-AR antagonist at the time of admission. These findings suggest that use of α<sub>1</sub>-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.
Supplemental Figure S1 from Loss of <i>ARID1A</i> Activates <i>ANXA1</i>, which Serves as a Predictive Biomarker for Trastuzumab Resistance (2023)

&lt;p&gt;Supplemental Figure S1: ARID1A loss activates PI3K/AKT and has no effect on MAPK/ERK signaling in BT474 cells&lt;/p&gt;
Supplementary Table S1 from PGP9.5 Methylation in Diffuse-Type Gastric Cancer (2023)

&lt;p&gt;Primer sequence&lt;/p&gt;
COMPUTATION OF THE ONE-DIMENSIONAL UNWRAPPED PHASE (2013)

In this paper, the computation of the unwrapped phase of the discretetime Fourier transform (DTFT) of a one-dimensional finite-length signal is explored. The phase of the DTFT is not unique, and may contain integer multiple of 2π discontinuities. The unwrapped phase is the instance of the phase function chosen to ensure continuity. This paper compares existing algorithms for computing the unwrapped phase. Then, two composite algorithms are proposed that build upon the existing ones. The core of the proposed methods is based on recent advances in polynomial factoring. The proposed methods are implemented and compared to the existing ones.
5(6)-anti-Substituted-2-azabicyclo[2.1.1]hexanes: A Nucleophilic Displacement Route (2009)

Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y-difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N(3), Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position.
Development of a trispecific antibody conjugate that directs two distinct tumor-associated antigens to CD64 on myeloid effector cells (1999)

A trispecific F(ab')3 antibody conjugate (TAC) with specificities for the Fc gamma receptor I (Fc gamma RI/CD64), the epidermal growth factor receptor (EGFR) and the HER2/neu antigen has been developed to redirect effector cell-mediated cytotoxicity against cancer cells expressing both or either of the tumor-associated antigens. The TAC was constructed in two steps using the sulfhydryl-specific cross-linker o-phenylenedimaleimide (o-PDM). In step one, a bispecific antibody was prepared by linking the Fab' fragments of mAb m22 (a murine IgG1 specific for Fc gamma RI) and mAb H425 (a humanized IgG1 antibody recognizing EGFR). The conjugation efficiency was about 60%. In the second step, the Fab' fragment of mAb 520C9, a murine IgG1 specific for HER2/neu, was coupled to the bispecific antibody made in step one. About 40% of the bispecific conjugate was derivatized to form the trispecific antibody. The purity of the TAC was more than 90% after gel filtration purification. The TAC was characterized in vitro for its ability to bind specifically to all the three antigens and to kill target cells expressing the tumor antigens. In contrast to bispecific conjugates that can only target cells expressing either of the tumor antigens, the TAC was able to bind both the antigens more efficiently in cell-binding assays and to kill tumor cells expressing EGFR and HER2/neu antigens.
Performance limitations of a Y-branch directional-coupler-based polymeric high-speed electro-optical modulator (2004)

To find the optimal driving voltage and bandwidth for electro-optic polymer-waveguide-based directional couplers, four electrode structures are investigated. They are the microstrip line (MSL), the asymmetric coplanar waveguide with ground (ACWG), the coplanar waveguide with ground (CPWG), and the edge-coupled microstrip line (CMSL). UV15:Polymethyl methacrylate/dispersed-red 1:UV11-3-based directional couplers are evaluated. The CPWG and the ACWG have almost the same driving voltages, which are about twice the driving voltage of the CMSL. The MSL has the largest driving voltage, which is 20 to 25% higher than the diving voltages of the CPWG and ACWG. Simulation results further conclude that the MSL has the largest bandwidth, and its bandwidth is about 1.6 times that of the bandwidth of the CMSL, which has the narrowest bandwidth. The bandwidths of the ACWG and CPWG are 1.4 and 1.2 times that of the CMSL, respectively. The driving voltages for the four different devices are experimentally confirmed.
Extreme Light Infrastructure (ELI): Physics and Lasers at the ultra-intense frontier (2010)

ELI has been put on the European Roadmap for Research infrastructures by the European Strategy Forum on Research Infrastructures (ESFRI). It will be the first Paneuropean Infrastructure utilizing an ultra-intense laser with a peak-power of 200 PW for interaction experiments with electric field strength well above the PV/m (1015 V/m ). With the high focused intensity (above 4 ×1024W/cm2) it will be possible to enter the ultra-relativistic regime when protons are accelerated to nearly the speed of light at a distance in the order of the wavelength of the driving extreme light. Fundamental physics phenomena can be investigated for the first time including nonlinear vacuum interaction and pair generation. ELI intermediate beam lines with peak-powers in the few PW range but higher repetition rates (10 Hz) will enable scientific and societal including medical applications based on laser particle acceleration (proton therapy) and x-ray generation. The photonuclear facility will explore nuclei with hard x-ray and gamma-ray photons produced by high intensity interaction with matter. The Attosecond science laser driver with its high repetition rate (1 kHz) and high average power (&gt;1 kW, 5-10fs) opens the way to ultrafast investigations in different scientific and technological areas with time resolutions in the Attosecond and may by even faster (zeptosecond) time domains using very brilliant VUV-light and x-rays generated by harmonics from gases or solids.
Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells (2014)

The availability of human pluripotent stem cells (hPSCs) offers the opportunity to generate lineage-specific cells to investigate mechanisms of human diseases specific to brain regions. Here, we report a differentiation paradigm for hPSCs that enriches for hippocampal dentate gyrus (DG) granule neurons. This differentiation paradigm recapitulates the expression patterns of key developmental genes during hippocampal neurogenesis, exhibits characteristics of neuronal network maturation, and produces PROX1+ neurons that functionally integrate into the DG. Because hippocampal neurogenesis has been implicated in schizophrenia (SCZD), we applied our protocol to SCZD patient-derived human induced pluripotent stem cells (hiPSCs). We found deficits in the generation of DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of spontaneous neurotransmitter release. Our approach offers important insights into the neurodevelopmental aspects of SCZD and may be a promising tool for drug screening and personalized medicine.