gebhart/patrepeval huggingface dataset:
Selexipag for the Treatment of Pulmonary Arterial Hypertension (2015)

Among patients with pulmonary arterial hypertension, the risk of the primary composite end point of death or a complication related to pulmonary arterial hypertension was significantly lower with selexipag than with placebo. There was no significant difference in mortality between the two study groups. (Funded by Actelion Pharmaceuticals; GRIPHON ClinicalTrials.gov number, NCT01106014.).
Toward Off-Policy Learning Control with Function Approximation (2010)

We present the first temporal-difference learning algorithm for off-policy control with unrestricted linear function approximation whose per-time-step complexity is linear in the number of features. Our algorithm, Greedy-GQ, is an extension of recent work on gradient temporal-difference learning, which has hitherto been restricted to a prediction (policy evaluation) setting, to a control setting in which the target policy is greedy with respect to a linear approximation to the optimal action-value function. A limitation of our control setting is that we require the behavior policy to be stationary. We call this setting latent learning because the optimal policy, though learned, is not manifest in behavior. Popular off-policy algorithms such as Q-learning are known to be unstable in this setting when used with linear function approximation. In reinforcement learning, the term “off-policy learning” refers to learning about one way of behaving, called the target policy, from data generated by another way of selecting actions, called the behavior policy. The target policy is often an approximation to the optimal policy, which is typically deterministic, whereas the behavior policy is often stochastic, exploring all possible actions in each state as part of finding the optimal policy. Freeing the behavior policy from the target policy enables a greater variety of exploration strategies to be used. It also enables learning from training data generated by unrelated controllers, including manual human control, and from previously collected data. A third reason for interest in off-policy learning is that it permits learning about multiple target policies (e.g., optimal policies for multiple subgoals) from a single stream of data generated by a
Confinement-Induced Entropic Recoil of Single DNA Molecules in a Nanofluidic Structure (2002)

The behavior of DNA molecules is observed in a nanofluidic device near the interface of two regions that produce different configuration entropies. An electric field is applied to drive the molecules partway across the interface. Upon removal of the field, the molecules recoil to the higher-entropy region with a profile characteristic of a force localized to the interface and independent of length. This is consistent with a confinement-mediated entropic force, distinct from the well-known entropic elasticity common to all polymers. An estimate of the hydrodynamic drag is used to produce a lower bound for the force. The phenomenon can be exploited to separate long-strand polyelectrolytes according to length.
Strong signal increase in STED fluorescence microscopy by imaging regions of subdiffraction extent (2017)

Photobleaching remains a limiting factor in superresolution fluorescence microscopy. This is particularly true for stimulated emission depletion (STED) and reversible saturable/switchable optical fluorescence transitions (RESOLFT) microscopy, where adjacent fluorescent molecules are distinguished by sequentially turning them off (or on) using a pattern of light formed as a doughnut or a standing wave. In sample regions where the pattern intensity reaches or exceeds a certain threshold, the molecules are essentially off (or on), whereas in areas where the intensity is lower, that is, around the intensity minima, the molecules remain in the initial state. Unfortunately, the creation of on/off state differences on subdiffraction scales requires the maxima of the intensity pattern to exceed the threshold intensity by a large factor that scales with the resolution. Hence, when recording an image by scanning the pattern across the sample, each molecule in the sample is repeatedly exposed to the maxima, which exacerbates bleaching. Here, we introduce MINFIELD, a strategy for fundamentally reducing bleaching in STED/RESOLFT nanoscopy through restricting the scanning to subdiffraction-sized regions. By safeguarding the molecules from the intensity of the maxima and exposing them only to the lower intensities (around the minima) needed for the off-switching (on-switching), MINFIELD largely avoids detrimental transitions to higher molecular states. A bleaching reduction by up to 100-fold is demonstrated. Recording nanobody-labeled nuclear pore complexes in <i>Xenopus laevis</i> cells showed that MINFIELD-STED microscopy resolved details separated by <25 nm where conventional scanning failed to acquire sufficient signal.
Role of the Guanosine Triphosphatase Rac2 in T Helper 1 Cell Differentiation (2000)

T helper 1 (TH1) cells mediate cellular immunity, whereas TH2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine TH1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative Rac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression.
Titanium dioxide (TiO2)-based gate insulators (1999)

Titanium dioxide has been deposited on silicon for use as a high-permittivity gate insulator in an effort to produce low-leakage films with oxide equivalent thicknesses below 2.0 nm. Excellent electrical characteristics can be achieved, but TEM and electrical measurements have shown the presence of a low-resistivity interfacial layer that we take to be SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> . The leakage current follows several mechanisms depending on the bias voltage. Reasonably good agreement has been seen between current-voltage measurements and a 1D quantum transport model.
Bioseparation in Antibody Manufacturing: The Good, The Bad and The Ugly (2008)

Improvements in upstream production have boosted productivity in the biomanufacturing industry, but this is leading to bottlenecks in downstream processing as current technology platforms reach their limits of throughput and scalability. Although chromatography remains an indispensible component of downstream processing due to its simplicity and high resolving power (The Good), there is virtually no economy of scale effect so more product translates almost linearly into greater production costs. Bind-and-elute processes (such as the initial capture step in antibody manufacturing) are volume-driven and therefore have knock-on effects that impact on the entire production facility since the space required for preparation, storage, and cleaning steps has to be similarly adapted (The Bad). During long-term operations with multiple cycles, thorough cleaning is necessary to prevent progressive fouling and microbial contamination (The Ugly). Innovative solutions are required, which may include revisiting simpler and less expensive separation technologies, the use of disposable modules, and the integration of improved processes that are scalable to cope with increased demands. Among the alternatives that have been put forward, membrane adsorbers are beginning to make a real impact on the industry, particularly for flow-through applications such as polishing and viral clearance.
The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines (2007)

ATF5, a transcription factor important in differentiation, proliferation and survival, has been found to be highly expressed in neural progenitor cells and in certain tumors including glioblastomas (GBMs), but its expression in other normal and neoplastic tissues has not been extensively investigated. A tissue microarray immunostained for ATF5 showed diffuse nuclear expression (as defined by the presence in greater than 25% of cells) in 63% (117/186) of neoplastic samples, when compared to only 32% (20/62) in nonneoplastic tissues. When analyzed by histologic subtype, a significantly greater proportion of adenocarcinomas, transitional cell carcinomas, squamous cell carcinomas and metastatic carcinomas of various tissue origins had nuclear staining when compared to nonneoplastic tissues. There was no significant difference in ATF5 expression in renal cell carcinomas, lymphomas and seminomas, when compared to nonneoplastic tissues. An expanded series of nonarray breast resection specimens revealed a significantly greater proportion of ATF5 positivity in ductal and lobular carcinomas, when compared to normal breast tissue. Past work found that loss of ATF5 function triggers death of GBM cells, but not of normal activated astrocytes. Here, we observed that loss of ATF5 function caused significant apoptotic death of neoplastic breast cell lines, but not of nonneoplastic breast cell lines. Our data demonstrate elevated ATF5 expression in a wide variety of neoplasms and that interference with ATF5 function selectively triggers death of breast carcinoma cells. Such findings may have potential therapeutic application.
History in a National Framework (2006)

History's place in schools continues to shape debate over the subject's status and relevance. A number of historians and educationists fear that the current teaching approaches (such as Studies of Society and Environment, or SOSE) have damaged the discipline beyond repair, while others view this integrated approach as nationally and educationally 'relevant'.
Anti-Human Immunodeficiency Virus Drug Combination Strategies (1998)

It is now generally accepted that mono- and bitherapy for human immunodeficiency virus type 1 (HIV-1) infection are only transiently efficient mainly due to virus drug resistance. To obtain a sustained benefit from antiviral therapy, current guidelines recommend at least triple-drug combinations, or the so-called highly active antiretroviral therapy (HAART). In some patients, HAART can be problematic, either because it is difficult to remain compliant or because previous suboptimum therapies have limited the choice of drugs. For compliant drug-naive patients, HAART should be able to offer long-term virus suppression, when changing from first- to second- to third-line HAART at drug failure. Long-term treatment might ultimately result in multi-drug resistant virus leaving few options for salvage therapy. HIV drug resistance testing to guide this salvage therapy and the development of new drugs to allow new options will therefore remain priorities in anti-HIV drug research.
The Dawkins disaster (1989)

Australia as a new and distant country started at a considerable disadvantage in regard to University education. In From Deserts the Prophets Come. Geoffrey Serle has written that even prior to World War II ...universities continued to operate on a pinchpenny basis; it was common for a professor to teach half a dozen courses with the help of one or two lamentably paid junior assistants. Research was a luxury, not reasonably to be expected.
In Vivo Association Between Low Wall Shear Stress and Plaque in Subjects With Asymmetrical Carotid Atherosclerosis (1997)

The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.
Evaluation of Readministration of a Recombinant Adeno-Associated Virus Vector Expressing Acid Alpha-Glucosidase in Pompe Disease: Preclinical to Clinical Planning (2015)

A recombinant serotype 9 adeno-associated virus (rAAV9) vector carrying a transgene that expresses codon-optimized human acid alpha-glucosidase (hGAA, or GAA) driven by a human desmin (DES) promoter (i.e., rAAV9-DES-hGAA) has been generated as a clinical candidate vector for Pompe disease. The rAAV9-DES-hGAA vector is being developed as a treatment for both early- and late-onset Pompe disease, in which patients lack sufficient lysosomal alpha-glucosidase leading to glycogen accumulation. In young patients, the therapy may need to be readministered after a period of time to maintain therapeutic levels of GAA. Administration of AAV-based gene therapies is commonly associated with the production of neutralizing antibodies that may reduce the effectiveness of the vector, especially if readministration is required. Previous studies have demonstrated the ability of rAAV9-DES-hGAA to correct cardiac and skeletal muscle pathology in Gaa(-/-) mice, an animal model of Pompe disease. This article describes the IND-enabling preclinical studies supporting the program for a phase I/II clinical trial in adult patients with Pompe. These studies were designed to evaluate the toxicology, biodistribution, and potential for readministration of rAAV9-DES-hGAA injected intramuscularly into the tibialis anterior muscle using an immune modulation strategy developed for this study. In the proposed clinical study, six adult participants with late-onset Pompe disease will be enrolled. The goal of the immune modulation strategy is to ablate B-cells before the initial exposure of the study agent in one leg and the subsequent exposure of the same vector to the contralateral leg four months after initial dosing. The dosing of the active agent is accompanied by a control injection of excipient dosing in the contralateral leg to allow for blinding and randomization of dosing, which may also strengthen the evidence generated from gene therapy studies in the future. Patients will act as their own controls. Repeated measures, at baseline and during the three months following each dosing will assess the safety, biochemical, and functional impact of the vector.
Using state‐dependency of transcranial magnetic stimulation (TMS) to investigate letter selectivity in the left posterior parietal cortex: a comparison of TMS‐priming and TMS‐adaptation paradigms (2008)

The state-dependency of transcranial magnetic stimulation (TMS) can be used to investigate the neural properties of subregions of the stimulated region. The objective of the present study was to determine whether state-dependency can reveal letter selectivity in the left posterior parietal cortex (PPC), a region known to contain letter-selective neurons. In two experiments, we used visual priming and adaptation to modulate the initial activation state of the left PPC prior to application of TMS. In the priming experiment, TMS was applied over the left PPC during the delay between the prime and the target stimulus on each experimental trial. Left PPC TMS reversed the effects of priming by facilitating the detection of non-primed letters, whereas detection of primed letters was unaffected. As neurons tuned to non-primed letters were less active at the time of TMS application than neurons tuned to the primed letters, this finding demonstrates that TMS preferentially facilitates the detection of attributes encoded by the less active neural populations. A similar facilitation of the less active neural populations was observed when adaptation was used to suppress letter-selective neurons prior to application of TMS. Our study demonstrates that TMS-priming and TMS-adaptation paradigms can reveal letter selectivity in the left PPC and thus be useful in the study of language processes. Our results also show that the state-dependent TMS effects obtained with visual priming are similar to those found with TMS adaptation: in both cases, attributes encoded by the less active neural populations are preferentially facilitated.
Major Biological Effects of Neurotrophic Factors on Retinal Ganglion Cells in Mammals (1998)

The mammalian visual system, particularly retinal ganglion cells, has been used for studying the functions of neurotrophic factors on neurons for many years. The major biological effects of neurotrophic factors on retinal ganglion cells observed so far are the promotion of viability and axonal regeneration. However, there are still some controversies regarding the effects of neurotrophic factors on retinal ganglion cells in the literature. This review is aimed to summarize the available information on the biological actions of these neurotrophic factors on survival and axonal regeneration of retinal ganglion cells and the expressions of neurotrophic factor receptors in the retina. Generally, brain-derived neurotrophic factor, neurotrophin-4/5, fibroblast growth factor and glial cell line-derived neurotrophic factor increase the survival of retinal ganglion cells while the effect of ciliary neurotrophic factor on the viability of adult retinal ganglion cells is controversial. The ciliary neurotrophic factor is the only effective factor in promoting long distance axonal regeneration of retinal ganglion cells whereas brain-derived neurotrophic factor and neurotrophin-4/5 only enhance neurite sprouting within the retina.
PET Imaging of Tumor Integrin Expression (2006)

The expression of integrin /spl alpha//sub v//spl beta//sub 3/ on sprouting capillary cells and their interaction with specific extracellular matrix ligands play a key role in tumor angiogenesis and metastasis. In several malignancies, tumor expression of integrin /spl alpha//sub v//spl beta//sub 3/ correlates well with tumor progression. Non-invasive imaging methods to visualize and quantify integrin /spl alpha//sub v//spl beta//sub 3/ expression in vivo are crucial for the success of anti-angiogenic therapy targeting integrin. Suitably labeled RGD peptides (potent integrin /spl alpha//sub v//spl beta//sub 3/ antagonists) and antibodies have been developed for PET, SPECT and NIR fluorescence imaging of small animals. Due to the high sensitivity and adequate spatial and temporal resolution of PET, development of PET probes for integrin expression imaging has been the mainstay of active research. We improved the tumor targeting efficacy and in vivo pharmacokinetics by applying polyvalency effect and designed /sup 18/F- and /sup 64/Cu-labeled dimeric and multimeric RGD peptides for both imaging and imaging-guided internal radiotherapy applications.
Optimal Quantum Control Using Randomized Benchmarking (2014)

We present a method for optimizing quantum control in experimental systems, using a subset of randomized benchmarking measurements to rapidly infer error. This is demonstrated to improve single- and two-qubit gates, minimize gate bleedthrough, where a gate mechanism can cause errors on subsequent gates, and identify control crosstalk in superconducting qubits. This method is able to correct parameters so that control errors no longer dominate and is suitable for automated and closed-loop optimization of experimental systems.
Practicing the Novolac deep-UV portable conformable masking technique (1981)

Deep-UV portable conformable masking, a double-layer resist patterning technique, combines the advantages of a noncontact submicron printing technique such as refractive projection imaging or scanning electron-beam patterning with those of deep-UV conformable printing. Feasibility studies were reported earlier.1,2 Here, the processes leading to fabrication of 1-μm MOSFET devices by e-beam and step-and-repeat optical projection printing will be presented. These include processing steps to retain or remove the top resist layer, to obtain resist image profiles suitable for liftoff or for reactive ion etching (RIE), to improve adhesion, to treat the interfacial layer between the two resists, to prevent cracking, and to monitor the development of the two resist layers. Electrical testing results on pin hole density are given, followed by uncapped and capped resist images of 1-μm double-poly-Si MOSFET test sites as well as 0.8-μm thick Al lifted-off images.
The effect of temperature on the performance and stability of thermophilic anaerobic digestion (2008)

Sustainable operation of an anaerobic sewage sludge digester requires the effective shuttling of carbon from complex organic material to methane gas. The accumulation of intermediates and metabolic products such as volatile fatty acids and hydrogen gas not only reveal inefficiency within the digestion process, but can be detrimental to reactor operation at sufficiently high levels. Eight anaerobic digesters (1 mesophilic and 7 thermophilic) were operated in order to determine the effect of steady-state digestion temperature on the operational stability and performance of the digestion process. Replicate reactors operated at 57.5 degrees C, the highest temperature studied, were prone to accumulation of volatile fatty acids (4052 and 3411 mg/L as acetate) and gaseous hydrogen. Reactors operated at or below 55 degrees C showed no such accumulation of intermediate metabolites. Overall methanogenesis was also greatly reduced at 57.5 degrees C (0.09 L CH4/g VS fed) versus optimal methane formation at 53 degrees C (0.40 L CH4/g VS fed). Microbial community assessment and free energy calculations suggest that the accumulation of fatty acids and hydrogen, and relatively poor methanogenic performance at 57.5 degrees C are likely due to temperature limitations of thermophilic aceticlastic methanogens.
Soft Microfluidic Assemblies of Sensors, Circuits, and Radios for the Skin (2014)

When mounted on the skin, modern sensors, circuits, radios, and power supply systems have the potential to provide clinical-quality health monitoring capabilities for continuous use, beyond the confines of traditional hospital or laboratory facilities. The most well-developed component technologies are, however, broadly available only in hard, planar formats. As a result, existing options in system design are unable to effectively accommodate integration with the soft, textured, curvilinear, and time-dynamic surfaces of the skin. Here, we describe experimental and theoretical approaches for using ideas in soft microfluidics, structured adhesive surfaces, and controlled mechanical buckling to achieve ultralow modulus, highly stretchable systems that incorporate assemblies of high-modulus, rigid, state-of-the-art functional elements. The outcome is a thin, conformable device technology that can softly laminate onto the surface of the skin to enable advanced, multifunctional operation for physiological monitoring in a wireless mode.
Elastolytic Activity in Pulmonary Lavage Fluid from Patients with Adult Respiratory-Distress Syndrome (1981)

To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (alpha-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (> 80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P < 0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in alpha-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients with ARDS, high levels of neutrophil elastolytic activity in the lungs are associated with reduced alpha-1-AP function.