gebhart/patrepeval huggingface dataset:
Design and Development of NS5B Polymerase Non‐nucleoside Inhibitors for the Treatment of Hepatitis C Virus Infection (2013)

The hepatitis C virus (HCV) infects an estimated 130–170 million people worldwide and is associated with life‐threatening liver diseases. The recent introduction of the first two HCV direct‐acting antivirals (DAAs) as a complement to the interferon/ribavirin standard of care has provided patients with improved outcomes. Still, 25–30% of subjects infected with genotype 1 HCV do not respond adequately to treatment owing to the emergence of resistant virus and many suffer from severe side effects. A paradigm shift towards the development of interferon‐free combinations of DAAs with complementary modes of action is currently taking place. Virally encoded proteins and enzymes have become the target of HCV drug discovery efforts and several promising new agents are currently being evaluated in the clinic for treatment of chronic HCV infection. The NS5B RNA‐dependent RNA polymerase is responsible for replication of viral RNA and plays a pivotal role in the virus life cycle. NS5B is undoubtedly the most druggable HCV target and is susceptible to several classes of allosteric inhibitors that bind to four distinct sites on the enzyme. This chapter describes successful strategies that have led to the discovery of HCV NS5B antivirals. It is divided according to allosteric sites and describes how each of the known families of inhibitors was discovered, characterized and optimized to provide clinical candidates. When available, the strategies adopted by medicinal chemists to optimize initial leads and address challenges and liabilities encountered on the path to candidate selection are described, along with reported clinical outcomes.
IMMU-13. COMBINED MODULATION OF THE TGF-Β PATHWAY AND GITR IMMUNE CHECKPOINT SIGNALING PROMOTES ANTI-TUMOR IMMUNITY IN SYNGENEIC GLIOMA MODELS (2021)

Abstract The profound local immunosuppressive microenvironment is one hallmark of glioblastoma, which results in resistance to most immunotherapeutic strategies that have been explored so far. Reverting this condition in order to reinvigorate anti-glioma immunity might be a promising therapeutic approach. Transforming growth factor (TGF)-β signaling is deregulated in different cancer types and contributes to the malignant phenotype of glioma cells. Glioma-derived TGF-β is also a major immunosuppressive factor in the tumor microenvironment. Furthermore, intratumoral regulatory T (Treg) cells and activated T effector cells express high levels of the co-stimulatory immune checkpoint glucocorticoid-induced tumor necrosis factor receptor (GITR). Agonistic anti-GITR antibodies have been explored in preclinical tumor models and are under investigation in clinical trials for the treatment of solid tumors. We evaluated the effect of TGF-β and GITR targeting on anti-tumor immune responses in syngeneic mouse glioma models. In co-culture settings, GITR modulation with a GITR ligand (GITRL)-Fc fusion protein, given alone or in combination with a pharmacological TGF-β receptor inhibitor, led to increased T cell activation. Furthermore, the combined targeting of the two pathways resulted in significantly higher immune cell-mediated tumor cell killing than either treatment alone. In vivo, TGF-β inhibition and GITR signaling modulation resulted in a higher fraction of long-term surviving glioma-bearing mice than single-agent treatment. Surviving mice were resistant to tumor re-challenge, suggesting adaptive immunity as an underlying mechanism. These data support the assumption that combined immunotherapeutic strategies may represent a promising approach for the treatment of glioma.
Heterocycles from ylides. Part 7. Reactivity of 3-arylmethyleneindolin-2-ones with stabilized sulphur ylides (1979)

3-Arylmethyleneindolin-2-ones react with carbonyl-stabilized sulphur ylides yielding spiro[cyclopropane-1,3′-indolin-2′-ones] whose structure and stereochemistry were assigned on the basis of spectroscopic data.
Suitability of Oil Palm Empty Fruit Bunch and Sago Waste for Auricularia polytricha Cultivation (2014)

Zona laxa
Efficient implementation of high performance Read out Integrated Circuit (2014)

The Read out Integrated Circuit (ROIC) consists of charge integration, charge to voltage conversion, Pixel voltage multiplexing, signal transfer and amplification stages. The control circuit manages all the sequential events from charge integration to amplification stage. Design and optimization of ROIC for hybrid detectors has multidimensional challenges including requirement for long simulation time for specified 25 to 100 Hz frame rate. Normally useful simulation data starts after 3 frame time and minimum transient simulation required for the same is 10 ms for 100 Hz frame rate. The simulation time for each input condition is ∼120 hours with traditional simulators. ROIC critical specifications i.e. charge handling capacity and linearity has to be checked before chip integration to Pad. The linearity check requirs at least six point simulation and lead to 1 month simulation time on state of the art servers. Fast spice simulator with set_sim_level 5 has been used for the first time and reduces simulation time to 230 hours on same machine for the linearity simulation of ROIC. Test chip 4×4 ROIC has been fabricated using UMC 180 nm CMOS process and experimental results matched within 0.4% variation w.r.t. fast spice simulation results.
Cairn detection in southern arabia using a supervised automatic detection algorithm and multiple sample data spectroscopic clustering (2010)

Excavating cairns in southern Arabia is a way for anthropologists to understand which factors led ancient settlers to transition from a pastoral lifestyle and tribal narrative to the formation of states that exist today. Locating these monuments has traditionally been done in the field, relying on eyewitness reports and costly searches through the arid landscape.
In this thesis, an algorithm for automatically detecting cairns in satellite imagery is presented. The algorithm uses a set of filters in a window based approach to eliminate background pixels and other objects that do not look like cairns. The resulting set of detected objects constitutes fewer than 0.001% of the pixels in the satellite image, and contains the objects that look the most like cairns in imagery. When a training set of cairns is available, a further reduction of this set of objects can take place, along with a likelihood-based ranking system.
To aid in cairn detection, the satellite image is also clustered to determine land-form classes that tend to be consistent with the presence of cairns. Due to the large number of pixels in the image, a subsample spectral algorithm called Multiple Sample Data Spectroscopic clustering is used. This multiple sample procedure is motivated by perturbation studies on single sample spectral algorithms. The studies, presented in this thesis, show that sampling variability in the single sample approach can cause an unsatisfactory level of instability in results. The multiple sample data spectroscopic algorithm is intended to stabilize this perturbation by combining information from different samples. While sampling variability is still present, the use of multiple samples mitigates its effect on cluster results.
Finally, a step-through of the cairn detection algorithm and satellite image are given for an image in the Hadramawt region of Yemen. The top ranked detected objects are presented, and a discussion of parameter selection and future work follows.
Volterra series estimation of transient soot emissions from a diesel engine (2010)

This paper describes the development of a Volterra series model for predicting transient soot emissions from a diesel engine with fuel flow rate and engine speed as the two inputs to the model. These two signals are usually available as outputs of the power management controller in diesel hybrids. Therefore, an accurate offline estimation of the transient soot emissions using these signals is instrumental in optimizing the control strategy for both fuel economy and emissions. In order to develop the model, transient soot data are first collected by Engine-in-the-loop experiments of conventional and hybrid vehicles. The data are then used to construct a third-order multiple-input single-output (MISO) Volterra series to successfully model this system. Parametric complexity of the model is reduced using proper orthogonal decomposition (POD), and the model is validated on various datasets. It is shown that the prediction accuracy of transient soot, both qualitatively and quantitatively, significantly improves over the steady-state maps, while the model still remains computationally efficient for systems level work.
The gut microbiota regulates bone mass in mice (2012)

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4(+) T cells and CD11b(+) /GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis.
Quantitative Rezeptor-PET in der präklinischen Bildgebung: Vergleich von intravenöser und intraperitonealer Radiotracerapplikation anhand des Beispiels des Adenosin A1 Rezeptor-Tracers F-18-CPFPX (2023)

Ziel/Aim Bei präklinischen Positronen-Emissions-Tomographie (PET) -Studien an Nagern erfolgt standardmäßig die Injektion des Radiotracers über die Schwanzvene des Tieres. Insbesondere wenn die Tiere im Rahmen longitudinaler Ansätze untersucht werden sollen, birgt die wiederholte Punktion der Schwanzvene erhöhte Schwierigkeiten. Als Alternative kann die intraperitoneale Injektion dienen. In dieser Arbeit wurde die Bindung des Adenosin A1 Rezeptor (A1AR)-Radiotracers F-18-CPFPX nach intraperitonealer (i.p.) und intravenöser (i.v.) Injektion vergleichend mittels kinetischer Modellierung quantitativ analysiert.
A porous porphyrin organic polymer (PPOP) for visible light triggered hydrogen production (2017)

A visible light active porphyrin-based porous organic polymer having high chemical stability and surface area has been synthesized and its ability to influence the photocatalytic activity of large band gap-TiO<sub>2</sub> nanoparticles has been tested. The resultant composite shows improved photocatalytic activity as compared to the parent precursors. This study provides insights into the photosensitizing ability of the polymer in addition to its ability to firmly harbor nanoparticles onto its surface.
Value of thyroid stimulating antibody in the diagnosis of thyroid associated ophthalmopathy of euthyroid patients (1997)

These results suggest that the activity of TSAb is a more sensitive marker of euthyroid TAO than is TBII, and could be a useful criterion in the diagnosis of TAO of euthyroid patients.
The Clinical relevance of Polygenic Risk Scores to Type 2 Diabetes Mellitus in Korean Population (2023)

Abstract The potential clinical utility of type 2 diabetes mellitus (T2DM) polygenic risk scores (PRS) is not thoroughly evaluated in the East Asian population. We aimed to assess whether T2DM PRS could have prognostic value and be used as a clinical instrument. We constructed T2DM PRS for Korean individuals using large East Asian Biobank data with samples of 269,487 and evaluated the PRS in a prospective longitudinal study of Korean with 5490 samples with baseline and additional seven follow-ups. Our analysis demonstrated that T2DM PRS could predict not only the progress from non-diabetes to T2DM, but also normal glucose tolerance to prediabetes and prediabetes to T2DM. Moreover, T2DM patients in the top decile PRS group were more likely to be treated with insulin with HR = 1.69 (p-value = 2.31E-02) than the remaining PRS groups. T2DM PRS was significantly high in severe diabetic subgroups with insulin resistance and \(\beta\)-cell dysfunction (p-value = 0.0012). PRS could modestly improve the prediction accuracy of the Harrel’s C-index by 9.88% (p-value &lt; 0.001) in T2DM prediction models. By utilizing prospective longitudinal study data and extensive clinical risk factors, our analysis provides insights into the clinical utility of the T2DM PRS.
A tiny VIS-NIR snapshot multispectral camera (2015)

Spectral imaging can reveal a lot of hidden details about the world around us, but is currently confined to laboratory environments due to the need for complex, costly and bulky cameras. Imec has developed a unique spectral sensor concept in which the spectral unit is monolithically integrated on top of a standard CMOS image sensor at wafer level, hence enabling the design of compact, low cost and high acquisition speed spectral cameras with a high design flexibility. This flexibility has previously been demonstrated by imec in the form of three spectral camera architectures: firstly a high spatial and spectral resolution scanning camera, secondly a multichannel snapshot multispectral camera and thirdly a per-pixel mosaic snapshot spectral camera. These snapshot spectral cameras sense an entire multispectral data cube at one discrete point in time, extending the domain of spectral imaging towards dynamic, video-rate applications. This paper describes the integration of our per-pixel mosaic snapshot spectral sensors inside a tiny, portable and extremely user-friendly camera. Our prototype demonstrator cameras can acquire multispectral image cubes, either of 272x512 pixels over 16 bands in the VIS (470-620nm) or of 217x409 pixels over 25 bands in the VNIR (600-900nm) at 170 cubes per second for normal machine vision illumination levels. The cameras themselves are extremely compact based on Ximea xiQ cameras, measuring only 26x26x30mm, and can be operated from a laptop-based USB3 connection, making them easily deployable in very diverse environments.
Measurements of inclusive and differential fiducial cross-sections of $$t\bar{t}\gamma $$ production in leptonic final states at $$\sqrt{s}=13~\text {TeV}$$ in ATLAS (2019)

Inclusive and differential cross-sections for the production of a top-quark pair in association with a photon are measured with proton-proton collision data corresponding to an integrated luminosity of 36.1 fb -1 , collected by the ATLAS detector at the LHC in 2015 and 2016 at a centreof-mass energy of 13 TeV. The measurements are performed in single-lepton and dilepton final states in a fiducial volume. Events with exactly one photon, one or two leptons, a channel-dependent minimum number of jets, and at least one b-jet are selected. Neural network algorithms are used to separate the signal from the backgrounds. The fiducial cross-sections are measured to be 521 9(stat.) 41(sys.) fb and 69 3(stat.) 4(sys.) fb for the single-lepton and dilepton channels, respectively. The differential cross-sections are measured as a function of photon transverse momentum, photon absolute pseudorapidity, and angular distance between the photon and its closest lepton in both channels, as well as azimuthal opening angle and absolute pseudorapidity difference between the two leptons in the dilepton channel. All measurements are in agreement with the theoretical predictions.
A scientific computing gui agent for parallel monte carlo in a distributed environment (2000)

Monte Carlo applications, such as Brownian Langevin simulations of biomedical molecules, are often computationally intensive, since reducing stochastic errors calls for more samplings and the order of this reduction is proportional to the square root of the number of samples. 
For the last 15 years, there has been a continuing trend away from main frame computers and towards distributed PCs. In this new environment (parallel PC pools), the network throughput bottleneck, PC instability, heterogeneousness, and security issues must be addressed anew. 
We developed a web-based graphical user interface (WB-GUI) agent for distributed Monte Carlo computations that significantly improves our Brownian Langevin simulation time. The GUI agent is built upon the Condor cycle scavenging system and consists of the Scalable Parallel Random Number Generator library (SPRNG), the remote compiler, and the cycle server. 
The WB-GUI reduces the complexity of using the underlying distributed computer systems. Users only need upload codes and download results via the WB-GUI. Parallel random number support (via SPRNG), preparing tasks for heterogeneous platforms (via remote compiler), and using Condor to migrate a job from a busy or dead computer to an idle one, are all integrated seamlessly; they are transparent to users. At the same time, the GUI agent acts as a gate-keeper for the PC pool: no user account is needed on pool computers; users are assigned web accounts instead. Jobs only run at machine idle time and the executing machine file systems are never touched by them. 
With the aid of this tool, we studied the sensitivity of the results of a Brownian Langevin application to a suite of random number generators. We were able to run the application in parallel on available hardware in a reasonable time.
Adaptive Interference Alignment with CSI Uncertainty (2012)

Interference alignment (IA) is known to significantly increase sum-throughput at high SNR in the presence of multiple interfering nodes, however, the reliability of IA is little known, which is the subject of this paper. We study the error performance of IA and compare it with conventional orthogonal transmission schemes. Since most IA algorithms require extensive channel state information (CSI), we also investigate the impact of CSI imperfection (uncertainty) on the error performance. Our results show that under identical rates, IA attains a better error performance than the orthogonal scheme for practical signal to noise ratio (SNR) values but is more sensitive to CSI uncertainty. We design bit loading algorithms that significantly improve error performance of the existing IA schemes. Furthermore, we propose an adaptive transmission scheme that not only considerably reduces error probability, but also produces robustness to CSI uncertainty.
A fuzzy sketch with trapdoor (2006)

In 1999, Juels and Wattenberg introduce an effective construction of Fuzzy Sketch, i.e., a way of handling errors into string verification. This allows them to consider data varying in time, such as, for instance, answers to a list of subjective questions. To this end, they use an error-correcting code. We show here how to embed a trapdoor into Fuzzy Sketches, reducing to authorized people the ability to correct errors and thus to verify the fuzzy equality to the Fuzzy Sketch.
Figure S4 from High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy (2023)

&lt;p&gt;Figure S4. Effect of HIFU alone at 24, 48 and 72 hrs on circulating cytokines.&lt;/p&gt;
Autoregulation of capillary pressure and filtration rate in isolated rat hindquarters (1985)

The hypothesis that skeletal muscle capillary pressure and/or capillary filtration rate are autoregulated was tested in 10 isolated rat hindquarters. Capillary pressure was directly assessed with the venous occlusion technique as abdominal aortic pressure was reduced in 25-mmHg decrements from 125 to 25 mmHg. Capillary pressure was not altered by reduction of arterial pressure from 125 to 100 mmHg, but it decreased progressively when arterial pressure was reduced from 100 to 25 mmHg. As perfusion pressure was reduced, capillary filtration rate decreased progressively, while the capillary filtration coefficient increased. The progressive decrease in capillary pressures was less than that predicted for a totally passive system, implying that capillary pressure was autoregulated to some degree. However, analysis of pre- to postcapillary resistance ratios suggested that the degree of capillary pressure autoregulation was minimal when perfusion pressures varied over a range of 100-25 mmHg. Capillary filtration rate was maintained better than would be predicted from the measured fall in capillary pressure by readjustments of interstitial Starling forces. These results indicate that capillary pressure is poorly autoregulated in rat skeletal muscle but that compensatory readjustments in interstitial Starling forces help maintain fluid balance and prevent excess dehydration of the interstitium of skeletal muscle as arterial pressure is reduced.
Compacting of Stainless Steel Powders (2015)

Abstract This article provides an overview of the compaction of metal powder in a rigid die and reviews the compaction characteristics of stainless steel powders, including green density, compressibility, green strength, apparent density, flow rate, and sintered density. It describes the influence of compaction characteristics of stainless steel powders in tool materials selection, lubrication, annealing, double pressing/double sintering, and warm compaction.
Task-Relevant Adversarial Imitation Learning (2019)

We show that a critical vulnerability in adversarial imitation is the tendency of discriminator networks to learn spurious associations between visual features and expert labels. When the discriminator focuses on task-irrelevant features, it does not provide an informative reward signal, leading to poor task performance. We analyze this problem in detail and propose a solution that outperforms standard Generative Adversarial Imitation Learning (GAIL). Our proposed method, Task-Relevant Adversarial Imitation Learning (TRAIL), uses constrained discriminator optimization to learn informative rewards. In comprehensive experiments, we show that TRAIL can solve challenging robotic manipulation tasks from pixels by imitating human operators without access to any task rewards, and clearly outperforms comparable baseline imitation agents, including those trained via behaviour cloning and conventional GAIL.
Supplementary Data Figure S1 from ARX788, a Site-specific Anti-HER2 Antibody–Drug Conjugate, Demonstrates Potent and Selective Activity in HER2-low and T-DM1–resistant Breast and Gastric Cancers (2023)

&lt;p&gt;Amino acid sequence of the antibody used in ARX788. The complementarity determining regions (CDRs) are underlined, and the pAF is depicted as a "U".&lt;/p&gt;
A new FPGA detailed routing approach via search-based Boolean satisfiability (2002)

Boolean-based routing methods transform the geometric FPGA routing task into a large but atomic Boolean function with the property that any assignment of input variables that satisfies the function specifies a valid routing solution. We present a new search-based satisfiability (SAT) FPGA detailed routing formulation that handles all channels in an FPGA simultaneously. The formulation has the virtue that it considers all nets concurrently allowing higher degrees of freedom for each net, in contrast to the classical one-net-at-a-time approaches and is able to prove the unroutability of a given circuit by demonstrating the absence of a satisfying assignment to the routing Boolean function. To demonstrate the effectiveness of this method, we first present comparative experimental results between integer linear programming (ILP)-based routing, which is an alternative concurrent method, and SAT-based routing. We also present the. first comparisons of search-based Boolean SAT routing results to other conventional routers and offer the first evidence that SAT methods can actually demonstrate the unroutability of a layout. Preliminary experimental results suggest that our approach compares very favorably with both the ILP-based approach and conventional FPGA routers.