gebhart/patrepeval huggingface dataset:
ACTR-29. FINAL RESULTS FROM THE AXIG TRIAL: A RANDOMIZED PHASE II CLINICAL TRIAL INVESTIGATING AXITINIB ALONE OR IN COMBINATION WITH CCNU IN PATIENTS WITH RECURRENT GLIOBLASTOMA (2016)

Axitinib is a small molecule TKI with high affinity and specificity for the VEGFRs and has demonstrated anti-tumor activity in patients with recurrent glioblastoma (rGB). The AXIG trial (NCT01562197) is a randomized clinical trial investigating at first the activity of axitinib monotherapy (AXI-arm) versus physicians best alternative choice of therapy (Duerinck et al. JNO Mar2016) and, following amendment, axitinib monotherapy versus axitinib plus lomustine (Duerinck et al. ASCO AM2016) in patients with rGB. A pooled analysis including all patients exposed to axitinib was performed. Between August 2011 and July 2015, 78 pts were enrolled in the trial and initiated axitinib monotherapy (N:50; AXI) or axitinib plus lomustine (N:28; AXILOM). Median age was 55y [range 18–80], 50M/28F. Baseline characteristics were well balanced between study arms. Thirteen pts in the AXI-arm crossed-over at the time of progression(AXIseqLOM). Treatment was generally well tolerated. AXILOM pts were at higher risk for grade 3/4 neutropenia (0% vs. 21%) and thrombocytopenia (4% vs 29%). BORR in the AXI arm was 26% (2CR/11PR) vs. 43% in the AXILOM-arm (1CR/11PR). BORR after adding CCNU to axitinib at progression on axitinib (AXIseqLOM) was 1 PR and 8SD. 6mPFS and OS rates were respectively 26% (95% CI 14–38) vs 17% (95% CI 2–32), and 54% (95% CI40-68) vs. 53% (95% CI34-73) for pts treated in the AXI vs. AXILOM-arms. When the time-to-second progression was taken into account for the 9 AXIseqLOM patients who experienced PR or SD following the addition of lomustine at first PD on axitinib, 6-mths PFS was 39% (95% CI21-57). No significant correlation was found between clinical outcome measures and the MGMT promoter methylation status or IDH1/2 mutation status. Axitinib has single-agent activity in patients with rGB; upfront combination of axitinib and LOM did not significantly increase progression-free or overall survival in patients with recurrent glioblastoma.
Advances in industrial biopharmaceutical batch process monitoring: Machine‐learning methods for small data problems (2018)

Biopharmaceutical manufacturing comprises of multiple distinct processing steps that require effective and efficient monitoring of many variables simultaneously in real-time. The state-of-the-art real-time multivariate statistical batch process monitoring (BPM) platforms have been in use in recent years to ensure comprehensive monitoring is in place as a complementary tool for continued process verification to detect weak signals. This article addresses a longstanding, industry-wide problem in BPM, referred to as the "Low-N" problem, wherein a product has a limited production history. The current best industrial practice to address the Low-N problem is to switch from a multivariate to a univariate BPM, until sufficient product history is available to build and deploy a multivariate BPM platform. Every batch run without a robust multivariate BPM platform poses risk of not detecting potential weak signals developing in the process that might have an impact on process and product performance. In this article, we propose an approach to solve the Low-N problem by generating an arbitrarily large number of in silico batches through a combination of hardware exploitation and machine-learning methods. To the best of authors' knowledge, this is the first article to provide a solution to the Low-N problem in biopharmaceutical manufacturing using machine-learning methods. Several industrial case studies from bulk drug substance manufacturing are presented to demonstrate the efficacy of the proposed approach for BPM under various Low-N scenarios.
Hyperbranched Polymers by Visible Light Induced Self-Condensing Vinyl Polymerization and Their Modifications (2013)

Visible light induced self-condensing vinyl polymerization is explored using 2-bromoethyl methacrylate (2-BEMA) and methyl methacrylate (MMA) as inimer and comonomer, respectively, in the presence of dimanganese decacarbonyl (Mn2(CO)10) for the preparation of hyperbranched polymers. Upon photoexcitation in the visible range, Mn2(CO)10 undergoes irreversible decomposition leading to the formation of initiating radicals through bromine abstraction from 2-BEMA. Depending on the concentrations of 2-BEMA and Mn2(CO)10 and irradiation time, hyperbranched polymers with different branching density and cross-linked polymers were formed. The resulting polymers possess unreacted bromide groups in the structure which allow postfunctionalization through visible light photopolymerization and Cu(I)-catalyzed click reactions.
UCov: a user‐defined coverage criterion for test case intent verification (2016)

Summary The goal of regression testing is to ensure that the behaviour of existing code, believed correct by previous testing, is not altered by new program changes. This paper argues that the primary focus of regression testing should be on code associated with (1) earlier bug fixes and (2) particular application scenarios considered to be important by the developer or tester. Existing coverage criteria do not enable such focus, for example, 100% branch coverage does not guarantee that a given bug fix is exercised or a given application scenario is tested. Therefore, there is a need for a new and complementary coverage criterion in which the user can define a test requirement characterizing a given behaviour to be covered as opposed to choosing from a pool of pre‐defined and generic program elements. This paper proposes this new methodology and calls it UCov , a user‐defined coverage criterion wherein a test requirement is an execution pattern of program elements, and possibly predicates, that a test case must satisfy. The proposed criterion is not meant to replace existing criteria, but to complement them as it focuses the testing on important code patterns that could go untested otherwise. UCov supports test case intent verification . For example, following a bug fix, the testing team may augment the regression suite with the test case that revealed the bug. However, this test case might become obsolete due to code modifications not related to the bug. But if a test requirement characterizing the bug was defined by the user, UCov would determine that test case intent verification failed. The UCov methodology was implemented for the Java platform, was successfully applied onto 10 real‐life case studies and was shown to have advantages over JUnit . The implementation comprises the following tools: (1) TRSpec : allows the user to easily specify complex test requirements; (2) TRCheck : checks whether user‐defined test requirements were satisfied, that is, supports test case intent verification; and (3) TRMigrate : migrates user‐defined test requirements to subsequent versions of a given program. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Supplemental Figure 5 from Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in Metastatic Uveal Melanoma (2023)

&lt;p&gt;Supplementary Figure 5: cMET expression by flow and IGF signaling.&lt;/p&gt;
Simplified simulation and modeling technique for integrated magnetic components in power electronic converters (2005)

The inductance modeling technique is used as the traditional method for analyzing magnetic components. This model is simple to generate for individual components, i.e., an inductor and a transformer. However, it becomes difficult to realize this model for the integrated magnetic structures where multiple inductors and transformers exist on one assembly. In addition, it is difficult to model the effect of the magnetic saturation in the inductance model. This work presents a simple model for the discreet as well as integrated magnetic components. In this model, the magnetic circuit is converted to a pure electric circuit with capacitors; every winding is replaced with a pair of current controlled voltage sources, namely a Gyrator. Finally, the complete simulation model for the isolated Cuk converter with integrated magnetics is presented as an illustrative example.
Flow-cytometric evaluation of lymphocyte subpopulations in synchronously developing Schistosoma mansoni egg and Sephadex bead pulmonary granulomas. (1988)

Synchronous models of T-cell-mediated and foreign body granulomas were induced in mice by intravenous embolization of Schistosoma mansoni eggs and Sephadex beads, respectively. The authors then performed flow-cytometric analysis of lymphocytes from dispersed granulomas, spleens, and peripheral blood at 4, 8, 16, and 32 days corresponding to the induction, growth, and maintenance, and resolution of these lesions. Lymphocytes were identified on the basis of light scatter characteristics, and the nature of the cells was confirmed by cell sorting and electron-microscopic examination. Lymphocyte subpopulations were characterized with antibodies to lymphocyte surface markers, specifically Ig, Thy 1.2, Lyt 1, Lyt 2, and L3T4. Natural killer cells were identified with anti-asialo GM1. Egg-induced granulomas had more lymphocytes of all phenotypes at all time points. Surprisingly, there was a significant number of cells staining positive for asialo GM1. On Day 16 after embolization there was a greater percentage of helper T cells, as defined by positive staining with L3T4, in the egg model, compared with the bead model. There was no obvious shift of lymphocytes from either the blood or spleen into the granuloma. These data confirm the importance of T cells in the direct participation of granulomatous inflammation, and the large numbers of asialo GM1-positive cells suggest a role for natural killer cells.
A safe path vector protocol (2002)

An IP routing protocol is safe if it is guaranteed to converge in the absence of network topology changes. BGP, currently the only interdomain routing protocol employed on the Internet, is not safe in this sense. It may seem that the source of BGP's potential divergence is inherent in the requirements for any interdomain routing protocol-policy-based metrics must be allowed to override distance-based metrics, and each autonomous system must be allowed to independently define its routing policies with little or no global coordination. In this paper we present a simple path vector protocol (SPVP) that captures the underlying semantics of BGP by abstracting away all nonessential details. We then add a dynamically computed attribute to SPVP routing messages, called the route history. Protocol oscillations caused by policy conflicts produce routes whose histories contain cycles. These cycles identify the policy conflicts and the autonomous systems involved. SPVP is made safe by automatically suppressing routes whose histories contain cycles. We discuss how this safe SPVP can be used in the design of a safe BGP.
Target and afferents interact to control developmental cell death in the mesencephalic parabigeminal nucleus of the rat (1996)

During the period of natural cell death in the developing mammalian brain, both target cells and afferents have been shown to be important for neuronal survival. Here we demonstrate that afferents and targets have interactive roles in the maintenance of cells during development of the mesencephalic parabigeminal nucleus (PB) in rats. Pyknotic nuclei were counted in the PB of developing rats that received a bilateral lesion of the superior colliculus on the day of birth (PO). We observed that simultaneous deafferentation and deefferentation leads to a large peak of cell death at P1–2 in all three divisions of PB. Later the rate of pyknosis decreases and a second period of elevated cell death is observed just before the complete disappearance of the nucleus at P7–8. Counts of healthy neurones indicates two separate periods of increased neuronal loss. The first period occurs at P1–2, and the last and dramatic episode of cell loss at P8 leads to the disappearance of the PB. The combined effects of simultaneous target removal and deafferentation were different from the sum of the individual effects, indicating that the axonal targets and the afferents interact to control cell survival in the PB. © 1996 Wiley-Liss, Inc.
Controlling Light Transmission Through Highly Scattering Media Using Semi-Definite Programming as a Phase Retrieval Computation Method (2017)

Abstract Complex Semi-Definite Programming (SDP) is introduced as a novel approach to phase retrieval enabled control of monochromatic light transmission through highly scattering media. In a simple optical setup, a spatial light modulator is used to generate a random sequence of phase-modulated wavefronts, and the resulting intensity speckle patterns in the transmitted light are acquired on a camera. The SDP algorithm allows computation of the complex transmission matrix of the system from this sequence of intensity-only measurements, without need for a reference beam. Once the transmission matrix is determined, optimal wavefronts are computed that focus the incident beam to any position or sequence of positions on the far side of the scattering medium, without the need for any subsequent measurements or wavefront shaping iterations. The number of measurements required and the degree of enhancement of the intensity at focus is determined by the number of pixels controlled by the spatial light modulator.
The effect of flosequinan in patients with acute-onset heart failure complicating acute myocardial infarction. (1989)

We studied the hemodynamic effect of a single dose of the new direct-acting vasodilator, flosequinan, in 25 patients with severe acute-onset heart failure complicating acute myocardial infarction, which was resistant to high doses of diuretics, nitrates and dobutamine given intravenously. Flosequinan was added to conventional therapy within 3.7 +/- 0.8 days of the infarction in the form of a single oral dose of 100 mg. Hemodynamic monitoring was performed every hour for 4 hours after the administration, without any other drug being added. Flosequinan produced hemodynamic improvement in all patients. The effect peaked at 1 to 2 hours and remained at this level at 4 hours. Pulmonary capillary wedge pressure decreased from 28.4 +/- 4.5 to 17.8 +/- 5.7 mmHg and cardiac output increased from 3.5 +/- 0.3 to 4.0 +/- 0.4 L/min (p less than 0.05 for both). Pulmonary arterial and pulmonary vascular resistances were also significantly reduced. Heart rate was not significantly altered. Mean systemic arterial pressure was slightly but not significantly reduced. Administration of flosequinan was not associated with symptomatic hypotension, cardiac arrhythmias or other adverse events and the hemodynamic effect was not related to the pre-treatment serum sodium concentration. We conclude that flosequinan is effective in producing acute hemodynamic improvement in patients with heart failure complicating acute myocardial infarction which is resistant to conventional therapy. Flosequinan is well tolerated in this group of patients and therefore further studies to determine the duration of action of the drug in this condition are appropriate.
Shared memory consistency models: a tutorial (1996)

The memory consistency model of a system affects performance, programmability, and portability. We aim to describe memory consistency models in a way that most computer professionals would understand. This is important if the performance-enhancing features being incorporated by system designers are to be correctly and widely used by programmers. Our focus is consistency models proposed for hardware-based shared memory systems. Most of these models emphasize the system optimizations they support, and we retain this system-centric emphasis. We also describe an alternative, programmer-centric view of relaxed consistency models that describes them in terms of program behavior, not system optimizations.
Ring-Closing Metathesis-Based Synthesis of (3R,4R,5S)-4-Acetylamino-5-amino-3-hydroxy- cyclohex-1-ene-carboxylic Acid Ethyl Ester:  A Functionalized Cycloalkene Skeleton of GS4104 (2006)

(3R,4R,5S)-4-Acetylamino-5-amino-3-hydroxy-cyclohex-1-ene-carboxylic acid ethyl ester, a functionalized cyclohexene skeleton of GS4104, was diastereoselectively synthesized. A major advantage of this synthesis is the use of readily available L-serine to replace frequently used (-)-shikimic acid or (-)-quinic acid as the starting material. Ring-closing metathesis and diastereoselective Grignard reactions successfully served as the key steps. Absolute configurations of the key intermediates were confirmed by corresponding two-dimensional NMR studies.
Genetics of Group A Streptococci (2019)

<i>Streptococcus pyogenes</i> (group A streptococcus) is remarkable in terms of the large number of diseases it can cause in humans and for the large number of streptococcal factors that have been identified as potential virulence determinants for these diseases. A challenge is to link the function of potential virulence factors to the pathogenesis of specific diseases. An exciting advance has been the development of sophisticated genetic systems for the construction of loss-of-function, conditional, hypomorphic, and gain-of-function mutations in targeted <i>S. pyogenes</i> genes that can be used to test specific hypotheses regarding these genes in pathogenesis. This will facilitate a mechanistic understanding of how a specific gene function contributes to the pathogenesis of each streptococcal disease. Since the first <i>S. pyogenes</i> genome was completed in 2001, hundreds of complete and draft genome sequences have been deposited. We now know that the average <i>S. pyogenes</i> genome is approximately 1.85 Mb and encodes ∼1,800 genes and that the function of most of those genes in pathogenesis remains to be elucidated. However, advances in the development of a variety of genetic tools for manipulation of the <i>S. pyogenes</i> genome now provide a platform for the interrogation of gene/phenotype relationships for individual <i>S. pyogenes</i> diseases, which may lead to the development of more sophisticated and targeted therapeutic interventions. This article presents an overview of these genetic tools, including the methods of genetic modification and their applications.
ChemInform Abstract: SELECTIVITIES IN THE REACTIONS OF ALKYL‐, ARYL‐ AND HETEROSUBSTITUTED ORGANOTITANIUM COMPOUNDS. PRELIMINARY COMMUNICATION (1981)

Abstract Die Titel‐Tita.nverbindungen (I) sind durch Umsetzung entsprechender Chloro‐Titanderivate mit Organolithium‐ oder Grignardverbindungen allgemein zugänglich.
Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos. (1995)

The dorsoventral axis is established early in Xenopus development and may involve signaling by Wnts, a family of Wnt1-protooncogene-related proteins. The protein kinase shaggy functions in the wingless/Wnt signaling pathway, which operates during Drosophila development. To assess the role of a closely related kinase, glycogen synthase kinase 3 beta (GSK-3 beta), in vertebrate embryogenesis, we cloned a cDNA encoding a Xenopus homolog of GSK-3 beta (XGSK-3 beta). XGSK-3 beta-specific transcripts were detected by Northern analysis in Xenopus eggs and early embryos. Microinjection of the mRNA encoding a catalytically inactive form of rat GSK-3 beta into a ventrovegetal blastomere of eight-cell embryos caused ectopic formation of a secondary body axis containing a complete set of dorsal and anterior structures. Furthermore, in isolated ectodermal explants, the mutant GSK-3 beta mRNA activated the expression of neural tissue markers. Wild-type XGSK-3 beta mRNA suppressed the dorsalizing effects of both the mutated GSK-3 beta and Xenopus dishevelled, a proposed upstream signaling component of the same pathway. These results strongly suggest that XGSK-3 beta functions to inhibit dorsoventral axis formation in the embryo and provide evidence for conservation of the Wnt signaling pathway in Drosophila and vertebrates.
Age-Dependent Effects of Peripheral Inflammation on the Electrophysiological Properties of Neonatal Rat Dorsal Horn Neurons (2002)

The aim of this study was to investigate the postnatal development of spinal cord neurophysiological mechanisms of inflammatory pain. The effect of hindpaw inflammation on the properties of neonatal spinal dorsal horn cells was investigated in urethane-anesthetized newborn rats using in vivo single-unit extracellular recordings. Responses to cutaneous mechanical and electrical A and C fiber stimulation were recorded at postnatal day (P) 3, 10, and 21 in pups that had received a unilateral intraplantar carageenan injection (1%, 1 microl/g body wt) 2-5 h earlier and compared with age-matched controls. At all three ages, carageenan inflammation increased A fiber evoked sensitization, spontaneous activity, and the suprathreshold response magnitude of dorsal horn cells. Receptive field size, which normally decreases with postnatal age, was unaffected by inflammation in P3 and P10 pups but significantly increased at P21 so that the size distribution closely resembled that in control P3 pups. Mechanical thresholds of individual dorsal horn neurons were not altered by carageenan inflammation at any age. The results show that some dorsal horn cell properties that are likely to underlie inflammatory hypersensitivity such as increased spontaneous activity and response magnitude are observed from the earliest postnatal age examined (P3). However inflammation induced expansion of mechanical receptive field size is not observed until at least the second postnatal week. These results have implications for the postnatal processing of inflammatory pain.
EVALUATION OF A WORD RECOGNITION SYSTEM USING SYNTAX ANALYSIS. (1977)

A speech recognition system has been implemented which accepts reasonably natural English sentences spoken as isolated words. The major components of the system are a speaker-dependent word recognizer, a programmed grammar, and a syntax analyzer. The system permits formulation of complete sentences from a vocabulary of 127 words. The set of sentences selected for investigation is intended for use as requests in an automated travel information system. Results are presented of evaluations for speakers using their own stored reference patterns, the reference patterns of other speakers, and composite reference patterns averaged over several speakers. For speakers using their own reference patterns the median error rate for acoustic recognition of the individual words is 11.7 percent. When syntax analysis is applied to the complete sentence, word recognition errors can be corrected and the error rate reduced to 0.4 percent.
How They Vote: Issue-Adjusted Models of Legislative Behavior (2012)

We develop a probabilistic model of legislative data that uses the text of the bills to uncover lawmakers ’ positions on specific political issues. Our model can be used to explore how a lawmaker’s voting patterns deviate from what is expected and how that deviation depends on what is being voted on. We derive approximate posterior inference algorithms based on variational methods. Across 12 years of legislative data, we demonstrate both improvement in heldout predictive performance and the model’s utility in interpreting an inherently multi-dimensional space. 1