gebhart/patrepeval huggingface dataset:
Data from AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-x<sub>L</sub>, Induces Tumor Regression in Hematologic Cancer Models without Dose-limiting Thrombocytopenia (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Targeting Bcl-2 family members upregulated in multiple cancers has emerged as an important area of cancer therapeutics. While venetoclax, a Bcl-2–selective inhibitor, has had success in the clinic, another family member, Bcl-x&lt;sub&gt;L&lt;/sub&gt;, has also emerged as an important target and as a mechanism of resistance. Therefore, we developed a dual Bcl-2/Bcl-x&lt;sub&gt;L&lt;/sub&gt; inhibitor that broadens the therapeutic activity while minimizing Bcl-x&lt;sub&gt;L&lt;/sub&gt;–mediated thrombocytopenia.&lt;/p&gt;Experimental Design:&lt;p&gt;We used structure-based chemistry to design a small-molecule inhibitor of Bcl-2 and Bcl-x&lt;sub&gt;L&lt;/sub&gt; and assessed the activity against &lt;i&gt;in vitro&lt;/i&gt; cell lines, patient samples, and &lt;i&gt;in vivo&lt;/i&gt; models. We applied pharmacokinetic/pharmacodynamic (PK/PD) modeling to integrate our understanding of on-target activity of the dual inhibitor in tumors and platelets across dose levels and over time.&lt;/p&gt;Results:&lt;p&gt;We discovered AZD4320, which has nanomolar affinity for Bcl-2 and Bcl-x&lt;sub&gt;L&lt;/sub&gt;, and mechanistically drives cell death through the mitochondrial apoptotic pathway. AZD4320 demonstrates activity in both Bcl-2– and Bcl-x&lt;sub&gt;L&lt;/sub&gt;–dependent hematologic cancer cell lines and enhanced activity in acute myeloid leukemia (AML) patient samples compared with the Bcl-2–selective agent venetoclax. A single intravenous bolus dose of AZD4320 induces tumor regression with transient thrombocytopenia, which recovers in less than a week, suggesting a clinical weekly schedule would enable targeting of Bcl-2/Bcl-x&lt;sub&gt;L&lt;/sub&gt;–dependent tumors without incurring dose-limiting thrombocytopenia. AZD4320 demonstrates monotherapy activity in patient-derived AML and venetoclax-resistant xenograft models.&lt;/p&gt;Conclusions:&lt;p&gt;AZD4320 is a potent molecule with manageable thrombocytopenia risk to explore the utility of a dual Bcl-2/Bcl-x&lt;sub&gt;L&lt;/sub&gt; inhibitor across a broad range of tumor types with dysregulation of Bcl-2 prosurvival proteins.&lt;/p&gt;&lt;/div&gt;
Effect of bromination on the electrochemistry, frontier orbitals, and spectroscopy of metallocorroles (2011)

A series of fully β-pyrrole brominated triarylcorrole metal complexes has been prepared for investigating the changes in visible spectra and redox potentials relative to the non-brominated derivatives, as well as for comparing the effect of bromination in corroles and porphyrins. The results reveal that bromination has a much larger effect on the electrochemistry of metallocorroles relative to metalloporphyrins, for both macrocycle- and metal-centered redox processes. The HOMO–LUMO gap energy of the triarylcorrole post-transition metal complexes decreases upon bromination because the effect on the LUMO is about twice as large of as on the HOMO; and both the HOMO and the LUMO are more affected in corroles than in porphyrins. Spectroscopic examinations of the transition metal complexes reveal that the synthetic access to divalent metallocorroles becomes feasible for the brominated derivatives.
Efficient Targeted Learning of Heterogeneous Treatment Effects for Multiple Subgroups (2022)

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this paper, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we further expand this path of research by looking at a variation of the one-step TMLE that is robust to the presence of small estimated propensity scores in finite samples. From our simulations, our method demonstrates substantial finite sample improvements compared to conventional methods. In a case study, our method unveils the potential treatment effect heterogeneity of rs12916-T allele (a proxy for statin usage) in decreasing Alzheimer's disease risk.
Characterization of angular channel response with lowpass filters by using semi-directional antennas (2006)

The use of semi-directional antennas with signal processing in the angular frequency domain of the received voltage signal is proposed to improve characterization of the angular channel measurements. Direct deconvolution of the received signal with the gain function of the deployed antennas has been proposed to extract an angular channel estimation from a measured signal received by rotating an antenna in a given environment. In practice, significant erroneous results are caused by noise variations and the overly sensitive nature of the measurement system. In this paper, we describe the error mechanisms in the channel characterization and a method of producing angle of arrival (AoA) information independent of features of the measurement antenna patterns by filtering in the angular frequency domain. Our proposed scheme enhances the flexibility and tolerance of the angular channel sounding systems.
ARQ Concept for the UMTS Long-Term Evolution (2006)

Work is ongoing in 3GPP to significantly extend the performance of UMTS in the work item long term evolution (LTE). LTE contains a new system architecture with fewer infrastructure nodes and it has been decided to terminate the ARQ functionality in the evolved node B. This paper describes the requirements that exists for an LTE ARQ concept and outlines a solution that fulfills these requirements in the new LTE architecture. The solution builds on two layered ARQ feedback mechanisms that provide sufficient reliability with a low resource cost for the feedback The paper contains thorough stepwise argumentation how we arrived at the proposed ARQ concept.
Augmenting web pages and search results to support credibility assessment (2011)

The presence (and, sometimes, prominence) of incorrect and misleading content on the Web can have serious consequences for people who increasingly rely on the internet as their information source for topics such as health, politics, and financial advice. In this paper, we identify and collect several page features (such as popularity among specialized user groups) that are currently difficult or impossible for end users to assess, yet provide valuable signals regarding credibility. We then present visualizations designed to augment search results and Web pages with the most promising of these features. Our lab evaluation finds that our augmented search results are particularly effective at increasing the accuracy of users'" credibility assessments, highlighting the potential of data aggregation and simple interventions to help people make more informed decisions as they search for information online.
Gas hold‐up and bubble behavior in an upflow packed bed column in the limit of low flow rate (2019)

Significance Gas–liquid up‐flow in a packed bed is studied experimentally in the limit of zero flow rate. Two patterns of bubble behavior are detected based on the magnitude of the Bond number ( Bo ). The gas hold‐up of the bed is found to be nonmonotonic with a maximum around Bo of unity. The bubble to particle diameter ratio is found to scale inversely with Bo .
HyCube: A distributed hash table based on a variable metric (2016)

proved to be scalable decentralized systems providing efficient resource location. This paper concentrates on efficiency and resilience to node failures of DHT systems and presents a novel model of a distributed hash table based on a hierarchical hypercube geometry, called HyCube. The DHT geometry, the choice of the metric defining logical distances between nodes, and the routing algorithm have fundamental influence on routing efficiency and resilience. The use of the one-dimensional model (placing the nodes logically on a ring) allows the nodes to maintain sets of references called sequential neighbors -certain numbers of neighbors that are the closest existing nodes in both directions on the ring. Such a model yields a very high level of resilience to node failures. The new approach, presented in the paper, employs a variable multi-dimensional metric adopting the Steinhaus transform. Routing, lookup and search algorithms are discussed, as well as routing table nodes selection and selforganization techniques. It is shown that the new approach allows reaching a higher level of resilience to node failures, as well as a shorter average routing path length than with the use of the sequential neighbors sets.
Monoallelic Heb/Tcf12 Deletion Reduces the Requirement for NOTCH1 Hyperactivation in T-Cell Acute Lymphoblastic Leukemia (2022)

Early T-cell development is precisely controlled by E proteins, that indistinguishably include HEB/TCF12 and E2A/TCF3 transcription factors, together with NOTCH1 and pre-T cell receptor (TCR) signalling. Importantly, perturbations of early T-cell regulatory networks are implicated in leukemogenesis. NOTCH1 gain of function mutations invariably lead to T-cell acute lymphoblastic leukemia (T-ALL), whereas inhibition of E proteins accelerates leukemogenesis. Thus, NOTCH1, pre-TCR, E2A and HEB functions are intertwined, but how these pathways contribute individually or synergistically to leukemogenesis remain to be documented. To directly address these questions, we leveraged <i>Cd3e</i>-deficient mice in which pre-TCR signaling and progression through β-selection is abrogated to dissect and decouple the roles of pre-TCR, NOTCH1, E2A and HEB in SCL/TAL1-induced T-ALL, <i>via</i> the use of <i>Notch1</i> gain of function transgenic (<i>Notch1IC</i><sup>tg</sup>) and <i>Tcf12</i><sup>+/-</sup> or <i>Tcf3</i><sup>+/-</sup> heterozygote mice. As a result, we now provide evidence that both HEB and E2A restrain cell proliferation at the β-selection checkpoint while the clonal expansion of SCL-LMO1-induced pre-leukemic stem cells in T-ALL is uniquely dependent on <i>Tcf12</i> gene dosage. At the molecular level, HEB protein levels are decreased <i>via</i> proteasomal degradation at the leukemic stage, pointing to a reversible loss of function mechanism. Moreover, in <i>SCL-LMO1</i>-induced T-ALL, loss of one <i>Tcf12</i> allele is sufficient to bypass pre-TCR signaling which is required for <i>Notch1</i> gain of function mutations and for progression to T-ALL. In contrast, <i>Tcf12</i> monoallelic deletion does not accelerate <i>Notch1IC</i>-induced T-ALL, indicating that <i>Tcf12</i> and <i>Notch1</i> operate in the same pathway. Finally, we identify a tumor suppressor gene set downstream of HEB, exhibiting significantly lower expression levels in pediatric T-ALL compared to B-ALL and brain cancer samples, the three most frequent pediatric cancers. In summary, our results indicate a tumor suppressor function of HEB/TCF12 in T-ALL to mitigate cell proliferation controlled by NOTCH1 in pre-leukemic stem cells and prevent NOTCH1-driven progression to T-ALL.
Gouverner (par) les finances publiques (2011)

Résumé L’étude des relations financières et fiscales intergouvernementales constitue une branche dynamique de la science politique et de l’économie dans les pays anglo-saxons à structure fédérale, matière largement méconnue dans les pays unitaires comme la France. Après en avoir présenté l’objet et quelques grands questionnements et apports, on soulignera l’ampleur des décalages entre modèles théoriques de répartition des compétences et responsabilités fiscales, et réalités empiriques : les gouvernements infranationaux sont incapables de couvrir leurs dépenses par des revenus autonomes, ce qui implique des transferts verticaux, qui érodent les responsabilités fiscales ; la répartition des compétences entre les niveaux de gouvernement est floue. Ces phénomènes nourrissent des comportements de transfert de blâme entre les élites de différents niveaux. Ce chapitre le montre à partir d’une relecture de trente années de relations financières intergouvernementales en France. Il souligne au final que la décentralisation a pu créer un terreau favorable au développement de comportements opportunistes, de la part des élites tant centrales que locales, et présente une étude des réformes récentes des finances et de la fiscalité locales, réformes qui s’efforcent de réguler à ces compromis inflationnistes.
Generation of sub-200-fs microjoule pulses from an all-fiber CPA system (2011)

Chirped-pulse amplification (CPA) is an established scheme for the generation of high-energy femtosecond pulses. At the wavelength of 1 μm a standard fiber stretcher exhibiting normal second-order dispersion β2 can be used in combination with a grating compressor. But for ultrashort pulses with broad spectra, this scheme is disadvantageous due to the cumulative positive third-order dispersion (TOD) β3 of the stretcher and the compressor. As a consequence, the advantages of the fiber stretcher as a waveguide device are accompanied by longer minimum pulse durations compared to the use of a grating stretcher, unless the TOD is addressed by a more complicated compressor setup with gratings and prisms.
Electrotonic load triggers remodeling of repolarizing current Ito in ventricle (2004)

A change in activation sequence electrically remodels ventricular myocardium, causing persistent changes in repolarizing currents (T-wave memory). However, the underlying mechanism for triggering activation sequence-dependent remodeling is unknown. Optical action potentials were mapped with high resolution from the epicardial surface of the arterially perfused canine wedge preparation (n = 23) during 30 min of baseline endocardial stimulation, followed by 40 min of epicardial stimulation, and, finally, restoration of endocardial stimulation. Immediately after the change from endocardial to epicardial stimulation, phase 1 notch amplitude of epicardial cells was attenuated by 74 +/- 8% (P < 0.001) compared with baseline and continued to diminish during the period of epicardial pacing, suggesting progressive remodeling of the transient outward current (Ito). When endocardial pacing was restored, notch amplitude did not immediately recover but remained attenuated by 23 +/- 10% (P < 0.001), also consistent with a remodeling effect. Peak Ito current measured from isolated epicardial myocytes changed by 12 +/- 4% (P < 0.025), providing direct evidence for Ito remodeling occurring on a surprisingly short time scale. The mechanism for triggering remodeling of Ito was a significant reduction (by 14 +/- 4%, P < 0.001) of upstroke amplitude in epicardial cells during epicardial stimulation. Reduction in upstroke amplitude during epicardial pacing was explained by electrotonic load on epicardial cells by fully repolarized downstream endocardial cells. These data suggest a novel mechanism for triggering electrical remodeling in the ventricle. Electrotonic load imposed by a change in activation sequence reduces upstroke amplitude, which, in turn, attenuates Ito according to its known voltage-dependent properties, triggering downregulation of current.
Optimum Diversity-Multiplexing Tradeoff in the Multiple Relays Network (2007)

In this paper, a multiple-relay network in considered, in which $K$ single-antenna relays assist a single-antenna transmitter to communicate with a single-antenna receiver in a half-duplex mode. A new Amplify and Forward (AF) scheme is proposed for this network and is shown to achieve the optimum diversity-multiplexing trade-off curve.
Prediction of Peptide Affinity to HLA DRB1*0401 (1994)

Hydrogen bonding between conserved amino acids in the HLA DR and the peptide backbone of the ligand both provide the majority of free energy of binding and force the peptide ligands to adopt a similar extended conformation. Consequently the corresponding side chains of all peptides interact with similar pockets in the binding site. For peptides of a common length the contribution of the peptide backbone can be treated as a constant and the differential affinity can be viewed as a simple sum of the side chain interactions. These can be quantified by measuring the effects of each of the naturally occurring amino acids in the context of a simplified polyalanine backbone containing an aromatic amino acid to orient the peptide unequivocally in the binding site. The dataset of the relative contributions can be used to predict quantitatively the affinity of any peptide sequence.
Clash of the Titans (2009)

In this work we focus on creating a benchmark suite of concurrent programs for various programming languages to evaluate the bug detection capabilities of various tools and techniques. We have compiled a set of Java benchmarks from various sources and our own efforts. For many of the Java examples we have created equivalent C# programs. All the benchmarks are available for download. In our multi-language benchmark suite we compare results from various tools: CalFuzzer, ConTest, CHESS, and Java Pathfinder. In Java Pathfinder we provide extensive results for state-less random walk, randomized depth-first search, and guided search using abstraction refinement. Using data from our study we argue that iterative context-bounding and dynamic partial order reduction are not sufficient to render model checking for testing concurrent programs tractable and secondary techniques such as guidance strategies are required. As part of this work, we have also created a wiki to publish benchmark details and data from various tools on those benchmarks to a broader research community.
Cooperative dynamics in coupled noisy dynamical systems near a critical point: The dc superconducting quantum interference device as a case study (2006)

Dynamical systems that operate near the onset of coupling-induced oscillations can exhibit enhanced sensitivity to external perturbations under suitable operating parameters. This cooperative behavior and the attendant enhancement in the system response (quantified here via a signal-to-noise ratio at the fundamental of the coupling-induced oscillation frequency) are investigated in this work. As a prototype, we study an array of dc superconducting quantum interference device (SQUID) rings locally coupled, unidirectionally as well as bidirectionally, in a ring configuration; it is well known that each individual SQUID can be biased through a saddle-node bifurcation to oscillatory behavior. We show that biasing the array near the bifurcation point of coupling-induced oscillations can lead to a significant performance enhancement.
Supplementary Figure 3 from NEDD9 Promotes Oncogenic Signaling in Mammary Tumor Development (2023)

Supplementary Figure 3 from NEDD9 Promotes Oncogenic Signaling in Mammary Tumor Development
Memory Dependence Prediction in Multimedia Applications. (2000)

We identify that a set of multimedia applications exhibit highly regular read-after-read (RAR) and read-after-write (RAW) memory dependence streams. We exploit this regularity to predict both RAW and RAR memory dependences. We also study how two previously proposed memory dependence prediction-based memory latency reduction techniques perform for this multimedia workload. In the first technique, a load can obtain a value by simply naming a preceding load (or store) with which a RAR (or RAW) dependence is predicted. The second technique speculatively converts a series of LOAD 1 -USE 1 ,...,LOAD N -USE N (or DEF-STORE-LOAD-USE) chains into a single LOAD 1 -USE 1 ...USE N (or DEF-USE) producer/consumer graph. We show that via memory dependence prediction it is possible to correctly predict 33.3% of all loads on the average. Moreover, the two memory dependence prediction based techniques result on average performance improvements of 2.6% over a highly-aggressive, out-of-order, ...
CD57 defines a functionally unique subset of NK cells in humans (134.1) (2009)

Abstract CD57 is a marker of terminal differentiation on human CD8+ T cells and possibly on human NK cells. Newborn and fetal NK cells do not express CD57, however the frequency of CD57-bearing NK cells increases with age. Utilizing PBMC obtained from healthy donors we are assessing the phenotypic and functional differences between CD57+ and CD57neg NK cells. CD57+ NK cells express different activation markers and a distinct repertoire of NK receptors suggestive of a more mature phenotype. Preliminary data also indicate that there is a higher frequency of IFNγ CD57+ NK cells compare to CD57neg NK cells when stimulated through their activating receptors, CD57+ NK cells are less sensitive to activation-induced apoptosis, and interestingly, proliferate less when co-cultured with target cells and/or cytokines. The combination of a more activated phenotype and a decreased capacity to proliferate suggests CD57+ NK cells are terminally differentiated. Studies are underway to assess the phenotypic and functional differences of CD57+ and CD57neg NK cells during infection with HIV and other viruses. Funding: NIH. SLV is a Cancer Research Institute/Irvington Institute Fellow. LLL is an American Cancer Society Professor.
Overview of SMARTCAT - Systematic, Material-oriented Approach using Rational design to develop break-Through Catalyst s for commercial automotive PEMFC (2015)

Communication orale
Targeted therapy for high-risk endometrial carcinoma (2012)

SUMMARY Type II endometrial cancers exhibit distinct histopathology, underlying pathogenesis and clinical behavior. These high-risk cancers are associated with an aggressive clinical course and a relatively poor prognosis that underscores the need for the development of novel rational therapeutic strategies that exploit their distinct underlying molecular pathway alterations. In this review, we describe the extent of disease burden and molecular characterization of type II endometrial cancers, summarize the historical development to support current standards of care and delineate the most recent preclinical and clinical advances in immunotherapy, cytotoxic agents and small-molecule inhibitors for this disease.
Statistical Model Using Geometrical-Optical Space Classification: Expansion of Applicable Frequencies to the 5 GHz Band (2018)

The method for estimating propagation loss that classifies receiving points into multiple groups by focusing on the number of reflections and diffractions, and applies a separate statistical model to each group was extended from only 2.4 GHz band to both 2.4 GHz and 5 GHz band. The extended statistical model was created from received power measurements. First, an appropriate grouping method was investigated based on the fitting error of statistical model. Non-line-of-sight (NLOS) receiving points were grouped in order of points that a wave reflected one time reaches, points that a wave reflected two times reaches, and points that a wave diffracted one time reaches. Next, the effectiveness of the proposed method was verified by comparison with conventional statistical models (one-slope, dual-slope, multi-wall, partitioned) on three office floors that differ from the environment used to create the statistical model. The average NLOS estimation error for the three evaluation environments was 4.9 dB, demonstrating that the proposed method has accuracy equal to or better than that of conventional methods.