gebhart/patrepeval huggingface dataset:
Use of cMet Crystal Structures to Identify Potential Drug‐Resistant Mutants (2009)

For Oncology drugs targeted to tyrosine kinases, drug‐resistance often occurs from selection of cells harboring mutations in the kinase domain of the target. The identification of potential drug‐resistant mutants in advance of patient treatment allows for early design of second‐generation drugs that retain selectivity for these mutants. Towards this goal, co‐crystal structures of two diverse inhibitors were generated. Based on these structures, 11 mutants at 5 positions within the ATP pocket were examined. The kinetic parameters for the mutants were compared to wild‐type (WT) for both the basal and activated enzyme forms. Numerous differences were observed, but most notably the activated M1229 and Y1230 mutants had elevated catalytic efficiencies relative to WT. Two distinct inhibitors were studied against this panel, the oxindole SU11274 and the diaminopyrimidine compound 1. Two mutants (I1084L, M1229I) had higher affinity than WT for both inhibitors in both conformations and the gatekeeper L1157I mutant had substantially lower affinity. SU11274 also had reduced affinity for Y1230 and D1228 mutants, whereas the shifts were much less pronounced with compound 1. These data expand the repertoire of mutations in the ATP pocket that retain or enhance enzymatic activity and show that these mutants can display divergent effects on the potency of inhibitors from different chemical series.
A Tale of Seemingly “Identical” Silicon Quantum Dot Families: Structural Insight into Silicon Quantum Dot Photoluminescence (2020)

“Two quantum dots, both alike in composition, but differing in structure, where we lay our scene, From broader classes, to bring deeper understanding, to the crystalline core that drives the quantum dot’s sheen.” In this contribution we examine two families of silicon quantum dots (SiQDs) that bring to mind the Capulets and the Montagues in Shakespeare’s Romeo and Juliet because of their stark similarities and differences. SiQDs are highly luminescent, heavy-metal-free, and based upon earth-abundant elements. As such, they have attracted attention for far-reaching applications ranging from biological imaging to luminescent solar concentrators to light-emitting diodes that rely on their size-dependent optical response. Unfortunately, correlating SiQDs “size” to their photoluminescence (PL) maximum is often challenging. Herein, we provide essential structural insight into the correlation between the dimensions and PL maximum of SiQDs through a direct comparison of samples that exhibit statistically identical physical dimensions (dTEM) and chemical compositions but different crystallite size (dXRD) and PL maxima. We then expand the scope of this investigation and systematically compare groupings of SiQDs: one in which the dXRD and dTEM agree and one where dXRD < dTEM. This latter comparison clearly shows that dXRD better predicts SiQD optical response when using the well-established effective mass approximation.
Metallocenes with Cp Ring-Fused to Chalcogen Heterocycles: Synthesis and Polymerization Results (2005)

Abstract Substituted metallocene ligands containing cyclopentadiene ring fused to either selenophene or benzo[b]tellurophene were prepared following methods previously developed for analogs containing sulfur. 5-Methyl-4,5-dihydro-cyclopenta[b]-selenophen-6-one ( 2 ) and 3-Methyl-3,4-dihydro-benzo[b]cyclopenta[d]telluraphen-2-one ( 7 ) (major isomers) were prepared by polyphosphoric acid catalyzed Friedel-Crafts acylation/Nazarov cyclization of methacrylic acid onto selenophene and respectively benzo[b]tellurophene. Following reduction of the ketone to alcohol, then dehydration, the chalcogen-containing cyclopentadiene olefins were prepared. The olefins were deprotonated with n-butyllithium followed by either bridging with dichlorodimethylsilane, deprotonation and metallation, or deprotonation and direct metallation. In this manner, isomeric mixtures of –rac/-meso dimethylsilanediylbis(η5-5-Methyl-cyclopenta[b]selenophen-yl)zirconium dichloride ( 5 ) Bis(η5−2-methyl-cyclopenta[b][1 Brintzinger, H. H., Fischer, D., Mülhaupt, R., Rieger, B. and Waymouth, R. 1995. Angew. Chem., 107: 1255[Crossref] , [Google Scholar]]benzotelluraphen-yl)zirconium dichloride ( 9 ) were prepared and characterized. Complexes formed active olefin polymerization catalyst when activated with methylalumoxane. Polymerization results with ethylene and propylene are included.
Simulation and experimental results of source harmonic tuning on linearity of power GaAs FET under class AB operation (2002)

Nonlinearity of GaAs FET amplifiers under class AB operation such as an abrupt increase of the output power against the input power can be effectively reduced by suppressing even-order harmonic distortion in the gate RF voltage. In this paper, we demonstrate the effect of the source harmonic tuning and condition for improving the linearity of power GaAs FETs under class AB operation by the source harmonic tuning technique.
Intelligent battery management for cellular networks with hybrid energy supplies (2016)

Green communications has received much attention in recent years. In cellular networks, base stations (BSs) account for more than 50 percent of the energy consumption. Reducing energy consumption of BSs is essential to realize green cellular networks. Utilizing green energy to power BSs is a promising way to reduce the on-grid energy consumption. Owing to the dynamics of both mobile traffic loads and green energy, the mismatch between the energy demands and green energy generation in a BS results in inefficient green energy utilization. Managing the battery in BSs can control the green energy usage in individual time slots, thus alleviating the inefficiency caused by the mismatch. In this paper, we propose an intelligent battery management mechanism to optimize the green energy utilization in BSs based on the Markov Decision Process (MDP). A large number of states in the Markov chain are required to model the dynamics of solar radiation and BS workload demands. Thus, the original MDP optimal policy iteration method incurs a high computational complexity. Therefore, we propose some heuristics to approximate the optimal energy dispatching strategy with low computational complexity, and validate the performance of the proposed algorithm through extensive simulations.
Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy (2021)

We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.
Identification of QTL Associated with Regrowth Vigor Using the Nested Association Mapping Population in Switchgrass (2022)

Switchgrass (<i>Panicum virgatum</i> L.) is a warm-season perennial grass species that is utilized as forage for livestock and biofuel feedstock. The stability of biomass yield and regrowth vigor under changing harvest frequency would help manage potential fluctuations in the feedstock market and would provide a continuous supply of quality forage for livestock. This study was conducted to (i) assess the genetic variation and (ii) identify the quantitative trait loci (QTL) associated with regrowth vigor after multiple cuttings in lowland switchgrass. A nested association mapping (NAM) population comprising 2000 pseudo F<sub>2</sub> progenies was genotyped with single nucleotide polymorphism (SNP) markers derived from exome-capture sequencing and was evaluated for regrowth vigor in 2017 and 2018. The results showed significant variation among the NAM families in terms of regrowth vigor (<i>p</i> < 0.05). A total of 10 QTL were detected on 6 chromosomes: 1B, 5A, 5B, 6B, 7B, and 8A, explaining the phenotypic variation by up to 4.7%. The additive genetic effects of an individual QTL ranged from -0.13 to 0.26. No single QTL showed a markedly large effect, suggesting complex genetics underlying regrowth vigor in switchgrass. The homologs of candidate genes that play a variety of roles in developmental processes, including plant hormonal signal transduction, nucleotide biosynthesis, secondary metabolism, senescence, and responses to both biotic and abiotic stresses, were identified in the vicinity of QTL.
Active management of data caches by exploiting reuse information (1999)

As microprocessor speeds continue to outpace memory subsystems in speed, minimizing average data access time grows in importance. Multilateral caches afford an opportunity to reduce the average data access time by active management of block allocation and replacement decisions. We evaluate and compare the performance of traditional caches and multilateral caches with three active block allocation schemes: MAT, NTS, and PCS. We also compare the performance of NTS and PCS to multilateral caches with a near-optimal, but nonimplementable policy, pseudo-opt, that employs future knowledge to achieve both active allocation and active replacement. NTS and PGS are evaluated relative to pseudo-opt with respect to miss ratio, accuracy of predicting reference locality, actual usage accuracy, and tour lengths of blocks in the cache. Results show that the multilateral schemes do outperform traditional cache management schemes, but fall short of pseudo-opt; increasing their prediction accuracy and incorporating active replacement decisions would allow them to more closely approach pseudo-opt performance.
Reverberation-Time Prediction Method for Room Impulse Responses Simulated with the Image-Source Model (2007)

The image-source method has become a ubiquitous tool in many fields of acoustics and signal processing. A technique was recently proposed to predict the energy decay (energy-time curve) in room impulse responses simulated using the image-source model. The present paper demonstrates how this technique can be efficiently used to determine the enclosure's absorption coefficients in order to achieve a desired reverberation level, even with a non-uniform distribution of the sound absorption in the room. As shown in this work, classical expressions for the prediction of an enclosure's reverberation time, such as Sabine and Eyring's formulae, do not provide accurate results when used in conjunction with the image method. The proposed approach hence ensures that the image-source model effectively generates impulse responses with a proper reverberation time, which is of particular importance, for instance, for the purpose of assessing the performance of audio signal processing algorithms operating in reverberant conditions.
Don't Trade Privacy for Security (2005)

It has been suggested that the midbrain periaqueductal gray (PAG) is a neural integrating site for the interaction between the muscle pressor reflex and the arterial baroreceptor reflex. The underlying mechanisms are poorly understood. The purpose of this study was to examine the roles of GABA and nitric oxide (NO) in modulating the PAG integration of both reflexes. To activate muscle afferents, static contraction of the triceps surae muscle was evoked by electrical stimulation of the L7 and S1 ventral roots of 18 anesthetized cats. In the first group of experiments (n = 6), the pressor response to muscle contraction was attenuated by bilateral microinjection of muscimol (a GABA receptor agonist) into the lateral PAG [change in mean arterial pressure (DeltaMAP) = 24 +/- 5 vs. 46 +/- 8 mmHg in control]. Conversely, the pressor response was significantly augmented by 0.1 mM bicuculline, a GABAA receptor antagonist (DeltaMAP = 65 +/- 10 mmHg). In addition, the effect of GABAA receptor blockade on the reflex response was significantly blunted after sinoaortic denervation and vagotomy (n = 4). In the second group of experiments (n = 8), the pressor response to contraction was significantly attenuated by microinjection of L-arginine into the lateral PAG (DeltaMAP = 26 +/- 4 mmHg after L-arginine injection vs. 45 +/- 7 mmHg in control). The effect of NO attenuation was antagonized by bicuculline and was reduced after denervation. These data demonstrate that GABA and NO within the PAG modulate the pressor response to muscle contraction and that NO attenuation of the muscle pressor reflex is mediated via arterial baroreflex-engaged GABA increase. The results suggest that the PAG plays an important role in modulating cardiovascular responses when muscle afferents are activated.
Parallel AFM imaging and force spectroscopy using two‐dimensional probe arrays for applications in cell biology (2011)

Atomic force microscopy (AFM) investigations of living cells provide new information in both biology and medicine. However, slow cell dynamics and the need for statistically significant sample sizes mean that data collection can be an extremely lengthy process. We address this problem by parallelizing AFM experiments using a two-dimensional cantilever array, instead of a single cantilever. We have developed an instrument able to operate a two-dimensional cantilever array, to perform topographical and mechanical investigations in both air and liquid. Deflection readout for all cantilevers of the probe array is performed in parallel and online by interferometry. Probe arrays were microfabricated in silicon nitride. Proof-of-concept has been demonstrated by analyzing the topography of hard surfaces and fixed cells in parallel, and by performing parallel force spectroscopy on living cells. These results open new research opportunities in cell biology by measuring the adhesion and elastic properties of a large number of cells. Both properties are essential parameters for research in metastatic cancer development.
Surface-enhanced Raman scattering of the tear film (2003)

When human tear film’s constituents are identified, it is diagnostically useful. Surface enhanced Raman scattering (SERS) can quickly measure, the components at their low concentrations. Reproducible spectra were collected from evaporated gold thin film and silver mirror reaction glass substrates. Synthetic tears were measured on optimised substrates as proof of principle. Further analysis was used to discriminate between diseased and normal tears.
Synthesis of copolymers of ethylene and (meth)acrylates or styrene by an original dual radical/catalytic mechanism (2012)

Neutral Ni II complexes, classically used for catalytic ethylene polymerization, can play an additional role as radical initiators of the homo- and copolymerizations of (meth)acrylates and styrene. Benefiting from this duality, the copolymerization of ethylene and various (meth)acrylates or styrene was successfully performed. Multiblock copolymers containing sequences of both ethylene and (meth)acrylates were prepared for the first time from an original dual radical/catalytic mechanism.
B Cell Antigen Receptor-Induced Activation of Akt Promotes B Cell Survival and Is Dependent on Syk Kinase (2000)

Signaling through the B cell Ag receptor (BCR) is a key determinant in the regulation of B cell physiology. Depending on additional factors, such as microenvironment and developmental stage, ligation of the BCR can trigger B lymphocyte activation, proliferation, or apoptosis. The regulatory mechanisms determining B cell apoptosis and survival are not known. Using the chicken B lymphoma cell line DT40 as a model system, we investigated the role of the serine/threonine kinase Akt in B cell activation. While parental DT40 cells undergo apoptosis in response to BCR cross-linking, cells overexpressing Akt show a greatly diminished apoptotic response. By contrast, limiting the activation of Akt, either by inhibiting phosphatidylinositol 3-kinase or by ectopic expression of the phospholipid phosphatase MMAC1, results in a significant increase in the percentage of apoptotic cells after BCR cross-linking. Using various DT40 knockout cell lines, we further demonstrate that the tyrosine kinase Syk is required for Akt activation and that Lyn tyrosine kinase inhibits Akt activation. Taken together, the data demonstrate that Akt plays an important role in B cell survival and that Akt is activated in a Syk-dependent pathway.
Pan-Nematoda Transcriptomic Elucidation of Essential Intestinal Functions and Therapeutic Targets With Broad Potential (2015)

The nematode intestine is continuous with the outside environment, making it easily accessible to anthelmintics for parasite control, but the development of new therapeutics is impeded by limited knowledge of nematode intestinal cell biology. We established the most comprehensive nematode intestinal functional database to date by generating transcriptional data from the dissected intestines of three parasitic nematodes spanning the phylum, and integrating the results with the whole proteomes of 10 nematodes (including 9 pathogens of humans or animals) and 3 host species and 2 outgroup species. We resolved 10,772 predicted nematode intestinal protein families (IntFams), and studied their presence and absence within the different lineages (births and deaths) among nematodes. Conserved intestinal cell functions representing ancestral functions of evolutionary importance were delineated, and molecular features useful for selective therapeutic targeting were identified. Molecular patterns conserved among IntFam proteins demonstrated large potential as therapeutic targets to inhibit intestinal cell functions with broad applications towards treatment and control of parasitic nematodes.
Reducing channel state information feedback for downlink distributed antenna system (2009)

This paper addresses the channel state information (CSI) feedback problem for downlink transmission in a distributed antenna system (DAS). One feedback-and-transmission scheme is proposed, where channel response ratios of the nondominant paths (e.g. paths other than that from the nearest site) to the dominant path (e.g. that from the nearest site) are quantized and fed back, from each user, to the coordination center. Vector quantization with log squared error as a distortion measure is introduced to design codebook for quantizing these ratios. Zero-forcing transmitter or zero-forcing dirty-paper-coding transmitter can be designed based on the feedback information and be used for downlink joint transmission. Performance of the proposed scheme in a system with three single-antenna sites and three single-antenna users is evaluated. Simulation results indicate that to achieve the same performance, the proposed scheme requires feedback amount less than half of that needed with a straightforward scheme, where all channel elements are fed back directly.
Rotor Flapping for a Triangular Quadrotor (2014)

The triangular quadrotor is a novel, more efcient conguration of quadrotor aircraft that uses a single large central rotor for lift and three smaller rotors for counter-torque and manoeuvering. Early experiments exhibited a precession eect due to the uncompensated gyroscopics of the main rotor. In this paper we discuss two techniques to x this problem: feedback linearisation and a mechanical apping joint. Simulations indicate that, contrary to expectations, feedback linearisation is not viable due to delays in the control system. The rotor apping approach is shown to be a more eective solution, both in simulation and ight experiments.
4.2 A 12nm Autonomous-Driving Processor with 60.4TOPS, 13.8TOPS/W CNN Executed by Task-Separated ASIL D Control (2021)

Autonomous driving systems, when deployed to market, will require accurate and high-speed recognition, judgment and operation. Convolutional neural networks (CNNs) require large amounts of computation for pattern recognition. The CNN performance required for level-3 autonomous driving systems is 120TOPS or higher. As shown in Fig. 4.2.1, recent CNN implementations are oriented toward high performance and low power [1] -[4]. In previously reported SoCs for autonomous driving [5], power consumption is more than 70W, requiring a heavy and expensive water-cooling system. To save weight and cost by using an air-cooling system for an in-vehicle electronics control unit (ECU), power consumption less than 25W is indispensable and around half of that can be assigned for the SoC. Consequently, achieving 120TOPS with 10TOPS/W is necessary for an autonomous driving system. At the same time, achieving the ASIL D standard, the highest safety level defined in ISO 26262, is also required for SoCs for autonomous driving. Dual-core lock step (DCLS) is a technique to satisfy ASIL D by comparing the results of parallel execution of the same process in duplicated hardware. However, simple full-time DCLS doubles power consumption and degrades power efficiency. In this paper, we achieve 60.4TOPS CNN performance with 13.8TOPS/W efficiency in an application processor having high-reliability ASIL D targeted safety mechanisms for autonomous driving system. One and two-device configurations achieving performance of 60 and 120TOPS, respectively, for ADAS and autonomous driving offer practical solutions for products.
RNA-guided transcriptional regulation (2023)

Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.
Effects of Somatostatin on Plasma Glucose and Glucagon Levels in Human Diabetes Mellitus (1974)

To evaluate the role of pancreatic alpha-cell dysfunction in human diabetes mellitus, somatostatin, an inhibitor of glucagon secretion, was infused (1 mg over two hours) in 10 insulin-dependent diabetic subjects. Fasting plasma glucagon fell from 150 ± 15 (mean ± S.E.M.) to 77 ± 10 pg per milliliter (p<0.001), and plasma glucose from 260 ± 20 to 191 ± 21 mg per 100 ml (p<0.001). Similar responses occurred in a hypophysectomized diabetic patient, indicating that these effects of somatostatin were independent of suppression of growth hormone secretion. Somatostatin (4 mg subcutaneously) was active transiently. In additional studies, somatostatin infusion combined with insulin completely abolished post-meal hyperglycemia in four diabetic patients and was more effective than insulin alone. These results indicate that excessive glucagon secretion accounts for about 25 per cent of the fasting plasmaglucose levels in such patients. Furthermore, somatostatin may be a useful adjunct to insulin in treating diabetes mellitus. (N Engl J Med 291:544–547, 1974)
Buffer cache management: predicting the future from the past (2003)

Efficient and effective management of the buffer cache in the operating system becomes increasingly important as the speed gap between microprocessors and hard disks becomes wider This paper presents different techniques for predicting the future disk access patterns from the access history of each block and the access patterns detected for related blocks. The first part of the paper focuses on a block replacement policy called LRFU (least recently/frequently used) that subsumes the well-known LRU (least recently used) and the LFU (least frequently used) policies. Then, the next part discusses techniques for handling regular references such as sequential and looping references. Finally, the results from both trace-driven simulations and our implementation of the techniques within a real operating system are presented.