gebhart/patrepeval huggingface dataset:
A Qualified Success: Discovery of a New Series of ATAD2 Bromodomain Inhibitors with a Novel Binding Mode Using High-Throughput Screening and Hit Qualification (2019)

The bromodomain of ATAD2 has proved to be one of the least-tractable proteins within this target class. Here, we describe the discovery of a new class of inhibitors by high-throughput screening and show how the difficulties encountered in establishing a screening triage capable of finding progressible hits were overcome by data-driven optimization. Despite the prevalence of nonspecific hits and an exceptionally low progressible hit rate (0.001%), our optimized hit qualification strategy employing orthogonal biophysical methods enabled us to identify a single active series. The compounds have a novel ATAD2 binding mode with noncanonical features including the displacement of all conserved water molecules within the active site and a halogen-bonding interaction. In addition to reporting this new series and preliminary structure-activity relationship, we demonstrate the value of diversity screening to complement the knowledge-based approach used in our previous ATAD2 work. We also exemplify tactics that can increase the chance of success when seeking new chemical starting points for novel and less-tractable targets.
LCL Pickup Circulating Current Controller for Inductive Power Transfer Systems (2012)

This paper proposes a fast switching control topology for a series–parallel-tuned LCL pickup for inductive power transfer systems. This topology employs a similar idea to traditional controlled rectifiers that regulate the average output current through the rectifier. The proposed topology is able to provide continuous power regulation and smooth power transitions between the fully ON and fully OFF state. Due to the way in which the circuit operates, the proposed controller necessarily introduces additional reflected reactive power back onto the primary power supply. A steady-state analysis is presented enabling this reflected real and reactive power to be investigated and compared against SPICE simulations. These results are further verified by practical measurements on a 1.5-kW 300-V dc output pickup controller prototype which achieves an efficiency of 95% at full load and is still above 85% when operating at one third of its rated power.
The Effect of Diet and Lysine:Calorie Ratio on Body Composition and Kidney Health in Geriatric Cats (2007)

Study 1: A study was conducted to determine the effects of geriatric foods utilizing 40 healthy geriatric cats (≥12 years, initially 4.6 kg). Cats were fed a control food during a 30-day pre-feeding period, blocked by age, gender, and body fat percentage, and randomly assigned to 1 of 4 foods (A = experimental geriatric food, B = Iams Active Maturity, C = Royal Canin Mature 28, and D = Purina ONE Senior Protection Formula) for the 90-day testing period. Chemistry screens and microalbuminuria were evaluated at Day 30 and Day 90 along with dual-energy x-ray absorptiometry (DEXA) scan at Day 90. Cats fed all foods maintained weight and body fat content throughout the study. At Day 90, cats fed food D had reduced (P < 0.01) bone mineral content. Cats fed food A and C had reduced (P < 0.03) lean. Cats fed food A tended to have a lower percentage of cats with renal damage (P < 0.08) compared with cats fed food B. For vital organ measures, cats fed food A had lower (P < 0.03) blood urea nitrogen (BUN) levels compared with cats fed food D. Cats fed food A had lower (P < 0.01) creatinine compared with cats fed food B. Study 2: A second trial was conducted to evaluate the effect of altering the lysine: calorie ratio in feline geriatric foods utilizing 36 healthy geriatric cats (≥12 years, initially
Agonist-Induced Endocytosis of Rat Somatostatin Receptor 1 (2006)

Somatostatin-receptor 1 (sst1) is an autoreceptor in the central nervous system that regulates the release of somatostatin. Sst1 is present intracellularly and at the cell surface. To investigate sst1 trafficking, rat sst1 tagged with epitope was expressed in rat insulinoma cells 1046-38 (RIN-1046-38) and tracked by antibody labeling. Confocal microscopic analysis revealed colocalization of intracellularly localized rat sst1-human simplex virus (HSV) with Rab5a-green fluorescent protein and Rab11a-green fluorescent protein, indicating the distribution of the receptor in endocytotic and recycling organelles. Somatostatin-14 induced internalization of cell surface receptors and reduction of binding sites on the cell surface. It also stimulated recruitment of intracellular sst1-HSV to the plasma membrane. Confocal analysis of sst1-HSV revealed that the receptor was initially transported within superficial vesicles. Prolonged stimulation of the cells with the peptide agonist induced intracellular accumulation of somatostatin-14. Because the number of cell surface binding sites did not change during prolonged stimulation, somatostatin-14 was internalized through a dynamic process of continuous endocytosis, recycling, and recruitment of intracellularly present sst1-HSV. Accumulated somatostatin-14 bypassed degradation via the endosomal-lysosomal route and was instead rapidly released as intact and biologically active somatostatin-14. Our results show for the first time that sst1 mediates a dynamic process of endocytosis, recycling, and re-endocytosis of its cognate ligand.
Cross-Layer Design of Coded Multicast for Wireless Random Access Networks (2011)

Joint optimization of network coding and Aloha-based medium access control (MAC) for multi-hop wireless networks is considered. The multicast throughput with a power consumption-related penalty is maximized subject to flow conservation and MAC achievable rate constraints to obtain the optimal transmission probabilities. The relevant optimization problem is inherently non-convex and hence difficult to solve even in a centralized manner. A successive convex approximation technique is employed to obtain a Karush-Kuhn-Tucker solution. A separable problem structure is obtained and the dual decomposition technique is adopted to develop a distributed solution. The algorithm is thus applicable to large networks, and amenable to online implementation. Numerical tests verify performance and complexity advantages of the proposed approach over existing designs. A network simulation with implementation of random linear network coding shows performance very close to the one theoretically designed.
Investigating the Structural Variability and Binding Modes of the Glioma Targeting NFL-TBS.40–63 Peptide on Tubulin (2015)

NFL-TBS.40-63 is a 24 amino acid peptide corresponding to the tubulin-binding site located on the light neurofilament subunit, which selectively enters glioblastoma cells, where it disrupts their microtubule network and inhibits their proliferation. We investigated its structural variability and binding modes on a tubulin heterodimer using a combination of NMR experiments, docking, and molecular dynamics (MD) simulations. Our results show that, while lacking a stable structure, the peptide preferentially binds on a specific single site located near the β-tubulin C-terminal end, thus giving us precious hints regarding the mechanism of action of the NFL-TBS.40-63 peptide's antimitotic activity at the molecular level.
Developing experimental methods to measure phase change in fluoropolymer binders (Progress Summary) (2019)

Understanding fluoropolymer binder structure and aging response continues to be an important goal for the prediction and assessment of polymer bonded explosive compositions. Fluoropolymer (FP) binders are commonly only a few percent of the composite material - they are thin films that coat explosives, binding them together. Although FPs are a small fraction of the composite, they are essential for the mechanical integrity of the part. As part of ongoing efforts within NNM, we are developing new methods to quantify crystallization and chemical degradation within aged Fluoropolymer materials.
Filter bank design based on discriminative feature extraction (2002)

A filter bank model, which achieves minimum error, is investigated in this paper. A bank-of-filter feature extractor module is comprehensively optimized with the classifier's parameters for minimization of the errors occurring at the back-end classifier. The method has been applied to readjusting Mel-scale and Bark-scale based filter banks for the Japanese vowel recognition task, the framework being provided by the minimum classification error (MCE)/generalised probabilistic descent method (GPD). The results show suggestive phenomena underlying the accuracy of the proposed approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Accelerated Ions from a Laser Driven Z-pinch (2015)

Intense laser acceleration of ions is inherently difficult due to the velocity mismatch between laser pulses moving at the speed of light and slowly moving massive ions. Instead of directly accelerating the ions, current approaches rely on TV/m laser fields to ionize and drive out electrons. The ions are then accelerated by the resulting electrostatic fields from charge separation. Here we report experimental and numerical acceleration of ions by means of laser driven Z-pinch exiting a sharp plasma interface. This is achieved by first driving a plasma wakefield in the self-modulated bubble regime. Cold return currents are generated to maintain quasi-neutrality of the plasma. The opposite current repel and form an axial fast current and a cylindrical-shell cold return current with a large (100 MG) azithmuthal field in between. These conditions produce a Z-pinch that compresses the fast electrons and ions on axis. If this process is terminated at a sharp plasma interface, a beam of ions are then accelerated in the forward direction as the Z-pinch collapses. These results provide a new route towards laser-accelerated ions as well as potential laboratory scale modeling of z-pinches in astrophysical events.
HuBERT: Self-Supervised Speech Representation Learning by Masked Prediction of Hidden Units (2021)

Self-supervised approaches for speech representation learning are challenged by three unique problems: (1) there are multiple sound units in each input utterance, (2) there is no lexicon of input sound units during the pre-training phase, and (3) sound units have variable lengths with no explicit segmentation. To deal with these three problems, we propose the Hidden-Unit BERT (HuBERT) approach for self-supervised speech representation learning, which utilizes an offline clustering step to provide aligned target labels for a BERT-like prediction loss. A key ingredient of our approach is applying the prediction loss over the masked regions only, which forces the model to learn a combined acoustic and language model over the continuous inputs. HuBERT relies primarily on the consistency of the unsupervised clustering step rather than the intrinsic quality of the assigned cluster labels. Starting with a simple k-means teacher of 100 clusters, and using two iterations of clustering, the HuBERT model either matches or improves upon the state-of-the-art wav2vec 2.0 performance on the Librispeech (960h) and Libri-light (60,000h) benchmarks with 10min, 1h, 10h, 100h, and 960h fine-tuning subsets. Using a 1B parameter model, HuBERT shows up to 19% and 13% relative WER reduction on the more challenging dev-other and test-other evaluation subsets.
3-Dimensional Laser Radar Range Imaging (1987)

This paper describes work done to design a three dimensional laser radar imaging system accurate to .004" and techniques for 3-D scene analysis used at the Environmental Research Institute of Michigan (ERIM).
Enhancing lignin depolymerization via a dithionite-assisted organosolv fractionation of birch sawdust (2021)

A dithionite-assisted organosolv fractionation process is presented, for the treatment of raw lignocellulose and the concomitant production of cellulosic pulp and the reductive conversion of lignin into phenolic monomers and short oligomers.
Model composition for scheduling analysis in platform design (2002)

We present a compositional approach to analyze timing behavior of complex platforms with different scheduling strategies. The approach uses event interfacing in order to couple previously incompatible analysis techniques which provide subsystem and component behavior. Based on these interfaces, event propagation using abstract models is used to derive global system timing properties.
Measles virus-substance P receptor interactions. Possible novel mechanism of viral fusion. (1990)

Measles virus (MV) encodes the fusion protein (F) that mediates cell fusion and intercellular spread of the virus, and is homologous to the carboxy terminus of the neuropeptide substance P (SP). In addition, the oligopeptide Z-D-Phe-L-Phe-Gly, also homologous to F and SP, inhibits MV fusion with target cells. These observations raise the question of whether MV uses the SP receptor (SPR) during a specific phase of its infectious cycle. In this report, we examine the structural and functional consequences of this interaction and show, using cross-linking studies, that MV and SP specifically bind to a 52-58-kD protein, previously reported to comprise the SPR on human IM-9 lymphoblasts. Moreover, bound MV and SP are shown to reciprocally displace each other from these cells. In addition, we demonstrate that anti-SP antisera inhibits the cell-to-cell spread of MV, and that SP blocks MV fusion with target cells. These results indicate the presence of MV-SPR interactions during viral fusion, and suggest possible novel mechanisms for viral entry into cells.
An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates (2015)

Even with effective antiretroviral drugs, HIV remains an enormous global health burden. Vaccine development has been problematic in part due to the high degree of diversity and poor immunogenicity of the HIV Env protein. Studies suggest that a relevant HIV vaccine will likely need to induce broad cellular and humoral responses from a simple vaccine regimen due to the resource-limited setting in which the HIV pandemic is most rampant. DNA vaccination lends itself well to increasing the amount of diversity included in a vaccine due to the ease of manufacturing multiple plasmids and formulating them as a single immunization. By increasing the number of Envs within a formulation, we were able to show an increased breadth of responses as well as improved functionality induced in a nonhuman primate model. This increased breadth could be built upon, leading to better coverage against circulating strains with broader vaccine-induced protection.
Self-Contained Power Amplifier for 5G (2020)

The paper is related to 5G power amplifier architecture which is robust to the environment variations. One of the main PA challenges is to control the phase of the PA while maintaining its RF performances according to the manufacturing process variations (PVT). Another challenge is to achieve high efficiency, while providing very good linearity. In such conditions, the PA phase control is a major advantage. This work first quantifies the impact of the phased-array antenna impedance variations on the power amplifier RF performances (gain, phase shift). Then, 130nm SiGe BiCMOS9 and 65nm CMOS-SOI measurements of 5G self-contained PAs demonstrate the robustness against VSWR antenna variations and address the phase control issue.
Supplementary Figure 2 from A Human Single-Domain Antibody Elicits Potent Antitumor Activity by Targeting an Epitope in Mesothelin Close to the Cancer Cell Surface (2023)

&lt;p&gt;PDF file - 782K, Binding of the SS1, HN1 or SD1 VH domain to mesothelin (MSLN).&lt;/p&gt;
Temporal context as cortical spatial codes (2009)

It is largely unknown how the brain deals with time. The new field of research on autonomous development must enable machines to develop intelligent behaviors that respond not only to spatial features, but also temporal features. Hidden Markov Model (HMM) has a probability based mechanism to deal with time warping, but no effective online method exists that can deal with general temporal structure and temporal abstraction. By online, we mean that the agent must respond to spatial and temporal context immediately while the sensory stream flows in. By general temporal context, we mean various desirable temporal subsets, such as deletion (e.g., stop words) and variable temporal lengths (e.g., beyond bigrams and trigrams). By temporal abstraction, we mean using abstract meaning of context, instead of concrete forms. This paper proposes a brain inspired online scheme for making sequential decisions based on general temporal context. By sequential decisions, the action from the network depends on not only inputs and outputs but also emergent internal context states. In our neuromorphic scheme, the internal states are not predefined symbols, but distributed context depending on the internal attention. Our complexity analysis shows how this scheme greatly reduces the exponential time complexity O(2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sup> ) of all the possible number of contexts of length t down to linear time complexity O(cnt), where n is the number of neurons in the network and c is the average number of synapses of each neuron. In this paper, we concentrate on processing sequential text inputs by an online agent network under motor-supervised learning.
Gas analysis in gasification of biomass and waste : Guideline report: Document 2 - Factsheets on gas analysis techniques (2018)

Gasification is generally acknowledged as one of the technologies that will enable the large-scale production of biofuels and chemicals from biomass and waste. One of the main technical challenges ...
Mark my words! (2011)

The psycholinguistic theory of communication accommodation accounts for the general observation that participants in conversations tend to converge to one another's communicative behavior: they coordinate in a variety of dimensions including choice of words, syntax, utterance length, pitch and gestures. In its almost forty years of existence, this theory has been empirically supported exclusively through small-scale or controlled laboratory studies. Here we address this phenomenon in the context of Twitter conversations. Undoubtedly, this setting is unlike any other in which accommodation was observed and, thus, challenging to the theory. Its novelty comes not only from its size, but also from the non real-time nature of conversations, from the 140 character length restriction, from the wide variety of social relation types, and from a design that was initially not geared towards conversation at all. Given such constraints, it is not clear a priori whether accommodation is robust enough to occur given the constraints of this new environment. To investigate this, we develop a probabilistic framework that can model accommodation and measure its effects. We apply it to a large Twitter conversational dataset specifically developed for this task. This is the first time the hypothesis of linguistic style accommodation has been examined (and verified) in a large scale, real world setting.
Infrastructure free 6 DOF location and pose estimation for mixed reality systems (2009)

Mixed reality training systems using Head Mounted Displays (HMDs) require very high precision knowledge of the 3D location and 3D orientation of the user's head. This is required by the system to know where to insert the synthetic actors and objects in the HMD. The inserted objects must appear stable and not jitter or drift. Moreover latency of less than 5 milliseconds for pose estimation is required for lag-free see-through HMD operation. We describe how to achieve this performance using a multi-camera based visual navigation system mounted on the HMD. A Kalman filter is used to integrate high rate estimates from an IMU with a visual odometry system and to predict head motion. Landmark matching and GPS when available are used to correct any drifts.
Potential antitumor agents. 26. Anionic congeners of the 9-anilinoacridines (1978)

To investigate the possible importance of small levels of sulfonamide anion in the antileukemia (L1210) 4'-(9-acridinylamino)methanesulfonanilides, an anionic derivative was prepared, in which -COOH replaced -NHSO2CH3, and shown to have experimental antitumor activity. Analogue synthesis and evaluation show that acceptable placement of the carboxylate function on the 9-anilino ring is restricted to the 1'-position. While the 1'-COOH and 1'-(CH2)2COOH analogues proved active, the intermediate acetate variant (1'-CH2COOH) was inactive. There were marked differences in the effects of added acridine ring substituents, on biologic activity, depending on the function attached to the 9-anilino ring (1'-NHSO2CH3 or 1'-COOH). Consideration of the vector components of possible drug-binding forces, acting on a DNA-intercalated agent, suggests that there may be low-energy barriers to two-dimensional reorientation of a planar, intercalated chromophore in relation to the neighboring purine-pyrimidine base pairs. It is proposed that site forces from an added substituent could lead to modified DNA-binding orientations. Observed acridine-ring substituent effects on biologic activity would then depend on the 9-anilino ring function (1'-NHSO2CH3, 1'-COOH) employed.
Improvement of the extinction ratio performance of a fiber laser based rangefinder by using successive real-time statistical algorithms (2017)

Today, it is commonly agreed that mid-range rangefinders (typical range: 10 km) based on fiber laser technology, constitute the best trade-off between performance and reliability. But to intend to compete with long-range devices and propose an alternative to bulk solid state laser systems, it is essential to increase significantly their extinction ratio (ER) compared to the state of the art. In this paper, we report on successive real-time statistical algorithms performed on 2 different fiber laser rangefinders and the feasability to achieve an extinction ratio up to 45dB in an eye-safety burst mode. Based on a bi-static architecture and equipped with a 38 &mu;J and 125 &mu;J, 10 ns pulse fiber laser, their intrinsic ER in single-pulse emission has been measured respectively at 28 and 33 dB. A 45 mm optical aperture receiver and a specially designed compact electronics complete the device. This alternative to solid-states systems dedicated to long range application, represents then a cost-effective solution.
Cell-phone battery charger miniaturization (2002)

A fast off-line travel battery charger for cellular telephones is typically as large, or larger than some cellular telephones. This paper presents a miniaturized off-line travel battery charger for cellular phones. The aim of the work was to explore the theoretical and practical limitations of reducing the size of such a battery charger. The difficulty in miniaturizing such a charger arises from the wide input line (85-265 Vac) and load range (0-7.5 V, 0-880 mA) that is required for operation. This makes it difficult to design a highly efficient power conversion circuit for this power (10 W) level. A thermal study of the limitations on the maximum power dissipation allowable provided a lower boundary limit on efficiency for a feasible solution. A topology such as an LLC resonant converter can operate efficiently at high frequencies, and its use of parasitics reduces the need for extra components. New components with the appropriate form factor for denser packaging were used. A special thermal management scheme inside the box was required to keep component temperatures within specifications. A prototype with a volume of 26 cm/sup 3/ (existing solution 58 cm/sup 3/, for 7 V and 700 mA) was built and tested to assess the validity of the preliminary studies, to provide insight into potential practical problems, and to determine the feasibility of a 14 cm/sup 3/ charger.