gebhart/patrepeval huggingface dataset:
Molecular recognition of S-nitrosothiol substrate by its cognate protein denitrosylase (2018)

Protein <i>S</i>-nitrosylation mediates a large part of nitric oxide's influence on cellular function by providing a fundamental mechanism to control protein function across different species and cell types. At steady state, cellular <i>S</i>-nitrosylation reflects dynamic equilibria between <i>S</i>-nitrosothiols (SNOs) in proteins and small molecules (low-molecular-weight SNOs) whose levels are regulated by dedicated <i>S</i>-nitrosylases and denitrosylases. <i>S</i>-Nitroso-CoA (SNO-CoA) and its cognate denitrosylases, SNO-CoA reductases (SCoRs), are newly identified determinants of protein <i>S</i>-nitrosylation in both yeast and mammals. Because SNO-CoA is a minority species among potentially thousands of cellular SNOs, SCoRs must preferentially recognize this SNO substrate. However, little is known about the molecular mechanism by which cellular SNOs are recognized by their cognate enzymes. Using mammalian cells, molecular modeling, substrate-capture assays, and mutagenic analyses, we identified a single conserved surface Lys (Lys-127) residue as well as active-site interactions of the SNO group that mediate recognition of SNO-CoA by SCoR. Comparing SCoR<sup>K127A</sup><i>versus</i> SCoR<sup>WT</sup> HEK293 cells, we identified a SNO-CoA-dependent nitrosoproteome, including numerous metabolic protein substrates. Finally, we discovered that the SNO-CoA/SCoR system has a role in mitochondrial metabolism. Collectively, our findings provide molecular insights into the basis of specificity in SNO-CoA-mediated metabolic signaling and suggest a role for SCoR-regulated <i>S</i>-nitrosylation in multiple metabolic processes.
Lack of SSBP2, a Candidate Leukemia Suppressor, Promotes T Cell Lymphomagenesis in p53 Null Mice. (2007)

Abstract Our laboratory positionally cloned a candidate myeloid leukemia suppressor gene, sequence-specific single-stranded DNA binding protein 2 (SSBP2) from chromosome 5q13.3-5q14.1 interval. SSBP2 expression is lost in primary acute myelogenous leukemia (AML) and myelodysplasia (MDS) cells. AML cells induced to express SSBP2 show growth arrest and partial differentiation. SSBP2 directly binds the adaptor protein Ldb1 (LIM domain-binding protein1), which in turn binds LIM domain containing nuclear factors. Although LDB1, SSBP2 containing transcriptional complexes are ubiquitously expressed, they have been best characterized in erythroid differentiation. Stabilization of Ldb1 by its direct interaction with SSBP2 upregulated the transcriptional activity of the Ldb1-Lmo2-E2A/TAL1-containing complex on an erythroid specific gene promoter. Here, we report the generation and characterization of Ssbp2 null mice. Mice with homozygous disruption of Ssbp2 (Ssbp2−/−) are viable and fertile, with no gross hematopoietic abnormalities observed up to six months of age. In order to examine if and how loss of SSBP2 promotes transformation, we crossed Ssbp2−/− mice with p53−/− null mice. Ssbp2−/−, p53−/− mice succumbed to thymic lymphomas with a median survival of 122 days compared to a median survival of 182 days for p53−/− mice (P = 0.0002). Moreover, the spectrum of tumors observed in the Ssbp2−/−, p53−/− mice included 62.5% thymic lymphomas (20/32), whereas only 26.7% of the p53−/− mice developed thymic lymphomas (8/30). In addition, Ldb1 protein levels but not transcript levels were decreased in the thymi of Ssbp2−/−, and Ssbp2−/−, p53−/− mice. Thus, loss of Ssbp2 appears to abrogate Ldb1-Lmo2-mediated T cell differentiation by promoting Ldb1 degradation. Such a block in differentiation cooperates with the loss of cell cycle arrest and apoptosis due to loss of p53. Our findings demonstrate for the first time a functional cooperation between the candidate leukemia suppressor SSBP2 and tumor suppressor p53. Furthermore, these results suggest the Ldb1-Lmo2 complexes to be novel targets for therapeutic intervention in hematologic malignancies.
Distributed Quantization for Sparse Time Sequences (2020)

Analog signals processed in digital hardware are quantized into a discrete bit-constrained representation. Quantization is typically carried out using analog-to-digital converters (ADCs), operating in a serial scalar manner. In some applications, a set of analog signals are acquired individually and processed jointly. Such setups are referred to as distributed quantization. In this work we propose a distributed quantization scheme for representing a set of sparse time sequences acquired using conventional scalar ADCs. Our approach utilizes tools from secure group testing theory to exploit the sparse nature of the acquired analog signals, obtaining a compact and accurate representation while operating in a distributed fashion. We then show how our technique can be implemented when the quantized signals are transmitted over a multihop communication network providing a low-complexity network policy for routing and signal recovery. Our numerical evaluations demonstrate that the proposed scheme notably outperforms conventional methods based on the combination of quantization and compressed sensing tools.
Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations. (1985)

The etiologic agent for the acquired immunodeficiency syndrome (AIDS) is now firmly established as the retrovirus termed the human T-lymphotropic virus type III (HTLV-III) or the lymphadenopathy-associated virus, LAV. The disease is characterized by profound and progressive loss of immunity, but molecular evidence indicates that only a few cells in peripheral blood are being productively infected with this virus. In the present study we have investigated a disrupted HTLV-III viral preparation for biologic effects on normal lymphoid cells. Relatively dilute concentrations of this preparation were found to stimulate immunoglobulin secretion by peripheral blood lymphocytes; at the same dosages, the preparation was inhibitory for the B-cell differentiation responses that are induced with other known polyclonal B-cell activators, pokeweed mitogen, Staphylococcus aureus, and Epstein-Barr virus. This preparation was also inhibitory at high concentrations for T-lymphocyte proliferative responses to phytomitogens and antigens and resulted in a reduced expression of Tac antigen on phytohemagglutinin-activated lymphocytes. Paradoxically, incubation of lymphocytes of certain healthy donors with the HTLV-III preparation alone resulted in increased expression of Tac and Leu-12 antigens. These findings show that a disrupted preparation of HTLV-III virus can mimic many of the immunologic abnormalities present in patients with HTLV-III infection. Nonviable viral proteins may be responsible for some of the immunologic perturbations that occur in HTLV-III-infected states.
Structural and Functional Analysis of the NLRP4 Pyrin Domain (2012)

NLRP4 is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family of cytosolic receptors and a member of an inflammation signaling cascade. Here, we present the crystal structure of the NLRP4 pyrin domain (PYD) at 2.3 Å resolution. The NLRP4 PYD is a member of the death domain (DD) superfamily and adopts a DD fold consisting of six α-helices tightly packed around a hydrophobic core, with a highly charged surface that is typical of PYDs. Importantly, however, we identified several differences between the NLRP4 PYD crystal structure and other PYD structures that are significant enough to affect NLRP4 function and its interactions with binding partners. Notably, the length of helix α3 and the α2-α3 connecting loop in the NLRP4 PYD are unique among PYDs. The apoptosis-associated speck-like protein containing a CARD (ASC) is an adaptor protein whose interactions with a number of distinct PYDs are believed to be critical for activation of the inflammatory response. Here, we use co-immunoprecipitation, yeast two-hybrid, and nuclear magnetic resonance chemical shift perturbation analysis to demonstrate that, despite being important for activation of the inflammatory response and sharing several similarities with other known ASC-interacting PYDs (i.e., ASC2), NLRP4 does not interact with the adaptor protein ASC. Thus, we propose that the factors governing homotypic PYD interactions are more complex than the currently accepted model, which states that complementary charged surfaces are the main determinants of PYD-PYD interaction specificity.
Multicore Fiber Fabricated by Modified Cylinder Method (2020)

MCF made by modified cylinder method (MCM) is demonstrated. Optimized cylinder with single hole show potentials for cost reduction and higher productivity. Attenuation loss of the MCF made by MCM is 0.190dB/km at 1550nm.
Embedding classical communication topologies in the OPAM architecture (2002)

The authors present a novel method for embedding parallel programs of multiple processes exhibiting classical communication topologies into optical parallel architecture model (OPAM) parallel architecture. OPAM consists of a large number of processors that are connected by a two level, crossbar based interconnection network. The authors show the mapping of parallel programs using graph contraction methods. Classical communication topologies such as rings, trees, two dimensional grids, etc. are considered. Using the OPAM concept with these embedding techniques can save communication latency in large parallel processing interconnection networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High-speed confocal laser scanning microscopy using acousto-optic deflectors and a digital micromirror device (2004)

Neurons are known to possess active computational properties. To investigate these properties, it is desirable to study the electrical and chemical properties not only at a living neuron's cell body, but also at many sites within its dendritic arborization. However, currently available recording techniques force a tradeoff between spatial and temporal resolution. To overcome these limitations, we have developed a confocal microscope that can make multisite optical recordings at an effective frame rate that is sufficient to measure fast neuronal events, such as action potentials, that occur on a timescale of milliseconds. We accomplished this by combining acousto-optic deflectors for addressable point illumination with a digital micromirror device for addressable point detection. After developing a registration algorithm to ensure synchronicity between point illumination and point detection, we used light-scattering test preparations to demonstrate that our system is capable of optical sectioning and therefore capable of imaging in living brain tissue. Furthermore, we have shown that fluorescence changes can be monitored at an effective frame rate of 25 kHz.
Polarization-maintaining fiber based optical coherence tomography for polarization-sensitive measurements (2009)

We present a polarization-maintaining (PM) fiber based optical coherence tomography system for polarization-sensitive and phase-sensitive measurements. Using a single detector, a single depth scan accurately yields retardance and polarization-insensitive reflectivity information along an A-line. Interference patterns on the orthogonal polarization channels are frequency multiplexed and extracted by digital band-pass filters. Images are insensitive to sample rotation in plane perpendicular to ranging. The use of PM-fibers allows direct calculation of birefringence without correcting the polarization transformations known in single-mode non-PM fibers. The system can be configured for differential phase measurements with minor modifications. In this case, a dual detector setup in the detection arm is used, and frequency multiplexing is not utilized.
3-Aminopyrrolidinone Farnesyltransferase Inhibitors:  Design of Macrocyclic Compounds with Improved Pharmacokinetics and Excellent Cell Potency (2002)

A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic properties with a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due to attenuated clearance. It was observed that in vivo clearance correlated with the flexibility of the molecules and this concept proved useful in the design of FTIs that exhibited low clearance, such as FTI 78. X-ray crystal structures of compounds 49 and 66 complexed with farnesyltransferase (FTase)-farnesyl diphosphate (FPP) were determined, and they provide details of the key interactions in such ternary complexes. Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date.
Miniaturized Filter-Aided Sample Preparation (MICRO-FASP) Method for High Throughput, Ultrasensitive Proteomics Sample Preparation Reveals Proteome Asymmetry in Xenopus laevis Embryos (2020)

We report a miniaturized filter aided sample preparation method (micro-FASP) for low-loss preparation of submicrogram proteomic samples. The method employs a filter with ∼0.1 mm<sup>2</sup> surface area, reduces the total volume of reagents to <10 μL, and requires only two sample transfer steps. The method was used to generate 25 883 unique peptides and 3069 protein groups from 1000 MCF-7 cells (∼100 ng protein content), and 13 367 peptides and 1895 protein groups were identified from 100 MCF-7 cells (∼10 ng protein content). Single blastomeres from <i>Xenopus laevis</i> embryos at the 50-cell stage (∼200 ng yolk free protein/blastomere) generated 20 943 unique peptides and 2597 protein groups; the proteomic profile clearly differentiated left and right blastomeres and provides strong support for models in which this asymmetry is established early in the embryo. The parallel processing of 12 samples demonstrates reproducible label free quantitation of 1 μg protein homogenates.
Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain (2014)

The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution.
Cell-density independent increased lymphocyte production and loss rates post-autologous HSCT (2021)

Lymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and lifespan increase homeostatically when lymphocyte numbers are low and, vice versa, return to normal once cell numbers have normalized. This widely accepted concept is largely based on experiments in mice, but is hardly investigated in vivo in humans. Here we quantified lymphocyte production and loss rates in vivo in patients 0.5-1 year after their autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T- and B-cell subsets in autoHSCT-patients were two to eight times higher than in healthy controls, but went hand in hand with a threefold to ninefold increase in cell loss rates. Both rates also did not normalize when cell numbers did. This shows that increased lymphocyte production and loss rates occur even long after autoHSCT and can persist in the face of apparently normal cell numbers.
Space‐Charge Distribution across Internal Interfaces in Electroceramics Using Electron Holography: I, Pristine Grain Boundaries (1997)

The role and importance of interface charge and the associated space‐charge in governing the electrical activity of interfaces are well appreciated, and have been the focus of a large number of investigations. Despite a considerable progress in this area, the direct determination of the sign, magnitude of the interface charge, and the space‐charge potential associated with the interface double‐Schottky barrier has remained elusive. We propose electron holography as a bulk sensitive tool with subnanometer resolution to obtain direct real‐space evidence of space‐charge, as well as determine the electrical activity of individual grain boundaires (GBs) in electroceramics. Part I of this investigation is focused on the theory and practice of electron holography of interfaces, in the context of pristine (undoped) GBs in SrTiO 3 . We show that pristine GBs exhibit very little electron phase change, and that the phase change is associated with a reduction in the mean inner potential and with any residual charge, both present by the virtue of the GB. This investigation forms the basis for the electron holography investigation of doped (charged) GBs in Part II. It is shown that quantitative information about the magnitude, sign, and spatial extent of electrical potential and charge, as well as defect densities across individual GBs in electroceramics, can be obtained using transmission electron holography.
A depth map representation for real-time transmission and view-based rendering of a dynamic 3D scene (2003)

View-based 3D video streaming requires the compression and transmission of depth maps along with the video sequence. The requirements for representing these depth maps include moderately high compression, preservation of depth discontinuities, low complexity decoding, and to be in a form that is suitable for real-time rendering using graphics cards. This motivates a mesh-based representation for the depth map. We adapt a mesh generation algorithm used in real-time height field rendering for depth map representation and produce a regular mesh for each depth map. Then we propose a compression technique that encodes the triangulated depth map as a set of single bit enabled flags that mark the split of triangles, and depth values at the vertices with Huffman code. By coding the vertices in the rendering order, we achieve depth map decoding and striped triangles for OpenGL based rendering in one loop, thus greatly reducing the complexity at the rendering end.
Tree Automata, Mu-Calculus and Determinacy (Extended Abstract) (1991)

We show that the propositional Mu-Calculus is equivalent in expressive power to finite automata on infinite trees. Since complementation is trivial in the Mu-Calculus, our equivalence provides a radically simplified, alternative proof of Rabin&amp;apos;s complementation lemma for tree automata, which is the heart of one of the deepest decidability results. We also show how Mu-Calculus can be used to establish determinacy of infinite games used in earlier proofs of complementation lemma, and certain games used in the theory of on-line algorithms.
Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor (2023)

Our data demonstrate that heterogeneity in the half-life of FVIII concentrates in patients with hemophilia A is primarily attributable to variability in the clearance of endogenous VWF.
An Organic Spin‐Ladder Molecular Material (1997)

Pairs of stacks of organic donors D in the salt [(DT-TTF)2][Au(mnt)2] (DT-TTF = dithiophene-tetrathiafulvalene, mnt = maleonitriledithiolate) form a classical ladder structure due to three close S …︁ S interactions (see picture). Below 225 K the double stack of donor molecules forms a spin ladder with two legs, which arises through localization of unpaired electrons in the (DT-TTF)2 dimers.
Optimization and scale-up production of Zika virus ΔNS1 in Escherichia coli: application of Response Surface Methodology (2019)

Diagnosing Zika virus (ZIKV) infections has been challenging due to the cross-reactivity of induced antibodies with other flavivirus. The concomitant occurrence of ZIKV and Dengue virus (DENV) in endemic regions requires diagnostic tools with the ability to distinguish these two viral infections. Recent studies demonstrated that immunoassays using the C-terminal fragment of ZIKV NS1 antigen (ΔNS1) can be used to discriminate ZIKV from DENV infections. In order to be used in serological tests, the expression/solubility of ΔNS1 and growth of recombinant E. coli strain were optimized by Response Surface Methodology. Temperature, time and IPTG concentration were evaluated. According to the model, the best condition determined in small scale cultures was 21 °C for 20 h with 0.7 mM of IPTG, which predicted 7.5 g/L of biomass and 962 mg/L of ΔNS1. These conditions were validated and used in a 6-L batch in the bioreactor, which produced 6.4 g/L of biomass and 500 mg/L of ΔNS1 in 12 h of induction. The serological ELISA test performed with purified ΔNS1 showed low cross-reactivity with antibodies from DENV-infected human subjects. Denaturation of ΔNS1 decreased the detection of anti-ZIKV antibodies, thus indicating the contribution of conformational epitopes and confirming the importance of properly folded ΔNS1 for the specificity of the serological analyses. Obtaining high yields of soluble ΔNS1 supports the viability of an effective serologic diagnostic test capable of differentiating ZIKV from other flavivirus infections.
Bandit problems in networks: Asymptotically efficient distributed allocation rules (2011)

This paper studies the multi-agent bandit problem in a distributed networked setting. The setting considered assumes only one bandit (the major bandit) has accessible reward information from its samples, whereas the rest (the minor bandits) have unobservable rewards. Under the assumption that the minor bandits are aware of the sampling pattern of the major bandit (but with no direct access to its rewards), a lower bound on the expected average network regret is obtained. The lower bound resembles the logarithmic optimal regret attained in single (classical) bandit problems, but in addition is shown to scale down with the number of agents. A collaborative and adaptive distributed allocation rule DA is proposed and is shown to achieve the lower bound on the expected average regret for a connected inter-bandit communication network. In particular, it is shown that under the DA allocation rule, the minor bandits attain sub-logarithmic expected regrets as opposed to logarithmic in the single agent setting.
Localization of disease-related PrP in Danish patients with different subtypes of prion disease. (2009)

There was a good morphological and anatomical concordance between what was found with PET-blot and IHC in all patients. In some specific cases, the PET-blot was superior to IHC in sensitivity. To our knowledge, this is the first report where PET-blot analysis is applied to hereditary forms of human transmissible spongiform encephalopathies and compared with sporadic cases of Creutzfeldt-Jakob disease.