gebhart/patrepeval huggingface dataset:
Direct Evidence of Conformational Heterogeneity in Human Pancreatic Glucokinase from High-Resolution Nuclear Magnetic Resonance (2010)

High-resolution nuclear magnetic resonance is used to investigate the conformational dynamics of human glucokinase, a 52 kDa monomeric enzyme that displays kinetic cooperativity. (1)H-(15)N transverse relaxation optimized spectra of uniformly labeled glucokinase, recorded in the absence and presence of glucose, reveal significant cross-peak overlap and heterogeneous peak intensities that persist over a range of temperatures. (15)N-specific labeling of isoleucines and tryptophans, reporting on backbone and side chain dynamics, respectively, demonstrates that both unliganded and glucose-bound enzymes sample multiple conformations, although glucose stabilizes certain conformations. These results provide the first direct evidence of glucokinase conformational heterogeneity and hence shed light on the molecular basis of cooperativity.
Identification of a Highly Conserved Hypothetical Protein TON_0340 as a Probable Manganese-Dependent Phosphatase (2016)

A hypothetical protein TON_0340 of a Thermococcus species is a protein conserved in a variety of organisms including human. Herein, we present four different crystal structures of TON_0340, leading to the identification of an active-site cavity harboring a metal-binding site composed of six invariant aspartate and glutamate residues that coordinate one to three metal ions. Biochemical and mutational analyses involving many phosphorous compounds show that TON_0340 is a Mn2+-dependent phosphatase. Mg2+ binds to TON_0340 less tightly and activates the phosphatase activity less efficiently than Mn2+. Whereas Ca2+ and Zn2+ are able to bind to the protein, they are unable to activate its enzymatic activity. Since the active-site cavity is small and largely composed of nearly invariant stretches of 11 or 13 amino acids, the physiological substrates of TON_0340 and its homologues are likely to be a small and the same molecule. The Mn2+-bound TON_0340 structure provides a canonical model for the ubiquitously present TON_0340 homologues and lays a strong foundation for the elucidation of their substrate and biological function.
Gene mediated insulin‐like growth factor‐I delivery to the synovium (2001)

The feasibility of articular gene therapy using insulin-like growth factor-I transgene expression in synovial tissues was assessed in vitro by transfection of synovial explant and monolayer cultures. Synovial membrane was harvested from horses and distributed for explant culture in multiwell plates or digested for monolayer culture in multiwell plates and chamber slides. Synovial monolayers were cultured for 48 h after infection with 0, 100, 200, or 500 moi adenovirus-IGF-I (AdeIGF-I) to establish an optimum dose. Explants were then either infected with AdeIGF-I or adenoviral LacZ and cultured for 8 days, treated with 100 ng/ml recombinant IGF-I as a positive control, or remained as uninfected untreated culture controls. Expression of IGF-I in explants and monolayers was assessed by in situ hybridization and quantitative polymerase chain reaction (PCR), and translation confirmed by IGF-I radioimmunoassay (RIA) and tissue immunoreaction. Effects of IGF-I on synovial function was assessed by proteoglycan and hyaluronan assay, and northern blot assessment of decorin and collagen type I expression. Significant transgene expression in synovial cells was present for all AdeIGF-I concentrations. Similarly, medium IGF-I concentrations were significantly elevated in AdeIGF-I infected synovial monolayer and explant cultures at all time points. Peak IGF-I concentration of 246 +/- 43 ng/ml developed in explant cultures on day 4; IGF-I levels in control explant groups were unchanged over baseline values. In situ hybridization and immunolocalization for IGF-I indicated focal IGF-I expression in intimal and subintimal layers of infected explants, with diffuse immunoreaction throughout infected subintimal and fibrous layers. For monolayer cultures, intracellular immunoreaction to IGF-I was markedly higher in infected cells, and was most prominent at 100 moi. Effects of IGF-I on synoviocyte cultures were evident on northern blots, which showed decreased decorin expression and elevated type I collagen production in AdeIGF-I infected monolayers. Proteoglycan concentration in the medium from explant cultures rose over the initial 4 days but was similar between treatment groups. The concentration of hyaluronan in medium from explant cultures did not differ significantly within or between treated and control groups during the 8-day study period. These data indicate that IGF-I can be successfully introduced to synovial structures by adenoviral vectors and results in effective IGF-I ligand synthesis without untoward synovial morphologic effects.
Neuromuscular Adaptations to Constant vs. Variable Resistance Training in Older Men (2013)

This study examined the effects of constant or variable external resistance training on neuromuscular adaptations in the lower limbs of older men. 37 subjects (age 65±4 year) were quasi-randomly assigned to the constant or variable training group, or a non-training control group. Training consisted of a 20-week medium-intensity, high volume resistance training program. Maximum bilateral concentric and isometric force production of the leg extensors as well as repetitions-to-failure test were performed pre-, mid- and post-training. Vastus lateralis muscle cross-sectional area was assessed by ultrasound and lean leg mass was assessed by dual-energy x-ray absorptiometry. Both training groups significantly increased force production of the leg extensors (variable: 26 kg, 95% CI=12-39, P<0.01; constant: 31 kg, 95% CI=19-43, P<0.01) and VL cross-sectional area (variable: 1.5 cm2, 95% CI=0.03-3.1, P=0.046; constant: 3 cm2, 95% CI=1.2-4.8, P=0.002). However, only the variable training group significantly improved repetitions to failure performance (704 kg, 95% CI=45-1 364, P=0.035). Only the variable resistance training group improved fatigue-resistance properties, which may be an important adaptation to maintain exercise and functional capacity in older individuals.
Early Diagnosis and Staging of Prostate Cancer Using Magnetic Resonance Imaging (2018)

Prostate cancer is the second most common cancer among men in the United States after skin cancer. Although it can be a serious disease, early diagnosis of prostate cancer can significantly prevent the growth of cancerous cells. The feature extraction is the process of defining and deriving from the prostate region computational entities that form a sort of prostate cancer signature. Full computer-aided diagnosis (CAD) systems presented in several studies have reported the use of engineered features obtained from multimodal magnetic resonance imaging (MRI) to detect prostate cancer. Similar to other medical imaging CAD systems, the computer-aided diagnosis of prostate cancer using MRI framework encompasses four stages, namely: pre-processing, prostate region extraction, features extraction, and classification. Identifying the region of interest in the MR images is essential to reduce the complexity of the next stages and enhance the performance of the overall CAD system.
Motion ID: Human Authentication Approach (2023)

We introduce a novel approach to user authentication called Motion ID. The method employs motion sensing provided by inertial measurement units (IMUs), using it to verify the persons identity via short time series of IMU data captured by the mobile device. The paper presents two labeled datasets with unlock events: the first features IMU measurements, provided by six users who continuously collected data on six different smartphones for a period of 12 weeks. The second one contains 50 hours of IMU data for one specific motion pattern, provided by 101 users. Moreover, we present a two-stage user authentication process that employs motion pattern identification and user verification and is based on data preprocessing and machine learning. The Results section details the assessment of the method proposed, comparing it with existing biometric authentication methods and the Android biometric standard. The method has demonstrated high accuracy, indicating that it could be successfully used in combination with existing methods. Furthermore, the method exhibits significant promise as a standalone solution. We provide the datasets to the scholarly community and share our project code.
Robust automatic segmentation of corneal layer boundaries in SDOCT images using graph theory and dynamic programming (2011)

Segmentation of anatomical structures in corneal images is crucial for the diagnosis and study of anterior segment diseases. However, manual segmentation is a time-consuming and subjective process. This paper presents an automatic approach for segmenting corneal layer boundaries in Spectral Domain Optical Coherence Tomography images using graph theory and dynamic programming. Our approach is robust to the low-SNR and different artifact types that can appear in clinical corneal images. We show that our method segments three corneal layer boundaries in normal adult eyes more accurately compared to an expert grader than a second grader-even in the presence of significant imaging outliers.
Silica glass based nonlinear optical fibers (2006)

This paper reviews silica glass based nonlinear optical fiber designs for signal processing using optical Kerr effect. The requirements for designing nonlinear fibers are described first. Then the design concept is discussed and design examples are shown to illustrate the tradeoffs among the different fiber properties such as effective area, dispersion and attenuation. Furthermore, fiber designs with distributed Brillouin frequency shift to mitigate the effect of simulated Brillouin scattering in nonlinear fibers are discussed in detail. SBS threshold increase of 7 dB over conventional nonlinear fibers is experimentally demonstrated.
The Immunoregulator Soluble TACI Is Released by ADAM10 and Reflects B Cell Activation in Autoimmunity (2014)

BAFF and a proliferation-inducing ligand (APRIL), which control B cell homeostasis, are therapeutic targets in autoimmune diseases. TACI-Fc (atacicept), a soluble fusion protein containing the extracellular domain of the BAFF-APRIL receptor TACI, was applied in clinical trials. However, disease activity in multiple sclerosis unexpectedly increased, whereas in systemic lupus erythematosus, atacicept was beneficial. In this study, we show that an endogenous soluble TACI (sTACI) exists in vivo. TACI proteolysis involved shedding by a disintegrin and metalloproteinase 10 releasing sTACI from activated B cells. The membrane-bound stub was subsequently cleaved by γ-secretase reducing ligand-independent signaling of the remaining C-terminal fragment. The shed ectodomain assembled ligand independently in a homotypic way. It functioned as a decoy receptor inhibiting BAFF- and APRIL-mediated B cell survival and NF-κB activation. We determined sTACI levels in autoimmune diseases with established hyperactivation of the BAFF-APRIL system. sTACI levels were elevated both in the cerebrospinal fluid of the brain-restricted autoimmune disease multiple sclerosis correlating with intrathecal IgG production, as well as in the serum of the systemic autoimmune disease systemic lupus erythematosus correlating with disease activity. Together, we show that TACI is sequentially processed by a disintegrin and metalloproteinase 10 and γ-secretase. The released sTACI is an immunoregulator that shares decoy functions with atacicept. It reflects systemic and compartmentalized B cell accumulation and activation.
Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a Phase I trial. (1980)

The serum half-life of 5-fluorouracil (5-FUra) in humans is best described as a biexponential decay function, with t1/2 alpha = 7.8 +/- 2.6 (S.E.) min and t1/2 beta = 36.8 +/- 13.5 min during initial courses of this drug alone. Pharmacokinetics of 5-FUra during courses of daily therapy (for 5 days) revealed prolongation of t1/2 in both components of the decay curve, which has not been previously reported. Despite the efficacy of thymidine (dThd) given as a continous i.v. infusion of 8 g/sq m/day in prevention of high-dose methotrexate toxicity, continuous infusion of dThd at this dose does not prevent the toxicity of 5-FUra orreverse inhibition of DNA and RNA synthesis by 5-fura. On the contrary, continuous infusion of dThd appears to increase the toxicity of 5-FUra during continuous dThd infusion revealed prolongation of the 5-FUra t1/2 which remained stable through the course of 5 days of 5-FUra with dThd. This protracted t1/2 is believed to account at least in part for the increased toxicity of 5-FUra with dThd. Dose-limiting mucositis, myelosuppression, and gastrointestinal toxicity were observed at 5-FUra doses ranging from one-half to two-thirds the customarily tolerated dose of 5-FUra alone in similar courses of daily bolus therapy (for 5 days).
Site-specific Tn7 transposition into the human genome (2005)

The bacterial transposon, Tn7, inserts into a single site in the Escherichia coli chromosome termed attTn7 via the sequence-specific DNA binding of the target selector protein, TnsD. The target DNA sequence required for Tn7 transposition is located within the C-terminus of the glucosamine synthetase (glmS) gene, which is an essential, highly conserved gene found ubiquitously from bacteria to humans. Here, we show that Tn7 can transpose in vitro adjacent to two potential targets in the human genome: the gfpt-1 and gfpt-2 sequences, the human analogs of glmS. The frequency of transposition adjacent to the human gfpt-1 target is comparable with the E.coli glmS target; the human gfpt-2 target shows reduced transposition. The binding of TnsD to these sequences mirrors the transposition activity. In contrast to the human gfpt sequences, Tn7 does not transpose adjacent to the gfa-1 sequence, the glmS analog in Saccharomyces cerevisiae. We also report that a nucleosome core particle assembled on the human gfpt-1 sequence reduces Tn7 transposition by likely impairing the accessibility of target DNA to the Tns proteins. We discuss the implications of these findings for the potential use of Tn7 as a site-specific DNA delivery agent for gene therapy.
In-Situ Evaluation of the Diffusion of Epoxy and Amine in Thermoplastic Polymers (1998)

Abstract The current study investigates the diffusion of a bisphenol A type epoxy resin and a diamine curing agent into polysulfone (PSU) using a Fourier Transform Infrared Spectroscopy-Attenuated Total Reflectance (FTIR-ATR) technique. The diffusion of epoxy or amine through the film was monitored in real time by measuring the changing intensity of selected characteristic absorbance bands in each of the polymers. The diffusion coefficients for the epoxy and amine were determined independently using the appropriate solution to the diffusion equation and the experimental data. Diffusivities were evaluated at several temperatures, and an Arrhenius relationship was observed. Results show that the diffusivity of amine is an order of magnitude greater than the diffusivity of epoxy at each temperature tested. Furthermore, the epoxy diffusion appears to be Fickian, while the diffusion of amine appears to be non-Fickian.
Efficient probabilistic collision detection for non-convex shapes (2017)

We present new algorithms to perform fast probabilistic collision queries between convex as well as non-convex objects. Our approach is applicable to general shapes, where one or more objects are represented using Gaussian probability distributions. We present a fast new algorithm for a pair of convex objects, and extend the approach to non-convex models using hierarchical representations. We highlight the performance of our algorithms with various convex and non-convex shapes on complex synthetic benchmarks and trajectory planning benchmarks for a 7-DOF Fetch robot arm.
Replacement of aromatic fluorine by a methoxy group during reaction with methyl iodide inN,N-dimethylformamide solvent (1987)

The DNA base uracil was derivatized with pentafluorobenzoyl chloride, followed by methylation with methyl iodide in the presence of N,N-dimethylformamide (DMF). In addition to a 3-pentafluorobenzoyl-1-methyl derivative of uracil, GC/MS analysis of the reaction mixture revealed the formation of an unusual product, whose molecular weight was 12 U higher than that of the prior derivative. This unexpected product has been identified as the 3-(para-methoxytetrafluorobenzoyl)-1-methyl derivative of uracil. Isotopic labeling and related experiments have revealed that the DMF solvent contributes the oxygen atom of the methoxy group that replaces the para fluorine atom. This work allowed a single derivative to be obtained for the methylation reaction by changing the solvent to acetonitrile.
On the Diastereoselectivity of Ru-Catalyzed [5 + 2] Cycloadditions (2003)

[reaction: see text]. Ru-catalyzed cycloisomerization of cyclopropylenynes proceeds with good to high diastereoselectivities to form hexahydroazulenes.
The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation (2019)

We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes.
New Lignans from Anogeissus acuminata with HIV-1 Reverse Transcriptase Inhibitory Activity (1994)

Anolignan A [1] and anolignan B [3] are new dibenzylbutadiene lignans isolated from Anogeissus acuminata. Compounds 1 and 3 were identified as the active HIV-1 reverse transcriptase (RT) inhibitory constituents of this plant obtained by bioassay-guided fractionation. Compound 3, which was very weakly active when tested alone, showed high activity when combined with 1. The activity of 1 was likewise enhanced in the presence of 3. A concave isobole obtained from a plot of data derived from assays with 1 and 3 in combination indicated their synergistic effects. Another new lignan, anolignan C [5], and a known lignan, (-)-secoisolariciresinol [10], were also isolated from this plant. Compounds 5 and 10 did not have activity against HIV-1 RT. Compounds 1, 3 and 5 were either weakly cytotoxic or noncytotoxic when tested in various cancer cell lines. The structures of 1-5 and 10 were established by spectroscopic methods, especially by 1D and 2D nmr experiments.
Sandia National Laboratories High Flux Neutron Radiography Facility image characterization (1991)

In 1990 a project was initiated to upgrade the neutron radiography facility for the Annular Core Research Reactor (ACRR). This new system was designed to produce a thermal neutron flux suitable for performing high quality real-time imaging of dynamic events. A variation of the design presented at the First International Topical Meeting on Neutron Radiography System Design and Characterization was built in 1991. Static image characterization of the facility was achieved by using the procedures of ASTM Standard E545-86 for film radiography. The real-time radiography capabilities were determined with a Precise Optics imaging tube and various CCD cameras. The overall performance of the facility has been excellent. At a reactor power of 2.0 MW(t), film radiographs can be taken with Kodak SR film in 5 seconds. The signal-to-noise ratio for real-time radiography has been significantly improved and is as high as 157:1.
High-Pressure Synthesis of Double Perovskite Ba<sub>2</sub>NiIrO<sub>6</sub>: In Search of a Ferromagnetic Insulator (2020)

Double perovskite oxides with d<sup>8</sup>-d<sup>3</sup> electronic configurations are expected to be ferromagnetic from the Goodenough-Kanamori rules, such as ferromagnetic La<sub>2</sub>NiMnO<sub>6</sub>. In search of new ferromagnetic insulators, double perovskite Ba<sub>2</sub>NiIrO<sub>6</sub> was successfully synthesized by high-pressure and high-temperature methods (8 GPa and 1573 K). Ba<sub>2</sub>NiIrO<sub>6</sub> crystallizes in a cubic double perovskite structure (space group: <i>Fm</i>3̅<i>m</i>), with an ordered arrangement of NiO<sub>6</sub> and IrO<sub>6</sub> octahedra. X-ray absorption near-edge spectroscopy confirms the nominal Ni(II) and Ir(VI) valence states. Ba<sub>2</sub>NiIrO<sub>6</sub> displays an antiferromagnetic order at 51 K. The positive Weiss temperature, however, indicates that ferromagnetic interactions are dominant. Isothermal magnetization curves at low temperatures support a field-induced spin-flop transition.
Activation and Tolerance in CD4+ T Cells Reactive to an Immunoglobulin Variable Region (2004)

Antibody diversity creates an immunoregulatory challenge for T cells that must cooperate with B cells, yet discriminate between self and nonself. To examine the consequences of T cell reactions to the B cell receptor (BCR), we generated a transgenic (Tg) line of mice expressing a T cell receptor (TCR) specific for a kappa variable region peptide in monoclonal antibody (mAb) 36-71. The kappa epitope was originally generated by a pair of somatic mutations that arose naturally during an immune response. By crossing this TCR Tg mouse with mice expressing the kappa chain of mAb 36-71, we found that kappa-specific T cells were centrally deleted in thymi of progeny that inherited the kappaTg. Maternally derived kappaTg antibody also induced central deletion. In marked contrast, adoptive transfer of TCR Tg T cells into kappaTg recipients resulted in T and B cell activation, lymphadenopathy, splenomegaly, and the production of IgG antichromatin antibodies by day 14. In most recipients, autoantibody levels increased with time, Tg T cells persisted for months, and a state of lupus nephritis developed. Despite this, Tg T cells appeared to be tolerant as assessed by severely diminished proliferative responses to the Vkappa peptide. These results reveal the importance of attaining central and peripheral T cell tolerance to BCR V regions. They suggest that nondeletional forms of T tolerance in BCR-reactive T cells may be insufficient to preclude helper activity for chromatin-reactive B cells.