gebhart/patrepeval huggingface dataset:
A super-linear minimization scheme for the nudged elastic band method (2003)

In this article, we present a superlinear minimization scheme for the nudged elastic band (NEB) method, which determines a minimum-energy path (MEP) of a reaction via connecting intermediate “replicas” between the reactant and the product. The minimization scheme is based on a quasi-Newton method: the adopted basis Newton–Raphson (ABNR) minimization scheme. In each step of ABNR minimization, the Newton–Raphson procedure is performed in a subspace of a user-defined dimension. The tangent directions of the path at a new Newton–Raphson step are determined self-consistently in the subspace. The acceleration of the proposed scheme over the quenched molecular-dynamic minimization, the current practice for minimizing a path using NEB, is demonstrated in three nontrivial test cases: isomerization of an alanine dipeptide, α-helix to π-helix transition of an alanine decapeptide, and oxidation of dimethyl sulfide. New features are also added such that the distances between replicas can be defined in the root of mean squared (RMS) best-fit space with flexible weighting options. This offers a way to incorporate the effects of a mobile solvent in the process with a finite number of replicas. MEPs obtained from various initial structures can be used to investigate different proposed reaction mechanisms, and the speedup of minimizing a path enhances the applicability of the NEB method. The combination of NEB force projection procedures, the flexible distance definition in the RMS best fit space with arbitrary weighting options, and the superlinear minimization scheme provides a framework to aid in the study of transition processes of biological molecules as such proteins.
Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening (2013)

Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal population involved in the higher cognitive functions of the human and are particularly affected by psychiatric diseases with developmental manifestations such as schizophrenia and autism. Differentiation protocols of human pluripotent stem cells (PSC) into cortical neurons have been achieved, opening the way to in vitro modeling of neuropsychiatric diseases. However, these protocols commonly result in the asynchronous production of neurons typical for the different layers of the cortex within an extended period of culture, thus precluding the analysis of specific subtypes of neurons in a standardized manner. Addressing this issue, we have successfully captured a stable population of self-renewing late cortical progenitors (LCPs) that synchronously and massively differentiate into glutamatergic cortical neurons of the upper layers. The short time course of differentiation into neurons of these progenitors has made them amenable to high-throughput assays. This has allowed us to analyze the capability of LCPs at differentiating into post mitotic neurons as well as extending and branching neurites in response to a collection of selected bioactive molecules. LCPs and cortical neurons of the upper layers were successfully produced from patient-derived-induced PSC, indicating that this system enables functional studies of individual-specific cortical neurons ex vivo for disease modeling and therapeutic purposes.
A Novel Blue Light Emitting Material Prepared from 2-(o-Hydroxyphenyl)benzoxazole (1994)

Abstract A new organozinc compound, zinc bis-2-(o-hydroxyphenyl)benzoxazolate, was prepared from 2-(o-hydroxyphenyl)benzoxazole and electroluminescent properties of the compound was investigated. An electroluminescent device was composed of glass substrate/indium-tin-oxide/hole transporting layer/zinc benzoxazolate/Al thin films. The electroluminescence of blue light was observed with the electric field of over 90 MV/m.
Synthesis of a New Reagent, Ethyl 4‐azidobenzoylaminoacetimidate, and Its Use for RNA‐Protein Cross‐linking within Escherichia coli Ribosomal 30‐S Subunits (1980)

A new reagent, ethyl 4-azidobenzoylaminoacetimidate, was prepared in a four-step synthesis starting from 4-aminobenzoic acid. This compound was used to cross-link RNA with proteins within the Escherichia coli 30-S ribosomal subunits. Following the reaction of the imidoester function with protein NH2 groups, photoactivation of the azide binds the other end of the reagent to RNA. The cross-linked proteins were labelled with 125I and identified by bidimensional gel electrophoresis. Proteins S3, S4, S5, S7, S9, S17, S18, and in a lower and more variable yield, S12, S13, S14 and S16 were bound to 16-S RNA. These results were confirmed by isolating cross-linked protein-oligonucleotide complexes from 30-S subunits containing 32P-labelled RNA.
Ligand and Coactivator Identity Determines the Requirement of the Charge Clamp for Coactivation of the Peroxisome Proliferator-activated Receptor γ (2003)

The activation function 2 (AF-2)-dependent recruitment of coactivator is essential for gene activation by nuclear receptors. We show that the peroxisome proliferator-activated receptor gamma (PPARgamma) (NR1C3) coactivator-1 (PGC-1) requires both the intact AF-2 domain of PPARgamma and the LXXLL domain of PGC-1 for ligand-dependent and ligand-independent interaction and coactivation. Although the AF-2 domain of PPARgamma is absolutely required for PGC-1-mediated coactivation, this coactivator displayed a unique lack of requirement for the charge clamp of the ligand-binding domain of the receptor that is thought to be essential for LXXLL motif recognition. The mutation of a single serine residue adjacent to the core LXXLL motif of PGC-1 led to restoration of the typical charge clamp requirement. Thus, the unique structural features of the PGC-1 LXXLL motif appear to mediate an atypical mode of interaction with PPARgamma. Unexpectedly, we discovered that various ligands display variability in terms of their requirement for the charge clamp of PPARgamma for coactivation by PGC-1. This ligand-selective variable requirement for the charge clamp was coactivator-specific. Thus, distinct structural determinants, which may be unique for a particular ligand, are utilized by the receptor to recognize the coactivator. Our data suggest that even subtle differences in ligand structure are perceived by the receptor and translated into a unique display of the coactivator-binding surface of the ligand-binding domain, allowing for differential recognition of coactivators that may underlie distinct pharmacological profiles observed for ligands of a particular nuclear receptor.
Temperature dependence of cell-cell fusion induced by the envelope glycoprotein of human immunodeficiency virus type 1 (1995)

We investigated cell-cell fusion induced by the envelope glycoprotein of human immunodeficiency virus type 1 strain IIIB expressed on the surface of CHO cells. These cells formed syncytia when incubated together with CD4-positive human lymphoblastoid SupT1 cells or HeLa-CD4 cells but not when incubated with CD4-negative cell lines. A new assay for binding and fusion was developed by using fluorescent phospholipid analogs that were produced in SupT1 cells by metabolic incorporation of BODIPY-labeled fatty acids. Fusion occurred as early as 10 min after mixing of labeled SupT1 cells with unlabeled CHO-gp160 cells at 37 degrees C. When both the fluorescence assay and formation of syncytia were used, fusion of SupT1 and HeLa-CD4 cells with CHO-gp160 cells was observed only at temperatures above 25 degrees C, confirming recent observations (Y.-K. Fu, T.K. Hart, Z.L. Jonak, and P.J. Bugelski, J. Virol. 67:3818-3825, 1993). This temperature dependence was not observed with influenza virus-induced cell-cell fusion, which was quantitatively similar at both 20 and 37 degrees C, indicating that cell-cell fusion in general is not temperature dependent in this range. gp120-CD4-specific cell-cell binding was found over the entire 0 to 37 degrees C range but increased markedly above 25 degrees C. The enhanced binding and fusion were reduced by cytochalasins B and D. Binding of soluble gp120 to CD4-expressing cells was equivalent at 37 and 16 degrees C. Together, these data indicate that during gp120-gp41-induced syncytium formation, initial cell-cell binding is followed by a cytoskeleton-dependent increase in the number of gp120-CD4 complexes, leading to an increase in the avidity of cell-cell binding. The increased number of gp120-CD4 complexes is required for fusion, which suggests that the formation of a fusion complex consisting of multiple CD4 and gp120-gp41 molecules is a step in the fusion mechanism.
GaussSense (2012)

This work presents GaussSense, which is a back-of-device sensing technique for enabling input on an arbitrary surface using stylus by exploiting magnetism. A 2mm-thick Hall sensor grid is developed to sense magnets that are embedded in the stylus. Our system can sense the magnetic field that is emitted from the stylus when it is within 2cm of any non-ferromagnetic surface. Attaching the sensor behind an arbitrary thin surface enables the stylus input to be recognized by analyzing the distribution of the applied magnetic field. Attaching the sensor grid to the back of a touchscreen device and incorporating magnets into the corresponding stylus enable the system 1) to distinguish touch events that are caused by a finger from those caused by the stylus, 2) to sense the tilt angle of the stylus and the pressure with which it is applied, and 3) to detect where the stylus hovers over the screen. A pilot study reveals that people were satisfied with the novel sketching experiences based on this system.
Supplementation with evening primrose oil in atopic dermatitis: Effect on fatty acids in neutrophils and epidermis (1991)

We investigated the effect of oral supplementation with evening primrose oil, containing 72% linoleic acid (18:2n-6) and 10% gamma-linolenic acid (18:3n-6), on the epidermal and neutrophil phospholipid fatty acid composition in 15 patients with atopic dermatitis (AD). Three different dose levels, 4, 8 and 12 capsules per day containing 0.5 g oil, were given to three groups of patients. The only n-6 fatty acid showing a significant (p less than 0.05) dose-related increase was dihomo-gamma-linolenic acid (20:3n-6) in neutrophil phospholipids. The highest dose increased dihomo-gamma-linolenic acid by 45% in neutrophil phospholipids, by 46% in lesion-free epidermal phosphatidylcholine, and by 15% in lesion-free epidermal phosphatidylethanolamine. In both lesional and lesion-free epidermis, supplementation resulted in a rise in the ratio between n-6 and monounsaturated fatty acids, reaching significance (p less than 0.05) in lesional epidermis. This study shows that moderate and favorable fatty acid changes can be obtained in the epidermis of AD patients, when given 6 g per day of oil rich in n-6 fatty acids. The abnormal lipid and fatty acid pattern of the atopic epidermis may be involved in the pathogenesis of the disease, and should therefore be the target for future therapeutic approaches with fatty acid supplements.
Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. (2003)

Epratuzumab represents an excellent anti-CD22 ligating agent, highly efficacious in inducing CD22 internalization, and can induce phosphorylation. Although we cannot unequivocally demonstrate here that epratuzumab-induced internalization and signaling of CD22 directly contribute to its therapeutic efficacy, these properties are the fundamental characteristics of the target CD22 and its interaction with epratuzumab. Similar results were observed when epratuzumab was tested in vitro on Burkitt B cell lines as well as on primary normal B cells and neoplastic B cells separated from fresh peripheral blood samples from patients with chronic lymphocytic leukemia.
Heterogeneous 2D/3D photonic integrated microsystems (2016)

The continuing trend of exponential growth in data communications and processing are driving the need for large-scale heterogeneous integration. Similar to the trend we have observed in electronic integrated circuit development, we are witnessing a growing trend in 3D photonic integrated circuits (PICs) development in addition to that in 2D PICs. There are two main methods for fabricating 3D PICs. The first method, which utilizes ultrafast laser inscription (ULI), offers freeform shaping of waveguides in arbitrary contours and formations. The second method, which utilizes multilayer stacking and coupling of planar PICs, exploits relatively mature 2D PIC fabrication processes applied to each layer sequentially. Both the fabrication methods for 3D PICs have advantages and disadvantages such that certain applications may favor one method over the other. However, a joining of 2D PICs with 3D PICs can help develop integrated microsystems with new functionalities such as non-mechanical beam steering, space-division multiplexing (SDM), programmable arbitrary beam shaping, and photonic signal processing. We discuss examples of 3D PICs and 2D/3D integrated PICs in two applications: SDM via orbital-angular-momentum (OAM) multiplexing/demultiplexing and optical beam steering using optical phased arrays. Although a 2D PIC by itself can function as an OAM multiplexer or demultiplexer, it has limitations in supporting both polarizations. Alternatively, a 3D PIC fabricated by ULI can easily support both polarizations with low propagation loss. A combination of a 3D PIC and a 2D PIC designed and fabricated for OAM applications has successfully multiplexed and demultiplexed 15 OAM states to demonstrate polarization-diversified SDM coherent optical communications using multiple OAM states. Coherent excitation of multi-ring OAM states can allow highly scalable SDM utilizing Laguerre-Gaussian modes or linearly polarized (LP) modes. The preliminary fabrication of multi-ring OAM multiplexers and demultiplexers using the multilayer 3D PIC method and the ULI 3D PIC method has also been pursued. Large-scale (for example, 16×16 optical phased array) 3D PICs fabricated with the ULI technique have been demonstrated. Through these examples, we show that heterogeneous 2D/3D photonic integration retains the advantages of 2D PICs and 3D waveguides, which can potentially benefit many other applications.
Potent, Orally Active GPIIb/IIIa Antagonists Containing a Nipecotic Acid Subunit. Structure−Activity Studies Leading to the Discovery of RWJ-53308 (1999)

Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-activity surrounding the prototype fibrinogen receptor antagonist RWJ-50042 (racemate of 1), which was derived from a unique approach involving the gamma-chain of fibrinogen (Hoekstra et al. J. Med. Chem. 1995, 38, 1582). Our analogue studies culminated in the discovery of RWJ-53308 (2), a potent, orally active GPIIb/IIIa antagonist. To progress from RWJ-50042 to a suitable candidate for clinical development, we conducted a series of optimization cycles that employed solid-phase parallel synthesis for the rapid, efficient preparation of nearly 250 analogues, which were assayed for fibrinogen receptor affinity and inhibition of platelet aggregation induced by four different activators. This strategy produced several promising analogues for advanced study, including 3-(3,4-methylenedioxybenzene)-beta-amino acid analogue 3 (significant improved in vivo potency) and 3-(3-pyridyl)-beta-amino acid 2 (significantly improved potency, oral absorption, and duration of action). In dogs, 2 displayed significant ex vivo antiplatelet activity on oral administration at 1.0 mg/kg, 16% systemic oral bioavailability, minimal metabolic transformation, and an excellent safety profile. Additionally, 2 was found to be efficacious in three in vivo thrombosis models: canine arteriovenous (AV) shunt (0.01-0.1 mg/kg, iv), guinea pig photoactivation-induced injury (0.3-3 mg/kg, iv), and guinea pig ferric chloride-induced injury (0.3-1 mg/kg, iv). On the basis of its noteworthy preclinical data, RWJ-53308 (2) was selected for clinical evaluation.
Effect of Low-Intensity (3.75-25 J/cm 2 ) Near-Infrared (810 nm) Laser Radiation on Red Blood Cell ATPase Activities and Membrane Structure (2004)

Near-infrared laser light radiation (810 nm) induced long-term conformational transitions of red blood cell membrane which were related to the changes in the structural states of both erythrocyte membrane proteins and lipid bilayer and which manifested themselves as changes in fluorescent parameters of erythrocyte membranes and lipid bilayer fluidity. This resulted in the modulation of membrane functional properties: changes in the activity of membrane ion pumps and, thus, changes in membrane ion flows.
<title>MEMS infrastructure: the multiuser MEMS processes (MUMPs)</title> (1995)

In order to help provide access to advanced MEMS technologies, and lower the barriers for both industry and academia, MCNC, and ARPA have developed a program which works to provide users with access to both MEMS processes and advanced integration techniques. The two distinct aspects of this program, the MUMPs and Smart MEMS, will be described in this paper. The multi-user MEMS processes (MUMPs) is an ARPA-supported program created to provide inexpensive access to MEMS technology in a multi-user environment. MUMPs is a proof-of-concept and educational tool to aid the developemnt of MEMS in the domestic community. MUMPs technologies currently include a 3-layer polysilicon surface micromachining process and LIGA processes that provide reasonable design flexibility within set guidelines. Smart MEMS is the development of advanced electronics integration techniques for MEMS through the application of flip chip technology.
Procoagulant activity in cancer cells is dependent on tissue factor expression. (1994)

Procoagulant activity of pairs of cell lines, which were derived from the same original cell type but which possess different growth characteristics and metastatic properties, was examined. The following characteristics were considered suggestive of a greater likelihood of metastatic potential: high histological grade; establishment of the line from a metastatic rather than a nonmetastatic cancer; increased tumorigenicity in nude mice; and/or estrogen receptor-negative mammary cancer. Procoagulant activity was evaluated by a two stage clotting assay. Procoagulant activity was highly variable, with up to a 1,300-fold difference, among the cancer cell lines examined. The rate of clot formation was factor VII dependent and was totally inhibited by an anti tissue factor monoclonal antibody, indicating that tissue factor was the only significant procoagulant present in these cancer cells. Tissue factor antigen expression, evaluated by ELISA, correlated with procoagulant activity. In all pairs of cancer cell lines, those with characteristics of increased proliferative potential had increased tissue factor levels compared to cell lines that originated from the same cell type, but which possess less aggressive characteristics. Tissue factor activity in these cancer cells was increased by cell lysis or by exposure of intact cells to a calcium ionophore, similar to results previously obtained in fibroblasts. Tissue factor mRNA was evaluated by northern blot analysis using a specific probe complementary to tissue factor mRNA. The previously described predominant tissue factor mRNA species of 2.2 kb was identified in the majority of cancer cell lines examined, but tissue factor mRNA species of 3.2 to 3.4 kb were also identified.(ABSTRACT TRUNCATED AT 250 WORDS)
Controlling the Electrophoretic Mobility of Single-Walled Carbon Nanotubes:  A Comparison of Theory and Experiment (2007)

The electrophoretic mobilities of single-walled carbon nanotubes (SWNTs) in agarose gels subjected to negatively charged covalent functionalization and noncovalent anionic surfactant adsorption are compared using a simplified hydrodynamic model. Net charges are calculated on the basis of estimated friction coefficients for cylindrical rodlike particles. The effects of functionalization with negatively charged 4-hydroxybenzene diazonium and anionic sodium cholate are quantified and compared with model predictions. The adsorption of Na+ counterions into the nonionic surfactant layer adsorbed on SWNTs (Triton-X-405) is shown to induce a positive charge and reverse the mobility under select conditions. This effect has not been identified or quantified for nanoparticle systems and may be important in the processing of these systems.
Identification and characterization of large DNA deletions affecting oil quality traits in soybean seeds through transcriptome sequencing analysis (2016)

Identification and characterization of a 254-kb genomic deletion on a duplicated chromosome segment that resulted in a low level of palmitic acid in soybean seeds using transcriptome sequencing. A large number of soybean genotypes varying in seed oil composition and content have been identified. Understanding the molecular mechanisms underlying these variations is important for breeders to effectively utilize them as a genetic resource. Through design and application of a bioinformatics approach, we identified nine co-regulated gene clusters by comparing seed transcriptomes of nine soybean genotypes varying in oil composition and content. We demonstrated that four gene clusters in the genotypes M23, Jack and N0304-303-3 coincided with large-scale genome rearrangements. The co-regulated gene clusters in M23 and Jack mapped to a previously described 164-kb deletion and a copy number amplification of the Rhg1 locus, respectively. The coordinately down-regulated gene clusters in N0304-303-3 were caused by a 254-kb deletion containing 19 genes including a fatty acyl-ACP thioesterase B gene (FATB1a). This deletion was associated with reduced palmitic acid content in seeds and was the molecular cause of a previously reported nonfunctional FATB1a allele, fap nc . The M23 and N0304-304-3 deletions were located in duplicated genome segments retained from the Glycine-specific whole genome duplication that occurred 13 million years ago. The homoeologous genes in these duplicated regions shared a strong similarity in both their encoded protein sequences and transcript accumulation levels, suggesting that they may have conserved and important functions in seeds. The functional conservation of homoeologous genes may result in genetic redundancy and gene dosage effects for their associated seed traits, explaining why the large deletion did not cause lethal effects or completely eliminate palmitic acid in N0304-303-3.
A diversity of SERCA Ca2+ pump inhibitors (2011)

The SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) is probably the most extensively studied membrane protein transporter. There is a vast array of diverse inhibitors for the Ca2+ pump, and many have proved significant in helping to elucidate both the mechanism of transport and gaining conformational structures. Some SERCA inhibitors such as thapsigargin have been used extensively as pharmacological tools to probe the roles of Ca2+ stores in Ca2+ signalling processes. Furthermore, some inhibitors have been implicated in the cause of diseases associated with endocrine disruption by environmental pollutants, whereas others are being developed as potential anticancer agents. The present review therefore aims to highlight some of the wide range of chemically diverse inhibitors that are known, their mechanisms of action and their binding location on the Ca2+ ATPase. Additionally, some ideas for the future development of more useful isoform-specific inhibitors and anticancer drugs are presented.