gebhart/patrepeval huggingface dataset:
Native Chemical Ligation: A Boon to Peptide Chemistry (2014)

The use of chemical ligation within the realm of peptide chemistry has opened various opportunities to expand the applications of peptides/proteins in biological sciences. Expansion and refinement of ligation chemistry has made it possible for the entry of peptides into the world of viable oral therapeutic drugs through peptide backbone cyclization. This progression has been a journey of chemical exploration and transition, leading to the dominance of native chemical ligation in the present advances of peptide/protein applications. Here we illustrate and explore the historical and current nature of peptide ligation, providing a clear indication to the possibilities and use of these novel methods to take peptides outside their typically defined boundaries.
Design of Chiral Phase Transfer Catalyst with Conformationally Fixed Biphenyl Core:  Application to Asymmetric Alkylation of Glycine Derivatives (2007)

Chiral phase transfer catalysts (S)-1a and (S)-1b with a conformationally fixed biphenyl core were conveniently prepared from the known (S)-6,6‘-dimethylbiphenyl-2,2‘-diol 2 in five steps. These catalysts, (S)-1a and (S)-1b, are readily applicable to asymmetric alkylation of glycine derivatives with excellent enantioselectivity. In particular, catalyst (S)-1b was found to exhibit a unique temperature effect on the enantioselectivity, and asymmetric alkylation of glycine derivatives at room temperature gave a higher ee than that at 0 °C.
Comparison of lumbar paravertebral EMG patterns in chronic low back pain patients and non-patient controls (1988)

According to myogenic models that relate abnormal EMG patterns to the experience of pain, lumbar paravertebral muscle activity has been considered to play an important role in chronic low back pain. In the present study, 40 chronic low back pain patients and 40 matched non-patient controls were compared on lumbar paravertebral EMG during mechanically stabilized static and dynamic postures. Differences between groups in lumbar curvature and spinal range of motion were determined using a dual goniometer technique. Although the two groups did not differ on absolute levels of EMG during quiet standing, significant differences were found for EMG patterns during dynamic postures. In addition, most patients did not show the flexion-relaxation response or the expected pattern of EMG responses during trunk rotation, most likely because of restricted range of motion and/or compensatory posturing. These findings provide support for the biomechanical model of chronic pain and indicate the need for further research pertaining to pain behavior and movement-related lumbar muscle activity.
MAL Expression in Lymphoid Cells: Further Evidence for MAL as a Distinct Molecular Marker of Primary Mediastinal Large B-Cell Lymphomas (2002)

The MAL mRNA was initially identified during T-cell development and was later found in myelin-forming cells and certain polarized epithelial cell lines. It encodes a proteolipid believed to participate in membrane microdomains stabilization, transport machinery and signal transduction. Using a differential display reverse-transcription approach, we identified MAL as a distinct molecular marker of primary mediastinal large B-cell lymphoma compared with nonmediastinal diffuse large B-cell lymphomas. In the present study, we used immunohistochemistry to extend MAL expression analysis to normal lymphoid tissues; to 185 lymphomas representing most B, T, and Hodgkin lymphoma entities; and to the primary mediastinal large B-cell lymphoma derived B-cell line MedB-1. In addition, B and T cells from peripheral blood, tonsil, and spleen were analyzed by flow cytometry. Our results show that MAL is highly expressed in thymocytes, in a large percentage of peripheral CD4 T cells, and in a lower proportion of CD8 peripheral T cells. In the normal B-cell compartment, MAL expression appears to be restricted to a minor subpopulation of thymic medullary B cells and to occasional mature plasma cells located in the interfollicular areas of tonsil and lymph nodes. Among B-cell lymphomas (n = 110), MAL expression in tumor cells was observed in 21/33 primary mediastinal large B-cell lymphomas (70%) and in 3/5 plasmacytoma/myeloma, but not in all other B-cell lymphomas with the exception of 1/33 nonmediastinal diffuse large B-cell lymphomas. The MedB-1 B-cell line was also MAL positive. Among T-cell neoplasms, MAL was highly expressed in lymphoblastic tumors (5/6), whereas mature T-cell lymphomas were essentially MAL negative (27/28). Among 41 Hodgkin lymphomas, 3 nodular-sclerosing cases with mediastinal involvement showed MAL-positive Reed Sternberg cells. In conclusion, this study further supports thymic B cells as the putative normal counterpart of primary mediastinal large B-cell lymphomas and supports MAL as a distinct molecular marker of this lymphoma subtype among diffuse large B-cell lymphomas.
Fabrication and characteristics of GaN/AlGaN multilayer structure for terahertz quantum-cascade laser (2006)

The GaN/AlGaN multilayer structure for the active regions of terahertz quantum cascade lasers (QCLs) was grown by metal organic chemical vapor deposition (MOCVD). The surface morphology of the grown sample showed good surface quality with an average roughness of less than 1 nm. The x-ray diffraction pattern and transmission electron microscopy images showed that the well-controlled quantum cascade GaN/AlGaN layers were grown. The Fourier transform infrared spectrometer measurement showed a distinct A<sub>1</sub> (LO) phonon frequency at 822 cm<sup>-1</sup> that is red-shifted with respect to the single Al<sub>0.2</sub>Ga<sub>0.8</sub>N layer due to the good periodicity of the grown quantum cascade GaN/Al<sub>0.2</sub>Ga<sub>0.8</sub>N structure. MOCVD growth should be a viable technique for fabrication of AlGaN/GaN quantum cascade laser and phonon frequency shift should be a key indicator for the good periodicity of the grown QCL structure.
Neutrophil Extracellular Trap (NET) Impact on Deep Vein Thrombosis (2012)

Deep vein thrombosis (DVT) is a major health problem that requires improved prophylaxis and treatment. Inflammatory conditions such as infection, cancer, and autoimmune diseases are risk factors for DVT. We and others have recently shown that extracellular DNA fibers produced in inflammation and known as neutrophil extracellular traps (NETs) contribute to experimental DVT. NETs stimulate thrombus formation and coagulation and are abundant in thrombi in animal models of DVT. It appears that, in addition to fibrin and von Willebrand factor, NETs represent a third thrombus scaffold. Here, we review how NETs stimulate thrombosis and discuss known and potential interactions of NETs with endothelium, platelets, red blood cells, and coagulation factors and how NETs could influence thrombolysis. We propose that drugs that inhibit NET formation or facilitate NET degradation may prevent or treat DVT.
A simple, accurate method to calculate spread spectrum multiple access error probabilities (2002)

A simple-to-use approximation for the bit error probability is given. The accuracy should be acceptable in most engineering studies. In fact, although the standard approximation may be inaccurate, it is actually sufficient in many cases. Even in those cases, the approach presented can be used with greater confidence with insignificant additional complexity, or it can be used as a quick indicator of the sufficiency of the standard approximation. The approach naturally leads to the identification of key parameters for analysis. The approach is more generally applicable and its applicability and accuracy are being studied for other SSMA (spread spectrum multiple access) problems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Leader Delegation, Task Significance, and Trust in Global Software Development Teams (2007)

Partially distributed global teams form an important work structure in software development projects. However, little is known about the challenges such team structures create in supporting team members' motivation and maintaining member job satisfaction. This study investigates the effects of leader delegation, task significance and trust between local and distributed members of a team on team member motivation and job satisfaction. The paper also proposes a research model and a set of hypotheses regarding these effects. A pilot study performed on student teams is described which tests portions of the research model. The study found that distributed software team leaders delegate more to competent teams and that delegation is positively correlated with team member satisfaction with their leader and with team member motivation. The results form this work suggest both that global team leaders need to assess team competence when delegating tasks and also that organizations putting together global teams should strive to create highly competent teams since member distribution entrains higher delegation.
Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor (2017)

Targeted delivery of antisense oligonucleotides (ASO) to hepatocytes via the asialoglycoprotein receptor (ASGR) has improved the potency of ASO drugs ∼30-fold in the clinic (1). In order to fully characterize the effect of GalNAc valency, oligonucleotide length, flexibility and chemical composition on ASGR binding, we tested and validated a fluorescence polarization competition binding assay. The ASGR binding, and in vitro and in vivo activities of 1, 2 and 3 GalNAc conjugated single stranded and duplexed ASOs were studied. Two and three GalNAc conjugated single stranded ASOs bind the ASGR with the strongest affinity and display optimal in vitro and in vivo activities. 1 GalNAc conjugated ASOs showed 10-fold reduced ASGR binding affinity relative to three GalNAc ASOs but only 2-fold reduced activity in mice. An unexpected observation was that the ASGR also appears to play a role in the uptake of unconjugated phosphorothioate modified ASOs in the liver as evidenced by the loss of activity of GalNAc conjugated and unconjugated ASOs in ASGR knockout mice. Our results provide insights into how backbone charge and chemical composition assist in the binding and internalization of highly polar anionic single stranded oligonucleotides into cells and tissues.
The Glutathione Transferase Structural Family Includes a Nuclear Chloride Channel and a Ryanodine Receptor Calcium Release Channel Modulator (2001)

The ubiquitous glutathione transferases (GSTs) catalyze glutathione conjugation to many compounds and have other diverse functions that continue to be discovered. We noticed sequence similarities between Omega class GSTs and a nuclear chloride channel, NCC27 (CLIC1), and show here that NCC27 belongs to the GST structural family. The structural homology prompted us to investigate whether the human Omega class glutathione transferase GSTO1-1 forms or modulates ion channels. We find that GSTO1-1 modulates ryanodine receptors (RyR), which are calcium channels in the endoplasmic reticulum of various cells. Cardiac RyR2 activity was inhibited by GSTO1-1, whereas skeletal muscle RyR1 activity was potentiated. An enzymatically active conformation of GSTO1-1 was required for inhibition of RyR2, and mutation of the active site cysteine (Cys-32 --> Ala) abolished the inhibitory activity. We propose a novel role for GSTO1-1 in protecting cells containing RyR2 from apoptosis induced by Ca(2+) mobilization from intracellular stores.
Synthesis and Characterization of Poly(glycerol−succinic acid) Dendrimers (2001)

The syntheses of novel dendrimers composed of glycerol and succinic acid are described. These “biodendrimers” are composed entirely of building blocks known to be biocompatible or degradable in vivo to natural metabolites and are prepared using a high yield divergent approach. Moreover, the synthetic strategy employed is amenable to the design and development of new materials as demonstrated by the attachment of a photopolymerizable group.
Guanine nucleotide exchange factors for Rho GTPases: turning on the switch (2002)

Rho GTPases control many aspects of cell behavior through the regulation of multiple signal transduction pathways (Van Aelst and D’Souza-Schorey 1997; Hall 1998). Rho, Rac, and Cdc42 were first recognized in the early 1990s for their unique ability to induce specific filamentous actin structures in fibroblasts; stress fibers, lamellipodia/membrane ruffles, and filopodia, respectively (Hall 1998). Over the intervening years, evidence has accumulated to show that in all eukaryotic cells, Rho GTPases are involved in most, if not all, actin-dependent processes such as those involved in migration, adhesion, morphogenesis, axon guidance, and phagocytosis (Kaibuchi et al. 1999; Chimini and Chavrier 2000; Luo 2000). In addition to their well-established roles in controlling the actin cytoskeleton, Rho GTPases regulate the microtubule cytoskeleton, cell polarity, gene expression, cell cycle progression, and membrane transport pathways (Van Aelst and D’Souza-Schorey 1997; Daub et al. 2001; Etienne-Manneville and Hall 2001). With such a prominent role in so many aspects of cell biology, it is not surprising that they are themselves highly regulated. Like all GTPases, Rho proteins act as binary switches by cycling between an inactive (GDP-bound) and an active (GTP-bound) conformational state (Fig. 1; Van Aelst and D’Souza-Schorey 1997). The cell controls this switch by regulating the interconversion and accessibility of these two forms in a variety of ways. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP to generate the activated form, which is then capable of recognizing downstream targets, or effector proteins. GTPase activating proteins (GAPs) accelerate the intrinsic GTPase activity of Rho family members to inactivate the switch. Finally, guanine nucleotide dissociation inhibitors (GDIs) interact with the prenylated, GDP-bound form to control cycling between membranes and cytosol. In theory, activation of a Rho GTPase could occur through stimulation of a GEF or inhibition of a GAP. In practice, however, all the evidence points to GEFs being the critical mediators of Rho GTPase activation, and this paper reviews our present understanding of how they do this. Structural features
Synthesis and Electroluminescence Properties of 3-(Trifluoromethyl)phenyl-Substituted 9,10-Diarylanthracene Derivatives for Blue Organic Light-Emitting Diodes (2017)

Diaryl-substituted anthracene derivatives containing 3-(trifluoromethyl)phenyl) groups, 9,10-diphenyl-2-(3-(trifluoromethyl)phenyl)anthracene (1), 9,10-di([1,1′-biphenyl]-4-yl)-2-(3-(trifluoromethyl)phenyl)anthracene (2), and 9,10-di(naphthalen-2-yl)-2-(3-(trifluoromethyl)phenyl)anthracene (3) were synthesized and characterized. The compounds 1–3 possessed high thermal stability and proper frontier-energy levels, which make them suitable as host materials for blue organic light-emitting diodes. The electroluminescent (EL) emission maximum of the three N,N-diphenylamino phenyl vinyl biphenyl (DPAVBi)-doped (8 wt %) devices for compounds 1–3 was exhibited at 488 nm (for 1) and 512 nm (for 2 and 3). Among them, the 1-based device displayed the highest device performances in terms of brightness (Lmax = 2153.5 cd·m−2), current efficiency (2.1 cd·A−1), and external quantum efficiency (0.8%), compared to the 2- and 3-based devices.
Cantilever-based bio-chemical sensor integrated in a microliquid handling system (2002)

The cantilevers have integrated piezoresistive readout which, compared to optical readout, enables simple measurements on even non-transparent liquids, such as blood. First, we introduce a simple theory for using piezoresistive cantilevers as surface stress sensors. Then, the sensor fabrication based on conventional microfabrication is described and the sensor characterization is discussed. During the characterization we found a stress sensitivity of (/spl Delta/R/R)=4.6:10/sup -4/ (N/m)/sup -1/ and a minimum detectable surface stress change of 2.6 mN/m. Aqua regia etch of gold on top of the cantilevers has been monitored, and immobilization of single-stranded thiol modified DNA-oligos has been detected by the sensor. Finally, it is demonstrated that it is possible to analyze two samples simultaneously by utilizing the laminar flow in the microliquid handling system.
Mutational Analysis of Bovine Viral Diarrhea Virus RNA-Dependent RNA Polymerase (1999)

Recombinant bovine viral diarrhea virus (BVDV) nonstructural protein 5B (NS5B) produced in insect cells has been shown to possess an RNA-dependent RNA polymerase (RdRp) activity. Our initial attempt to produce the full-length BVDV NS5B with a C-terminal hexahistidine tag in Escherichia coli failed due to the expression of insoluble products. Prompted by a recent report that removal of the C-terminal hydrophobic domain significantly improved the solubility of hepatitis C virus (HCV) NS5B, we constructed a similar deletion of 24 amino acids at the C terminus of BVDV NS5B. The resulting fusion protein, NS5BDeltaCT24-His, was purified to homogeneity and demonstrated to direct RNA replication via both primer-dependent (elongative) and primer-independent (de novo) mechanisms. Furthermore, BVDV RdRp was found to utilize a circular single-stranded DNA as a template for RNA synthesis, suggesting that synthesis does not require ends in the template. In addition to the previously described polymerase motifs A, B, C, and D, alignments with other flavivirus sequences revealed two additional motifs, one N-terminal to motif A and one C-terminal to motif D. Extensive alanine substitutions showed that while most mutations had similar effects on both elongative and de novo RNA syntheses, some had selective effects. Finally, deletions of up to 90 amino acids from the N terminus did not significantly affect RdRp activities, whereas deletions of more than 24 amino acids at the C terminus resulted in either insoluble products or soluble proteins (DeltaCT179 and DeltaCT218) that lacked RdRp activities.
Linear Rheological Response of a Series of Densely Branched Brush Polymers (2011)

We have examined the linear rheological responses of a series of well-defined, dense, regularly branched brush polymers. These narrow molecular weight distribution brush polymers had polynorobornene backbones with degrees of polymerization (DP) of 200, 400, and 800 and polylactide side chains with molecular weight of 1.4 kDa, 4.4 kDa, and 8.7 kDa. The master curves for these brush polymers were obtained by time temperature superposition (TTS) of the dynamic moduli over the range from the glassy region to the terminal flow region. Similar to other long chain branched polymers, these densely branched brush polymers show a sequence of relaxation. Subsequent to the glassy relaxation, two different relaxation processes can be observed for samples with the high molecular weight (4.4 and 8.7 kDa) side chains, corresponding to the relaxation of the side chains and the brush polymer backbone. Influenced by the large volume fraction of high molecular weight side chains, these brush polymers are unentangled. The lowest plateau observed in the dynamic response is not the rubbery entanglement plateau but is instead associated with the steady state recoverable compliance. Side chain properties affect the rheological responses of these densely branched brush polymers and determine their glassy behaviors.
Cooperative scheduling of multiple resources (2003)

Obtaining simultaneous and timely access to multiple resources is known to be an NP-complete problem. Complete resource decoupling is, therefore, often used for managing end-to-end delays in distributed real-time system where each processor is scheduled independent of the others. This decoupling approach unfortunately fails when multiple resources must be managed within a single node. Resources such as disk bandwidth and network bandwidth are available on a single node but must be managed by their host processor by means of device drivers, filesystem or protocol services. The host processor acting as a controlling resource, therefore, must play multiple roles. One, it is used by applications on that node. Two, it is used to control and manage other (time-shared) controlled resources including disk bandwidth and network bandwidth. These two roles, unfortunately can often be at odds with one another. In this paper we investigate the problem of co-scheduling controlling and controlled resources. We propose the use of a Cooperative Scheduling Server (CS S), which is a dedicated server that manages one specific controlled resource (like disk bandwidth, network bandwidth, inter-process communication, etc.) while using a controlling resource (like the processor). Two core ideas underlie our approach. First, a single (aperiodic) server is created on a controlling resource (such as a CPU) to handle all local requests for a controlled resource (such as disk bandwidth). This implies that conjuctive admission control must be carried out on both the controlling and controlled resources. Secondly, timing constraints at the application level are partitioned into multiple stages, each of which will be guaranteed to complete on a particular resource. RTFS is a real-time filesystem that provides disk bandwidth guarantees under light CPU loads. With a cooperative scheduling server (FS-CSS) for this disk-based filesystem, disk bandwidth guarantees can be obtained under both heavy CPU and disk workloads. We describe the design and implementation of FS-CSS for providing disk bandwidth guarantees. We conclude with a detailed performance evaluation of FS-CSS.
IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection (2008)

Suppression of T-cell responses by host-derived regulatory factors is a key event leading to viral persistence. Antibody blockade of either IL-10 or programmed death-ligand 1 (PD-L1) during viral persistence enhances T-cell function and reduces viral titers. Because blockade of these immunoregulatory networks represents a powerful approach to establish immune control during persistent infection, it is important to determine whether these immunoinhibitory factors act independently or jointly and if combined blockade of these factors further enhances T-cell immunity and viral clearance. Herein, we demonstrate that the IL-10 and PD-L1 immunosuppressive pathways are mechanistically distinct. As a result, simultaneous blockade of IL-10 and PD-L1 was significantly more effective in restoring antiviral T-cell responses than blockade of either alone, and led to substantially enhanced control of an established persistent viral infection. Thus, combinatorial blockade of multiple immune-regulatory molecules may ultimately restore the T-cell responses required to tip the balance from viral persistence to immune-mediated control or elimination of persistent infection.
Deregulated Signaling Pathways in Glioblastoma Multiforme: Molecular Mechanisms and Therapeutic Targets (2012)

Glioblastoma multiforme (GBM) is the most malignant and aggressive type of brain tumor with an average life expectancy of less than 15 months. This is mostly due to the highly mutated genome of GBM, which is characterized by the deregulation of many key signaling pathways involving growth, proliferation, survival, and apoptosis. It is critical to explore novel diagnostic and therapeutic strategies that target these pathways to improve the treatment of malignant glioma in the future. This review summarizes the most common and important pathways that are highly mutated or deregulated in GBM and discusses potential therapeutic strategies targeting these pathways.