gebhart/patrepeval huggingface dataset:
Alpha-1-antitrypsin-Pittsburgh. A potent inhibitor of human plasma factor XIa, kallikrein, and factor XIIf. (1986)

Alpha-1-antitrypsin-Pittsburgh is a human variant that resulted from a point mutation in the plasma protease inhibitor, alpha 1-antitrypsin (358 Met----Arg). This defect in the alpha 1-antitrypsin molecule causes it to have greatly diminished anti-elastase activity but markedly increased antithrombin activity. In this report, we demonstrate that this variant protein also has greatly increased inhibitory activity towards the arginine-specific enzymes of the contact system of plasma proteolysis (Factor XIa, kallikrein, and Factor XIIf), in contrast to normal alpha 1-antitrypsin, which has modest to no inhibitory activity towards these enzymes. We determined the second-order-inactivation rate constant (k'') of purified, human Factor XIa by purified alpha 1-antitrypsin-Pittsburgh and found it to be 5.1 X 10(5) M-1 s-1 (23 degrees C), which is a 7,700-fold increase over the k'' for Factor XIa by its major inhibitor, normal purified alpha 1-antitrypsin (i.e., 6.6 X 10(1) M-1 s-1). Human plasma kallikrein, which is poorly inhibited by alpha 1-antitrypsin (k'' = 4.2 M-1 s-1), exhibited a k'' for alpha 1-antitrypsin-Pittsburgh of 8.9 X 10(4) M-1 s-1 (a 21,000-fold increase), making it a more efficient inhibitor than either of the naturally occurring major inhibitors of kallikrein (C-1-inhibitor and alpha 2-macroglobulin). Factor XIIf, which is not inhibited by normal alpha 1-antitrypsin, displayed a k'' for alpha 1-antitrypsin-Pittsburgh of 2.5 X 10(4) M-1 s-1. This enhanced inhibitory activity is similar to the effect of alpha 1-antitrypsin-Pittsburgh that has been reported for thrombin. In addition to its potential as an anticoagulant, this recently cloned protein may prove to be clinically valuable in the management of septic shock, hereditary angioedema, or other syndromes involving activation of the surface-mediated plasma proteolytic system.
Rapid classification of partial waxy wheats using PCR-based markers (2002)

Mutations in the three homeologous waxy loci Wx-A1, Wx-B1, and Wx-D1 of a waxy wheat line have previously been characterized at the molecular level. Using combinations of these mutations, six types of partial waxy wheat plus wild type and waxy wheat (types 1-8) can be produced. Here, we describe primer sets for all three loci that can be used under a single set of conditions, allowing 32 lines to be characterized as types 1-8 in a single PCR run using a 96-well plate. Using multiplex PCR, mutations at the Wx-B1 and Wx-D1 loci can be identified in a single PCR, reducing the number of reactions necessary to identify and select the desired partial waxy wheat line. A single multiplex PCR can be used to detect all three mutations when products are analyzed using capillary electrophoresis on a microchip device. The PCR conditions and primers are effective with a number of cultivars from other countries, indicating that the mutations found at the Wx-A1 and Wx-B1 loci of these cultivars likely have the same origins as the mutations in the corresponding loci of the waxy wheat line used in this study. The PCR selection method described here is an easy and effective alternative to the commonly used SDS-PAGE methods for identification of null alleles.
Comparison of backbone structures of glucose isomerase from Streptomyces and Arthrobacter (1987)

The C alpha backbones of the glucose isomerase molecules of Streptomyces rubiginosus and Arthrobacter have been determined by X-ray crystallography and compared. Each molecule is a tetramer of eight-stranded alpha/beta barrels, and the mode of association of the tetramers is identical in each case. The Arthrobacter electron density shows four additional amino acids at the carboxyl terminus. There is also an insertion of six amino acids at position 277, and two individual insertions at about positions 348 and 357 (numbering according to the Streptomyces structure). There is a close structural homology throughout the whole molecule, which is most accurate up to position 325. The r.m.s. displacement for 315 homologous C alpha positions up to this position is 0.92 A.
Performance of IEEE 802.11b wireless LAN in an emulated mobile channel (2004)

The performance of 802.11b wireless LANs is well understood for indoor environments. However, their behavior in outdoor and mobile environments has remained largely unexplored. We have performed experiments to bridge this knowledge gap by empirically measuring the performance of an 802.11b system in a broad spectrum of emulated environments. The goal of our work is to contribute to the evolution of currently existing wireless standards by measuring the effects of different channel phenomena on 802.11b. Our results show that current implementations of the 802.11b standard may not be well suited to use in a mobile environment, but that they could conceivably be modified to have better performance in such situations.
A Facile Approach to Synthesis of the Di‐O‐methyl Ethers of (−)‐Agatharesinol, (−)‐Sugiresinol, (+)‐Nyasol and (+)‐Tetrahydronyasol (2007)

Abstract The facile enantioselective synthesis of the di‐ O ‐methyl ethers of (−)‐agatharesinol ( 1b ), (−)‐sugiresionl ( 2b ), (+)‐nyasol ( 3b ) and (+)‐tetrahydronyasol ( 4 ) were achieved in high yield. The absolute configuration of (+)‐ 3a was confirmed via first total synthesis of (+)‐ 3b and (+)‐ 4 .
Indium oxides by reactive ion beam assisted evaporation: From material study to device application (2009)

Indium oxides were deposited by reactive ion beam assisted e-beam evaporation at room temperature. A material study was conducted through a variety of material characterization including crystal structure, electrical properties, optical properties, and chemical composition, along with an investigation of material properties as a function of primary deposition parameters such as ion flux and deposition rate. Implementing the developed semiconducting indium oxide as a channel material, the authors further demonstrated high-performance indium oxide thin-film transistors (TFTs) with conventional silicon dioxide gate dielectric derived by plasma-enhanced chemical vapor deposition (PECVD). The n-channel TFT has a threshold voltage of ∼2.0 V, a field-effect mobility of 33 cm2/V s at a gate bias of 20 V, an ON/OFF current ratio of 108, and a subthreshold slope of 2.0 V/decade. The stability study displays a small threshold voltage shift of ∼0.6 V under a 60 h constant current stress condition. The TFT reported here has one of the best performance characteristics in terms of field-effect mobility, ON/OFF current ratio, OFF current and device stability, using conventional and large-area foundry-compatible PECVD gate dielectrics. The device performance coupled with PECVD dielectrics makes ion beam assisted e-beam evaporation derived indium oxide TFT a promising candidate for active matrix flat-panel displays.
Substrate replenishment and byproduct removal improve yeast cell-free protein synthesis (2013)

Cell-free protein synthesis (CFPS) platforms are now considered a powerful tool for synthesizing a variety of proteins at scales from pL to 100 L with accelerated process development pipelines. We previously reported the advancement of a novel yeast-based CFPS platform. Here, we studied factors that cause termination of yeast CFPS batch reactions. Specifically, we characterized the substrate and byproduct concentrations in batch, fed-batch, and semi-continuous reaction formats through high-performance liquid chromatography (HPLC) and chemical assays. We discovered that creatine phosphate, the secondary energy substrate, and nucleoside triphosphates were rapidly degraded during batch CFPS, causing a significant drop in the reaction's energy charge (E.C.) and eventual termination of protein synthesis. As a consequence of consuming creatine phosphate, inorganic phosphate accumulated as a toxic byproduct. Additionally, we measured amino acid concentrations and found that aspartic acid was rapidly consumed. By adopting a semi-continuous reaction format, where passive diffusion enables substrate replenishment and byproduct removal, we achieved over a 70% increase in active superfolder green fluorescent protein (sfGFP) as compared with the batch system. This study identifies targets for the future improvement of the batch yeast CFPS reaction. Moreover, it outlines a detailed, generalized method to characterize and improve other CFPS platforms.
Expanded molecular diversity generation during directed evolution by trinucleotide exchange (TriNEx) (2008)

Trinucleotide exchange (TriNEx) is a method for generating novel molecular diversity during directed evolution by random substitution of one contiguous trinucleotide sequence for another. Single trinucleotide sequences were deleted at random positions in a target gene using the engineered transposon MuDel that were subsequently replaced with a randomized trinucleotide sequence donated by the DNA cassette termed SubSeq(NNN). The bla gene encoding TEM-1 beta-lactamase was used as a model to demonstrate the effectiveness of TriNEx. Sequence analysis revealed that the mutations were distributed throughout bla, with variants containing single, double and triple nucleotide changes. Many of the resulting amino acid substitutions had significant effects on the in vivo activity of TEM-1, including up to a 64-fold increased activity toward ceftazidime and up to an 8-fold increased resistance to the inhibitor clavulanate. Many of the observed amino acid substitutions were only accessible by exchanging at least two nucleotides per codon, including charge-switch (R164D) and aromatic substitution (W165Y) mutations. TriNEx can therefore generate a diverse range of protein variants with altered properties by combining the power of site-directed saturation mutagenesis with the capacity of whole-gene mutagenesis to randomly introduce mutations throughout a gene.
Cross-dimensional gestural interaction techniques for hybrid immersive environments (2005)

We present a set of cross-dimensional interaction techniques for a hybrid user interface that integrates existing 2D and 3D visualization and interaction devices. Our approach is built around one-and two-handed gestures that support the seamless transition of data between co-located 2D and 3D contexts. Our testbed environment combines a 2D multi-user, multi-touch, projection surface with 3D head-tracked, see-through, head-worn displays and 3D tracked gloves to form a multi-display augmented reality. We address some of the ways in which we can interact with private data in a collaborative, heterogeneous workspace. We also report on a pilot usability study to evaluate the effectiveness and ease of use of the cross-dimensional interactions.
XFCB: a high speed complementary bipolar process on bonded SOI (2003)

A fabrication process was developed to obtain full, dielectrically isolated complementary bipolar transistors. Direct-wafer-bonding silicon-on-insulator and deep-trench-isolation technologies were used. Polysilicon was used as the emitter for both NPN and PNP transistors. A single layer of polysilicon was used to fabricate both transistor types. The process is characterized by a 12 V breakdown and yields transistors with a cutoff frequency of 4.5 GHz and 2.5 GHz for the NPN and PNP devices, respectively.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T‐cell co‐stimulation by DC (2008)

A major question in immunology is how DC can display limited amounts of individual peptide-MHC complexes and still induce cross-linking of T-cell receptors to initiate cellular responses. One suggested mechanism is that MHC exists at the cell surface in high avidity multimers, and tetraspanin proteins, known to laterally associate with both MHC classes I and II, promote MHC multimerisation. To validate this theory, we tested the ability of DC deficient in either one of two typical tetraspanin molecules: CD37 or CD151 to present peptide to Ag-specific T cells. Surprisingly, although they exhibited no developmental or maturation defects, DC lacking either CD37 or CD151 expression were hyper-stimulatory to T cells. We demonstrate that CD37 and CD151 control DC-mediated T-cell activation by two different mechanisms: CD151 regulates co-stimulation whereas CD37 regulates peptide/MHC presentation. The implications of these results on the model suggesting that tetraspanins promote MHC multimerisation are discussed.
Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol. (1994)

Clearance of excess cholesterol from cells by HDL is facilitated by the interaction of HDL apolipoproteins with cell-surface binding sites or receptors, a process that may be important in preventing atherosclerosis. In this study, synthetic peptides containing 18-mer amphipathic helices of the class found in HDL apolipoproteins (class A) were tested for their abilities to remove cholesterol and phospholipid from cultured sterol-laden fibroblasts and macrophages and to interact with cell-surface HDL binding sites. Lipid-free peptides containing two identical tandem repeats of class A amphipathic helices promoted cholesterol and phospholipid efflux from cells and depleted cellular cholesterol accessible for esterification by acyl CoA/cholesterol acyltransferase, similar to what was observed for purified apolipoprotein A-I. Peptide-mediated removal of plasma membrane cholesterol and depletion of acyl CoA/cholesterol acyltransferase-accessible cholesterol appeared to occur by separate mechanisms, as the latter process was less dependent on extracellular phospholipid. The dimeric amphipathic helical peptides also competed for high-affinity HDL binding sites on cholesterol-loaded fibroblasts and displayed saturable high-affinity binding to the cell surface. In contrast, peptides with a single helix had little or no ability to remove cellular cholesterol and phospholipid, or to interact with HDL binding sites, suggesting that cooperativity between two or more helical repeats is required for these activities. Thus, synthetic peptides comprising dimers of a structural motif common to exchangeable apolipoproteins can mimic apolipoprotein A-I in both binding to putative cell-surface receptors and clearing cholesterol from cells.
Development of biologically active peptides based on antibody structure. (1989)

Antibody molecules are composed of several functional domains, including a variable domain that contacts antigen and a constant domain. The hypervariable regions of antibody molecules play an integral role in determining their specificity. However, the delineation of specific residues most critical in binding is difficult. We have been studying a monoclonal antibody (87.92.6) that binds to the reovirus type 3 receptor on a number of cell types, down-modulates the receptor, and inhibits DNA synthesis in the cells. We have shown that a peptide derived from the second complementarity-determining region of the monoclonal antibody 87.92.6 light-chain variable region can reproduce both of these effects. We were also able to demonstrate specific amino acid residues and structural features involved in producing these effects. The study of antibody structure, coupled with molecular synthetic techniques, can lead to the development of biologically active substances with potential clinical use.
μ-Opioid Receptor Activates Signaling Pathways Implicated in Cell Survival and Translational Control (1998)

The mu-opioid receptor mediates the analgesic and addictive properties of morphine. Despite the clinical importance of this G-protein-coupled receptor and many years of pharmacological research, few intracellular signaling mechanisms triggered by morphine and other mu-opioid agonists have been described. We report that mu-opioid agonists stimulate three different effectors of a phosphoinositide 3-kinase (PI3K)-dependent signaling cascade. By using a cell line stably transfected with the mu-opioid receptor cDNA, we show that the specific agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) stimulates the activity of Akt, a serine/threonine protein kinase implicated in protecting neurons from apoptosis. Activation of Akt by DAMGO correlates with its phosphorylation at serine 473. The selective PI3K inhibitors wortmannin and LY294002 blocked phosphorylation of this site, previously shown to be necessary for Akt enzymatic activity. DAMGO also stimulates the phosphorylation of two other downstream effectors of PI3K, the p70 S6 kinase and the repressors of mRNA translation, 4E-BP1 and 4E-BP2. Upon mu-opioid receptor stimulation, p70 S6 kinase is activated and phosphorylated at threonine 389 and at threonine 421/serine 424. Phosphorylation of p70 S6 kinase and 4E-BP1 is also repressed by PI3K inhibitors as well as by rapamycin, the selective inhibitor of FRAP/mTOR. Consistent with these findings, DAMGO-stimulated phosphorylation of 4E-BP1 impairs its ability to bind the translation initiation factor eIF-4E. These results demonstrate that the mu-opioid receptor activates signaling pathways associated with neuronal survival and translational control, two processes implicated in neuronal development and synaptic plasticity.
DNA intercalation and cleavage of an antitumor antibiotic dynemicin that contains anthracycline and enediyne cores. (1990)

Dynemicin is a hybrid containing anthraquinone and enediyne cores, which contribute to binding and cleavage of DNA, respectively. DNA strand scission by the antitumor antibiotic is significantly enhanced by the addition of NADPH or thiol compounds. The preferential cutting site of dynemicin is on the 3' side of purine bases (i.e., 5'-GC, -GT, and -AG) and is clearly different from the cutting sites of esperamicin and calicheamicin. The double-stranded and the stem regions of single-stranded DNAs are preferentially cleaved by dynemicin. Therefore, dynemicin may be a useful reagent for probing secondary structures of DNA. Pretreatment of DNA with Adriamycin and actinomycin D alters the cutting mode of dynemicin. Dynemicin-mediated DNA breakage is strongly inhibited by pretreatment of the DNA with distamycin A and anthramycin, suggesting that dynemicin interacts with the minor groove of the DNA helix. Intercalation of the anthraquinone core into the DNA followed by the attack of the phenyl diradical formed from the enediyne core is considered as a possible mechanism of action of dynemicin.
Phosphodiesterase Inhibitors for Cognitive Enhancement (2005)

An effective treatment for age-related cognitive deficits remains an unmet medical need. Currently available drugs for the symptomatic treatment of Alzheimer's disease or other dementias have limited efficacy. This may be due to their action at only one of the many neurotransmitter systems involved in the complex mechanisms that underlie cognition. An alternative approach would be to target second messenger systems that are utilized by multiple neurotransmitters. Cyclic adenosine monophosphate (cAMP) is a second messenger that plays a key role in biochemical processes that regulate the cognitive process of memory consolidation. Prolongation of cAMP signals can be accomplished by inhibiting phosphodiesterases (PDEs). Eleven PDE families, comprised of more than 50 distinct members, are currently known. This review summarizes the evidence demonstrating that rolipram, a selective inhibitor of cAMP-selective PDE4 enzymes, has positive effects on learning and memory in animal models. These data provide support for the general approach of second messenger modulation as a potential therapy for cognitive dysfunction, and specifically suggest that PDE4 inhibitors may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases.
Effect of Aerosolized Recombinant Human DNase on Exacerbations of Respiratory Symptoms and on Pulmonary Function in Patients with Cystic Fibrosis (1994)

In patients with cystic fibrosis, the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms, resulted in slight improvement in pulmonary function, and was well tolerated.
The choice and outcome of the fertility treatment of 38 couples in whom the male partner has a Yq microdeletion (2005)

Despite the improvement of assisted reproductive technology, ICSI could be offered only to patients with an AZFc deletion. Insemination with donor sperm is a potential alternative for other patients.
Therapeutic antibodies against CGRP or its receptor (2015)

CGRP is an extensively studied neuropeptide that has been implicated in the pathophysiology of migraine. While a number of small molecule antagonists against the CGRP receptor have demonstrated that targeting this pathway is a valid and effective way of treating migraine, off-target hepatoxicity and formulation issues have hampered the development for regulatory approval of any therapeutic in this class. The development of monoclonal antibodies to CGRP or its receptor as therapeutic agents has allowed this pathway to be re-investigated. Herein we review why CGRP is an ideal target for the prevention of migraine and describe four monoclonal antibodies against either CGRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine. We describe what has been publically disclosed about their clinical trials and future clinical development plans.
A 1.2 Gb/s recursive polyphase cascaded integrator-comb prefilter for high speed digital decimation filters in 0.18-&#x03BC;m CMOS (2010)

Recursive polyphase cascaded integrator-comb (CIC) prefilters are proposed to greatly increase the speed of digital decimation so as to address demands of high speed sigma-delta ADCs that over-sample at several GHz. The recursive computations in the new method avoid the substantial area/complexity increases in traditional polyphase decomposition implementations. Clock rate improvements by factors of 2 or 4 can be achieved, in comparison to those of traditional CIC filters. Implemented in a 0.18-μm CMOS process, a decimate-by-16 prefilter achieves a 1.2 Gb/s clock rate in the slow corner after post-route extraction, while occupying 0.08 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> area.
Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy (2020)

The programmed cell death 1 (PD-1) receptor on the surface of immune cells is an immune checkpoint molecule that mediates the immune escape of tumor cells. Consequently, antibodies targeting PD-1 have shown efficacy in enhancing the antitumor activity of T cells in some types of cancers. However, the potential effects of PD-1 on tumor cells remain largely unknown. Here, we show that PD-1 is expressed across a broad range of tumor cells. The silencing of PD-1 or its ligand, PD-1 ligand 1 (PD-L1), promotes cell proliferation and colony formation in vitro and tumor growth in vivo. Conversely, overexpression of PD-1 or PD-L1 inhibits tumor cell proliferation and colony formation. Moreover, blocking antibodies targeting PD-1 or PD-L1 promote tumor growth in cell cultures and xenografts. Mechanistically, the coordination of PD-1 and PD-L1 activates its major downstream signaling pathways including the AKT and ERK1/2 pathways, thus enhancing tumor cell growth. This study demonstrates that PD-1/PD-L1 is a potential tumor suppressor and potentially regulates the response to anti-PD-1/PD-L1 treatments, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.