gebhart/patrepeval huggingface dataset:
A Novel α-Conotoxin, PeIA, Cloned from Conus pergrandis, Discriminates between Rat α9α10 and α7 Nicotinic Cholinergic Receptors (2005)

The alpha9 and alpha10 nicotinic cholinergic subunits assemble to form the receptor believed to mediate synaptic transmission between efferent olivocochlear fibers and hair cells of the cochlea, one of the few examples of postsynaptic function for a non-muscle nicotinic acetylcholine receptor (nAChR). However, it has been suggested that the expression profile of alpha9 and alpha10 overlaps with that of alpha7 in the cochlea and in sites such as dorsal root ganglion neurons, peripheral blood lymphocytes, developing thymocytes, and skin. We now report the cloning, total synthesis, and characterization of a novel toxin alpha-conotoxin PeIA that discriminates between alpha9alpha10 and alpha7 nAChRs. This is the first toxin to be identified from Conus pergrandis, a species found in deep waters of the Western Pacific. Alpha-conotoxin PeIA displayed a 260-fold higher selectivity for alpha-bungarotoxin-sensitive alpha9alpha10 nAChRs compared with alpha-bungarotoxin-sensitive alpha7 receptors. The IC50 of the toxin was 6.9 +/- 0.5 nM and 4.4 +/- 0.5 nM for recombinant alpha9alpha10 and wild-type hair cell nAChRs, respectively. Alpha-conotoxin PeIA bears high resemblance to alpha-conotoxins MII and GIC isolated from Conus magus and Conus geographus, respectively. However, neither alpha-conotoxin MII nor alpha-conotoxin GIC at concentrations of 10 microM blocked acetylcholine responses elicited in Xenopus oocytes injected with the alpha9 and alpha10 subunits. Among neuronal non-alpha-bungarotoxin-sensitive receptors, alpha-conotoxin PeIA was also active at alpha3beta2 receptors and chimeric alpha6/alpha3beta2beta3 receptors. Alpha-conotoxin PeIA represents a novel probe to differentiate responses mediated either through alpha9alpha10 or alpha7 nAChRs in those tissues where both receptors are expressed.
Characterization of a candidate bcl-1 gene. (1991)

The t(11;14)(q13;q32) translocation has been associated with human B-lymphocytic malignancy. Several examples of this translocation have been cloned, documenting that this abnormality joins the immunoglobulin heavy-chain gene to the bcl-1 locus on chromosome 11. However, the identification of the bcl-1 gene, a putative dominant oncogene, has been elusive. In this work, we have isolated genomic clones covering 120 kb of the bcl-1 locus. Probes from the region of an HpaII-tiny-fragment island identified a candidate bcl-1 gene. cDNAs representing the bcl-1 mRNA were cloned from three cell lines, two with the translocation. The deduced amino acid sequence from these clones showed bcl-1 to be a member of the cyclin gene family. In addition, our analysis of expression of bcl-1 in an extensive panel of human cell lines showed it to be widely expressed except in lymphoid or myeloid lineages. This observation may provide a molecular basis for distinct modes of cell cycle control in different mammalian tissues. Activation of the bcl-1 gene may be oncogenic by directly altering progression through the cell cycle.
Rational design of a new class of protease inhibitors for the potential treatment of coronavirus diseases (2020)

ABSTRACT The coronavirus main protease, M pro , is a key protein in the virus life cycle and a major drug target. Based on crystal structures of SARSCoV2 M pro complexed with peptidomimetic inhibitors, we recognized a binding characteristic shared with proline-containing inhibitors of hepatitis C virus protease. Initial tests showed that this subclass of HCV protease inhibitors indeed exhibited activity against M pro . Postulating a benefit for a preorganized backbone conformation, we designed new ketoamide-based M pro inhibitors based on central proline rings. One of the designed compounds, ML1000, inhibits M pro with low-nanomolar affinity and suppresses SARSCoV2 viral replication in human cells at sub-micromolar concentrations. Our findings identify ML1000 as a promising new pre-organized scaffold for the development of anti-coronavirus drugs.
Relationship between urinary sodium excretion and pioglitazone‐induced edema (2010)

To investigate the factors contributing to pioglitazone-induced edema, we analyzed sodium excretion and several clinical parameters before and after administration of pioglitazone. We analyzed these parameters before and after 8 weeks of administration of pioglitazone to female subjects with type 2 diabetes. When we evaluated whether a significant correlation was found between salt excretion and blood pressure, six patients showed such correlation and 20 patients did not. After 8 weeks of pioglitazone administration, five patients had developed edema, and, surprisingly, such correlation was not found in all five subjects. Salt excretion after administration of pioglitazone was significantly lower in subjects who developed edema and those who showed the correlation, and the hematocrit was significantly lower after administration in the subjects who showed the correlation, but not in the edema group. Pioglitazone-induced edema would be caused not only by fluid retention, but also by other factors, such as vascular permeability. (J Diabetes Invest, doi: 10.1111/ j.2040-1124.2010.00046.x, 2010).
Consensus Problems in Networks of Agents With Switching Topology and Time-Delays (2004)

In this paper, we discuss consensus problems for networks of dynamic agents with fixed and switching topologies. We analyze three cases: 1) directed networks with fixed topology; 2) directed networks with switching topology; and 3) undirected networks with communication time-delays and fixed topology. We introduce two consensus protocols for networks with and without time-delays and provide a convergence analysis in all three cases. We establish a direct connection between the algebraic connectivity (or Fiedler eigenvalue) of the network and the performance (or negotiation speed) of a linear consensus protocol. This required the generalization of the notion of algebraic connectivity of undirected graphs to digraphs. It turns out that balanced digraphs play a key role in addressing average-consensus problems. We introduce disagreement functions for convergence analysis of consensus protocols. A disagreement function is a Lyapunov function for the disagreement network dynamics. We proposed a simple disagreement function that is a common Lyapunov function for the disagreement dynamics of a directed network with switching topology. A distinctive feature of this work is to address consensus problems for networks with directed information flow. We provide analytical tools that rely on algebraic graph theory, matrix theory, and control theory. Simulations are provided that demonstrate the effectiveness of our theoretical results.
WAMDII: wide-angle Michelson Doppler imaging interferometer for Spacelab (1985)

A wide-angle Michelson Doppler imaging interferometer (WAMDII) is described that is intended to measure upper atmospheric winds and temperatures from naturally occurring visible region emissions, using Spacelab as a platform. It is an achromatic field-widened instrument, with good thermal stability, that employs four quarterwave phase-stepped images to generate full images of velocity, temperature, and emission rate. For an apparent emission rate of 5 kR and binning into 85 × 105 pixels, the required exposure time is 1 sec. The concept and underlying principles are described, along with some fabrication details for the prototype instrument. The results of laboratory tests and field measurements using auroral emissions are described and discussed.
Quantitative carbamylation as a stable isotopic labeling method for comparative proteomics (2007)

A method was developed that uses urea to both solublize and isotopically label biological samples for comparative proteomics. This approach uses either light or heavy urea ((12)CH(4)(14)N(2)O or (13)CH(4)(15)N(2)O, respectively) at a concentration of 8 M and a pH of 7 to dissolve the samples prior to digestion. After the sample is digested using standard proteomic protocols and dried, isotopic labeling is completed by resuspending the sample in a solution of 8 M urea at a pH of 8.5, using the same isotopic species of urea as used for digestion and incubating for 4 h at 80 degrees C. Under these conditions, carbamylation occurs only on the primary amines of the peptides. The effects of complete carbamylation on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) (collision-induced dissociation (CID)) were examined. Peptides that had a C-terminal carbamylated lysine residue were found to have a reduced intensity when viewed by MALDI-TOFMS. CID of a tryptic peptide that was carbamylated on both the N-terminus and the C-terminus was found to have a more uniform distribution of b- and y-ions, as well as prominent ions from loss of water. Reversed-phase chromatography coupled to ESI-MS/MS was used to identify and quantify the isotopically labeled standard proteins, bovine serum albumin (BSA), bovine transferrin, and bovine alpha-casein. Quantitative error between theoretical and observed data ranged from 1.7-10.0%. Relative standard deviations for protein quantitation ranged from 5.2-27.8% over a dynamic range from 0.1-10 (L/H). The development of a method utilizing urea-assisted carbamylation of lysines and N-termini to globally labeled samples for comparative proteomics may prove useful for samples that require a strong chaotrope prior to proteolysis.
Tramadol extended-release in the management of chronic pain-0 (2011)

Chronic, noncancer pain such as that associated with osteoarthritis of the hip and knee is typically managed according to American College of Rheumatology guidelines. Patients unresponsive to first-line treatment with acetaminophen receive nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. However, many patients may have chronic pain that is refractory to these agents, or they may be at risk for the gastrointestinal, renal, and cardiovascular complications associated with their use. Tramadol, a mild opioid agonist and norepinephrine and serotonin reuptake inhibitor, is recommended by current guidelines for the treatment of moderate to moderately severe pain in patients who have not responded to previous oral therapy, or in patients who have contraindications to COX-2 inhibitors and nonselective NSAIDs. An extended-release (ER) formulation of tramadol was approved by the US Food and Drug Administration in September 2005. In contrast with immediate-release (IR) tramadol, this ER formulation allows once-daily dosing, providing around-the-clock analgesia. In clinical studies, tramadol ER has demonstrated a lower incidence of adverse events than that reported for IR tramadol. Unlike nonselective NSAIDs and COX-2 inhibitors, tramadol ER is not associated with gastrointestinal, renal, or cardiovascular complications. Although tramadol is an opioid agonist, significant abuse has not been demonstrated after long-term therapy. It is concluded that tramadol ER has an efficacy and safety profile that warrants its early use for the management of chronic pain, either alone or in conjunction with nonselective NSAIDs and COX-2 inhibitors.
Coupling of the adhesive receptor CD11b/CD18 to functional enhancement of effector macrophage tissue factor response. (1991)

Initiation and regulation of localized selective proteolysis is an important effector property of cells of macrophage (Mo) lineage. Among such effector responses is the induced expression of tissue factor (TF) by cells of Mo lineage. In characterizing the regulation of the Mo responses that may influence the magnitude of the effector phase of the cellular immune response, we have identified a role for the cell surface adhesive receptor CD11b/CD18 (Mac-1, CR3) to amplify the induced TF response. Occupancy of CD11b/CD18 by MAb as surrogate ligands does not directly initiate a TF response. In contrast, after either T cell-derived cytokine or LPS as initial signals, engagement of CD11b/CD18 by MAb induces a two- to eight-fold functional enhancement of the TF response in murine and human Mo. This pathway of CD11b/CD18 enhancement of this Mo effector response was also confirmed with recognized ligands for CD11b/CD18 by exposure of Mo to immobilized fibrinogen. A quantitative increase of Mo surface expression of TF was validated by flow cytometry. We suggest that engagement of CD11b/CD18 by complementary ligands including adherence to extracellular matrix, and possibly in antigen-driven TH:Mo collaborative responses, results in the transduction of cellular signals that quantitatively enhance the expression of TF per se and thereby enhance the inflammatory component of Mo mediated response.
Alternatives for Landmine Detection (2003)

At the rate that government and nongovernmental organizations are clearing existing landmines, it will take 450–500 years to rid the world of them. Concerned about the slow pace of demining, the Office of Science and Technology asked RAND to assess potential innovative technologies being explored and to project what funding would be required to foster the development of the more promising ones. The authors of this report suggest that the federal government undertake a research and development effort to develop a multisensor mine detection system over the next five to eight years.
The Production of Capsules, Hyaluronic Acid and Hyaluronidase by Group A and Group C Streptococci (1956)

Summary: Some capsulated group A and group C streptococci were found to produce both hyaluronic acid and hyaluronidase during active growth; thus confirming and extending the work of Pike (1948 b). In a group C strain, LM, the free hyaluronic acid in liquid culture represents an excess of synthesis over destruction, the balance being influenced by the aeration of the culture. Within the limits examined the degree of aeration did not, however, influence hyaluronidase or hyaluronic acid production by strains producing either the enzyme or its substrate exclusively. A non-capsulated, hyaluronidase producing mutant of strain LM was isolated but capsulated cells, free from this variant, also produced the enzyme. Evidence is presented that the spreading activity of strain LM preparations in rabbit dermis is due to hyaluronidase rather than to capsular material as suggested by Pradhan (1937).
Adh locus in maize for detection of mutagens in the environment. (1981)

The advantages of the maize Adh system for low level mutagenesis studies are discussed. They include high mutation rate and the availability of both a strong selection system for null mutants and a sensitive method for detection of variants. The null selection involves treatment of pollen with allyl alcohol which is converted by the Adh enzyme to the toxic acrylaldehyde. Adh variants can be detected by alteration in affinity for phytic acid as well as thermal stability and electrophoretic mobility.
Purification and characterization of a high molecular weight glycoprotein detectable in human milk and breast carcinomas. (1985)

The murine monoclonal antibody (MAb) designated DF3 has defined a high m.w. antigen detectable in human breast carcinomas and in human milk. DF3 antigen is detectable on apical borders of secretory mammary epithelial cells and in the cytosol of less differentiated malignant cells. DF3 antigen expression has been shown to correlate with the degree of human breast tumor differentiation, and the detection of a cross-reactive species in human milk has suggested that DF3 antigen might be useful as a biochemical marker of differentiated mammary epithelial cells. To further characterize DF3 antigen, we have developed an approach to purify the cross-reactive species by using gel filtration and antibody affinity chromatography. The affinity column-purified DF3 antigen was absorbed by wheat germ agglutinin and peanut agglutinin, but not by concanavalin A or lentil lectin. In contrast, wheat germ agglutinin inhibited MAb DF3 reactivity with the purified antigen, whereas there was little, if any, inhibition when using peanut agglutinin. These findings are thus consistent with the involvement of terminal N-acetyl-D-neuraminic acid and/or N-acetylglucosamine residues in the antigenic site. DF3 antigenicity was also sensitive to neuraminidase, but not chondroitinase ABC, chondroitinase AC, chondroitin-4-sulfatase, or hyaluronidase. Furthermore, DF3 antigen was sensitive to Pronase, subtilisin BPN', and alpha-chymotrypsin. The presence of O-glycosidic linkages between carbohydrate and protein in the DF3 antigenic site was further supported by the presence of NaBH4-sensitive sites. Together, these results suggest that sialyl oligosaccharides present on a peptide backbone are required for maintaining DF3 antigenicity. Similar findings have been demonstrated for DF3 antigen purified from both human milk and breast cancer effusions. However, the DF3 antigen in human milk consisted of a single high m.w. species, whereas the tumor-associated antigen consisted of two distinct glycoproteins with m.w. of 330,000 and 450,000. These findings may be relevant to the recent demonstration that distinct high m.w. DF3 antigens are elevated in the circulation of patients with breast carcinoma.
Optical gain in materials with indirect transitions (2003)

Based on a simple two-level system, we discuss optical gain in materials with indirect optical transitions. We show that contrary to direct materials the absolute value of the negative absorption coefficient, which describes the optical gain, can be orders of magnitude larger in indirect semiconductors than the positive absorption coefficient measured under equilibrium conditions. These results are in contrast to previously published work and suggest that the question as to whether laser operation based on band–band transitions in bulk crystalline silicon is possible or not, in principle, needs to be readdressed. In addition, it is shown that indirect optical transitions can provide negative absorption, i.e., optical gain without an electronic population inversion.
Imaging brain function in humans at 7 Tesla (2001)

Abstract This article describes experimental studies performed to demonstrate the feasibility of BOLD fMRI using echo‐planar imaging (EPI) at 7 T and to characterize the BOLD response in humans at this ultrahigh magnetic field. Visual stimulation studies were performed in normal subjects using high‐resolution multishot EPI sequences. Changes in R arising from visual stimulation were experimentally determined using fMRI measurements obtained at multiple echo times. The results obtained at 7 T were compared to those at 4 T. Experimental data indicate that fMRI can be reliably performed at 7 T and that at this field strength both the sensitivity and spatial specificity of the BOLD response are increased. This study suggests that ultrahigh field MR systems are advantageous for functional mapping in humans. Magn Reson Med 45:588–594, 2001. © 2001 Wiley‐Liss, Inc.
Negative Caching of DNS Queries (DNS NCACHE) (1998)

RFC1034] provided a description of how to cache negative responses. It however had a fundamental flaw in that it did not allow a name server to hand out those cached responses to other resolvers, thereby greatly reducing the effect of the caching. This document addresses issues raise in the light of experience and replaces [RFC1034 Section 4.3.4].
Gait analysis in prosthetics (2002)

A review was performed of the literature of the last eleven years (1990-2000) with the topic: "clinical use of instrumented gait analysis in patients wearing a prosthesis of the lower limb". To this end a literature search was performed in Embase, Medline and Recal. Forty-five (45) articles were identified for study from which 34 were reviewed. The reviews were divided into five subtopics: 1) adaptive strategies in gait (12 studies); 2) the influence of different parts of the prosthesis on gait (12 studies); 3) pressure measurements in the socket in gait studies (4 studies); 4) the influence of the mass of the prostheses on gait (5 studies); 5) energy considerations in gait (2 studies). A considerable part of the studies concerned the adaptive strategies of the amputee in walking and running and the evaluation of different prosthetic feet. All aspects and outcomes were reviewed concerning the clinical relevance.
Cloning and Characterization of a Human STE20-like Protein Kinase with Unusual Cofactor Requirements (1997)

We cloned and characterized a novel human member of the STE20 serine/threonine protein kinase family named mst-3. Based on its domain structure, mst-3 belongs to the SPS1 subgroup of STE20-like proteins, which includes germinal center (GC) kinase, hematopoietic progenitor kinase (HPK), kinase homologous to STE20/SPS-1 (KHS), kinases responsive to stress (KRS1/2), the mammalian STE20-like kinases (mst1/2), and the recently published STE20/oxidant stress response kinase SOK-1. mst-3 is most closely related to SOK-1, with 88% amino acid similarity in the kinase domain. The similarity of the mst-3 kinase domain to STE20 is 42%. The mst-3 transcript is ubiquitously expressed, and the protein was found in all human, mouse, and monkey cell lines tested. An in vitro kinase assay showed that mst-3 can phosphorylate basic exogenous substrates as well as itself. Interestingly, mst-3 prefers Mn2+ to Mg2+ as a divalent cation and can use both GTP and ATP as phosphate donors. Like SOK-1, mst-3 is activated by autophosphorylation. However, a physiological stimulus of mst-3 activity was not identified. mst-3 activity does not change upon exposure to several mitogenic and stress stimuli. Overexpression of mst-3 wild-type or kinase dead protein affects neither the extracellular signal-regulated kinases (ERK1/2 or ERK6), c-Jun N-terminal kinase (JNK), p38, nor pp70S6 kinase, suggesting that mst-3 is part of a novel signaling pathway.
Scattering of Electromagnetic Waves from Concentric Infinite Cylinders* (1961)

The solution for the scattering of radiant energy in the form of electromagnetic waves by concentric isotropic infinitely long circular cylinders is given for the incident energy traveling perpendicular to the cylinder axis.
CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma (2012)

The prevalence of CD44+/CD24- tumor cells varied greatly in invasive ductal carcinomas, with the occurrence of this phenotype high in primary tumors with high PR status and in secondary tumors. Moreover, this phenotype was significantly associated with shorter cumulative DFS and OS. Thus, the CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.
Tilted Cat Helmet Mounted Display (1989)

Honeywell has developed a new helmet mounted display (HMD) with a 60° field of view (FOV) by using a unique Tilted Cat (Catadioptric) Combiner. The Tilted Cat display concept allows a wide FOV display to be designed: with a 3:1 display brightness improvement over the conventional folded catadioptric approach; provides a similar improvement in combiner see through transmissions; and only requires a small tilt on the optically powered combiner which minimizes the complexity of the optics. Large FOV HMD&apos;s with see through capability require tilted optically powered surfaces with complex optical systems for the display projection and relay. The optical performance of a tilted powered element becomes more asymetric as the tilt increases, and to maintain a resultant well resolved symmetric display image, additional non-symmetric, tilted, decentered lens elements are required. The Tilted Cat combiner permitted a practical display optical system to be defined for a 60° FOV. The high resolution performance levels of the smaller FOV displays was obtained, with the resolution limited only by the CRT&apos;s resolution. A summary of the design considerations, the development of, and the demonstrated performance data for the 60° Tilted Cat HMD will be presented.