gebhart/patrepeval huggingface dataset:
GPS documentation available (1991)

The University Navstar Consortium facility announces that an investigator's manual and a number of technical reports are available. The Investigator's Manual is intended primarily for UNAVCO members interested in using the UNAVCO facilities for GPS field projects, but it may also be of interest to others planning GPS fieldwork. For users with Internet access, the manual is available via anonymous ftp as a postscript file. A hard copy may be requested from Barbara Perin at UNAVCO (address below).
Simultaneous Quantification of Six Human Cytokines in a Single Sample Using Microparticle-based Flow Cytometric Technology (1999)

The study of cytokines has been of great interest to researchers in many scientific disciplines, including cell biology and immunology. Cytokines form a sophisticated network that serves to modulate a myriad of cellular events. Within such a network, and through complex feedback mechanisms, cytokine functions are mostly interdependent. Because of the extreme complexity of the cytokine network, a simultaneous measurement of multiple cytokines in a single sample represents a desirable and effective approach.

Several methods are available to measure cytokines and their messenger RNAs. To measure cytokines secreted from cells, researchers commonly use conventional ELISA techniques. ELISA methods are generally cost-effective but restricted to measuring one cytokine at a time. Consequently, the ELISA approach requires not only multiple sample aliquots but also repetitive execution of the procedures for each cytokine of interest. The ability of flow cytometry to simultaneously acquire data for numerous particles and subsequently analyze multiple characteristics for each particle makes it a powerful technique for cell sorting and cell analyses. The application is fundamentally built on the high sensitivity of a flow cytometer to discern characteristics either within or on the surface of a cell. Several investigators have constructed microparticle-based immunoassays that use a flow cytometer …
Evidence-Based Practice: Definition and Process (2008)

EBP aims to integrate research and practice so that they are not parallel processes, but intimately integrated at every step. EBP is not to be confused with empirically-supported treatments or outcome evaluation. Both confuse the part for the whole. Evidenced-based practitioners use a practical process that places client's benefits as the highest priority. This process has five major stages: asking answerable questions, investigating the evidence efficiently and effectively, appraising the evidence, applying and adapting the evidence, and evaluating the results. There are two major caricatures of EBP that distort its definition. One of these is so flexible; it accepts virtually anything as evidence. The other is so rigid; it does not allow for any flexibility. This chapter argues for a middle path — one with high scientific standards as well as clinical sensitivity. It also addresses a common pitfall for each stage in the process.
Allosteric modulation of group III metabotropic glutamate receptor 4: A potential approach to Parkinson's disease treatment (2003)

Parkinson's disease (PD) is a debilitating movement disorder that afflicts >1 million people in North America. Current treatments focused on dopamine-replacement strategies ultimately fail in most patients because of loss of efficacy and severe adverse effects that worsen as the disease progresses. The recent success of surgical approaches suggests that a pharmacological intervention that bypasses the dopamine system and restores balance in the basal ganglia motor circuit may provide an effective treatment strategy. We previously identified the metabotropic glutamate receptor 4 (mGluR4) as a potential drug target and predicted that selective activation of mGluR4 could provide palliative benefit in PD. We now report that N-phenyl-7-(hydroxylimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) is a selective allosteric potentiator of mGluR4. This compound selectively potentiated agonist-induced mGluR4 activity in cultured cells expressing this receptor and did not itself act as an agonist. Furthermore, PHCCC potentiated the effect of l-(+)-2-amino-4-phosphonobutyric acid in inhibiting transmission at the striatopallidal synapse. Modulation of the striatopallidal synapse has been proposed as a potential therapeutic target for PD, in that it may restore balance in the basal ganglia motor circuit. Consistent with this, PHCCC produced a marked reversal of reserpine-induced akinesia in rats. The closely related analogue 7-(hydroxylimino)cyclopropachromen-1a-carboxamide ethyl ester, which does not potentiate mGluR4, had no effect in this model. These results are evidence for in vivo behavioral effects of an allosteric potentiator of mGluRs and suggest that potentiation of mGluR4 may be a useful therapeutic approach to the treatment of PD.
Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia (1998)

Local hypoxemia and stasis trigger thrombosis. We have demonstrated previously that in a murine model of normobaric hypoxia pulmonary fibrin deposition is a result of expression of tissue factor, especially in oxygen-deprived mononuclear phagocytes (MPs). We now show that transcription factor early-growth-response gene product (Egr-1) is rapidly activated in hypoxia, both in vitro and in vivo, and is responsible for transcription and expression of tissue factor in hypoxic lung. MPs and HeLa cells subjected to hypoxia (pO2 approximately 13 torr) had increased levels of tissue factor transcripts (approximately 18-fold) and an increased rate of transcription (approximately 15-fold), based on nuclear run-on analysis. Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells demonstrated increased DNA-binding activity at the serum response region (SRR; -111/+14 bp) of the tissue factor promoter at Egr-1 motifs. Using 32P-labeled Egr consensus oligonucleotide, we observed induction of DNA-binding activity in nuclear extracts from hypoxic lung and HeLa cells because of activation of Egr-1, by means of supershift analysis. Transient transfection of HeLa cells with chimeric plasmids containing wild-type or mutant SRR from the tissue factor promoter showed that intact Sp1 sites are necessary for basal promoter activity, whereas the integrity of Egr-1 sites was required for hypoxia-enhanced expression. A central role for Egr-1 in hypoxia-mediated tissue factor expression was confirmed by experiments with homozygous Egr-1 null mice; wild-type mice subjected to oxygen deprivation expressed tissue factor and showed fibrin deposition, but hypoxic homozygous Egr-1 null mice displayed neither tissue factor nor fibrin. These data delineate a novel biology for hypoxia-induced fibrin deposition, in which oxygen deprivation-induced activation of Egr-1, resulting in expression of tissue factor, has an unexpected and central role.
Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes (2010)

We reveal a plasma miRNA signature for DM that includes loss of endothelial miR-126. These findings might explain the impaired peripheral angiogenic signaling in patients with DM.
Direct Synthesis of Polymer Nanocapsules: Self-Assembly of Polymer Hollow Spheres through Irreversible Covalent Bond Formation (2010)

A detailed study of the direct synthesis of polymer nanocapsules, which does not require any template, and core removal, is presented. Thiol-ene "click" reaction between a CB[6] derivative (1) with 12 allyloxy groups at the periphery and dithiols directly produced polymer nanocapsules with a highly stable structure and relatively narrow size distribution. Based on a number of observations including the intermediates detected by DLS, TEM, and SEM studies, a mechanism of the nanocapsule formation was proposed, which includes 2D oligomeric patches turning into a hollow sphere. A theoretical study supports that the formation of a hollow sphere from a disk-shaped intermediate can be thermodynamically favorable under certain conditions. In particular, the effects of various factors such as monomer concentration, reaction temperature, and medium on the formation of polymer nanocapsules have been investigated, which qualitatively agree with those predicted by our theoretical model. An interesting feature of the polymer nanocapsules was that the polymer shell made of a CB[6] derivative allows facile tailoring of its surface properties in a noncovalent and modular manner by virtue of the unique recognition properties of the accessible molecular cavities exposed on the surface. Furthermore, this approach appears to be applicable to any building unit with a flat core and multiple polymerizable groups at the periphery which can direct polymer growth in lateral directions. Other reactions, such as amide bond formation, can be used for the synthesis of polymer nanocapsules in this approach. This novel approach to polymer nanocapsules represents a rare example of self-assembly of molecular components into nanometer-scale objects with interesting structures, shapes, and morphology through irreversible covalent bond formation.
The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells (2000)

The induction of immune responses in vivo is typically performed with antigens administered in external adjuvants, like alum, complete Freund's adjuvant, LPS and, more recently, monophosphoryl lipid A (MPL). However, the role of the adjuvant is still poorly defined. The aim of this study was to test whether the MPL affects the function of antigen-presenting cells (APC) in vitro and in vivo. Antigen-pulsed APC [including macrophages, B cells and dendritic cells (DC)] were incubated or not with MPL, and their ability to sensitize naive T cells was tested in vitro and in vivo. The data show that MPL enhances the ability of macrophages and B cells to sensitize naive T cells, and confers to them the capacity to induce the development of T(h)1 and T(h)2. Administration of MPL i.v. in mice results in the redistribution of fully mature DC in the T cell area of the spleen. These observations suggest that MPL may induce an antigen-specific primary immune response by provoking the migration and maturation of DC that are the physiological adjuvant of the immune system.
A Spliced Isoform of Interleukin 6 mRNA Produced by Renal Cell Carcinoma Encodes for an Interleukin 6 Inhibitor (2005)

Interleukin 6 (IL-6) is a multifunctional and pleiotropic cytokine and in renal cell carcinoma (RCC), this cytokine exerts proinflammatory, immunosuppressive and growth stimulating properties. A spliced isoform of IL-6 mRNA has been described in peripheral blood mononuclear cells and encodes for a potential protein lacking IL-6 activity. In the present study, a novel spliced form of IL-6 mRNA was found detectable in RCC cell lines, normal renal cells, but not in other tumor cells. This splicing resulted in a frameshift and the generation of multiple stop codon in the spliced IL-6 mRNA. However, two ATG of the third IL-6 exon were identified as translation initiation sites and two truncated IL-6 (tIL-6) with the expected molecular weight were recovered from transfected cell supernatant. The cDNA of a spliced form of IL-6 mRNA detected in RCC lines was cloned, and expressed in a baculovirus expression vector. The functional properties of the tIL-6 were investigated and this protein blocked IL-6 bioactivity, including mitogenic activity on tumor cells. In conclusion, this spliced form of IL-6 mRNA detected in RCC encodes for a truncated IL-6 with IL-6 antagonist properties.
The 100-kDa 2′,5′-Oligoadenylate Synthetase Catalyzing Preferentially the Synthesis of Dimeric pppA2′p5′A Molecules Is Composed of Three Homologous Domains (1999)

The 2-5A synthetases represent a family of proteins implicated in the mechanism of the antiviral action of interferon. When activated by double-stranded RNA, these proteins polymerize ATP into 2'-5'-linked oligomers with the general formula pppA(2'p5'A)n, n >/= 1. Three forms of human 2-5A synthetases have been described corresponding to proteins of 40/46 (p40/p46), 69/71 (p69/p71), and 100 kDa (p100). Here we describe the molecular cloning and characterization of p100. By screening a cDNA expression library with a specific p100 polyclonal antibody, we first isolated a 590-nucleotide cDNA fragment which was subsequently used to isolate the full-length 6365-nucleotide cDNA. This cDNA recognizes a distinct interferon-induced messenger RNA of 7 kilobases. It has an open reading frame encoding a protein of 1087 amino acids including the sequence of seven peptides obtained by microsequencing of the natural p100 protein, which was purified from interferon-treated human cells. p100 is composed of three adjacent domains, each homologous to the previously defined catalytic unit of 350 amino acids, which is present as one unit in p40/p46 and as two units in p69/p71. The recombinant p100 synthesized preferentially dimeric 2', 5'-oligoadenylate molecules and displayed parameters for maximum enzyme activity similar to the natural p100. These results confirm that the enzymatic activity of p100 is distinct compared with that of p40/p46 and p69/p71.
Increased risk for type I (insulin‐dependent) diabetes in relatives of patients with alopecia areata (AA) (1994)

The prevalence of various chronic diseases was compared in 517 individuals with alopecia areata, and 2,969 of their first degree relatives. As previous reports have suggested an increased incidence of diabetes in relatives of patients with alopecia areata, special attention was given to the prevalence of Type 1 and Type 2 diabetes in the patients and in their relatives. Several immunologic diseases were increased in alopecia probands and relatives. Thyroid disease, vitiligo, Addison disease, and pernicious anemia were more prevalent in probands and in their relatives than in the general population. Specifically, a high rate of thyroid disease was found in probands (14.7%) and in their first degree relatives (4.2%). Only one proband had Type 1 diabetes, yet there were 14 sibs with Type 1 diabetes. Thus, Type 1 diabetes was significantly more prevalent in the sibs (1.2%) than in either the probands with alopecia (0.2%), or the general population (0.12-0.25%) (P < 0.05)). In contrast, Type 2 diabetes was not more common in probands or in sibs than in the general population. These data suggest that alopecia areata protects against Type 1 diabetes in predisposed individuals. The high rate of thyroid disease suggests that screening probands and first degree relatives for thyroid disease should be considered.
Rapid Antimicrobial Susceptibility Testing of Patient Urine Samples Using Large Volume Free-Solution Light Scattering Microscopy (2019)

The emergence of antibiotic resistance has prompted the development of rapid antimicrobial susceptibility testing (AST) technologies that will enable evidence-based treatment and promote antimicrobial stewardship. To date, many rapid AST methods have been developed, but few are able to be performed on clinical samples directly. Here we developed a large volume light scattering microscopy technique that tracks phenotypic features of single bacterial cells directly in clinical urine samples without sample enrichment or culturing. The technique demonstrated rapid (90 min) detection of <i>Escherichia coli</i> in 24 clinical urine samples with 100% sensitivity and 83% specificity and rapid (90 min) AST in 12 urine samples with 87.5% categorical agreement with two antibiotics, ampicillin and ciprofloxacin.
Influence of Culture Medium on Smooth Muscle Cell Differentiation from Human Bone Marrow–Derived Mesenchymal Stem Cells (2008)

Human bone marrow-derived mesenchymal stem cells (hMSCs) represent an appealing source of smooth muscle cells (SMCs) for engineering small-diameter vascular grafts due to the limited availability and replicative capacity of somatic SMCs. However, lack of standardization of hMSC culture conditions has limited some progress in hMSC research. Because, at the moment, a chemically defined, serum-free medium without growth factors is not capable of amplifying hMSCs in vitro, the usage of serum (either human serum or fetal bovine serum [FBS]) continues in hMSC research. The emergence of commercial hMSCs and hMSC media opened a series of questions regarding the compatibility of commercial and homemade hMSCs and hMSC media. In this study, two types of commonly used FBS-containing hMSC media-MSCGM (containing 10% FBS) and MesenPro (containing 2% FBS), along with our homemade medium (low-glucose Dulbecco's modified Eagle's medium plus 10% selected lot FBS)-were compared in their ability to support SMC differentiation from hMSCs. The effects of FBS level, medium supplements (ascorbic acid, copper, etc.), and growth factors (transforming growth factor beta1) were also examined for their impact on SMC differentiation. It was discovered that MesenPro and transforming growth factor beta1 are the strongest SMC inducers from hMSCs. In contrast, hMSCs grown in homemade (10% Dulbecco's modified Eagle's medium) and commercial MSCGM media remained undifferentiated. FBS concentration did not affect SMC differentiation when 10% FBS was compared with 2%. Finally, the mechanism underlying SMC differentiation from hMSCs grown in FBS-containing medium was explored by following the expression changes of serum response factor during the establishment of hMSC culture.
Successful targeting of mouse Y chromosome genes using a site‐directed insertion vector (2002)

Gene targeting via homologous recombination in mouse ES cells is now a routine method for addressing gene function in vivo. Several hundred genes mapping to all autosomes and the X chromosome have been mutated and analyzed in this way. In contrast, despite repeated attempts in several laboratories, including our own, there have been no reports of successful targeting of mouse Y chromosome genes. We show here that this problem can be overcome through the use of insertional targeting, rather than the usual replacement strategy. Using this method we have successfully targeted the mouse Y located Dby (dead box Y) and Eif2s3y (elongation initiation factor) genes. In addition, as Y chromosome genes are transcribed in ES cells, successful targeting and disruption of gene expression can be easily confirmed by RTPCR analysis of selected clones.
Helminthosporium velutinum and H. aquaticum sp. nov. from aquatic habitats in Yunnan Province, China (2016)

Helminthosporium species from submerged wood in streams in Yunnan Province, China were studied based on morphology and DNA sequence data. Descriptions and illustrations of Helminthosporium velutinum and a new species H. aquaticum are provided. A combined phylogenetic tree, based on SSU, ITS and LSU sequence data, place the species in Massarinaceae, Pleosporales. The polyphyletic nature of Helminthosporium species within Massarinaceae is shown based on ITS sequence data available in GenBank.
The interaction of a Ca2+-dependent monoclonal antibody with the protein C activation peptide region. Evidence for obligatory Ca2+ binding to both antigen and antibody. (1988)

Protein C undergoes Ca2+-induced conformational changes required for activation by the thrombin-thrombomodulin complex. A Ca2+-dependent monoclonal antibody (HPC4) that blocks protein C activation was used to study conformational changes near the activation site in protein C. The half-maximal Ca2+ dependence was similar for protein C and gamma-carboxy-glutamic acid-domainless protein C for binding to HPC4 (205 +/- 23 and 110 +/- 29 microM Ca2+, respectively), activation rates (214 +/- 22 and 210 +/- 37 microM), and intrinsic fluorescence of gamma-carboxyglutamic acid-domainless protein C (176 +/- 34 microM). Protein C heavy chain binding to HPC4 was half-maximal at 36 microM Ca2+, although neither the heavy chain nor HPC4 separately bound Ca2+ with high affinity. The epitope was lost when the activation peptide was released. A synthetic peptide, P (6-17), which spans the activation site, exhibited Ca2+-dependent binding to HPC4 (half-maximal binding = 6 microM Ca2+). Thus, each decrease in antigen structure resulted in a reduced Ca2+ requirement for binding to HPC4. Tb3+ and Ca2+ binding studies demonstrated a Ca2+-binding site in HPC4 required for high affinity antigen binding. These studies provide the first direct evidence for a Ca2+-induced conformational change in the activation region of a vitamin K-dependent zymogen. Furthermore, Ca2+ binding to HPC4 is required for antigen binding. The multiple roles of Ca2+ described may be useful in interpretation of other metal-dependent antibody/antigen interactions.
Learning diverse rankings with multi-armed bandits (2008)

Algorithms for learning to rank Web documents usually assume a document's relevance is independent of other documents. This leads to learned ranking functions that produce rankings with redundant results. In contrast, user studies have shown that diversity at high ranks is often preferred. We present two online learning algorithms that directly learn a diverse ranking of documents based on users' clicking behavior. We show that these algorithms minimize abandonment, or alternatively, maximize the probability that a relevant document is found in the top k positions of a ranking. Moreover, one of our algorithms asymptotically achieves optimal worst-case performance even if users' interests change.
Direct Determination of Solution Binding Constants for Noncovalent Complexes between Bacterial Cell Wall Peptide Analogues and Vancomycin Group Antibiotics by Electrospray Ionization Mass Spectrometry (1998)

We report a method based on electrospray ionization (ESI) mass spectrometry to determine solution association constants (KA) for complexes between glycopeptide antibiotics (vancomycin and ristocetin) and several peptide ligands. The measured KA values are in good agreement with previously reported values obtained by standard spectroscopic titration techniques. The pH stability of the ristocetin−diacetyl-l-lysyl-d-alanyl-d-alanine complex was investigated by ESI mass spectrometry and circular dichroism (CD) spectroscopy. The two methods produce very similar results, demonstrating that the ESI mass spectra reflect the pH stability of the complex. In solution, the antibiotics bind stereospecifically to peptides containing a C-terminal d-Ala-d-Ala sequence, whereas no complex formation is observed with peptides containing the l-Ala-l-Ala stereoisomer. To investigate whether electrospray ionization is able to reflect the structurally specific interaction between antibiotics and d-Ala-d-Ala peptide ligands, an equimolar mixture of vancomycin, diacetyl-l-lysyl-d-alanyl-d-alanine, and the deuterium-labeled stereoisomer diacetyl-l-lysyl-l-alanyl-l-alanine-d6 was analyzed by ESI mass spectrometry. In agreement with solution-phase behavior, only ions corresponding to a complex between diacetyl-l-lysyl-d-alanyl-d-alanine and vancomycin are observed.