gebhart/patrepeval huggingface dataset:
Human monoclonal antibodies to HIV-1 gp140 from mice bearing YAC-based human immunoglobulin transloci (2011)

Mice carrying human immunoglobulin transloci were immunised with HIV-1 gp140 antigen to gain insight into the range and nature of human monoclonal antibodies (mAbs) that can be elicited from such humanised mice. Using five-feature mice that harbour YAC-based germline-configuration human IgM, Igκ and Igλ transloci in a mouse background disrupted for endogenous mouse IgH and Igκ expression, gp140-specific human IgM mAbs were readily elicited following serial immunisation. These mAbs were converted to human IgG1 format and were found to bind diverse epitopes within gp140, exhibiting high functional affinity for the antigen-typically in the nanomolar or sub-nanomolar range. The number of specific, stable hybridomas per mouse was, however, low (typically around five) with the hybridomas within individual mice often being clonally related. Nevertheless, different mice used B cell clones expressing varied V(D)J combinations, with affinity maturation through somatic hypermutation making a critical contribution. Thus, a wide range of distinct high-affinity mAbs can be obtained by immunising multiple animals. The results confirm the utility of the translocus-mouse approach and give insight into strategies for possible future improvement.
Multifunctional Tandem Peptide Modified Paclitaxel-Loaded Liposomes for the Treatment of Vasculogenic Mimicry and Cancer Stem Cells in Malignant Glioma (2015)

The chemotherapy of aggressive glioma is usually accompanied by a poor prognosis because of the formation of vasculogenic mimicry (VM) and brain cancer stem cells (BCSCs). VM provided a transporting pathway for nutrients and blood to the extravascular regions of the tumor, and BCSCs were always related to drug resistance and the relapse of glioma. Thus, it is important to evaluate the inhibition effect of antiglioma drug delivery systems on both VM and BCSCs. In this study, paclitaxel-loaded liposomes modified with a multifunctional tandem peptide R8-c(RGD) (R8-c(RGD)-Lip) were used for the treatment of glioma. An in vitro cellular uptake study proved the strongest targeting ability to be that of R8-c(RGD)-Lip to glioma stem cells. Drug loaded R8-c(RGD)-Lip exhibited an efficient antiproliferation effect on BCSCs and could induce the destruction of VM channels in vitro. The following pharmacodynamics study demonstrated that R8-c(RGD)-modified drug-loaded liposomes achieved both anti-VM and anti-BCSC effects in vivo. Finally, no significant cytotoxicity of the blood system or major organs of the drug-loaded liposomes was observed under treatment dosage in the safety evaluation. In conclusion, all of the results proved that R8-c(RGD)-Lip was a safe and efficient antiglioma drug delivery system.
Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans. (1993)

Leishmaniasis is a major tropical disease for which current chemotherapies, pentavalent antimonials, are inadequate and cause severe side effects. It has been reported that trifluralin, a microtubule-disrupting herbicide, is inhibitory to Leishmania amazonensis. In this study, the in vitro effect of trifluralin on different species of trypanosomatid protozoans was determined. In addition to L. amazonensis, trifluralin is effective against Leishmania major and Leishmania tropica, which cause cutaneous infections, Leishmania donovani, which causes visceral disease, Leishmania panamensis, which may cause mucocutaneous infection, and Trypanosoma brucei, an important human and veterinary pathogen. Moreover, most encouragingly, trifluralin is effective in vivo as a topical ointment against L. major and Leishmania mexicana murine cutaneous leishmaniasis. Thus, trifluralin is a promising lead drug for several related, prevalent tropical diseases: leishmaniasis, trypanosomiasis of animals, and, possibly, African trypanosomiasis in humans.
Pandemic Influenza: An Inconvenient Mutation (2009)

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Case study for running HPC applications in public clouds (2010)

Cloud computing is emerging as an alternative computing platform to bridge the gap between scientists' growing computational demands and their computing capabilities. A scientist who wants to run HPC applications can obtain massive computing resources 'in the cloud' quickly (in minutes), as opposed to days or weeks it normally takes under traditional business processes. Due to the popularity of Amazon EC2, most HPC-in-the-cloud research has been conducted using EC2 as a target platform. Previous work has not investigated how results might depend upon the cloud platform used. In this paper, we extend previous research to three public cloud computing platforms. In addition to running classical benchmarks, we also port a 'full-size' NASA climate prediction application into the cloud, and compare our results with that from dedicated HPC systems. Our results show that 1) virtualization technology, which is widely used by cloud computing, adds little performance overhead; 2) most current public clouds are not designed for running scientific applications primarily due to their poor networking capabilities. However, a cloud with moderately better network (vs. EC2) will deliver a significant performance improvement. Our observations will help to quantify the improvement of using fast networks for running HPC-in-the-cloud, and indicate a promising trend of HPC capability in future private science clouds. We also discuss techniques that will help scientists to best utilize public cloud platforms despite current deficiencies.
Robot-Aided Neurorehabilitation: A Robot for Wrist Rehabilitation (2007)

In 1991, a novel robot, MIT-MANUS, was introduced to study the potential that robots might assist in and quantify the neuro-rehabilitation of motor function. MIT-MANUS proved an excellent tool for shoulder and elbow rehabilitation in stroke patients, showing in clinical trials a reduction of impairment in movements confined to the exercised joints. This successful proof of principle as to additional targeted and intensive movement treatment prompted a test of robot training examining other limb segments. This paper focuses on a robot for wrist rehabilitation designed to provide three rotational degrees-of-freedom. The first clinical trial of the device will enroll 200 stroke survivors. Ultimately 160 stroke survivors will train with both the proximal shoulder and elbow MIT-MANUS robot, as well as with the novel distal wrist robot, in addition to 40 stroke survivor controls. So far 52 stroke patients have completed the robot training (ongoing protocol). Here, we report on the initial results on 36 of these volunteers. These results demonstrate that further improvement should be expected by adding additional training to other limb segments.
Structure-driven crawler generation by example (2006)

Many Web IR and Digital Library applications require a crawling process to collect pages with the ultimate goal of taking advantage of useful information available on Web sites. For some of these applications the criteria to determine when a page is to be present in a collection are related to the page content. However, there are situations in which the inner structure of the pages provides a better criteria to guide the crawling process than their content. In this paper, we present a structure-driven approach for generating Web crawlers that requires a minimum effort from users. The idea is to take as input a sample page and an entry point to a Web site and generate a structure-driven crawler based on navigation patterns, sequences of patterns for the links a crawler has to follow to reach the pages structurally similar to the sample page. In the experiments we have carried out, structure-driven crawlers generated by our new approach were able to collect all pages that match the samples given, including those pages added after their generation.
Improving Survival of Culture Bacteria in Frozen Desserts by Microentrapment (1993)

Lactobacillus bulgaricus cells were entrapped in beads of calcium alginate and evaluated for their ability to survive freezing processes. Cells survived freezing (without agitation) in ice milk mix much better than in distilled water, and more entrapped cells survived than did cells that were not entrapped. Glycerol and mannitol were cryoprotective, but glucose was not, when each was added (6%) separately to the beads. Entrapment protected the lactobacilli in batch frozen and continuously frozen ice milk mixes. The percentage of survival for entrapped and unentrapped cells in continuously frozen ice milk approximated 90 and 40%, respectively. Lactobacilli survived better in beads with mean diameters > 30 microns than in those averaging 15 microns. Addition of entrapped lactobacilli had no measurable effect on the sensory characteristics of the ice milk.
Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta. (1986)

We have determined the primary structure of human placental factor XIIIa, an enzyme [fibrinoligase, transglutaminase, fibrin-stabilizing factor, EC 2.3.2.13 (protein-glutamine:amine gamma-glutamyltransferase)] that forms intermolecular isopeptide bonds between fibrin molecules as the last step in blood coagulation. Placental factor XIIIa is an unglycosylated polypeptide chain of 730 amino acid residues (Mr = 83,005) that appears to be identical to the a subunit of the plasma zymogen factor XIII. Ca2+-dependent activation of factor XIIIa by thrombin removes a blocked amino-terminal peptide and unmasks a reactive thiol group at Cys-314. A second specific cleavage after Lys-513 by thrombin inactivates factor XIIIa and produces an amino-terminal 56-kDa fragment and a 24-kDa fragment. The amino acid sequence of factor XIIIa is unique and does not exhibit internal homology, but its active center is similar to that of the thiol proteases. The probable Ca2+-binding site of factor XIIIa has been identified by homology to the high-affinity sites in calmodulins. Knowledge of the primary structure of factor XIIIa will aid elucidation of the mechanism of its enzymatic action and that of the many tissue transglutaminases of which it is the prototype. This will also facilitate production of factor XIIIa by recombinant DNA technology for use in treatment of congenital factor XIII deficiencies and in the postoperative healing of wounds.
Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I–II clinical trial (2009)

Our data show that MSCs injection can be used for the treatment of end-stage liver disease with satisfactory tolerability. Furthermore, this treatment may improve clinical indices of liver function in end-stage liver disease.
Stereoselective Double Alkylation of Ethyl N-Boc-pyroglutamate (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective Double Alkylation of Ethyl N-Boc-pyroglutamateJesus Ezquerra, Concepcion Pedregal, Almudena Rubio, Juan Jose Vaquero, Maria Paz Matia, Justina Martin, Adolfo Diaz, J. L. G. Navio, and Jack B. DeeterCite this: J. Org. Chem. 1994, 59, 15, 4327–4331Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/jo00094a057https://doi.org/10.1021/jo00094a057research-articleACS PublicationsRequest reuse permissionsArticle Views683Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Abstract 2172: Pharmacological Inhibition of Epsilon PKC Prevents the Progression of Hypertension-induced Heart Failure (2006)

Introduction: Genetically manipulated mice provided conflicting data on whether protein kinase C epsilon (ϵPKC) should be inhibited or activated to cause heart failure. Hypothesis: we hypothesized ...
Transport, Manipulation, and Reaction of Biological Cells On-Chip Using Electrokinetic Effects (1997)

A microfluidic system was fabricated on a glass chip to study mobilization of biological cells on-chip. Electroosmotic and/or electrophoretic pumping were used to drive the cell transport within a network of capillary channels. Whole cells such as Saccharomyces cerevisiae, canine erythrocyte, and Escherichia coli were employed in this work. Photographs are presented to illustrate how cells are selected and transported from one location to another within the capillary network, with velocities up to about 0.5 mm/s in capillaries with a 15- x 55-microns cross section. The mixing of canine erythrocytes with the lysing agent sodium dodecyl sulfate, at an intersection within the chip, was performed to demonstrate that cell selection and subsequent reaction can be accomplished within the microchip.
Gene targeting in hemostasis hepsin (2001)

Hepsin is a type II transmembrane serine protease abundantly expressed on the surface of hepatocytes. Biochemical studies have shown that hepsin is an enzyme of 51 kDa with the trypsin-like substrate specificity. Several in vitro studies have suggested that hepsin may play a role in blood coagulation, hepatocyte growth, and fertilization. To determine the functional importance of hepsin, hepsin-deficient mice were generated by homologous recombination. Homozygous hepsin-/- mice were viable and fertile, and grew normally. When analyzed in hemostasis assays, such as tail bleeding time and plasma clotting times, and in vivo modes, such as disseminated intravascular coagulation, septic shock, and acute liver regeneration, hepsin-/- mice had similar phenotypes as wild-type controls. Liver weight and serum concentrations of liver-derived proteins or enzymes were also similar in hepsin-/- and wild-type mice. No abnormalities were identified in major organs in hepsin-/- mice in histological examinations. These results indicate that hepsin is not an essential enzyme for normal hemostasis, embryogenesis, and maintenance of normal liver function. Unexpectedly, serum concentrations of bone-derived alkaline phosphatase were approximately two-fold higher in both male and female hepsin-/- mice than those in wild-type controls. The underlying mechanism for this phenotype and long-term effects of hepsin deficiency remain to be determined.
Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-A antibody (2006)

Disruption of cholinergic neurotransmission contributes to the memory impairment that characterizes Alzheimer disease (AD). Since the amyloid cascade hypothesis of AD pathogenesis postulates that amyloid beta (A beta) peptide accumulation in critical brain regions also contributes to memory impairment, we assessed cholinergic function in transgenic mice where the human A beta peptide is overexpressed. We first measured hippocampal acetylcholine (ACh) release in young, freely moving PDAPP mice, a well-characterized transgenic mouse model of AD, and found marked A beta-dependent alterations in both basal and evoked ACh release compared with WT controls. We also found that A beta could directly interact with the high-affinity choline transporter which may impair steady-state and on-demand ACh release. Treatment of PDAPP mice with the anti-A beta antibody m266 rapidly and completely restored hippocampal ACh release and high-affinity choline uptake while greatly reducing impaired habituation learning that is characteristic of these mice. Thus, soluble "cholinotoxic" species of the A beta peptide can directly impair cholinergic neurotransmission in PDAPP mice leading to memory impairment in the absence of overt neurodegeneration. Treatment with certain anti-A beta antibodies may therefore rapidly reverse this cholinergic dysfunction and relieve memory deficits associated with early AD.
Monocyte‐derived neutrophil chemotactic factor/interleukin‐8 is a potential mediator of crystal‐induced inflammation (1991)

The physical interaction of particulates with resident mononuclear phagocytes is a consistent feature in certain forms of crystal-induced inflammation. In this study, we observed that monosodium urate crystals stimulated the rapid release of neutrophil chemotactic activity from monocytes, and that this activity steadily increased over 24 hours. Because the release of monocyte-derived neutrophil chemotactic activity was markedly diminished by pretreatment of the monocytes with cycloheximide, and was completely removed from conditioned media by adsorption to heparin-agarose, we addressed the possibility that monocyte-derived neutrophil chemotactic factor/interleukin-8 (IL-8), a heparin-binding neutrophil-activating polypeptide, might modulate these activities. Urate crystal-induced IL-8 secretion from monocytes was verified by radioimmunoassay. In addition, an IL-8-specific antibody markedly inhibited the neutrophil-activating capacity of the conditioned media from monocytes activated by urate crystals, as well as by inflammatory silica crystals. Last, IL-8 was significantly increased in gouty synovial fluids (range 3.0-16.8 ng/ml, mean 8.4 ng/ml, n = 6) relative to osteoarthritic synovial fluids (range 1.1-1.7 ng/ml, mean 1.5 ng/ml, n = 6) (P = 0.006). We conclude that microcrystal-induced secretion of IL-8 by mononuclear phagocytes may mediate a number of forms of crystal-induced inflammation.
ROCK inhibition enhances the recovery and growth of cryopreserved human embryonic stem cells and human induced pluripotent stem cells (2009)

Poor recovery of cryopreserved human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells is a significant impediment to progress with pluripotent stem cells. In this study, we demonstrate that Y-27632, a specific inhibitor of Rho kinase (ROCK) activity, significantly enhances recovery of hES cells from cryopreserved stocks when cultured with or without a growth inactivated feeder layer. Furthermore, treatment with the ROCK inhibitor for several days increased the number of colonies and colony size of hES cells compared to shorter exposures. Remarkably, hES cells that had formed relatively few colonies 5 days after thawing exhibited rapid growth upon addition of Y-27632. Additionally, we determined that Y-27632 significantly improves the recovery of cryopreserved human iPS cells and their growth upon subculture. Thus, Y-27632 provides a means to "kick-start" slow-growing human pluripotent stem cells, especially after being thawed from frozen stocks. Together, these results argue that Y-27632 is a useful tool in overcoming obstacles to studies involving the cultivation of both hES cells and human iPS cells.
First-Trimester Prediction of Hypertensive Disorders in Pregnancy (2009)

This study aimed to establish a method of screening for pregnancy hypertension by a combination of maternal variables, including mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor in early pregnancy. The base-cohort population constituted of 7797 singleton pregnancies, including 34 case subjects who developed preeclampsia (PE) requiring delivery before 34 weeks (early PE) and 123 with late PE, 136 with gestational hypertension, and 7504 cases subjects (96.3%) who were unaffected by PE or gestational hypertension. Maternal history, uterine artery pulsatility index, mean arterial pressure, and pregnancy-associated plasma protein-A were recorded in all of the cases in the base cohort, but placental growth factor was measured only in the case-control population of 209 cases who developed hypertensive disorders and 418 controls. In each case the measured mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor were converted to a multiple of the expected median (MoM) after correction for maternal characteristics found to affect the measurements in the unaffected group. Early PE and late PE were associated with increased mean arterial pressure (1.15 MoM and 1.08 MoM) and uterine artery pulsatility index (1.53 MoM and 1.23 MoM) and decreased pregnancy-associated plasma protein-A (0.53 MoM and 0.93 MoM) and placental growth factor (0.61 MoM and 0.83 MoM). Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. It was estimated that, with the algorithm for early PE, 93.1%, 35.7%, and 18.3% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 5% false-positive rate and that 1 in 5 pregnancies classified as being screen positive would develop pregnancy hypertension. This method of screening is far superior to the traditional approach, which relies entirely on maternal history.
Generation of tissue-specific transgenic birds with lentiviral vectors (2005)

Birds are of great interest for a variety of research purposes, and effective methods for manipulating the avian genome would greatly accelerate progress in fields that rely on birds as model systems for biological research, such as developmental biology and behavioral neurobiology. Here, we describe a simple and effective method for producing transgenic birds. We used lentiviral vectors to produce transgenic quails that express GFP driven by the human synapsin gene I promoter. Expression of GFP was specific to neurons and consistent across multiple generations. Expression was sufficient to allow visualization of individual axons and dendrites of neurons in vivo by intrinsic GFP fluorescence. Tissue-specific transgene expression at high levels provides a powerful tool for biological research and opens new avenues for genetic manipulation in birds.
A candidate prostate cancer susceptibility gene encodes tRNA 3' processing endoribonuclease (2003)

tRNA 3' processing endoribonuclease (3' tRNase) is an enzyme responsible for the removal of a 3' trailer from precursor tRNA (pre-tRNA). We purified approximately 85 kDa 3' tRNase from pig liver and determined its partial sequences. BLAST search of them suggested that the enzyme was the product of a candidate human prostate cancer susceptibility gene, ELAC2, the biological function of which was totally unknown. We cloned a human ELAC2 cDNA and expressed the ELAC2 protein in Escherichia coli. The recombinant ELAC2 was able to cleave human pre-tRNA(Arg) efficiently. The 3' tRNase activity of the yeast ortholog YKR079C was also observed. The C-terminal half of human ELAC2 was able to remove a 3' trailer from pre-tRNA(Arg), while the N-terminal half failed to do so. In the human genome exists a gene, ELAC1, which seems to correspond to the C-terminal half of 3' tRNase from ELAC2. We showed that human ELAC1 also has 3'-tRNase activity. Furthermore, we examined eight ELAC2 variants that seem to be associated with the occurrence of prostate cancer for 3'-tRNase activity. Seven ELAC2 variants which contain one to three amino acid substitutions showed efficient 3'-tRNase activities, while one truncated variant, which lacked a C-terminal half region, had no activity.