gebhart/patrepeval huggingface dataset:
Asymmetric Synthesis of 1,3‐Dithiolane Nucleoside Analogues (2002)

Abstract We report the ready asymmetric synthesis of nucleoside analogues containing a 1,3‐dithiolane ring that mimics the sugar moiety of natural nucleosides. The synthesis is accomplished in three main steps from benzoyloxyethanal 1,3‐dithiolane, the key step being its conversion into a chiral monosulfoxide by a modified Sharpless sulfo‐oxygenation reaction. The nucleoside analogues were obtained in good overall yields and with excellent enantiomeric excesses. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
A Toxicity Study of Multiple-Administration Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys (2011)

Therapies based on stem cells have shown very attractive potential in many clinical studies. However, the data about the safety of stem cells application remains insufficient. The present study was designed to evaluate the overall toxicology of human umbilical cord mesenchymal stem cells (hUC-MSCs) in cynomolgus monkeys with repeated administrations. hUC-MSCs were administered by intravenous injection once every 2 weeks for 6 weeks. The dose levels employed in this study were 2×10(6), 1×10(7) cells/kg body weight. Toxicity was evaluated by clinical observations (body weight, body temperature, and ophthalmology exams), pathology (blood cell counts, clinical biochemistry, urinalysis, and bone marrow smears), immunologic consequences (lymphoproliferation assay, the secretion of interferon-γ and interleukin-4, the percentage of CD3, CD4, CD8 T cells, and the ratio of CD4 and CD8 T cells) and anatomic pathology. Pharmacodynamics in blood and distribution of hUC-MSCs in the tissues of cynomolgus monkeys were measured by real-time polymerase chain reaction. All animals survived until scheduled euthanasia. No stem cells transplantation-related toxicity was found in this study. hUC-MSCs could be found in the blood of cynomolgus monkeys beyond 8 h. The findings of this 6-week toxicity study showed that the transplantation of hUC-MSCs did not affect the general health of cynomolgus monkeys.
Occurrence, function and evolutionary origins of ‘2A-like’ sequences in virus genomes (2008)

2A is an oligopeptide sequence mediating a ribosome 'skipping' effect, producing an apparent 'cleavage' of polyproteins. First identified and characterized in picornaviruses, '2A-like' sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were inserted into a reporter polyprotein to determine their cleavage activity. Our analyses showed that these sequences fall into two categories. The majority mediated very high (complete) cleavage to separate proteins and a few sequences mediated cleavage with lower efficiency, generating appreciable levels of the uncleaved form. Phylogenetic analyses of 2A-like sequences and RNA-dependent RNA polymerases (RdRps) indicated multiple, independent, acquisitions of these sequences at different stages during virus evolution. Within a virus family, 2A sequences are (probably) homologous, but diverge due to other evolutionary pressures. Amongst different families, however, 2A/2A-like sequences appear to be homoplasic.
Antigenic Surveillance of the Influenza Virus by Mass Spectrometry (1999)

The use of a mass spectrometric-based immunoassay to survey the antigenic identity of a type A influenza strain is described. Antigenic surveillance of the influenza virus remains a critical step in the identification of new viral strains and the subsequent use of such strains or synthetic constructs in vaccine preparations. The immunoassay is shown to be capable of detecting a determinant of a single hemagglutinin antigen, responsible for the initial stages of infection, in a mixture of viral proteins with high sensitivity and specificity. The determinant comprises residues 207-225 of the hemagglutinin HA1 chain of the type A strain which occupies a highly accessible region of beta-sheet atop the antigen. Peptide determinants are identified without the need to immobilize antibody or isolate antibody-peptide complexes which are shown to be preserved during mass spectrometric analysis. This immunoassay achieves optimal sensitivity (femtomole level) with minimal sample handling and is amenable to high sample throughput and automation. Determinants are identified by a direct comparison of the matrix-assisted laser desorption ionization mass spectra obtained for an antibody reaction mixture and unreacted control. The sequence and antigenic identity of a component antigen can be rapidly identified by searching protein databases with the mass spectral data in conjunction with tandem mass spectrometric sequencing.
Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation (2000)

CD26 is a T cell activation antigen known to bind adenosine deaminase and have dipeptidyl peptidase IV activity. Cross-linking of CD26 and CD3 with immobilized mAbs can deliver a costimulatory signal that contributes to T cell activation. Our earlier studies revealed that cross-linking of CD26 induces its internalization, the phosphorylation of a number of proteins involved in the signaling pathway, and subsequent T cell proliferation. Although these findings suggest the importance of internalization in the function of CD26, CD26 has only 6 aa residues in its cytoplasmic region with no known motif for endocytosis. In the present study, we have identified the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIR) as a binding protein for CD26 and that mannose 6-phosphate (M6P) residues in the carbohydrate moiety of CD26 are critical for this binding. Activation of peripheral blood T cells results in the mannose 6 phosphorylation of CD26. In addition, the cross-linking of CD26 with an anti-CD26 antibody induces not only capping and internalization of CD26 but also colocalization of CD26 with M6P/IGFIIR. Finally, both internalization of CD26 and the T cell proliferative response induced by CD26-mediated costimulation were inhibited by the addition of M6P, but not by glucose 6-phosphate or mannose 1-phosphate. These results indicate that internalization of CD26 after cross-linking is mediated in part by M6P/IGFIIR and that the interaction between mannose 6-phosphorylated CD26 and M6P/IGFIIR may play an important role in CD26-mediated T cell costimulatory signaling.
Human Immunodeficiency Virus Type 1 Recombination: Rate, Fidelity, and Putative Hot Spots (2002)

Previously, we reported that human immunodeficiency virus type 1 (HIV-1) recombines approximately two to three times per genome per replication cycle, an extremely high rate of recombination given the relatively small genome size of HIV-1. However, a recombination hot spot involving sequence of nonretroviral origin was identified in the vector system utilized, raising the possibility that this hot spot skewed the rate of recombination, and the rate of recombination observed was an overestimation. To address this issue, an HIV-1-derived vector system was used to examine the rate of recombination between autologous HIV-1 sequences after restricting replication to a single cycle in the absence of this hot spot. Viral DNA and RNA were analyzed by a combination of the heteroduplex tracking assay, restriction enzyme analysis, DNA sequencing, and reverse transcription-PCR. The results indicate that HIV-1 undergoes recombination at a minimum rate of 2.8 crossovers per genome per cycle. Again, this is a very high rate given the small size of the HIV-1 genome. The results also suggested that there might be local hot spots of recombination at different locations throughout the genome since 13 of the 33 strand transfers identified by DNA sequencing shared the same site of recombination with one or two other clones. Furthermore, identification of crossover segments also allowed examination of mutations at the point of recombination, since it has been predicted from some studies of cell-free systems that mutations may occur with a frequency of 30 to 50% at crossover junctions. However, DNA sequence analysis of crossover junctions indicated that homologous recombination during viral replication was not particularly mutagenic, indicating that there are other factors or conditions not yet reproduced in cell-free systems which contribute to fidelity during retroviral recombination.
Membrane Glycolipids and Human Immunodeficiency Virus Infection of Primary Macrophages (1996)

The membrane glycolipids galactosylceramide (GalCer) and sulfatide (SGalCer) have been reported to act as receptors of human immunodeficiency virus (HIV) on CD4- cell lines. We show here that these glycolipids are present on CD4+ cells purified from human blood and on in vitro-differentiated monocyte-derived macrophages (MDMs). We investigated the role they could play in HIV infection. Glycolipids of MDMs were characterized at the molecular level by immunolabeling and thin-layer chromatography immune overlay, using a panel of human-, rabbit-, or murine-specific antibodies. GalCer and SGalCer were expressed at the surface of MDMs as assessed by indirect immunofluorescence and flow cytometry analysis, and they could be characterized with specific antibodies in the cellular glycolipid extracts in addition to GM1, GM3, and GD1b gangliosides. Recombinant 125-I-labeled gp160 specifically bound to GalCer, SGalCer, GM1, and GM3 as well as to phospholipids (phosphatidylethanolamine and phosphatidylserine) from MDM extracts. Anti-SGalCer monoclonal antibodies (MAbs), but not anti-GalCer antibodies, entailed limited (30-40%) but significant inhibition of gp160 binding to MDMs. However, the four human anti-SGalCer MAbs and the three murine or rabbit ant-GalCer antibodies tested did not inhibit HIV infection of MDMs, in contrast to CD4 antibody anti-Leu3a tested in parallel. These findings suggests that although HIV envelope glycoprotein can bind to SGalCer and GalCer from CD4+ MDM extracts, these glycolipids do not apparently act as HIV coreceptors nor are they involved in HIV infection of these cells.
Predictive algorithms in the management of computer systems (2002)

Predictive algorithms play a crucial role in systems management by alerting the user to potential failures. We report on three case studies dealing with the prediction of failures in computer systems: (1) long-term prediction of performance variables (e.g., disk utilization), (2) short-term prediction of abnormal behavior (e.g., threshold violations), and (3) short-term prediction of system events (e.g., router failure). Empirical results show that predictive algorithms can be successfully employed in the estimation of performance variables and the prediction of critical events.
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen (2017)

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.
Rapid detection of neonatal sepsis using polymerase chain reaction (1997)

Clinical diagnosis of sepsis in newborn infants is not easy and there is no laboratory test with 100% specificity and sensitivity, with the exception of blood culture, the results of which are not available for at least 48-72 h. Polymerase chain reaction methodology has been used to diagnose different bacterial, viral and protozoal infections, and the possibility of amplifying the DNA region common to all bacteria could represent an optimal method for the diagnosis of sepsis. The authors have performed PCR in a group of 33 neonates at risk for early-onset sepsis, correlating molecular data with blood culture results. The presence of bacterial DNA in blood samples was evaluated, amplifying the DNA region encoding the 16S rRNA. There were no false negative results (four positive blood cultures and four positive PCR), with competitive costs and time. This method also allows the diagnosis of sepsis due to uncommon species and also, using a second PCR with specific primers, an aetiological diagnosis.
Retrieval Analysis of Total Joint Replacement Components: A Six-Year Experience (1985)

Total joint replacement components have been examined as part of an ongoing implant retrieval analysis program. Examination of 65 fractured metal femoral components from total hip replacements revealed that all were caused by a fatigue mechanism and that factors such as stem position, material defects, cement technique, patient weight and activity, and stem design played an important role. Metal components from total knee replacements faired better, except those from metal-on-metal constrained designs, which were subject to fracture and considerable wear. Ultrahigh molecular weight polyethylene components showed several modes of damage, including surface wear, permanent deformation, and fracture. Subjective damage grading of 75 acetabular and 57 tibial components revealed significant correlations with patient weight and implantation time.
CHIP has a protective role against oxidative stress-induced cell death through specific regulation of Endonuclease G (2013)

Oxidative stress is implicated in carcinogenesis, aging, and neurodegenerative diseases. The E3 ligase C terminus of Hsc-70 interacting protein (CHIP) has a protective role against various stresses by targeting damaged proteins for proteasomal degradation, and thus maintains protein quality control. However, the detailed mechanism by which CHIP protects cells from oxidative stress has not been demonstrated. Here, we show that depletion of CHIP led to elevated Endonuclease G (EndoG) levels and enhanced cell death upon oxidative stress. In contrast, CHIP overexpression reduced EndoG levels, and resulted in reduced or no oxidative stress-induced cell death in cancer cells and primary rat cortical neurons. Under normal conditions Hsp70 mediated the interaction between EndoG and CHIP, downregulating EndoG levels in a Hsp70/proteasome-dependent manner. However, under oxidative stress Hsp70 no longer interacted with EndoG, and the stabilized EndoG translocated to the nucleus and degraded chromosomal DNA. Our data suggest that regulation of the level of EndoG by CHIP in normal conditions may determine the sensitivity to cell death upon oxidative stress. Indeed, injection of H2O2 into the rat brain markedly increased cell death in aged mice compared with young mice, which correlated with elevated levels of EndoG and concurrent downregulation of CHIP in aged mice. Taken together, our findings demonstrate a novel protective mechanism of CHIP against oxidative stress through regulation of EndoG, and provide an opportunity to modulate oxidative stress-induced cell death in cancer and aging.
Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities (2011)

Detecting and characterizing single nanoparticles and airborne viruses are of paramount importance for disease control and diagnosis, for environmental monitoring, and for understanding size dependent properties of nanoparticles for developing innovative products. Although single particle and virus detection have been demonstrated in various platforms, single-shot size measurement of each detected particle has remained a significant challenge. Here, we present a nanoparticle size spectrometry scheme for label-free, real-time and continuous detection and sizing of single Influenza A virions, polystyrene and gold nanoparticles using split whispering-gallery-modes (WGMs) in an ultra-high-Q resonator. We show that the size of each particle and virion can be measured as they continuously bind to the resonator one-by-one, eliminating the need for ensemble measurements, stochastic analysis or imaging techniques employed in previous works. Moreover, we show that our scheme has the ability to identify the components of particle mixtures.
The Kw Recombinase, an Integrase from Kluyveromyces Waltii (1997)

Site-specific recombinases of the integrase family share limited amino-acid-sequence similarity, but use a common reaction mechanism to recombine distinct DNA target sites. Here we report the characterisation of the Kw site-specific recombinase, encoded on the 2 mu-like plasmid pKWS1 from the yeast Kluyveromyces waltii. Using in vitro-translated Kw recombinase, we show that the protein is able to bind and to recombine its putative DNA target site. Recombination is conservative and the Kw target site has a spacer of seven base pairs. We show that Kw recombinase is able to mediate recombination in a mammalian cell line, thus, it has potential for use as a tool for genomic manipulation in heterologous systems.
Experimental Evaluation of Dynamic Force Distribution Method for EV Motion Control (2007)

The purpose of this paper is to evaluate the effectiveness of the dynamic force distribution methods, which are used for perfect traction force control of in-wheel motored EVs. Integrated with maneuverability improvement control system, the proposed method dynamically distributes the total driving force among the available in-wheel driving motors by according to the working conditions of tires. Due to such precise distribution, the motors can be purposely controlled with different force commands. Therefore, the wheels can be driven in a special way to realize the traction forces and moments, which are required for the motion control. It helps improve turning maneuverability and keep stability of EV, especially in the marginal turning conditions. Experiment results indicate that the control system with the proposed dynamic force distribution method much more greatly improve EV turning characteristics than the one which uses the equal force distribution method.
The Effects of Environmental and Physiological Conditions of Culex Tritaeniorhynchus on the Pattern of Transmission of Japanese Encephalitis Virus (1976)

Journal Article The Effects of Environmental and Physiological Conditions of Culex Tritaeniorhynchus on the Pattern of Transmission of Japanese Encephalitis Virus Get access Mitsuo Takahashi Mitsuo Takahashi 1Department of Medical Entomology, National Institute of Health, Shinagawaku, Tokyo 141, Japan, and Laboratory of Medical Zoology, Niigata University School of Medicine, Niigata City, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Medical Entomology, Volume 13, Issue 3, 8 December 1976, Pages 275–284, https://doi.org/10.1093/jmedent/13.3.275 Published: 08 December 1976
A force display system for virtual environments and its evaluation (2003)

This paper describes a virtual-force display system that presents force sensations during the manipulation of objects in a virtual environment. In the tasks that have interactions with the environment, force sensation is the most important information used to recognize the interactions between the objects. The authors discuss a method of virtually generating the constraint forces in the model world, and propose a virtual force display system. In this system, the operator obtains the visual information from a graphic display and feels real-time reaction forces through an operating handle. This operating handle is used for the force exertion and the motion sensing. These visual and kinesthetic senses help the operator to understand the virtual world with high fidelity. Using this system, the performed experiments to confirm its effectiveness. In the experiments, an operator manipulates an object in model space using a 4-DOF master arms as an operating handle. Results of the experimental operation show that the operator can feel the contact state with a realistic sensation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Donor Lymphocyte Infusion: The Use of Alloreactive and Tumor-Reactive Lymphocytes for Immunotherapy of Malignant and Nonmalignant Diseases in Conjunction with Allogeneic Stem Cell Transplantation (2002)

Donor lymphocyte infusion (DLI), pioneered in Jerusalem in January 1987, represents the first proof of principle of the absolute efficacy of immunotherapy as a means of curing cancer. Immunotherapy with alloreactive donor lymphocytes can eliminate "the last tumor cell" even in patients with hematological malignancies resistant to maximally tolerated doses of chemoradiotherapy. Alloreactive lymphocytes that can mediate anti-tumor effects following induction of host-versus-graft tolerance induced by transplantation of donor stem cells, can induce graft-versus-malignancy (GVM) effects which are usually accompanied by graft-versus-host disease (GVHD). However, occasionally GVM effects may also be accomplished independently of clinically overt GVHD. Interestingly, allogeneic donor lymphocytes may also eliminate undesirable host-derived hematopoietic cells in a large number of nonmalignant indications including genetic diseases, diseases caused by deficiency of stem cell products, and autoimmune disorders mediated by self-reactive lymphocytes. The cumulative clinical experience suggests feasibility of effective induction of graft-versus-leukemia (GVL); graft-versus-lymphoma (GVLy); graft-versus-multiple myeloma, as well as graft-versus-solid tumors (GVT), well-documented in patients with renal and breast cancer, even in patients with resistant disease that have failed myeloablative chemoradiotherapy. These observations that suggested that cell therapy by donor lymphocytes is the main therapeutic benefit of bone marrow transplantation (BMT) led to development of the nonmyeloablative approach for safer allogeneic stem cell transplantation. Nonmyeloablative stem cell transplantation (NST) makes it possible to offer an option for cure to elderly patients with no upper age limit, as well as to patients with poor performance status not considered eligible for conventional BMT. Using well-tolerated NST regimen, allogeneic stem cell transplantation can be accomplished with minimal procedure-related toxicity and mortality, possibly even on an outpatient basis. Immunotherapy mediated by adoptive allogeneic cell-mediated immunotherapy can be further improved by utilizing specifically immune donor lymphocytes, thus maximizing their efficacy against undesirable target cells of host origin on the one hand, while minimizing their ontoward efficacy against normal cells of host origin that could result in GVHD on the other. Taken together, DLI and subsequently NST, may have opened new horizons for treatment of life-threatening malignant and nonmalignant disorders correctable by allogeneic stem cell transplantation. It is anticipated that further improvement of reactivity and specificity of donor lymphocytes will lead to safer clinical application of cell therapy for a larger number of indications toward improving disease-free survival in a large number of indications while minimizing immediate and late procedure-related complications.