gebhart/patrepeval huggingface dataset:
Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study (2021)

SARS-CoV-2 mRNA vaccines have proven high efficacy, however, limited data exists on the duration of immune responses and their relation to age and side effects. We studied the antibody and memory T cell responses after the two-dose BNT162b2 vaccine in 122 volunteers up to 6 months and correlated the findings with age and side effects. We found a robust antibody response to Spike protein after the second dose. However, the antibody levels declined at 12 weeks and 6 months post-vaccination, indicating a waning of the immune response over time. At 6 months after the second dose, the Spike antibody levels were similar to the levels in persons vaccinated with one dose or in COVID-19 convalescent individuals. The antibodies efficiently blocked ACE2 receptor binding to SARS-CoV-2 Spike protein of five variants of concern at one week but this was decreased at three months. 87% of individuals developed Spike-specific memory T cell responses, which were lower in individuals with increased proportions of immunosenescent CD8+ TEMRA cells. We found antibody response to correlate negatively with age and positively with the total score of vaccination side effects. The mRNA vaccine induces a strong antibody response to SARS-CoV-2 and five VOCs at 1 week post-vaccination that decreases thereafter. T cell responses, although detectable in the majority, were lower in individuals with higher T cell immunosenescence. The deterioration of vaccine response suggests the need to monitor for the potential booster vaccination.
Achieving high efficiency in a double conversion transformerless UPS (2005)

This paper describes the design of a transformerless UPS that uses two high frequency PWM power converters in series without sacrificing efficiency compared to their transformed forerunners. It has long been accepted, however, that a high frequency PWM converter will have higher losses than a diode rectifier or SCR phase control rectifier and that the loss in efficiency is simply one way to bare the cost for the increased performance. The advantages of using a high frequency PWM converter for the AC-to-DC stage are generally well known: improved input power factor; improved input current THD; and improved performance on a generator. This paper presents, as a case study, how one UPS design addressed the efficiency issue and controlled the losses to produce a product with efficiency equal to or better than the SCR forerunner.
Protein arginine methyltransferase 5 is essential for growth of lung cancer cells (2012)

PRMT5 (protein arginine methyltransferase 5) is an enzyme that catalyses transfer of methyl groups from S-adenosyl methionine to the arginine residues of histones or non-histone proteins and is involved in a variety of cellular processes. Although it is highly expressed in some tumours, its direct role in cancer growth has not been fully investigated. In the present study, in human lung tissue samples we found that PRMT5 was highly expressed in lung cancer cells, whereas its expression was not detectable in benign lung tissues. Silencing PRMT5 expression strongly inhibited proliferation of lung adenocarcinoma A549 cells in tissue culture, and silencing PRMT5 expression in A549 cells also abolished growth of lung A549 xenografts in mice. In vitro and in vivo studies showed that the cell growth arrest induced by loss of PRMT5 expression was partially attributable to down-regulation of fibroblast growth factor receptor signalling. These results suggest that PRMT5 and its methyltransferase activity is essential for proliferation of lung cancer cells and may serve as a novel target for the treatment of lung cancer.
Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells (2009)

T-cell development follows a defined set of stage-specific differentiation steps. However, molecular and cellular events occurring at early stages of human T-cell development remain to be fully elucidated. To address this, human umbilical cord blood (UCB) hematopoietic stem cells (HSCs) were induced to differentiate to the T lineage in OP9-DL1 cocultures. A developmental program involving a sequential and temporally discrete expression of key differentiation markers was revealed. Quantitative clonal analyses demonstrated that CD34(+)CD38(-) and CD34(+)CD38(lo) subsets of UCB contain a similarly high T-lineage progenitor frequency, whereas the frequency in CD34(+)CD38(+/hi) cells was 5-fold lower. Delta-like/Notch-induced signals increased the T-cell progenitor frequency of CD34(+)CD38(-/lo) cells differentiated on OP9-DL1, and 2 distinct progenitor subsets, CD34(+)CD45RA(+)CD7(++)CD5(-)CD1a(-) (proT1) and CD34(+)CD45RA(+)CD7(++)CD5(+)CD1a(-) (proT2), were identified and their thymus engrafting capacity was examined, with proT2 cells showing a 3-fold enhanced reconstituting capacity compared with the proT1 subset. Furthermore, in vitro-generated CD34(+)CD7(++) progenitors effectively engrafted the thymus of immunodeficient mice, which was enhanced by the addition of an IL-7/IL-7 antibody complex. Taken together, the identification of T-progenitor subsets readily generated in vitro may offer important avenues to improve cellular-based immune-reconstitution approaches.
Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. (1987)

Little is known of the role of T-cell mediated immune responses in the clearance and pathogenesis of respiratory syncytial virus (RSV) infection. In this study, we established persistent pulmonary RSV infections in athymic nu/nu BALB/c mice or immunodeficient irradiated BALB/c mice, and examined the patterns of virus clearance following adoptive transfer of splenic memory T cells. Primed T cells transferred between Day 5 and Day 8 of infection will clear lung RSV from both nu/nu mice and irradiated mice within 10 days of transfer. Partially purified Lyt 2+ T cells are more effective than L3T4+-selected T cells. No RSV-specific serum antibody could be detected, suggesting that clearance is by an antibody-independent mechanism. In contrast, delayed (Day 14) transfer of primed L3T4+-selected cells clears lung RSV from nu/nu mice, and this correlates with RSV-specific serum antibody production. Clearance is not seen following Day 14 transfer of total primed T cells or T cells selected for the Lyt 2+ subset.
Terahertz Time-Domain Spectroscopy of Human Blood (2013)

In the continuing development of terahertz technology to enable the determination of tissue pathologies in real-time during surgical procedures, it is important to distinguish the measured terahertz signal from biomaterials and fluids, such as blood, which may mask the signal from tissues of interest. In this paper, we present the frequency-dependent absorption coefficients, refractive indices, and Debye relaxation times of whole blood, red blood cells, plasma, and a thrombus.
Congenital Disorders of Glycosylation and Their Effects on the Liver (2010)

Glycoprotein synthesis is one of the major duties of the liver. During the last decade a large number of inherited disorders in protein glycosylation have been identified that alter the architecture and function of the liver. Many congenital disorders of glycosylation (CDG) compromise the synthesis of a host of membrane and secreted glycoproteins often leading to steatosis, hepatic fibrosis, and abnormal bile duct architecture. Misfolded glycoproteins accumulate in the endoplasmic reticulum (ER) and improperly glycosylated plasma proteins are frequently unstable, leading to pro- or anti-coagulant status. CDG patients with liver pathology often present with a host of abnormalities in other systems, including the gastrointestinal tract causing protein-losing enteropathy, hypotonia, hypoglycemia, developmental delay, and seizures. In some cases, pathology is primarily confined to the liver. Effective therapy is available for only one of the more than 20 types of CDG. A simple and inexpensive serum transferrin glycosylation test can suggest a glycosylation disorder and should be used early on in a diagnostic workup of any patients with unknown liver-related pathology, especially if it occurs in combination with abnormalities in other organ systems. Many CDG patients probably remain undiagnosed.
Complete sequence of the murine invariant chain (I1) gene (1989)

Complete sequence of the murine invariant chain (I1) gene Get access Li Zhu, Li Zhu Department of Biological Sciences, Stanford UniversityStanford, CA 94305-5020, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia P. Jones Patricia P. Jones Department of Biological Sciences, Stanford UniversityStanford, CA 94305-5020, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 17, Issue 1, 11 January 1989, Pages 447–448, https://doi.org/10.1093/nar/17.1.447 Published: 11 January 1989 Article history Received: 28 November 1988 Published: 11 January 1989
Identification of CD47/integrin-associated protein and alpha(v)beta3 as two receptors for the alpha3(IV) chain of type IV collagen on tumor cells. (1999)

Previous studies from our laboratories demonstrated that a peptide from the noncollagenous domain of the alpha3 chain of basement membrane collagen (COL IV), comprising residues 185-203, inhibits polymorphonuclear leukocyte activation and melanoma cell proliferation independently of its ability to promote cell adhesion; these properties require the presence of the triplet -SNS- at residues 189-191 (J. C. Monboisse et al., J. Biol. Chem., 269: 25475-25482, 1994; J. Han et al., J. Biol. Chem., 272: 20395-20401, 1997). More recently, we demonstrated that native COL IV and -SNS-containing synthetic peptides (10 microg/ml) added to culture medium inhibit the proliferation of not only melanoma cells but also breast, pancreas, and stomach tumor cells up to 82% and prostate tumor cells by 15%. This inhibition was shown to be dependent on a COL IV- or peptide-induced increase in intracellular cAMP (T. A. Shahan et al., Connect. Tissue Res., 40: 221-232, 1999). Attempts to identify the putative receptor(s) on tumor cells led to the isolation of five proteins (Mr 33,000, 52,000, 72,000, 95,000, and 250,000) from melanoma and prostate cells by affinity purification with the alpha3(IV)179-208 peptide. The Mr 52,000, 95,000, and 250,000 proteins were shown to be CD47/integrin-associated protein(IAP), the integrin beta3 subunit, and the alpha(v)beta3 integrin complex, respectively. The Mr 33,000 and 72,000 proteins have not yet been identified. To confirm the specificity of ligand binding to the receptors, cell membranes from either melanoma or prostate tumor cells were pretreated with the unlabeled ligand alpha3(IV)187-191 (-YYSNS-); alternatively, the peptide was pretreated with a peptide-reactive monoclonal antibody (A5D7) before receptor isolation. These treatments inhibited the purification of CD47/IAP, the integrin beta3 subunit, and the alpha(v)beta3 integrin complex from tumor cells. Furthermore, cells treated with CD47/IAP- or the alpha(v)beta3 integrin-reactive antibodies prevented the alpha3(IV)185-203 peptide from inhibiting cell proliferation and the subsequent rise in intracellular cAMP. Pretreating cells with the alpha3(IV)187-191 (-YYSNS-) peptide also inhibited their adhesion to the alpha3(IV)185-203 peptide substrate, whereas the inactive alpha1(IV)185-203 peptide, from the same region of the alpha1 chain as the alpha3(IV)185-203 peptide, had no effect. Incubation of cells with either CD47/IAP and/or alpha(v)beta3 integrin-reactive antibodies inhibited their adhesion to the alpha3(IV)185-203 peptide, whereas antibodies to the beta1 and beta2 integrin subunits were without effect. These data suggest that ALC-COL IV, through its alpha3(IV) chain, inhibits tumor cell proliferation using the receptors CD47/IAP and the alpha(v)beta3 integrin.
A Bioinorganic Perspective on Matrix Metalloproteinase Inhibition (2004)

The zinc-dependent enzymes known as matrix metalloproteinases (MMPs) are medicinal targets due to the activity of these enzymes associated with diseases such as cancer, heart disease, and arthritis. The development of most MMP inhibitors (MPIs) has followed a basic design formula: a peptidomimetic backbone is attached to a zinc-binding group (ZBG). MPI backbones have varied enormously and improved with increased knowledge of MMP structure and function while hydroxamic acids have been used as the ZBG in most inhibitors. The problems associated with hydroxamic acid and other current ZBGs have been identified; the incorporation of more potent and selective ZBGs for the active site zinc(II) ion is necessary to improve the development of second-generation inhibitors. Herein, we highlight ZBGs that have been proposed as alternatives to hydroxamic acids. In addition, techniques used to identify new ZBGs are also discussed. New insights from a bioinorganic approach using model complexes of the MMP active site are presented as tools in examining the mode of binding for various known and novel ZBGs. Novel computational methods are highlighted that allow for modeling the drug-protein interactions with non-hydroxamate inhibitors of MMPs. We suggest that significant efforts to augment ZBGs combined with the available information on inhibitor backbone design will accelerate the discovery of improved MPIs. Newly devised drug design methods will help to realize this proposal.
Multiple Drug Resistance to Nucleoside Analogues and Nonnucleoside Reverse Transcriptase Inhibitors in an Efficiently Replicating Human Immunodeficiency Virus Type 1 Patient Strain (1996)

A human immunodeficiency virus type 1 (HIV-1)-seropositive patient was treated sequentially with the dideoxynucleoside (ddN) analogues zidovudine, didanosine, zalcitabine, stavudine, and lamivudine and the nonnucleoside HIV-1-specific reverse transcriptase inhibitor (NNRTI) loviride (alpha-APA). Accumulation of drug resistance mutations (mainly V75I, F77L, K103N, F116Y, Q151M, and M184V) eventually resulted in a strain that was genotypically and phenotypically resistant to all tested ddNs and the majority of NNRTIs. However, the multidrug-resistant virus retained wild type sensitivities to drugs such as foscarnet, phosphonomethoxyethyl adenine, dextran sulfate, JM3100, saquinavir, and NNRTI TSAO-m3T. Drug-resistant isolates showed replication kinetics and infectivity in an in vitro peripheral blood mononuclear cell system similar to those of the wild type isolate from the same patient. The multi-ddN-resistant isolate was not eliminated in a competition culture with the wild type isolate. Sequential therapy did not prevent the appearance of multidrug-resistant virus with a conserved replication rate.
Signal transduction pathway of TonB-dependent transporters (2006)

Transcription of the ferric citrate import system is regulated by ferric citrate binding to the outer membrane transporter FecA. A signal indicating transporter occupancy is relayed across the outer membrane to energy-transducing and regulatory proteins embedded in the cytoplasmic membrane. Because transcriptional activation is not coupled to ferric citrate import, an allosteric mechanism underlies this complex signaling mechanism. Using evolution-based statistical analysis we have identified a sparse but structurally connected network of residues that links distant functional sites in FecA. Functional analyses of these positions confirm their involvement in the mechanism that regulates transcriptional activation in response to ferric citrate binding at the cell surface. This mechanism appears to be conserved and provides the structural basis for the allosteric signaling of TonB-dependent transporters.
Ripple joins for online aggregation (1999)

We present a new family of join algorithms, called ripple joins, for online processing of multi-table aggregation queries in a relational database management system (DBMS). Such queries arise naturally in interactive exploratory decision-support applications. Traditional offline join algorithms are designed to minimize the time to completion of the query. In contrast, ripple joins are designed to minimize the time until an acceptably precise estimate of the query result is available, as measured by the length of a confidence interval. Ripple joins are adaptive, adjusting their behavior during processing in accordance with the statistical properties of the data. Ripple joins also permit the user to dynamically trade off the two key performance factors of on-line aggregation: the time between successive updates of the running aggregate, and the amount by which the confidence-interval length decreases at each update. We show how ripple joins can be implemented in an existing DBMS using iterators, and we give an overview of the methods used to compute confidence intervals and to adaptively optimize the ripple join “aspect-ratio” parameters. In experiments with an initial implementation of our algorithms in the POSTGRES DBMS, the time required to produce reasonably precise online estimates was up to two orders of magnitude smaller than the time required for the best offline join algorithms to produce exact answers.
Immediate Uricosuric Effect of Probenecid in Normal Humans (1955)

Urinary uric acid output of 2 healthy male subjects on an hourly feeding regimen was markedly increased on the first day of probenecid ingestion. The amount of uric acid excreted the second day of probenecid administration was greater than normal but not as great as on the first day. This is in contrast to the previous finding that patients with normal amounts of body urate do not show a long term uricosuria after probenecid or phenylbutazone. It is suggested that these drugs induce uricosuria in all cases but that this uricosuria is self-limiting in subjects with no body stores of urate since equilibrium between urate production and disposal must be re-established.
Hydrogen sulfide is an endogenous modulator of leukocyte‐mediated inflammation (2006)

Hydrogen sulfide (H2S) is increasingly recognized as an important signaling molecule in the cardiovascular and nervous systems. Recently, H2S donors were reported to induce neutrophil apoptosis and to suppress expression of some leukocyte and endothelial adhesion molecules. Using rats, we examined the possibility that H2S is an endogenous regulator of key inflammatory events at the leukocyte-endothelial interface. Via intravital microscopy, we observed that H2S donors (NaHS and Na2S) inhibited aspirin-induced leukocyte adherence in mesenteric venules (ED50 of 5.0 micromol/kg for Na2S), likely via activation of ATP-sensitive K+ (K(ATP)) channels. Inhibition of endogenous H2S synthesis elicited leukocyte adherence. Leukocyte infiltration in an air pouch model was also suppressed by H2S donors (NaHS, Lawesson's reagent, and N-acetylcysteine; ED50 of 42.7, 1.3, and 29.9 micromol/kg, respectively) and exacerbated by inhibition of endogenous H2S synthesis. Carrageenan-induced paw edema was suppressed by H2S donors (NaHS and Na2S; ED50s of 35 and 28 micromol/kg, respectively) to the same extent as by diclofenac and enhanced by an inhibitor of H2S synthesis. Suppression of edema formation by H2S donors was mimicked by a K(ATP) channel agonist and reversed by an antagonist of this channel. These results suggest that endogenous H2S is an important mediator of acute inflammation, acting at the leukocyte-endothelium interface. These findings have important implications for anti-inflammatory drug development.
Philadelphia chromosome positive childhood acute lymphoblastic leukemia (1980)

In a 3-yr period, the Philadelphia chromosome (Ph1) was found in 4 of 43 children with acute lymphoblastic leukemia (ALL) in whom chromosomes were studied at diagnosis. The clinical, morphological, cytochemical, and immunologic findings in the Ph1-positive (PH1+) CASES WERE CONsistent with typical childhood ALL, indicating that identification of cases requires chromosome studies. A review of all reported cases of Ph1 + childhood ALL shows that Ph1 + patients are older and have higher initial platelet and white blood cell counts (WBC) than most children with ALL. However, a life table comparison between the reported cases of Ph1 + ALL in children and randomly selected age-, sex-, and WBC- matched controls with ALL shows the duration of first marrow remission to be significantly shorter (p less than 0.02) for the Ph1 + cases Ph1 + ALL is a distinct subtype of childhood ALL that is not rare and can be identified only by cytogenetic studies. The prognosis is poor. Cytogenetic studies should be done prospectively in a large group of children with ALL to define further the subgroup of patients and to confirm the findings of this retrospective analysis.
SleepScale: Runtime joint speed scaling and sleep states management for power efficient data centers (2014)

Power consumption in data centers has been growing significantly in recent years. To reduce power, servers are being equipped with increasingly sophisticated power management mechanisms. Different mechanisms offer dramatically different trade-offs between power savings and performance penalties. Considering the complexity, variety, and temporally-varying nature of the applications hosted in a typical data center, intelligently determining which power management policy to use and when is a complicated task. In this paper we analyze a system model featuring both performance scaling and low-power states. We reveal the interplay between performance scaling and low-power states via intensive simulation and analytic verification. Based on the observations, we present SleepScale, a runtime power management tool designed to efficiently exploit existing power control mechanisms. At run time, SleepScale characterizes power consumption and quality-of-service (QoS) for each low-power state and frequency setting, and selects the best policy for a given QoS constraint. We evaluate SleepScale using workload traces from data centers and achieve significant power savings relative to conventional power management strategies.
Long-Term Survival of Kidney Allografts in Dogs after Withdrawal of Immunosuppression with Ciclosporin and Azathioprine (1989)

We have examined the immunosuppressive effects of combined azathioprine (Aza) and ciclosporin (CS) in two groups of mongrel dogs receiving kidney allografts. In group 1, Aza and CS were given together daily after transplantation and in group 2 twice the dose of each drug was given separately on alternate days. Doses were halved in each group at successive 84-day intervals and all immunosuppression was stopped on day 336. Thus the same total amounts of Aza and CS were given to all recipients in both groups. Up to day-60 the incidence of rejection in each group was similar, thereafter recipients in group 1 were more susceptible to fatal infection and marrow hypoplasia. This accounted for the difference in long-term survival between the two groups (1/14 in group 1, 5/12 in group 2 at day 420). Subsequently, two long-term survivors in group 2 died, 1 on day 452 from chronic rejection and the other on day 529 from gastroenteritis with a histologically normal allograft kidney. An in vitro analysis of the alloreactive repertoire of two healthy recipients in group 2, bearing each other's kidneys for more than 2.5 years and more than 500 days without immunosuppression, showed a profound donor-specific defect which could account for their operationally tolerant state.