gebhart/patrepeval huggingface dataset:
Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients (2010)

Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received >or=2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12-week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non-lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.
Surface Sialic Acid Prevents Loss of GPIbα during Platelet Storage and Rescues In Vivo Survival of Murine Platelets. (2007)

Abstract Platelet processing and storage are associated with platelet lesion, e.g. shape change, activation, release reaction and apoptosis, which is partially due to loss of surface receptors. Surface sialic acid is considered to be a key determinant for the survival of circulating blood cells and glycoproteins. However, its role in platelet receptor loss and platelet survival is unclear. In this study, the relationship between surface sialic acid and platelet receptor loss was investigated in vitro and in vivo. Murine platelets stored at room temperature for 6 hours lost surface sialic acid, as evidenced by flow cytometry using FITC conjugated RCA I lectin, which recognizes exposed galactose residues. This loss correlated with a 30–60% loss of surface receptors GPIbα and GPV, but not GPIX and integrin αIIbβ3, as measured by flow cytometry. Treatment of murine platelets with the neuraminidase (NA) substrate fetuin partially decreases the loss of GPIbα and GPV to 10–20%. In vitro, sialic acid was cleaved from the platelet surface by adding NA (α2-3,6,8-NA (V. cholerae) or α2-3,6,-NA (C. perfringens)) to murine platelets. Removal of sialic acid correlated with the removal of 50–60% of surface GPIbα and GPV, but not GPIX and integrin αIIbβ3. Addition of fetuin, or the more specific NA inhibitor 2,3-dehydro-2-deoxy-, sodium salt (DANA), completely prevented this loss, as determined by both flow cytometry and Western blot analysis. Murine platelets treated with α2-3,6,8-NA (V. cholerae) ± the addition of DANA were labeled with the green dye CMFDA and transfused into age-, strain- and sex-matched C57BL/6 mice to measure platelet survival. NA-treated platelets were cleared within minutes after transfusion, whereas the addition of DANA rescued platelet survival to control-count increments. Our study shows that inhibiting the loss of surface sialic acid prevents platelet surface GPIbα and GPV loss during storage in vitro and rescues platelet survival in vivo.
Efficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches (2007)

Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these mice with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation.
Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition. (1994)

The deposition of certain Bence Jones proteins as tubular casts, basement membrane precipitates, or amyloid fibrils results in the human light-chain-associated renal and systemic diseases--myeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosis. To determine if light-chain nephrotoxicity or amyloidogenicity is related to the propensity of these components to form high molecular weight aggregates under physiological conditions, we used a size-exclusion chromatographic system to study 40 different Bence Jones proteins. Each samples was tested over a wide range of protein concentration in three different buffers varying in pH, osmolality, and the presence or absence of low concentrations of urea. Thirty-three of the 35 proteins found clinically and/or experimentally to form in vivo pathologic light-chain deposits were shown to undergo high-order self-association and form high molecular weight aggregates. In contrast, of five nonpathologic proteins, one showed polymerization under the chromatographic conditions used. The correlation between the in vivo results achieved by size-exclusion chromatography and that found in vivo provides (i) a rapid diagnostic method to identify potential nephrotoxic or amyloidogenic Bence Jones proteins and (ii) an experimental means to gain new insight into the physicochemical basis of light-chain aggregation and the treatment of those invariably fatal disorders associated with pathologic light-chain deposition.
Dimensionality-reduction using connectionist networks (1989)

A method is presented for using connectionist networks of simple computing elements to discover a particular type of constraint in multidimensional data. Suppose that some data source provides samples consisting of n-dimensional feature-vectors, but that this data all happens to lie on an m-dimensional surface embedded in the n-dimensional feature space. Then occurrences of data can be more concisely described by specifying an m-dimensional location of the embedded surface than by reciting all n components of the feature vector. The recording of data in such a way is known as dimensionality-reduction. A method is presented for performing dimensionality-reduction in a wide class of situations for which an assumption of linearity need not be made about the underlying constraint surface. The method takes advantage of self-organizing properties of connectionist networks of simple computing elements. The authors present a scheme for representing the values of continuous (scalar) variables in subsets of units.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Workshop on mobile computing systems and applications, December 1994 (1995)

The goal of this two-day meeting was to foster interaction between active workers in mobile computing, with a view toward cross-fertilization of ideas. Given the youth of the field, such interactions could have substantial impact on its future direction. In keeping with this goal, the conference organizers chose to have a small, informal workshop rather than a larger and more formal conference. The workshop was sponsored by the IEEE Computer Society Technical Committee on Operating Systems, in cooperation with ACM SIGOPS and USENIX.The workshop was held on Thursday and Friday December 8-9 1994 at the Dream Inn in Santa Cruz. The weather was beautiful and the oceanside locale spectacular --- alas, it is not clear whether these helped or hindered the workshop, since many longing looks were evident on the faces of participants as they gazed out of the windows! The General Chair, Darrell Long, had done an excellent job of selecting the workshop site and setting the stage for the workshop. He was assisted in local arrangements by two student volunteers, Jim Cummiskey and Chane Fullmer.What follows is a summary of the discussions that took place during the workshop. It is based on notes taken by four student volunteers (Peter Grillo, C.K. Toh, Adrian Friday, and N. Asokan). They did an excellent job of taking detailed and complete notes. Any errors or omissions in this document are certainly my responsibility, not theirs.This digest is intended to be a supplement to the papers in the proceedings, not a substitute. Rather than producing a verbatim transcript, I've tried to focus on those interactions that seemed most insightful, controversial or evoked most response from the audience. Such a report must, by its very nature, be subjective. I've tried to be as objective as possible, but I'm sure there are places where my personal biases show through. My apologies in advance if you attended the workshop and your favorite comment, question or discussion isn't mentioned here.
Monoclonal antibodies detect conformationl abnormality of uracil DNA glycosylase in Bloom's syndrome cells (1987)

The immunoreactivity of normal human and Bloom's syndrome uracil DNA glycosylase was examined using a series of three anti-human placental uracil DNA glycosylase monoclonal antibodies. Immunoreactivity was determined by three separate and independent criteria: enzyme-linked immunosorbent assay (ELISA), enzyme inhibition studies and immunoblot analysis. As defined by each criteria, normal human uracil DNA glycosylase was immunoreactive with each antibody (37.04.12, 40.10.09 and 42.08.07). In contrast, each glycosylase purified from two separate non-transformed Bloom's syndrome cell strains was not reactive with antibody 40.10.09. First, no ELISA reactivity was observed with each glycosylase protein. Second, catalysis by each Bloom's syndrome glycosylase was not inhibited by antibody 40.10.09. However, each Bloom's syndrome enzyme was immunoreactive with antibodies 37.04.12 and 42.08.07. No immunoreactive glycosylase species was observed during the induction of the Bloom's syndrome enzyme during cell proliferation. However, immunoreactivity of the denatured Bloom's syndrome enzyme with 40.10.09 antibody was observed by immunoblot analysis. These results suggest that Bloom's syndrome uracil DNA glycosylase is characterized by a structural alteration in the native glycosylase protein secondary to the primary antigenic site recognized by the 40.10.09 antibody. This altered antigenicity may provide an immunological marker for the identification of this human genetic syndrome.
Aza‐scanning of the Potent Melanocortin Receptor Agonist Ac‐His‐d‐Phe‐Arg‐Trp‐NH2 (2006)

The melanocortin pathway is an important participant in the regulation of skin pigmentation, steroidogenesis, obesity, energy homeostasis, and exocrine gland function. Melanocortin agonists contain the putative sequence 'His-Phe-Arg-Trp', which has been designated as the 'message' sequence for melanocortin peptides, and this sequence has been hypothesized to adopt a bioactive reverse turn conformation. Exploring the relationship between its structure and biological activity, we report the synthesis and evaluation of seven aza-analogs of the potent melanocortin receptor agonist Ac-His-D-Phe-Arg-Trp-NH2. Aza-amino acids, in which the alpha-carbon was replaced by nitrogen, were inserted along the peptide sequence to probe the importance of local configuration and turn conformation on the biology of this tetrapeptide. Although systematic substitution of aza-amino acids for the D-Phe and Arg residues led to a significant loss of activity relative to the parent peptide for all melanocortin receptor subtypes examined, substitution of aza-amino acids at the C-terminal Trp residue gave analogs equipotent to the parent peptide. In summary, the aza-scan has demonstrated that recognition of this tetrapeptide by the melanocortin receptors is particularly sensitive to modifications of configuration and conformation at the D-Phe and Arg residues versus the Trp amino acid. In light of aza-residues imparting resistance from enzymatic degradation, C-terminal aza-amino acid analogs may be used to design new peptide mimics with enhanced metabolic stability.
The lipase/acyltransferase from Candida parapsilosis (2002)

Candida parapsilosis has been previously shown to produce a lipase (i.e. able to catalyze efficiently the hydrolysis of insoluble lipid esters such as triacylglycerols) that preferentially catalyses transfer reactions such as alcoholysis in the presence of suitable nucleophiles other than water, even in aqueous media with high (> 0.9) water thermodynamic activity. The present work describes the cloning and the overexpression of the gene coding for this enzyme. Two ORFs (CpLIP1 and CpLIP2) were isolated. The deduced 465-amino-acid protein sequences contained the consensus motif (G-X-S-X-G) which is conserved among lipolytic enzymes. Only one of the two deduced proteins (CpLIP2) contained peptide sequences obtained from the purified lipase/acyltransferase. Homology investigations showed that CpLIP2 has similarities principally with 11 lipases produced by C. albicans (42-61%) and the lipase A from Candida antarctica (31%) but not with the other lipases sequenced so far. Both CpLIP1 and CpLIP2 were expressed in Saccharomyces cerevisiae, but only CpLIP2 coded for an active protein. The substrate specificity and the catalytic behavior of purified recombinant CpLIP2, with or without a C-terminal histidine tag, were not changed compared to those of the native lipase.
Structure-Based Discovery of M-89 as a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein–Protein Interaction (2019)

Inhibition of the menin-mixed lineage leukemia (MLL) protein-protein interaction is a promising new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein our structure-based design, synthesis, and evaluation of a new class of small-molecule inhibitors of the menin-MLL interaction (hereafter called menin inhibitors). Our efforts have resulted in the discovery of highly potent menin inhibitors, as exemplified by compound <b>42</b> (M-89). M-89 binds to menin with a <i>K</i><sub>d</sub> value of 1.4 nM and effectively engages cellular menin protein at low nanomolar concentrations. M-89 inhibits cell growth in the MV4;11 and MOLM-13 leukemia cell lines carrying MLL fusion with IC<sub>50</sub> values of 25 and 55 nM, respectively, and demonstrates >100-fold selectivity over the HL-60 leukemia cell line lacking MLL fusion. The determination of a co-crystal structure of M-89 in a complex with menin provides the structural basis for their high-affinity interaction. Further optimization of M-89 may lead to a new class of therapy for the treatment of MLL leukemia.
Dietary factors and pulmonary function: a cross sectional study in middle aged men from three European countries (1999)

In three European countries a high intake of fruit and vegetables was positively associated with pulmonary function. A high intake of all three antioxidants tended to be positively associated with pulmonary function before, but not after, adjustment for energy intake. Associations of individual antioxidants with pulmonary function were not consistent across countries.
The Effects of Lithium, Valproic Acid, and Carbamazepine During Pregnancy and Lactation (2001)

The chronic, complex, and episodic course of bipolar mood disorder presents a particularly formidable challenge to the clinician making a treatment plan for the onset or recurrence of the illness during pregnancy and lactation. Women treated with anti-manic drugs who become pregnant are commonly considered to be at high risk for fetal complications during the pregnancy or during lactation. The risks of antimanic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer-term neurobehavioral sequela. The use of medications during pregnancy and lactation requires critical attention to the timing of exposure, dosage, duration of use, and fetal susceptibility. The postnatal period is a time of increased onset and relapse of mental illness. No antimanic drug can be proven completely safe. Prescribing antimanic medications with a long safety record, avoiding exposure in the first trimester; avoiding multidrug regimens, and prescribing the lowest dose for the shortest duration will minimize the fetal risk. This review considers treatment with lithium, valproic acid, and carbamazepine. It assesses the risk to the fetus, the perinatal risks for the infant, the risks associated with treatment during the puerperium and breast-feeding, and the risks to the later development of the child.
Against the Rules: Human Keratin K80 (2010)

Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. K80 possesses a number of highly unusual properties. Structurally, it is distinctly closer to type II hair keratins than to type II epithelial keratins. Nonetheless, it is found in virtually all types of epithelia (stratified keratinizing/non-keratinizing, hard-keratinizing, as well as non-stratified tissues, and cell cultures thereof). This conspicuously broad expression range implies an unprecedented in vivo promiscuity of K80, which involves more than 20 different type I partners for intermediate filament (IF) formation. Throughout, K80 expression is related to advanced tissue or cell differentiation. However, instead of being part of the cytoplasmic IF network, K80 containing IFs are located at the cell margins close to the desmosomal plaques, where they are tightly interlaced with the cytoplasmic IF bundles abutting there. In contrast, in cells entering terminal differentiation, K80 adopts the "conventional" cytoplasmic distribution. In evolutionary terms, K80 is one of the oldest keratins, demonstrable down to fish. In addition, KRT80 mRNA is subject to alternative splicing. Besides K80, we describe a smaller but fully functional splice variant K80.1, which arose only during mammalian evolution. Remarkably, unlike the widely expressed K80, the expression of K80.1 is restricted to soft and hard keratinizing epithelial structures of the hair follicle and the filiform tongue papilla.
Il-7 supports D-J but not V-DJ rearrangement of TCR-β gene in fetal liver progenitor cells (1996)

The rearrangement of TCR-beta gene, one of the earliest events in T cell development, consists of two consecutive steps: D-J rearrangement and V-DJ rearrangement. The present study examined the signals supporting D-J beta and V-DJ beta rearrangements during early T cell development from progenitor cells that reside in fetal liver. We have found that there is an interval of 1 to 2 days between D-J beta and V-DJ beta rearrangements during the early T cell development from fetal liver progenitor cells in deoxyguanosine-treated thymus lobes. We have also found that IL-7, a cytokine expressed in the subcapsular area of the thymus, can promote D-J beta rearrangement of fetal liver progenitor cells, and that anti-IL-7 and anti-IL-7R Abs inhibit the D-J beta rearrangement and further T cell development of fetal liver progenitor cells in the thymus environment. Interestingly, unlike the thymus environment, IL-7 alone was not capable of supporting V-DJ beta rearrangement in the fetal liver cell cultures. These results indicate that D-J beta rearrangement during fetal liver-derived early T cell development is supported in the thymus by IL-7. Furthermore, the present results demonstrate that IL-7, supporting D-J beta rearrangement, does not promote V-DJ beta rearrangement of fetal liver progenitor cells, suggesting that intrathymic molecules promoting V-DJ beta rearrangement are distinct from IL-7 that supports the D-J beta rearrangement.
Interaction of urokinase‐type plasminogenactivator (u‐PA) with its cellular receptor (u‐PAR) induces phosphorylation on tyrosine of a 38 kDa protein (1993)

We demonstrate by immunoprecipitation that u-PAR is associated with a 38 kDa protein that is phosphorylated on tyrosine after u-PA treatment of cells. As tyrosine phosphorylation is the hallmark of many signal transduction pathways that promote growth and differentiation, these data suggest that u-PA, besides its role as a regulatory protease, might act as a para- or autocrine hormone.
The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia (2012)

Increased systemic inflammation in sPE and SIR does not correlate with increased anti-angiogenic factors, which were specifically elevated in sPE indicating that excessive systemic inflammation is unlikely to be the main contributor to severe preeclampsia.
Petri Net Modeling of the Cooperation Behavior of a Driver and a Copilot in an Advanced Driving Assistance System (2011)

As the traffic on roads becomes increasingly heavy, driving safety has widely become a concern. Thus, an advanced driving-assistance system (ADAS) becomes much more important, because it can improve driving safety. It is composed of a human driver and an automated system called a copilot. To make it effective, they should properly cooperate. Hence, it is very important to define and model their cooperation behavior such that an ADAS can effectively be designed and realized. This paper presents the colored hybrid Petri net (CHPN) model to describe their cooperation behavior. It shows how switch between the driver and the copilot should be done to control the vehicle. The model is shown to be deadlock-free and conflict-free. Therefore, it is useful for ADAS design, analysis, and simulation.
Tumor progression in the human melanocytic system. (1989)

The isolation and routine tissue culture of melanocytic cells from normal skin, precursor nevi, primary and metastatic melanomas has allowed the experimental study of different stages of tumor progression. Characteristic differences between cultured normal melanocytes and highly malignant metastatic melanoma cells were: 1) limited life span for normal melanocytes and non-malignant nevus cells versus infinite growth for malignant melanoma cells; 2) inability to grow anchorage-independently versus high colony forming-efficiency in soft agar; 3) non-tumorigenicity versus tumorigenicity in athymic nude mice; 4) dependence on exogenous growth factors and other mitogens versus autonomous growth in protein-free medium; 5) expression of melanocyte-associated antigens versus expression of melanoma-associated antigens; and 6) diploid karyotype versus non-random chromosomal abnormalities. The only major distinction found between advanced primary and metastatic melanomas was that only metastatic melanoma cells proliferated continuously in the absence of growth factors or other proteins. However, advanced primary melanoma cells could be clearly distinguished from dysplastic nevus cells by their growth behavior and growth factor requirements. Only limited information is available on the biologic, genetic, immunologic and molecular properties of dysplastic nevus cells and early (radial growth phase) primary melanoma cells but these cells appear to differ markedly from advanced primary and metastatic cells. The availability of cells from sequential steps of tumor progression in the human melanocytic system offers a unique experimental model for the study of malignant transformation.