gebhart/patrepeval huggingface dataset:
Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly‐available database (2005)

HUPO initiated the Plasma Proteome Project (PPP) in 2002. Its pilot phase has (1) evaluated advantages and limitations of many depletion, fractionation, and MS technology platforms; (2) compared PPP reference specimens of human serum and EDTA, heparin, and citrate-anti-coagulated plasma; and (3) created a publicly-available knowledge base (www.bioinformatics.med.umich.edu/hupo/ppp; www.ebi.ac.uk/pride). Thirty-five participating laboratories in 13 countries submitted datasets. Working groups addressed (a) specimen stability and protein concentrations; (b) protein identifications from 18 MS/MS datasets; (c) independent analyses from raw MS-MS spectra; (d) search engine performance, subproteome analyses, and biological insights; (e) antibody arrays; and (f) direct MS/SELDI analyses. MS-MS datasets had 15 710 different International Protein Index (IPI) protein IDs; our integration algorithm applied to multiple matches of peptide sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified with two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, OMIM, and immunoassay-based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs. We recommend use of plasma instead of serum, with EDTA (or citrate) for anticoagulation. To improve resolution, sensitivity and reproducibility of peptide identifications and protein matches, we recommend combinations of depletion, fractionation, and MS/MS technologies, with explicit criteria for evaluation of spectra, use of search algorithms, and integration of homologous protein matches. This Special Issue of PROTEOMICS presents papers integral to the collaborative analysis plus many reports of supplementary work on various aspects of the PPP workplan. These PPP results on complexity, dynamic range, incomplete sampling, false-positive matches, and integration of diverse datasets for plasma and serum proteins lay a foundation for development and validation of circulating protein biomarkers in health and disease.
Replacing the first epidermal growth factor-like domain of factor IX with that of factor VII enhances activity in vitro and in canine hemophilia B. (1997)

Using the techniques of molecular biology, we made a chimeric Factor IX by replacing the first epidermal growth factor-like domain with that of Factor VII. The resulting recombinant chimeric molecule, Factor IXVIIEGF1, had at least a twofold increase in functional activity in the one-stage clotting assay when compared to recombinant wild-type Factor IX. The increased activity was not due to contamination with activated Factor IX, nor was it due to an increased rate of activation by Factor VIIa-tissue factor or by Factor XIa. Rather, the increased activity was due to a higher affinity of Factor IXVIIEGF1 for Factor VIIIa with a Kd for Factor VIIIa about one order of magnitude lower than that of recombinant wild-type Factor IXa. In addition, results from animal studies show that this chimeric Factor IX, when infused into a dog with hemophilia B, exhibits a greater than threefold increase in clotting activity, and has a biological half-life equivalent to recombinant wild-type Factor IX.
Phosphorylation of recombinant tau by cAMP-dependent protein kinase. Identification of phosphorylation sites and effect on microtubule assembly. (1993)

Tau protein is an integral component of paired helical filaments, a pathological feature of Alzheimer's disease. tau extracted from these filaments displays decreased electrophoretic mobility due to aberrant phosphorylation. Here we show that recombinant human tau can be phosphorylated by cAMP-dependent protein kinase resulting in decreased electrophoretic mobility. Phosphorylation of tau by cAMP-dependent protein kinase caused a 92% decrease in the maximum rate of tau-induced microtubule assembly. The sites of phosphorylation were identified by digesting phosphorylated tau with proteases, separating the peptides by reversed-phase HPLC, and analyzing the isolated peptides by liquid-secondary ion mass spectrometry and solid-phase N-terminal sequencing. Five phosphorylation sites were identified, two of which were located within microtubule binding domains. One site was previously shown to be the sole phosphorylation site for CaM kinase II; phosphorylation at this site by CaM kinase II was sufficient to cause decreased electrophoretic mobility (Steiner, B., Mandelkow, E. M., Biernat, J., Gustke, N., Meyer, H. E., Schmidt, B., Mieskes, G., Soling, H. D., Drechsel, D., Kirschner, M. W., Goedert, M., and Mandelkow, E. (1990) EMBO J. 9, 3539-3544). Thus two different second messenger-dependent protein kinases can phosphorylate tau at the same site and induce a shift in tau mobility like that seen in Alzheimer's disease.
Tau is a candidate gene for chromosome 17 frontotemporal dementia (1998)

Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, bradykinesia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21-22 in a 2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP-17 families revealed nine DNA sequence variants, eight of which were also identified in controls and are thus polymorphisms. A ninth variant (Val279Met) was found in one FTDP-17 family but not in the second FTDP-17 family. Three lines of evidence indicate that the Val279Met change is an FTDP-17 causative mutation. First, the mutation site is highly conserved, and a normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co-segregates with the disease in family A. Third, the mutation is not found in normal controls.
Inhibition of 15-PGDH prevents ischemic renal injury by the PGE2/EP4signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2Areceptors (2020)

In the present study, we demonstrated the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia-reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. PGE<sub>2</sub> is vasodilatory in the kidney, but it is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE<sub>2</sub> levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI renal morphology injury scores and tubular apoptosis and markedly reduced biomarkers of renal injury that included blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high-mobility group box 1, and malondialdehyde. Protective effects of SW033291 were mediated by PGE<sub>2</sub> signaling, as they could be blocked by pharmacological inhibition of PGE<sub>2</sub> synthesis. Consistent with activation of PGE<sub>2</sub> signaling, SW033291 induced renal levels of both EP<sub>4</sub> receptors and cAMP, along with other vasodilatory effectors, including AMP, adenosine, and the adenosine A<sub>2A</sub> receptor. The protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Inhibition of 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.
The unfolded protein response sensor IRE1α is required at 2 distinct steps in B cell lymphopoiesis (2005)

B lymphocyte differentiation is coordinated with the induction of high-level Ig secretion and expansion of the secretory pathway. Upon accumulation of unfolded proteins in the lumen of the ER, cells activate an intracellular signaling pathway termed the unfolded protein response (UPR). Two major proximal sensors of the UPR are inositol-requiring enzyme 1alpha (IRE1alpha), an ER transmembrane protein kinase/endoribonuclease, and ER-resident eukaryotic translation initiation factor 2alpha (eIF2alpha) kinase (PERK). To elucidate whether the UPR plays an important role in lymphopoiesis, we carried out reconstitution of recombinase-activating gene 2-deficient (rag2-/-) mice with hematopoietic cells defective in either IRE1alpha- or PERK-mediated signaling. IRE1alpha-deficient (ire1alpha-/-) HSCs can proliferate and give rise to pro-B cells that home to bone marrow. However, IRE1alpha, but not its catalytic activities, is required for Ig gene rearrangement and production of B cell receptors (BCRs). Analysis of rag2-/- mice transplanted with IRE1alpha trans-dominant-negative bone marrow cells demonstrated an additional requirement for IRE1alpha in B lymphopoiesis: both the IRE1alpha kinase and RNase catalytic activities are required to splice the mRNA encoding X-box-binding protein 1 (XBP1) for terminal differentiation of mature B cells into antibody-secreting plasma cells. Furthermore, UPR-mediated translational control through eIF2alpha phosphorylation is not required for B lymphocyte maturation and/or plasma cell differentiation. These results suggest specific requirements of the IRE1alpha-mediated UPR subpathway in the early and late stages of B lymphopoiesis.
Trusted distribution of software over the Internet (2002)

The paper offers a solution to a problem of software distribution on the lnternet. The problem is that malicious software can be posted to the public with no accountability. When this software is run, it inherits the privileges of the user who runs it. Unfortunately, it is very common for users to execute software obtained on the Internet with no assurance that it is genuine. The solution offered here utilizes a trusted third party that signs certificates to identify the author of a program and to secure its integrity. A detailed design is provided. Finally, Bellcore's Trusted Software Integrity (Betsi) System, an implementation of the design, is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins (2021)

Fluorescently labeled antibody and aptamer probes are used in biological studies to characterize binding interactions, measure concentrations of analytes, and sort cells. Fluorescent nanoparticle labels offer an excellent alternative to standard fluorescent labeling strategies due to their enhanced brightness, stability and multivalency; however, challenges in functionalization and characterization have impeded their use. This work introduces a straightforward approach for preparation of fluorescent nanoparticle probes using commercially available reagents and common laboratory equipment. Fluorescent polystyrene nanoparticles, Thermo Fisher Scientific FluoSpheres, were used in these proof-of-principle studies. Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles, neutralizing the surface charge from - 43 to - 15 mV. A conjugation-annealing handle and DNA aptamer probe were attached to the azide-PEG nanoparticle surface either through reaction of pre-annealed handle and probe or through a stepwise reaction of the nanoparticles with the handle followed by aptamer annealing. Nanoparticles functionalized with DNA aptamers targeting histidine tags and VEGF protein had high affinity (EC<sub>50</sub>s ranging from 3 to 12 nM) and specificity, and were more stable than conventional labels. This protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments.
Nutritional Requirement for Taurine in Patients Receiving Long-Term Parenteral Nutrition (1985)

Animals fed diets lacking the amino acid taurine have low plasma and tissue levels of taurine and ultimately have retinal dysfunction. Since parenteral nutrition does not ordinarily provide taurine, we looked for evidence of taurine deficiency in 21 children and 23 adults undergoing long-term parenteral nutrition at home for an average of 27 +/- 23 (S.D.) months. The fasting plasma taurine level was reduced in children as compared with controls (26 +/- 13 vs. 57 +/- 16 mumol per liter, P less than 0.001). In adults with less than 25 per cent intestinal absorption of the recommended caloric intake, the plasma taurine level was also significantly reduced and correlated inversely with the duration of parenteral nutrition. Electroretinograms were abnormal in each of eight children who were examined. Addition of taurine to the intravenous solutions restored plasma levels to normal in four children; the electroretinograms of three of these children also became normal. The plasma taurine level became abnormally low again in two of three children one year after the intravenous taurine was discontinued. We conclude that children and possibly adults receiving long-term parenteral nutrition have a nutritional requirement for taurine.
Infectious tolerance via the consumption of essential amino acids and mTOR signaling (2009)

Infectious tolerance describes the process of CD4(+) regulatory T cells (Tregs) converting naïve T cells to become additional Tregs. We show that antigen-specific Tregs induce, within skin grafts and dendritic cells, the expression of enzymes that consume at least 5 different essential amino acids (EAAs). T cells fail to proliferate in response to antigen when any 1, or more, of these EAAs are limiting, which is associated with a reduced mammalian target of rapamycin (mTOR) signaling. Inhibition of the mTOR pathway by limiting EAAs, or by specific inhibitors, induces the Treg-specific transcription factor forkhead box P3, which depends on both T cell receptor activation and synergy with TGF-beta.
Innovazione materica e design (2008)

Quante volte, nel ruolo di studenti, docenti o di progettisti professionisti, ci siamo trovati di fronte alla scelta di quale materiale adottare o suggerire per la realizzazione di uno specifico prodotto industriale o di un manufatto architettonico? In realtà dovrebbe essere proprio l'iter progettuale seguito a suggerirci la risposta. Ma se fino a ieri la scelta era ristretta a poche famiglie di materiali, oggi l'avvento di nuove tecnologie ha comportato un proliferazione di materiali più o meno innovativi che spesso sfociano nel prodotto-moda che di per se può distrarre il progettista da valori ben più "alti" che dovrebbero invece essere associati alla realtà del prodotto industriale contemporaneo. Se il progetto di design (o di architettura) venisse maggiormente contestualizzato all'oggi, alle problematiche etiche, industriali, economiche e, non ultime, ambientali che ci troviamo a dover affrontare e risolvere, allora anche i criteri di scelta dovrebbero seguire nuove strade rispetto a quelle percorse sino ad oggi. La nascita recente (si parla di un periodo di non più di dieci anni ad oggi, con punte di sviluppo negli ultimi cinque) di banche dati virtuali e reali di materiali innovativi sofisticati o ricchi di appeal, spesso travalicano le capacità di scelta che un utente progettista può effettuare in modo consapevole. Se da un lato questi tool non sono spesso esaustivi dal punto di vista di informazioni ambientali fornite, dall'altro molti progettisti non sono ancora pronti a vedere oltre la fascinazione e capire i rischi sull'ambiente che vengono innescati da una scelta scorretta. Ma questo è probabilmente da imputare a fattori di marketing (le aziende produttrici dei materiali innovativi non forniscono sempre "dati caldi" sul loro tipo di prodotto) e, non ultima, alla ancora scarsa capacità da parte dei progettisti di imporre dei vincoli alle loro stesse scelte o ai produttori cui fanno riferimento. Il distacco esistente tra "strumento banca dati" e "utente progettista" è preoccupante, quando invece una più diretta collaborazione fra gli interessati condurrebbe a risultati positivi dell'intero ciclo progettuale/produttivo nei confronti dell'ambiente. Obiettivo di questo scritto è quello di provare a sensibilizzare l'attenzione verso questo gap, di evidenziare certe carenze o qualità di fondo presenti nelle banche dati odierne e, parallelamente, di proporre una prima ipotesi di "repertorio materico", sottoforma di lettura critica di alcuni materiali innovativi significativi di ultima generazione, nella speranza che tale operazione possa fungere da embrione e spunto da cui partire per creare e sviluppare in modo più strutturato uno strumento operativo a servizio del progettista ecoconsapevole
Phonon-pumped terahertz gain in n-type GaAs/AlGaAs superlattices (2001)

Local population inversion and far-IR gain are proposed and theoretically analyzed for an unbiased n-doped GaAs/Al0.15Ga0.85As superlattice pumped solely by phonons. The lasing transition occurs at the Brillouin zone boundary of the superlattice wave vector kz between the two conduction minibands CB1 and CB2 of the opposite curvature in kz space. The proposed waveguided structure is contacted above and below by heat sinks at 300 K and 77 K, respectively. Atop the superlattice, a heat buffer layer confines longitudinal optical phonons for enhanced optical-phonon pumping of CB1 electrons. A gain of 345 cm−1 at 4.5 THz is predicted for a doping density of 2.8×1016 cm−3.
Mechanisms of hormonal regulation of hepatic glucose metabolism (1987)

Acute hormonal regulation of liver carbohydrate metabolism mainly involves changes in the cytosolic levels of cAMP and Ca2+. Epinephrine, acting through beta 2-adrenergic receptors, and glucagon activate adenylate cyclase in the liver plasma membrane through a mechanism involving a guanine nucleotide-binding protein that is stimulatory to the enzyme. The resulting accumulation of cAMP leads to activation of cAMP-dependent protein kinase, which, in turn, phosphorylates many intracellular enzymes involved in the regulation of glycogen metabolism, gluconeogenesis, and glycolysis. These are (1) phosphorylase b kinase, which is activated and, in turn, phosphorylates and activates phosphorylase, the rate-limiting enzyme for glycogen breakdown; (2) glycogen synthase, which is inactivated and is rate-controlling for glycogen synthesis; (3) pyruvate kinase, which is inactivated and is an important regulatory enzyme for glycolysis; and (4) the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase bifunctional enzyme, phosphorylation of which leads to decreased formation of fructose 2,6-P2, which is an activator of 6-phosphofructo-1-kinase and an inhibitor of fructose 1,6-bisphosphatase, both of which are important regulatory enzymes for glycolysis and gluconeogenesis. In addition to rapid effects of glucagon and beta-adrenergic agonists to increase hepatic glucose output by stimulating glycogenolysis and gluconeogenesis and inhibiting glycogen synthesis and glycolysis, these agents produce longer-term stimulatory effects on gluconeogenesis through altered synthesis of certain enzymes of gluconeogenesis/glycolysis and amino acid metabolism. For example, P-enolpyruvate carboxykinase is induced through an effect at the level of transcription mediated by cAMP-dependent protein kinase. Tyrosine amino-transferase, serine dehydratase, tryptophan oxygenase, and glucokinase are also regulated by cAMP, in part at the level of specific messenger RNA synthesis. The sympathetic nervous system and its neurohumoral agonists epinephrine and norepinephrine also rapidly alter hepatic glycogen metabolism and gluconeogenesis acting through alpha 1-adrenergic receptors. The primary response to these agonists is the phosphodiesterase-mediated breakdown of the plasma membrane polyphosphoinositide phosphatidylinositol 4,5-P2 to inositol 1,4,5-P3 and 1,2-diacylglycerol. This involves a guanine nucleotide-binding protein that is different from those involved in the regulation of adenylate cyclase. Inositol 1,4,5-P3 acts as an intracellular messenger for Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)
Susceptibility of white-tailed deer (Odocoileus virginianus) to infection with Ehrlichia chaffeensis, the etiologic agent of human ehrlichiosis (1994)

Although more than 320 cases of human ehrlichiosis have been diagnosed in 27 states since 1986, the reservoir host or hosts remain unknown. Since antibodies reactive to Ehrlichia chaffeensis, the etiologic agent of human ehrlichiosis, have been found in white-tailed deer (Odocoileus virginianus), we experimentally evaluated the susceptibilities of four white-tailed deer to infection with E. chaffeensis and Ehrlichia canis, a closely related species. A fifth deer served as a negative control. Isolation and nested PCR amplification results from peripheral blood indicated that E. chaffeensis circulated for at least 2 weeks. The deer developed antibodies to E. chaffeensis by day 10 after inoculation, but there was no indication of clinical disease. Immunohistochemical staining identified E. chaffeensis within macrophage-type cells in lymph nodes. The deer inoculated with E. canis did not become infected and did not seroconvert. These results indicate that white-tailed deer can support an E. chaffeensis infection with resulting rickettsemia of at least 2 weeks. The resistance to infection and the absence of seroconversion upon exposure to E. canis indicate that antibody responses previously detected among wild deer are not E. canis cross-reactions. The role of deer as competent reservoirs in the life cycle of E. chaffeensis remains to be explored with suspected tick vectors.
High-quality streamable free-viewpoint video (2015)

We present the first end-to-end solution to create high-quality free-viewpoint video encoded as a compact data stream. Our system records performances using a dense set of RGB and IR video cameras, generates dynamic textured surfaces, and compresses these to a streamable 3D video format. Four technical advances contribute to high fidelity and robustness: multimodal multi-view stereo fusing RGB, IR, and silhouette information; adaptive meshing guided by automatic detection of perceptually salient areas; mesh tracking to create temporally coherent subsequences; and encoding of tracked textured meshes as an MPEG video stream. Quantitative experiments demonstrate geometric accuracy, texture fidelity, and encoding efficiency. We release several datasets with calibrated inputs and processed results to foster future research.