gebhart/patrepeval huggingface dataset:
Biologic activities of natural and synthetic type I interferons. (1997)

Because alpha-interferon (IFN-alpha) has a number of therapeutic applications in the treatment of various human cancers and diseases of viral origin, an understanding of how this family of proteins interacts with cells to induce their pleiotropic biologic activities is essential. Available data suggest that recombinant IFN-alphas from both natural and synthetic genes bind to a common cell surface receptor and induce antiviral activity in a variety of cell lines. IFN-alphas were found to differ significantly in their abilities to bind to cells; this difference varied with the types of IFN-alpha and cell type used. Consensus interferon (IFN-con1), a nonnaturally occurring synthetic IFN, and IFN-alpha2b competed about equally well for receptor binding sites on Daudi and CaKi cells and were followed by IFN-alpha8 in the ability to compete. Results of affinity cross-linking experiments indicated that all three IFN-alphas interacted similarly with the multichain IFN-alpha receptor. IFN-alpha7, however, competed poorly for binding sites on both cell lines. Each of the IFN-alphas tested displayed discrete biologic differences, which also varied with the assay system used. IFN-con1 and IFN-alpha2b displayed similar antiviral activities on CaKi cells using vesicular stomatitis virus; the viral activities of these IFNs were significantly greater than those of IFN-alpha7 or IFN-alpha8. Studies with murine transfectants demonstrated significant differences in the various IFNs to interact with the IFN-alpha receptor-1 chain of the type I IFN receptor. It is yet to be established, however, that these various in vitro distinctions result in differences in clinical benefit or toxicity between the various subtypes.
Genetic variants of human serum albumin: molecular defects and biological stability. (1995)

Because of recent studies, more heritable structural variants of serum albumin are known than for any other human protein except haemoglobin. However, alloalbumins are benign and thus they are detected only by screening of blood proteins in studies of population genetics or during routine clinical electrophoresis. We report the results of a collaborative study undertaken on genetic variants to define the structural changes and correlate these with the molecular properties of albumin. Our strategy consists in CNBr cleavage of the alkylated purified variants followed by isoelectric focusing (IEF) analysis to identify the fragment in which the substitution occurs. The abnormal peptide is then purified and digested with trypsin or V8 protease. A map of the digests is obtained by Rp-HPLC, the variant peptide is purified, and its amino-acid composition and sequence are determined. This procedure has so far allowed the identification of the molecular defects in 20 among the 26 alloalbumins detected in Italy. In the present study the mutations of the characterized variants are correlated with their frequency, geographic distribution, and biological stability. Point mutations, with only a few exceptions which are discussed, do not affect the stability of the protein. Alterations at the N-terminal, as in the case of proalbumins or Arg-Albumin, and extensive modifications at the C-terminal of the molecule, as well as changes involving the disulfide bridges, reduce the amount of the circulating protein.
TIGR Gene Indices clustering tools (TGICL): a softwaresystem for fast clustering of large EST datasets (2003)

TGICL is a pipeline for analysis of large Expressed Sequence Tags (EST) and mRNA databases in which the sequences are first clustered based on pairwise sequence similarity, and then assembled by individual clusters (optionally with quality values) to produce longer, more complete consensus sequences. The system can run on multi-CPU architectures including SMP and PVM.
Demonstration that the leukocyte common antigen (CD45) is a protein tyrosine phosphatase (1988)

It has been proposed on the basis of amino acid sequence homology that the leukocyte common antigen CD45 represents a family of catalytically active, receptor-linked protein tyrosine phosphatases [Charbonneau, H., Tonks, N. K., Walsh, K. A., & Fischer, E. H. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7182-7186]. The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. First, a mouse monoclonal antibody to CD45 (mAb 9.4) specifically eliminated, by precipitation, PTPase activity from a high Mr fraction containing CD45, prepared by gel filtration (Sephacryl S200) of a Triton X-100 extract of human spleen. Second, PTPase activity was demonstrated in a highly purified preparation of CD45 that was eluted with a high pH buffer from an affinity column, constructed from the same antibody. Third, on sucrose density gradient centrifugation, PTPase activity was only found in those fractions that contained CD45 as determined by Western analysis. When CD45 was caused to aggregate, first by reacting it with mAb 9.4 and then adding a secondary, cross-linking anti-mouse mAb, the PTPase activity shifted to the same higher Mr fractions that contained CD45. No shift in CD45 or PTPase was observed following addition of a control IgG2a. On this basis, it is concluded that CD45 is a protein tyrosine phosphatase.
Germ Line Fanconi Anemia Complementation Group C Mutations and Pancreatic Cancer (2005)

Biallelic mutations in Fanconi anemia complementation group genes disrupt DNA repair and result in the complex Fanconi anemia phenotype. In addition, germ line mutations in the BRCA2/FANCD1 Fanconi anemia complementation group gene have also been implicated in predisposition to a number of cancers including pancreatic cancer. The recent identification of FANCC and FANCG mutations in resected pancreatic tumors selected for loss of heterozygosity on chromosome 9, some of which were present in the germ line DNA, suggests that inactivation of these and other Fanconi complementation group genes may contribute to pancreatic cancer. To further assess the relevance of FANCC and FANCG mutations to pancreatic cancer we conducted a mutation screen of these genes in DNA from blood of 421 sequentially collected pancreatic cancer cases diagnosed at the Mayo Clinic. Two truncating FANCC mutations but no truncating FANCG mutations were identified in young onset (<55 years) pancreatic cancer cases with no family history of pancreatic cancer. Both mutations were associated with loss of heterozygosity of the wild-type allele in corresponding pancreatic tumors. In addition, no truncating mutations were identified in germ line DNA from blood of 658 control individuals undergoing routine colonoscopy. Taken together these data support the assertion that inherited mutations in FANCC can predispose to pancreatic cancer.
Room-temperature repositioning of individual C60 molecules at Cu steps: Operation of a molecular counting device (1996)

C60 molecules absorbed on a monoatomic Cu step have been reversibly repositioned at room temperature with the tip of a scanning tunneling microscope by performing controlled displacements along the step direction. We demonstrate the feasibility of building an abacus on the nanometer scale using single molecules as ‘‘counters,’’ Cu monoatomic steps as ‘‘rods’’ that constrain the molecular motion to one dimension, and the scanning tunneling microscope as an ‘‘actuator’’ for counting operations.
Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology (2017)

Cellular processes often depend on interactions between proteins and the formation of macromolecular complexes. The impairment of such interactions can lead to deregulation of pathways resulting in disease states, and it is hence crucial to gain insights into the nature of macromolecular assemblies. Detailed structural knowledge about complexes and protein-protein interactions is growing, but experimentally determined three-dimensional multimeric assemblies are outnumbered by complexes supported by non-structural experimental evidence. Here, we aim to fill this gap by modeling multimeric structures by homology, only using amino acid sequences to infer the stoichiometry and the overall structure of the assembly. We ask which properties of proteins within a family can assist in the prediction of correct quaternary structure. Specifically, we introduce a description of protein-protein interface conservation as a function of evolutionary distance to reduce the noise in deep multiple sequence alignments. We also define a distance measure to structurally compare homologous multimeric protein complexes. This allows us to hierarchically cluster protein structures and quantify the diversity of alternative biological assemblies known today. We find that a combination of conservation scores, structural clustering, and classical interface descriptors, can improve the selection of homologous protein templates leading to reliable models of protein complexes.
Coherent light scattering by in vitro cell arrays observed with angle-resolved low-coherence interferometry (2005)

Angle-resolved low coherence interferometry enables depth-resolved measurements of scattered light. The scattered light measurements can be used to recover structural information from sub-surface layers, such as the size of cell nuclei. Measurements of nuclear morphology, however, can be complicated by coherent scattering between adjacent cell nuclei. Previous studies have eliminated this component by applying a window filter to Fourier transformed data based upon the justification that the coherent scattering must necessarily occur over length scales greater than the cell nucleus size. To fully study this effect, we now present results of experiments designed to test the validity of this approach. We examine light scattered by regular cell arrays, created using stamped adhesive micro-patterned substrates. By varying the array spacing, the influence of cell-to-cell correlations on light scattering distributions is determined. The impact on nuclear morphology measurements within intact tissue samples is discussed.
Cannabinoids and appetite stimulation (1994)

Appetite stimulation by cannabinoids is highly variable. Four within-subject design studies explored the effects of age, gender, satiety status, route of drug administration, and dose on intake. One study involved a single oral administration of active drug (15 mg males, 10 mg females) or placebo to an age and gender stratified sample of 57 healthy, adult light marijuana users. Eleven subjects received single doses by oral, sublingual, and inhaled routes in a second study. In the third study, 10 subjects ingested a single oral dose in fasted and fed states. A 2.5 mg dose was administered b.i.d. for 3 days by oral and rectal suppository routes in the fourth study. Mean daily energy intake was significantly elevated following chronic dosing by rectal suppository, but not oral capsule, relative to all acute dosing regimens except inhalation. Total daily energy intake was comparable on fed and fasted days, suggesting satiety mechanisms were not impaired by the drug. Subject age, gender, reported "high," and plasma drug level were not significantly associated with drug effects on food intake.
Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. (1999)

To examine the mechanism by which free fatty acids (FFAs) induce insulin resistance in vivo, awake chronically catheterized rats underwent a hyperinsulinemic-euglycemic clamp with or without a 5-h preinfusion of lipid/heparin to raise plasma FFA concentrations. Increased plasma FFAs resulted in insulin resistance as reflected by a approximately 35% reduction in the glucose infusion rate (P < 0.05 vs. control). The insulin resistance was associated with a 40-50% reduction in 13C nuclear magnetic resonance (NMR)-determined rates of muscle glycogen synthesis (P < 0.01 vs. control) and muscle glucose oxidation (P < 0.01 vs. control), which in turn could be attributed to a approximately 25% reduction in glucose transport activity as assessed by 2-[1,2-3H]deoxyglucose uptake in vivo (P < 0.05 vs. control). This lipid-induced decrease in insulin-stimulated muscle glucose metabolism was associated with 1) a approximately 50% reduction in insulin-stimulated insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity (P < 0.05 vs. control), 2) a blunting in insulin-stimulated IRS-1 tyrosine phosphorylation (P < 0.05, lipid-infused versus glycerol-infused), and 3) a four-fold increase in membrane-bound, or active, protein kinase C (PKC) theta (P < 0.05 vs. control). We conclude that acute elevations of plasma FFA levels for 5 h induce skeletal muscle insulin resistance in vivo via a reduction in insulin-stimulated muscle glycogen synthesis and glucose oxidation that can be attributed to reduced glucose transport activity. These changes are associated with abnormalities in the insulin signaling cascade and may be mediated by FFA activation of PKC theta.
To Die or Not to Die (1998)

The death of cells in tissues of humans and other multicellular organisms is neither always abnormal nor always detrimental. Although necrosis ensues at the sites of massive cellular injury, most cells in the body die through a more subtle, noninflammatory, energy-dependent form of cell death called apoptosis. The number of cells in tissues is determined by the homeostatic balance between proliferation of new cells and death of senescent cells; the rates of proliferation and apoptosis vary widely from tissue to tissue. Recent research into the molecular mechanisms of apoptosis has revealed that apoptosis is a genetically programmed process that can become deranged when the components of the cellular apoptotic machinery are mutated or present in inappropriate quantities. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease, and other disorders. Products of genes involved in the regulation and execution of apoptosis are potentially excellent targets for diagnosis and therapeutic intervention in disease processes, and they offer renewed hope for cures and treatments for a wide array of maladies.
Proteome, salicylic acid, and jasmonic acid changes in cucumber plants inoculated with Trichoderma asperellum strain T34 (2007)

Trichoderma spp. is one of the most commonly used biological control agents against plant pathogens. This fungus produces changes in plant metabolism, thus increasing growth and enhancing resistance to biotic and abiotic stresses. However, its modes of action remain to be defined. In the first hours of interaction between cucumber plant roots and Trichoderma asperellum strain T34, salicylic and jasmonic acid levels and typical antipathogenic peroxidase activity increase in the cotyledons to different degrees depending on the applied concentration of the fungi. The use of 2-DE protein profiling and MS analysis allowed us to identify 28 proteins whose expression was affected in cotyledons after cucumber root colonization by Trichoderma applied at high concentrations: 17 were found to be up-regulated while 11 were down-regulated. Proteins involved in ROS scavenging, stress response, isoprenoid and ethylene biosynthesis, and in photosynthesis, photorespiration, and carbohydrate metabolism were differentially regulated by Trichoderma. The proteome changes found in this study help to give an understanding of how Trichoderma-treated plants become more resistant to pathogen attacks through the changes in expression of a set of defence-oriented proteins which can directly protect the plant or switch the metabolism to a defensive, nonassimilatory state.
Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis (2009)

In the clinical management of early-stage cutaneous melanoma, it is critical to determine which patients are cured by surgery alone and which should be treated with adjuvant therapy. To assist in this decision, many groups have made an effort to use molecular information. However, although there are hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the course of cutaneous melanoma, at this time, no molecular method to improve risk stratification is part of recommended clinical practice. To help understand this disconnect, we conducted a systematic review and meta-analysis of the published literature that reported immunohistochemistry-based protein biomarkers of melanoma outcome. Three parallel search strategies were applied to the PubMed database through January 15, 2008, to identify cohort studies that reported associations between immunohistochemical expression and survival outcomes in melanoma that conformed to the REMARK criteria. Of the 102 cohort studies, we identified only 37 manuscripts, collectively describing 87 assays on 62 distinct proteins, which met all inclusion criteria. Promising markers that emerged included melanoma cell adhesion molecule (MCAM)/MUC18 (all-cause mortality [ACM] hazard ratio [HR] = 16.34; 95% confidence interval [CI] = 3.80 to 70.28), matrix metalloproteinase-2 (melanoma-specific mortality [MSM] HR = 2.6; 95% CI = 1.32 to 5.07), Ki-67 (combined ACM HR = 2.66; 95% CI = 1.41 to 5.01), proliferating cell nuclear antigen (ACM HR = 2.27; 95% CI = 1.56 to 3.31), and p16/INK4A (ACM HR = 0.29; 95% CI = 0.10 to 0.83, MSM HR = 0.4; 95% CI = 0.24 to 0.67). We further noted incomplete adherence to the REMARK guidelines: 14 of 27 cohort studies that failed to adequately report their methods and nine studies that failed to either perform multivariable analyses or report their risk estimates were published since 2005.
[Temporary sacral neuromodulation in patients with urge incontinence]. (2001)

We studied the effect of temporary sacral (S3) nerve stimulation in patients with urge incontinence (UI) who were subjected to percutaneous nerve evaluation of the S3 roots as a temporary screening test during 12 days to determine response to neuromodulation. All 18 patients (14 women and 4 men) underwent S3 neuromodulation. The response was assessed by a detailed voiding diary, symptom score and objective outcome was analyzed with urodynamic studies. We noticed a decrease of the average voiding frequency, the number of leakage episodes and pads use per 24 h in 10 days of S3 neuromodulation and returning to baseline symptoms in 20 days after completing S3 neuromodulation. Cystometrograms demonstrated increased cystometric capacity and decreased frequency and amplitude of unstable contractions. Correlation between symptomatic and urodynamic effects was incomplete. Temporary S3 neuromodulation relieved symptoms in UI patients.
Talking to Strangers: Authentication in Ad-Hoc Wireless Networks. (2002)

In this paper we address the problem of secure commu-nication and authentication in ad-hoc wireless networks. This is a difficult problem, as it involves bootstrapping trust between strangers. We present a user-friendly solution, which provides secure authentication using almost any es-tablished public-key-based key exchange protocol, as well as inexpensive hash-based alternatives. In our approach, devices exchange a limited amount of public information over a privileged side channel, which will then allow them to complete an authenticated key exchange protocol over the wireless link. Our solution does not require a public key infrastructure, is secure against passive attacks on the privileged side channel and all attacks on the wireless link, and directly captures users ’ intuitions that they want to talk to a particular previously unknown device in their physical proximity. We have implemented our system in Java for a variety of different devices, communication media, and key exchange protocols. 1.
Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5′-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide (1986)

With the use of a continuous spectrophotometric assay and initial rates determined by the method of Waley [Biochem. J. (1981) 193, 1009-1012] methotrexate was found to be a non-competitive inhibitor, with Ki(intercept) = 72 microM and Ki(slope) = 41 microM, of 5-aminoimidazole-4-carboxamide ribotide transformylase, whereas a polyglutamate of methotrexate containing three gamma-linked glutamate residues was a competitive inhibitor, with Ki = 3.15 microM. Pentaglutamates of folic acid and 10-formylfolic acid were also competitive inhibitors of the transformylase, with Ki values of 0.088 and 1.37 microM respectively. Unexpectedly, the pentaglutamate of 10-formyldihydrofolic acid was a good substrate for the transformylase, with a Km of 0.51 microM and a relative Vmax. of 0.72, which compared favourably with a Km of 0.23 microM and relative Vmax. of 1.0 for the tetrahydro analogue. An analysis of the progress curve of the transformylase-catalysed reaction with the above dihydro coenzyme revealed that the pentaglutamate of dihydrofolic acid was a competitive product inhibitor, with Ki = 0.14 microM. The continuous spectrophotometric assay for adenosine deaminase based on change in the absorbance at 265 nm was shown to be valid with adenosine concentrations above 100 microM, which contradicts a previous report [Murphy, Baker, Behling & Turner (1982) Anal. Biochem. 122, 328-337] that this assay was invalid above this concentration. With the spectrophotometric assay, 5-aminoimidazole-4-carboxamide riboside was found to be a competitive inhibitor of adenosine deaminase, with (Ki = 362 microM), whereas the ribotide was a competitive inhibitor of 5'-adenylate deaminase, with Ki = 1.01 mM. Methotrexate treatment of susceptible cells results in (1) its conversion into polyglutamates, (2) the accumulation of oxidized folate polyglutamates, and (3) the accumulation of 5-aminoimidazole-4-carboxamide riboside and ribotide. The above metabolic events may be integral elements producing the cytotoxic effect of this drug by (1) producing tighter binding of methotrexate to folate-dependent enzymes, (2) producing inhibitors of folate-dependent enzymes from their tetrahydrofolate coenzymes, and (3) trapping toxic amounts of adenine nucleosides and nucleotides as a result of inhibition of adenosine deaminase and 5'-adenylate deaminase respectively.
Does the storage time of transfused red blood cells influence regional or global indexes of tissue oxygenation in anemic critically ill patients?* (2004)

Transfusion of stored leukodepleted red cells to euvolemic, anemic, critically ill patients has no clinically significant adverse effects on gastric tonometry or global indexes of tissue oxygenation. These findings do not support the use of fresh red cells in critically ill patients.