gebhart/patrepeval huggingface dataset:
Protein Identification by In-Gel Digestion and Mass Spectrometric Analysis (2005)

This chapter describes the analysis of proteins that have been separated by one-(or two-) dimensional gel electrophoresis. In-gel digestion of the protein bands or spots from 1-D gels is detailed. Normally the proteins are digested with trypsin, which cleaves after lysine and arginine. Therefore, due to the specificity of this protease, this results in basic charges at both the amino-terminal and carboxy-terminal ends of most peptides. Not all peptides will have basic groups at both ends, since the N-terminus of an intact protein is commonly blocked by an acetyl or a number of other modifications and the C-terminus may well not be a lysine or arginine. Doubly charged peptide species will, however, predominate. These are of high energy, and fragment more easily in tandem (including ion-trap) mass spectrometry (1) . This results in substantial sequence information, leading to more powerful database analysis. There are programs available, such as Sequest (2), that allow the databases to be searched directly with the peptide fragment data (tandem MS-MS data). This results in a large saving of time and effort, since the data need not be interpreted into tentative peptide sequences, which can be extremely tedious. Glu-C may also be used in place of trypsin, although fewer doubly charged species will result and analysis may be limited to the mass fingerprint data. This is perhaps more suitable to mass analysis on the highly sensitive matrixassisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometers, where few sequence or mass fragment data are obtained in any case.
Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2 (2009)

The mammalian target of rapamycin (mTOR) has emerged as an important therapeutic target for diffuse large B-cell lymphoma (DLBCL), as recent studies have demonstrated that 30% of relapsed patients respond to mTOR inhibitors. Why some lymphomas are resistant is incompletely understood. In the present study, we demonstrated that rapamycin inhibits mTORC1 in DLBCL lines and primary tumors but is minimally cytotoxic. Subsequent investigations revealed that rapamycin also activated eIF4E and the mTORC2 target Akt, suggesting a potential mechanism of rapamycin resistance. Furthermore, knockdown of the mTORC2 component rictor, but not the mTORC1 component raptor, inhibited rapamycin-induced Akt phosphorylation in lymphoma cells. Addition of the histone deacetylase inhibitor (HDI) LBH589 (LBH) overcame rapamycin resistance by blocking mTOR, thus preventing Akt activation. Further studies support the involvement of the protein phosphatase PP1 in LBH-mediated Akt dephosphorylation, which could be mimicked by knockdown of HDAC3. This is the first demonstration that a HDI such as LBH can overcome rapamycin resistance through a phosphatase that antagonizes mTORC2 activation. These results provide a mechanistic rationale for a clinical trial of a combination of HDI and mTOR inhibitors for DLBCL.
Neutralization of IL‐17 rescues amyloid‐β‐induced neuroinflammation and memory impairment (2019)

This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.
Homocysteine in the Plasma of Renal Transplant Recipients: Effects of Cofactors for Methionine Metabolism (1981)

1. Homocysteine which is formed during the metabolism of methionine is readily oxidized and is measured by the amino acid analyser as cysteine—homocysteine mixed disulphide and homocystine. We measured plasma amino acid concentrations after an overnight fast in 27 stable long-term renal transplant recipients and 25 age-and sex-matched normal subjects with particular emphasis on sulphur-containing amino acids. 2. Plasma cysteine—homocysteine mixed disulphide was increased in the patients (mean 6.0 ± sd 3.2 μmol/l; normal 3.1 ± 0.9 μmol/l, P &amp;lt; 0.001) and homocystine was detectable in low concentration (&amp;lt; 1.0 μmol/l) in 24; the elevation in cysteine—homocysteine was related to serum creatinine (r = 0.60, P &amp;lt; 0.002). Cystine was also increased (91.6 ± 29.3 μmol/l; normal subjects 64.0 ± 16.7 μmol/l, P &amp;lt; 0.001), but methionine concentrations were normal. 3. When pyridoxine, folic acid and vitamin B12, cofactors for homocysteine metabolism, were administered sequentially to 11 arbitrarily selected transplant recipients cysteine—homocysteine decreased from 7.3 ± 2.1 to 4.3 ± 0.8 μmol/l (P &amp;lt; 0.001) and homocystine became undetectable. the response coincided with the giving of folic acid and occurred without alteration in serum creatinine and with normal serum folate and vitamin B12 concentrations. 4. in eight patients in whom pretreatment erythrocyte folate was measured, folic acid therapy reduced cysteine—homocysteine from 9.0 ± 3.1 to 5.4 ± 1.6 μmol/l over a 4 week period (P &amp;lt; 0.001), the largest response being in the one patient with subnormal erythrocyte folate; values were in the low-normal or normal range in the other seven. 5. We conclude that plasma homocysteine is increased in renal transplant recipients when serum creatinine is only moderately elevated and that the homocysteine concentrations are decreased by treatment with folic acid, suggesting that both reduced homocysteine excretion and relative shortages of folic acid are responsible.
Role of HMGB1 in apoptosis-mediated sepsis lethality (2006)

Severe sepsis, a lethal syndrome after infection or injury, is the third leading cause of mortality in the United States. The pathogenesis of severe sepsis is characterized by organ damage and accumulation of apoptotic lymphocytes in the spleen, thymus, and other organs. To examine the potential causal relationships of apoptosis to organ damage, we administered Z-VAD-FMK, a broad-spectrum caspase inhibitor, to mice with sepsis. We found that Z-VAD-FMK-treated septic mice had decreased levels of high mobility group box 1 (HMGB1), a critical cytokine mediator of organ damage in severe sepsis, and suppressed apoptosis in the spleen and thymus. In vitro, apoptotic cells activate macrophages to release HMGB1. Monoclonal antibodies against HMGB1 conferred protection against organ damage but did not prevent the accumulation of apoptotic cells in the spleen. Thus, our data indicate that HMGB1 production is downstream of apoptosis on the final common pathway to organ damage in severe sepsis.
Modification of Galactose Oxidase to Introduce Glucose 6-Oxidase Activity (2002)

Combinatorial saturation mutagenesis was applied to create a mutant of the copper enzyme galactose oxidase with novel activity. The selective oxidation of the 6-hydroxyl group of D-glucose to introduce an aldehyde functionality is not catalyzed by known oxidase enzymes but was achieved through mutagenesis experiments. The mutant enzyme produced is a possible starting point for the development of glucose 6-oxidase for synthetic use in food, pharmaceuticals, and materials applications.
Diet during pregnancy and levels of maternal pregnancy hormones in relation to the risk of breast cancer in the offspring (2005)

Birth weight is positively associated with the risk of breast cancer in the offspring and the underlying process is likely to involve the pregnancy endocrine milieu. We have examined the association of diet and related factors during pregnancy with the levels (at the 16th and 27th gestational week) of maternal pregnancy oestradiol, oestriol, sex hormone-binding globulin (SHBG), progesterone and prolactin, in a cohort of 270 Caucasian women who delivered in a major hospital in Boston, USA. Oestradiol and oestriol were not strongly associated with any of the diet-related variables, but SHBG was significantly and consistently related inversely to pre-pregnancy body mass index and weight gain during pregnancy, and positively to vegetable and pulses intake. Pregnancy progesterone was associated positively with alcohol and inversely with polyunsaturated lipid and vitamin B12 intake, whereas pregnancy prolactin was inversely associated with cereal consumption. If the pregnancy hormones studied are indeed involved in the intra-uterine origin of breast cancer, these findings, if confirmed, would focus dietary advice to pregnant women, with a view to reducing the risk of breast cancer in the offspring, towards avoidance of excess energy intake and an emphasis on plant foods. This advice does not contradict current dietary advice on prudent diet during pregnancy and throughout life.
Effect of Annealing Temperature on Film Morphology of Organic–Inorganic Hybrid Pervoskite Solid‐State Solar Cells (2014)

Organic–inorganic hybrid perovskites have attracted attention as successful light harvesting materials for mesoscopic solid‐state solar cells and led to record breaking efficiencies. The photovoltaic performance of these devices is greatly dependent on the film morphology, which in turn is dependent on the deposition techniques and subsequent treatments employed. In this work the perovskite film is deposited by spin‐coating a precursor solution of PbCl 2 and CH 3 NH 3 I (1 to 3 molar ratio) in dimethylformamide. Here, the role of the temperature used in the annealing process required to convert the as deposited solution into the perovskite material is investigated. It is found that the conversion requires sufficiently high temperatures to ensure the vaporization of solvent and the crystallization of the perovskite material. However, increasing the annealing temperature too high leads to the additional formation of PbI 2 , which is detrimental to the photovoltaic performance. Furthermore, the effect of the annealing temperature on the film formation, morphology, and composition is examined and correlated with the photovoltaic performance and device working mechanisms.
Effects of cultivar, nitrogen fertilization rate and environment on yield and grain quality of barley (1998)

Ten barley cultivars, including covered and naked types, varying in their content of total starch, amylose, protein and β-glucan, were grown in different years, at various locations and nitrogen fertilization rates. The barley cultivars showed a large variation in yield (3250–6690 kg ha−1), thousand kernel weight (40–50 g), bulk weight (660–815 g litre−1), starch (51–67% of DM), protein (8–15% of DM), β-glucan (3·5–5·9% of DM) and ash (1·9–2·5% of DM). The naked cultivar SW 8775 had the highest starch content and the high amylopectin cultivar (SW 7142-92, waxy) had the lowest. The waxy starch barleys had the highest protein content, while the normal starch barleys (Golf and Lina) had the lowest protein content at each N-rate. Higher content of β-glucan was found in the waxy cultivars (5·0–5·9% of DM) and high amylose cultivars (5·6–5·9% of DM) than in the other barley cultivars (3·5–4·8% of DM). The results were evaluated by analysis of variance (ANOVA) and principal component analysis (PCA), and both confirmed that nitrogen fertilization rate was of great importance for the protein content. PCA revealed that protein and β-glucan were negatively correlated with starch and yield. The ANOVA showed that the cultivar factor was significant for all variables, but especially for the β-glucan content, which responded differently to the nitrogen fertilization rate during the 2 years. In this study, environmental effects were generally of less importance than the barley cultivars for the different variables. © 1998 Society of Chemical Industry.
Production of target‐specific recombinant human polyclonal antibodies in mammalian cells (2006)

We describe the expression and consistent production of a first target-specific recombinant human polyclonal antibody. An anti-Rhesus D recombinant polyclonal antibody, Sym001, comprised of 25 unique human IgG1 antibodies, was produced by the novel Sympress expression technology. This strategy is based on site-specific integration of antibody genes in CHO cells, using the FRT/Flp-In recombinase system. This allows integration of the expression construct at the same genomic site in the host cells, thereby reducing genomic position effects. Different bioreactor batches of Sym001 displayed highly consistent manufacturing yield, antibody composition, binding potency, and functional activity. The results demonstrate that diverse recombinant human polyclonal antibody compositions can be reproducibly generated under conditions directly applicable to industrial manufacturing settings and present a first recombinant polyclonal antibody which could be used for treatment of hemolytic disease of the newborn and/or idiopathic thrombocytopenic purpura.
Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein. (1992)

A novel trypsin-like protease associated with rat bronchiolar epithelial Clara cells, named Tryptase Clara, was purified to homogeneity from rat lung by a series of standard chromatographic procedures. The enzyme has apparent molecular masses of 180 +/- 16 kDa on gel filtration and 30 +/- 1.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Its isoelectric point is pH 4.75. Studies with model peptide substrates showed that the enzyme preferentially recognizes a single arginine cleavage site, cleaving Boc-Gln-Ala-Arg-4-methylcoumaryl-7-amide most efficiently and having a pH optimum of 7.5 with this substrate. The enzyme is strongly inhibited by aprotinin, diisopropylfluorophosphate, antipain, leupeptin, and Kunitz-type soybean trypsin inhibitor, but inhibited only slightly by Bowman-Birk soybean trypsin inhibitor, benzamidine, and alpha 1-antitrypsin. Immunohistochemical studies indicated that the enzyme is located exclusively in the bronchiolar epithelial Clara cells and colocalized with surfactant. An immunoreactive protein with a molecular mass of 28.5 kDa was also detected in airway secretions by Western blotting analyses, suggesting that the 30-kDa protease in Clara cells is processed before or after its secretion. Proteolytic cleavage of the hemagglutinin of influenza virus is a prerequisite for the virus to become infectious. Tryptase Clara was shown to cleave the hemagglutinin and activate infectivity of influenza A virus in a dose-dependent way. These results suggest that the enzyme is a possible activator of inactive viral fusion glycoprotein in the respiratory tract and thus responsible for pneumopathogenicity of the virus.
Classification with Hybrid Generative/Discriminative Models (2003)

Although discriminatively trained classifiers are usually more accurate when labeled training data is abundant, previous work has shown that when training data is limited, generative classifiers can out-perform them. This paper describes a hybrid model in which a high-dimensional subset of the parameters are trained to maximize generative likelihood, and another, small, subset of parameters are discriminatively trained to maximize conditional likelihood. We give a sample complexity bound showing that in order to fit the discriminative parameters well, the number of training examples required depends only on the logarithm of the number of feature occurrences and feature set size. Experimental results show that hybrid models can provide lower test error and can produce better accuracy/coverage curves than either their purely generative or purely discriminative counterparts. We also discuss several advantages of hybrid models, and advocate further work in this area.
Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. (1994)

Atherosclerosis develops rapidly in patients with diabetes or renal insufficiency. Plasma lipoprotein profiles are frequently abnormal in these conditions and reflect an elevation in the level of the apoprotein B (ApoB)-containing components very low density lipoprotein (VLDL) and low density lipoprotein (LDL). High levels of circulating advanced glycation end products (AGEs) also occur in diabetes and end-stage renal disease (ESRD). These products arise from glucose-derived Amadori products and include AGE-modified peptides (AGE-peptides) which result from the catabolism of AGE-modified tissue proteins. AGE-peptides have been shown to crosslink protein amino groups and to accumulate in plasma as a consequence of renal insufficiency. To address potential mechanisms for the dyslipidemia of diabetes and ESRD, we investigated the possibility that circulating AGEs react directly with plasma lipoproteins to prevent their recognition by tissue LDL receptors. AGE-specific ELISA showed a significantly increased level of AGE-modified LDL in the plasma of diabetic or ESRD patients compared with normal controls. AGE-LDL formed readily in vitro when native LDL was incubated with either synthetic AGE-peptides or AGE-peptides isolated directly from patient plasma. LDL which had been modified by AGE-peptides in vitro to the same level of modification as that present in the plasma of diabetics with renal insufficiency exhibited markedly impaired clearance kinetics when injected into transgenic mice expressing the human LDL receptor. These data indicate that AGE modification significantly impairs LDL-receptor-mediated clearance mechanisms and may contribute to elevated LDL levels in patients with diabetes or renal insufficiency. This hypothesis was further supported by the observation that the administration of the advanced glycation inhibitor aminoguanidine to diabetic patients decreased circulating LDL levels by 28%.
Spatial Localization of the Ebola Virus Glycoprotein Mucin-Like Domain Determined by Cryo-Electron Tomography (2014)

The Ebola virus glycoprotein mucin-like domain (MLD) is implicated in Ebola virus cell entry and immune evasion. Using cryo-electron tomography of Ebola virus-like particles, we determined a three-dimensional structure for the full-length glycoprotein in a near-native state and compared it to that of a glycoprotein lacking the MLD. Our results, which show that the MLD is located at the apex and the sides of each glycoprotein monomer, provide a structural template for analysis of MLD function.
Tissue-Level Thresholds for Axonal Damage in an Experimental Model of Central Nervous System White Matter Injury (2000)

In vivo, tissue-level, mechanical thresholds for axonal injury were determined by comparing morphological injury and electrophysiological impairment to estimated tissue strain in an in vivo model of axonal injury. Axonal injury was produced by dynamically stretching the right optic nerve of an adult male guinea pig to one of seven levels of ocular displacement (Nlevel = 10; Ntotal = 70). Morphological injury was detected with neurofilament immunohistochemical staining (NF68, SM132). Simultaneously, functional injury was determined by the magnitude of the latency shift of the N35 peak of the visual evoked potentials (VEPs) recorded before and after stretch. A companion set of in situ experiments (Nlevel = 5) was used to determine the empirical relationship between the applied ocular displacement and the magnitude of optic nerve stretch. Logistic regression analysis, combined with sensitivity and specificity measures and receiver operating characteristic (ROC) curves were used to predict strain thresholds for axonal injury. From this analysis, we determined three Lagrangian strain-based thresholds for morphological damage to white matter. The liberal threshold, intended to minimize the detection of false positives, was a strain of 0.34, and the conservative threshold strain that minimized the false negative rate was 0.14. The optimal threshold strain criterion that balanced the specificity and sensitivity measures was 0.21. Similar comparisons for electrophysiological impairment produced liberal, conservative, and optimal strain thresholds of 0.28, 0.13, and 0.18, respectively. With these threshold data, it is now possible to predict more accurately the conditions that cause axonal injury in human white matter.
Cloning and analysis of the first cry gene from Bacillus popilliae (1997)

An 80-kDa parasporal crystal protein was detected in protein extracts of sporangia of Bacillus popilliae isolated from a diseased larva of the common cockchafer (Melolontha melolontha L.). Amino acid analysis of tryptic peptides revealed significant homology to the Cry2Aa endotoxins of Bacillus thuringiensis. The gene cryBP1 (cry18Aa1), which codes for the parasporal crystal protein, was found in a putative cry operon on the bacterial chromosome, which contains at least one further (smaller) open reading frame, orf1. The 706-amino-acid-long CryBP1 (Cry18Aa1) protein has a predicted molecular mass of 79 kDa and shows about 40% sequence identity to the Cry2 polypeptides of B. thuringiensis. In the light of published observations which suggest that the parasporal crystal proteins of B. popilliae are slightly toxic to their grub hosts, we propose the following survival strategy of B. popilliae. As an obligate pathogen of grubs, B. popilliae germinates in the gut of a grub and the parasporal crystal proteins are released and activated. The activated protein does not cause colloid osmotic lysis but instead damages the gut wall somehow to allow the vegetative cells to enter the hemolymph more easily. By becoming a parasite, B. popilliae can continue to proliferate efficiently while the living grub provides a food supply. This process is in contrast to that of B. thuringiensis, which rapidly kills the insect and is then limited to growth on the larval carcass.
Distributed source coding: symmetric rates and applications to sensor networks (2002)

We address the problem of distributed source coding using a practical and constructive approach, referred to as distributed source coding using syndromes (DISCUS), with applications to sensor networks. We propose low complexity encoding and decoding methods based on linear codes, to achieve all points in the achievable rate region of the Slepian-Wolf (1973) problem. The extension of these concepts to the construction of Euclidean-space codes is also studied and analyzed for the case of trellis and lattice codes. The performance of these symmetric methods for encoding with a fidelity criterion is shown to be the same as that of asymmetric encoding. Simulations are presented to corroborate these results.
MDMX Overexpression Prevents p53 Activation by the MDM2 Inhibitor Nutlin (2006)

The p53 tumor suppressor plays a key role in maintaining genomic stability and protection against malignant transformation. MDM2 and MDMX are both p53-binding proteins that regulate p53 stability and activity. Recent development of the MDM2 inhibitor Nutlin 3 has greatly facilitated functional analysis of MDM2-p53 binding. We found that although MDMX is homologous to MDM2 and binds to the same region on p53 N terminus, Nutlin does not disrupt p53-MDMX interaction. The ability of Nutlin to activate p53 is compromised in tumor cells overexpressing MDMX. Combination of Nutlin with MDMX siRNA resulted in synergistic activation of p53 and growth arrest. These results suggest that MDMX is also a valid target for p53 activation in tumor cells. Development of novel compounds that are MDMX-specific or optimized for dual-inhibition of MDM2 and MDMX are necessary to achieve full activation of p53 in tumor cells.