gebhart/patrepeval huggingface dataset:
Expanding Proteome Coverage with Orthogonal-specificity α-Lytic Proteases (2014)

Bottom-up proteomics studies traditionally involve proteome digestion with a single protease, trypsin. However, trypsin alone does not generate peptides that encompass the entire proteome. Alternative proteases have been explored, but most have specificity for charged amino acid side chains. Therefore, additional proteases that improve proteome coverage through cleavage at sequences complementary to trypsin's may increase proteome coverage. We demonstrate the novel application of two proteases for bottom-up proteomics: wild type α-lytic protease (WaLP) and an active site mutant of WaLP, M190A α-lytic protease (MaLP). We assess several relevant factors, including MS/MS fragmentation, peptide length, peptide yield, and protease specificity. When data from separate digestions with trypsin, LysC, WaLP, and MaLP were combined, proteome coverage was increased by 101% relative to that achieved with trypsin digestion alone. To demonstrate how the gained sequence coverage can yield additional post-translational modification information, we show the identification of a number of novel phosphorylation sites in the Schizosaccharomyces pombe proteome and include an illustrative example from the protein MPD2 wherein two novel sites are identified, one in a tryptic peptide too short to identify and the other in a sequence devoid of tryptic sites. The specificity of WaLP and MaLP for aliphatic amino acid side chains was particularly valuable for coverage of membrane protein sequences, which increased 350% when the data from trypsin, LysC, WaLP, and MaLP were combined.
Differential tissue expression of Annexin VIII in human (1994)

The expression of Annexins V and VIII by human lung, liver, kidney, skin, heart, uterus, spleen and skeletal muscle was investigated by ELISA. All investigated tissues contained Annexin V. Its level varied with the tissue from around 5 microgram (skin) to approximately 120 micrograms (spleen) per g of wet tissue. Contradistinctionally Annexin VIII expression was less ubiquitous and less abundant. Only lung, skin, liver, and kidney expressed Annexin VIII. Its levels were approximately 100-fold less then the Annexin V levels. Immunohistochemical analysis of lung sections revealed Annexin VIII presence exclusively in the endothelia. Annexin V and VIII levels of cultured human umbilical vein endothelial cells, human arterial smooth muscle cells, human lung fibroblasts and HeLa cells were measured by ELISA. All cell types expressed Annexin V whereas only HeLa cells had detectable levels of Annexin VIII. The results indicate a tissue specific expression of Annexin VIII by lung endothelium, suggesting a highly specialised function.
Facile selective detritylation of 5′‐primary alcohols of pyrimidine nucleosides using tetra‐n‐butylammonium peroxydisulfate (1997)

Tetra-n-butylammonium peroxydisulfate has been found to be a good deprotecting reagent for removal of the trityl group: Treatment of 5′-O-dimethoxytrityl uridine or thymidine with tetra-n-butylammonium peroxydisulfate gave the corresponding dedimethoxytritylated nucleosides in excellent yields under neutral and mild conditions and without causing any side reactions such as cleavage of the glycosidic bond. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8: 435–438, 1997
The Role of Signal Transducer and Activator of Transcription-2 in the Interferon Response (2012)

The signal transducer and activator of transcription-2 (STAT2) was discovered as a cellular component of the DNA binding complex known as interferon (IFN) stimulated gene factor-3. Numerous studies have confirmed that STAT2 operates as a positive regulator in the transcriptional activation response elicited by IFNs. In this article, we highlight the progress made in elucidating the pivotal role of STAT2 in driving the expression of IFN-induced genes, innate antiviral immunity, apoptosis, and cancer. A better understanding of the functional role of STAT2 in the IFN response and how STAT2 is regulated will uncover new clues to its role in diseases.
Angewandte Chemie in Light of the Science Citation Index (2001)

The evaluation of the publications in Angewandte Chemie as well as the journal as a whole, in terms of the numbers of citations in the Science Citation Index (SCI) and the Journal Impact Factor (JIF), are studied with regard to errors resulting from the publication of two editions of the journal.
Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia (2009)

This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons.
Matrix Metalloproteinases and Their Multiple Roles in Alzheimer’s Disease (2014)

Alzheimer's disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), as well as neuronal death and synaptic loss. Matrix metalloproteinases (MMPs) play an important role as inflammatory components in the pathogenesis of AD. MMP-2 might be assumed to have a protective role in AD and is the major MMP which is directly linked to Aβ in the brain. Synthesis of MMP-9 can be induced by Aβ, and the enzymes appear to exert multiple effects in AD in senile plaque homoeostasis. The proaggregatory influence on tau oligomer formation in strategic brain regions may be a potential neurotoxic side effect of MMP-9. MMP-3 levels are correlated to the duration of AD and correlate with the CSF T-tau and P-tau levels in the elderly controls. Elevated brain levels of MMP-3 might result in increased MMP-9 activity and indirectly facilitate tau aggregation. At present, the clinical utility of these proteins, particularly in plasma or serum, as potential early diagnostic biomarkers for AD remains to be established. More research is needed to understand the diverse roles of these proteases to design specific drugs and devise therapeutic strategies for AD.
A rapid cytokinin response assay inArabidopsisindicates a role for phospholipase D in cytokinin signalling (2002)

Seedlings of Arabidopsis thaliana harboring a fusion of the cytokinin-responsive ARR5 gene promoter and the GUS reporter gene were used for a pharmacological approach to study cytokinin signal transduction. The assay was shown to be rapid, sensitive, dose-dependent and highly specific for cytokinins, both adenine and phenylurea derivatives. Numerous inhibitors of known signalling pathways were tested and some were shown to suppress reporter gene induction. Particularly, primary alcohols that specifically inhibit phospholipase D (PLD) partially prevented cytokinin-induced GUS activity and reduced the accumulation of ARR5 gene transcripts. This indicates a role for PLD early during cytokinin signalling.
Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women (1992)

Hormone therapy should probably be recommended for women who have had a hysterectomy and for those with coronary heart disease or at high risk for coronary heart disease. For other women, the best course of action is unclear.
Interrupting Vibrio cholerae infection of human epithelial cells with engineered commensal bacterial signaling (2008)

Vibrio cholerae El Tor serotypes are largely responsible for outbreaks of cholera in the developing world. The infection cycle for some strains of V. cholerae is coordinated, at least in part, through quorum sensing. That is, the expression of virulence genes depends on the concentration of V. cholerae autoinducers cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2). High concentrations of CAI-1 and AI-2 have been shown previously to inhibit virulence gene expression. We have demonstrated here that a commensal bacterium, E. coli Nissle 1917 (Nissle), can be engineered to express CAI-1 (Nissle expresses AI-2 natively) and effectively interrupt V. cholerae virulence. We engineered Nissle to express CAI-1 under control of the lac promoter, and demonstrated inhibition of V. cholerae expression of cholera toxin (CT, as indicated by presence of the CT subunit B (CTB)) and of the toxin co-regulated pilus (TCP, as indicated by the relative transcript of TCP subunit A (TCPA)) in both monocultures of V. cholerae and co-cultures with epithelial cells, Nissle, and V. cholerae. In the model system of Caco-2 epithelia incubated with V. cholerae, we demonstrated that co-cultures with Nissle expressing CAI-1 activity reduced CTB binding to Caco-2 cells by 63% over co-cultures with wild-type Nissle. Further, cultures with Nissle expressing CAI-1 had significantly lower TCPA transcription than controls with wild-type Nissle. These results represent a significant step towards a prophylactic method for combating enteric disease through engineered quorum signaling within a commensal bacterial strain.
Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. (1989)

Mucin glycoproteins are major secretory products of the colon and contain O-linked oligosaccharides synthesized on a polypeptide backbone. The initial step in the synthesis of O-linked oligosaccharides is the addition of N-acetylgalactosamine to serine or threonine residues forming the Tn antigen. This substance can then receive additional carbohydrate residues such as sialic acid to form sialosyl-Tn antigen, or galactose to form T antigen. In the colon, the T antigen is an oncodevelopmental cancer-associated antigen but little is known about Tn and sialosyl-Tn expression. The present comparative immunohistochemical study was performed to analyze the expression of these antigens in fetal, normal adult, and malignant colorectal tissues with an aim toward elucidating whether Tn and sialosyl-Tn are also oncodevelopmental colon cancer-associated antigens and to gain insight into the earliest steps of mucin glycosylation in colonocytes. We used three reagents to detect Tn antigen (two monoclonal antibodies ETn1.01 and CU-1, and one lectin Vicia villosa), two reagents to detect sialosyl-Tn (monoclonal antibodies TKH2 and B72.3) and one to detect T antigen (monoclonal antibody AH9-16). Except for occasional reactivity with VVA and CU-1, cells of normal colonic mucosa did not express Tn, sialosyl-Tn, or T antigens. However, in the transitional mucosa immediately adjacent to cancer, all three antigens were expressed (ranging from 35 to 67% of cases depending upon the reagent). In colon cancers, the percentage of cases expressing each antigen were as follows: Tn 72-81%, sialosyl-Tn 93-96%, and T 71%. Unlike T antigen, which was preferentially expressed by moderately well- and well-differentiated adenocarcinomas, both Tn and sialosyl-Tn antigens were expressed by most histological subsets of colon cancers, including poorly differentiated adenocarcinomas and mucinous (colloid and signet ring cell type) carcinomas. The majority of cancers expressed both Tn and sialosyl-Tn, usually in association with T antigen. Only one cancer lacked all three antigens. Fetal colonic mucosal cells expressed all three antigens, particularly in goblet cell mucin. These results indicate that like T antigen, Tn and sialosyl-Tn are oncodevelopmental cancer-associated antigens in the colon. Moreover, Tn and sialosyl-Tn antigens appear to be useful markers of poorly differentiated adenocarcinomas and mucinous carcinomas: two histological subsets that often fail to express other cancer-associated antigens and that are often associated with a poor clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS)
Binding of N-dansylgalactosamine to the lectin from Erythrina cristagalli as followed by stopped-flow and pressure-jump relaxation kinetics (1985)

The binding kinetics of N-dansylgalactosamine to the lectin from Erythrina cristagalli have been studied using stopped-flow and pressure-jump chemical relaxation by monitoring ligand fluorescence. Both methods gave results which are consistent with a simple bimolecular association reaction. The association rate constant, k + 1 = 4.8 X 10(4) M-1 s-1, is far too low to be controlled by diffusion; the dissociation rate is 0.4-0.66 s-1, depending upon the method of determination and the experimental conditions. Identical reaction-rate parameters were obtained at pH 7.3, where soluble aggregates can be present in the lectin solution and at pH 4.7 where such aggregates are absent. The slow rates of carbohydrate binding seem to be characteristic for most lectins and lend support to the idea that they are evolutionary related and have structurally similar binding sites. Analysis of the relaxation amplitudes of the pressure-jump experiments yielded a molar reaction volume change, delta V0, upon binding of +7 ml/mol. This volume change can be caused by desolvation of the ligand upon binding.
Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor (1999)

Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipoprotein E and -apolipoprotein B antibodies, by chemical methods abrogating lipoprotein/LDL receptor interactions, and by inhibition with the endocytosis inhibitor phenylarsine oxide. Confirmatory evidence was provided by the lack of detectable LDL receptor on cells known to be resistant to BVDV infection. Endocytosis via the LDL receptor was shown to be mediated by complexing of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVDV system indicated that the LDL receptor may be the main but not exclusive means of cell entry of these viruses. Studies on other types of viruses indicated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associate with lipoprotein in the blood. These findings provide evidence that the family of LDL receptors may serve as viral receptors.
Disruption of contactin 4 in three subjects with autism spectrum disorder (2008)

CNTN4 plays an essential role in the formation, maintenance, and plasticity of neuronal networks. Disruption of this gene is known to cause developmental delay and mental retardation. This report suggests that mutations affecting CNTN4 function may be relevant to ASD pathogenesis.
Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells. (1983)

The culture media of three cell lines, a human prostate carcinoma (PC3), a rat Leydig cell tumor (Rice-500), and a rat carcinosarcoma (WRC-256), that were derived from tumors associated with humoral hypercalcemia of malignancy (HHM), were examined for stimulation of adenylate cyclase in ROS 17/2.8 osteoblastic cells and for bone resorptive activity in culture. Cells from a nonhypercalcemic variant of the WRC256 tumor served as control. Extracts from three solid human tumors, a lung adenocarcinoma from a patient with HHM and two adenocarcinoma from normocalcemic patients (lung and colon), were also examined for adenylate cyclase stimulation. We found excellent correlation between stimulation of cyclic AMP accumulation in ROS 17/2.8 cells and bone resorbing activity in culture, or production of HHM in vivo. Stimulation of adenylate cyclase by HHM factors was inhibited by the parathyroid hormone competitive inhibitor, [8norleucyl, 18norleucyl, 34tyrosinyl] bovine parathyroid hormone (3-34) amide.
GPS Pseudolite Signal Design (1994)

Pseudolites (PLs), ground-based satellites transmitting
GPS-like signals, are becoming increasingly useful for a
variety of applications, including differential GPS
correction broadcasting and aircraft precision approach -
Category I, II and III. PLs have the capability to augment
the GPS constellation, providing better geometry for
greater positioning accuracy, reliability, availability,
continuity, and integrity monitoring. In addition they can
be used to speed up integer ambiguity resolution in
differential carrier phase applications, due to the large
geometry change possible with the PL signal.
However the use of PLs is not without its problems, the
most notable being the “near-far problem”. This problem
occurs due to the large dynamic range between a PL and a
user, in contrast with the approximately constant distance
of the GPS satellites from the user. Within some range, a
PL signal can be orders of magnitude more powerful than
the GPS satellite signal, and thus jam a user’s receiver.
The paper discusses the design of a PL signal to mitigate
the near-far problem using CDMA methods. The use of
longer pseudo random (PR) code at C/A code rate, as well
as the use of faster code (P-Code rate) is explored. Longer
codes are formulated by concatenation of length- 1023 Gold
codes, scrambled by a ‘Switching Sequence’. By applying
selected switching sequences one can achieve signal-to-
interference level improvements of up to 6 dB.
Application of P-Code rate sequences shows even larger
improvements, from 23 dB.
Phase II Trial of the Use of Gemcitabine and 5-Fluorouracil in the Treatment of Advanced Pancreatic and Biliary Tract Cancer (2003)

In this phase II trial, we used the combination of gemcitabine and 5-fluorouracil (5-FU) to treat 26 patients: 17 (65%) with advanced pancreatic adenocarcinoma and 9 (35%) with advanced biliary tract adenocarcinoma (10 locally advanced and 16 metastatic); 15 (57.7%) male and 11 (42.3%) female; median age 58 (range, 39–68); median performance status 2 (range, 1–3). A total of 102 cycles were administered (median, 4 per patient). There were 8 objective responses, plus 1 complete response not confirmed by second-look laparotomy, thus the overall objective response rate was 30.7% (95% CI 12%-47%). Among the patients with biliary tract carcinoma, 33% (3/9) had PR. Six (23%) patients had stable disease (SD). All 8 responders and 3 of the patients with SD experienced clinical benefit (42%). The median overall survival was 9 months (range, 6–38), and the 1-year survival rate was 30%. The regimen was very well tolerated. One patient developed reversible World Health Organization grade IV febrile neutropenia. We observed grade III neutropenia in 11 (11%) cycles; grade III thrombocytopenia in 7 (7%) cycles; grade III mucositis in 7 (7%) cycles; and grade III diarrhea in 10 (10%) cycles. Asthenia grades I and II occurred in 30% of cycles and flulike syndrome grade II in 11 (11%) cycles. The combination of gemcitabine and 5-FU in patients with advanced pancreatic or biliary tract cancer produces promising activity and tolerability with the added potential for clinical benefit, and thus warrants further investigation.
Norepinephrine-mediated inhibition of antitumor cytotoxic T lymphocyte generation involves a beta-adrenergic receptor mechanism and decreased TNF-alpha gene expression. (1999)

We have previously shown that norepinephrine (NE) inhibits the in vitro generation of anti-MOPC-315 CTL activity by spleen cells from BALB/c mice rejecting a large MOPC-315 tumor as a consequence of low-dose melphalan (l -phenylalanine mustard (l -PAM)) treatment (l -PAM TuB spleen cells). Since TNF-alpha plays a key role in the generation of antitumor CTL activity in this system, we determined whether NE mediates this inhibition through inhibition of TNF-alpha production. Here, we show that NE inhibits the production of TNF-alpha protein and mRNA by l -PAM TuB spleen cells stimulated in vitro with mitomycin C-treated tumor cells. Flow cytometric analysis of intracellular expression of TNF-alpha revealed substantial NE-mediated decreases in the percentages of TNF-alpha+ cells among CD4+ and CD8+ T cells and F4/80+ activated macrophages. NE inhibition of CTL generation was largely overcome by addition of TNF-alpha to the stimulation cultures. When the beta-adrenergic antagonist propranolol was added to the stimulation cultures of l -PAM TuB spleen cells at a concentration that prevented NE-induced cAMP elevation, the NE-mediated decrease in TNF-alpha mRNA and NE-mediated inhibition of CTL generation were reversed. Collectively, these results suggest that NE inhibits antitumor CTL generation, at least in part, by inhibiting TNF-alpha synthesis through a mechanism(s) involving beta-adrenergic receptor signaling.
New schemes for improving non data-aided symbol timing recovery for QAM receivers in flat fading channels (2002)

In this paper we present a digital symbol timing synchronization algorithm based on maximum likelihood theory. The algorithm can be totally implemented in discrete time either by a DSP processor, or in a VLSI chip. The channel average fade duration (AFD) and level crossing rates (LCR) are incorporated into a new estimation approach that improves the symbol timing recovery. The schemes are: (1) smoothed post processing (SPP) estimates, and (2) fade envelope weighted (FEW) estimates. Both schemes incorporate fading statistics into the symbol estimator in order to enhance the estimate while the signal is in fade. We first present their implementations, then compare their performance using computer simulation experiments.
[Rosacea, acne and other diseases of the seborrheic spectrum]. (2000)

Diseases of seborrhoic origin include rosacea, acne, gram-negative folliculitis, demodex-folliculorum, perioral dermatitis as well as seborrhoic dermatitis. An important prerequisite for adequate therapy is the knowledge of these different diseases. Unfortunately, topic steroids are often applied, resulting in well known corticosteroid side-effects like skin atrophy and teleangiectasias. The different clinical diseases of seborrhoic origin are reviewed here and a treatment guide is presented.
Topological generation and analysis of voltage multiplier circuits (1977)

Voltage multipliers are used for transformerless conversion of an ac input voltage <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\upsilon_i(t)= E \sin \omega t</tex> into a dc output voltage <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V_{out} = nE</tex> , where <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n \geq 2</tex> . This paper investigates the topological properties of voltage multiplier circuits and presents a unified approach for generating new voltage-multiplier circuit structures. In particular, an algorithm is presented for generating <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> -fold voltage multipliers with <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> capacitors and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> diodes. A theorem is presented for finding the dc capacitor voltages by inspection when no load current is drawn. For the case with load, explicit formulas for the output de voltage and the output resistance are given. Using the algorithm developed in this paper, three new voltage quadrupler circuits are generated and shown to have an output resistance only one-half of the conventional ladder quadrupler circuit.