gebhart/patrepeval huggingface dataset:
A Mathematical Framework for the Selection of an Optimal Set of Peptides for Epitope-Based Vaccines (2008)

Epitope-based vaccines (EVs) have a wide range of applications: from therapeutic to prophylactic approaches, from infectious diseases to cancer. The development of an EV is based on the knowledge of target-specific antigens from which immunogenic peptides, so-called epitopes, are derived. Such epitopes form the key components of the EV. Due to regulatory, economic, and practical concerns the number of epitopes that can be included in an EV is limited. Furthermore, as the major histocompatibility complex (MHC) binding these epitopes is highly polymorphic, every patient possesses a set of MHC class I and class II molecules of differing specificities. A peptide combination effective for one person can thus be completely ineffective for another. This renders the optimal selection of these epitopes an important and interesting optimization problem. In this work we present a mathematical framework based on integer linear programming (ILP) that allows the formulation of various flavors of the vaccine design problem and the efficient identification of optimal sets of epitopes. Out of a user-defined set of predicted or experimentally determined epitopes, the framework selects the set with the maximum likelihood of eliciting a broad and potent immune response. Our ILP approach allows an elegant and flexible formulation of numerous variants of the EV design problem. In order to demonstrate this, we show how common immunological requirements for a good EV (e.g., coverage of epitopes from each antigen, coverage of all MHC alleles in a set, or avoidance of epitopes with high mutation rates) can be translated into constraints or modifications of the objective function within the ILP framework. An implementation of the algorithm outperforms a simple greedy strategy as well as a previously suggested evolutionary algorithm and has runtimes on the order of seconds for typical problem sizes.
Pilot-tone-based nonlinearity compensation for optical OFDM systems (2010)

We propose a pilot-tone based phase noise compensation method for the mitigation of nonlinearities in OFDM transmission. This scheme allows for the compensation of XPM-induced transmission impairments without direct knowledge of the optical field of the co-propagating channels.
Crystal Structure of 6α-(Hydroxymethyl)penicillanate Complexed to the TEM-1 β-Lactamase from Escherichia coli:  Evidence on the Mechanism of Action of a Novel Inhibitor Designed by a Computer-Aided Process (1996)

The crystal structure of the complex of the TEM-1 β-lactamase from Escherichia coli inhibited by 6α-(hydroxymethyl)penicillanic acid (1) is reported herein. This is the first structure for an acyl-enzyme intermediate with a substrate reported for a native class A β-lactamase. This compound was designed and synthesized as a molecule that would acylate the active site of the enzyme, but would resist deacylation by virtue of the fact that its C6α hydroxymethyl moiety was expected to occupy the space near the hydrolytic water molecule (J. Am. Chem. Soc. 1995, 117, 11055). The crystal structure of the acyl-enzyme species is closely similar to one of the two energy-minimized acyl-enzyme models generated in the course of the design aspect of the work. The crystal structure provides evidence for a number of mechanistic features for the inhibition process and the ultimate recovery of the activity. Our results reported herein are consistent with the side-chain carboxylate of Glu-166 being the active-site basic function that activates the hydrolytic water for the deacylation step in the course of catalysis by class A β-lactamases. The design principles applied for compound 1 hold the promise of general utility for development of novel inhibitors for other hydrolytic enzymes.
Alzheimerʼs disease—a spirochetosis? (1993)

THE aetiology of Alzheimer's disease (AD), which affects a large proportion of the aged population is unknown and the treatment unresolved. The role of beta amyloid protein (βA4), derived from a larger amyloid precursor protein (APP) in AD is the subject of intense research. Here I report observations that in 14 autopsy cases with histopathologically confirmed AD, spirochetes were found in blood and cerebrospinal fluid and, moreover, could be isolated from brain tissue. Thirteen age-matched control cases were without spirochetes. Reference strains of spirochetes and those isolated from brains of AD patients, showed positive immunoreaction with monoclonal antibody against the β amyloid precursor protein. These observations suggest that spirochetes may be one of the causes of AD and that they may be the source of the β amyloid deposited in the AD brain.
The accumulation of novobiocin by Escherichia coli and Staphylococcus aureus (1994)

The accumulation of novobiocin by Escherichia coli was shown to be a nonsaturable process. Inhibitors or uncouplers of respiration had no effect on accumulation in cells grown in Isosensitest broth, whereas, bacteria grown in nutrient broth demonstrated an energy-dependent efflux mechanism. In contrast, accumulation of novobiocin by Staphylococcus aureus was found to have a Km of 74 microM and uncouplers and inhibitors of respiration reduced the accumulation suggesting that in S. aureus novobiocin is transported actively.
Identification and characterization of the thymidine kinase gene of Yaba virus (1995)

DNA of Yaba virus, a member of the poxviruses, was mapped by cross-hybridization between fragments of various restriction enzymes. The genome was approximately 135 kb in length and possessed two characteristic features of poxviruses: cross-links and inverted terminal repeats at both termini. Hybridization of fragments of Yaba virus DNA to known vaccinia virus DNA fragments indicated that the thymidine kinase (TK) gene mapped within the 0.9 kb XhoI-HincII fragment between 52.5 and 53.5 kb from the left end of the genome. The fragment could rescue the TK+ phenotype in TK- cells preinfected with a TK vaccinia virus mutant. Nucleotide sequencing of the fragment revealed an ORF capable of encoding 181 amino acids. The sequence TAAAAATGAAAAATTA upstream of the ORF was considered to be the promoter and the downstream sequence TTTTTAT to be the early transcription termination signal. These sequences are in good accord with the consensus regulatory sequences for the expression of early genes of other known poxviruses. The amino acid sequence similarity among the poxvirus TK genes suggests that Yaba virus is most closely related to swinepox virus and less similar to fowlpox virus.
Cell Type Specificity of Lung Cancer Associated with Arsenic Ingestion (2004)

Arsenic is a well-documented human carcinogen. Previous studies on urinary bladder and skin cancers have shown that arsenic can cause specific cell types of malignancy. To evaluate whether this is also true for lung cancers, we conducted a study on 243 townships in Taiwan. We identified patients through the National Cancer Registry Program and compared the proportion of each major cell type between an endemic area of arsenic intoxication with exposures through drinking water, which includes 5 of the townships and the other 238 townships. To control for gender and age, we analyzed data on men and women separately and divided patients into four age groups. A total of 37,290 lung cancer patients, including 26,850 men and 10,440 women, was diagnosed between January 1, 1980 and December 31, 1999 in study townships. Patients from the endemic area had higher proportions of squamous cell and small cell carcinomas, but a lower proportion of adenocarcinomas. These findings were similar across all age groups in both genders, although the lack of data on smoking is a limitation of our study. The results suggested that the carcinogenicity of arsenic on lungs is also cell type-specific: squamous cell and small cell carcinomas appeared to be related to arsenic ingestion, but not adenocarcinoma. Whereas data in the literature are limited, the association between adenocarcinoma and arsenic exposures through inhalation appeared to be stronger than that of squamous cell carcinoma. Therefore, we speculate that arsenic may give rise to different mechanisms in the development of lung cancers through different exposure routes.
Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses (2009)

The mechanisms by which mucus helps prevent viruses from infecting mucosal surfaces are not well understood. We engineered non-mucoadhesive nanoparticles of various sizes and used them as probes to determine the spacing between mucin fibers (pore sizes) in fresh undiluted human cervicovaginal mucus (CVM) obtained from volunteers with healthy vaginal microflora. We found that most pores in CVM have diameters significantly larger than human viruses (average pore size 340 ± 70 nm; range approximately 50–1800 nm). This mesh structure is substantially more open than the 15–100-nm spacing expected assuming mucus consists primarily of a random array of individual mucin fibers. Addition of a nonionic detergent to CVM caused the average pore size to decrease to 130 ± 50 nm. This suggests hydrophobic interactions between lipid-coated “naked” protein regions on mucins normally cause mucin fibers to self-condense and/or bundle with other fibers, creating mucin “cables” at least three times thicker than individual mucin fibers. Although the native mesh structure is not tight enough to trap most viruses, we found that herpes simplex virus (approximately 180 nm) was strongly trapped in CVM, moving at least 8,000-fold slower than non-mucoadhesive 200-nm nanoparticles. This work provides an accurate measurement of the pore structure of fresh, hydrated ex vivo CVM and demonstrates that mucoadhesion, rather than steric obstruction, may be a critical protective mechanism against a major sexually transmitted virus and perhaps other viruses.
Molecular genetics of von Willebrand disease. (1998)

Von Willebrand disease (vWD), the most common congenital bleeding disorder in man, is related to quantitative and/or qualitative abnormalities of von Willebrand factor (vWF). This multimeric glycoprotein serves as carrier protein of factor VIII, an essential cofactor of coagulation in plasma, and promotes platelet adhesion to the damaged vessel and platelet aggregation. Distinct abnormalities of vWF are responsible for the three types of vWD. Types 1 and 3 are characterized by a quantitative defect of vWF whereas type 2, comprising subtypes 2A, 2B, 2M and 2N, refers to molecular variants with a qualitative defect of vWF. The knowledge of the structure of the vWF gene and the use of Polymerase Chain Reaction (PCR) have led to the identification of the molecular basis of vWD in a significant number of patients. Type 2A is characterized by a decreased platelet-dependent function of vWF associated with the absence of high molecular weight (HMW) multimers of vWF. Most of the type 2A mutations have been identified in the A2 domain of vWF which contains a proteolytic site, while a few others have been found within the propeptide and the C-terminal part of vWF which are involved in its multimerization and dimerization, respectively. In type 2B, defined by an increased affinity of vWF to platelet glycoprotein Ib (GPIb), various amino-acid (aa) substitutions or insertion have been localized within the A1 domain containing the GPIb binding site. In the latter domain have been also identified the few molecular abnormalities described in type 2M which is defined by a decreased platelet-dependent function not caused by the absence of HMW multimers. In type 2N, characterized by a defective binding of vWF to factor VIII, several aa substitutions have been identified within the factor VIII-binding domain in the N-terminal part of vWF. The identification of gene defects remains difficult in types 1 and 3. Whereas various abnormalities (total, partial or point deletions, point insertions, nonsense mutations) have already been identified in type 3, the molecular basis of type 1 is still unresolved in most cases. The characterization of the molecular basis of vWD is of fundamental interest in providing further insight into the structure-function relationship and the biosynthesis of vWF.
Role of thePseudomonas aeruginosa lasandrhlquorum-sensing systems inrhlIregulation (2002)

In Pseudomonas aeruginosa the LasR–LasI and RhlR–RhlI quorum-sensing (QS) systems control expression of numerous virulence genes in a population density-dependent fashion. In this study, we investigated regulation of the autoinducer synthase gene rhlI, which is responsible for C4-HSL signal production. Primer extension analysis was used to map the rhlI transcriptional start site and an upstream regulatory region was identified. Expression studies revealed that (i) this regulatory region is important for rhlI expression and (ii) although the rhl QS system will induce rhlI, las is the dominant regulator. Furthermore, we found that control of rhlI in Escherichia coli is markedly different than in P. aeruginosa.
Emerging drugs for the treatment of ulcerative colitis (2009)

The translational application of new discoveries in the basic understanding of UC pathogenesis is continuing and critical for the development of novel treatment strategies. Design of novel biologic therapies to treat UC has the challenge of addressing potential safety issues, while more traditional drugs should be further developed to facilitate patient compliance to treat this chronic, debilitating disease.
NOE Pumping. 2. A High-Throughput Method To Determine Compounds with Binding Affinity to Macromolecules by NMR (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNOE Pumping. 2. A High-Throughput Method To Determine Compounds with Binding Affinity to Macromolecules by NMRAidi Chen and Michael J. ShapiroView Author Information Department of Analytics Novartis Institute for Biomedical Research 556 Morris Avenue, Summit, New Jersey 07901 Cite this: J. Am. Chem. Soc. 2000, 122, 2, 414–415Publication Date (Web):December 31, 1999Publication History Received21 July 1999Revised23 November 1999Published online31 December 1999Published inissue 1 January 2000https://doi.org/10.1021/ja992588jCopyright © 2000 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views791Altmetric-Citations85LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (27 KB) Get e-AlertsSUBJECTS:Carbohydrates,Ligands,Nuclear magnetic resonance spectroscopy,Receptors,Screening assays Get e-Alerts
A translocation breakpoint cluster disrupts the newly defined 3' end of the SNURF-SNRPN transcription unit on chromosome 15 (2001)

Balanced translocations affecting the paternal copy of 15q11--q13 are a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. Here we report on the cytogenetic and molecular characterization of a de novo balanced reciprocal translocation t(X;15)(q28;q12) in a female patient with atypical PWS. The translocation breakpoints in this patient and two previously reported patients map 70-80 kb distal to the SNURF-SNRPN gene and define a breakpoint cluster region. The breakpoints disrupt one of several hitherto unknown 3' exons of this gene. Using RT--PCR we demonstrate that sequences distal to the breakpoint, including the recently identified C/D box small nucleolar RNA (snoRNA) gene cluster HBII-85 as well as IPW and PAR1, are not expressed in the patient. Our data suggest that lack of expression of these sequences contributes to the PWS phenotype.
Some basic stress diffusion solutions for fluid‐saturated elastic porous media with compressible constituents (1976)

This is a study of the formulation, some basic solutions, and applications of the Biot linearized quasistatic elasticity theory of fluid‐infiltrated porous materials. Whereas most previously solved problems are based on idealizing the fluid and solid constituents as separately incompressible, full account is taken here of constituent compressibility. Previous studies are reviewed and the Biot constitutive equations relating strain and fluid mass content to stress and pore pressure are recast in terms of new material parameters, more directly open to physical interpretation as the Poisson ratio and induced pore pressure coefficient in undrained deformation. Different formulations of the coupled deformation/diffusion field equations and their analogues in coupled thermoelasticity are discussed, and a new formulation with stress and pore pressure as basic variables is presented that leads, for plane problems, to a convenient complex variable representation of solutions. The problems solved include those of the suddenly introduced edge dislocation and concentrated line force and of the suddenly pressurized cylindrical and spherical cavity. The dislocation solution is employed to represent that for quasi‐static motions along a shear fault, and a discussion is given, based on fracture mechanics models for fault propagation, of phenomena involving coupled behavior between the rupturing solid and its pore fluid, which could serve to stabilize a fault against rapid spreading. Also, the solution for a pressurized cylindrical cavity leads to a time‐dependent stress field near the cavity wall, and its relevance to time effects in the inception of hydraulic fractures from boreholes, or from drilled holes in laboratory specimens, is discussed. Various limiting cases are identified, and numerical values of the controlling porous media elastic parameters are given for several rocks.
Binding of intimin from enteropathogenic Escherichia coli to Tir and to host cells (1999)

Enteropathogenic Escherichia coli (EPEC) induce characteristic attaching and effacing (A/E) lesions on epithelial cells. This event is mediated, in part, by binding of the bacterial outer membrane protein, intimin, to a second EPEC protein, Tir (translocated intimin receptor), which is exported by the bacteria and integrated into the host cell plasma membrane. In this study, we have localized the intimin-binding domain of Tir to a central 107-amino-acid region, designated Tir-M. We provide evidence that both the amino- and carboxy-termini of Tir are located within the host cell. In addition, using immunogold labelling electron microscopy, we have confirmed that intimin can bind independently to host cells even in the absence of Tir. This Tir-independent interaction and the ability of EPEC to induce A/E lesions requires an intact lectin-like module residing at the carboxy-terminus of the intimin polypeptide. Using the yeast two-hybrid system and gel overlays, we show that intimin can bind both Tir and Tir-M even when the lectin-like domain is disrupted. These data provide strong evidence that intimin interacts not only with Tir but also in a lectin-like manner with a host cell intimin receptor.
Detection and molecular characterization of adenoviruses in Korean children hospitalized with acute gastroenteritis (2012)

Human adenoviruses (HAdVs) are an important cause of acute gastroenteritis in children. However, few studies on the epidemiology or types of HAdVs associated with acute gastroenteritis have been conducted in Korea. Therefore, in the present study, the incidence of HAdV in 2064 stool samples from Korean children hospitalized with acute gastroenteritis (2004-2006) was assessed and the types of viruses present determined. Polymerase chain reaction, sequencing, and phylogenic analyses revealed that 113 samples (5.5%) were HAdV-positive. While HAdVs were mainly detected during July to October, no seasonal difference between the enteric and non-enteric viruses in the incidence of HAdV was observed. HAdV-41 and HAdV-40 were found in 54 (47.8%) and 3 (2.6%) HAdV-positive samples, respectively. HAdV-3, HAdV-7, HAdV-2, HAdV-31, HAdV-4, and HAdV-37 were detected in 11 (9.7%), 5 (4.4%), 2 (1.7%), 2 (1.7%), 1 (0.8%), and 1 (0.8%) of sample(s), respectively. Thus, not only enteric, but also non-enteric, HAdVs may play an important role in acute gastroenteritis in Korean children.
Hypoxia activates the capacity of tumor‐associated carbonic anhydrase IX to acidify extracellular pH (2004)

Acidic extracellular pH (pHe) is a typical attribute of a tumor microenvironment, which has an impact on cancer development and treatment outcome. It was believed to result from an accumulation of lactic acid excessively produced by glycolysis. However, metabolic profiles of glycolysis-impaired tumors have revealed that CO2 is a significant source of acidity, thereby indicating a contribution of carbonic anhydrase (CA). The tumor-associated CA IX isoform is the best candidate, because its extracellular enzyme domain is highly active, expression is induced by hypoxia and correlates with poor prognosis. This study provides the first evidence for the role of CA IX in the control of pHe. We show that CA IX can acidify the pH of the culture medium in hypoxia but not in normoxia. This acidification can be perturbed by deletion of the enzyme active site and inhibited by CA IX-selective sulfonamides, which bind only to hypoxic cells containing CA IX. Our findings suggest that hypoxia regulates both expression and activity of CA IX in order to enhance the extracellular acidification, which may have important implications for tumor progression.
Effect of Endothelial Shear Stress on the Progression of Coronary Artery Disease, Vascular Remodeling, and In-Stent Restenosis in Humans (2003)

The present study represents the first experience in humans relating ESS to subsequent outcomes in native and stented arteries. Regions of low ESS develop progressive atherosclerosis and outward remodeling, areas of physiological ESS remain quiescent, and areas of increased ESS exhibit outward remodeling. ESS may have a limited role in in-stent restenosis. This technology can predict areas of minor plaque likely to exhibit progression of atherosclerosis.
2-keto-3-deoxygluconate transport system in Erwinia chrysanthemi (1987)

In Erwinia chrysanthemi, the gene kdgT encodes a transport system responsible for the uptake of ketodeoxyuronates. We studied the biochemical properties of this transport system. The bacteria could grow on 2,5-diketo-3-deoxygluconate but not on 2-keto-3-deoxygluconate. The 2-keto-3-deoxygluconate entry reaction displayed saturation kinetics, with an apparent Km of 0.52 mM (at 30 degrees C and pH 7). 5-Keto-4-deoxyuronate and 2,5-diketo-3-deoxygluconate appeared to be competitive inhibitors, with Kis of 0.11 and 0.06 mM, respectively. The 2-keto-3-deoxygluconate permease could mediate the uptake of glucuronate with a low affinity. kdgT was cloned on an R-prime plasmid formed by in vivo complementation of a kdgT mutation of Escherichia coli. After being subcloned, it was mutagenized with a mini-Mu-lac transposable element able to form fusions with the lacZ gene. We introduced a kdgT-lac fusion into the E. chrysanthemi chromosome by marker exchange recombination and studied its regulation. kdgT product synthesis was not induced by external 2-keto-3-deoxygluconate in the wild-type strain but was induced by galacturonate and polygalacturonate. Two types of regulatory mutants able to grow on 2-keto-3-deoxygluconate as the sole carbon source were studied. Mutants of one group had a mutation in the operator region of kdgT; mutants of the other group had a mutation in kdgR, a regulatory gene controlling kdgT expression.