gebhart/patrepeval huggingface dataset:
Label-free protein assay based on a nanomechanical cantilever array (2002)

We demonstrate continuous label-free detection of two cardiac biomarker proteins (creatin kinase and myoglobin) using an array of microfabricated cantilevers functionalized with covalently anchored anti-creatin kinase and anti-myoglobin antibodies. This method allows biomarker proteins to be detected via measurement of surface stress generated by antigen–antibody molecular recognition. Reference cantilevers are used to eliminate thermal drifts, undesired chemical reactions and turbulences from injections of liquids by calculating differential deflection signals with respect to sensor cantilevers. The sensitivity achieved for myoglobin detection is below 20 µg ml−1. Both myoglobin and creatin kinase could be detected independently using cantilevers functionalized with the corresponding antibodies, in unspecific protein background. This approach permits the use of up to seven different antigen–antibody reactions simultaneously, including an additional thermomechanical and chemical in situ reference. Applications lie in the field of early and rapid diagnosis of acute myocardial infarction.
Hybrids of a Genetically Engineered Antibody and a Carbon Nanotube Transistor for Detection of Prostate Cancer Biomarkers (2012)

We developed a novel detection method for osteopontin (OPN), a new biomarker for prostate cancer, by attaching a genetically engineered single-chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube field-effect transistor (NT-FET). Chemical functionalization using diazonium salts is used to covalently attach scFv to NT-FETs, as confirmed by atomic force microscopy, while preserving the activity of the biological binding site for OPN. Electron transport measurements indicate that functionalized NT-FET may be used to detect the binding of OPN to the complementary scFv protein. A concentration-dependent increase in the source-drain current is observed in the regime of clinical significance, with a detection limit of approximately 30 fM. The scFv-NT hybrid devices exhibit selectivity for OPN over other control proteins. These devices respond to the presence of OPN in a background of concentrated bovine serum albumin, without loss of signal. On the basis of these observations, the detection mechanism is attributed to changes in scattering at scFv protein-occupied defect sites on the carbon nanotube sidewall. The functionalization procedure described here is expected to be generalizable to any antibody containing an accessible amine group and to result in biosensors appropriate for detection of corresponding complementary proteins at fM concentrations.
Masquerade detection using enriched command lines (2004)

A masquerade attack, in which one user impersonates another, is among the most serious forms of computer abuse, largely because such attacks are often mounted by insiders, and can be very difficult to detect. Automatic discovery of masqueraders is sometimes undertaken by detecting significant departures from normal user behavior, as represented by user profiles based on users ’ command histories. A series of experiments performed by Schonlau et al. [12] achieved moderate success in masquerade detection based on a data set comprised of truncated command lines, i.e., single commands, stripped of any accompanying flags, arguments or elements of shell grammar such as pipes or semi-colons. Using the same data, Maxion and Townsend [8] improved on the Schonlau et al. results by 56%, raising the detection rate from 39.4 % to 61.5 % at false-alarm rates near 1%. The present paper extends this work by testing the hypothesis that a limitation of these approaches is the use of truncated command-line data, as opposed to command lines enriched with flags, shell grammar, arguments and information about aliases. Enriched command lines were found to facilitate correct detection at the 82 % level, far exceeding previous results, with a corresponding 30% reduction in the overall cost of errors, and only a small increase in false alarms. Descriptions of pathological cases illustrate strengths and limitations of both the data and the detection algorithm. 1.
Chemoenzymatic approaches to glycoprotein synthesis (2007)

The construction of homogeneous glycoproteins presents a formidable challenge to the synthetic chemist. Over the past few years there has been an explosion in the number of methods developed to address this problem. These methods include the development of novel ligation technologies for the synthesis of the protein backbone, as well chemical and enzymatic approaches for introducing complex glycans into the peptide backbone. This tutorial review discusses the application of these techniques to the synthesis of peptides and proteins possessing well defined glycans.
Strong reduction of AGO2 expression in melanoma and cellular consequences (2013)

We identified melanoma-specific downregulation of AGO2 and corresponding reduced RNAi efficiency. These findings will help to understand the molecular basis of malignant melanoma and can potentially lead to an improvement of therapeutic strategies.
Modulation of B lymphocyte signalling by the B subunit of Escherichia coli heat‐labile enterotoxin (2002)

The non-toxic B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is a potent mucosal adjuvant and immunomodulator capable of blocking autoimmune disease. These effects are linked with its ability to modulate lymphocyte populations--a feature that is dependent on binding to ubiquitously expressed cell surface receptors. Here, we demonstrate that EtxB can trigger up-regulated expression of class II MHC and CD25 on purified populations of B lymphocytes, suggesting that EtxB can directly activate biochemical signalling pathways in these cells. The nature of the intracellular signalling events was investigated. B cells cultured with EtxB, but not a non-receptor binding mutant protein, EtxB(G33D), caused the activation of the extracellular signal-regulated kinase (Erk) forms of mitogen-activated protein (MAP) kinase in a process that was dependent on MAPK/Erk kinase (MEK), phosphoinositide 3-kinase (PI3-kinase) and protein kinase C (PKC), as determined by the use of specific inhibitors. PI3-kinase was critical not only in the activation of MAP kinase but also in the up-regulation of both class II and CD25. However, MEK inhibition only partially abrogated the EtxB-mediated up-regulation of MHC class II expression and did not affect CD25 expression--findings suggesting that additional pathways downstream of PI3-kinase are involved. A role for PKC in these processes was suggested by the finding that inhibitors of PKC completely blocked EtxB-mediated CD25 up-regulation. Thus, we have shown that receptor binding by EtxB triggers multiple signalling pathways in B cells that regulate the expression of key cell surface molecules.
Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18). (1994)

The divalent cation-dependent interaction of the beta 2 integrin CR3 (CD11b/CD18) with the major complement opsonic C3 fragment iC3b is an important component of the central role of CR3 in inflammation and immune clearance. In this investigation we have identified the iC3b binding site in CR3. A recombinant fragment representing the CR3 A-domain, a 200-amino acid region in the ectodomain of the CD11b subunit, bound to iC3b directly and in a divalent cation-dependent manner. The iC3b binding site was further localized to a short linear peptide that also bound iC3b directly and inhibited iC3b binding to the A-domain as well as to CR3 expressed by human neutrophils. These data establish a major recognition function for the integrin A-domain and have important implications for development of novel antiinflammatory therapeutics.
Galactose at the nonreducing terminus of O-linked oligosaccharides of mouse egg zona pellucida glycoprotein ZP3 is essential for the glycoprotein's sperm receptor activity. (1988)

During fertilization in mice, zona pellucida glycoprotein ZP3 mediates initial sperm-egg interactions by serving as receptor for sperm. Purified egg ZP3, as well as ZP3-derived O-linked oligosaccharides, exhibit sperm receptor activity in vitro. We report that treatment of purified egg ZP3 and ZP3-derived O-linked oligosaccharides with either alpha-galactosidase or galactose oxidase results in loss of sperm receptor activity. In the latter case, sperm receptor activity can be restored to the oxidized glycoprotein and O-linked oligosaccharides by treatment with sodium borohydride. We conclude that galactose, located in alpha-linkage at the nonreducing terminus of O-linked oligosaccharides, is at least one of the sugar determinants on ZP3 responsible for binding of sperm to the zona pellucida.
Isolation of Mycobacterium avium subsp. paratuberculosis from Free-Ranging Birds and Mammals on Livestock Premises (2005)

Surveys for Mycobacterium avium subsp. paratuberculosis infection in free-ranging mammals and birds were conducted on nine dairy and beef cattle farms in Wisconsin and Georgia. Specimens were collected from 774 animals representing 25 mammalian and 22 avian species. Specimens of ileum, liver, intestinal lymph nodes, and feces were harvested from the larger mammals; a liver specimen and the gastrointestinal tract were harvested from birds and small mammals. Cultures were performed by using radiometric culture and acid-fast isolates were identified by 16S/IS900/IS1311 PCR and mycobactin dependency characteristics. M. avium subsp. paratuberculosis was cultured from tissues and feces from 39 samples from 30 animals representing nine mammalian and three avian species. The prevalence of infected wild animals by premises ranged from 2.7 to 8.3% in Wisconsin and from 0 to 6.0% in Georgia. Shedding was documented in seven (0.9%) animals: three raccoons, two armadillos, one opossum, and one feral cat. The use of two highly polymorphic short sequence repeat loci for analysis of 29 of the 39 strains identified 10 alleles. One allelic pattern broadly shared in domestic ruminants ("7,5") appeared in approximately one-third of the wildlife M. avium subsp. paratuberculosis isolates studied. Given the few cases of shedding by free-ranging animals compared to the volume of contaminated manure produced by infected domestic ruminant livestock, contamination of the farm environment by infected wildlife was negligible. Wildlife may, however, have epidemiological significance for farms where M. avium subsp. paratuberculosis recently has been eliminated or on farms free of M. avium subsp. paratuberculosis but located in the geographic vicinity of farms with infected livestock.
Association of Morbid Obesity With FTO and INSIG2 Allelic Variants (2008)

Increased BMI in morbid obesity is associated with a combination of FTO and INSIG2 SNPs.
Genetic evidence that the Tat proteins of human immunodeficiency virus types 1 and 2 can multimerize in the eukaryotic cell nucleus (1993)

The formation of dimers or higher-order multimers is critical to the biological activity of many eukaryotic regulatory proteins. However, biochemical analyses of the multimerization capacity of the Tat trans activator of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) have yielded contradictory results. We used the two-hybrid genetic assay for protein-protein interactions in the eukaryote Saccharomyces cerevisiae (S. Fields and O.-K. Song, Nature [London] 340:245-246, 1989) to examine the multimerization of Tat in vivo. Both HIV-1 and HIV-2 Tat are shown to form specific homo- but not heteromultimers in the yeast cell nucleus. Mutational analysis indicates a critical role for the essential core motif of Tat in mediating this interaction but demonstrates that efficient Tat multimerization does not require an intact cysteine motif. These data raise the possibility that the multimerization of Tat may be important for Tat function in higher eukaryotes.
Human hepatitis delta virus RNA subfragments contain an autocleavage activity. (1989)

Hepatitis delta virus (HDV) contains a single-stranded circular RNA genome of 1.7 kilobases. In this report we demonstrate that subfragments of HDV RNA can undergo autocatalytic cleavage. This cleavage requires at least 500 microM of Mg2+ or Ca2+, is not affected by varying the pH from 5.0 to 9.1, and occurs with RNA fragments as small as 133 nucleotides. The larger RNA fragments containing additional HDV sequences have a lower efficiency of cleavage. Deletion analysis at both ends of RNA subfragments suggested that the catalytic ability of HDV RNA resides in a stretch of no more than 117 nucleotides around the cleavage site. The cleavage occurs at the phosphodiester bond between nucleotides 688 and 689 on the HDV genomic map, generating a 5' fragment with a terminal uridyl 2',3'-cyclic monophosphate residue and a 3' fragment with a guanosyl residue with a 5'-hydroxyl group. The smallest autocleaving RNA does not contain the "hammerhead" sequence required for the autocleavage of other known self-cleaving RNA. The cleavage of HDV RNA occurs at a much faster rate, even at a very low Mg2+ concentration, than that of other "ribozymes." Thus, HDV RNA represents a distinct class of ribozyme.
Minimal carcinoma in prostate needle biopsy specimens: diagnostic features and radical prostatectomy follow-up. (1998)

Prostate cancer screening and early detection efforts have resulted in the identification of smaller volume carcinomas of the prostate. We evaluated the diagnostic features of minimal (< 1 mm) carcinoma in sextant needle biopsy specimens of the prostate and in follow-up analyzed the features of the corresponding carcinomas in the whole gland. We reviewed specimens from 50 consecutive patients who had minimal carcinoma in needle biopsy tissue and who had undergone radical prostatectomy. Histologic grade, tumor size, pathologic stage, and margin status of the 50 carcinomas in the whole gland in which the carcinoma size was minimal in the sextant needle biopsy specimen were compared with those of 50 carcinomas in the whole gland in which carcinoma size was greater than 1 mm in the needle biopsy specimen. The most common morphologic features of these minimal carcinomas were nucleomegaly (96%), infiltrative growth pattern (88%), intraluminal secretions (78%), prominent nucleoli (64%), associated high-grade prostatic intraepithelial neoplasia (40%), amphophilic cytoplasm (36%), hyperchromatic nuclei (30%), and intraluminal crystalloids (22%). Perineural invasion (2%), collagenous micronodules (2%) and mitotic figures (2%) were uncommon. The mean tumor volume in the whole gland of carcinomas corresponding to minimal carcinoma in a needle biopsy specimen was significantly smaller (P=.029) at 1.1 mL than it was in carcinomas with tumor greater than 1 mm in the needle biopsy specimen at 1.6 mL, but other pathologic features of carcinoma in the whole gland were not significantly different. In conclusion, a constellation of morphologic attributes is important for establishment of a diagnosis of minimal carcinoma of the prostate in needle biopsy specimen. Most (82%) of the corresponding prostate cancers in the whole gland were pathologically significant.
First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution (2020)

DSR was well tolerated in both animals and human subjects and produced substantially greater sodium removal than standard PD solution. Additional research evaluating the use of DSR as a method to prevent and treat hypervolemia in heart failure is warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03801226.
Dual band aperture coupled antenna using spur line (1997)

A new dual band microstrip antenna is presented. A spur line is embedded in the nonradiating edges of the patch to obtain dual band operation at two separate frequencies with good radiation characteristics. Very good agreement between the simulation and the measurements is obtained.
Localization and synthesis of an antigenic determinant of herpes simplex virus glycoprotein D that stimulates the production of neutralizing antibody (1984)

An antigenic determinant capable of inducing type-common herpes simplex virus (HSV)-neutralizing antibodies has been located on glycoprotein D (gD) of HSV type 1 (HSV-1). A peptide of 16 amino acids corresponding to residues 8 to 23 of the mature glycoprotein (residues 33 to 48 of the predicted gD-1 sequence) was synthesized. This peptide reacted with an anti-gD monoclonal antibody (group VII) previously shown to neutralize the infectivity of HSV-1 and HSV-2. The peptide was also recognized by polyclonal antibodies prepared against purified gD-1 but was less reactive with anti-gD-2 sera. Sera from animals immunized with the synthetic peptide reacted with native gD and neutralized both HSV-1 and HSV-2.
Prognostic Significance of Simultaneous Infiltration of HLA-DR-Positive Dendritic Cells and Tumor Infiltrating Lymphocytes into Human Esophageal Carcinoma. (1993)

The distribution of HLA-DR-positive dendritic cells (DR+DCs) and tumor infiltrating lymphocytes (TILs) was investigated in 67 patients with squamous cell carcinoma of the esophagus. DR+DCs were chiefly present among the cancer cell nests, and few were seen in the stroma. As clusters, UCHL-1-positive T-cells (UCHL1-Ts) were detected in the tissue around the cancer cell nests and as individual cells within tumor nests. Some UCHL1-Ts in the tumor nests showed direct contact with DR+DCs. In addition, a few OPD4-positive helper/inducer T cells were found among cancer cells, and were densely present in the stroma. A correlation was demonstrated between the number of DR+DCs and UCHL1-Ts in each patient (R = 0.4547, p < 0.01). In addition, dense tumor infiltration by both DR+DCs and UCHL1-Ts within the cancer cell nests was related to a better prognosis (p < 0.01).
Forcing Characteristics of Easter Lily Bulbs Exposed to Elevated-ethylene and -carbon Dioxide and Low-oxygen Atmospheres (1991)

Exposure of bulbs of Easter Lily (Lilium longiflorum Thunb.) to a maximum of 2 μl ethylene/liter during vernalization delayed flowering by 5 to 7 days and decreased the number of flower buds. Ethylene exposure for 5 days at 21C after vernalization accelerated shoot emergence and flowering by up to 3 days. No floral or plant abnormalities were observed after bulb exposure to ethylene. Exposure to atmospheres with 0%, 0.5%, or 1% O 2 at 21C for up to 2 weeks before or 10 days after vernalization did not “significantly impair subsequent bulb forcing. Storage in 1% 0 2 at 21C for 1 week before vernalization resulted in nearly one additional secondary bud initiated per plant. Exposure to up to 15% CO 2 at 21C for up to 2 weeks before or 10 days after vernalization did not significantly impair subsequent forcing.
Aerosol and Solution Modification of Particle-Polymer Interfaces (1998)

Abstract In recent years several investigators have focused on the synthesis of uniformly and continuously coated particles to impart improved chemical stability, mechanical strength, morphology and/or dispersibility to powders required for preparing next-generation composities. This paper reviews two in situ reaction methods employed at Clarkson University to selectively coat individual particles having widely different shape, size and chemical composition. The aerosol procedure allows core particles to become coated using room temperature liquid-gas reactions. Alternatively, coating particles dispersed in a solvent containing reactive precursors is more applicable to industrial processing. Uniform, well-adhering coatings of polyurea on titania powder, of polydivinylbenzene on silica beads, and of carbon and boron nitride on silicon carbide whiskers were made by selecting the correct precursors and reaction chemistries. Qualitative assessment of adhesion between the coatings and cores is given. Key Words: Particle coatingsilicon carbide whiskersboron nitride coatingpolymer coatingparticle interfacescoating adhesion
Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF) (2003)

Inherited hearing impairment affects one in 2,000 newborns. Nonsyndromic prelingual forms are inherited mainly as autosomal recessive traits, for which 16 genes are currently known. Mutations in the genes encoding connexins 26 and 30 account for up to 50% of these cases. However, the individual contribution of the remaining genes to the whole remains undetermined. In addition, for most of the genes there is a need for studies on genotype-phenotype correlations, to identify distinctive clinical features which may direct the molecular diagnosis to specific genes. Here we present a mutation analysis and a genotype-phenotype correlation study on the gene encoding otoferlin (OTOF), responsible for the DFNB9 subtype of prelingual hearing impairment. Four novel mutations were identified: c.2122C>T (p.Arg708Ter), c.4275G>A (p.Trp1425Ter), c.4362+2T>G, and c.5860_5862delATC (p.Ile1954del). A total of 37 subjects with mutations in OTOF were studied clinically. They were phenotypically homogeneous, having profound hearing impairment with very early onset, as shown by pure-tone audiometry and auditory brainstem responses. Magnetic resonance imaging and computed tomography did not reveal any inner ear malformation. Unexpectedly, transient evoked otoacoustic emissions (TEOAEs) were present, either bilaterally or unilaterally in 11 subjects. Altogether, clinical data of these subjects met the diagnostic criteria of auditory neuropathy. A total of 10 subjects had been successfully provided with cochlear implants. The results of our study indicate that genetic diagnosis of subjects with auditory neuropathy and profound hearing impairment should be directed to the otoferlin gene. Our data are of concern to universal screening programs which use TEOAEs as the first detection test for hearing impairment in newborns, since this technique may overlook a nonnegligible proportion of cases.
Small molecule ISRIB suppresses the integrated stress response within a defined window of activation (2019)

Activation of the integrated stress response (ISR) by a variety of stresses triggers phosphorylation of the α-subunit of translation initiation factor eIF2. P-eIF2α inhibits eIF2B, the guanine nucleotide exchange factor that recycles inactive eIF2•GDP to active eIF2•GTP. eIF2 phosphorylation thereby represses translation. Persistent activation of the ISR has been linked to the development of several neurological disorders, and modulation of the ISR promises new therapeutic strategies. Recently, a small-molecule ISR inhibitor (ISRIB) was identified that rescues translation in the presence of P-eIF2α by facilitating the assembly of more active eIF2B. ISRIB enhances cognitive memory processes and has therapeutic effects in brain-injured mice without displaying overt side effects. While using ISRIB to investigate the ISR in picornavirus-infected cells, we observed that ISRIB rescued translation early in infection when P-eIF2α levels were low, but not late in infection when P-eIF2α levels were high. By treating cells with varying concentrations of poly(I:C) or arsenite to induce the ISR, we provide additional proof that ISRIB is unable to inhibit the ISR when intracellular P-eIF2α concentrations exceed a critical threshold level. Together, our data demonstrate that the effects of pharmacological activation of eIF2B are tuned by P-eIF2α concentration. Thus, ISRIB can mitigate undesirable outcomes of low-level ISR activation that may manifest neurological disease but leaves the cytoprotective effects of acute ISR activation intact. The insensitivity of cells to ISRIB during acute ISR may explain why ISRIB does not cause overt toxic side effects in vivo.
The Effect of Vagal Nerve Stimulation on Voice (2001)

Vagal nerve implantation devices create significant but well-tolerated vocal side effects. Investigation of these devices increases our understanding of laryngeal physiology and may give insight into future laryngeal pacing. Preimplantation laryngeal examination should be performed routinely to rule out laryngeal pathology that could lead to significant complications.