gebhart/patrepeval huggingface dataset:
Disulfide by Design™: a computational method for the rational design of disulfide bonds in proteins (2003)

http://www.ehscenter.org/dbd/
Actin accumulation at sites of bacterial adhesion to tissue culture cells: basis of a new diagnostic test for enteropathogenic and enterohemorrhagic Escherichia coli (1989)

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) adhere to the intestinal mucosa and produce an attaching and effacing (AE) lesion in the brush border microvillous membrane; the AE lesion is characterized by localized destruction of microvilli and intimate attachment of bacteria to the apical enterocyte membrane. A similar lesion is seen when bacteria adhere in vitro to a variety of human tissue culture cell lines. In both cases, dense concentrations of microfilaments are present in the apical cytoplasm beneath attached bacteria. Using a fluorescein-labeled phallotoxin, we have shown that these microfilaments are composed of actin. Cells infected with EPEC and EHEC strains known from electron microscopic studies to produce the AE lesion all exhibited intense spots of fluorescence which corresponded in size and position with each adherent bacterium; cells infected with adherent E. coli strains known not to produce the AE lesion did not produce this striking pattern of fluorescence and were indistinguishable from uninfected control cells. These results indicate that such site-specific concentrations of cytoskeletal actin are characteristic of the AE membrane lesion and can form the basis of a simple, highly sensitive diagnostic test for EPEC and EHEC.
Decreased expression of annexin A10 in gastric cancer and its overexpression in tumor cell growth suppression. (2010)

Gastric carcinoma is the most common neoplasm in Southeast Asian populations and is the second leading cause of cancer death worldwide. Annexins are a family of cytosolic calcium and membrane binding proteins that have been implicated in a wide variety of cell functions. Recent studies have suggested that Annexin A10 (ANXA10), a member of the Annexin protein family, is down-regulated in specific types of cancer. However, the underlying molecular mechanisms of the dysregulation of ANXA10 remain to be elucidated. In the present study, to investigate the biological effects of ANXA10 on gastric carcinoma, aberrant expression of ANXA10 was evaluated by Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), in gastric cancer tissues and cell lines. Decreased expression of ANXA10 was observed in five selected gastric cancer tissues compared to the normal surrounding mucosa. In the cancer cell lines, seven out of nine selected gastric cancer cell lines had no detectable ANXA10 by RT-PCR. Among these, when an ANXA10 expressing plasmid was introduced into MKN-1 cells, cell growth was suppressed and apoptosis augmented. The results of this study demonstrated that ANXA10 was aberrantly regulated in gastric carcinoma and suggests that down-regulation of ANXA10 might be involved in gastric carcinogenesis. In addition, ANXA10 may play a role, as a tumor suppressor, in the development and progression of gastric cancer.
Jasmonate signaling mutants ofArabidopsisare susceptible to the soil fungusPythium irregulare (1998)

Jasmonic acid has properties of a plant hormone, including the induction of specific genes associated with plant defense. We previously described jar1-1, an Arabidopsis jasmonate response mutant that exhibits reduced sensitivity to methyl jasmonate. We have further characterized this mutant and two new alleles; jar1-2 from a gamma irradiated population, and jar1-4 from a T-DNA mutant population. Seedling root growth in jar1-1 was equally insensitive to methyl jasmonate and jasmonic acid, indicating that the defect was not in the conversion of methyl jasmonate to the acid. None of the jar1 mutants showed an altered sensitivity to auxin, cytokinin, or the ethylene precursor 1-aminocyclopropane-1-carboxylic acid, indicating that the lesion does not affect the general uptake or transport of hormones. A soil fungus, Pythium irregulare, was found to blight jar1-1. Cultures of this organism caused the symptoms in all three jar1 mutants but not in wild type, indicating that increased susceptibility was due to the lesion in the JAR1 locus. A fatty acid desaturase triple mutant that is defective in the biosynthesis of jasmonic acid (J. Browse, Washington State University) was also susceptible, confirming that jasmonate is involved in resistance. The jar1-1 locus was mapped to the lower end of chromosome 2, about 11.4 cM from as1 and 1.6 cM from cer8. These results establish that jasmonate signaling plays an important role in resistance to soil micro-organisms in plants.
Small forwarding tables for fast routing lookups (1997)

For some time, the networking community has assumed that it is impossible to do IP routing lookups in software fast enough to support gigabit speeds. IP routing lookups must find the routing entry with the longest matching prefix, a task that has been thought to require hardware support at lookup frequencies of millions per second.We present a forwarding table data structure designed for quick routing lookups. Forwarding tables are small enough to fit in the cache of a conventional general purpose processor. With the table in cache, a 200 MHz Pentium Pro or a 333 MHz Alpha 21164 can perform a few million lookups per second. This means that it is feasible to do a full routing lookup for each IP packet at gigabit speeds without special hardware.The forwarding tables are very small, a large routing table with 40,000 routing entries can be compacted to a forwarding table of 150-160 Kbytes. A lookup typically requires less than 100 instructions on an Alpha, using eight memory references accessing a total of 14 bytes.
αvβ5 Integrin Receptor-mediated Endocytosis of Vitronectin Is Protein Kinase C-dependent (1995)

Previous studies have demonstrated that the alpha v beta 5 integrin receptor functions in the endocytosis and degradation of matrix-bound vitronectin by human skin fibroblasts (Panetti, T. S., and McKeown-Longo, P. J. (1993) J. Biol. Chem. 268, 11988-11993; Panetti, T. S., and McKeown-Longo, P. J. (1993) J. Biol. Chem. 268, 11492-11495). These earlier studies demonstrated that vitronectin degradation was inhibited by either antibodies to the beta 5 integrin or exogenous heparin, suggesting that both integrin receptors and cell surface heparan sulfate proteoglycans are involved in the endocytosis and degradation of vitronectin. The present study was done to define intracellular signaling pathways involved in endocytosis of vitronectin and to evaluate the relative contribution of cell surface heparan sulfate proteoglycans and the alpha v beta 5 integrin in the activation of these signaling pathways. The addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, to monolayers of human skin fibroblasts, increased vitronectin degradation. Staurosporine and calphostin C, inhibitors of protein kinase C, blocked internalization and subsequent degradation of vitronectin, while KT5720, an inhibitor of protein kinase A, had no effect on the degradation of vitronectin. PMA was also able to reverse the inhibition of vitronectin degradation seen when cells were pretreated with heparinase or incubated with exogenous heparin. In contrast, the inhibitory effect of either RGD peptides or anti-alpha v beta 5 antibodies on vitronectin degradation were not overcome by the addition of PMA. These data suggest that the internalization of vitronectin from the matrix is mediated by the alpha v beta 5 integrin following activation of protein kinase C.
A Role for Oxidative Stress in Apoptosis: Oxidation and Externalization of Phosphatidylserine Is Required for Macrophage Clearance of Cells Undergoing Fas-Mediated Apoptosis (2002)

Exposure of phosphatidylserine (PS) on the surface of apoptotic cells has been suggested to serve as an important recognition signal for macrophages. In this work we show that triggering of the death receptor Fas on Jurkat cells results in the generation of reactive oxygen species with oxidation and externalization of PS but not of the other major aminophospholipid, phosphatidylethanolamine. These cells were readily ingested by several classes of macrophages, whereas Raji cells, which are defective for Fas-induced PS exposure, remained unengulfed. However, when Raji cells were incubated with the thiol-reactive agent N-ethylmaleimide to induce PS exposure in the absence of other features of apoptosis, these cells were also engulfed by macrophages. Phagocytosis of Fas-triggered Jurkat cells was inhibited by superoxide dismutase and catalase, which prevent oxidation of PS while allowing PS to remain externalized on these cells. Moreover, liposomes containing oxidized PS (PS-OX) were more potent inhibitors of phagocytosis than those containing its nonoxidized counterpart. Finally, enrichment of the plasma membrane of Jurkat or Raji cells, or myeloid leukemic HL-60 cells, with exogenous PS resulted in phagocytic cell clearance, and this process was further enhanced when PS was substituted for by PS-OX. Taken together, our data suggest that the presence of PS-OX in conjunction with nonoxidized PS on the cell surface is an important signal for macrophage clearance of apoptotic cells.
A Janus Kinase Inhibitor, JAB, Is an Interferon-γ–Inducible Gene and Confers Resistance to Interferons (1998)

Abstract It has been shown that interferons (IFNs) exert their signals through receptor-associated Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). However, molecular mechanism of regulation of IFN signaling has not been fully understood. We have reported novel cytokine-inducible SH2 protein (CIS) and JAK binding protein (JAB) family genes that can potentially modulate cytokine signaling. Here we report that JAB is strongly induced by IFN-γ but not by IFN-β in mouse myeloid leukemia M1 cells and NIH-3T3 fibroblasts. NIH-3T3 cells ectopically expressing JAB but not CIS3 lost responsiveness to the antiviral effect of IFN-β and IFN-γ. M1 leukemic cells stably expressing JAB were also resistant to IFN-γ and IFN-β–induced growth arrest. In both NIH-3T3 and M1 transformants expressing JAB, IFN-γ did not induce tyrosine phosphorylation and DNA binding activity of STAT1. Moreover, IFN-γ–induced activation of JAK1 and JAK2 and IFN-β–induced JAK1 and Tyk2 activation were inhibited in NIH-3T3 JAB transformants. These results suggest that JAB inhibits IFN signaling by blocking JAK activity. We also found that IFN-resistant clones derived from LoVo cells and Daudi cells expressed high levels of JAB without stimulation. In IFN-resistant Daudi cells, IFN-induced STAT1 and JAK phosphorylation was partially reduced. Therefore, overexpression of JAB could be, at least in part, a mechanism of IFN resistance. © 1998 by The American Society of Hematology.
Optimizing search engines using clickthrough data (2002)

This paper presents an approach to automatically optimizing the retrieval quality of search engines using clickthrough data. Intuitively, a good information retrieval system should present relevant documents high in the ranking, with less relevant documents following below. While previous approaches to learning retrieval functions from examples exist, they typically require training data generated from relevance judgments by experts. This makes them difficult and expensive to apply. The goal of this paper is to develop a method that utilizes clickthrough data for training, namely the query-log of the search engine in connection with the log of links the users clicked on in the presented ranking. Such clickthrough data is available in abundance and can be recorded at very low cost. Taking a Support Vector Machine (SVM) approach, this paper presents a method for learning retrieval functions. From a theoretical perspective, this method is shown to be well-founded in a risk minimization framework. Furthermore, it is shown to be feasible even for large sets of queries and features. The theoretical results are verified in a controlled experiment. It shows that the method can effectively adapt the retrieval function of a meta-search engine to a particular group of users, outperforming Google in terms of retrieval quality after only a couple of hundred training examples.
Trajectory-Based Visual Localization in Underwater Surveying Missions (2015)

We present a new vision-based localization system applied to an autonomous underwater vehicle (AUV) with limited sensing and computation capabilities. The traditional EKF-SLAM approaches are usually expensive in terms of execution time; the approach presented in this paper strengthens this method by adopting a trajectory-based schema that reduces the computational requirements. The pose of the vehicle is estimated using an extended Kalman filter (EKF), which predicts the vehicle motion by means of a visual odometer and corrects these predictions using the data associations (loop closures) between the current frame and the previous ones. One of the most important steps in this procedure is the image registration method, as it reinforces the data association and, thus, makes it possible to close loops reliably. Since the use of standard EKFs entail linearization errors that can distort the vehicle pose estimations, the approach has also been tested using an iterated Kalman filter (IEKF). Experiments have been conducted using a real underwater vehicle in controlled scenarios and in shallow sea waters, showing an excellent performance with very small errors, both in the vehicle pose and in the overall trajectory estimates.
Neuronal Survival or Death after Dendrite Transection Close to the Perikaryon: Correlation with Electrophysiologic, Morphologic, and Ultrastructural Changes (1985)

We investigated the probability of survival of mouse spinal neurons in monolayer cultures after transection lesions of dendrites made within 400 microns of the perikarya. Based on a total of 650 lesioned neurons, the following observations were made. First, neuronal survival is a function of lesion distance from the perikaryon and of process diameter at the lesion site. For an average lesion diameter of 3 microns, dendrite transections at 50 microns, 100 microns, and 150 microns were associated with survival probabilities of 30%, 53%, and 70%, respectively. Second, the fate of the injured cells was definitely established 24 hours after injury and very likely was determined as early as 2 hours. Third, early stages of deterioration leading to cell death were associated with cytoplasmic phase brightness on light microscopy, correlating with an appearance of numerous, small, electron-lucent vacuoles and swollen mitochondria on electron microscopy. The cytoplasm of these moribund cells stained darkly and contained no visible microtubules or neurofilaments. Fourth, the magnitude and time course of injury potentials recorded at the somata were a function of the lesion distance and did not return to prelesion levels within 30 minutes after transection. Fifth, at 24 hours after injury, the average membrane potential of lesioned neurons was 8% below that of control neurons. Sixth, at a lesion distance of approximately 300 microns both the injury potential and the probability of cell death approach zero. We conclude that, in the model system used, neuronal survival after dendrite amputation depends on physical parameters of the lesion that determine the magnitude of the injury current reaching the soma. Survival is not assured if the injury is inflicted within 250 microns of the cell body, and cell death is likely for lesions within 50 microns of the soma. The below-normal membrane potentials at 24 hours after injury suggest a possible greater vulnerability of recovering neurons to secondary insults. The characteristic mitochondrial disruption and loss of microtubules implies that the calcium component of the injury current contributes to cell death.
Cutting Edge: Expression of the C-C Chemokine Receptor CCR3 in Human Airway Epithelial Cells (2001)

Chemokine-induced eosinophil chemotaxis is mediated primarily through the C-C chemokine receptor, CCR3. We have now detected CCR3 immunoreactivity on epithelial cells in biopsies of patients with asthma and other respiratory diseases. CCR3 mRNA was detected by Northern blot analysis after TNF-alpha stimulation of the human primary bronchial epithelial cells as well as the epithelial cell line, BEAS-2B; IFN-gamma potentiated the TNF-alpha-induced expression. Western blots and flow cytometry confirmed the expression of CCR3 protein. This receptor is functional based on studies demonstrating eotaxin-induced intracellular Ca(2+) flux and tyrosine phosphorylation of cellular proteins. The specificity of this functional response was confirmed by blocking these signaling events with anti-CCR3 mAb (7B11) or pertussis toxin. Furthermore, (125)I-eotaxin binding assay confirmed that CCR3 expressed on epithelial cells have the expected ligand specificity. These studies indicate that airway epithelial cells express CCR3 and suggest that CCR3 ligands may influence epithelial cell functions.
CpG DNA and immunotherapy of allergic airway diseases (2003)

Atopic asthma is a highly prevalent and serious health problem for which no therapy currently offers the hope of a cure. Preindustrialized and rural populations appear relatively protected from the asthma epidemic; the hygiene hypothesis ascribes this protection to the effects of microbes and microbial products. An important immunostimulant component of microbes is DNA; bacterial DNA contains sequence motifs centred on the CpG dinucleotide, which are suppressed in mammalian DNA. Oligonucleotides containing these motifs (CpG ODN), like bacterial DNA, promote Th1 and regulatory-type immune responses. Using CpG ODN, we and others have demonstrated in murine studies that CpG ODN are effective in preventing the development of atopic airways disease. Moreover, when administered in conjunction with experimental allergen, they promote the reversal of established eosinophilic inflammation. These data suggest that CpG ODN may be a novel therapeutic tool for the treatment of atopic asthma.
Prostate Cancer: Image Guidance and Adaptive Therapy (2007)

Image-guided radiation therapy implies the use of a variety of imaging techniques in the treatment room to determine the location of target areas with the patient in the treatment position. This is particularly relevant for prostate cancer radiation therapy since the prostate gland can differ in its position within the pelvis from one treatment to another. The different imaging techniques include transabdominal ultrasound, in-room X-rays with and without the use of intraprostatic implanted fiducials, kilovoltage and megavoltage CT techniques, and even in-room MRI. The workflow and capabilities of each imaging system need to be evaluated and investigated individually.
Specificity of skin test with varicella-zoster virus antigen in varicella-zoster and herpes simplex virus infections (1987)

Specificity of the skin test with varicella-zoster virus (VZV) antigen was examined in guinea pigs infected with herpes simplex virus (HSV) type 1 or VZV and in children with a history of HSV infection who developed varicella. Infected guinea pigs responded positively only to homologous virus. No cross-reaction between HSV and VZV was detected in the skin test, as well as in the neutralization test in infected guinea pigs, suggesting that the VZV skin test is specific for immunity to VZV infection. Twelve children were infected with HSV during an HSV epidemic and subsequently developed varicella in institutional settings. During the 2.5-month period between the HSV and VZV infections, the immune status of the children to VZV was negative both in the skin test and in the antibody test, although antibody to HSV was detected by an immune adherence hemagglutination test. After VZV infection, all responded positively both in the skin test and in the antibody test (immune adherence hemagglutination test) to VZV. These results suggest that the VZV skin test is specific for immunity to VZV infection, not cross-reactive to HSV infection in humans. This specificity will be of value in screening susceptibility or immunity to VZV, irrespective of prior HSV infection.
Chondroitin sulphate. A new intraperitoneal treatment for postoperative adhesion prevention in the rabbit. (1987)

A study was designed to test chondroitin sulphate and other high-molecular-weight solutions, using the rabbit uterus as the surgical model, in the prevention of postoperative adhesions. Eighty-five mature white female New Zealand rabbits underwent surgical injury of each uterine horn, with surgical repair of the left horn only in all animals using 9-0 nylon. The rabbits were randomly divided into five groups: groups A, B and C received 25 mL of chondroitin sulphate, sodium carboxymethylcellulose or 32% dextran 70, respectively. The remaining two groups received either 50 mL of normal saline (D) or no solution (E). Postoperatively the animals were killed, and the adhesions were carefully scored. The results clearly demonstrated the superiority of chondroitin sulphate as an intraperitoneal treatment for the prevention of postoperative adhesions (P less than .001 vs. carboxymethyl cellulose, dextran, saline and control).
Induction of p53-Dependent Senescence by the MDM2 Antagonist Nutlin-3a in Mouse Cells of Fibroblast Origin (2007)

Cellular senescence is emerging as an important in vivo anticancer response elicited by multiple stresses, including currently used chemotherapeutic drugs. Nutlin-3a is a recently discovered small-molecule antagonist of the p53-destabilizing protein murine double minute-2 (MDM2) that induces cell cycle arrest and apoptosis in cancer cells with functional p53. Here, we report that nutlin-3a induces cellular senescence in murine primary fibroblasts, oncogenically transformed fibroblasts, and fibrosarcoma cell lines. No evidence of drug-induced apoptosis was observed in any case. Nutlin-induced senescence was strictly dependent on the presence of functional p53 as revealed by the fact that cells lacking p53 were completely insensitive to the drug, whereas cells lacking the tumor suppressor alternative reading frame product of the CDKN2A locus underwent irreversible cell cycle arrest. Interestingly, irreversibility was achieved in neoplastic cells faster than in their corresponding parental primary cells, suggesting that nutlin-3a and oncogenic signaling cooperate in activating p53. Our current results suggest that senescence could be a major cellular outcome of cancer therapy by antagonists of the p53-MDM2 interaction, such as nutlin-3a.
Purification and identification of bovine liver gamma-carboxylase. (1992)

The microsomal gamma-carboxylase catalyzes modification of a limited set of glutamyl residues to gamma-carboxyglutamyl residues in a vitamin K-dependent reaction that also utilizes O2 and CO2. We report the purification to apparent homogeneity of the bovine liver microsomal carboxylase. Affinity chromatography exploiting the association of the carboxylase with prothrombin precursor and carboxylase binding to the propeptide sequence were combined with ion-exchange chromatography and fractionation using immobilized lectins. A 3.5 x 10(5)-fold purification was obtained, which is the highest purification, by a factor of 35, yet reported for this enzyme. A single 98-kDa protein is obtained from this isolation. Carboxylase activity is associated with this protein by two different criteria. Antibodies prepared against the carboxylase detected the 98-kDa protein when used in Western analysis. In addition, the single 98-kDa protein was shown to comigrate with activity when electrophoresed in a nondenaturing gel system. The availability of purified preparations of carboxylase will facilitate an increased understanding of the complex biochemical reaction carried out by this protein.