gebhart/patrepeval huggingface dataset:
The Clinically Approved Proteasome Inhibitor PS-341 Efficiently Blocks Influenza A Virus and Vesicular Stomatitis Virus Propagation by Establishing an Antiviral State (2010)

ABSTRACT Recently it has been shown that the proinflammatory NF-κB pathway promotes efficient influenza virus propagation. Based on these findings, it was suggested that NF-κB blockade may be a promising approach for antiviral intervention. The classical virus-induced activation of the NF-κB pathway requires proteasomal degradation of the inhibitor of NF-κB, IκB. Therefore, we hypothesized that inhibition of proteasomal IκB degradation should impair influenza A virus (IAV) replication. We chose the specific proteasome inhibitor PS-341, which is a clinically approved anticancer drug also known as Bortezomib or Velcade. As expected, PS-341 treatment of infected A549 cells in a concentration range that was not toxic resulted in a significant reduction of progeny virus titers. However, we could not observe the proposed suppression of NF-κB-signaling in vitro . Rather, PS-341 treatment resulted in an induction of IκB degradation and activation of NF-κB as well as the JNK/AP-1 pathway. This coincides with enhanced expression of antiviral genes, such as interleukin-6 and, most importantly, MxA, which is a strong interferon (IFN)-induced suppressor of influenza virus replication. This suggests that PS-341 may act as an antiviral agent via induction of the type I IFN response. Accordingly, PS-341 did not affect virus titers in Vero cells, which lack type I IFN genes, but strongly inhibited replication of vesicular stomatitis virus (VSV), a highly IFN-sensitive pathogen. Thus, we conclude that PS-341 blocks IAV and VSV replication by inducing an antiviral state mediated by the NF-κB-dependent expression of antivirus-acting gene products.
Mass Spectrometry Imaging (2010)

Mass spectrometry (MS) offers unmatched capabilities for the detection, characterization, and identification of a broad range of analytes. Mass spectrometry imaging (MSI) integrates MS data with infor
Interaction of ABC Multidrug Transporters with Anticancer Protein Kinase Inhibitors: Substrates and/or Inhibitors? (2009)

Protein kinase inhibitors (PKI) are becoming key agents in modern cancer chemotherapy, and combination of PKIs with classical chemotherapeutic drugs may help to overcome currently untreatable metastatic cancers. Since chemotherapy resistance is a recurrent problem, mechanisms of resistance should be clarified in order to help further drug development. Here we suggest that in addition to PKI resistance based on altered target structures, the active removal of these therapeutic agents by the MDR-ABC transporters should also be considered as a major cause of clinical resistance. We discuss the occurring systemic and cellular mechanisms, which may hamper PKI efficiency, and document the role of selected MDR-ABC transporters in these phenomena through their interactions with these anticancer agents. Moreover, we suggest that PKI interactions with ABC transporters may modulate overall drug metabolism, including the fate of diverse, chemically or target-wise unrelated drugs. These effects are based on multiple forms of MDR-ABC transporter interaction with PKIs, as these compounds may be both substrates and/or inhibitors of an ABC transporter. We propose that these interactions should be carefully considered in clinical application, and a combined MDR-ABC transporter and PKI effect may bring a major advantage in future drug development.
Hyper-Stain Inspector: A Framework for Robust Registration and Localised Co-Expression Analysis of Multiple Whole-Slide Images of Serial Histology Sections (2017)

In this paper, we present a fast method for registration of multiple large, digitised whole-slide images (WSIs) of serial histology sections. Through cross-slide WSI registration, it becomes possible to select and analyse a common visual field across images of several serial section stained with different protein markers. It is, therefore, a critical first step for any downstream co-localised cross-slide analysis. The proposed registration method uses a two-stage approach, first estimating a fast initial alignment using the tissue sections' external boundaries, followed by an efficient refinement process guided by key biological structures within the visual field. We show that this method is able to produce a high quality alignment in a variety of circumstances, and demonstrate that the refinement is able to quantitatively improve registration quality. In addition, we provide a case study that demonstrates how the proposed method for cross-slide WSI registration could be used as part of a specific co-expression analysis framework.
A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy (2008)

Autosomal recessive nonsyndromic hearing impairment (NSHI) is a heterogeneous condition, for which 53 genetic loci have been reported, and 29 genes have been identified to date. One of these, OTOF, encodes otoferlin, a membrane-anchored calcium-binding protein that plays a role in the exocytosis of synaptic vesicles at the auditory inner hair cell ribbon synapse. We have investigated the prevalence and spectrum of deafness-causing mutations in the OTOF gene. Cohorts of 708 Spanish, 83 Colombian, and 30 Argentinean unrelated subjects with autosomal recessive NSHI were screened for the common p.Gln829X mutation. In compound heterozygotes, the second mutant allele was identified by DNA sequencing. In total, 23 Spanish, two Colombian and two Argentinean subjects were shown to carry two mutant alleles of OTOF. Of these, one Colombian and 13 Spanish subjects presented with auditory neuropathy. In addition, a cohort of 20 unrelated subjects with a diagnosis of auditory neuropathy, from several countries, was screened for mutations in OTOF by DNA sequencing. A total of 11 of these subjects were shown to carry two mutant alleles of OTOF. In total, 18 pathogenic and four neutral novel alleles of the OTOF gene were identified. Haplotype analysis for markers close to OTOF suggests a common founder for the novel c.2905_2923delinsCTCCGAGCGCA mutation, frequently found in Argentina. Our results confirm that mutation of the OTOF gene correlates with a phenotype of prelingual, profound NSHI, and indicate that OTOF mutations are a major cause of inherited auditory neuropathy.
The Syntheses of Amphiphilic Camouflaged Carboranes as Modules for Supramolecular Construction (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThe Syntheses of Amphiphilic Camouflaged Carboranes as Modules for Supramolecular ConstructionA. Maderna, A. Herzog, Carolyn B. Knobler, and M. Frederick HawthorneView Author Information The University of California at Los Angeles Department of Chemistry and Biochemistry 405 Hilgard Avenue, Los Angeles, California 90095 Cite this: J. Am. Chem. Soc. 2001, 123, 42, 10423–10424Publication Date (Web):September 28, 2001Publication History Received6 August 2001Published online28 September 2001Published inissue 1 October 2001https://pubs.acs.org/doi/10.1021/ja016768ghttps://doi.org/10.1021/ja016768grapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views482Altmetric-Citations25LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Amphiphiles,Cluster chemistry,Molecular structure,Reaction products,Solution chemistry Get e-Alerts
Hemostatic Activation and Outcome After Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke (2006)

Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis.
THE SOUL-HOUSES. RIFEH (2013)

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Nurses and ethical conflict with employer organisations. (2012)

It is just over 25 years since Yarling and McElmurry (1986) famously argued that nurses 'are often not free to be moral' (p63). What was meant by this provocative claim was not that nurses lacked 'freedom of will' to think morally and to experience moral problems. Rather the contention was that nurses did not have 'freedom of action in the sense that acts are free from unforced choice' and thus they were often 'not free to fulfil their moral obligations to the patient' when the interests of the patient were in conflict with the interests of their employing organisation (Yarling and McElmurry 1986, p65).
Role stressors, burnout, mediators, and job satisfaction: A stress-strain-outcome model and an empirical test (1998)

The purpose of this study was to develop and empirically evaluate a model that delineated the processes whereby clinical social workers experience burnout and job dissatisfaction in their workplaces. First, on the basis of an array of relevant variables as stress-strain (burnout)-outcome (job dissatisfaction), the proposed model specified interrelationships among work stressors and burnout, the intervening factors between burnout and job satisfaction, and the final outcome variable, job satisfaction. Then the theoretical model was translated into an empirically testable model. Finally, the model was tested with a sample of 165 clinical social workers in Florida by using linear structural relation (LISREL) techniques. The results of analysis of components fit indicated that role conflict did intensify the amount of burnout and job dissatisfaction. Social support acted as an intervening and moderating factor between burnout and job dissatisfaction. Implications for social work practice are provided.
Wide intrascene dynamic range CMOS APS using dual sampling (1997)

A CMOS active pixel sensor (APS) that achieves wide intrascene dynamic range using dual sampling is reported. A 64/spl times/64 element prototype sensor with dual output architecture was fabricated using a 1.2 /spl mu/m n-well CMOS process with 20.4 /spl mu/m pitch photodiode-type active pixels. The sensor achieves an intrascene dynamic range of 109 dB without nonlinear companding.
Transforming viruses directly reduce the cellular growth requirement for a platelet derived growth factor (1978)

Abstract Early passage mouse embryo fibroblasts, mouse 3T3 cell lines, and early passage diploid human fibroblasts grew to higher cell densities in tissue culture medium supplemented with serum than in medium supplemented with defibrinogenated platelet‐poor plasma (PPP). Unlike the mouse cells, the human fibroblasts displayed this differential growth response only in the presence of hypophysiologic concentrations of calcium. The addition of heat‐treated extracts of human platelets to PPP‐supplemented medium stimulated the replication of both the normal mouse cells and early passage human embryo fibroblasts. Human or mouse fibroblasts transformed by either retroviruses or by SV40, including SV40 infected “serum revertants” and “flat transformants,” grew to equal cell densities in medium supplemented with either serum or PPP. Infection of Balb/c‐3T3 cells with SV40 rapidly induced them to grow in PPP‐supplemented medium demonstrating that the ability of SV40‐transformed cell lines to proliferate in PPP‐supplemented medium does not arise from the cell culture selection procedures usually employed to obtain stable virus‐transformed cell lines. 3T3 cells infected but not transformed by retroviruses do not replicate in PPP‐supplemented medium demonstrating that reduction of the growth requirement for the platelet growth factor(s) by retroviruses is a transformation‐specific response. Cell cultures that did not proliferate well in PPP‐supplemented medium did not form tumors when inoculated into athymic nude mice. Many, although not all, of the lines which grew well in PPP medium were tumorigenic in nude mice. Together, these findings indicate that: (1) normal fibroblast‐like cells display a growth requirement for factor(s) present in serum but not found in PPP; (2) this serum specific growth factor is derived from platelets; (3) a primary response to viral transforming genes is a reduction in the growth requirement for these platelet‐derived factors; and (4) cells that have a reduced requirement for the platelet‐derived growth factor are often tumorigenic.
A Novel Rabies Vaccine Based on a Recombinant Parainfluenza Virus 5 Expressing Rabies Virus Glycoprotein (2012)

Untreated rabies virus (RABV) infection leads to death. Vaccine and postexposure treatment have been effective in preventing RABV infection. However, due to cost, rabies vaccination and treatment have not been widely used in developing countries. There are 55,000 human death caused by rabies annually. An efficacious and cost-effective rabies vaccine is needed. Parainfluenza virus 5 (PIV5) is thought to contribute to kennel cough, and kennel cough vaccines containing live PIV5 have been used in dogs for many years. In this work, a PIV5-vectored rabies vaccine was tested in mice. A recombinant PIV5 encoding RABV glycoprotein (G) (rPIV5-RV-G) was administered to mice via intranasal (i.n.), intramuscular (i.m.), and oral inoculation. The vaccinated mice were challenged with a 50% lethal challenge dose (LD(50)) of RABV challenge virus standard 24 (CVS-24) intracerebrally. A single dose of 10(6) PFU of rPIV5-RV-G was sufficient for 100% protection when administered via the i.n. route. The mice vaccinated with a single dose of 10(8) PFU of rPIV5-RV-G via the i.m. route showed very robust protection (90% to 100%). Intriguingly, the mice vaccinated orally with a single dose of 10(8) PFU of rPIV5-RV-G showed a 50% survival rate, which is comparable to the 60% survival rate among mice inoculated with an attenuated rabies vaccine strain, recombinant LBNSE. This is first report of an orally effective rabies vaccine candidate in animals based on PIV5 as a vector. These results indicate that rPIV5-RV-G is an excellent candidate for a new generation of recombinant rabies vaccine for humans and animals and PIV5 is a potential vector for oral vaccines.
Influence of Gluconeogenic Phosphoenolpyruvate Carboxykinase (PCK) Expression on Succinic Acid Fermentation in Escherichia coli Under High Bicarbonate Condition (2006)

This work was funded by the Genome-based Integrated
Bioprocess Development Project from the Korean Ministry
of Science and Technology. P. Kim was partly supported
by the Catholic University of Korea research fund 2006.
EXTRACELLULAR ENZYMES AND PATHOGENESIS OF SOFT-ROT ERWINIA (1994)

Historically the genus Erwinia has served as a repository for plant-pathogenic or plant-associated bacteria (25, 96, 128). Consequently, diverse bacteria that occupy different habitats on or within plants and plant remains have been lumped into this genus. Their diversity is also reflected in the range of symp­ toms, i.e. necrosis, wilts, galls, and rots elicited in a wide range of plants. This diversity notwithstanding, these bacteria are related genetically to other en­ terobacteria such as Escherichia coli and Salmonella typhimurium that have served well as model systems for genetic and physiological studies. Microbi­ ologists and plant pathologists alike were initially attracted to Erwinia because of the potential for the use of genetic tools developed for the E. coli system. Thus, several Erwinia species were selected as model systems for the analysis
The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds (2009)

Cell-surface pili are important virulence factors that enable bacterial pathogens to adhere to specific host tissues and modulate host immune response. Relatively little is known about the structure of Gram-positive bacterial pili, which are built by the sortase-catalyzed covalent crosslinking of individual pilin proteins. Here we report the 1.6-A resolution crystal structure of the shaft pilin component SpaA from Corynebacterium diphtheriae, revealing both common and unique features. The SpaA pilin comprises 3 tandem Ig-like domains, with characteristic folds related to those typically found in non-pilus adhesins. Whereas both the middle and the C-terminal domains contain an intramolecular Lys-Asn isopeptide bond, previously detected in the shaft pilins of Streptococcus pyogenes and Bacillus cereus, the middle Ig-like domain also harbors a calcium ion, and the C-terminal domain contains a disulfide bond. By mass spectrometry, we show that the SpaA monomers are cross-linked in the assembled pili by a Lys-Thr isopeptide bond, as predicted by previous genetic studies. Together, our results reveal that despite profound dissimilarities in primary sequences, the shaft pilins of Gram-positive pathogens have strikingly similar tertiary structures, suggesting a modular backbone construction, including stabilizing intermolecular and intramolecular isopeptide bonds.
0.18-V input charge pump with forward body biasing in startup circuit using 65nm CMOS (2010)

In this paper, a 0.18-V input three-stage charge pump circuit applying forward body bias is proposed. In the developed charge pump, all the MOSFETs are forward body biased by using the inter-stage/output voltages. By applying the proposed charge pump as the startup in the boost converter, the lower kick-up input voltage of the boost converter can be achieved. To verify the circuit characteristics, four test circuits have been implemented by using 65nm CMOS process. The measured available output current of the proposed charge pump under 0.18-V input voltage can be improved more than 150%. In addition, the boost converter can successfully been boosted from 0.18-V input to the 0.74-V output under 6mA output current. The proposed circuit is suitable for extremely low voltage applications such as harvesting energy sources.
Plasma Membrane Voltage-dependent Anion Channel Mediates Antiestrogen-activated Maxi Cl– Currents in C1300 Neuroblastoma Cells (2003)

The cell membrane large conductance voltage-dependent chloride channel (Maxi Cl- channel) has been recorded in different cell types following excision of membrane patches or stimulation by antiestrogens under whole-cell recording conditions. However, both its molecular nature and relevance to cell physiology await elucidation. Its electrophysiological properties resemble those of the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. This observation has led to the controversial hypothesis that VDAC could be the molecular correlate of the plasma membrane Maxi Cl- channel. We have investigated the cellular localization of VDAC and its relationship with the antiestrogen-activated Maxi Cl- current in C1300 neuroblastoma cells. The presence of a plasma membrane VDAC was demonstrated by immunoblotting of membrane fractions with monoclonal antibodies against the VDAC and by reverse transcription-PCR using primers that hybridize to a VDAC sequence coding for an N-terminal leader peptide required for its plasma membrane sorting. Besides, VDAC colocalized with markers of plasma membrane lipid rafts (cholera toxin beta subunit) but not caveolin-1. Transfection of C1300 cells with an antisense oligonucleotide directed against the specific membrane leader sequence of VDAC markedly reduced both VDAC immunostaining and antiestrogen-activated Maxi Cl- currents, suggesting that VDAC forms the plasma membrane Maxi Cl- channel or a part thereof.
A Common Polymorphism in the 5′-Untranslated Region of the VEGF Gene Is Associated With Diabetic Retinopathy in Type 2 Diabetes (2002)

Vascular endothelial growth factor (VEGF), a major mediator of vascular permeability and angiogenesis, may play a pivotal role in mediating the development and progression of diabetic retinopathy. In the present study, we examined the genetic variations of the VEGF gene to assess its possible relation to diabetic retinopathy in type 2 diabetic patients. Among seven common polymorphisms in the promoter region, 5'-untranslated region (UTR) and 3'UTR of the VEGF gene, genotype distribution of the C(-634)G polymorphism differed significantly (P = 0.011) between patients with (n = 150) and without (n = 118) retinopathy, and the C allele was significantly increased in patients with retinopathy compared with those without retinopathy (P = 0.0037). The odds ratio (OR) for the CC genotype of C(-634)G to the GG genotype was 3.20 (95% CI 1.45-7.05, P = 0.0046). The -634C allele was significantly increased in patients with nonproliferative diabetic retinopathy (non-PDR) (P = 0.0026) and was insignificantly increased in patients with proliferative diabetic retinopathy (PDR) (P = 0.081) compared with patients without retinopathy, although frequencies of the allele did not differ significantly between the non-PDR and PDR groups. Logistic regression analysis revealed that the C(-634)G polymorphism was strongly associated with an increased risk of retinopathy (P = 0.0018). Furthermore, VEGF serum levels were significantly higher in healthy subjects with the CC genotype of the C(-634)G polymorphism than in those with the other genotypes. These data suggest that the C(-634)G polymorphism in the 5'UTR of the VEGF gene is a novel genetic risk factor for diabetic retinopathy.
New Sesquiterpene Lactones from Sunflower Root Exudate as Germination Stimulants for Orobanche cumana (2013)

Orobanche cumana is a serious threat for cultivation of sunflower in Europe and Asia. Germination of the parasite is induced by metabolites released from the host root system. The first germination stimulant from sunflower root exudate was recently identified as dehydrocostus lactone, a sesquiterpene lactone. Bioassay-guided fractionation of root exudates now showed the release of additional sesquiterpene lactones. Besides dehydrocostus lactone, costunolide, tomentosin, and 8-epixanthatin were purified and identified spectroscopically. All four compounds induced germination of O. cumana at nano- to micromolar concentrations. Costunolide and dehydrocostus lactone concentrations above 1 μM reduced the activity, and application of 100 μM inhibited germination irreversibly. Seeds of Phelipanche ramosa could not be induced with costunolide. O. cumana seeds also germinated with GR24, a synthetic strigolactone. No bioactive fraction of sunflower contained compounds of this type. This supports previous findings that sesquiterpene lactones instead of strigolactones trigger the sunflower/O. cumana interaction.