gebhart/patrepeval huggingface dataset:
Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions (2004)

Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is localized to the sarcolemma. In rare cases, however, this labelling is equivocal and similar to that observed in controls making diagnosis difficult. We report here that in such instances immunolabelling with antibodies to the neuronal form of nitric oxide synthase (nNOS) can be useful in suspecting a dystrophinopathy with a mutation in the 'hot-spot' rod domain and help to direct molecular analysis. nNOS localizes to the sarcolemma of mature muscle fibres via several components of the dystrophin-associated protein complex (DAPC) including dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very low or absent because of deletions in critical regions of the rod domain. We report three cases who presented with only mild or no muscle weakness but had elevated serum creatine kinase activity and dystrophin immunolabelling indistinguishable from normal, making a pathological diagnosis difficult. All three cases had a complete absence of sarcolemmal nNOS and were subsequently found to have an in-frame deletion in the common rod domain exons (in these cases 48, 45-51, 47-53) compatible with a BMD. In addition, we observed that nNOS appears to be developmentally regulated with the antibody used and was often absent from the sarcolemma of immature fibres. These findings demonstrate the value of including antibodies to nNOS in routine immunohistochemical studies and that absence of nNOS can be a more sensitive marker than up-regulation of utrophin for diagnosis of BMD. Immaturity of fibres, however, needs to be taken into account, especially in neonates.
Comparison of Standardized and Nonstandardized Nuclear Grade of Renal Cell Carcinoma to Predict Outcome Among 2,042 Patients (2002)

We compared the ability of original nuclear grades from surgical pathology reports and grades reviewed by a urologic pathologist to predict death due to renal cell carcinoma (RCC) for 2,042 patients treated with radical nephrectomy between January 1970 and December 1998. Reviewed grade I tumors had small, round nuclei with inconspicuous nucleoli visible at x400; grade 2 contained round to slightly irregular nuclei with mildly enlarged nucleoli visible at x200; grade 3 had round to irregular nuclei with prominent nucleoli visible at x100; grade 4 contained enlarged pleomorphic or giant cells. Predictive abilities were compared using R2 values from Cox proportional hazards models. There were 1,733 (84.87%) clear cell, 222 (10.87%) papillary, and 87 (4.26%) chromophobe tumors. Reviewed grades were more predictive of death due to RCC than original grades for clear cell (R2, 21% vs 16%), papillary (R2, 16% vs 13%), and chromophobe (R2, 39% vs 27%) RCC. Among patients with clear cell and papillary RCC, this difference was apparent even after adjusting for the 1997 TNM stage. Standardized nuclear grades were more predictive of death due to RCC than nonstandardized grades for all subtypes studied.
Potent New Antiviral Compound Shows Similar Inhibition and Structural Interactions with Drug Resistant Mutants and Wild Type HIV-1 Protease (2007)

The potent new antiviral inhibitor GRL-98065 (1) of HIV-1 protease (PR) has been studied with PR variants containing the single mutations D30N, I50V, V82A, and I84V that provide resistance to the major clinical inhibitors. Compound 1 had inhibition constants of 17-fold, 8-fold, 3-fold, and 3-fold, respectively, for PR(D30N), PR(I50V), PR(V82A), and PR(I84V) relative to wild type PR. The chemically related darunavir had similar relative inhibition, except for PR(D30N), where inhibitor 1 was approximately 3-fold less potent. The high resolution (1.11-1.60 Angstrom) crystal structures of PR mutant complexes with inhibitor 1 showed small changes relative to the wild type enzyme. PR(D30N) and PR(V82A) showed compensating interactions with inhibitor 1 relative to those of PR, while reduced hydrophobic contacts were observed with PR(I50V) and PR(I84V). Importantly, inhibitor 1 complexes showed fewer changes relative to wild type enzyme than reported for darunavir complexes. Therefore, inhibitor 1 is a valuable addition to the antiviral inhibitors with high potency against resistant strains of HIV.
Secretory Production of Recombinant Protein by a High Cell Density Culture of a Protease Negative Mutant Escherichia coli Strain (1999)

Several protease negative mutant strains including HM114, HM126, and HM130 as well as their parent strain KS272 were compared for their growth and secretory production of a model fusion protein, protein A-beta-lactamase. HM114, a strain deficient in two cell envelope proteases, grew slightly faster and produced more fusion protein than the other strains deficient in more proteases. HM114 was grown to a cell dry weight of 47.86 g/L in 29 h using pH-stat, fed-batch cultivation. The beta-lactamase activity was 11.25 x 10(4) U/L, which was 30% higher than that obtained with its parent strain KS272. Up to 96% of protein A-beta-lactamase fusion protein could be recovered by a simple cold osmotic shock method. The specific beta-lactamase activity obtained with HM114 after fractionation was 4.5 times higher than that obtained with KS272.
MET protein is phosphorylated in human clear cell renal carcinoma (2006)

1652 It was well known that inactivation of VHL gene predisposes human clear renal cell carcinoma (CCRC). But details about critical roles of VHL inactivation during early stage of tumorigenisis are still unknown. MET protein is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF) to regulate cell growth, cell morphology, and cell motility. We previously reported that MET protein was overexpressed and phosphorylated without HGF/SF in established CCRC cells, 786-O, UMRC-3 and UMRC-6. This constitutive phosphorylation of MET protein in was inhibited by the rescue of exogenous wild-type VHL gene without decrease in expression level of MET protein. Additionally, K252a, MET specific inhibitor, inhibited cell growth and tumorigenesis of established CCRC cells (AACR annual meeting 2005). These results were based on the established CCRC cells. The phosphorylation status of MET protein in human CCRC tumor tissues has not been reported. In this study, we analyzed the phosphorylation status of MET protein in 18 CCRC tumor tissues and normal kidney tissue gained by surgeries. MET protein was overexpressed in 14 CCRC tissues (78%) compared with that in normal kidney tissues. The phosphorylation level of MET protein in CCRC tumor was increased in all of 18 tumor tissues compared with normal tissue. Interestingly MET protein was hyperphosphorylated compared with that in normal tissue in all of 4 CCRC tissues with the same expression level of MET protein as that in normal tissue. This result meant that MET protein was phosphorylated in CCRC dependently on its expression levels. We concluded that MET protein had potency as a target molecule for renal carcinoma therapy.
Erenumab (AMG 334) in episodic migraine (2017)

This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life.
Expression of Follistatin-Related Genes Is Altered in Heart Failure (2008)

Follistatins play roles in diverse biological processes including cell proliferation, wound healing, inflammation, and skeletal muscle growth, yet their role in the heart is currently unknown. We have investigated the myocardial expression profile and cellular distribution of follistatin (FST) and the FST-like genes FSTL1 and FSTL3 in the normal and failing heart. Expression was further analyzed in the novel setting of recovery from heart failure in myocardium obtained from patients who received combined mechanical (left ventricular assist device) and pharmacological therapy. Real-time PCR revealed that FSTL1 and FSTL3 expression was elevated in heart failure but returned to normal after recovery. FSTL3 expression levels correlated with molecular markers of disease severity and FSTL1 with the endothelial cell marker CD31, suggesting a potential link with vascularization. FSTL1 levels before treatment correlated with cardiac function after recovery, suggesting initial levels may influence long-term outcome. Immunohistochemistry revealed that FST was primarily localized to fibroblasts and vascular endothelium within the heart, whereas FSTL1 was localized to myocytes, endothelium, and smooth muscle cells and FSLT3 to myocytes and endothelium. Microarray analysis revealed that FST and FSTL1 were associated with extracellular matrix-related and calcium-binding proteins, whereas FSTL3 was associated mainly with cell signaling and transcription. These data show for the first time that elevated myocardial expression of FST-like genes is a feature of heart failure and may be linked to both disease severity and mechanisms underlying recovery, revealing new insight into the pathogenesis of heart failure and offering novel therapeutic targets.
A Comparison and Evaluation of Multi-View Stereo Reconstruction Algorithms (2006)

This paper presents a quantitative comparison of several multi-view stereo reconstruction algorithms. Until now, the lack of suitable calibrated multi-view image datasets with known ground truth (3D shape models) has prevented such direct comparisons. In this paper, we first survey multi-view stereo algorithms and compare them qualitatively using a taxonomy that differentiates their key properties. We then describe our process for acquiring and calibrating multiview image datasets with high-accuracy ground truth and introduce our evaluation methodology. Finally, we present the results of our quantitative comparison of state-of-the-art multi-view stereo reconstruction algorithms on six benchmark datasets. The datasets, evaluation details, and instructions for submitting new models are available online at http://vision.middlebury.edu/mview.
LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators (2011)

The LIM kinases 1 and 2 (LIMK1 and LIMK2) are dual specificity (serine/threonine and tyrosine) kinases. Although they show significant structural similarity, LIMK1 and LIMK2 show different expression, subcellular localization, and functions. They are involved in many cellular functions, such as migration, cycle, and neuronal differentiation and also have a role in pathological processes, such as cancer cell invasion and metastatis, as well as in neurodevelopmental disorders (namely, the William's syndrome). LIM kinases have a relevant number of known partners that are able to induce or limit the ability of LIMK1 and LIMK2 to phosphorylate and inactivate their major substrate, cofilin. On the contrary, only a limited number of small molecules that interact with the two proteins to modulate their kinase activity have been identified. In this review, the most important partners of LIM kinases and their modulating activity toward LIMKs are described. The small compounds identified as LIMK1 and LIMK2 modulators are also reported, as well as their role as possible therapeutic agents for LIMK-induced diseases.
Influence of cytokinins and novel cytokinin antagonists on the senescence of detached leaves of Arabidopsis thaliana (2007)

Cytokinins N6-benzyladenine (BA) and 1-(2-chloropyridin-4-yl)-3-phenylurea (4PU-30) delayed the senescence of detached leaves (3rd to 7th leaf node) of wild and ethylene insensitive eti5 mutant of Arabidopsis thaliana. The novel anticytokinins, structural analogues of purine and phenylurea cytokinins also affected the senescence of detached rosette leaves of A. thaliana. They diminished to a significant extent the cytokinin-induced delay of chlorophyll destruction, but without a considerable difference in their action against both types of cytokinins. These results correlated with changes observed in ribonuclease (RNase) activity.
Potential of Nasopharynx-associated Lymphoid Tissue for Vaccine Responses in the Airways (2011)

Nasopharynx-associated lymphoid tissue (NALT), constituting Waldeyer's ring in humans, is a unique inductive site for B-cell responses and plasma cell generation. This makes the nasal route of vaccine administration interesting for induction of mucosal and systemic antibodies. The unpaired nasopharyngeal tonsil (adenoids) and the paired palatine tonsils are prominent NALT structures, functionally similar to the paired rodent NALT structures located dorsal to the cartilaginous soft palate. Human NALT is more strategically located, however, because its elements are exposed to both airborne and alimentary antigens and have antigen-retaining crypts. It also shows similarities with lymph nodes and participates both in systemic- and secretory-type mucosal immunity. Primary follicles occur at 16 weeks of gestation, which is similar to Peyer's patches but different from rodent NALT whose organogenesis begins at birth. The formation of germinal centers reflecting B-cell activation does not take place until shortly after birth, and terminal differentiation of plasma cell can be seen about 2 weeks postnatally. Germinal centers arise in T cell-dependent B-cell responses and are associated with somatic hypermutation of Ig V-region genes. Downstream switching to various Ig isotypes also takes place, with or without concurrent expression of the J-chain gene. The J chain is a crucial part of dimeric IgA and pentameric IgM, making these Ig polymers able to interact with the epithelial polymeric Ig receptor. This interaction is central in the formation of secretory IgA and secretory IgM. Accumulating evidence suggests a major role for NALT in antibody immunity of the respiratory tract and associated glands.
The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis. (1988)

The environmental contaminant 2,3,7,8-tetra-chlorodibenzo-p-dioxin produces its biological effects by binding to an intracellular protein (the Ah receptor). The dioxin-Ah receptor complex activates cytochrome P1-450 gene transcription by interacting with dioxin-responsive enhancers. Here, we report that the dioxin-Ah receptor complex binds to DNA containing the "core" sequence 5'-TA/TGCGTG-3', which is present in each of three receptor-dependent enhancers. Functional analyses indicate that binding of the liganded Ah receptor to the core sequence fails to generate an active enhancer and that nucleotides flanking the core sequence must contribute to enhancer function and dioxin action.
Web Security Sourcebook (1998)

Caught in Our Own Web. Basic Browser Security. Advanced Browser Security and User Privacy. Interpreting Scripts in the Browser. Basic Server-Side Security. Advanced Server-Side Security. Creating Secure CGI Scripts. Firewalls and the Web. Transaction Security and the Web. Securing Web Commerce. What's Next? Security in a Rapidly Changing World. Appendices. Index.
Distinctive gene expression patterns in human mammary epithelial cells and breast cancers (1999)

cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors. Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples. By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster, the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined. Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples. Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectively. Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis. These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors.
Laboratory evaluations of the immediate and sustained effectiveness of lotilaner (Credelio™) against three common species of ticks affecting dogs in Europe (2017)

The high and sustained efficacy against the three common species of ticks in Europe, R. sanguineus, I. ricinus and D. reticulatus, demonstrates that lotilaner can be a valuable tool in the treatment of canine tick infestations. Lotilaner flavoured chewable tablets were well tolerated and effectiveness was sustained through at least 35 days.
Oligomeric complexes involved in translocation of proteins across the membrane of the endoplasmic reticulum (1999)

Proteins involved in protein translocation across the membrane of the endoplasmic reticulum assemble into different oligomeric complexes depending on their state of function. To analyse such membrane protein complexes we fractionated proteins of mammalian rough microsomes and analysed them using blue native PAGE and immunoblotting. Among the proteins characterised are the Sec61p complex, the oligosaccharyl transferase (OST) complex, the translocon-associated protein (TRAP) complex, the TRAM and RAMP4 proteins, the signal recognition particle (SRP) and the SRP receptor (SR). Interestingly, the RAMP4 protein, SR and OST complex display more than one oligomeric form.
Quantification of free polysaccharide in meningococcal polysaccharide-diphtheria toxoid conjugate vaccines. (2000)

A precipitation method using deoxycholate/HCI has been applied successfully to separate unconjugated free polysaccharide from carrier protein-bound material in meningococcal polysaccharide-diphtheria toxoid conjugate vaccines. The method effectively separated free and bound polysaccharide in conjugate vaccines prepared from Neisseria meningitidis serotypes A, C, W135 and Y. Free polysaccharide remained in the supernatant after deoxycholate treatment while protein-bound polysaccharide was fully precipitated. Testing by both colorimetric assay and high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has confirmed the selective loss of protein-bound polysaccharide in samples of conjugate vaccine or conjugate vaccine mixed with known amounts of free polysaccharide. This rapid separation method requires minimum sample handling and is specific, reproducible, and allows assessment of free polysaccharide levels in vaccines at final container concentration.
A 2-1600 MHz 1.2-2.5 V CMOS clock-recovery PLL with feedback phase-selection and averaging phase-interpolation for jitter reduction (2003)

The clock-recovery PLL requires >50% VCO tuning range to accommodate CMOS process variations. In a macro-cell PLL used in applications at different frequencies, the tuning range must be even larger. This requires special techniques for initial locking, since no phase detector for NRZ data operates reliability with a large initial frequency offset. A modification of the circuit results in a PLL that first generates a number of clock phases and than selects one of these phases as the recovered clock. In most communication systems, the data rate is specified to within a few hundred ppm, so an appropriate choice of f/sub ref/ and N makes the generated clocks have a frequency close to the data rate, avoiding initialization/start-up procedures.
Discussion Reporting of 14C Data (1977)

Count rates, representing the rate of 14 C decay, are the basic data obtained in a 14 C laboratory. The conversion of this information into an age or geochemical parameters appears a simple matter at first. However, the path between counting and suitable 14 C data reporting (table 1) causes headaches to many. Minor deflections in pathway, depending on personal interpretations, are possible and give end results that are not always useful for inter-laboratory comparisons. This discussion is an attempt to identify some of these problems and to recommend certain procedures by which reporting ambiguities can be avoided.
Amino Acid Phosphoramidate Monoesters of 3‘-Azido-3‘-deoxythymidine:  Relationship between Antiviral Potency and Intracellular Metabolism (2000)

A series of phosphoramidate monoesters of 3'-azido-3'-deoxythymidine (AZT) bearing aliphatic amino acid methyl esters (3a, 3c, 4a, 4c, 5-7) and methyl amides (3b, 3d, 4b, 4d) was prepared and evaluated for anti-HIV-1 activity in peripheral blood mononuclear cells (PBMCs). These compounds, which showed no cytotoxicity at concentrations of 100 microM, were effective at inhibiting HIV-1 replication at concentrations of 0.08-30 microM. Since the D-phenylalanine and D-tryptophan derivatives exhibited equivalent or enhanced antiviral activity compared to their L-counterparts, there appears to be no specific stereochemical requirement for the amino acid side chain. In addition, except for the D-phenylalanine derivatives, the methyl amides had greater antiviral activity than the corresponding methyl esters. On the basis of the observed antiviral activity of AZT phosphoramidate monoesters 3a and 4a in PBMCs and CEM cells, the mechanism of action of these two compounds was investigated. AZT-MP and substantial amounts of either phosphoramidate were detected in PBMCs and CEM cells treated with either 3a or 4a. Biological mechanistic studies demonstrated that 3a and 4a affect viral replication at a stage after virus entry and preceding viral DNA integration. Quantitation of the intracellular levels of AZT-TP in PBMCs and CEM cells treated with 3a and 4a in the presence and absence of exogenous thymidine correlated the intracellular levels of AZT-TP to the antiviral activity and suggested that AZT-TP was responsible for the activity observed. In addition, the reduced toxicity of 3a and 4a toward CEM cells relative to AZT correlated with reduced levels of total phosphorylated AZT and not AZT-TP. Stable carbamate analogues of 3a and 4a were prepared and shown to inhibit the production of AZT-MP from cell-free extracts of CEM cells, further suggesting that a phosphoramidate hydrolase may be responsible for intracellular P-N bond cleavage. Taken together, these results suggest that the biological activity and intracellular metabolism of nucleoside phosphoramidate monoesters are distinct from that of phosphoramidate diesters.
Free Radicals Produced from the Derivatives of Pyrylium Salts in Solution by Photoillumination (1985)

Abstract The photoreactions of 2,4,6-triphenyl- (TPP), 2-t-butyl-4,6-diphenylpyrylium (2BDPP) and 2,4,6-triphenylthiopyrylium (TPTP) salts in tetrahydrofuran (THF) and/or 1,2-dimethoxyethane were investigated. Photoproducts were identified to be pyranyl radicals on the basis of photochemical behavior and ESR spectra. Quantum yields of one-electron reduction reactions of TPP, 2BDPP, and TPTP were obtained to be 0.21, 0.047, and 0.53, respectively. The hf coupling constants of protons in the radicals were determined by simulation. The photoillumination of TPP in THF at low temperatures revealed that a certain intermediate radical species was involved in this one-electron photoreduction.