gebhart/patrepeval huggingface dataset:
Radiation victim management and the haematologist in the future: Time to revisit therapeutic guidelines? (2010)

The European Response Category (RC) concept represents an attempt to integratively assess haematological/extrahematological radiation-induced lesions. Based on the frequently observed heterogeneity of bone marrow damage in accidental/intentional irradiations, the stimulation of residual stem cells using granulocyte Colony-stimulating factor remains the therapeutic standard after exposure to less than the lethal dose 50 % (Haematopoietic[H] score 3-H3). Allogeneic stem cell transplantation is indicated in case of medullary eradication (Haematopoietic score 4-H4) whereas extramedullary toxicity may determine the outcome. Especially in case of numerous casualties exhibiting acute radiation syndrome, the administration of survival factor combinations remains questionable, at least as a palliative treatment. In addition pleiotropic cytokines injection such as erythropoietin and keratinocyte growth factor and grafting multipotent mesenchymal stem cells - from underexposed bone marrow areas or fat tissues - could be proposed to prevent multiple organ failure syndrome development. Multi-disciplinary teams should be prepared to manage such patients.
Oligonucleotide gap-fill ligation for mutation detection and sequencingin situ (2015)

In clinical diagnostics a great need exists for targeted in situ multiplex nucleic acid analysis as the mutational status can offer guidance for effective treatment. One well-established method uses padlock probes for mutation detection and multiplex expression analysis directly in cells and tissues. Here, we use oligonucleotide gap-fill ligation to further increase specificity and to capture molecular substrates for in situ sequencing. Short oligonucleotides are joined at both ends of a padlock gap probe by two ligation events and are then locally amplified by target-primed rolling circle amplification (RCA) preserving spatial information. We demonstrate the specific detection of the A3243G mutation of mitochondrial DNA and we successfully characterize a single nucleotide variant in the ACTB mRNA in cells by in situ sequencing of RCA products generated by padlock gap-fill ligation. To demonstrate the clinical applicability of our assay, we show specific detection of a point mutation in the EGFR gene in fresh frozen and formalin-fixed, paraffin-embedded (FFPE) lung cancer samples and confirm the detected mutation by in situ sequencing. This approach presents several advantages over conventional padlock probes allowing simpler assay design for multiplexed mutation detection to screen for the presence of mutations in clinically relevant mutational hotspots directly in situ.
II.—WHAT IS AN EMOTION ? (1884)

Journal Article II.—WHAT IS AN EMOTION ? Get access WILLIAM JAMES WILLIAM JAMES Search for other works by this author on: Oxford Academic Google Scholar Mind, Volume os-IX, Issue 34, 1 April 1884, Pages 188–205, https://doi.org/10.1093/mind/os-IX.34.188 Published: 01 April 1884
Influenza virus infections and immunity: a review of human and animal models. (1992)

Studies of the pathogenesis of influenza infection have involved the extensive use of animal models. The development of the current concepts of immunity to influenza and of the contribution the secretory immune system makes toward the protection of mucosal surfaces against influenza infection would have been impossible without this use of animals. The pathology and clinical signs of influenza infection in both natural and experimental hosts, the advantages and disadvantages of the most common experimental influenza infection models, and the contribution of animal models to the understanding of local and systemic immunity to influenza infection are discussed.
The structural basis of damaged DNA recognition and endonucleolytic cleavage for very short patch repair endonuclease (2001)

Endonucleases in DNA repair must be able to recognize damaged DNA as well as cleave the phosphodiester backbone. These functional prerequisites are manifested in very short patch repair (Vsr) endonuclease through a common endonuclease topology that has been tailored for recognition of TG mismatches. Structural and biochemical comparison with type II restriction enzymes illustrates how Vsr resembles these endonucleases in overall topology but also how Vsr diverges in terms of the detailed catalytic mechanism. A histidine and two metal-water clusters catalyze the phosphodiester cleavage. The mode of DNA damage recognition is also unique to Vsr. All other structurally characterized DNA damage-binding enzymes employ a nucleotide flipping mechanism for substrate recognition and for catalysis. Vsr, on the other hand, recognizes the TG mismatch as a wobble base pair and penetrates the DNA with three aromatic residues on one side of the mismatch. Thus, Vsr endonuclease provides important counterpoints in our understanding of endonucleolytic mechanisms and of damaged DNA recognition.
Genetic characterization of a brain-specific form of the type I regulatory subunit of cAMP-dependent protein kinase. (1988)

An isoform (RI beta) of the regulatory type I subunit gene of cAMP-dependent protein kinase (EC 2.7.1.37) has been characterized in mouse. The open reading frame of the RI beta cDNA is 72% identical in nucleotide sequence with the previously cloned RI gene, now referred to as RI alpha. Both genes code for a protein of 380 amino acids and their proteins are 82% identical in amino acid sequence. Sequence similarity is highest in the regions that form the pseudosubstrate-binding site of the catalytic subunit and the two cAMP binding domains. The amino-terminal portion shows the greatest dissimilarity, suggesting that the isoforms may differ in their dimerization properties or interaction with other proteins. In contrast to RI alpha, which is constitutively expressed in all tissues, RI beta is expressed in a highly tissue-specific manner. Brain and spinal cord contained significant levels of RI beta mRNA, testis RNA gave a detectable signal, and all other tissues tested were negative. Expression of a RI beta cDNA in NIH 3T3 cells resulted in the appearance of a RI subunit protein that migrated more slowly than RI alpha after NaDodSO4/PAGE. The native form of RI beta in brain could also be distinguished from RI alpha by its abnormal migration on NaDodSO4/PAGE. RI beta protein produced in 3T3 cells was shown to be functional by its ability to form a cAMP-dependent holoenzyme with the catalytic subunit.
Amplification and expression of the human cyclin D gene in esophageal cancer. (1992)

Amplification of the hst-1 and int-2 genes on chromosome 11q13 has previously been found in over 20% of human primary esophageal cancers. However, these two genes do not appear to be transcribed in appreciable amounts. Recently, the human cyclin D gene (also referred to as prad1) has been mapped to the 11q13 locus. Here, we report coamplification of the cyclin D and hst-1 genes in 5 of 20 (25%) human squamous esophageal tumors. We also detected significant levels of cyclin D transcription in two esophageal carcinoma cell lines, even though they did not express detectable amounts of hst-1 transcription. These findings provide the first evidence for the amplification of a cyclin gene in human esophageal cancer and suggest that an increase in cyclin D gene dosage could be an important factor in the pathogenesis of esophageal cancer. Additionally, because the 11q13 locus is found to be amplified in many types of human tumors, cyclin gene amplification could also play an important role in the development of other forms of human cancer.
A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis (2009)

The caspase-3 zymogen has essentially zero activity until it is cleaved by initiator caspases during apoptosis. However, a mutation of V266E in the dimer interface activates the protease in the absence of chain cleavage. We show that low concentrations of the pseudo-activated procaspase-3 kill mammalian cells rapidly and, importantly, this protein is not cleaved nor is it inhibited efficiently by the endogenous regulator XIAP (X-linked inhibitor of apoptosis). The 1.63 A (1 A = 0.1 nm) structure of the variant demonstrates that the mutation is accommodated at the dimer interface to generate an enzyme with substantially the same activity and specificity as wild-type caspase-3. Structural modelling predicts that the interface mutation prevents the intersubunit linker from binding in the dimer interface, allowing the active sites to form in the procaspase in the absence of cleavage. The direct activation of procaspase-3 through a conformational switch rather than by chain cleavage may lead to novel therapeutic strategies for inducing cell death.
Therapeutic Drug Monitoring by Dried Blood Spot: Progress to Date and Future Directions (2014)

This article discusses dried blood spot (DBS) sampling in therapeutic drug monitoring (TDM). The most important advantages of DBS sampling in TDM are the minimally invasive procedure of a finger prick (home sampling), the small volume (children), and the stability of the analyte. Many assays in DBS have been reported in the literature over the previous 5 years. These assays and their analytical techniques are reviewed here. Factors that may influence the accuracy and reproducibility of DBS methods are also discussed. Important issues are the correlation with plasma/serum concentrations and the influence of hematocrit on spot size and recovery. The different substrate materials are considered. DBS sampling can be a valid alternative to conventional venous sampling. However, patient correlation studies are indispensable to prove this. Promising developments are dried plasma spots using membrane and hematocrit correction using the potassium concentration.
Empyema: the use of broad range 16S rDNA PCR for pathogen detection (2004)

Background: An increase in the incidence of thoracic empyema in children has been reported. The causative pathogen is often unknown as pleural fluid is frequently sterile at the time of culture. The role of unusual organisms is unclear. Aims: (1) To compare the detection of organisms in pleural fluid from children with empyema using a molecular technique (16S rDNA polymerase chain reaction (PCR)) and bacterial culture. (2) To compare the concordance of organisms identified using the two techniques and the influence of prior antibiotic treatment on positive detection rate. Methods: Pleural fluid from children admitted with empyema between January 2000 and February 2002 was cultured and additionally analysed using broad range 16S rDNA PCR. Results: Pleural fluid was cultured from 32 patients, aged 1 month–16 years. Median duration of previous antibiotic therapy was 8 days (range 1–42 days). Six samples were culture positive and 22 were PCR positive. A causal organism was detected by PCR alone, after considering results from the local hospital, in 14 patients. There was complete concordance in organisms cultured and detected by PCR. Additional organisms detected by PCR were predominantly S pneumoniae , S pyogenes , and anaerobes. Conclusions: Analysis of pleural fluid by broad range 16S rDNA PCR in addition to culture, increases organism identification in empyema.
Development of alginate-based aggregate inoculants ofMethylobacteriumsp. andAzospirillum brasilensetested underin vitroconditions to promote plant growth (2013)

These findings could be extended to other PGP bacterial species to develop multigeneric bioinoculants with multiple benefits for various crops.
Binding and Active Transport of Large Analogues of Acetylcholine by Cholinergic Synaptic Vesicles In Vitro (1992)

A previous structure-activity investigation of acetylcholine (ACh) revealed a positive correlation between additional hydrophobic bulk and increased potency for inhibition of active transport of [3H]ACh by synaptic vesicles isolated from the electric organ of Torpedo. In the current study, several ACh analogues that are significantly larger than previously studied "false transmitters" were synthesized in the tritiated form by chemical means and tested for active transport. These are analogue 14 [(+/-)-(cis,trans)-1-benzyl-1-methyl-3-acetoxypyrrolidinium iodide], analogue 15 [(+/-)-1,1-dimethyl-3-benzoyloxypyrrolidinium iodide], and analogue 16/17 [(+/-)-(cis,trans)-1-benzyl-1-methyl-3-benzoyloxypyrrolidinium iodide]. These analogues place significant additional hydrophobic bulk on one or the other (analogues 14 and 15) or both (analogue 16/17) of the two pharmacophores of a small, conformationally constrained analogue of ACh. [3H]Analogue 14 and [3H]analogue 15 are actively transported, with Vmax values the same as or less than that of ACh, depending on the vesicle preparation. The observation that Vmax is the same for an analogue and ACh in some vesicle preparations suggests that the rate-limiting step does not involve ACh bound to the transporter. [3H]Analogue 16/17 is actively transported very poorly. Km values for ACh and for transported ACh analogues vary by up to two- to threefold in different vesicle preparations. The ACh transporter is much less selective for transported substrates than anticipated.
Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection. Protection by T cells is MHC-restricted and MHC-regulated; a model for MHC-disease associations. (1986)

The in vivo importance of class I MHC regulation of the Tc response to a natural pathogenic agent of high virulence was studied on the basis of our previous demonstration of a major difference in the capacity to generate a Sendai virus-specific Tc response between C57BL/6 (B6, H-2b) mice and H-2Kb mutant B6.C-H-2bm1 (bm 1) mice. These two mouse strains differ from each other only in three amino acids in the crucial H-2Kb restriction element for this response. bm 1 mice, in contrast to B6 mice, are Tc nonresponders against this virus, but show Sendai-specific T cell proliferation, antibody production, and DTH reactions, as well as NK cell activity, equal to those of B6 mice. B6, Sendai Tc-deficient bm 1 and T cell-deficient B6 nu/nu mice differ from each other in susceptibility to lethal pneumonia induced by i.n. inoculation of virulent Sendai virus. The lethal dose (LD50) in B6 mice averaged 152 TCID50, in bm 1 mice, 14 TCID50 and in B6 nu/nu mice 0.5 TCID50. The importance of Tc was also shown by the complete protection of B6 nu/nu mice against infection with a lethal virus dose by i.v. injection of a Sendai virus-specific, IL-2-dependent and H-2Kb-restricted B6 Tc clone. In vivo protection by this Tc clone was H-2Kb-restricted. Apart from Tc, an important role for virus-specific Th cells is evident from the difference in susceptibility between bm 1 and B6 nu/nu mice. This conclusion was supported by the demonstration that the mean survival time of B6 nu/nu and bm 1 nu/nu mice could be significantly prolonged, in an I-Ab-restricted manner, by the injection of in vitro-propagated, Sendai-specific B6 or bm 1 Th clones after a lethal dose of Sendai virus, and by the demonstration that inoculation of these Th clones provided help to virus-specific Tc by means of IL-2 production. Strikingly, Th and Tc cooperate in anti-Sendai virus immunity, since permanent survival of lethally infected nu/nu mice was only achieved by inoculation of a mixture of Tc and Th clones or a mixture of a Tc clone and rIL-2. This study provides a unique model for the study of MHC-disease associations.
Synthesis of N,N’-Diarylalkanediamides and Their Antimycobacterial and Antialgal Activity (2000)

A set of N,N'-diarylalkanediamides was synthesized. The compounds were tested for their antimycobacterial and antialgal activity. The antimycobacterial activity of N,N'-diarylalkanediamides depends on the lipophilicity of the respective acid. Antimycobacterially active substances were found only in the series of N,N'-diarylethanediamides and N,N'-diarylbutanediamides. Other compounds (derivatives of pentane-, hexane-, octane- and nonanediamide) were inactive against various strains of mycobacteria. The compounds inhibited growth and chlorophyll production in Chlorella vulgaris. Their relatively low antialgal activity is probably connected with their lowered aqueous solubility, and hence by a restricted passage of the inhibitor through the hydrophilic regions of thylakoid membranes.
Cellular System Design and Optimization (1996)

From the Publisher:
Professionals working within the wireless industry will want this book to be part of their technical resource library as a practical guide to design, optimize, and expand. You'll find design principles, and proven troubleshooting techniques and a wealth of engineering case studies. The book is unique in that it proposes the reporting schemes and organization structure that are required for system design and optimization.
Noninvasive Prediction of Intracranial Pressure Curves Using Transcranial Doppler Ultrasonography and Blood Pressure Curves (1997)

These results demonstrate that this method constitutes a promising step toward a noninvasive ICP prediction that may be clinically applicable under well-defined conditions.
Biochemical Characterization of Enzyme Fidelity of Influenza A Virus RNA Polymerase Complex (2010)

Our study indicates that IAV Pol is a high fidelity enzyme. We envision that the high fidelity nature of IAV Pol may be important to counter-balance the multiple rounds of IAV genome amplification per infection cycle, which provides IAV Pol with ample opportunities to generate and amplify genomic founder mutations, and thus achieve optimal viral mutagenesis for its evolution.
Supramolecular Thiophene Nanosheets (2013)

Alternating copolymers consisting of phenyl-capped bithiophene (red units) and oligo(ethylene glycol) hierarchically self-assemble into nanosheets through polymer folding in some organic solvents. The lateral size of the nanosheet is controllable by temperature and concentration of the solution. The nanosheet surface can be chemically modified by using copper-catalyzed Huisgen cycloaddition without disrupting the nanosheet structure.
Differential Effects of Polyadenylation Regions on Gene Expression in Mammalian Cells (1986)

The steady-state level attained for any protein in mammalian cells is in part determined by its steady-state level of mRNA. Sequence information in and around the 3' end of an RNA which is involved in specifying and regulating polyadenylation [poly(A)] may have important consequences on mRNA levels, and ultimately on expression of the protein product. In this report we compare the effects on gene expression which result from placing several different poly(A) regions, or no poly(A) region, downstream from a marker gene (galactokinase or galK) that can be readily assayed in mammalian cells. Our results demonstrate that the presence of a poly(A) region is important for efficient gene expression and that the use of the poly(A) region of bovine growth hormone (bGH) reproducibly results in three times higher expression than that of SV40 early or human collagen poly(A) regions. We further demonstrate that changing the promoter region on these chimeric transcription units does not change the effect of the poly(A) region. Neither does changing the assay gene, since comparison of the same poly(A) regions behind another marker gene (xanthine-guanine phosphoribosyl transferase or xgprt) leads to identical differences in expression. When we examine the levels of poly(A)+ RNA that result from each transcription unit, we find that they correlate precisely with the gene expression levels. Apparently the 3' end of an RNA is a determinant of steady-state mRNA levels and, in turn, the subsequent production of the protein product.
Chimpanzee Adenovirus Antibodies in Humans, Sub-Saharan Africa (2006)

Human sera from the United States, Thailand, and sub-Saharan Africa and chimpanzee sera were tested for neutralizing antibodies to 3 chimpanzee adenoviruses. Antibodies were more common in humans residing in sub-Saharan Africa than in humans living in the United States or Thailand. This finding suggests cross-species transmission of chimpanzee adenoviruses.
New synthetic approaches to 3‐carhoxamides of 4‐hydroxy‐2H‐1,2‐benzothiazine 1,1‐dioxide (1976)

Abstract Two new synthetic approaches to the title compounds are reported. In the first of these, starting with N ‐carbobenzyloxysarcosine, four synthetic steps are employed to finally assemble the C 3 C 4 bond of the 1,2‐benzothiazine ring. In the second approach, an enol ether is employed as a protecting group to allow formation of the 3‐carboxamide function, which is followed by cleavage of the ether function to yield the desired 4‐hydroxy‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide.
Complement activation during storage of whole blood, red cells, plasma, and buffy coat (1997)

The study demonstrated activation of complement during the storage of whole blood and plasma but not in red cells in storage solution. The transfusion of larger volumes of stored whole blood or plasma may contribute to the risk of development of organ dysfunction. Therefore, it is advisable to use red cells in storage solution.
Acquisition of a Specific and Potent PTP1B Inhibitor from a Novel Combinatorial Library and Screening Procedure (2001)

Protein-tyrosine phosphatases (PTPases) form a large family of enzymes that serve as key regulatory components in signal transduction pathways. Defective or inappropriate regulation of PTPase activity leads to aberrant tyrosine phosphorylation, which contributes to the development of many human diseases including cancers and diabetes. For example, recent gene knockout studies in mice identify PTP1B as a promising target for anti-diabetes/obesity drug discovery. Thus, there is intense interest in obtaining specific and potent PTPase inhibitors for biological studies and pharmacological development. However, given the highly conserved nature of the PTPase active site, it is unclear whether selectivity in PTPase inhibition can be achieved. We describe a combinatorial approach that is designed to target both the active site and a unique peripheral site in PTP1B. Compounds that can simultaneously associate with both sites are expected to exhibit enhanced affinity and specificity. We also describe a novel affinity-based high-throughput assay procedure that can be used for PTPase inhibitor screening. The combinatorial library/high-throughput screen protocols furnished a small molecule PTP1B inhibitor that is both potent (K(i) = 2.4 nm) and selective (little or no activity against a panel of phosphatases including Yersinia PTPase, SHP1, SHP2, LAR, HePTP, PTPalpha, CD45, VHR, MKP3, Cdc25A, Stp1, and PP2C). These results demonstrate that it is possible to acquire potent, yet highly selective inhibitors for individual members of the large PTPase family of enzymes.
Integrating Service Composition Flow with User Interactions (2008)

Web service technologies are best exploited by composing services, and BPEL (Web Services Business Process Execution Language) is adopted industrial-wide as the defacto service composition standard. However, BPEL is applied mainly in the design of composite services and fully automated processes, and user interaction, that should be included in service delivery, but presently is not included in the BPEL standard. To integrate the composite service flow with user interactions, in this work we propose a framework to extend BPEL to new activities that describe user involvement and user interfaces. An enhanced BPEL engine with a UI rendering engine was accordingly developed.
Antiphlogistische 2.3‐Dihydro‐1H‐pyrrolizine, 4. Mitt. Oxidative Ringöffnung von 6.7‐Diphenyl‐2.3‐dihydro‐1H‐pyrrolizin (DADHP) durch m‐Chlorperbenzoesäure (1986)

Abstract m‐Chlorperbenzoesäure oxidiert DADHP 1 zum N‐(2.3‐Diphenylprop‐1‐yl‐1.3‐dion)‐2‐pyrrolidon ( 2 ). Anhand der NMR‐spektroskopischen Daten und durch Umsetzung mit Hydrazin zum 2‐Pyrazolinon‐Derivat 7 läßt sich die Struktur von 2 sichern. Ein Mechanismus für die oxidative Ringöffnung wird diskutiert.