gebhart/patrepeval huggingface dataset:
Genetic Basis for the Structural Difference between Streptococcus pneumoniae Serotype 15B and 15C Capsular Polysaccharides (2003)

In a search for the genetic basis for the structural difference between the related Streptococcus pneumoniae capsular serotypes 15B and 15C and for the reported reversible switching between these serotypes, the corresponding capsular polysaccharide synthesis (cps) loci were investigated by keeping in mind that at the structural level, the capsules differ only in O acetylation. The cps locus of a serotype 15B strain was identified, partially PCR amplified with primers based on the related serotype 14 sequence, and sequenced. Sequence analysis revealed, among other open reading frames, an intact open reading frame (designated cps15bM) whose product, at the protein level, exhibited characteristics of previously identified acetyltransferases. Genetic analysis of the corresponding region in a serotype15C strain indicated that the same gene was present but had a premature stop in translation. Closer analysis indicated that the serotype 15B gene contained a short tandem TA repeat consisting of eight TA units. In serotype 15C, this gene contained nine TA units that resulted in a frameshift and a truncated product. Genetic analysis of 17 serotype 15B and 15C clinical isolates revealed a perfect correlation between the serotype and the length of the short tandem repeat in the putative O-acetyltransferase gene. The number of TA repeating units varied between seven and nine in the various isolates. Together, the data strongly suggest that the structural difference between serotypes 15B and 15C is based on variation in the short tandem TA repeat in the O-acetyltransferase gene and that the transition between serotypes is due to slipped-strand mispairing with deletion or insertion of TA units in the cps15bM gene.
Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin (2011)

The exposure to tamsulosin is increased upon co-administration of strong CYP2D6 inhibitors and even more so of strong 3A4 inhibitors, but neither PK alteration was accompanied by clinically significant haemodynamic changes during orthostatic stress testing.
Incidence and Time to Return to Training for Stress Fractures during Military Basic Training (2014)

Currently, little is known about the length of time required to rehabilitate patients from stress fractures and their return to preinjury level of physical activity. Previous studies have looked at the return to sport in athletes, in a general population, where rehabilitation is not as controlled as within a captive military population. In this study, a longitudinal prospective epidemiological database was assessed to determine the incidence of stress fractures and the time taken to rehabilitate recruits to preinjury stage of training. Findings demonstrated a background prevalence of 5% stress fractures in Royal Marine training; femoral and tibial stress fractures take 21.1 weeks to return to training with metatarsal stress fractures being the most common injury taking 12.2 weeks. Rehabilitation from stress fractures accounts for 814 weeks of recruit rehabilitation time per annum. Stress fracture incidence is still common in military training; despite this stress fracture recovery times remain constant and represent a significant interruption in training. It takes on average 5 weeks after exercise specific training has restarted to reenter training at a preinjury level, regardless of which bone has a stress fracture. Further research into their prevention, treatment, and rehabilitation is required to help reduce these burdens.
Silver particles on stochastic quartz substrates providing tenfold increase in Raman enhancement (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSilver particles on stochastic quartz substrates providing tenfold increase in Raman enhancementM. Meier, A. Wokaun, and T. Vo-DinhCite this: J. Phys. Chem. 1985, 89, 10, 1843–1846Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/j100256a002https://doi.org/10.1021/j100256a002research-articleACS PublicationsRequest reuse permissionsArticle Views155Altmetric-Citations61LEARN 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 options Get e-Alerts
3-Aminopyridazine derivatives with atypical antidepressant, serotonergic and dopaminergic activities (1989)

Minaprine [3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine dihydrochloride] is active in most animal models of depression and exhibits in vivo a dual dopaminomimetic and serotoninomimetic activity profile. In an attempt to dissociate these two effects and to characterize the responsible structural requirements, a series of 47 diversely substituted analogues of minaprine were synthesized and tested for their potential antidepressant, serotonergic, and dopaminergic activities. The structure-activity relationships show that dopaminergic and serotonergic activities can be dissociated. Serotonergic activity appears to be correlated mainly with the substituent in the 4-position of the pyridazine ring whereas the dopaminergic activity appears to be dependent on the presence, or in the formation, of a para-hydroxylated aryl ring in the 6-position of the pyridazine ring.
The biological effects of antiadhesion agents on activated RAW264.7 macrophages (2002)

The objective of this study is to determine the biological effects of various antiadhesion agents on macrophages, which play an essential role in wound healing and adhesion. To determine these effects, RAW264.7 macrophages were activated with lipopolysaccharide in the presence of antiadhesion agents: oxidized regenerated cellulose (oxyC), sodium hyaluronate (HA), dexamethasone (Dex), or chondroitin sulfate (CS). The release of nitric oxide (NO), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), or matrix metalloproteinases (MMPs) from RAW264.7 was measured. We found that oxyC reduced the release of NO, IL-6, MMP-2, and MMP-9, whereas it enhanced the release of VEGF. HA reduced the release of MMP-2, whereas it enhanced the release of VEGF and NO. HA exhibited no significant effect on the release of IL-6 or MMP-9. Dex reduced the release of NO, VEGF, IL-6, MMP-2, and MMP-9. CS reduced the release of VEGF, IL-6, and MMP-2, although it had no significant effect on the release of NO and MMP-9. Antiadhesion agents, which have been clinically used as physical barriers, modulated the functions of macrophages.
Wavelength reuse scheme in a WDM unidirectionalring network using a proper fibregrating add/drop multiplexer (1995)

An experimental optical WDM ring network is proposed. It uses a proper add/drop multiplexer based on a fibre grating filter. Both-way transmission using a wavelength reuse scheme is successfully demonstrated without any crosstalk.
Vaccine-Induced Canine Distemper in a Lesser Panda (1976)

A fatal disease occurred in a lesser panda (Ailurus fulgens) 2 weeks after vaccination with modified live distemper vaccine. The disease clinically resembled canine distemper. Pathologically there was giant cell pneumonia, with canine distemper viral inclusion bodies in pulmonary and digestive tract epithelium. Viral isolates were indicative of an attenuated strain rather than virulent types.
A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme (2005)

The formylglycine (FGly)-generating enzyme (FGE) uses molecular oxygen to oxidize a conserved cysteine residue in all eukaryotic sulfatases to the catalytically active FGly. Sulfatases degrade and remodel sulfate esters, and inactivity of FGE results in multiple sulfatase deficiency, a fatal disease. The previously determined FGE crystal structure revealed two crucial cysteine residues in the active site, one of which was thought to be implicated in substrate binding. The other cysteine residue partakes in a novel oxygenase mechanism that does not rely on any cofactors. Here, we present crystal structures of the individual FGE cysteine mutants and employ chemical probing of wild-type FGE, which defined the cysteines to differ strongly in their reactivity. This striking difference in reactivity is explained by the distinct roles of these cysteine residues in the catalytic mechanism. Hitherto, an enzyme-substrate complex as an essential cornerstone for the structural evaluation of the FGly formation mechanism has remained elusive. We also present two FGE-substrate complexes with pentamer and heptamer peptides that mimic sulfatases. The peptides isolate a small cavity that is a likely binding site for molecular oxygen and could host reactive oxygen intermediates during cysteine oxidation. Importantly, these FGE-peptide complexes directly unveil the molecular bases of FGE substrate binding and specificity. Because of the conserved nature of FGE sequences in other organisms, this binding mechanism is of general validity. Furthermore, several disease-causing mutations in both FGE and sulfatases are explained by this binding mechanism.
Mcl-1 Is a Novel Therapeutic Target for Human Sarcoma (2004)

A combination of Mcl-1 antisense oligonucleotides with low-dose cyclophosphamide provides a synergistic antitumor effect and might qualify as a promising strategy to overcome chemoresistance in human sarcoma.
Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. (1994)

TCR stimulation results in the tyrosine phosphorylation of a number of cellular substrates. We have recently identified a 70-kDa protein tyrosine kinase, ZAP-70, which associates with the human TCR zeta-chain after TCR stimulation. We report here the isolation and sequence of a cDNA clone that encodes murine ZAP-70. Murine and human ZAP-70 share 93% amino acid identity and are homologous to the 72-kDa protein tyrosine kinase Syk. Syk has been implicated in the signal transduction pathways of the B cell membrane Ig and high affinity IgE receptors, Fc epsilon RI. In addition, we examined the tissue distribution of ZAP-70 and Syk in human and murine thymocyte subsets, B cells, and peripheral T cell subsets. ZAP-70 protein is expressed in all major thymocyte populations, with the level of expression being comparable to that found in both CD4+ and CD8+ peripheral T cells. Although Syk protein is also present in all thymocyte subsets, expression of Syk protein is down-regulated threefold to fourfold in peripheral T cells. In contrast to ZAP-70, expression of Syk is 12- to 15-fold higher in peripheral B cells when compared with peripheral T cells. In addition, whereas T cell stimulation results in down-regulation of Lck, no significant change in ZAP-70 or Syk protein is detected. Finally, we provide evidence that both ZAP-70 and Syk can associate with the TCR after TCR stimulation. With the use of a heterologous expression system, we show that, like ZAP-70, Syk is dependent upon a Src-family protein tyrosine kinase for association with the phosphorylated zeta-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development.
Immortalization of mouse neural precursor cells by the c-myc oncogene. (1988)

Immortalized cell lines have been generated from embryonic mouse neuroepithelium by infection with a retrovirus containing the c-myc oncogene. The morphology and the antigenic phenotype of the cloned cell lines are characteristic of normal neuroepithelium. Although the cell lines are stable and do not spontaneously differentiate, morphological changes can be induced with both acidic and basic fibroblast growth factor. Fibroblast growth factor at 5 ng/ml stimulates differentiation of the neuroepithelial cells, and it has been shown that the cloned cell line 2.3D can differentiate into astrocytes, containing glial fibrillary acidic protein, and neurons, expressing the A2B5 marker and neurofilaments. This indicates that some cells in the neuroepithelium at embryonic day 10 are multipotent and are not restricted to either the glial or neuronal cell lineage. The cell lines also can be induced with interferon gamma to express class I and class II histocompatibility antigens. The response of the c-myc-immortalized cell lines to these two factors is similar to that observed with freshly isolated neuroepithelium and suggests that such immortalized precursor populations are representative of the cells found in the developing neuroepithelium.
Translocation of an antibody transgene requires AID and occurs by interchromosomal switching to all switch regions except the mu switch region (2011)

Immunoglobulin (Ig) class switch recombination (CSR) occurs most often by intrachromosomal recombinations between switch (S) regions located on a single chromosome, but it can also occur by interchomosomal recombinations between Ig heavy chain (Igh) S regions located on chomosomal homologs. Interchromosomal recombinations have also been found between chromosomes that are not homologs; examples are Igh/c-myc and Igh/transgene translocations. Most, but not all, studies have indicated that activation-induced cytidine deaminase (AID) is important in Igh/c-myc translocations. The role of AID has not been determined for Igh/transgene translocations. We now show that the majority of Igh/transgene translocations between non-homologs from an Ig transgenic mouse are dependent on AID, but we also find a small number of these translocations that can occur in the absence of AID. Surprisingly, our results also indicate that, although Sγ switch sequences in the endogenous Igh locus participate in chromosomal translocations with the non-homolog transgene-bearing chromosome, Sμ switch sequences do not. This contrasts with the fact that both endogenous Sμ and Sγ sequences participate in intrachromosomal CSR. Our findings suggest the operation of a regulatory mechanism that can differentially control the accessibility of Sμ and Sγ regions for non-homolog translocations even when both are accessible for intrachromosomal recombination.
Patterning of zinc oxide thin films (2003)

Zinc oxide (ZnO) thin films were accurately and reliably delineated by wet chemical etching in 5% NH/sub 4/Cl in water and by reactive ion etching in a SiCl/sub 4/ plasma. With the etch solution at 55 degrees C, the ZnO etch rate was approximately 300 nm/min. Aluminum, silicon and silicon dioxide were not attacked by the etch solution. In the RIE process, substrate heating was essential during plasma etching. With a RF power density of 0.3 W/cm/sup 2/ and substrate temperature of 150 degrees C, well defined clean ZnO thin film features were obtained with an etch rate of 25 nm/min.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Iron Acquisition and Regulation in Campylobacter jejuni (2004)

Iron affects the physiology of bacteria in two different ways: as a micronutrient for bacterial growth and as a catalyst for the formation of hydroxyl radicals. In this study, we used DNA microarrays to identify the C. jejuni genes that have their transcript abundance affected by iron availability. The transcript levels of 647 genes were affected after the addition of iron to iron-limited C. jejuni cells. Several classes of affected genes were revealed within 15 min, including immediate-early response genes as well as those specific to iron acquisition and metabolism. In contrast, only 208 genes were differentially expressed during steady-state experiments comparing iron-rich and iron-limited growth conditions. As expected, genes annotated as being involved in either iron acquisition or oxidative stress defense were downregulated during both time course and steady-state experiments, while genes encoding proteins involved in energy metabolism were upregulated. Because the level of protein glycosylation increased with iron limitation, iron may modulate the level of C. jejuni virulence by affecting the degree of protein glycosylation. Since iron homeostasis has been shown to be Fur regulated in C. jejuni, an isogenic fur mutant was used to define the Fur regulon by transcriptome profiling. A total of 53 genes were Fur regulated, including many genes not previously associated with Fur regulation. A putative Fur binding consensus sequence was identified in the promoter region of most iron-repressed and Fur-regulated genes. Interestingly, a fur mutant was found to be significantly affected in its ability to colonize the gastrointestinal tract of chicks, highlighting the importance of iron homeostasis in vivo. Directed mutagenesis of other genes identified by the microarray analyses allowed the characterization of the ferric enterobactin receptor, previously named CfrA. Chick colonization assays indicated that mutants defective in enterobactin-mediated iron acquisition were unable to colonize the gastrointestinal tract. In addition, a mutation in a receptor (Cj0178) for an uncharacterized iron source also resulted in reduced colonization potential. Overall, this work documents the complex response of C. jejuni to iron availability, describes the genetic network between the Fur and iron regulons, and provides insight regarding the role of iron in C. jejuni colonization in vivo.
Dynamic detection of object capability violations through model checking (2014)

In this paper we present a new tool called DOCaT (Dynamic Object Capability Tracer), a model checker for JavaScript that detects capability leaks in an object capability system. DOCaT includes an editor that highlights the sections of code that can be potentially transferred to untrusted third-party code along with a trace showing how the code could be leaked in an actual execution. This code highlighting provides a simple way of visualizing the references untrusted code potentially has access to and helps programmers to discover if their code is leaking more capabilities then required. DOCaT is implemented using a combination of source code rewriting (using Sweet.js, a JavaScript macro system), dynamic behavioral intercession (Proxies, introduced in ES6, the most recent version of JavaScript), and model checking. Together these methods are able to locate common ways for untrusted code to elevate its authority.
Neurotrophin gene expression by cell lines derived from human gliomas (1993)

The expression of neurotrophin (NGF, BDNF, and NT-3) mRNAs in 24 cell lines derived from human malignant gliomas was studied by Northern analysis. Widespread expression of neurotrophin genes was found with BDNF being the most abundantly expressed. Nearly all cell lines expressed BDNF, and about two-thirds of the cell lines expressed NGF and NT-3. Half of the cell lines analyzed expressed all three neurotrophins. Secretion of NGF into the medium of several cell lines could be detected by ELISA and a PC12 neurite outgrowth assay. Immuno- and bioactive NGF was isolated from conditioned medium of one cell line. No evidence of expression of the neurotrophin receptors trk and trkB by Northern analysis was found. Receptor crosslinking with radiolabeled cognate ligands failed to detect functional receptors in all but one cell line. In this cell line a receptor complex for BDNF was found that corresponded to truncated trkB receptors that lack the signal transducing tyrosine kinase domain. Neurotrophins did not stimulate mitosis of the glioma cultures. The findings suggest that production of neurotrophins by glioma cells is a general phenomenon, although neurotrophins made by gliomas lacking their receptors may not play an autocrine but rather a paracrine role.
A T-cell–directed chimeric antigen receptor for the selective treatment of T-cell malignancies (2015)

Options for targeted therapy of T-cell malignancies remain scarce. Recent clinical trials demonstrated that chimeric antigen receptors (CARs) can effectively redirect T lymphocytes to eradicate lymphoid malignancies of B-cell origin. However, T-lineage neoplasms remain a more challenging task for CAR T cells due to shared expression of most targetable surface antigens between normal and malignant T cells, potentially leading to fratricide of CAR T cells or profound immunodeficiency. Here, we report that T cells transduced with a CAR targeting CD5, a common surface marker of normal and neoplastic T cells, undergo only limited fratricide and can be expanded long-term ex vivo. These CD5 CAR T cells effectively eliminate malignant T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma lines in vitro and significantly inhibit disease progression in xenograft mouse models of T-ALL. These data support the therapeutic potential of CD5 CAR in patients with T-cell neoplasms.
Expression of BIRC7 protein and mRNA in non-Hodgkin's lymphoma (2006)

Studies have shown that BIRC7, a new member of inhibitor of the apoptosis protein family, is expressed in fetal tissues and most solid tumors in humans. However, there are no reported data concerning BIRC7 expression in lymphomas. We investigated the expression of BIRC7, survivin, Bcl-2, Bax, p53 and p170 proteins in 167 cases of non-Hodgkin's lymphoma (NHL) and 10 cases of non-specific lymphadenitis by tissue microarray-based immunohistochemistry. BIRC7 mRNA in three cell lines and 16 cases of NHL were detected by reverse transcriptase-polymerase chain reaction. BIRC7 protein was exhibited in the cytoplasm of cells in 25 (31%) of 80 cases of B-NHLs, 32 (37%) of 87 cases of T-NHLs, and none in non-specific lymphadenitis. The positive rate of BIRC7 was lower than that of survivin in almost all types of NHL with no significant differences, and similar to that of Bcl-2, Bax or p53. There was no correlation of protein expression between BIRC7 and any other detected markers, except p170 in T-NHL (P < 0.001). BIRC7 expression did not correlate with clinic pathologic factors such as sex, age, stage and grade, but overexpression of BIRC7 was positively correlated with aggression of NHL cells (P < 0.05). BIRC7 mRNA expressed in six (38%) of 16 cases of NHLs. BIRC7 mRNA expression was approximately consistent with BIRC7 protein in NHL. Our results indicate that the BIRC7 gene might play a role in the development and aggression of NHL and that the inhibition of BIRC7 expression may be important in NHL treatment.