gebhart/patrepeval huggingface dataset:
Large-Scale Production of Pseudotyped Lentiviral Vectors Using Baculovirus GP64 (2003)

Unlike oncoretroviruses, lentiviral vectors can insert large genes and can target both dividing and nondividing cells; thus they hold unique promise as gene transfer agents. To enhance target range, the native lentiviral envelope glycoprotein is replaced (pseudotyped) with vesicular stomatitis virus G (VSVG), and the genes of interest are packaged in nonreplicating vectors by transient transfection with three plasmids. However, because of cytotoxic effects of VSVG expression in producer cells (293T cells) it has been difficult to generate a packaging cell line, required for even modest scale-up of vector production. Here we introduce a pseudotyped lentivirus vector using the baculovirus GP64 envelope glycoprotein. Compared with VSVG, GP64 vectors exhibited a similar broad tropism and similar native titers. GP64-pseudotyped vectors were usually highly concentrated without much loss of titer. Because, unlike VSVG, GP64 expression does not kill cells, we generated 293T-based cell lines constitutively expressing GP64. Our results demonstrate that the baculovirus GP64 protein is an attractive alternative to VSVG for viral vectors used in the large-scale production of high-titer virus required for clinical and commercial applications.
Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations (1993)

We analyzed blood samples from 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years, for apolipoprotein (apo) E isoforms and serum triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol. Parallel genotyping by means of polymerase chain reaction (PCR)-amplified DNA was performed in 200 subjects. Identical results were obtained by genotyping and phenotyping in 95% of all subjects analyzed. The apo E allelic frequencies were 7.8% for epsilon 2, 71.9% for epsilon 3, and 20.3% for epsilon 4. Compared with other Caucasian populations, the present population had a high relative allelic frequency of epsilon 4. The epsilon 4 frequency decreased with increasing age and was significantly lower in individuals > 60 years of age (14.7%). When controlling for age and sex, there were strong correlations between total serum and LDL cholesterol and the various epsilon alleles. The epsilon 4 and epsilon 3 alleles correlated positively with serum cholesterol and the epsilon 4 allele correlated positively with LDL cholesterol. In contrast, HDL cholesterol and serum triglycerides did not show any correlation to the allele types. Thus, the results demonstrate a considerable age variation of the epsilon allele frequency among healthy Swedes and an influence of apo E alleles on serum and LDL cholesterol concentrations.
Excess IL-1 Signaling Enhances the Development of Th17 Cells by Downregulating TGF-β–Induced Foxp3 Expression (2014)

IL-1R antagonist-deficient (Il1rn(-/-)) mice develop autoimmune arthritis in which IL-17A plays a crucial role. Although many studies have shown that Th17 cell differentiation is dependent on TGF-β and IL-6, we found that Th17 cells developed normally in Il1rn(-/-)Il6(-/-) mice in vivo. Then, we analyzed the mechanisms of Th17 cell differentiation in Il1rn(-/-)Il6(-/-) mice. We found that IL-21 production was increased in the lymph nodes of Il1rn(-/-) mice, naive Il6(-/-) CD4(+) T cells differentiated into Th17 cells when cultured with TGF-β and IL-21, and the differentiation was greatly enhanced when IL-1 was added to the culture. Th17 cell differentiation was not induced by either TGF-β or IL-1 alone or in combination. IL-21 induced IL-1R expression in naive CD4(+) T cells, and IL-1 inhibited TGF-β-induced Foxp3 expression, resulting in the promotion of Th17 cell differentiation. Furthermore, IL-1 augmented the expression of Th17 cell-specific transcription factors such as Nfkbiz and Batf. These results indicate that excess IL-1 signaling can overcome the requirement of IL-6 in the differentiation of Th17 cells by suppressing Foxp3 expression and inducing Th17 cell-specific transcription factors.
Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery (1999)

Poly(ethylenimine) (PEI) is one of a number of polycations that has been used successfully to transfer genes into living cells. Although PEI shows promise in the field of gene therapy, to date no rigorous proof of mechanism has been published regarding the fate of PEI/DNA administered for transfection. Here we show, by using fluorescent labeling and confocal microscopy, the paths of PEI/DNA complexes from endocytosis to gene expression. We found that complexes attach to cell surfaces and migrate into clumps that are endocytosed. The endocytotic vesicles grow in number and size and are occasionally seen to lyse. Most interesting is the fact that endocytosed PEI, whether administered with or without DNA, undergoes nuclear localization in the form of ordered structures.
Combination Chemotherapy in Advanced Pancreatic Cancer: Time to Raise the White Flag? (2007)

Gemcitabine has been the standard palliative chemotherapy in advanced pancreatic cancer since 1997; this standard was established by a phase III trial that randomly assigned 126 symptomatic patients with advanced pancreatic cancer to either gemcitabine or fluorouracil (FU). 1 Treatment with gemcitabine versus FU was associated with improvements in 1-year survival (18% v 2%, respectively) and clinical benefit response (24% v 5%, respectively). Subsequently, thousands of patients have participated in large phaseIIItrialscomparinggemcitabinealonewithgemcitabineplus a second cytotoxic agent. 2-5 In the current issue, Herrmann et al 6 present another such study, comparing gemcitabine plus capecitabine with gemcitabine alone in advanced disease. The trial by Herrmann et al 6 is of high quality and was based on evidence from earlier phase studies that suggested the combination had sufficient activity to warrant further testing. 7,8 Similar to all prior studies
Conservation of high efficiency promoter sequences inSaccharomyces cerevisiae (1982)

The position of the yeast phosphoglycerate kinase (PGK) gene has been mapped on a 2.95kb Hind III fragment. We have determined the nucleotide sequence of the 5' flanking region and compared this sequence with those from 16 other yeast genes. PGK, like all other yeast genes has an adenine residue at position -3. It has two possible TATA boxes at positions -114 and -152 and a CAAT box at -129. In addition we have defined a structure at position -63 to -39 that is common to all yeast genes that encode an abundant RNA. This structure is a CT-rich block followed, about 10 nucleotides later, by the sequence CAAG.
Development of Branched Poly(5-Amino-1-pentanol-co-1,4-butanediol Diacrylate) with High Gene Transfection Potency Across Diverse Cell Types (2016)

One of the most significant challenges in the development of polymer materials for gene delivery is to understand how topological structure influences their transfection properties. Poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (C32) has proven to be the top-performing gene delivery vector developed to date. Here, we report the development of branched poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (HC32) as a novel gene vector and elucidate how the topological structure affects gene delivery properties. We found that the branched structure has a big impact on gene transfection efficiency resulting in a superior transfection efficiency of HC32 in comparison to C32 with a linear structure. Mechanistic investigations illustrated that the branched structure enhanced DNA binding, leading to the formation of toroidal polyplexes with smaller size and higher cationic charge. Importantly, the branched structure offers HC32 a larger chemical space for terminal functionalization (e.g., guanidinylation) to further enhance the transfection. Moreover, the optimized HC32 is capable of transfecting a diverse range of cell types including cells that are known to be difficult to transfect such as stem cells and astrocytes with high efficiency. Our study provides a new insight into the rational design of poly(β-amino ester) (PAE) based polymers for gene delivery.
Improving services through partnership and consultation: a case example (2011)

Monitoring care quality is integral to modern health service delivery. This paper describes how a specialist mental health assessment and treatment inpatient service for people with intellectual disabilities put in place a process to improve and reprovide the service, following an audit, in partnership with local stakeholders. In describing the process the paper highlights the need for transparent and honest working relationships with stakeholders, along with the role of audit and monitoring of quality to determine the ‘health’ and effectiveness of services. This included evaluating the continuing need for service and maintaining an agenda driven by needs rather than beds, based on best practice.
Empiric Therapy with Amphotericin B in Febrile Granulocytopenic Patients (1991)

The early diagnosis of invasive fungal infection in granulocytopenic patients remains unreliable. Granulocytopenic patients who are persistently or recurrently febrile despite therapy with appropriate antibacterial agents are at high risk for the development of such infection. Two randomized clinical trials demonstrated that the empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients decreased the frequency, morbidity, and mortality of invasive fungal infection; these effects were especially marked in profoundly granulocytopenic patients who were not receiving antifungal prophylaxis. Current studies continue to indicate that prompt empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients ensures earlier treatment of deep mycoses. The roles of newer antifungal triazole compounds and of liposomal and lipid complexes of amphotericin B in empiric antifungal therapy must be investigated further in thoughtfully designed, randomized clinical trials.
Detection of cancer‐associated antigen(s) in urine of sarcoma patients (1979)

Tumor-associated antigens were demonstrated in concentrated and dialyzed urine of several sarcoma patients with large tumor burden. The antigens were detected by complement fixation using autologous and allogeneic sera from sarcoma patients. The antigenic activity in three patients who were studied sequentially disappeared after surgical ablation of tumor. In two of these three patients, the antigenic activity reappeared before tumor recurrence. The reactivity of the sarcoma sera to the urine could be abolished by absorption of the sera with human sarcoma cells but not by normal human liver cells, which indicates that the same antigen was present in the urine and on biopsy-obtained sarcoma cells. Urine from cancer patients with high tumor burden may be useful as a source of tumor-associated antigen. Further studies on the presence of these antigens in urine of sarcoma patients may lead to a method for detecting subclinical tumor recurrence.
Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea‐predominant irritable bowel syndrome (2012)

Our 16S rRNA sequence data demonstrates a community-level dysbiosis in D-IBS. The altered composition of the intestinal microbiota in D-IBS is associated with significant increases in detrimental and decreases in beneficial bacterial groups, and a reduction in microbial richness.
Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC. (2001)

Overall, this study demonstrates that multiple genes are differentially expressed in ESCC and provides the first evidence that oncogenes Fra-1 and Neogenin and cell cycle-related genes Id-1 and CDC25B are overexpressed in ESCC.
Trapping set analysis of protograph-based LDPC convolutional codes (2009)

It has been suggested that ¿near-codewords¿ may be a significant factor affecting decoding failures of LDPC codes over the AWGN channel. A near-codeword is a sequence that satisfies almost all of the check equations. These near-codewords can be associated with so-called `trapping sets' that exist in the Tanner graph of a code. In this paper, we analyse the trapping sets of protograph-based LDPC convolutional codes. LDPC convolutional codes have been shown to be capable of achieving the same capacity-approaching performance as LDPC block codes with iterative message-passing decoding. Further, it has been shown that some ensembles of LDPC convolutional codes are asymptotically good, in the sense that the average free distance grows linearly with constraint length. Here, asymptotic methods are used to calculate a lower bound on the trapping set growth rates for two ensembles of asymptotically good protograph-based LDPC convolutional codes. This can be used to predict where the error floor will occur for these codes under iterative message-passing decoding.
Structural Analysis of CTLA-4 Function In Vivo (2000)

CTLA-4-mediated inhibition of T cell activation may be accomplished by competition for ligands and/or by signals mediated through the intracellular domain. Studies have implicated Tyr201 in the cytoplasmic domain of CTLA-4 in regulating CTLA-4 signal transduction and intracellular trafficking. To investigate the mechanism of CTLA-4 function in vivo, transgenes encoding wild-type CTLA-4 (FL), a mutant lacking the cytoplasmic domain of CTLA-4 (DeltaCTLA-4 tail), or a CTLA-4 Tyr201 mutant (Y201V) were introduced into CTLA-4-deficient mice. CTLA-4-/- mice display an autoimmune lymphoproliferative disorder resulting in tissue destruction and early death. When either the FL or the Y201V transgene was bred into CTLA-4-/- animals, a complete rescue from lymphoproliferation and autoimmunity was observed. In contrast, CTLA-4-/- mice expressing the DeltaCTLA-4 tail transgene were long lived with no evidence of multiorgan lymphocytic infiltration, but exhibited lymphadenopathy and accumulated large numbers of activated T cells. Furthermore, these animals displayed a Th2-biased phenotype which conferred susceptibility to Leishmania infection. These results indicate that the inhibitory effect of CTLA-4 is mediated in part through the ability of the extracellular domain to compete for ligands. The cytoplasmic domain of CTLA-4, however, is required for complete inhibitory function of the receptor and for regulation of Th cell differentiation in vivo.
Plasma Membrane CFTR Regulates RANTES Expression via Its C-Terminal PDZ-Interacting Motif (2002)

Despite the identification of 1,000 mutations in the cystic fibrosis gene product CFTR, there remains discordance between CFTR genotype and lung disease phenotype. The study of CFTR, therefore, has expanded beyond its chloride channel activity into other possible functions, such as its role as a regulator of gene expression. Findings indicate that CFTR plays a role in the expression of RANTES in airway epithelia. RANTES is a chemokine that has been implicated in the regulation of mucosal immunity and the pathogenesis of airway inflammatory diseases. Results demonstrate that CFTR triggers RANTES expression via a mechanism that is independent of CFTR's chloride channel activity. Neither pharmacological inhibition of CFTR nor activation of alternative chloride channels, including hClC-2, modulated RANTES expression. Through the use of CFTR disease-associated and truncation mutants, experiments suggest that CFTR-mediated transcription factor activation and RANTES expression require (i) insertion of CFTR into the plasma membrane and (ii) an intact CFTR C-terminal PDZ-interacting domain. Expression of constructs encoding wild-type or dominant-negative forms of the PDZ-binding protein EBP50 suggests that EBP50 may be involved in CFTR-dependent RANTES expression. Together, these data suggest that CFTR modulates gene expression in airway epithelial cells while located in a macromolecular signaling complex at the plasma membrane.
Membrane-Bound Lytic Endotransglycosylase in Escherichia coli (1998)

The gene for a novel endotype membrane-bound lytic transglycosylase, emtA, was mapped at 26.7 min of the E. coli chromosome. EmtA is a lipoprotein with an apparent molecular mass of 22kDa. Overexpression of the emtA gene did not result in bacteriolysis in vivo, but the enzyme was shown to hydrolyze glycan strands isolated from murein by amidase treatment. The formation of tetra- and hexasaccharides, but no disaccharides, reflects the endospecificity of the enzyme. The products are characterized by the presence of 1,6-anhydromuramic acid, indicating a lytic transglycosylase reaction mechanism. EmtA may function as a formatting enzyme that trims the nascent murein strands produced by the murein synthesis machinery into proper sizes, or it may be involved in the formation of tightly controlled minor holes in the murein sacculus to facilitate the export of bulky compounds across the murein barrier.
Effect of fluorocarbon emulsions on the mechanical fragility of normal and sickle cells: in vitro studies. (1975)

Mechanical fragility measurements have been made in vitro on fluorocarbon emulsions mixed with normal and sickle cells in plasma to determine the effect of fluorocarbon. Emulsions of FC-80 with Pluronic F-68 were added to give final solutions of 0, 1, 5, 10, and 20% fluorocarbon emulsion. The effect of the fluorocarbon emulsion was observed in the presence and absence of oxygen. In the presence of oxygen, there was no effect of the fluorocarbon emulsion on the mechanical fragility of normal or sickle cells. In deoxygenated systems, however, there was significantly less hemoglobin in the plasma during the mechanical fragility test with fluorocarbon emulsion added to sickle cell blood. The normal blood was not affected by the fluorocarbon emulsion in the deoxygenated system. Five percent of fluorocarbon emulsion was required for a significant effect on the deoxygenated sickle cells. Since the effect of the fluorocarbon emulsion was in a deoxygenated condition, the effect is due to the presence of the fluorocarbon emulsion and not its oxygen carrying capability.
Membrane probe-spectral emission type detection system for mercury in water (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMembrane probe-spectral emission type detection system for mercury in waterRobert S. BramanCite this: Anal. Chem. 1971, 43, 11, 1462–1467Publication Date (Print):August 1, 1971Publication History Published online1 May 2002Published inissue 1 August 1971https://pubs.acs.org/doi/10.1021/ac60305a013https://doi.org/10.1021/ac60305a013research-articleACS PublicationsRequest reuse permissionsArticle Views109Altmetric-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-Alertsclose Get e-Alerts
Cultivable bacterial diversity from the human colon (2007)

Knowledge of the composition of the colonic microbiota is important for our understanding of how the balance of these microbes is influenced by diet and the environment, and which bacterial groups are important in maintaining gut health or promoting disease. Molecular methodologies have advanced our understanding of the composition and diversity of the colonic microbiota. Importantly, however, it is the continued isolation of bacterial representatives of key groups that offers the best opportunity to conduct detailed metabolic and functional studies. This also permits bacterial genome sequencing which will accelerate the linkage to functionality. Obtaining new human colonic bacterial isolates can be challenging, because most of these are strict anaerobes and many have rather exact nutritional and physical requirements. Despite this many new species are being isolated and described that occupy distinct niches in the colonic microbial community. This review focuses on these under-studied yet important gut anaerobes.
Prostate cancer: molecular biology of early progression to androgen independence. (1999)

To improve the therapy for prostate cancer, it will be necessary to address the problems of progression to androgen independence and the process of metastatic spread of tumour. The complexity of the latter condition is likely to mitigate against the immediate development of relevant therapeutic approaches. However, the basis of androgen independence appears to be a problem of simpler dimensions and more amenable to treatment with current therapeutic technology. Since early tumour progression can be detected by an incomplete prostate-specific antigen (PSA) response to androgen withdrawal therapy, a study of the molecular biology of PSA gene regulation may well provide insight into new methods for preventing or delaying this problem. Mounting evidence suggests that ligand-independent activation of the androgen receptor may be one underlying mechanism of androgen independence. In the absence of androgen, a compensatory increase in the activity of cAMP-dependent protein kinase (PKA) enhances the ability of the androgen receptor to bind to the response elements regulating PSA gene expression. The activation of the androgen receptor through up-regulation of the PKA signal transduction pathway involves the amino-terminus of the androgen receptor, the function of which may be altered either by modifications such as phosphorylation, or through interactions with co-regulators or other proteins. Of therapeutic interest is the fact that this effect can be counteracted experimentally by the anti-androgen, bicalutamide, and clinically by several other similar agents. We speculate that the inhibition of PKA-activated androgen receptor might also be accomplished by decoy molecules that can bind to the relevant activated site on the amino-terminus or competitively interact with proteins recruited by the PKA pathway that are responsible for activating the receptor in the absence of androgen. Such molecules might include small mimetic substances or agents that can gain access to the nucleus of the cell.
<title>Therapy monitoring of laser cyclophotocoagulation</title> (2002)

Laser induced ultrasound provides a powerful tool for solving a major problem of laser cyclophotocoagulation, which is caused by difficulties in localization and determination of optical properties. Furthermore it adds the possibility of an online control mechanism for the process of coagulation of the ciliary body. We have developed a transducer system which is based on a fiber with 600 micrometers core diameter surrounded by a ring shaped piezoelectric PVDF detector. With this detector it is possible to localize the lateral position of the ciliary body on enucleated pigs and rabbit eyes as well as its depth. Our findings correspond well with histological sections of the measured area. Additionally, the changes in the tissue's optical properties induced by coagulation with a diode laser have been detected in real time.