gebhart/patrepeval huggingface dataset:
NPHS2 Variation in Sporadic Focal Segmental Glomerulosclerosis (2007)

Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases and controls, and subsequently genotyped African-American and European-American cases and controls for five missense SNPs, three SNPs within introns, and four SNPs in the 3' untranslated region. No homozygotes or compound heterozygotes were observed for any missense mutation. R138Q carriers were more frequent among FSGS cases relative to controls (OR = 4.9, P = 0.06), but heterozygosity for the other four missense mutations was equally distributed among FSGS cases and controls. Finally, a common haplotype of noncoding SNPs carried by 20% of African-Americans, but not observed in European-Americans, was strongly associated with a 50% reduction in risk for sporadic FSGS (OR = 0.5, P = 0.001). These results indicate that genetic variation or mutation of NPHS2 may play a role in late-onset sporadic FSGS.
Gefitinib (Iressa®): a novel treatment for non-small cell lung cancer (2004)

Current standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) includes chemotherapy, which is often associated with limited efficacy and toxicity. Thus, there is an unmet need for novel anticancer agents that are both effective and well tolerated in patients with NSCLC. Gefitinib (Iressa) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in advanced clinical development, and the first agent of its kind to receive approval. Extensive evidence indicates that gefitinib provides significant antitumor activity in previously treated advanced NSCLC, along with fast symptom improvement. This orally administered agent is generally well tolerated. Gefitinib has also shown promising efficacy in other solid tumors that rely on EGFR-related mechanisms for growth and survival. This article reviews the profile of gefitinib and the evidence supporting its use in the treatment of NSCLC.
Mechanistic Study of the Pd/TOMPP‐Catalyzed Telomerization of 1,3‐Butadiene with Biomass‐Based Alcohols: On the Reversibility of Phosphine Alkylation (2011)

Abstract Liquid‐chromatography electrospray‐ionisation mass spectrometry (LC‐ESI‐MS) studies on reaction mixtures of the telomerization of 1,3‐butadiene with biomass‐based polyols revealed that the TOMPP (TOMPP=tris(2‐methoxyphenyl)phosphine) ligand is converted towards the corresponding (2,7‐octadienyl)phosphonium species during catalysis. The extent of ligand alkylation is substrate dependent and was identified as the primary cause of deactivation for carbohydrate substrates with anomeric hydroxyl groups. Coordination studies of the phosphonium cation with [Pd(dba) 2 ] (dba=dibenzylideneacetone) gave insight into the alkylation mechanism and showed that the formation of the phosphonium cation is fully reversible. The reaction yields the key cationic intermediate [Pd(1,2,3,7,8‐η 5 ‐octa‐2,7‐dien‐1‐yl)(TOMPP)] + , which, in the presence of the iodide anion, results in the formation of [Pd(1,2,3‐η 3 ‐octa‐2,7‐dien‐1‐yl)(I)(TOMPP)]. Both complexes were fully characterized by various techniques including single crystal X‐ray crystallography. Based on these results, an extension to the Pd/TOMPP‐catalyzed telomerization mechanism was formulated to include the 2,7‐octadienylphosphonium cation as a ligand reservoir. Catalytic tests show that the use of [Pd(dba) 2 ] as precatalyst improves the telomerization of glucose and xylose.
Distinct chemokine and cytokine gene expression pattern of murine dendritic cells and macrophages in response toMycobacterium tuberculosisinfection (2008)

In this study, the early innate cytokine and chemokine response of murine dendritic cells (DCs) and macrophages to Mycobacterium tuberculosis infection was compared. The findings indicate a dissimilar gene expression pattern between the two cell types. The expression of IL-12 and IL-23, important for promoting Th1 and Th17 cells, respectively, was up-regulated only in DCs. In addition, expression of CCL1 and CCL17, which are important in recruitment of T regulatory cells, was DC-specific, as was the expression of the immunosuppressive cytokine IL-10. Macrophages, in contrast, exhibited enhanced expression for CCL2 and CXCL10, chemokines that recruit cells to sites of inflammation, and for mycobactericidal molecules NO synthase 2 and TNF. Together, the findings suggest that a component of the innate DC response is not only programmed toward Th1 priming but is also for controlling the magnitude of the Th1 response, and part of the macrophage response is intended for recruiting cells to the lung and for mycobactericidal functions.
Standardized microtiter assay for determination of syncytium-inducing phenotypes of clinical human immunodeficiency virus type 1 isolates. (2020)

A standardized assay in 96-well microtiter plates for syncytium-inducing (SI) human immunodeficiency virus type 1 phenotype detection using MT-2 cells has been developed. SI variants were found in 67% of the patients with advanced human immunodeficiency virus disease. The occurrence of the SI phenotype increased with lower CD4+ counts. There was no association between p24 antigenemia and the SI phenotype.
A procedure for validating the sterility of individual gamma radiation sterilized production batches. (1987)

A method is described (Batch Release method) which allows the user to validate the sterility of individual batches of gamma radiation-sterilized medical devices. The method has been validated using a wide variety of products ranging from sutures to complex mechanical devices. It has been used in instances where product is available in limited quantities, or is prohibitively expensive. The method is a corollary to the AAMI Guidelines for Radiation Sterilization method Bl. It has been modified to accept a reduced sample size (20 instead of 130 samples) without a concomitant loss of accuracy or sensitivity.
The Heart of Sleep (2004)

Heart failure is associated with high rates of hospitalization and mortality as well as great economic burden in the United States. Recent data show that a high percentage of patients with depressed left ventricular ejection fractions suffer from sleep-disordered breathing, contributing to this incidence of morbidity and mortality. Since the signs and symptoms associated with sleep disorders do not differ significantly from chronic heart failure signs and symptoms, detection and recognition of sleep-disordered breathing is a clinical challenge. Thus clinicians frequently fail to recognize it as a possible contributor to the development of heart failure or as a consequence of the disease. This article discusses sleep, sleep-disordered breathing, its effects and consequences on the cardiovascular system, strategies for identifying at-risk individuals, and treatment options.
Impact of Reduced Lignin on Plant Fitness (2005)

Lignin content of crop plants has been reduced by traditional plant breeding, natural and induced mutations, and insertion of transgenes. The effects of these genes and associated lower lignin content have been examined in terms of agricultural fitness or with regard to economically harvestable yields of useful plant products, or, in the case of some perennial species, survivability over multiple years. In general, crop yields are depressed by significant reductions in lignin content. Other negative effects observed in plants with lowered lignin contents include lodging and reduction of long‐term survival of some perennial species. However, the interactions of genes involved in lignin metabolism with genetic background and the environment in which the low‐lignin crop is cultivated are substantial. Examples are provided that demonstrate that lignin can be reduced in specific lines or populations without damaging fitness. It is concluded that it will be essential to incorporate lignin reducing genes into numerous genetic backgrounds and combinations, and evaluate the resulting lines in diverse environments, to discover optimal combinations and to obtain a true measure of value and fitness in agricultural systems.
Tooth shade analysis and selection in prosthodontics: A systematic review and meta-analysis (2020)

The VES spectrophotometer reported the highest accuracy, reliability, and repeatability in shade selection followed by photo colorimetric method. The Vita 3D master shows more consistent results in repetitive shade selection. Knowledge and training of the shade selection protocol are necessary for proper shade matching.
Electrochromic dynamic windows for office buildings (2012)

The next generation of advanced fenestration products includes dynamic electrochromic (EC) windows which can modulate the solar energy entering a building by application of an applied voltage. The windows can be switched from 62% visible transmittance (Tvis), 0.47 solar heat gain coefficient (SHGC) to a fully tinted state with ⩽2% Tvis, 0.09 SHGC. EC windows save energy in buildings – the total energy use for an eight story ASHRAE 90.1 2007 commercial office building with EC windows was modeled using the eQuest building simulation program and compared with the energy use of the same building with a variety of static glazings. The simulations were carried out in three US climate zones, encompassing a broad range of environmental exposure conditions from hot and dry (Arizona) to very cold (Minnesota). For all climate zones, building energy savings with EC glass were ⩾45% when compared to single pane static glazings common in existing building stock. When EC glass was compared to ASHRAE 90.1 2007 code compliant glazings, energy savings greater than 20% were calculated for the same building configuration. Optimum EC window control and performance strategies were derived from the modeling results. The EC glass and dimmable electric lights were synergistically controlled to maximize the use of natural daylighting and minimize electricity for lighting. Since EC glass can tint to ⩽2%, shades and/or blinds are not required for glare reduction, and building occupants always have a comfortable working environment and an unobstructed view and connection to the outdoors. All static glazing systems were assumed to have manual shading devices that are pulled by building occupants when glare becomes uncomfortable. For integrated building control systems, the peak load is significantly reduced when dynamic glazings are part of the building envelope. Consequently, chiller costs are lower, and the upfront capital costs for new building construction are reduced. Another key benefit of EC glass, elucidated by the simulations is reduction of CO2 emissions. EC glass reduces peak load carbon emissions by as much as 35% in new construction and 50% in renovation projects.
B cell antigen receptor-mediated apoptosis. Importance of accessory molecules CD19 and CD22, and of surface IgM cross-linking. (1995)

Engagement of the B cell Ag receptor can induce a suicide pathway in various B cell types. Earlier studies showed that anti-IgM mAb treatment triggers apoptotic death in the Burkitt lymphoma-derived cell line, Ramos. We show that two B cell surface molecules, CD19 and CD22, which have been reported to interact either functionally or structurally with the B cell Ag receptor, also stimulate cell suicide when sufficiently aggregated, both in the Ramos and EBV-infected Ramos AW cell lines. In conditions of lower cross-linking, both molecules enhance the apoptotic response induced by a suboptimal dose of anti-IgM mAb in Ramos cells, reinforcing the notion that CD19 and CD22 may be involved in the death pathway and modulate Ag-induced B cell apoptosis. Similar outcomes were obtained with human tonsillar B cells, which enter the death program upon treatment with cross-linked anti-IgM, -CD19, or -CD22 mAbs. These results indicate that Ag-induced B cell suicide may affect mature B cells in the periphery and may be regulated via the interaction of CD19 and/or CD22 with their respective ligand(s). Early tyrosine phosphorylations were analyzed by Western blotting. The biologic outcome of these various treatments--cell survival or death--could not be related to any detectable new tyrosine-phosphorylated substrate, further questioning the biochemical basis of apoptosis signaling.
PAcM-AN: Poly(N-Acryloylmorpholine)-Conjugated Antisense Oligonucleotides (2000)

A new amphiphilic, high-molecular weight poly (N-acryloylmorpholine) (PAcM) polymer has been used to be linked to oligonucleotide chains through a liquid-phase stepwise synthesis. This new conjugate has been investigated for its melting property, nuclease stability and capacity to elicit RNase H activity. Its antisense activity against an HIV-1 target has been also evaluated.
Species-Specific Determinants in the IgG CH3 Domain Enable Fab-Arm Exchange by Affecting the Noncovalent CH3–CH3 Interaction Strength (2011)

A distinctive feature of human IgG4 is its ability to recombine half molecules (H chain and attached L chain) through a dynamic process termed Fab-arm exchange, which results in bispecific Abs. It is becoming evident that the process of Fab-arm exchange is conserved in several mammalian species, and thereby represents a mechanism that impacts humoral immunity more generally than previously thought. In humans, Fab-arm exchange has been attributed to the IgG4 core-hinge sequence (226-CPSCP-230) in combination with unknown determinants in the third constant H chain domain (CH3). In this study, we investigated the role of the CH3 domain in the mechanism of Fab-arm exchange, and thus identified amino acid position 409 as the critical CH3 determinant in human IgG, with R409 resulting in exchange and K409 resulting in stable IgG. Interestingly, studies with IgG from various species showed that Fab-arm exchange could not be assigned to a common CH3 domain amino acid motif. Accordingly, in rhesus monkeys (Macaca mulatta), aa 405 was identified as the CH3 determinant responsible (in combination with 226-CPACP-230). Using native mass spectrometry, we demonstrated that the ability to exchange Fab-arms correlated with the CH3-CH3 dissociation constant. Species-specific adaptations in the CH3 domain thus enable Fab-arm exchange by affecting the inter-CH3 domain interaction strength. The redistribution of Ag-binding domains between molecules may constitute a general immunological and evolutionary advantage. The current insights impact our view of humoral immunity and should furthermore be considered in the design and evaluation of Ab-based studies and therapeutics.
Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study (2007)

To evaluate the utility of transcript profiling for prediction of protein expression levels, we compared profiles across the NCI-60 cancer cell panel, which represents nine tissues of origin. For that analysis, we present here two new NCI-60 transcript profile data sets (A based on Affymetrix HG-U95 and HG-U133A chips; Affymetrix, Santa Clara, CA) and one new protein profile data set (based on reverse-phase protein lysate arrays). The data sets are available online at http://discover.nci.nih.gov in the CellMiner program package. Using the new transcript data in combination with our previously published cDNA array and Affymetrix HU6800 data sets, we first developed a "consensus set" of transcript profiles based on the four different microarray platforms. Using that set, we found that 65% of the genes showed statistically significant transcript-protein correlation, and the correlations were generally higher than those reported previously for panels of mammalian cells. Using the predictive analysis of microarray nearest shrunken centroid algorithm for functional prediction of tissue of origin, we then found that (a) the consensus mRNA set did better than did data from any of the individual mRNA platforms and (b) the protein data seemed to do somewhat better (P = 0.027) on a gene-for-gene basis in this particular study than did the consensus mRNA data, but both did well. Analysis based on the Gene Ontology showed protein levels of structure-related genes to be well predicted by mRNA levels (mean r = 0.71). Because the transcript-based technologies are more mature and are currently able to assess larger numbers of genes at one time, they continue to be useful, even when the ultimate aim is information about proteins.
Cofilin Promotes Actin Polymerization and Defines the Direction of Cell Motility (2004)

A general caging method for proteins that are regulated by phosphorylation was used to study the in vivo biochemical action of cofilin and the subsequent cellular response. By acute and local activation of a chemically engineered, light-sensitive phosphocofilin mimic, we demonstrate that cofilin polymerizes actin, generates protrusions, and determines the direction of cell migration. We propose a role for cofilin that is distinct from its role as an actin-depolymerizing factor.
Effect of Alkali Treatment of Coir Fiber on Its Morphology and Performance of the Fiber/LLDPE Bio-Composites (2010)

The morphology of the coir fiber by alkali treatment and untreated was analyzed by scanning electron microscope (SEM). The main component of wax layer on coir fiber surface and the mechanical performance of coir fiber/line low density polyethylene (LLDPE) bio-composites were studied. The flexural and impact strength of the composites after alkali treatment for the fibers were lower obviously than that of the composites without treatment. The result of Infrared Spectrumetry-Fouorier Transform (FTIR) shows that fatty acid and waxy material on the surface of the coir fiber were disposed of by alkali solution. The fatty acid and waxy material are compatible with non-polar LLDPE matrix. The compatibility between the coir and matrix was reduced obviously with loss of them. Therefore, the alkali treatment weakens significantly the compatibility between the coir and LLDPE, and this is a main reason that the mechanical performance of the composites was markedly declined.
Prospective Randomized Trial of the Treatment of Patients With Metastatic Melanoma Using Chemotherapy With Cisplatin, Dacarbazine, and Tamoxifen Alone or in Combination With Interleukin-2 and Interferon Alfa-2b (1999)

With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.
Gene therapy for muscle diseases (1994)

Duchenne muscular dystrophy involves progressive degeneration of the skeletal and cardiac muscles, resulting in premature death. A number of methods are currently being developed for the treatment of Duchenne muscular dystrophy and other neuromuscular disorders. A number of the viral vector systems, myoblast transfer, and direct injection techniques that are currently under investigation for the treatment of neuromuscular disorders are reviewed here.
Transport of l‐arginine and nitric oxide formation in human platelets (2003)

The results of the present study show that human platelets take up l-arginine by two transport systems which are compatible with the systems y+ and y+L. These Na+independent transporters have been distinguished by treating platelets with N-ethylmaleimide that blocks selectively system y+. System y+, that accounts for 30-40% of the total transport, is characterized by low affinity for l-arginine, is unaffected by l-leucine, is sensitive to changes of membrane potential and to trans-stimulation. The other component of l-arginine transport identified with the system y+L (approximately 60-70% of the total flux) shows high affinity for l-arginine, is insensitive to N-ethylmaleimide treatment, unaffected by changes in membrane potential, sensitive to trans-stimulation and inhibited by l-leucine in the presence of Na+. Moreover a strict correlation between l-arginine transport and nitric oxide (NO) production in whole cells was found. N-ethylmaleimide and l-leucine decreased NO production as well as cGMP elevation, and the effect on NO and cGMP were closely related. It is likely that the l-arginine transport systems y+ and y+L are both involved in supplying substrate for NO production and regulation in human platelets.
Review article: Fabrication of nanofluidic devices (2013)

Thanks to its unique features at the nanoscale, nanofluidics, the study and application of fluid flow in nanochannels/nanopores with at least one characteristic size smaller than 100 nm, has enabled the occurrence of many interesting transport phenomena and has shown great potential in both bio- and energy-related fields. The unprecedented growth of this research field is apparently attributed to the rapid development of micro/nanofabrication techniques. In this review, we summarize recent activities and achievements of nanofabrication for nanofluidic devices, especially those reported in the past four years. Three major nanofabrication strategies, including nanolithography, microelectromechanical system based techniques, and methods using various nanomaterials, are introduced with specific fabrication approaches. Other unconventional fabrication attempts which utilize special polymer properties, various microfabrication failure mechanisms, and macro/microscale machining techniques are also presented. Based on these fabrication techniques, an inclusive guideline for materials and processes selection in the preparation of nanofluidic devices is provided. Finally, technical challenges along with possible opportunities in the present nanofabrication for nanofluidic study are discussed.
In vivo selective gene expression and therapy mediated by adenoviral vectors for human carcinoembryonic antigen-producing gastric carcinoma. (1997)

Previously, we reported that adenoviral vectors carrying the carcinoembryonic antigen (CEA) promoter sequences to direct the Echerichia coli beta-galactosidase gene (AdCEA-lacZ) or cytosine deaminase (CD) gene (AdCEA-CD) confer selective gene expression on a CEA-positive gastric cancer cell line (MKN45) in vitro. Here, adenovirus-mediated tumor-specific gene therapy for CEA-positive gastric carcinoma in vivo was investigated. Using an animal model with i.p. disseminated MKN45 tumors, adenovirus-mediated tumor-specific transgene expression and therapeutic efficacy were analyzed. After an i.p. injection of AdCEA-lacZ, beta-galactosidase activity was confined to tumor xenografts. Moreover, CD mRNA was expressed exclusively in MKN45 tumor xenografts after infection with AdCEA-CD, despite the fact that an adenovirus-mediated transfer of CD DNA was detected in all tissues tested. In contrast, CD mRNA was detected not only in tumor xenografts but also in other organs of mice infected with AdCA-CD, in which CD gene expression is governed by an ubiquitous promoter. Suppression of tumor growth and prolongation of survival were noted in tumor-bearing mice treated with AdCEA-CD and 5-fluorocytosine (5FC) without observable adverse effects. In contrast, significant hepatic toxicity was noted in animals treated with AdCA-CD. These results reveal that the CEA promoter restricts CD gene expression to CEA-positive tumor cells in the adenoviral context in vivo, along with the beneficial therapeutic effects of 5FC treatment, suggesting the i.p. AdCEA-CD/5FC system may provide a novel approach to treatment of i.p. disseminated gastric cancer.