gebhart/patrepeval huggingface dataset:
Intravascular and Endobronchial DNA Delivery to Murine Lung Tissue Using a Novel, Nonviral Vector (2000)

Gene transfer to the lung can be achieved via either the airway or the pulmonary vasculature. We evaluated gene transfer and expression by intravascular and endobronchial routes, using DNA complexed with G9 PAMAM dendrimer or naked plasmid DNA. Intravascular tail vein delivery of dendrimer-complexed pCF1CAT plasmid resulted in high levels of transgene expression in the lung at 12 and 24 hr, followed by a second peak of expression 3 to 5 days after administration. After intravenous administration of the complexes, CAT expression was never observed in organs other than the lung. There were only minimal levels of CAT protein expressed in the lung after intravenous administration of naked plasmid DNA. Repeated intravascular doses of the dendrimer-complexed plasmid, administered four times at 4-day intervals, maintained expression at 15-25% of peak concentrations achieved after the initial dose. Endobronchial delivery of naked pCF1CAT plasmid produced significant amounts of CAT protein in the lung. Comparison of intratracheal and intranasal routes resulted in similar expression levels of CAT in the lung and trachea. However, in juxtaposition to vascular delivery, intranasal delivery of dendrimer-complexed plasmid DNA gave lower levels of CAT expression than that observed with naked plasmid DNA. In situ localization of CAT enzymatic activity suggested that vascular administration seemed to achieve expression in the lung parenchyma, mainly within the alveoli, while endobronchial administration primarily targeted bronchial epithelium. Our results show that intravenously administered G9 dendrimer is an effective vector for pulmonary gene transfer and that transgene expression can be prolonged by repeated administration of dendrimer-complexed DNA.
US foreign aid (2013)

Purpose – The purpose of this paper is to provide an overview of similarities and distinctions between development and educational assistance in the USA as compared with other countries, this paper provides a general review of relevant materials on US foreign aid. Design/methodology/approach – The paper reviews published books and articles as well as US government budget and Congressional reporting materials and Organization for Economic Cooperation and Development statistics. Findings – Beginning with the Marshall Plan following Second World War, the USA has always been a leader in foreign aid. In many ways, US development agencies resemble counterparts in other countries – foreign aid is part of larger network of bilateral relationships, funding requests must compete with requests from other sectors, etc. In other ways, the US stands apart. Because of US Congressional reporting requirements and for philosophical reasons, the US has been reluctant to join other countries in provision of budgetary support. The US coordinates its work with host country governments, but generally organizes its activities in project mode, relying largely on US contractors. The US Agency for International Development and the Department of State are the largest US government development agencies. Still, unlike other donors, development funding and technical assistance is provided by up to 25 agencies with relatively little coordination. US foreign aid has always included a security as well as humanitarian and development dimensions. In recent years, as development assistance is increasingly coordinated with diplomacy and defense, the military dimension has been heightened. Perhaps the most original finding is the notion that public and government support of US foreign aid has required both security and development/humanitarian rationales to remain viable. Originality/value – The paper brings together information from a range of existing sources, but provides a unique perspective on US foreign aid in education.
Disruption of the homeostatic balance between autoaggressive (CD4+CD40+) and regulatory (CD4+CD25+FoxP3+) T cells promotes diabetes (2008)

Although regulatory T cells (Tregs) are well described, identifying autoaggressive effector T cells has proven more difficult. However, we identified CD4loCD40+ (Th40) cells as being necessary and sufficient for diabetes in the NOD mouse model. Importantly, these cells are present in pancreata of prediabetic and diabetic NOD mice, and Th40 cells but not CD4+CD40(-) T cells transfer progressive insulitis and diabetes to NOD.scid recipients. Nonobese-resistant (NOR) mice have the identical T cell developmental background as NOD mice, yet they are diabetes-resistant. The seminal issue is how NOR mice remain tolerant to diabetogenic self-antigens. We show here that autoaggressive T cells develop in NOR mice and are confined to the Th40 subset. However, NOR mice maintain Treg numbers equivalent to their Th40 numbers. NOD mice have statistically equal numbers of CD4+CD25+forkhead box P3+intrinsic Tregs compared with NOR or nonautoimmune BALB/c mice, and NOD Tregs are equally as suppressive as NOR Tregs. A critical difference is that NOD mice develop expanded numbers of Th40 cells. We suggest that a determinant factor for autoimmunity includes the Th40:Treg ratio. Mechanistically, NOD Th40 cells have low susceptibility to Fas-induced cell death and unlike cells from NOR and BALB/c mice, have predominantly low Fas expression. CD40 engagement of Th40 cells induces Fas expression but further confers resistance to Fas-mediated cell death in NOD mice. A second fundamental difference is that NOD Th40 cells undergo much more rapid homeostatic expansion than Th40 cells from NOR mice.
The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression (2012)

The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs.
Code coverage based technique for prioritizing test cases for regression testing (2004)

Test case prioritization involves scheduling test cases in an order that increases their effectiveness in meeting some performance goals. One of the common performance goals is to run those test cases that achieve total code coverage at the earliest. In this work we propose a model that achieves 100% code coverage optimally during version specific regression testing.
Ketamine activates psychosis and alters limbic blood flow in schizophrenia (1995)

The non-competitive NMDA antagonist ketamine, given to schizophrenic individuals in subanesthetic doses, produced a short-lived, discrete activation of their psychotic symptoms, which had striking similarities to symptoms of their usual psychotic episodes. To further study this psychotomimetic property of ketamine, we administered 0.3 mg kg-1 of the drug to schizophrenic individuals during a [15O] water cerebral blood flow study. Regional cerebral blood flow (rCBF) was measured using H2(15)O and positron emission tomography (PET) before and after ketamine administration to identify regions of flow change, rCBF was increased in anterior cingulate cortex and was reduced in the hippocampus and primary visual cortex (lingual and fusiform gyri). These data encourage further consideration of altered glutamatergic transmission in schizophrenic and PCP-induced psychoses.
A Tumor Necrosis Factor Mimetic Peptide Activates a Murine Macrophage Cell Line To Inhibit Mycobacterial Growth in a Nitric Oxide-Dependent Fashion (1998)

The control of mycobacterial infections depends on the cytokine-mediated activation of mononuclear phagocytes to inhibit the growth of intracellular mycobacteria. Optimal activation requires the presence of T-cell-derived gamma interferon (IFN-gamma) and other signals, including tumor necrosis factor (TNF). Recently, an 11-mer peptide based on amino acids 70 to 80 of the human TNF sequence, TNF(70-80), was found to have TNF mimetic properties, which include the activation of human and mouse neutrophils to kill Plasmodia spp. Therefore, we investigated the capacity of TNF(70-80) to activate the murine macrophage cell line RAW264.7 infected with the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG). When RAW264.7 cells were pretreated with human TNF or TNF(70-80) in the presence of IFN-gamma, there was a dose-dependent reduction in the replication of BCG as measured by the uptake of 3H-labeled uracil and a concomitant release of nitric oxide as measured by the nitrite in the culture supernatants. TNF- or TNF(70-80)-induced macrophage activation was dependent on IFN-gamma and was inhibited by neutralizing monoclonal antibody to human TNF and by anti-IFN-gamma antisera. Both nitrite release and BCG growth inhibition were abrogated by competitive inhibitors of L-arginine, which blocked the activation of inducible nitric oxide synthase. A soluble form of the Type 1 TNF receptor blocked the activation of BCG-infected macrophages by human TNF and TNF(70-80), demonstrating that the effect of TNF(70-80) is dependent on signaling through TNF receptor I. The mimetic effects of TNF(70-80) on macrophage activation in vitro suggest that treatment with TNF(70-80) may modulate mycobacterial infections in vivo.
Dialysis access grafts: anatomic location of venous stenosis and results of angioplasty. (1995)

Performance of serial venous angioplasty procedures may help prolong the life of a graft, but the patency rates diminish with subsequent interventions.
Benzobisthiadiazole-based high-spin donor–acceptor conjugated polymers with localized spin distribution (2021)

This work indicates that carefully selected acceptor units can lead to a localized spin topology and a high-spin (<italic>S</italic>= 1) ground-state with a pure diradical (<italic>y</italic><sub>0</sub>= 1) character suitable for organic magnetic materials.
An analysis of higher‐order of a GaAs FET depending on IMD source impedance and its application to a design of low‐distortion MMIC power amplifiers (2002)

Abstract Although the π/4 phase shift modulation schemes used in quadrature phase shift keying (QPSK) are important approaches to ensuring efficient frequency usage in digital portable telephone systems, they also require linearity of the power amplifiers, they also require linearity of the power amplifiers, which is an undesirable constraint from the standpoint of efficiency. In this work, we describe a unified approach to this problem based on the idea that distortion can be effectively decreased by creating dips or “bumps” in the intermod characteristics, due to the dependence of the adjacent channel power (ACP) leakage on input power. For the special case of an impedance Z es connected to the gate of a FET, we use Volterra series to quantitatively demonstrate how the appearance of such dips or bumps is related both to Z es and to the fifth intermod (IM5). We then show analytically that when these dips or bumps are generated effectively, they can suppress IM5. Finally, we show that the resulting decrease in intermodulation distortion and improved efficiency make this method useful in the design of MMIC power amplifiers used in Personal Handy Phone (PHS) service. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 85(4): 10–21, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/ecjb.1100
A high-performance body-charge-modulated SOI sense amplifier (2002)

Dynamic CMOS SOI sensing circuits are prone to performance variation and mismatch in transfer characteristics (Kuang et al, 1997; Allen et al, 1999) as a result of hysteretic body potential and V/sub t/ differences. In dual-railed RAM and register file applications, repetitive polarized read operations performed by a sense amplifier can cause significant asymmetric charge accumulation, body voltage bias, sense point runaway, and consequent functional failures. Tracking of threshold voltages requires tight control of critical device body voltages in addition to matching of other layout and electrical parameters commonly deemed essential for analog designs. This paper presents a dynamic body charge modulation technique to address the history-induced mismatch in latch-type sense amplifiers while attaining high performance for every access cycle. The same method can also be applied to other cross-coupled differential circuit topologies where mismatch can not be tolerated. By symmetrically charging the FET bodies that are connected through two "flooding" FETs to a voltage rail, matching device characteristics can be achieved or restored each time the sense amplifier is activated. This charge flooding mechanism, as opposed to emptying the body of charges (Kuang et al, 1999), retains true and predictable low-V/sub t/ operation. By consistently elevating the sensing FET bodies to the same potential, we always start a high-performance read cycle with bodies well disposed.
Genome maintenance and transcription integrity in aging and disease (2013)

DNA damage contributes to cancer development and aging. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated aging (Schumacher et al., 2008). DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007). Cellular response mechanisms to stalled RNA polymerase II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the aging organism (Garinis et al., 2009). Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in aging and disease. We discuss how the nucleotide excision repair system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer.
RNA splicing in Borna disease virus, a nonsegmented, negative-strand RNA virus (1994)

Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus related to rhabdoviruses and paramyxoviruses. Unlike animal viruses of these two families, BDV transcribes RNAs in the nuclei of infected cells and produces high levels of transcripts containing multiple open reading frames. Previous Northern blot analysis of RNA from BDV-infected rat brain tissue has shown that two viral transcripts, a 6.1-kb RNA and a 1.5-kb RNA, lack regions that are internal to two otherwise identical transcripts, the 7.1-kb RNA and the 2.8-kb RNA, respectively (T. Briese, A. Schneemann, A. Lewis, Y. Park, S. Kim, H. Ludwig, and W. I. Lipkin, Proc. Natl. Acad. Sci. USA 91:4362-4366, 1994). To determine the precise location of this deletion, we performed reverse transcription PCR analysis using total RNA from BDV-infected rat brain tissue. This investigation resulted in the identification of two introns in the 7.1- and 2.8-kb RNAs, which can be alternatively spliced to yield additional RNA species, including the 6.1- and 1.5-kb RNAs. Transient transfection of COS-7 cells with a cDNA clone of the 2.8-kb RNA resulted in the production of both the 2.8-kb RNA and the 1.5-kb RNA, confirming the theory that the 2.8-kb RNA is a sufficient substrate for splicing in mammalian cells. Splicing has not previously been observed in nonsegmented, negative-strand RNA viruses and presumably serves as a mechanism by which expression of BDV proteins is regulated in infected cells.
Protective Host Immune Responses to Salmonella Infection (2015)

Salmonella enterica serovars Typhi and Paratyphi are the causative agents of human typhoid fever. Current typhoid vaccines are ineffective and are not widely used in endemic areas. Greater understanding of host-pathogen interactions during Salmonella infection should facilitate the development of improved vaccines to combat typhoid and nontyphoidal Salmonellosis. This review will focus on our current understanding of Salmonella pathogenesis and the major host immune components that participate in immunity to Salmonella infection. In addition, recent findings regarding host immune mechanisms in response to Salmonella infection will be also discussed, providing a new perspective on the utility of improved tools to study the immune response to Salmonella infections.
Local Accumulation of FOXP3+ Regulatory T Cells: Evidence for an Immune Evasion Mechanism in Patients with Large Condylomata Acuminata (2008)

Condylomata acuminata derived from the infection of human papillomavirus is a common sexually transmitted disease. Although T cell-mediated cellular immunity is considered as the main arm against such infection, the regulation of T cell immune responses in genital condylomata is unclear to date. In this study, we analyzed FOXP3(+) regulatory T cells in genital condylomata of patients. The results show that FOXP3(+) regulatory T cells with suppressive function accumulated in large warts. Consistently, the immunosuppressive milieu in large warts was characterized by high expression of IL-10 and TGF-beta1 and low expression of IL-2 and IFN-gamma. The responsiveness of wart-infiltrating T cells both in vitro and in vivo can be increased by depleting FOXP3(+) T cells. The accumulation of FOXP3(+) regulatory T cells in large warts can be partly ascribed to the chemotaxis of CCL17 and CCL22, derived from Langerhans cells and macrophages in wart. Although such accumulation favors the local immunosuppression, it seems not to influence the systemic immunity. In conclusion, these findings demonstrate that FOXP3(+) regulatory T cells play an important role in genital condylomata, which has multiple implications in the comprehensive treatment of condylomata acuminata.
Low circulating levels of gastrin-17 in patients with Barrett's esophagus (2005)

Serum levels of G-17fast tend to be lower in native patients with BE than in healthy controls.
Injectable Lyophilized Particulate Human Fascia Lata (Fascian) for Lip, Perioral, and Glabellar Enhancement (2000)

Texas Oculoplastic Consultants, Austin, Texas, U.S.A. Accepted October 8, 1999. Address correspondence and reprint requests to Dr. John W. Shore, Texas Oculoplastic Consultants, Inc., 3705 Medical Parkway, Suite 120, Austin, TX 78705, U.S.A.
Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver: technical aspects studied in a large animal model (2009)

In the porcine model a scout dose of (166)Ho-PLLA-MS can accurately predict the biodistribution of a treatment dose. Quantitative (166)Ho SPECT was validated for clinical application.
Efflux Mechanism, an Attractive Target to Combat Multidrug Resistant Plasmodium falciparum and Pseudomonas aeruginosa (2008)

Chemoresistance is a general health problem concerning infectious diseases and cancer treatments. In this context, the worldwide dissemination of << pandrug >> and << multidrug>> resistant pathogens has severely compromised the efficacy of our antimicrobial weapons and dramatically increased the occurence of therapeutic failure. To efficiently combat multi-resistant pathogens, it is necessary to clearly define the molecular basis of the general resistance mechanism associated with the expression of active efflux pumps, which strongly restrict the intracellular concentration of antimicrobial drugs. Several families of efflux systems capable of multiple drug extrusion have been described. The activity of some efflux systems requires ATP hydrolysis for drug transport while others require a sodium or proton antiport. In this review we focus on two important human pathogens, Plasmodium falciparum and Pseudomonas aeruginosa, which exhibit a high level of antimicrobial resistance associated with the expression of efflux mechanisms. The efflux mechanisms and the development of efflux pump inhibitors (EPIs) are discussed regarding these two pathogens.
Nickel(ii) macrocycles: highly efficient electrocatalysts for the selective reduction of CO2 to CO (2012)

A series of molecular materials that are structurally similar to the NiII macrocycle [Ni(cyclam)]2+ (cyclam = 1,4,8,11-tetraazacyclotetradecane) have been used as electrocatalysts for the reduction of CO2 at a mercury pool working electrode in aqueous solution. At pH 5, with an applied potential of −0.96 V vs. NHE (overpotential of −0.55 V), the complexes are highly efficient, having both high rate constants and Faradaic efficiencies (F.E.s) for the selective reduction of CO2 to CO. When the pH is below the pKa (pH < 2) of the Ni(H) species (pKas: 0.5–2), the F.E.s are still high but product selectivity changes to yield predominantly H2 from the reduction of water. At least two of the complexes investigated are better electrocatalysts than [Ni(cyclam)]2+, probably due to: (i) surface geometries that are suitable for adsorption onto the mercury electrode surface, and (ii) electronic effects of methyl groups or cyclohexane rings on the cyclam backbone. Mechanistic studies by pulse radiolysis show evidence of Ni(CO2) adducts for two of the catalysts, with KCO2 ∼ 10 M−1 for the reaction of NiI with CO2 in aqueous solution.