gebhart/patrepeval huggingface dataset:
A systematic study to determine the extent of gene silencing inNicotiana benthamianaand other Solanaceae species when heterologous gene sequences are used for virus‐induced gene silencing (2007)

Virus-induced gene silencing (VIGS) is a rapid and robust method for determining and studying the function of plant genes or expressed sequence tags (ESTs). However, only a few plant species are amenable to VIGS. There is a need for a systematic study to identify VIGS-efficient plant species and to determine the extent of homology required between the heterologous genes and their endogenous orthologs for silencing. Two approaches were used. First, the extent of phytoene desaturase (PDS) gene silencing was studied in various Solanaceous plant species using Nicotiana benthamiana NbPDS sequences. In the second approach, PDS sequences from a wide range of plant species were used to silence the PDS gene in N. benthamiana. The results showed that tobacco rattle virus (TRV)-mediated VIGS can be performed in a wide range of Solanaceous plant species and that heterologous gene sequences from far-related plant species can be used to silence their respective orthologs in the VIGS-efficient plant N. benthamiana. A correlation was not always found between gene silencing efficiency and percentage homology of the heterologous gene sequence with the endogenous gene sequence. It was concluded that a 21-nucleotide stretch of 100% identity between the heterologous and endogenous gene sequences is not absolutely required for gene silencing.
Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis. (1996)

We have generated transgenic mice overexpressing Bcl-2, an apoptosis suppression protein, in ovarian cells using the inhibit-alpha gene promoter/enhancer. Ovarian apoptotic DNA fragmentation induced in immature animals by a low dose (2 IU) of PMSG was suppressed by greater than 55% in transgenic mice compared to their wild-type littermates. Morphological and in situ DNA end-labeling analyses showed that granulosa cells in large antral follicles of wild-type animals undergo apoptosis, but most follicles in transgenic animals are healthy. When the animals were treated with a high dose (4 IU) of PMSG to stimulate follicular growth, spontaneous ovulation was observed in 14 of 23 (61%) of the transgenic animals, but in only 3 of 18 (17%) of wild-type siblings. Furthermore, transgenic females had a larger litter size (9.07 +/- 0.25 pups/litter; n = 29) than wild-type controls (7.54 +/- 0.26 pups/litter; n = 28; P < 0.01). These data suggested that decreased ovarian apoptosis in transgenic animals could lead to enhanced folliculogenesis and ovulatory potential. Moreover, aging transgenic mice are susceptible to the development of benign cystic ovarian teratoma (4 in 20 transgenic animals and 0 in 26 wild-type controls). Some tumor tissues showed respiratory and intestinal cell types, whereas others showed the development of central nervous system-like structures. Because the bcl-2 transgene in these animals is overexpressed in somatic cells, but not oocytes, these findings suggest that enhanced survival of selected somatic cells in transgenic mice could lead to germ cell tumorigenesis. Thus, overexpression of Bcl-2 protein in the ovary leads to decreased ovarian somatic cell apoptosis, enhanced folliculogenesis, and increased susceptibility to ovarian germ cell tumorigenesis in transgenic animals. The present mouse model allows future studies on intracellular signal pathways regulating follicular atresia and on the potential role of ovarian somatic cell factors in germ cell tumorigenesis.
Formation of a G-tetrad and higher order structures correlates with biological activity of the RelA (NF-kappaB p65) 'antisense' oligodeoxynucleotide (1997)

We have examined the behavior of the phosphorothioate antisense Rel A (NF-kappaB p65) oligodeoxynucleotide (oligo) and related molecules. Because of the presence of a G-tetrad near its 5'terminus, this molecule is capable of forming tetraplexes and other higher order structures in a temperature and time dependent manner. The G-tetrad in the phosphodiester congener is protected from methylation by dimethylsulfate when the oligomer is 3'-phosphorylated. However, this protection is completely lost when it is 5'phosphorylated, indicating that the formation of at least some higher order structures has been blocked. In addition, we also prevented tetraplex formation by substitution of 7-deazaguanosine (7-DG) for guanosine at several positions within and outside of the tetrad. This substitution retains Watson-Crick base pair hybridization but prevents Hoogsteen base-pair interactions. When murine K-Balb cells were treated with 20microM antisense RelA oligo, complete blockade of nuclear translocation of RelA was observed. However, this effect was virtually entirely abrogated in most cases by 7-DG substitution within the tetrad, but retained when the substitution was made 3' to the tetrad. The AS RelA-induced downregulation of Sp-1 activity behaved similarly after 7-DG substitution. Thus, the parent phosphorothioate AS RelA molecule cannot be a Watson-Crick antisense agent. However, these conclusions cannot be extrapolated to other G-tetrad containing oligomers and each must be evaluated individually.
Indoor people tracking based on dynamic weighted multidimensional scaling (2007)

Accurate location of people in indoor environments is a key aspect of many applications such as resource management or security. In this paper, we explore the use of short-range radio technologies to track people indoors. The network consists of two kind of radio nodes: static nodes (anchors) and mobile nodes (people). From a set of sparse connectivity matrices (people vs. people and people vs. anchors) at each time instant and people's dynamics, we infer people's trajectories. To combine connectivity and dynamic information, we propose an extension of Multidimensional Scaling(MDS), Dynamic Weighted MDS (DWMDS), that finds an embedding of people's trajectories (x and y coordinates of people through time). DWMDS has proven to be more accurate and effective, especially for low connectivity degree networks (i.e. sparse networks), compared to existing location algorithms. Extensive simulations show the effectiveness and robustness of the proposed algorithm.
Double-antibody sandwich enzyme-linked immunosorbent assay for quantitation of endoglucanase I of Trichoderma reesei (1991)

A sensitive and specific enzyme-liked immunosorbent assay for endoglucanase I (EG-I) has been developed. The monoclonal antibody a-EG-I 2, directed against an epitope on the core part of the enzyme, was used to capture the antigen in microtiter plate wells. A second, polyclonal antibody against the enzyme was then used to detect and quantitate the bound antigen. The test was specific for EG-I; neither endoglucanase II nor cellobiohydrolase I or II interfered. As little as 20 pg of EG-I protein could be detected. The coefficients of variation were 3.8% within plates and 6% between plates for a diluted Trichoderma reesei culture supernatant that contained 31 ng of EG-I per ml. Binding of the antigen to the monoclonal antibody was pH dependent and restricted to values between pH 6.5 and 10.5 with a maximum around pH 9. Standard solutions of EG-I were very stable at concentrations as low as 5 ng/ml when prepared in buffer that contained 1% bovine serum albumin and that was stored at -20 degrees C. After 37 weeks the antigenicity was still 97%. With this test it was possible to monitor the production of EG-I in a cellulase-producing strain of T. reesei and to demonstrate the apparent absence of the enzyme in a strain with the eglI gene deleted.
Therapeutic potential of neutralizing antibodies in the treatment of HIV-1 infection (2003)

In 1981 unusual cases of severe immune deficiency were reported. Two years later the cause of the acquired immuno- deficiency syndrome (AIDS) was identified: a retrovirus, designated the human immunodeficiency virus (HIV), that caused a loss of important immune functions leading to a dramatic vulnerability to a variety of bacterial, viral and fungal infections. The finding that the presence of neutral- izing antibodies correlated with the disease status suggested that infusion with hyperimmune plasma and human HIV- specific immunoglobulin (HIVIG) obtained from chronically HIV-1-infected asymptomatic donors may be of benefit to patients. However, early clinical studies were disappointing. No clear benefits were found for the majority of patients treated. 1 The introduction of highly active antiretroviral therapy (HAART) in 1996 caused great excitement. HAART drugs inhibit viral replication within infected cells by interfering with two crucial viral enzymes: reverse transcriptase and pro- tease. The initial hope that HIV could be eradicated in patients undergoing several years of HAART was not fulfilled and it became clear that HAART had major drawbacks. The high degree of severe side effects, short drug half-life, persistent viral reservoirs and the increasing prevalence of drug- resistant viruses underscored the need for additional thera- peutic approaches against HIV-1. Drugs that prevent viral replication at earlier steps such as virus entry into target cells and integration of the viral genome into the host genome are the focus of current drug development. Fusion inhibitors such as the T20 peptide, which prevents conformational changes in the viral membrane necessary for virus entry, are currently in clinical development. 2 However, T20 has to be injected daily owing to its short half-life, and induces adverse reactions at the site of administration. During the last decade several human monoclonal anti- bodies (hmAbs) were established to have an unusually high antiviral potential against HIV-1. The hmAbs neutralize the virus by binding to conserved epitopes of the proteins gp120 (antibodies 2G12, 3,4 IgG1b12 5 ) or gp41 (2F5, 6 4E10 7 ) representing 'natural' entry inhibitors with half-lives 50- 100 times longer than fusion inhibitor peptides. These anti- bodies inhibit replication of the majority of primary isolates with high potency. 8 Moreover, there is evidence that these antibodies are capable of lysing virus particles and infected cells by antibody-dependent cellular cytotoxicity (ADCC) and complement activation. 4,9 Although the high antiviral potential of these antibodies has been demonstrated in vitro, their usefulness for in vivo application was doubted by many. The unsatisfying results in HIVIG studies and the difficulties in hmAb large-scale technology were major hurdles for the development of antibody therapy.
Type I IFNs Regulate Effector and Regulatory T Cell Accumulation and Anti-Inflammatory Cytokine Production during T Cell–Mediated Colitis (2013)

We explored the function of endogenous type I IFNs (IFN-1) in the colon using the T cell adoptive transfer model of colitis. Colon mononuclear phagocytes (MPs) constitutively produced IFN-1 in a Toll/IL-1R domain-containing adapter-inducing IFN-β-dependent manner. Transfer of CD4(+)CD45RB(hi) T cells from wild-type (WT) or IFN-α/β receptor subunit 1 knockout (IFNAR1(-/-)) mice into RAG(-/-) hosts resulted in similar onset and severity of colitis. In contrast, RAG(-/-) × IFNAR1(-/-) double knockout (DKO) mice developed accelerated severe colitis compared with RAG(-/-) hosts when transferred with WT CD4(+)CD45RB(hi) T cells. IFNAR signaling on host hematopoietic cells was required to delay colitis development. MPs isolated from the colon lamina propria of IFNAR1(-/-) mice produced less IL-10, IL-1R antagonist, and IL-27 compared with WT MPs. Accelerated colitis development in DKO mice was characterized by early T cell proliferation and accumulation of CD11b(+)CD103(-) dendritic cells in the mesenteric lymph nodes, both of which could be reversed by systemic administration of IL-1R antagonist (anakinra). Cotransfer of CD4(+)CD25(+) regulatory T cells (Tregs) from WT or IFNAR1(-/-) mice prevented disease caused by CD4(+)CD45RB(hi) T cells. However, WT CD4(+)CD25(+)Foxp3(GFP+) Tregs cotransferred with CD4(+)CD45RB(hi) T cells into DKO hosts failed to expand or maintain Foxp3 expression and gained effector functions in the colon. To our knowledge, these data are the first to demonstrate an essential role for IFN-1 in the production of anti-inflammatory cytokines by gut MPs and the indirect maintenance of intestinal T cell homeostasis by both limiting effector T cell expansion and promoting Treg stability.
Molecular Characterization of Rab11 Interactions with Members of the Family of Rab11-interacting Proteins (2004)

The Rab11 subfamily of GTPases plays an important role in vesicle trafficking from endosomes to the plasma membrane. At least six Rab11 effectors (family of Rab11-interacting proteins (FIPs)) have been shown to interact with Rab11 and are hypothesized to regulate various membrane trafficking pathways such as transferrin recycling, cytokinesis, and epidermal growth factor trafficking. In this study, we characterized interactions of FIPs with the Rab11 GTPase using isothermal titration calorimetric studies and mutational analysis. Our data suggest that FIPs cannot differentiate between GTP-bound Rab11a and Rab11b in vitro (50-100 nm affinity) and in vivo. We also show that, although FIPs interact with the GDP-bound form of Rab11 in vitro, the binding affinity (>1000 nm) is not sufficient for FIP and GDP-bound Rab11 interactions to occur in vivo. Mutational analysis revealed that both the conserved hydrophobic patch and Tyr628 are important for the GTP-dependent binding of Rab11 to FIPs. The entropy and enthalpy analyses suggest that binding to Rab11a/b may induce conformational changes in FIPs.
Vaccine against norovirus (2014)

Noroviruses (NoVs) are important pathogens causing epidemic acute gastroenteritis affecting millions of people worldwide. Due to the inability to cultivate NoVs, current NoV vaccine development relies on bioengineering technologies to produce virus-like particles (VLPs) and other subviral particles of NoVs as subunit vaccines. The first VLP vaccine has reached phase II clinical trials and several others are under development in pre-clinical research. Several subviral complexes made from the protruding (P) domains of NoV capsid share common features of easy production, high stability and high immunogenicity and thus are candidates for low cost vaccines. These P domain complexes can also be used as vaccine platforms to present foreign antigens for potential dual vaccines against NoVs and other pathogens. Development of NoV vaccines also faces other challenges, including genetic diversity of NoVs, limit understanding of NoV immunology and evolution, and lack of an efficient NoV animal model for vaccine assessment, which are discussed in this article.
TOPICAL CAPSAICIN FOR CHRONIC NECK PAIN (1995)

Substance P is thought to be the principle neurotransmitter of nociceptive impulses in type C sensory neurons. Prolonged repeated applications of capsaicin cream depletes the sensory C-fibers of substance P. In an open-labeled prospective pilot study, 23 patients with chronic neck pain (greater than 3 mo) completed the study. Patients applied topical capsaicin (0.025%) cream four times a day to painful areas in the neck and shoulder girdle for a 5-wk treatment period. One patient dropped out because of intolerable burning. Statistically significant improvement was obtained in two primary outcome variables, the visual analog pain scale (P = 0.00013) and the pain relief scale (P = 0.002). Paired t tests failed to show a significant improvement in the McGill Pain Questionnaire. This study demonstrated that topically applied capsaicin cream may decrease subjective neck pain. A double-blind, placebo-controlled trial is needed to confirm this treatment effect.
NAP1 Strain Type Predicts Outcomes From Clostridium difficile Infection (2014)

NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity.
Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas (2009)

Despite major advances in the treatment of non-Hodgkin lymphoma (NHL), including the use of chemotherapeutic agents and the anti-CD20 antibody rituximab, the majority of patients eventually relapse, and salvage treatments with non-cross-resistant compounds are needed to further improve patient survival. Here, we evaluated the antitumor effects of the microtubule destabilizing agent monomethyl auristatin E (MMAE) conjugated to the humanized anti-CD19 antibody hBU12 via a protease-sensitive valine-citrulline (vc) dipeptide linker. hBU12-vcMMAE induced potent tumor cell killing against rituximab-sensitive and -resistant NHL cell lines. CD19 can form heterodimers with CD21, and high levels of CD21 were reported to interfere negatively with the activity of CD19-targeted therapeutics. However, we observed comparable internalization, intracellular trafficking, and drug release in CD21(low) and CD21(high), rituximab-sensitive and -refractory lymphomas treated with hBU12-vcMMAE. Furthermore, high rates of durable regressions in mice implanted with these tumors were observed, suggesting that both rituximab resistance and CD21 expression levels do not impact on the activity of hBU12-vcMMAE. Combined, our data suggest that hBU12-vcMMAE may represent a promising addition to the treatment options for rituximab refractory NHL and other hematologic malignancies, including acute lymphoblastic leukemia.
Identification of Active-Site Residues in Glycosidases (1996)

A strategy has been developed for the reliable labeling of the active site nucleophile in glycosidases which hydrolyse with net retention of anomeric configuration. Electrospray mass spectrometric analysis of the intact protein before and after inactivation allows facile determination of the stoichiometry of labeling. High performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) analysis of proteolytic digests of these samples with monitoring in the neutral loss mode allows identification of the peptide within the mixture which is labeled, without the need for radioactive tagging. Inspection of the sequence of the protein for candidate peptides of this mass allows the generation of a short list of possible peptides. The true identity of the labeled peptide can be determined after further ESI-MS/MS analysis of the peptide of interest in the product ion mass spectrum. Labeled peptides which do not undergo the necessary facile cleavage in the collision cell of the mass spectrometer can generally be identified within a mixture by comparison of HPLC-ESI-MS data from both unlabeled and labeled samples. A search is made for a peptide which is present in the labeled digest and absent in the unlabeled digest, and is heavier by the expected amount than a peptide which is missing from the labeled digest but present in the unlabeled digest. Examples of these approaches are described with the xylanase from Bacillus subtilis, human β-glucocerebrosidase and the exo-xylanase/glucanase from Cellulomonas fimi.
Mechanism of Action of Tubulysin, an Antimitotic Peptide from Myxobacteria (2006)

Tubulysin A is a highly cytotoxic peptide with antimitotic activity that induces depletion of cell microtubules and triggers the apoptotic process. Treated cells accumulated in the G2/M phase. Tubulysin A inhibited tubulin polymerization more efficiently than vinblastine and induced depolymerization of isolated microtubule preparations. Microtubule depolymerization could not be prevented by preincubation with epothilone B and paclitaxel, neither in cell-free systems nor in cell lines. In competition experiments, tubulysin A strongly interfered with the binding of vinblastine to tubulin in a noncompetitive way; the apparent Ki was 3 microM. Electron microscopy investigations showed that tubulysin A induced the formation of rings, double rings, and pinwheel structures. The mode of action of tubulysin A resembled that of peptide antimitotics dolastatin 10, phomopsin A, and hemiasterlin. Efforts are underway to develop this new group of compounds as anticancer drugs.
Federal and Local Interests in the Nation's Capital: Congress and District of Columbia Appropriations (1989)

Canadian political scientist Donald C. Rowat posits the thesis that there is a “conflict of interest” in all federal capital cities between the national government and the local residents. Federal and local interests in the nation's capital have been so intertwined that it is difficult to define or separate them. Congress has used the appropriations process to intervene in local policy matters even when the federal interest is not involved.
Complement receptor 1 inhibitors for prevention of immune-mediated red cell destruction: potential use in transfusion therapy (2003)

Activation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell (RBC) destruction, causing transfusion reactions and hemolytic anemia. In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. Using an in vitro alloimmune incompatibility model, sCR1 inhibited complement activation and prevented hemolysis. Following transfusion of human group O RBCs into mice lacking detectable pre-existing antibodies against the transfused RBCs, systemic coadministration of 10 mg/kg sCR1, a dose well tolerated in human subjects for prevention of tissue injury, completely inhibited the in vivo clearance of the transfused RBCs and surface C3 deposition in the first hour after transfusion, correlating with the half-life of sCR1 in the circulation. Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. We further identified potential functional domains in CR1 that can act to limit complement-mediated RBC destruction in vitro and in vivo. Collectively, our data highlight a potential use of CR1-based inhibitors for prevention of complement-dependent immune hemolysis.