gebhart/patrepeval huggingface dataset:
Selective In Vivo Targeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model (2014)

Current challenges for recombinant adeno-associated virus (rAAV) vector-based cancer treatment include the low efficiency and the lack of specificity in vivo. rAAV serotype 3 (rAAV3) vectors have previously been shown to be ineffective in normal mouse tissues following systemic administration. In the present study, we report that rAAV3 vectors can efficiently target and transduce various human liver cancer cells in vivo. Elimination of specific surface-exposed serine and threonine residues on rAAV3 capsids results in further augmentation in the transduction efficiency of these vectors, without any change in the viral tropism and cellular receptor interactions. In addition, we have identified a potential chemotherapy drug, shikonin, as a multifunctional compound to inhibit liver tumor growth as well as to significantly enhance the efficacy of rAAV vector-based gene therapy in vivo. Furthermore, we also document that suppression of tumorigenesis in a human liver cancer xenograft model can be achieved through systemic administration of the optimized rAAV3 vectors carrying a therapeutic gene, and shikonin at a dose that does not lead to liver damage. Our research provides a novel means to achieve not only targeted delivery but also the potential for gene therapy of human liver cancer.
FeCo nanowires with enhanced heating powers and controllable dimensions for magnetic hyperthermia (2015)

A detailed study of the magnetic properties and heating capacities of electrodeposited FeCo nanowires with varying lengths (2–40 μm) and diameters (100 and 300 nm) is reported. We find that specific absorption rate (SAR) increases rapidly with increasing wire length up to 10 μm, followed by a gradual increase for larger lengths. Magnetic and hyperthermia measurements have revealed the important effect of dipolar interactions between the nanowires on their magnetic and inductive heating responses. Both calorimetric and AC magnetometry methods consistently show that the physical movement contribution of the nanowires to the SAR is small, and that for applied fields exceeding the coercive field, the nanowires tend to align parallel to the field, thus enhancing the SAR. Maximum SAR values of ∼1500 W/g have been achieved for the largest wires at H = 300 Oe and f = 310 kHz.
EGFR and ADAMs Cooperate to Regulate Shedding and Endocytic Trafficking of the Desmosomal Cadherin Desmoglein 2 (2008)

Regulation of classic cadherins plays a critical role in tissue remodeling during development and cancer; however, less attention has been paid to the importance of desmosomal cadherins. We previously showed that EGFR inhibition results in accumulation of the desmosomal cadherin, desmoglein 2 (Dsg2), at cell-cell interfaces accompanied by inhibition of matrix metalloprotease (MMP)-dependent shedding of the Dsg2 ectodomain and tyrosine phosphorylation of its cytoplasmic domain. Here, we show that EGFR inhibition stabilizes Dsg2 at intercellular junctions by interfering with its accumulation in an internalized cytoplasmic pool. Furthermore, MMP inhibition and ADAM17 RNAi, blocked shedding and depleted internalized Dsg2, but less so E-cadherin, in highly invasive SCC68 cells. ADAM9 and 15 silencing also impaired Dsg2 processing, supporting the idea that this desmosomal cadherin can be regulated by multiple ADAM family members. In contrast, ADAM10 siRNA enhanced accumulation of a 100-kDa Dsg2 cleavage product and internalized pool of Dsg2. Although both MMP and EGFR inhibition increased intercellular adhesive strength in control cells, the response to MMP-inhibition was Dsg2-dependent. These data support a role for endocytic trafficking in regulating desmosomal cadherin turnover and function and raise the possibility that internalization and regulation of desmosomal and classic cadherin function can be uncoupled mechanistically.
Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease (2015)

These results support the therapeutic potential of lenalidomide for reducing maladaptive neuroinflammation in PD and related neuropathologies.
SELECTIVE CLEAVAGE OF THE METHIONYL PEPTIDE BONDS IN RIBONUCLEASE WITH CYANOGEN BROMIDE1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSELECTIVE CLEAVAGE OF THE METHIONYL PEPTIDE BONDS IN RIBONUCLEASE WITH CYANOGEN BROMIDE1Erhard Gross and Bernhard WitkopCite this: J. Am. Chem. Soc. 1961, 83, 6, 1510–1511Publication Date (Print):March 1, 1961Publication History Published online1 May 2002Published inissue 1 March 1961https://pubs.acs.org/doi/10.1021/ja01467a052https://doi.org/10.1021/ja01467a052research-articleACS PublicationsRequest reuse permissionsArticle Views587Altmetric-Citations380LEARN 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
Interaction of Graminicides Applied in Combination with Pyrithiobac (1996)

Field experiments were conducted from 1992 through 1994 to determine the effect of selected graminicides when applied in combination with pyrithiobac for johnsongrass control in cotton. Quizalofop-P, clethodim, sethoxydim, and fluazifop-P were applied at rates recommended for rhizome johnsongrass control with or without pyrithiobac at 70 g ae/ha. At 14 DAT johnsongrass control without pyrithiobac was more than 85% for all graminicides all years except sethoxydim in 1993. When graminicides were applied in combination with pyrithiobac, johnsongrass control was 86% or less and was lower than when each respective graminicide was applied alone. At 21 DAT, similar differences were apparent. Seed cotton yield, determined only one year, was not affected by reductions in johnsongrass control when either quizalofop or clethodim were used in combination with pyrithiobac. Pyrithiobac applied alone controlled johnsongrass 20 to 44% 14 DAT depending on year.
Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells (2011)

The generation of insulin-producing β-cells from human pluripotent stem cells is dependent on efficient endoderm induction and appropriate patterning and specification of this germ layer to a pancreatic fate. In this study, we elucidated the temporal requirements for TGFβ family members and canonical WNT signaling at these developmental stages and show that the duration of nodal/activin A signaling plays a pivotal role in establishing an appropriate definitive endoderm population for specification to the pancreatic lineage. WNT signaling was found to induce a posterior endoderm fate and at optimal concentrations enhanced the development of pancreatic lineage cells. Inhibition of the BMP signaling pathway at specific stages was essential for the generation of insulin-expressing cells and the extent of BMP inhibition required varied widely among the cell lines tested. Optimal stage-specific manipulation of these pathways resulted in a striking 250-fold increase in the levels of insulin expression and yielded populations containing up to 25% C-peptide+ cells.
The yin and yang of Activin A (2011)

In this issue of Blood , Sierra-Filardi and colleagues shed new light on the still poorly understood proinflammatory role of Activin A in macrophage polarization. 1
Validating MPEG-21 encapsulated functional metadata (2003)

We describe the validation process of a functional metadata document encapsulated in an MPEG-21 digital item. The validation starts with an MPEG-21 digital item containing the functional metadata and ends with a valid functional metadata document or with a list of error codes. Since the W3C schema language does not suffice to validate all relationships within a functional metadata document, a set of extra rules is defined. These rules are implemented through the use of transformations on functional metadata documents. These transformations are implemented using XSLT.
Revisiting the Evolution and Application of Assignment Problem: A Brief Overview (2016)

The assignment problem (AP) is incredibly challenging that can model many real-life problems.This paper provides a limited review of the recent developments that have appeared in the literature, meaning of assignment problem as well as solving techniques and will provide a review on a lot of research studies on different types of assignment problem taking place in present day real life situation in order to capture the variations in different types of assignment techniques.
Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles (2015)

Ligand activation of the aryl hydrocarbon (AHR) has profound effects upon the immunological status of the gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at the mucosal interface. However, the identity of the ligand(s) responsible for such AHR-mediated activation within the gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction and ligand structure activity analyses together with in silico modeling of the AHR ligand binding domain to identify indole, a microbial tryptophan metabolite, as a human-AHR selective agonist. Human AHR, acting as a host indole receptor may exhibit a unique bimolecular (2:1) binding stoichiometry not observed with typical AHR ligands. Such bimolecular indole-mediated activation of the human AHR within the gastrointestinal tract may provide a foundation for inter-kingdom signaling between the enteric microflora and the immune system to promote commensalism within the gut.
Epithelial-Mesenchymal Interactions in Pulmonary Fibrosis (2011)

Lung epithelial cells have emerged as a frequent target of injury, a driver of normal repair, and a key element in the pathobiology of fibrotic lung diseases. An important aspect of epithelial cells is their capacity to respond to microenvironmental cues by undergoing epithelial-mesenchymal transition (EMT). EMT is not simply widespread conversion of epithelial cells to fibroblasts but a graded response whereby epithelial cells reversibly acquire mesenchymal features and enhanced capacity for mesenchymal cross-talk. Recent studies elucidate distinct integrin-sensing systems that coordinate activity of TGFβ1, a critical signaling element regulating EMT, with the presence of proinflammatory signals and cell injury. Repeated injury superimposes persistent inflammation and hypoxia onto these highly regulated repair pathways, potentially overwhelming orderly repair and creating sustained fibrogenesis. Understanding specific signaling mechanisms driving the mesenchymal response to TGFβ1 may reveal therapeutics to attenuate fibrogenesis yet preserve the important homeostatic functions of TGFβ1.
Increased expression of the adipokine genes resistin and fasting-induced adipose factor in hypoxic/ischaemic mouse brain (2006)

Adipose tissue is the primary source of the adipokines resistin and fasting-induced adipose factor (FIAF). We reported that the brain is also a site of adipokine expression, although their function there is unknown. Peripheral resistin and fasting-induced adipose factor are reported to be inflammatory markers, and we hypothesized that they would be induced in the brain by hypoxia/ischaemia. We show that neonatal hypoxia/ischaemia rapidly increased fiaf mRNA in the injured cortex and hippocampus at 2 and 7 days after hypoxia/ischaemia. In contrast, resistin (retn) mRNA was increased in the cortex only at 21 days after hypoxia/ischaemia. As a lipopolysaccharide-induced inflammatory response did not increase brain fiaf and retn mRNA levels, we conclude that brain injury may be responsible for the novel hypoxia/ischaemia-induced changes in adipokine gene expression. In summary, our results indicate that brain injury, or an inflammatory stimulus, regulates the central expression of two genes normally considered to be adipose tissue-specific. These observations add to our previous evidence that the brain is an important site of adipokine gene expression.
B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis (2005)

Selective B-cell depletion with anti-CD20 therapy is a promising novel treatment option for patients with refractory autoimmune disease. The anti-CD20 antibody, rituximab, is the first therapeutic monoclonal antibody to have been approved by the European Medical Agency (EMEA) and the US Food and Drug Administration (FDA) for the treatment of relapsed, low-grade, follicular non-Hodgkin's lymphoma. Rituximab is now being studied in a range of autoimmune diseases, most notably rheumatoid arthritis, but also chronic immune thrombocytopenic purpura and systemic lupus erythematosus. Current data obtained from studies of rituximab single-agent therapy for autoimmune disease show good tolerability and sustained improvement in disease symptoms, although the precise mechanisms of action in autoimmunity remain to be fully clarified. Future research is likely to be focused on the optimization of responses with rituximab-based therapy. However, early observations suggest that this approach is likely to yield significant clinical benefits in a wide range of organ-specific and systemic autoimmune diseases.
A tool for graphical network modeling and analysis (1992)

GMA, a generic graphical modeling and analysis package that satisfies both commercial users and performance evaluation researchers is described. Using a graphical interface, both novices and experts can analyze the performance of diverse networks simply by loading a configuration file and traffic data. GMA accommodates a variety of networks and modeling techniques. Its structure and use are described, and a simple four-node network is analyzed as an example.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Isolation of a T-lymphotropic retrovirus from naturally infected sooty mangabey monkeys (Cercocebus atys). (1986)

Healthy mangabey monkeys in a colony at the Yerkes Regional Primate Research Center were found to be infected with a retrovirus related to human immunodeficiency virus (HIV). Virus was isolated from peripheral blood cells of 14 of 15 randomly selected mangabeys. All virus-positive animals had antibodies to the mangabey virus at the time of virus isolation and, in a retrospective study, 82% of mangabey serum samples obtained in 1981 had antibodies to the virus. The newly isolated retrovirus is (i) morphologically identical to HIV by electron microscopy; (ii) serologically related to the human virus by enzyme immunoassay, immunoblotting experiments, radioimmunoprecipitation, and neutralization; and (iii) cytopathic for human OKT4+ cells. The mangabey virus also shares these properties with the simian T-lymphotropic virus type III (STLV-III) recently isolated from diseased macaques and from healthy African green monkeys (STLV-IIIAGM). However, the mangabey virus, like STLV-IIIAGM, differs from both HIV and STLV-III in that it apparently does not cause clinical immunodeficiency or disease following natural infection of the host from which it was isolated. Comparison of the virus-host interactions of these isolates may be valuable in defining determinants of pathogenicity for cytopathic retroviruses.
Prostaglandin E2 production by rat peritoneal macrophages: role of cellular and humoral factors in vivo in transfusion-associated immunosuppression (1990)

The transfusion of blood is associated with long-term immunosuppression, which has been postulated to influence immunosurveillance and cancer cell killing. The mononuclear phagocyte synthesises large quantities of PGE2, and PGE2 has been shown to inhibit the activity of a range of immunocompetent cell types. The role of mononuclear phagocyte PGE2 synthesis in transfusion-associated immunosuppression, and the elements of transfused blood which control this immunosuppression, were investigated using a transfused rat model. A significant increase in macrophage PGE2 synthesis was detected 7 days after transfusion with blood and serum. The storage of blood for 24 h increased the stimulatory activity of transfused blood. The effects of storage and serum on macrophage PGE2 synthesis were greater than effects due to genetic differences between blood donor and recipient, and the serum effects indicated that a major factor activating PGE2-mediated immunosuppression in transfused subjects may be humoral in nature.
Functional analysis of the secretory precursor processing machinery of Bacillus subtilis: identification of a eubacterial homolog of archaeal and eukaryotic signal peptidases (1998)

Approximately 47% of the genes of the Gram-positive bacterium Bacillus subtilis belong to paralogous gene families. The present studies were aimed at the functional analysis of the sip gene family of B. subtilis, consisting of five chromosomal genes, denoted sipS, sipT, sipU, sipV, and sipW. All five sip genes specify type I signal peptidases (SPases), which are actively involved in the processing of secretory preproteins. Interestingly, strains lacking as many as four of these SPases could be obtained. As shown with a temperature-sensitive SipS variant, only cells lacking both SipS and SipT were not viable, which may be caused by jamming of the secretion machinery with secretory preproteins. Thus, SipS and SipT are of major importance for protein secretion. This conclusion is underscored by the observation that only the transcription of the sipS and sipT genes is temporally controlled via the DegS-DegU regulatory system, in concert with the transcription of most genes for secretory preproteins. Notably, the newly identified SPase SipW is highly similar to SPases from archaea and the ER membrane of eukaryotes, suggesting that these enzymes form a subfamily of the type I SPases, which is conserved in the three domains of life.
PROTECTIVE EFFICACY OF THE RTS,S/AS02 PLASMODIUM FALCIPARUM MALARIA VACCINE IS NOT STRAIN SPECIFIC (2003)

RTS,S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein (CSP) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen. It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers. In a recently completed trial in semi-immune Gambian adults, vaccine efficacy against natural infection was 34% (95% confidence interval = 8-53%, P = 0.014) during the malaria season following vaccination. Breakthrough P. falciparum parasites sampled from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes (csp-th2r and csp-th3r) to determine if the vaccine conferred a strain-specific effect. The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups. Also, the mean number of genotypes per infection in the RTS,S/AS02 group was not reduced compared with the controls.
Pathological CNS Autoimmune Disease Triggered by Traumatic Spinal Cord Injury: Implications for Autoimmune Vaccine Therapy (2002)

Lymphocytes respond to myelin proteins after spinal cord injury (SCI) and may contribute to post-traumatic secondary degeneration. However, there is increasing evidence that autoreactive T-lymphocytes may also convey neuroprotection and promote functional recovery after CNS injury. To clarify the role of myelin autoreactive lymphocytes after SCI, we performed contusion injuries in the thoracic spinal cord of transgenic (Tg) mice in which >95% of all CD4+ T-lymphocytes are reactive with myelin basic protein (MBP). We observed significantly impaired recovery of locomotor and reflex function in Tg mice compared with non-Tg (nTg) littermates. Measures of functional impairment in Tg mice correlated with significantly less white matter at the injury site, and morphometric comparisons of injured Tg and nTg spinal cords revealed increased rostrocaudal lesion expansion (i.e., secondary degeneration) in Tg mice. Rostrocaudal to the impact site in SCI-nTg mice, demyelination was restricted to the dorsal funiculus, i.e., axons undergoing Wallerian degeneration. The remaining white matter appeared normal. In contrast, lymphocytes were colocalized with regions of demyelination and axon loss throughout the white matter of SCI-Tg mice. Impaired neurological function and exacerbated neuropathology in SCI-Tg mice were associated with increased intraspinal production of proinflammatory cytokine mRNA; neurotrophin mRNA was not elevated. These data suggest that endogenous MBP-reactive lymphocytes, activated by traumatic SCI, can contribute to tissue injury and impair functional recovery. Any neuroprotection afforded by myelin-reactive T-cells is likely to be an indirect effect mediated by other non-CNS-reactive lymphocytes. Similar to the Tg mice in this study, a subset of humans that are genetically predisposed to autoimmune diseases of the CNS may be adversely affected by vaccine therapies designed to boost autoreactive lymphocyte responses after CNS trauma. Consequently, the safe implementation of such therapies requires that future studies define the mechanisms that control T-cell function within the injured CNS.
Variants in GLIS3 and CRY2 Are Associated with Type 2 Diabetes and Impaired Fasting Glucose in Chinese Hans (2011)

In conclusion, our results indicate the associations of GLIS3 locus with type 2 diabetes and impaired fasting glucose in Chinese Hans, partially mediated through impaired beta-cell function. In addition, we also found modest evidence for the association of CRY2-rs11605924 with combined IFG/type 2 diabetes.
Interferon-gamma inhibits arterial stenosis after injury. (1991)

These results show that gIFN is a potent inhibitor of the formation of arterial proliferative lesions in vivo. It is possible that gIFN could be useful in preventing arterial stenosis after surgery and angioplasty in man.
Use of Subatmospheric (VAC) Therapy to Improve Bioengineered Tissue Grafting in Diabetic Foot Wounds (2002)

The use of bioengineered tissue and topical subatmospheric pressure therapy have both been widely accepted as adjunctive therapies for the treatment of noninfected, nonischemic diabetic foot wounds. This article describes a temporally overlapping method of care that includes a period of simultaneous application of bioengineered tissue (Apligraf, Novartis Pharmaceuticals Corp, East Hanover, New Jersey) and subatmospheric pressure therapy delivered through the VAC (Vacuum Assisted Closure) system (KCI, Inc, San Antonio, Texas). Future descriptive and analytic works may test the hypothesis that combined therapies used at different and often overlapping periods during the wound-healing cycle may be more effective than a single modality.
A scar-y movie, starring IL-11 (2017)

IL-11 is found to be a critical mediator of TGFβ1-induced scarring and fibrosis in the heart and kidney.