gebhart/patrepeval huggingface dataset:
Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys (2008)

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-gamma(+)) and IFN-gamma(+)/tumor necrosis factor alpha(+) (TNF-alpha(+)) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2(+) (IL-2(+)) and polyfunctional IFN-gamma(+)/TNF-alpha(+)/IL-2(+) T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8(+) and CD4(+) T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.
Implications of NQO1 in cancer therapy (2015)

quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and -lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.
Organic Nitrosonium Salts. II. Stability Studies and Oxidations of Some Indole Derivatives (1990)

The s t a b l l ~t ~e s of various salts of tha 2.2.6.6-tetra-methylnloer~dlne-1-oxon~umIon were studled.2.2.6.6-Tstramathylplperldlne-1-oxonlurntetrafluoroborate was shown to react wlth 1.2.3.q-tetrahudrocarbazols(1-E-2.3.r.S-tetrahydrocarbazole) to glve.In the cresence OF weter.9-keto-1.2.3.~-tetrahydrocarbazol~ in good yleld.Under the sams condltlons.c y c l o p e n t ~J ~n d o 1 ~ and ~~c l o h e ~t ~b ] l n d o l e gave the corresponding keto derlvatlves.In th8 absence of water.the oxldatlon of tetrahydrocarbazole gave a mlxtura of drmers, probably dsrrved From the Dlels-Rlder self condensatlon of 1-H-2,3-dlhydrocarbazole.The condensatlon 1s reversible and, In acld, the dlmer rnrxture glves e salt of 1-H-2.3dlhydrocarbazolewhrch can be reduced wrth sodrum borohydrlds to glva back tetrahydrocarbezole.Orgenlc nltrosonlum salts, easlly darlved From well known nltroxrde rad~cals * bu oxldat~on.are S p e c ~F ~c oxldlzlng agents For a number of Functional groups.In addltlon to alcohols.amlnes.ketones, and benzyl sthers whlch were revlewed in our prevlous paper.' recent publlcatlons record the oxidatron OF N.N-5 6 dlalkylan~llnes end dlfunctlonal alcohols as vell as the nrtrosonlum Lon catalyzed hycochlnrltm oxrdatron of a l ~o h o l s .~ In thls paoer, we would llke to report th8 electrochem~cal oreparatlon of a nltrosonrurn salt.studles on the stablllty OF certaln nltrosonlum salts, and, Flnally, thelr reactions wlth some lndole der~vat~ves.
30-nm-channel-length c-axis aligned crystalline In-Ga-Zn-O transistors with low off-state leakage current and steep subthreshold characteristics (2015)

We report the world's smallest field effect transistors (FETs) with channel lengths of 32 nm including c-axis aligned crystalline (CAAC) In-Ga-Zn-O as their active layers, which achieve low off-state leakage currents. Furthermore, these FETs exhibit excellent subthreshold swing values despite having thick gate insulating film. The FET operation has been achieved owing to the 3D gate structure with a thin active layer, due to the FETs being accumulation-type FETs with intrinsic channels, and due to the dielectric anisotropy of the CAAC crystal structure.
Optimum Design and Depth Resolution of Lens-Sheet and Projection-Type Three-Dimensional Displays (1971)

The primary purpose of this paper is to propose a comprehensive optimum-design theory of lenticular-sheet three-dimensional pictures. The proposed theory features the use of depth resolution of a 3-D image as the measure of the 3-D picture quality. The optimum parameters in the picture taking process, the optimum lens pitch and the depth-resolution limitation, are discussed. The obtained results are also applicable to a specific type of integral photography and to the projection-type 3-D display including projection-type holography. It is found that the optimum pitch of the lens sheet or the lens-type direction selective screen ranges between 0.1 mm and 0.5 mm in most cases, whereas it ranges between 0.2 mm and 1 mm for the triple-mirror screen.
The future of rural hospitals. (1992)

In summary, the pressures facing our nation's rural hospitals are likely to continue without significant relief from either federal or state governments. The strategies we see evolving in this environment include increased research on efficient operation with limited resources as well as increased competition for scarce resources within America's urban sectors. Not a pretty picture, but survival oriented.
T cells in the control of organ-specific autoimmunity (2015)

Immune tolerance is critical to the avoidance of unwarranted immune responses against self antigens. Multiple, non-redundant checkpoints are in place to prevent such potentially deleterious autoimmune responses while preserving immunity integral to the fight against foreign pathogens. Nevertheless, a large and growing segment of the population is developing autoimmune diseases. Deciphering cellular and molecular pathways of immune tolerance is an important goal, with the expectation that understanding these pathways will lead to new clinical advances in the treatment of these devastating diseases. The vast majority of autoimmune diseases develop as a consequence of complex mechanisms that depend on genetic, epigenetic, molecular, cellular, and environmental elements and result in alterations in many different checkpoints of tolerance and ultimately in the breakdown of immune tolerance. The manifestations of this breakdown are harmful inflammatory responses in peripheral tissues driven by innate immunity and self antigen-specific pathogenic T and B cells. T cells play a central role in the regulation and initiation of these responses. In this Review we summarize our current understanding of the mechanisms involved in these fundamental checkpoints, the pathways that are defective in autoimmune diseases, and the therapeutic strategies being developed with the goal of restoring immune tolerance.
T cell costimulation by B7/BB1 induces CD8 T cell-dependent tumor rejection: an important role of B7/BB1 in the induction, recruitment, and effector function of antitumor T cells. (1994)

A successful antitumor T cell immune response involves induction, recruitment, and effector function of T cells. While B7/BB1 is known as a major costimulatory molecule in the induction of T cell responses, its role in T cell recruitment and effector function is still unclear. In this study, we show that introducing a major costimulatory molecule B7/BB1 into a major histocompatibility complex class II-negative tumor cell line, J558, results in a drastic reduction of its tumorigenicity. The tumor rejection depends on CD8 T cells but not CD4 T cells. However, unlike the previous reports on melanoma cell lines, B7/BB1-transfected J558 cells fail to induce cross-protection against parental J558 cells. The B7/BB1-transfected (J558-B7), but not untransfected J558 cells (J558-Neo) induce a CD8 T cell-dominant inflammatory response, and the T cells isolated from the tumor infiltrating lymphocytes (TIL) are polyclonal in terms of their T cell receptor V beta usage. Most surprisingly, the freshly prepared TIL have a potent, CD8 T cell-mediated cytotoxicity on tumor cells without any in vitro stimulation. The cytotoxic T lymphocyte (CTL) activity can be blocked by anti-CD8 monoclonal antibody (mAb). Interestingly, the CTL lyse J558-B7 about 10- to 80-fold more efficiently than untransfected J558-Neo cells. This preferential lysis cannot be attributed to recognition of B7/BB1-derived antigen by the T cells. This finding, together with the lack of the cross-protection between the J558-B7 and J558-Neo, suggests that B7/BB1 can also function at the effector phase of CTL responses. This notion is confirmed by our findings that the lysis of J558-B7 can be blocked by anti-B7 mAbs. Taken together, our results indicate that not only can the B7/BB1 molecule function as a costimulatory molecule at the initiation of immune response, it can also play a major role in T cell recruitment and effector function. This conclusion has significant implications for immunotherapy of tumors.
Specific molecular interaction sites on factor VII involved in factor X activation (1993)

Factor VII, a serine-protease zymogen, and tissue factor, the cellular receptor/coenzyme, are the protein components of the macromolecular complex which initiates the extrinsic pathway of the coagulation cascade. Previous studies were directed to the identification of functional sites on factor VII which mediate factor X activation, employing a series of potentially inhibitory synthetic peptides representing the primary structure of factor VII and antibodies to selected peptides. The involvement of at least four high-affinity interactive regions [factor VII (44-50), (196-229), (285-305) and (376-396) peptides] on the surface of factor VII was clearly demonstrated. The minimal sequences for the expression of inhibitory activity of these four molecular recognition domains on factor VII were identified using short and overlapping peptides. The short factor VII-(206-218)-peptide (most inhibitory peptide in the sequence 196-229 on factor VII) inhibited the binding of factor VII to the tissue-factor-expressing J82 cell line. Furthermore, radiolabeled [Tyr201] factor VII-(199-221)-peptide, with a tyrosine substituted for the normal tryptophan residue, was specifically bound to J82 cells, and also the binding of the radiolabeled peptide to this cell line was specifically inhibited by a monoclonal antibody to tissue factor, confirming that the interaction site for tissue factor on factor VII is present within the peptide sequence 196-229. Kinetic analyses suggested that the regions represented by factor VII-(285-305)- and factor VII-(376-396)-peptides are involved in factor X recognition and the chemical cross-linking of the radiolabeled peptides resulted in specific binding to factor X, confirming that these two regions on factor VII represent the substrate-recognition site. Furthermore, these radiolabeled peptides specifically interact with the heavy chain of factor X, suggesting that the complementary binding region for the substrate-recognition site on factor VII are present on the heavy chain of factor X.
Synergistic therapy of breast cancer with Y-90-chimeric L6 and paclitaxel in the xenografted mouse model: development of a clinical protocol. (1999)

Taxol given approximately 48 hours after RIT provides coincident peak deposition of Taxol and Y-90 in tumor, and no Taxol in the marrow during the major radiation dose to marrow, resulting in therapeutic enhancement without observable additive toxicity. A clinical trial of low dose Taxol given after RIT to patients with metastatic breast cancer is planned.
Detection of three types of hepatitis C virus in blood donors: investigation of type‐specific differences in serologic reactivity and rate of alanine aminotransferase abnormalities (1993)

The serologic reactivity and epidemiology associated with different hepatitis C virus (HCV) variants were investigated in a cohort of 113 anti-HCV-positive donors. In Scotland, HCV type 1 accounted for one-half of all infections; 40 percent of subjects were infected with HCV type 3, and the remainder were infected with type 2. Reactivity with the NS-4-encoded antigens in the first-generation anti-c100 assay was absent in 68 percent of donors infected with types 2 and 3, as compared with 10 percent for those infected with type 1. Even when combined with surrogate marker testing, first-generation tests would have failed to detect 12 percent of HCV-infected blood donors. The age distribution, incidence of past infection with hepatitis B virus, and reported risk factors were similar in donors infected with types 1 and 3 (mean ages were 31.9 and 29.9; 18 and 17.5% were positive for antibody to hepatitis B core antigen; and 47 and 48% had past intravenous drug abuse). However, the distributions of alanine aminotransferase levels were significantly different in those infected with type 3 (abnormally raised in 83%) and those infected with type 1 (55% abnormal alanine aminotransferase; p < 0.05) or type 2 (60%; p < 0.01) and those who were nonviremic (8%; p < 0.0001). These data suggest that HCV type 1 is the most common HCV infection in blood donors and that infection with HCV type 3 may be associated with more severe liver disease, because of more recent infection or because of a greater inherent pathogenicity of type 3 variants.
Force sensing and control for a surgical robot (2003)

The authors describe the use of force feedback in a surgical robot system (ROBODOC). The application initially being addressed is total hip replacement (THR) surgery, where the robot must prepare a cavity in the femur for an artificial implant. In this system, force feedback is used to provide safety, tactile search capabilities, and an improved man-machine interface. Output of the force sensor is monitored by a safety processor, which initiates corrective action if any of several application-defined thresholds are exceeded. The robot is able to locate objects using guarded moves and force control (ball-in-cone strategy). In addition, the force control algorithm provides an intuitive man-machine interface which allows the surgeon to guide the robot by leading its tool to the desired location. An application of force control currently under development is described, where the force feedback is used to modify the cutter feed rate (force controlled velocity).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Detection of Placental Alpha Microglobulin-1 versus Insulin-Like Growth Factor-Binding Protein-1 in Amniotic Fluid at Term: A Comparative Study (2011)

We compared two biochemical tests of premature rupture of membranes (PROM) in vitro: Actim PROM (Medix Biochemica, Kauniainen, Finland), which detects insulin-like growth factor binding protein-1, and AmniSure (AmniSure International LLC, Cambridge, MA), which detects placental alpha microglobulin-1. Samples of amniotic fluid were collected during caesarean section in 41 patients. A dilution series was prepared and both tests were performed twice at each dilution. Sensitivity, detection limit, response time, and reproducibility of both tests were compared. Both tests' sensitivity was 100% at dilution 1:10 and 1:20. AmniSure sensitivity was higher at dilution 1:40 and 1:80 ( P < 0.05). In 29 of 40 cases, AmniSure had a lower detection limit than Actim PROM. AmniSure response times were shorter and reproducibility was higher than Actim PROM ( P < 0.05). AmniSure had a lower detection limit of amniotic fluid than Actim PROM, with a shorter response time, a higher sensitivity, and a better reproducibility.
A Crystal Modulating Protein from Molluscan Nacre That Limits the Growth of Calcite in Vitro (2006)

Protein-mediated biomineral formation and polymorph selection in the mollusk shell involves the participation of a number of different proteins. One of these proteins, AP7, has been identified as a participant in nacre (aragonite) formation in the mollusk Haliotis rufescens. However, the role(s) of this protein in aragonite formation is (are) poorly understood, due to the fact that low quantities of this protein are recoverable from the nacre matrix. To overcome this problem, we employed stepwise solid-phase tBOC synthesis to recreate the 66-AA single-chain protein AP7 and utilized this synthetic form for in vitro mineralization studies. We find that the AP7 protein promotes incomplete or interrupted crystal growth and step edge roundening in a concentration-dependent fashion. Using synthetic peptides which represent the 30-AA N-terminal (AP7N) and 36-AA C-terminal (AP7C) subdomains of AP7, we have identified that the mineral modification activity of AP7 is localized to the unstructured, conformationally labile N-terminal subdomain. Interestingly, the 36-AA C-terminal subdomain has no observable direct effect on in vitro calcium carbonate crystal growth; however, we cannot rule out the possibility that AP7C plays an indirect role in AP7 mineralization activity. Qualitative structural studies reveal that AP7, although possessing Zn(II) fingerlike −His−(X)6−His, −Cys-(X)2−Cys−, and −Cys−(X)4−Cys− motifs within its C-terminal region, does not possess the structural characteristics of known Zn(II) finger polypeptides, as evidenced by the presence of an ordered, α-helical conformation within the C-terminal subdomain of apo-AP7. Given its associative nature with AP24 and the multifunctional capabilities of the 30-AA N-terminal domain, it is likely that the AP7 protein possesses multifunctional capabilities with regard to nacre formation within the mollusk shell.
Lymphokine Production by Human T Cells in Disease States (1994)

A large body of evidence suggests the existence of polarized human T cell responses, reminiscent of Th1 and Th2 subsets described for mouse T cells. Human Th1-like cells preferentially develop during infections by intracellular bacteria, protozoa, and viruses, whereas Th2-like cells predominate during helminthic infestations and in response to common environmental allergens. The cytokine profile of "natural immunity" evoked by different offending agents in the context of different host genetic backgrounds appears to be a critical factor in determining the phenotype of the subsequent specific response. Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, they can also promote different immunopathological reactions. Th1-type responses appear to be involved in organ specific autoimmunity, in contact dermatitis, and in some chronic inflammatory disorders of unknown etiology. In contrast, in genetically predisposed hosts, Th2-type responses against common environmental allergens are responsible for triggering of allergic atopic disorders. Altered profiles of lymphokine production may account for immune dysfunctions in some primary or acquired immunodeficiency syndromes. The role of lymphokines produced by T cells in the pathogenesis of systemic autoimmune disorders is less clear. Further work is also required to better clarify the role of T cell-derived lymphokines in protecting against tumors or in favoring their development.
Interleukin‐18 and Host Defense against Infection (2003)

Interferon (IFN)-gamma-inducing factor was previously termed interleukin (IL)-18. Although IL-12 is also an IFN-gamma-inducing factor, the activity of IL-18 (but not IL-12) in models of sepsis and death is dependent on the intracellular cysteine protease IL-1beta converting enzyme (caspase-1). Caspase-1 is required for cleavage of the inactive precursor form of IL-18 into an active cytokine, and caspase-1-deficient mice are resistant to lethal endotoxemia. The absence of IFN-gamma (but not IL-1beta) in caspase-1-deficient mice is responsible for this resistance. However, the role of IFN-gamma in murine defense against gram-negative infection is inconsistent. Mice deficient in IFN-gamma are not resistant to lethal endotoxemia but are resistant when treated with neutralizing antibodies to IL-18 and challenged with a lethal injection of some endotoxins. Anti-IL-18 treatment also reduces neutrophil accumulation in liver and lungs. Neutralizing IL-18 with the IL-18 binding protein protects mice against endotoxin- and ischemia-induced hepatic damage. Thus, blockade of IL-18 appears to be a viable clinical target to combat the pathologic consequences of sepsis via IFN-gamma mechanisms.
Electrochemically Grown Wires for Individually Addressable Sensor Arrays (2004)

We report on the electrochemical growth of micro/nanowire devices using e-beam-patterned electrolyte channels, potentially enabling the controlled fabrication of individually addressable arrays. The concept of growing single wires and small arrays using this technique is demonstrated by single and double wires of Pd and polypyrrole with 500-nm and 1-μm widths up to 7-μm lengths and 200-nm thicknesses. The use of Pd wires as hydrogen sensors and polypyrrole wires as pH sensors is demonstrated.
Association of Kaposi's sarcoma with second primary malignancies possible etiopathogenic implications (1980)

The association of Kaposi's sarcoma (KS) with second primary cancers, especially of the lymphoreticular system, has been frequently noted. To confirm these reports in a systematic way, data on a series of 92 patients with KS treated at Memorial Sloan-Kettering Cancer Center (MSKCC) 2949-1975 were subjected to extensive statistical analysis. Use was made also 4517 double primaries including all sites, diagnosed at MSKCC 1949-1974, and 1959 simultaneous double primaries from the Third National Cancer Survey. Some key results: (1) of KS patients had toher primary malignancies; (2) there was a 20-fold increase in the incidence of lymphoreticular malignancies after diagnosis of KS; (3) in the MSKCC series double primaries, lymphoreticular malignancies were involved in 8% of cases; for KS alone the corresponding figure was 58%. Our findings provide evidence in support of possible etiopathogenic mechanisms that may be involved in the natural course of KS.
Photothermal Generation of Thermoelastic Waves in Composite Media (1986)

L'accent est mis sur la comprehension des effets des parametres du materiau et dynamiques, sur le processus de generation thermoelastique. On decrit le couplage thermoelastique des modes de propagation et de non-propagation
A Large Outbreak ofClostridium difficile–Associated Disease with an Unexpected Proportion of Deaths and Colectomies at a Teaching Hospital Following Increased Fluoroquinolone Use (2005)

Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak