gebhart/patrepeval huggingface dataset:
Association of Disorders in Mineral Metabolism with Progression of Chronic Kidney Disease (2006)

Abnormalities of mineral metabolism are associated with increased mortality in patients with ESRD, but their effects in predialysis chronic kidney disease (CKD) are less well characterized. In this study, the associations between levels of serum phosphorus, calcium, and calcium-phosphorus product and progression of CKD were examined. Historical data were collected on 985 male US veterans (age 67.4 +/- 10.9; 23.9% black) with CKD stages 1 through 5. Unadjusted and multivariable-adjusted relative risks for progressive CKD (defined as the composite of ESRD or doubling of serum creatinine) were calculated for categories of serum phosphorus, calcium, and calcium-phosphorus product using Cox proportional hazards models. Higher phosphorus was associated with a higher risk for the composite end point (adjusted hazard ratio [HR] [95% confidence interval (CI)] for phosphorus levels 3.3 to 3.8, 3.81 to 4.3, and >4.3 versus <3.3 mg/dl 0.83 [0.54 to 1.27], 1.24 [0.82 to 1.88], and 1.60 [1.06 to 2.41]; P = 0.001 for trend). A 1-mg/dl higher phosphorus level was associated with an adjusted HR (95% CI) of 1.29 (1.12 to 1.48; P < 0.001). Higher calcium-phosphorus product also was associated with higher risk for progressive CKD (adjusted HR [95% CI] for calcium-phosphorus products 30 to 35, 36 to 40, and >40 versus <30 mg2/dl2 0.58 [0.36 to 0.94], 0.87 [0.57 to 1.34], and 1.37 [0.91 to 2.07]; P = 0.002 for trend). A 10-mg2/dl2 higher calcium-phosphorus product was associated with an adjusted HR (95% CI) of 1.29 (1.11 to 1.51; P = 0.001). Lower serum calcium showed a trend toward higher risk for progressive CKD but without statistical significance. Higher serum phosphorus and higher calcium-phosphorus product are associated with progression of CKD.
Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies. (2003)

Prominent expression of the proinflammatory factors TNF-alpha, IL-1 beta and NOS2 and caspase-1 is associated with muscle fibre damage, albeit when expressed to a low degree these factors may, like NGFR, contribute to muscle regeneration and healing.
Clinical implications of antiangiogenic therapies. (2005)

The most common subtype of aggressive non-Hodgkin's lymphoma is diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphoma represents a heterogeneous entity, with 5-year overall survival rates ranging from 26% to 73%. Microarray gene expression studies have confirmed that biologically distinct subgroups exist within DLBCL, and can be correlated with outcome. Initial management is usually guided by stage of disease at presentation. Approximately 25% of patients with DLBCL present with limited-stage disease and are treated with combined-modality therapy (brief chemotherapy and involved-field radiation). Most patients present with advanced-stage disease and require treatment with an extended course of chemotherapy. The CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy regimen has been the mainstay of therapy since its development in the 1970s, as more intensive chemotherapy regimens failed to show additional benefit. The era of monoclonal antibodies has transformed treatment practices for aggressive lymphoma and has led to a significant improvement in outcome. A randomized trial comparing the use of rituximab (Rituxan), a chimeric anti-CD20 IgG1 monoclonal antibody, combined with CHOP chemotherapy vs CHOP chemotherapy alone for elderly patients with advanced-stage DLBCL demonstrated a significant benefitfor the combination approach. This finding has now been confirmed in two additional randomized, controlled trials and a population-based analysis, making CHOP and rituximab the standard of care for all newly diagnosed patients with DLBCL. Despite this advance, newer therapies are needed and many are under active investigation. The insights gained from molecular techniques such as gene expression profiling should permit identification of additional lymphoma-specific therapeutic targets and the development of novel agents that take into account underlying biology and allow for greater tailoring of therapy.
Single chip PCI bridge and memory controller for PowerPC microprocessors (2002)

The MPC105 is a highly integrated single chip design which provides a bridge between a variety of PowerPC microprocessors and the Peripheral Component Interconnect (PCI) bus. The MPC105 also integrates secondary cache control and a high performance memory controller which supports DRAM, SDRAM, and ROM. System designers will be able to design systems using peripherals already designed for PCI, providing an easy and cost effective bridge to PowerPC processors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
New vaccines against tuberculosis. (1995)

It has proved difficult to vaccinate effectively against tuberculosis with mycobacterial components or even with whole dead mycobacteria; protection was always inferior to that obtained with the live attenuated vaccine known as bacillus Calmette-Guérin (BCG). We have found that this may no longer be the case. Expression of the gene for a single mycobacterial antigen (Mycobacterium leprae hsp65) in adult BALB/c mice resulted in substantial cell-mediated protection against challenge with M. tuberculosis, but only when it was generated as an endogenous antigen within antigen-presenting cells. CD4 and CD8 T cells cloned from spleens of immunized mice passively transferred protection to non-immunized mice, and CD8 cells selectively lysed macrophages infected with M. tuberculosis. The ability of the clones to protect recipient mice against challenge infection was most strongly associated with specific cytotoxic capacity and secondarily with IFN-gamma production. Three modes of expressing the gene have been tested: a) expression from a retroviral vector (pZIPNeoSV) in implanted J774 tumor cells, b) expression from the same vector via bone marrow cells transfected in vitro and used to reconstitute irradiated mice, and c) in a preliminary experiment, from cytomegalovirus (CMV) immediate-early and hydroxymethylglutaryl Co-A reductase promoters injected as plasmid DNA into muscle.
A Kernel‐Based Approach for Biomedical Named Entity Recognition (2013)

Support vector machine (SVM) is one of the popular machine learning techniques used in various text processing tasks including named entity recognition (NER). The performance of the SVM classifier largely depends on the appropriateness of the kernel function. In the last few years a number of task-specific kernel functions have been proposed and used in various text processing tasks, for example, string kernel, graph kernel, tree kernel and so on. So far very few efforts have been devoted to the development of NER task specific kernel. In the literature we found that the tree kernel has been used in NER task only for entity boundary detection or reannotation. The conventional tree kernel is unable to execute the complete NER task on its own. In this paper we have proposed a kernel function, motivated by the tree kernel, which is able to perform the complete NER task. To examine the effectiveness of the proposed kernel, we have applied the kernel function on the openly available JNLPBA 2004 data. Our kernel executes the complete NER task and achieves reasonable accuracy.
Dexamethasone, Cytarabine, Ifosfamide, and Cisplatin as Salvage Therapy in Non-Hodgkin Lymphoma (1999)

The authors conducted a phase II study to evaluate a new combination of chemotherapeutic drugs that includes dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma after prior exposure to both adriamycin and etoposide. All drugs were administered intravenously over 4 consecutive days. The daily dose of dexamethasone was 20 mg twice daily. The maximal daily doses of cytarabine, ifosfamide, and cisplatin were 75 mg/m2, 1,200 mg/m2, and 20 mg/m2, respectively. Cycles were repeated every 3 weeks. A total of 31 patients were entered in the trial. Thirty patients were evaluable for response. A complete response was seen in 11 patients (37%), and a partial response was noted in six patients (20%). A significantly higher complete response rate was seen in patients with relapsing non-Hodgkin lymphoma compared with those who failed to achieve a complete response with the last chemotherapy (10/14 vs. 1/16; p < 0.013). A complete response continues in two patients who received consolidation with high-dose chemotherapy for more than 49 months and more than 60 months for each patient. Median time to treatment failure and median survival were 3.3 months and 7.5 months, respectively, for the entire group and 11 months and 30 months, respectively, for complete responders. Myelosuppression was pronounced but was usually of short duration. Neutropenic fever developed in 13 patients (42%) and in 15 of 96 cycles (16%). Platelet transfusions were required in seven patients (23%). There was one drug-related death associated with myelotoxicity. Nonhematologic toxicity was not dose limiting. The authors conclude that dexamethasone, cytarabine, ifosfamide, and cisplatin is active and a relatively tolerable regime for patients with non-Hodgkin lymphoma previously treated with adriamycin and etoposide.
Genomic investigation of phenotypic variation in Campylobacter jejuni flagellin (1991)

Western blots of whole-cell sonicates of 10 different clones of a faecal isolate of Camphylobacter jejuni 533 detected the expression of flagella antigens of either 59 or 62 kDa. Other antigenic proteins appeared identical both in the parent and all the clones. The mechanism for this phenotypic variation was studied using Southern blotting with a flagellin-specific gene probe and products of a polymerase chain reaction (PCR) using flagellin-gene primers. Restriction-enzyme digestion and Southern blotting did not dected any genomic rearrangements in the flagellin genes of the different phenotypes nor did restriction-enzyme analysis of the PCR products.
Prolonged Elevation of IL-1 in Pseudomonas aeruginosa Ocular Infection Regulates Macrophage-Inflammatory Protein-2 Production, Polymorphonuclear Neutrophil Persistence, and Corneal Perforation (2000)

The kinetics of IL-1 (alpha and beta) production after Pseudomonas aeruginosa corneal infection was examined in susceptible (cornea perforates) C57BL/6J (B6) and resistant (cornea heals) BALB/cByJ (BALB/c) mice. IL-1alpha and -1beta (mRNA and protein) were elevated in both mouse strains, and levels peaked at 1 day postinfection (p.i. ). Significantly greater amounts of IL-1 protein were detected in B6 vs BALB/c mice at 1 and 3 days p.i. At 5 days p.i., IL-1alpha and -1beta (mRNA and protein) remained elevated in B6, but began to decline in BALB/c mice. To test the significance of elevated IL-1 in B6 mice, a polyclonal neutralizing Ab against IL-1beta was used to treat infected B6 mice. A combination of subconjunctival and i.p. administration of IL-1beta polyclonal Ab significantly reduced corneal disease. The reduction in disease severity in infected B6 mice was accompanied by a reduction in corneal polymorphonuclear neutrophil number, bacterial load, and macrophage inflammatory protein-2 mRNA and protein levels. These data provide evidence that IL-1 is an important contributor to P. aeruginosa corneal infection. At least one mechanism by which prolonged and/or elevated IL-1 expression contributes to irreversible corneal tissue destruction appears to be by increasing macrophage inflammatory protein-2 production, resulting in a prolonged stimulation of polymorphonuclear neutrophil influx into cornea. In contrast, a timely down-regulation of IL-1 appears consistent with an inflammatory response that is sufficient to clear the bacterial infection with less corneal damage.
Stereoselective first‐pass metabolism of highly cleared drugs: studies of the bioavailability of L‐ and D‐verapamil examined with a stable isotope technique. (1984)

The pharmacokinetics of dextro(+)- and levo(-)-verapamil were studied in five healthy volunteers following oral administration of pseudoracemic verapamil containing equal amounts of unlabelled (-)- and dideuterated (+)-isomer. (+)-verapamil exhibited approximately five times greater Cmax (+): 240 +/- 81.1 ng/ml, (-): 46.1 +/- 15.7 ng/ml, P less than 0.0001) and AUC than (-)-verapamil. The apparent oral clearance (CLo) for (+)-verapamil was significantly smaller than that for (-)-verapamil (+): 1.72 +/- 0.57 l/min, (-): 7.46 +/- 2.16 l/min, P less than 0.001). The bioavailability of (+)-verapamil (50%) was 2.5 times greater than that of (-)-verapamil (20%), P less than 0.005). Thus following oral administration verapamil exhibited a stereoselective first-pass metabolism. Neither tmax nor the elimination t1/2,z were different between the isomers. The elimination of t1/2,z for each verapamil isomer obtained following oral administration (+): 4.03 h, (-): 5.38 h) were similar to those previously obtained following intravenous administration (+): 4.15 h, (-): 5.38 h, respectively. Whereas the (+)- to (-)-verapamil plasma concentration ratio following oral administration was 4.92 +/- 0.48, the ratio following i.v. administration was approximately 2. (-)-verapamil has been demonstrated to possess 8 to 10 times more potent negative dromotropic effect on AV conduction than (+)-verapamil. Therefore, following oral administration the same concentration of plasma verapamil consisting of a two to three times smaller proportion of the more potent (-)-isomer appeared to be less potent than that following i.v. administration with regard to the negative dromotropic effects on the AV conduction.
Effectiveness of ipsapirone, a 5-HT-1A partial agonist, in major depressive disorder: support for the role of 5-HT-1A receptors in the mechanism of action of serotonergic antidepressants (1998)

Desensitisation of serotonin 1A (5-HT-1A) receptors is a leading hypothesis for the mechanism of action of antidepressants which block serotonin reuptake. This hypothesis predicts that direct-acting 5-HT-1A agonists should also exhibit anti-depressant properties. Here we report the results of the first large-scale controlled study of the efficacy and tolerability of a 5-HT-1A agonist in outpatients with major depressive disorder (MDD). Three hundred and seventy-three subjects meeting DSM-III-R criteria for MDD participated in this randomised, double-blind comparison of the 5-HT-1A partial agonist ipsapirone (5 mg, 7.5 mg and 10 mg t.i.d.) to placebo t.i.d. Improvement in depressive symptoms relative to placebo, as measured by the Hamilton Depression Rating Scale, occurred in the ipsapirone (7.5 mg t.i.d.) group with a magnitude of effect (D=-2.53 points) that was statistically significant (p=0.010). Adverse events occurred in 76% of the placebo patients and 92% of the ipsapirone patients. A dose-related increase in the incidence of adverse events led to discontinuation of treatment with the 10 mg t.i.d. Results of this study demonstrate that ipsapirone, at a dose of 7.5 mg t.i.d., is an effective antidepressant agent in the treatment of MDD, supporting the hypothesised role of 5-HT-1A receptors in the mechanism of action of serotonin reuptake inhibitors. However, as a potential therapeutic agent for depression, ipsapirone shows only a modest magnitude of drug-placebo differences as well as a side-effect profile less favorable than many of the newer antidepressants.
PROVIDE: a process visualization and debugging environment (1988)

The author introduces PROVIDE, a source-level process visualization and debugging environment currently under development at the University of Illinois at Chicago. PROVIDE is a modern coding and debugging environment that is designed to allow the user to configure interaction at a desired level of abstraction. It emphasizes the use of interactive computer graphics for the illustration of program execution, with special attention to the requirements of program debugging. The major features of PROVIDE are presented, especially the concepts of deferred-binding program animation, which allows users to interactively change the depiction of program execution during the debugging task, and process history consistency maintenance, which guarantees a consistent (automatically updated) record of program execution in the face of changes to program instructions and run-time data values. The current PROVIDE prototype is implemented on Macintosh workstations networked to a VAX 11/780 running 4.2 BSD Unix.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Protease-Activated Receptor-2 Expression in IgA Nephropathy (2003)

An increasing body of evidence suggests that proteases may play a key role in the pathogenesis of tissue fibrosis. Protease-activated receptor-2 (PAR-2) is cleaved and activated by trypsin-like proteolytic enzymes, including tryptase and activated coagulation factor X (FXa). Both these soluble mediators have been demonstrated, directly or indirectly, at the interstitial level in progressive renal diseases, including IgA nephropathy (IgAN). PAR-2 mRNA and protein levels were investigated by RT-PCR and immunohistochemistry, respectively, in 17 biopsies from IgAN patients and 10 normal kidneys. PAR-2 expression was also evaluated, by RT-PCR and western blotting, in cultured human mesangial and proximal tubular cells. Finally, gene expression of plasminogen activator inhibitor-1 (PAI-1) and TGF-beta, two powerful fibrogenic factors, was evaluated in FXa-, trypsin-, and PAR-2 activating peptide-stimulated human proximal tubular cells by Northern blot. In normal kidneys, PAR-2 gene expression was barely detectable, whereas in IgAN biopsies the mRNA levels for this protease receptor were strikingly increased and directly correlated with the extent of interstitial fibrosis. Immunohistochemical staining demonstrated that PAR-2 protein expression in IgAN biopsies was mainly localized in the proximal tubuli and within the interstitial infiltrate. Proximal tubular cells in culture expressed PAR-2. Activation of this receptor by FXa in tubular cells induced a striking increase in intracellular calcium concentration. In addition, incubation of both cell lines with trypsin, FXa, or PAR-2 activating peptide caused a marked upregulation of PAI-1 gene expression that was not counterbalanced by an increased expression of plasminogen activators. Finally, PAR-2 activation induced a significant upregulation of TGF-beta gene and protein expression in both mesangial and tubular cells. On the basis of our data, we can suggest that PAR-2 expressed by renal resident cells and activated by either mast cell tryptase or FXa may induce extracellular matrix deposition modifying the PAI-1/PA balance and inducing TGF-beta expression. These molecular mechanisms may underlie interstitial fibrosis in IgAN.
Activation of delta-globin gene expression by erythroid Krupple-like factor: a potential approach for gene therapy of sickle cell disease (1996)

Hemoglobin A2 (HbA2; alpha 2 delta 2) is a powerful inhibitor of HbS (alpha 2 beta 2(3)) polymerization. However, HbA2 levels are normally low in sickle cell patients. We show that a major reason for low delta-globin gene expression is the defective CACCC box at -90 in the delta-globin promoter. When the CACCC box defect in delta is corrected, expression of an HS2 delta /Luciferase reporter is equivalent to HS2 beta /Luciferase. Erythroid Krupple-like factor (EKLF), which binds to the CACCC box of the beta-globin gene and activates high-level expression, does not bind to the normal delta-globin promoter. Our goal is to design a modified EKLF that binds to the defective delta-globin promoter and enhances delta-globin gene expression. To test the feasibility of this strategy, we inserted the beta-globin CACCC box at -90 of the delta-globin gene promoter to produce an HS2 delta CAC-beta construct and quantitated human delta- and beta-globin mRNA in stably transformed murine erythroleukemia (MEL) cells. delta- Globin mRNA in these cells was 22.0% +/- 9.0% of total human globin mRNA (delta/delta + beta) as compared with 3.0% +/- 1.3% in the HS2 delta-beta control. In a second set of experiments a GAL4 DNA-binding site was inserted at -90 of the delta-globin gene to produce an HS2 delta GAL4-beta construct. This construct and a GAL4(1-147)/EKLF expression vector were stably transfected into MEL cells. delta-Globin mRNA in these cells was 27.8% +/- 7.1% of total human globin mRNA as compared with 9.9% +/- 2.5% in the HS2 delta GAL4-beta plus GAL4(1-147) control. These results show that delta-globin gene expression can be significantly increased by a modified EKLF. Based on these results, we suggest that modified EKLFs, which contain zinc fingers designed to bind specifically to the defective delta-globin CACCC box, may be useful in gene therapy approaches to increase HbA2 levels and inhibit HbS polymerization.
Superconductor-nanowire devices from tunneling to the multichannel regime: Zero-bias oscillations and magnetoconductance crossover (2013)

We present transport measurements in superconductor-nanowire devices with a gated constriction forming a quantum point contact. Zero-bias features in tunneling spectroscopy appear at finite magnetic fields and oscillate in amplitude and split away from zero bias as a function of magnetic field and gate voltage. A crossover in magnetoconductance is observed: Magnetic fields above $\ensuremath{\sim}$0.5 T enhance conductance in the low-conductance (tunneling) regime but suppress conductance in the high-conductance (multichannel) regime. We consider these results in the context of Majorana zero modes as well as alternatives, including the Kondo effect and analogs of 0.7 structure in a disordered nanowire.
A 2.8 GHz combined mode of vibration aluminum nitride MEMS resonator with high figure of merit exceeding 45 (2013)

This paper presents the first demonstration of a high frequency (2.8 GHz), lateral field excited (simple two masks fabrication process), combined lateral-thickness extensional mode of vibration aluminum nitride (AlN) micro-electromechanical systems (MEMS) resonator with unprecedentedly high figure of merit (k <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ·Q> 45). For the first time, a single interdigital electrode was employed to excite a high frequency mode of vibration in an AlN plate (1.5 μm thick) by making use of both the d <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">33</sub> and d <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">31</sub> AlN piezoelectric coefficients. The resulting MEMS resonator showed high quality factor, Q~2000, (thanks to the high quality AlN film directly deposit on top of the Silicon substrate) and the highest electromechanical coupling coefficient ever reported for AlN MEMS resonators employing a single electrode, k <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ~2.5% (thanks to the coherent combination of d <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">33</sub> and d <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">31</sub> coefficients to transduce one single mechanical mode of vibration).