Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative detection of T-cell activation markers by real-time PCR in renal transplant rejection and correlation with histopathologic evaluation1

Background. The quest for noninvasive methods to diagnose rejection in solid-organ transplants has been rejuvenated by recent observations that specific cytotoxic T-cell markers are up-regulated during rejection. Methods. We developed a one-step real-time polymerase chain reaction (PCR) method allowing reliable detection of the expression of several T-cell genes within a relatively short period of time. The assay is highly sensitive and reproducible with a wide dynamic range allowing accurate quantification of target mRNA in as little as 3 pg total RNA. The utility of this assay in detecting renal allograft rejection was evaluated. Peripheral blood mononuclear cells were collected from 27 patients undergoing kidney allograft biopsies for renal dysfunction after transplantation. Expression of the T-cell activation markers, granzyme B, perforin, and HLA-DRA, was quantified and correlated to the histopathologic changes in the renal biopsies. Results. In cases with allograft rejection (n=8), peripheral lymphocyte expression was increased for granzyme B (P <0.001) and perforin (P <0.08) compared with cases without rejection (n=19). Granzyme B mRNA up-regulation showed the highest specificity for detecting rejection (95%). Moreover, HLA-DRA mRNA was significantly up-regulated (P <0.0016) and had the highest sensitivity (88%) detecting rejection. The up-regulation of both granzyme B and HLA-DRA was most specific in detecting rejection, P <0.001. Conclusions. These data demonstrate that a rapid test of target gene up-regulation using real-time PCR can be used as an aid in the diagnosis of kidney allograft rejection. This is also the first report on the possible utility of HLA-DRA mRNA up-regulation as a marker for kidney transplant rejection.
The Adaptor Molecule Signaling Lymphocytic Activation Molecule-Associated Protein (SAP) Regulates IFN-γ and IL-4 Production in Vα14 Transgenic NKT Cells via Effects on GATA-3 and T-bet Expression1

NKT cells comprise a rare regulatory T cell population of limited TCR diversity, with most cells using a Vα14Jα18 TCR. These cells exhibit a critical dependence on the signaling adapter molecule, signaling lymphocytic activation molecule-associated protein (SAP), for their ontogeny, an aspect not seen in conventional αβ T cells. Prior studies demonstrate that SAP enhances TCR-induced activation of NF-κB in CD4+ T cells. Because NF-κB is required for NKT cell development, SAP might promote the ontogeny of this lineage by signaling to NF-κB. In this study, we demonstrate that forced expression of the NF-κB target gene, Bcl-xL, or inhibitory NF-κB kinase β, a catalytic subunit of the IκB kinase complex essential for NF-κB activation, fails to restore NKT cell development in sap−/− mice, suggesting that SAP mediates NKT cell development independently of NF-κB. To examine the role of SAP in NKT cell function, we generated NKT cells in sap−/− mice by expressing a transgene encoding the Vα14Jα18 component of the invariant TCR. These cells bound α-galactosylceramide-loaded CD1d tetramers, but exhibited a very immature CD24+NK1.1− phenotype. Although sap−/− tetramer-reactive cells proliferated in response to TCR activation, they did not produce appreciable levels of IL-4 or IFN-γ. The reduction in cytokine production correlated with the near absence of GATA-3 and T-bet, key transcription factors regulating cytokine expression and maturation of NKT cells. Ectopic expression of GATA-3 partially restored IL-4 production by the NKT cells. Collectively, these data suggest that by promoting GATA-3 and T-bet expression, SAP exerts control over NKT cell development and mature NKT cell cytokine production.
Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic Function

ABSTRACT Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0–∞) showed an increase in amprenavir AUC0–∞ of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC0–∞ was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC0–∞. The relationship between the total bilirubin concentration and the AUC0–∞ of amprenavir was well characterized by a simple Emax model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of α1-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.
Coda Wave Interferometry for Estimating Nonlinear Behavior in Seismic Velocity

In coda wave interferometry, one records multiply scattered waves at a limited number of receivers to infer changes in the medium over time. With this technique, we have determined the nonlinear dependence of the seismic velocity in granite on temperature and the associated acoustic emissions. This technique can be used in warning mode, to detect the presence of temporal changes in the medium, or in diagnostic mode, where the temporal change in the medium is quantified.
Microbiological, Physico-Chemical and Sensorial Characteristics of Serrano, an Artisanal Brazilian Cheese

The microbiological, chemical and sensory characteristics of licensed and unlicensed commercial Serrano cheese, a traditional product from the highlands of South Brazil, were studied. The average bacteria counts (log CFU/g) were 8.8, 3.4, 3.4, 5.1, and 8.8, for mesophilic bacteria, fecal coliforms, staphylococci, yeasts and moulds, and lactic acid bacteria (LAB), respectively. Differences in microbiological quality were detected between licensed and unlicensed cheeses. However, the presence of potential gastroentheric bacteria in both kind of cheeses is disturbing and point out the necessity of alternative manufacturing process and good manufacturing practices to minimize consumers’ health risks. The most prevalent LAB were Lactobacillus (91%), followed Lactococcus and Enterococcus. Lactobacillus isolates comprised L. plantarum (57.7%), L. paracasei (19.2%), L. rhamnosus (7.7%), L. acidophilus (7.7%), and 3.8% of both L. curvatus and L. fermentum. Non-significant physico-chemical differences were detected between licensed and unlicensed cheeses. Cheeses that received the highest sensorial scores exhibited the presence of both L. plantarum and L. paracasei, indicating that mixed populations of these species positively contributed to flavor development.
X-Structured Precoder Designs for Spatial-Multiplexing MIMO and MIMO Relay Systems

In multiple-input-multiple-output (MIMO) transmission, precoding has been considered a promising technique to improve the system performance. In general, the criterion of precoder design depends on the detector used at the receiver. For the maximum-likelihood (ML) detector, the criterion is to maximize the minimum distance of the received signal constellation. Unfortunately, the derivation of the optimum solution is known to be difficult, and suboptimum solutions have then been developed. One promising approach confines the precoder having an X-structure. Several methods have been developed to solve the X-structured precoder. However, most of them use numerical searches to find their solutions and require lookup tables during run time. In this paper, we propose a systematic design method to solve the problems. The proposed precoder has a simple closed-form expression, and no numerical searches and lookup tables are required. Simulation results show that the proposed method can yield almost the same performance as the existing methods. We also consider the problem of joint source/relay precoder design in a two-hop amplify-and-forward MIMO relay system. Since the problem is much more involved and a closed-form solution is intractable to find, we then extend the use of the proposed X-structured precoder so that the problem can be reformulated as a simple scalar-valued optimization problem. Simulations show that the proposed method can significantly outperform existing joint design methods.
Processing and Presentation of a Mycobacterial Antigen 85B Epitope by Murine Macrophages Is Dependent on the Phagosomal Acquisition of Vacuolar Proton ATPase and In Situ Activation of Cathepsin D1

Mycobacterium tuberculosis (strain H37Rv) and bacillus Calmette-Guérin (BCG) vaccine inhibit phagosome maturation in macrophages and their effect on processing, and presentation of a secreted Ag85 complex B protein, Ag85B, by mouse macrophages was analyzed. Macrophages were infected with GFP-expressing mycobacterial strains and analyzed for in situ localization of vacuolar proton ATPase (v-ATPase) and cathepsin D (Cat D) using Western blot analysis and immunofluorescence. H37Rv and BCG phagosomes excluded the v-ATPase and maintained neutral pH while the attenuated H37Ra strain acquired v-ATPase and acidified. Mycobacterial phagosomes acquired Cat D, although strains BCG and H37Rv phagosomes contained the inactive 46-kDa form, whereas H37Ra phagosomes had the active 30-kDa form. Infected macrophages were overlaid with a T cell hybridoma specific for an Ag85B epitope complexed with MHC class II. Coincident with active Cat D, H37Ra-infected macrophages presented the epitope to T cells inducing IL-2, whereas H37Rv- and BCG-infected macrophages were less efficient in IL-2 induction. Bafilomycin inhibited the induction of macrophage-induced IL-2 from T cells indicating that v-ATPase was essential for macrophage processing of Ag85B. Furthermore, the small interfering RNA interference of Cat D synthesis resulted in a marked decrease in the levels of macrophage-induced IL-2. Thus, a v-ATPase-dependent phagosomal activation of Cat D was required for the generation of an Ag85B epitope by macrophages. Reduced processing of Ag85B by H37Rv- and BCG-infected macrophages suggests that phagosome maturation arrest interferes with the efficient processing of Ags in macrophages. Because Ag85B is immunodominant, this state may lead to a decreased ability of the wild-type as well as the BCG vaccine to induce protective immunity.
Clinical trials in ovarian carcinoma: study methodology.

Summary of end point recommendations With all the above-mentioned considerations working group Bformulated the recommendations listed in Table 5. Acknowledgements This document summarizes the discussions held in the group Bsection during the 3rd Ovarian Cancer Consensus Conference,organized by the GCIG and held in Baden-Baden, Germany,3–5 September 2004. None of the participants in this sectionindicated any conﬂict of interest related to the sponsor of thisevent (Bristol-Myers Squibb). References 1. Sylvester R. Planning cancer clinical trials. In Buyse ME, Staquet MJ,Sylvester RJ (eds): Oxford Cancer Clinical Trials – Methods andPractice. 47–63. Oxford University Press 1982.2. Brady MF, Thigpen JT, Vermorken JB, Parmar MKB. Randomisedtrials in ovarian cancer: trial design considerations. Ann Oncol 1999;10 (Suppl 1): S75–S82.3. Cannistra SA. Cancer of the ovary. N Engl J Med 2004; 351:2519–2529.4. Berek JS, Bertelsen K, du Bois A et al. Advanced epithelial ovariancancer: 1998 consensus statements. Ann Oncol 1999; 10 (Suppl 1):S87–S92.5. Vergote I, De Brabanter J, Fyles A et al. Prognostic importance ofdegree of differentiation and cyst rupture in stage I invasive epithelialovarian carcinoma. Lancet 2001; 357: 176–182.6. Zanetta G. The accuracy of staging: an important prognostic determi-nator in stage I ovarian carcinoma. A multivariate analysis. Ann Oncol1998; 9: 1097–1101.7. Eisenhauer EA, Gore M, Neijt JP. Ovarian cancer: should we bemanaging patients with good and bad prognostic factors in the samemanner? Ann Oncol 1999; 10 (Suppl 1): S9–S15.8. Trope´ C, Kaern J, Hogberg T et al. Randomized study on adjuvantchemotherapy in stage I high-risk ovarian cancer with evaluation ofDNA-ploidy as prognostic instrument. Ann Oncol 2000; 11: 281–288.9. Eisenhauer EA, Vermorken JB, van Glabbeke M. Predictors of responseto subsequent chemotherapy in platinum pretreated ovarian cancer: ananalysis of 704 patients. Ann Oncol 1997; 8: 963–968.10. van Glabbeke M, Vermorken J, Eisenhauer E. Predictors of survival(OS) and time to progression (TTP) following 2
Intravenous Phenytoin and Phenobarbital: Anticonvulsant Action, Brain Content, and Plasma Binding in Rat

Summary: l4C‐phenytoin or 3H‐phenobarbital were given through indwelling jugular catheters to 65 rats. Anticonvulsant activity was tested by the maximal electroshock seizure test and was correlated with brain concentrations of phenytoin or phenobarbital. Free and total plasma drug levels were determined by equilibrium dialysis. The median effective cerebral phenytoin concentration (EC50) was 10.5 μM/kg (95% fiducial limits, 8.2 to 12.4) 3 min after infusion compared with 10.2 μM/kg 30 min after infusion. The EC50 of phenobarbital was 8.2 μM/kg (6.7 to 9.3 μM/kg) 3 min after infusion. Cerebellar concentrations were equivalent to cerebral concentrations for all rats (r= 0.98). Three minutes after infusion, cerebral:plasma free ratio of phenytoin was 3.73 ± 0.71 (± S.D.); the plasma protein bound:free ratio, 3.70 ± 0.98. For phenobarbital, the cerebral:plasma free ratio was 0.72 ± 0.10; the plasma protein bound:free ratio, 0.63 ± 0.12. Since the EC50 values of phenytoin 3 or 30 min after infusion did not differ, onset of anticonvulsant effect clearly occurred as soon as adequate brain concentrations were attained. Phenobarbital was effective 3 min after infusion, and although much higher free plasma levels were necessary, effective brain concentrations were similar to those of phenytoin. Brain content paralleled plasma protein binding, both being high for phenytoin and low for phenobarbital.
A monolithic unified approach for FSI and multi-fluid flow problems using the Particle Finite Element Method with fixed mesh

This paper describes a strategy to solve multifluid and Fluid Structure Interaction (FSI) problems using Lagrangian particles combined with a fixed Finite Element (FE) mesh . The method is an extension from the fluid-only PFEM-2 [14][15], which uses explicit integration over the streamlines to improve accuracy. As a result, the convective term does not appear in the set of equations solved in the fixed mesh. Enrichments in the pressure and field are used to improve the description of the interface between phases.
Nonrespiratory mortality and cancer incidence in a cohort of Canadian nickel workers

ABSTRACT Mortality and cancer incidence were examined for an updated cohort of nonsinter nickel workers in Sudbury and Port Colborne, Ontario, Canada. Abstract results are provided for those with ≥ 15 years since first exposure. For circulatory disease mortality, significant elevations were observed overall in many Sudbury work areas and in Port Colborne staff. Underground miners, with first exposure before 1960, displayed significant elevations for pneumoconiosis, as well as silicosis and anthrasilicosis, likely due to crystalline silica. Significant elevations in colorectal cancer incidence were observed in Sudbury underground mining, mining maintenance, and maintenance work areas. Given a case-control study is not practical, the next cohort update should include more detailed occupational exposure assessment, including dust exposure, diesel engine emissions, solvents, various metals, silica, and sulphur dioxide.
System Noise Assessment of Blended-Wing-Body Aircraft with Open Rotor Propulsion

An aircraft system noise study is presented for the hybrid wing–body aircraft concept with open-rotor engines mounted on the upper surface of the airframe. The aircraft chosen for the study is of a size comparable to the Boeing 787 aircraft. It is shown that, for such a hybrid wing–body aircraft, the cumulative effective perceived noise level is about 24 dB below the current aircraft noise regulations of stage 4. Although this makes the design acoustically viable in meeting the regulatory requirements, even with the consideration of more stringent noise regulations in the next decade or so, the design will likely meet stiff competition from aircraft with turbofan engines. The noise levels of the hybrid wing–body design are held up by the inherently high noise levels of the open-rotor engines and the limitation on the shielding benefit due to the practical design constraint on the engine location. Furthermore, it is shown that the hybrid wing–body design has high levels of noise from the main landing gear,.
Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

Abnormalities in fear extinction and recall are core components of posttraumatic stress disorder (PTSD). Data from animal and human studies point to a role of the ventromedial prefrontal cortex (vmPFC) in extinction learning and subsequent retention of extinction memories. Given the increasing interest in developing noninvasive brain stimulation protocols for psychopathology treatment, we piloted whether transcranial direct current stimulation (tDCS) during extinction learning, vs. during consolidation of extinction learning, might improve extinction recall in veterans with warzone‐related PTSD.
Magnetic Resonance Imaging Findings of Elevated Intracranial Pressure in Cerebral Venous Thrombosis Versus Idiopathic Intracranial Hypertension with Transverse Sinus Stenosis

ABSTRACT We wished to determine whether magnetic resonance imaging signs suggesting elevated intracranial pressure are more frequently found in patients with idiopathic intracranial hypertension (IIH) than in those with cerebral venous thrombosis (CVT). Among 240 patients who underwent standardised contrast-enhanced brain magnetic resonance brain imaging and venography at our institution between September 2009 and September 2011, 60 with abnormal imaging findings on magnetic resonance venography were included: 27 patients with definite and 2 patients with presumed idiopathic intracranial hypertension, and 31 with definite cerebral venous thrombosis. Medical records were reviewed, and imaging studies were prospectively evaluated by the same neuroradiologist to assess for presence or absence of transverse sinus stenosis, site of cerebral venous thrombosis if present, posterior globe flattening, optic nerve sheath dilation/tortuosity, and the size/appearance of the sella turcica. Twenty-nine patients with idiopathic intracranial hypertension (28 women, 19 black, median age: 28, median body mass index: 34 kg/m2) had bilateral transverse sinus stenosis. Thirty-one CVT patients (19 women, 13 black, median age: 46, median body mass index: 29) had thrombosis of the sagittal (3), sigmoid (3), cavernous (1), unilateral transverse (7), or multiple (16) sinuses or cortical veins (1). Empty/partially empty sellae were more common in IIH (3/29 and 24/29) than in cerebral venous thrombosis patients (1/31 and 19/31) (p < 0.001). Flattening of the globes and dilation/tortuosity of the optic nerve sheaths were more common in idiopathic intracranial hypertension (20/29 and 18/29) than in cerebral venous thrombosis (13/31 and 5/31) (p < 0.04). We conclude that although abnormal imaging findings suggestive of raised intracranial pressure are more common in IIH, they are not specific for that disorder and are found in patients with raised intracranial pressure from other causes such as cerebral venous thrombosis.
Hydrogen-oxidizing electron transport components in the hyperthermophilic archaebacterium Pyrodictium brockii

The hyperthermophilic archaebacterium Pyrodictium brockii grows optimally at 105 degrees C by a form of metabolism known as hydrogen-sulfur autotrophy, which is characterized by the oxidation of H2 by S0 to produce ATP and H2S. UV-irradiated membranes were not able to carry out the hydrogen-dependent reduction of sulfur. However, the activity could be restored by the addition of ubiquinone Q10 or ubiquinone Q6 to the UV-damaged membranes. A quinone with thin-layer chromatography migration properties similar to those of Q6 was purified by thin-layer chromatography from membranes of P. brockii, but nuclear magnetic resonance analysis failed to confirm its identity as a ubiquinone. P. brockii quinone was capable of restoring hydrogen-dependent sulfur reduction to UV-irradiated membranes. Hydrogen-reduced-minus-air-oxidized absorption difference spectra on membranes revealed absorption peaks characteristic of c-type cytochromes. A c-type cytochrome with alpha, beta, and gamma peaks at 553, 522, and 421 nm, respectively, was solubilized from membranes with 0.5% Triton X-100. Pyridine ferrohemochrome spectra confirmed its identity as a c-type cytochrome, and heme staining of membranes loaded on sodium dodecyl sulfate gels revealed a single heme-containing component of 13 to 14 kDa. Studies with the ubiquinone analog 2-n-heptyl-4-hydroxyquinoline-N-oxide demonstrated that the P. brockii quinone is located on the substrate side of the electron transport chain with respect to the c-type cytochrome. These first characterizations of the strictly anaerobic, presumably primitive P. brockii electron transport chain suggest that the hydrogenase operates at a relatively high redox potential and that the H2-oxidizing chain more closely resembles those of aerobic eubacterial H2-oxidizing bacteria than those of the H2-metabolizing systems of anaerobes or the hyperthermophile Pyrococcus furiosus.
Trust, distrust, and interpersonal problems: a circumplex analysis.

This study examined the self-reported interpersonal problems of individuals characteristically high or low in interpersonal trust. The interpersonal circumplex served as a guiding framework for assessing and interpreting these problems. As expected, extreme distrust was generally related to a symmetrical pattern of distress, with a peak at the hostile-dominant octant. Extreme high trust, on the other hand, was not associated with gullibility or with related interpersonal difficulties, supporting arguments that trust is essentially distinct from gullibility and exploitability. The Interpersonal Trust Scale and the Mach IV scale, the study's principal measures of trust, tap varieties of trust differing in their blends of dominance and hostility, leading to different problem patterns for extreme scorers