Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of tyrosinase‐reactive T cells by treatment with dacarbazine, cisplatin, interferon‐alpha ± interleukin‐2 in patients with metastatic melanoma

We have shown the presence of tyrosinase‐reactive T cells in the peripheral blood of melanoma patients, who had been in remission after treatment with IL‐2‐containing regimens. In this consecutive study, we analyzed the T‐cell response to various peptides derived from tyrosinase in serial blood samples obtained from 7 stage‐IV melanoma patients before, during and following treatment. All patients were treated within a randomized trial (EORTC 18951) with cisplatin (CDDP), dacarbazine (DTIC), interferon‐α (IFN‐α) ± interleukin‐2 (IL‐2). Using an ELISPOT assay detecting peptide‐specific IFN‐γ release, we measured the T‐cell response to 4 different HLA class I‐binding peptide epitopes derived from tyrosinase containing an HLA‐A2.1‐, HLA‐A24‐ or HLA‐B44‐binding motif in peripheral‐blood mononuclear cells (PBMC). In one patient, tyrosinase‐reactive T cells were detected before therapy. In 4 out of 7 patients, tyrosinase‐reactive T cells against both HLA‐A2.1‐binding peptides and the B44‐binding peptide became detectable at frequencies of up to 30 in 5 × 105 lymphocytes following treatment. These patients received CDDP, DTIC and IFN‐α, 2 of them without IL‐2 and 2 with IL‐2, resulting in one complete remission and 3 partial remissions. Two patients relapsed 8 and 9 months after treatment. At the time of relapse, no T cells reactive with tyrosinase were detectable. Our results show that high frequencies of tyrosinase‐reactive T cells in the peripheral blood of melanoma patients can be induced by chemotherapy in combination with IFN‐α, regardless of concomitant IL‐2 administration. Int. J. Cancer 80:39–43, 1999. © 1999 Wiley‐Liss, Inc.
Relation between size at birth and age-related cataract.

PURPOSE To determine whether poor fetal growth, as determined by size at birth, is associated with an increased risk of age-related cataract. METHODS A total of 741 men and women born in Sheffield, England between 1922 and 1930 and whose size at birth was available were traced and invited to take part in the study. Of these, 392 (53%) attended for ophthalmic examination. Lens opacity in these volunteers was graded using the Lens Opacities Classification System (LOCS) III. RESULTS After adjusting for age, gender, gestational age, and risk factors for cataract there were no consistent associations between size at birth and age-related cataract. However, the odds ratio for nuclear cataract (opalescence) among subjects whose birth weight was more than 8 lb was 2.4 (95% CI 1.2 to 5.0) compared with those who weighed under 6 lb 12 oz at birth. Risk of cortical cataract by contrast fell with increasing birth weight, but the trend was not significant and became weak after adjusting for gestational age and other risk factors for cataract. No relation was evident between risk of posterior subcapsular cataract and size at birth. CONCLUSIONS There is no consistent association between size at birth and age-related cataract. The higher risk of nuclear cataract with increased birth weight was contrary to the expected trend. The apparent difference in direction of the relation between birth weight and different subtypes of cataract may be a chance finding but warrants further exploration.
Design of a $\hbox{Nb}_{3}\hbox{Sn}$ Cable-in-Conduit Conductor to Withstand the 60 000 Electromagnetic Cycles of the ITER Central Solenoid

The performance of the ITER Nb3Sn cable-in-conduit conductor tested in Sultan for the toroidal field (TF) coils have shown some limited degradation with cycling, which is consistent with the conductor performance requirement, as the TF coils are designed for an upper limit of 1000 electromagnetic cycles. The first samples of the central solenoid (CS) Nb3Sn conductor tested in Sultan have also shown some degradation with electromagnetic and thermal cycling. However, this is not considered appropriate as the CS conductor has to sustain 60 000 electromagnetic cycles during the lifetime of the tokamak. A sample of a CS conductor based on a locked cable configuration including segregated copper strands and designed to achieve saturation versus cycling has been fabricated and tested successfully in the Sultan test facility. Additional samples of CS conductor fabricated on the same principle have confirmed the observed very low sensitivity to cycling. The Sultan test results show that a locked cable configuration achieved by a short twist pitch cable pattern can cure the problem of degradation versus cycling for both types of strand, internal Sn and bronze route.
Testing Spatial Dependence in Spatial Models with Endogenous Weights Matrices

Abstract In this study, we propose simple test statistics for identifying the source of spatial dependence in spatial autoregressive models with endogenous weights matrices. Elements of the weights matrices are modelled in such a way that endogenity arises when the unobserved factors that affect elements of the weights matrices are correlated with the unobserved factors in the outcome equation. The proposed test statistics are robust to the presence of endogeneity in the weights and can be used to detect spatial dependence in the dependent variable and/or the disturbance terms. The robust test statistics are easy to calculate as computationally simple estimations are needed for their calculations. Our Monte Carlo results indicate that these tests have good size and power properties in finite samples. We also provide an empirical illustration to demonstrate the usefulness of the robust tests in identifying the source of spatial dependence.
Nonadrenergic noncholinergic neurotransmitter of feline trachealis: VIP or nitric oxide?

We tested the hypothesis that vasoactive intestinal peptide (VIP) or nitric oxide (NO) is the nonadrenergic noncholinergic (NANC) neurotransmitter in feline trachealis. Isometric tension was measured in trachealis (open or closed tracheal rings) in vitro. Propranolol (10 microM) and atropine (1 microM) were present throughout the experiment, and smooth muscle tone was increased to 60-90% maximal with 5-hydroxytryptamine. We used three methodologies to reduce the relaxation function of VIP, which in turn should reduce NANC-mediated relaxation. 1) The putative VIP antagonist peptide T (10 microM) did not affect VIP concentration-response curves or electrical field stimulation- (EFS) induced NANC responses. 2) Incubation of tissue in specific VIP antiserum (16 h at 4 degrees C) did not reduce EFS-induced NANC relaxations relative to tissue incubated in normal rabbit serum (P > 0.05). On the basis of our passive immunization techniques, it is not possible to absolutely reject VIP as the NANC transmitter. We speculate that nonspecific peptidases present in normal serum and VIP antiserum reduce EFS-induced responses similarly. 3) VIP desensitization, confirmed by a significant rightward shift (P < 0.01) in the VIP concentration-response curve, was achieved by exposing tissues (n = 11) to 1.0 microM VIP for 30 min. Desensitization did not reduce the EFS-induced NANC relaxatory response (P < 0.05) compared with control tissues, suggesting that VIP is not the NANC mediator. (ABSTRACT TRUNCATED AT 250 WORDS)
Heparin‐grafted dialysis membrane allows minimal systemic anticoagulation in regular hemodialysis patients: A prospective proof‐of‐concept study

This prospective, multicenter, proof‐of‐concept study aimed to evaluate the possibility to reduce the ordinary heparin dose and the systemic anti‐Xa activity during hemodialysis (HD) sessions using a new heparin‐grafted HD membrane. In 45 stable HD patients, the use of a heparin‐grafted membrane with the ordinary heparin dose was followed by a stepwise weekly reduction of dose. Reduction was stopped when early signs of clotting (venous pressure, quality of rinse‐back) occurred during two out of three weekly HD sessions. Heparin dose was decreased for 67% of patients resulting in the lowering of these patients' anti‐Xa activity by 50%. Dose reductions were achieved with both types of heparin (low‐molecular‐weight heparin: 64 ± 14 to 35 ± 12 IU/kg, P < 0.0001; unfractionated heparin: 82 ± 18 to 46 ± 13 IU/kg, P < 0.0001) resulting in a decrease of anti‐Xa activity at dialysis session end (low‐molecular‐weight heparin: 0.51 ± 0.25 to 0.25 ± 0.11 IU/mL, P < 0.0001; unfractionated heparin: 0.28 ± 0.23 to 0.13 ± 0.07 IU/mL, P < 0.0001). Failure to further decrease heparin dose was related to signs of clotting in blood lines (57% of sessions), in dialyzer (9%), or both (34%). Significant reduction of heparin dose and anti‐Xa activity at the end of HD sessions was possible in stable HD patients using heparin‐grafted membrane. HD patients who require low anti‐Xa activity at the end of HD sessions might benefit from a heparin‐grafted membrane to reduce bleeding risk and other heparin adverse events.
Regulation of Glucose-6-phosphatase Gene Expression by Protein Kinase Bα and the Forkhead Transcription Factor FKHR

Glucose-6-phosphatase plays an important role in the regulation of hepatic glucose production, and insulin suppresses glucose-6-phosphatase gene expression. Recent studies indicate that protein kinase B and Forkhead proteins contribute to insulin-regulated gene expression in the liver. Here, we examined the role of protein kinase B and Forkhead proteins in mediating effects of insulin on glucose-6-phosphatasepromoter activity. Transient transfection studies with reporter gene constructs demonstrate that insulin suppresses both basal and dexamethasone/cAMP-induced activity of the glucose-6-phosphatasepromoter in H4IIE hepatoma cells. Both effects are partially mimicked by coexpression of protein kinase Bα. Coexpression of the Forkhead transcription factor FKHR stimulates the glucose-6-phosphatase promoter activity via interaction with an insulin response unit (IRU), and this activation is suppressed by protein kinase B. Coexpression of a mutated form of FKHR that cannot be phosphorylated by protein kinase B abolishes the regulation of theglucose-6-phosphatase promoter by protein kinase B and disrupts the ability of insulin to regulate theglucose-6-phosphatase promoter via the IRU. Mutation of the insulin response unit of the glucose-6-phosphatase promoter also prevents the regulation of promoter activity by FKHR and protein kinase B but only partially impairs the ability of insulin to suppress both basal and dexamethasone/cAMP-stimulated promoter function. Taken together, these results indicate that signaling by protein kinase B to Forkhead proteins can account for the ability of insulin to regulateglucose-6-phosphatase promoter activity via the IRU and that other mechanisms that are independent of the IRU, protein kinase B, and Forkhead proteins also are important in mediating effects of in insulin on glucose-6-phosphatase gene expression.
Efficient Simulation of Secondary Fluorescence Via NIST DTSA-II Monte Carlo

Abstract Secondary fluorescence, the final term in the familiar matrix correction triumvirate Z·A·F, is the most challenging for Monte Carlo models to simulate. In fact, only two implementations of Monte Carlo models commonly used to simulate electron probe X-ray spectra can calculate secondary fluorescence—PENEPMA and NIST DTSA-II a (DTSA-II is discussed herein). These two models share many physical models but there are some important differences in the way each implements X-ray emission including secondary fluorescence. PENEPMA is based on PENELOPE, a general purpose software package for simulation of both relativistic and subrelativistic electron/positron interactions with matter. On the other hand, NIST DTSA-II was designed exclusively for simulation of X-ray spectra generated by subrelativistic electrons. NIST DTSA-II uses variance reduction techniques unsuited to general purpose code. These optimizations help NIST DTSA-II to be orders of magnitude more computationally efficient while retaining detector position sensitivity. Simulations execute in minutes rather than hours and can model differences that result from detector position. Both PENEPMA and NIST DTSA-II are capable of handling complex sample geometries and we will demonstrate that both are of similar accuracy when modeling experimental secondary fluorescence data from the literature.
Pathology and Pathophysiology of Inhalational Anthrax in a Guinea Pig Model

ABSTRACT Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's “Animal Rule. ” However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 104 spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.
Disparities in Lung Cancer Staging with Positron Emission Tomography in the Cancer Care Outcomes Research and Surveillance (CanCORS) Study

Introduction:Disparities in treatment exist for nonwhite and Hispanic patients with non-small cell lung cancer, but little is known about disparities in the use of staging tests or their underlying causes. Methods:Prospective, observational cohort study of 3638 patients with newly diagnosed non-small cell lung cancer from 4 large, geographically defined regions, 5 integrated health care systems, and 13 VA health care facilities. Results:Median age was 69 years, 62% were men, 26% were Hispanic or nonwhite, 68% graduated high school, 50% had private insurance, and 41% received care in the VA or another integrated health care system. After adjustment, positron emission tomography (PET) use was 13% lower among nonwhites and Hispanics than non-Hispanic whites (risk ratio [RR] 0.87, 95% confidence interval [CI] 0.77–0.97), 13% lower among those with Medicare than those with private insurance (RR 0.87, 95% CI 0.76–0.99), and 24% lower among those with an elementary school education than those with a graduate degree (RR 0.76, 95% CI 0.57–0.98). Disparate use of PET was not observed among patients who received care in an integrated health care setting, but the association between race/ethnicity and PET use was similar in magnitude across all other subgroups. Further analysis showed that income, education, insurance, and health care setting do not explain the association between race/ethnicity and PET use. Conclusions:Hispanics and nonwhites with non-small cell lung cancer are less likely to receive PET imaging. This finding is consistent across subgroups and not explained by differences in income, education, or insurance coverage.
De novo morphogenesis in L‐forms via geometric control of cell growth

In virtually all bacteria, the cell wall is crucial for mechanical integrity and for determining cell shape. Escherichia coli's rod‐like shape is maintained via the spatiotemporal patterning of cell‐wall synthesis by the actin homologue MreB. Here, we transiently inhibited cell‐wall synthesis in E. coli to generate cell‐wall‐deficient, spherical L‐forms, and found that they robustly reverted to a rod‐like shape within several generations after inhibition cessation. The chemical composition of the cell wall remained essentially unchanged during this process, as indicated by liquid chromatography. Throughout reversion, MreB localized to inwardly curved regions of the cell, and fluorescent cell wall labelling revealed that MreB targets synthesis to those regions. When exposed to the MreB inhibitor A22, reverting cells regrew a cell wall but failed to recover a rod‐like shape. Our results suggest that MreB provides the geometric measure that allows E. coli to actively establish and regulate its morphology.
Neuronal responses to transient hypoglycaemia in the dorsal vagal complex of the rat brainstem

Several regions of the mammalian brain contain glucosensing neurones. In vivo studies have suggested that those located in the hypothalamus and lower brainstem are involved in glucoprivic feeding and homeostatic control of blood glucose. We have identified and characterized hypoglycaemia‐sensitive neurones in the dorsal vagal complex of the brainstem using in situ hybridization, single‐cell RT‐PCR and whole‐cell patch‐clamp recordings from rat brainstem slices. Approximately 80% of neurones did not respond to hypoglycaemia (changing artificial cerebrospinal fluid (ACSF) glucose from 10 mm to 0 mm) within 5 min (non‐responsive: NR). Another 10% depolarized within 155 ± 31 s (mean ±s.e.m.) of glucose removal (glucose‐inhibited: GI), and the remaining neurones hyperpolarized within 53 ± 7 s (glucose‐excited: GE). The hyperpolarization was reversed by the KATP channel blocker tolbutamide. Single‐cell RT‐PCR revealed that GI and GE, but not NR, cells expressed glucokinase (GLK). In contrast, SUR1, a KATP channel subunit, was expressed in GE and some NR cells. In situ hybridization with biotin‐labelled riboprobes in the dorsal vagal complex revealed ubiquitous expression of SUR1, and widespread, but sparse, expression of GLK. Identification of astrocytes using a GFAP (glial fibrillary acidic protein) antibody showed that GLK and GFAP were not colocalized. In summary, we have demonstrated that GI and GE neurones exist in the brainstem and that GLK is essential for their function. It seems likely that GE neurones work in a way analogous to pancreatic β‐cells in that they require both GLK and KATP channels.
The impact of revenue diversification on bank profitability and risk: evidence from MENA banking industry

ABSTRACT The aim of this paper is to investigate the effects of revenue diversification on bank performance while shedding light on the impact of the shift towards non-interest income sources. To this end, we use a sample of 275 banks from fourteen MENA countries over 1990–2011. The model estimation using the GMM system reveals that diversification, when taken as a whole, improves bank profitability. We also split the non-interest income and we find that trading-generating business lines contribute the most to boosting profitability and stability. Engaging in non-interest-related activities worsens the benefit-cost trade-off of diversification, induced by the increased insolvency risk.
More complications in patients with septic shock treated with dextran compared with crystalloids.

INTRODUCTION In recent years, the safety-profile of synthetic colloids has been questioned. The purpose of the present study was to elucidate the safety-profile of the colloid dextran-70 in relation to acute kidney injury (AKI) and death. METHODS We conducted a retrospective, observational study of patients admitted to our intensive care unit with septic shock and treated with dextran-70 in the period from 1 January 2009 to 31 December 2009. The controls were included from 1 March 2012 to 28 February 2013 when dextran-70 was replaced with crystalloids. RESULTS There were 91 patients in the dextran group and 150 patients in the non-dextran group. The urinary output was 17.93 ml/kg/24 h in the dextran group and 27.87 in the non-dextran group (p < 0.05). Continuous renal replacement therapy (CRRT) was used in 48% in the dextran group and in 23% in the non-dextran group (p < 0.05). Major bleeding episodes occurred in 32% in the dextran group compared with 15% in the control group (p < 0.05). The 90-day mortality was 42% in the dextran group and 35% in the non-dextran group (p = 0.08). CONCLUSION Patients in the dextran group had significantly more bleeding episodes, a higher need for CRRT and a lower urinary output than patients in the non-dextran group. Due to study design, it cannot be concluded that the use of dextran-70 is causally related to the development of AKI.
Life goals after brain injury in the light of the dual process approach: Empirical evidence and implications for neuropsychological rehabilitation

Sequelae of acquired brain injury endanger the realisation of important life-goals. Discrepancies arise between the importance attached to a goal and the success in realising it. This study investigates goal discrepancies and their influence on patients' subjective well-being (SWB) in different rehabilitation stages. Life-goals, SWB and daily functioning were assessed in 130 neurological inpatients and 42 outpatients by self-report questionnaires. Both patient groups reported greater discrepancies between importance and success of life-goals than a normative sample of healthy controls. In multiple regression modelling, goal discrepancy predicted SWB in the inpatient sample even when controlling for the influence of ABI-related functional limitations. Of significant influence were the discrepancies in the domains of intimacy and achievement. In the respective analysis of the outpatient sample, goal discrepancy was not a significant predictor of SWB when accounting for functional limitations. A post-hoc analysis examined the inter-relation between functional limitations and goal discrepancy. Functional limitations influenced the ratings of successful goal realisation, yet they had less impact on the importance attached to a goal. The findings highlight the importance of patients' life-goals for successful neuropsychological rehabilitation. They indicate a need for further research considering goal adjustment processes in the face of chronic functional impairment.
Superoxide radical generation and Mn‐ and Cu‐Zn superoxide dismutases activities in human leukemic cells

Mn‐ and Cu‐Zn superoxide dismutase (SOD) activities and generation of superoxide radicals (O 2− ) were assessed in leukemic cells from 10 patients with acute myeloid or monocytic leukemia (AML) and 10 patients with acute lymphoblastic leukemia (ALL), using a sensitive, specific chemiluminescence method. Leukemic cells were classified according to the French–American–British classification. M4 AML cells from two patients produced some O 2− upon stimulation with opsonized zymosan (OZ), phorbol myristate acetate (PMA) or N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP), but less than normal granulocytes or monocytes. M5b AML cells from one patient produced as much O 2− in response to these stimulants as normal monocytes. No O 2− generation was induced in other types of leukemic cells. Total SOD activity in AML cells was significantly greater in normal granulocytes, but was only half of the activity in ALL cells. Mn‐SOD in AML cells was very low or undetectable. These results suggest that except in M5b cells, decreased O 2− production may contribute to susceptibility to infections in AML patients. Decreased Mn‐SOD activity in AML cells may predispose them to oxidative stress. Copyright © 2002 John Wiley & Sons, Ltd.