Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of Human Pancreatic Ribonuclease with Human Ribonuclease Inhibitor

Mammalian ribonucleases interact very strongly with the intracellular ribonuclease inhibitor (RI). Eukaryotic cells exposed to mammalian ribonucleases are protected from their cytotoxic action by the intracellular inhibition of ribonucleases by RI. Human pancreatic ribonuclease (HPR) is structurally and functionally very similar to bovine RNase A and interacts with human RI with a high affinity. In the current study, we have investigated the involvement of Lys-7, Gln-11, Asn-71, Asn-88, Gly-89, Ser-90, and Glu-111 in HPR in its interaction with human ribonuclease inhibitor. These contact residues were mutated either individually or in combination to generate mutants K7A, Q11A, N71A, E111A, N88R, G89R, S90R, K7A/E111A, Q11A/E111A, N71A/E111A, K7A/N71A/E111A, Q11A/N71A/E111A, and K7A/Q11A/N71A/E111A. Out of these, eight mutants, K7A, Q11A, N71A, S90R, E111A, Q11A/E111A, N71A/E111A, and K7A/N71A/E111A, showed an ability to evade RI more than the wild type HPR, with the triple mutant K7A/N71A/E111A having the maximum RI resistance. As a result, these variants exhibited higher cytotoxic activity than wild type HPR. The mutation of Gly-89 in HPR produced no change in the sensitivity of HPR for RI, whereas it has been reported that mutating the equivalent residue Gly-88 in RNase A yielded a variant with increased RI resistance and cytotoxicity. Hence, despite its considerable homology with RNase A, HPR shows differences in its interaction with RI. We demonstrate that interaction between human pancreatic ribonuclease and RI can be disrupted by mutating residues that are involved in HPR-RI binding. The inhibitor-resistant cytotoxic HPR mutants should be useful in developing therapeutic molecules.
Pulse transit times to the capillary bed evaluated by laser Doppler flowmetry

The pulse transit time (PTT) of a wave over a specified distance along a blood vessel provides a simple non-invasive index that can be used for the evaluation of arterial distensibility. Current methods of measuring the PTT determine the propagation times of pulses only in the larger arteries. We have evaluated the pulse arrival time (PAT) to the capillary bed, through the microcirculation, and have investigated its relationship to the arterial PAT to a fingertip. To do so, we detected cardiac-induced pulse waves in skin microcirculation using laser Doppler flowmetry (LDF). Using the ECG as a reference, PATs to the microcirculation were measured on the four extremities of 108 healthy subjects. Simultaneously, PATs to the radial artery of the left index finger were obtained from blood pressure recordings using a piezoelectric sensor. Both PATs correlate in similar ways with heart rate and age. That to the microcirculation is shown to be sensitive to local changes in skin perfusion induced by cooling. We introduce a measure for the PTT through the microcirculation. We conclude that a combination of LDF and pressure measurements enables simultaneous characterization of the states of the macro and microvasculature. Information about the microcirculation, including an assessment of endothelial function, may be obtained from the responses to perturbations in skin perfusion, such as temperature stress or vasoactive substances.
Could a large scale asset purchase programme have mitigated the Great Depression

Since Friedman and Schwarz (1963), the role of the Federal Reserve during the Great Depression has been an issue of debate. In this paper, we focus on the purchases of government securities by the Federal Reserve over a four-month period in 1932. Using a Bayesian VAR model, we estimate the effect of an extension of this programme in conjunction with an interest rate cut on a range of variables capturing prices, output and macro-financial linkages. Our results indicate that this policy would have substantially shortened and reduced the impact of the Great Depression.
Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit.

The surviving members of 27 households in which someone had been infected with Ebola virus were interviewed in order to define the modes of transmission of Ebola hemorrhagic fever (EHF). Of 173 household contacts of the primary cases, 28 (16%) developed EHF. All secondary cases had direct physical contact with the ill person (rate ratio [RR], undefined; P < .001), and among those with direct contact, exposure to body fluids conferred additional risk (RR, 3.6; 95% confidence interval [CI], 1.9-6.8). After adjusting for direct contact and exposure to body fluids, adult family members, those who touched the cadaver, and those who were exposed during the late hospital phase were at additional risk. None of the 78 household members who had no physical contact with the case during the clinical illness were infected (upper 95% CI, 4%). EHF is transmitted principally by direct physical contact with an ill person or their body fluids during the later stages of illness.
Should national guidelines continue to recommend fetal scalp blood sampling during labor?

Abstract Intrapartum fetal scalp blood sampling (FBS) (pH or lactate) has not been shown to reduce emergency cesarean sections or operative vaginal births or improve long-term perinatal outcomes. In contrast, it is associated with rare but potentially very serious complications such as leakage of cerebro-spinal fluid (CSF) and perinatal hemorrhagic shock. Therefore, it does not fulfill the “First Do No Harm” principle and its use during labor should be critically re-evaluated.
Advancing to positions of power in parliament – does seniority matter?

ABSTRACT This article examines whether or not legislatures in which strict adherence to seniority rule is uncommon nevertheless follow seniority conventions when positions of power in parliament are appointed. For this purpose, career data is gathered on each of the 4,961 legislators who served in the sixteen German state parliaments between 1990 and 2012. In order to understand the linkages that describe career patterns within parliaments, the study refers to delegation theory. Differentiating between the offices of president of parliament, committee chair and parliamentary group leader, logistic regression analyses provide evidence that being the incumbent means being in the absolute best starting position to become (re-)selected. This finding holds for every one of the offices distinguished. Other facets of seniority, such as being a long-standing parliamentarian, a long-standing party member or a former government official, show up as being relevant from time to time. Socio-demographic factors, however, play only a minor role.
&ggr;-Aminobutyric Acid Receptor Type A Receptor Potentiation Reduces Firing of Neuronal Assemblies in a Computational Cortical Model

Background:The understanding of how general anesthetics act on individual cells and on global brain function has increased significantly during the last decade. What remains poorly understood is how anesthetics act at intermediate scales. Several major theories emphasize the importance of neuronal groups, sets of strongly connected neurons that fire in a time-locked fashion, in all aspects of brain function, particularly as a necessary substrate of consciousness. The authors have undertaken computer modeling to determine how ã-aminobutyric acid receptor type A (GABAA) receptor potentiating agents such as propofol may influence the dynamics of neuronal group formation and ongoing activity. Methods:A computer model of a cortical network with connections modified by synaptic plasticity was examined. At baseline, the model spontaneously formed neuronal groups. Direct effects of GABAA receptor potentiation and indirect effects on input drive were then examined to study their effects on this process. Results:Potentiation of GABAA inhibition and input drive reduction reduced the firing frequency of inhibitory and excitatory neurons in a dose-dependent manner. The diminution in spiking rates led to dramatic reductions in the firing frequency of neuronal groups. Simulated electroencephalographic output from the model at baseline exhibits gamma and theta rhythmicity. The direct and indirect GABAA effects reduce the amplitude of these underlying rhythms and modestly slow the gamma rhythm. Conclusions:GABAA facilitation both directly and indirectly inhibits the ability of neurons to form groups spontaneously. A lack of group formation is consistent with some theories of anesthetic-induced loss of memory formation and consciousness.
Cancer risk among men with, or at risk of, HIV infection in southern Europe

Objective:To evaluate the cancer risk in southern European men with, or at risk of, HIV infection. Design:An analysis of longitudinal data to assess time-dependent rare events. Methods:Data from a cohort of HIV seroconverters, and from two hospital-based HIV seroprevalent cohorts were combined and analysed. The number of cancer cases observed was compared with the expected number, obtained from cancer incidence rates among men in the general population. Age-standardized incidence ratios (SIR) and their 95% confidence intervals (CI) were computed. Results:A total of 19 609 person-years of observation were accumulated among HIV-positive men, and 7957 person-years among HIV-negative men. Among HIV-positive men, statistically significant increased SIR were seen for Hodgkin's disease (HD) (SIR = 8.7), liver cancer (SIR = 11.0), and cancer of the salivary glands (SIR = 33.6). An excess of lung cancer was seen among intravenous drug users (IDU), but not among homosexual men. When the risk of all non-AIDS-defining cancers was considered, HIV-positive men had a nearly twofold excess (95% CI: 1.2–2.8). A risk of similar magnitude emerged among HIV-negative IDU (95% CI: 1.0–4.5), largely attributable to lung cancer and HD. Conclusion:These findings confirm that HIV infection increases the risk of HD, whereas they suggest that the risk of hepatocellular carcinoma may also be enhanced by HIV infection. The observation of an elevated risk of lung cancer in both HIV-positive and HIV-negative IDU points to personal behaviours unrelated to HIV infection.
Experimental evaluation of analgesic and anti-inflammatory activity of simvastatin and atorvastatin

Aim: The aim of this study is to evaluate the analgesic and anti-inflammatory activities of atorvastatin and simvastatin in different experimental models in mice and rats. Materials and Methods: Analgesic activity of simvastatin and atorvastatin was assessed in tail flick model in rats (n = 6), where it was compared with aspirin and tramadol and in acetic acid induced writhing in mice (n = 6), where it was compared with aspirin. Anti-inflammatory activity of statins was evaluated using carrageenin induced paw edema and formalin induced arthritis in rats. Results: In the tail flick method, analgesic effect of tramadol was significantly more than the other drugs except at two observation times, when it was comparable to simvastatin and atorvastatin. Effect of simvastatin was found to be comparable to aspirin. In acetic acid induced writhing method, analgesic activity of simvastatin was comparable to that of aspirin while that of atorvastatin was significantly less. In carrageenin induced paw edema in rats, both simvastatin and atorvastatin showed anti-inflammatory activity which was comparable to aspirin. Both the statins exhibited significant anti-inflammatory activity (P < 0.01) in formalin induced arthritis model though less than aspirin (P < 0.05). Conclusion: The results of this study if substantiated by further experimental and clinical research suggest that simvastatin and atorvastatin may play an adjuvant role, which may be particularly beneficial in the treatment of inflammatory disorders, especially when there is coexisting dyslipidemia.
Influence of a genetic variant of the neuronal growth associated protein Stathmin 1 on cognitive and affective control processes: An event‐related potential study

Stathmin 1 (STMN1) is a neuronal growth associated protein (NGAP) that is involved in microtubule dynamics and plays an important role in neurite outgrowth and synaptic plasticity. It is highly expressed in the amygdala, but also in different areas of the neocortex including the frontal lobe. Based on previous findings regarding an impact of STMN1 on fear processing, the present study aimed at extending the evidence concerning its functional role to include the domain of executive (frontal lobe) functions. To this end, a group of 59 healthy volunteers stratified for the single‐nucleotide polymorphism rs182455 of the STMN1 gene was examined by means of three experimental paradigms probing different aspects of cognitive–affective functioning. Event‐related potential measures of cognitive response control, emotional interference processing, and action monitoring were analyzed. STMN1 genotype significantly affected the NoGo‐anteriorization (NGA)—a neurophysiological marker of cognitive response control associated with medial prefrontal cortex activation—as well as the modulation of the P300 by the valence of emotional Stroop stimuli. In both cases, carriers of the rs182455 C‐allele showed altered cognitive–affective processing; effects appeared to be more pronounced in females. Our findings indicate a functional impact of STMN1 on cognitive and affective control processes, thereby complementing previous evidence on its role in fear processing. Based on these results, an influence of STMN1 should be considered in studies aiming at the etiopathogenesis of a broad range of neuropsychiatric disorders with dysfunctional networking, including neurodegenerative disorders as well as schizophrenia, autism spectrum disorders, anxiety disorders, depression, and ADHD. © 2011 Wiley‐Liss, Inc.
Childhood Leukaemia in Scotland, 1939–68

Data from death certificates of 978 children who died from leukaemia in Scotland before their fifteenth birthday during 1939–68 were analysed. The main findings were the same as those reported for childhood leukaemia in England and Wales and the United States and were as follows: (1) Leukaemia mortality {principally lymphatic leukaemia) increased during the 1940's and 1950's with a slight decline during the 1960's; and (2) Mortality from lymphatic leukaemia rose to a peak at 3 to 4 years of age while mortality from myeloid and monocytic leukaemia was evenly distributed throughout the first 14 years of life. Leukaemia mortality in Scotland was lower than for the majority of countries. During the 1950's the rate was the fifth lowest for males (35 per million) and seventh lowest for females (26 per million) of 25 countries. There was no evidence of an urban-rural gradient or of seasonal variation of onset or mortality or of clustering of cases of leukaemia. Regional variations in leukaemia mortality in Scotland were not significant in contrast to a significant regional variation in leukaemia mortality for adults in Scotland observed by Court Brown et al. (1960).
Nowcasting emerging market’s GDP: the importance of dimension reduction techniques

ABSTRACT A number of recent studies in the macro-finance literature that addresses the link between asset prices and economic fluctuations have focused on the usefulness of various factor models in the context of now-casting using very big dataset. The issue of factor extraction is usually swept under the carpet in the factor model literature, where it seems that all that is needed is a large number of economic and financial variables. We contribute to this literature by analysing whether factor estimation methods matters for the performance of factor-based now-casting models based on selected emerging markets GDP. Ancillary findings based on our GDP now-casting experiments on major emerging market countries underscore the advantage of sparse principal component analysis-based factor estimation approach. These results show that imposing a sparse structure on the whole dataset is generally a useful step towards reducing the forecast errors in the context of GDP now-casting model specification.
The values of global citizenship education and implications for social justice

Target 4.7 of the Sustainable Development Goals promotes Global Citizenship Education as a vehicle to develop the skills, values and attitudes of learners so that they may work towards the resolution of the interconnected challenges facing the world today. Underpinning UNESCO’s approach to global citizenship education are ‘Universal Values’ said to apply to all people everywhere on the basis of a common humanity. I adopt the position that values act as motivators of action and that values also enable evaluation of which actions are deemed desirable and worthwhile. Which values are promoted can motivate action in directions which may serve some agendas over others. With the critique that UNESCO furthers the dominance of western powers, the role of universal values to motivate the action of global citizens towards mutual human wellbeing or towards action that serves the powerful, becomes a key area for analysis. Using a multimodal critical discourse analysis of 8 key documents within UNESCO’s Global Citizenship Education, I argue that UNESCO exhibit a controlled narrative around values and have defined the ‘appropriate’ global citizen. In so doing, UNESCO influence the subjectivities of global citizens according to UNESCO’s agenda and this furthers the agenda of western powers. Further, I argue that UNESCO’s values are abstract and divorced from social contexts. This denies recognition of alternative values and ways of doing global citizenship more suited to local contexts potentially engendering greater participation as global citizens. Drawing on Fraser’s concept of justice as Participatory Parity, I argue that UNESCO’s misrecognition of these alternatives is unjust and further that this is potentially generative of the injustices of misrepresentation and maldistribution, compounding a lack of participatory parity. I conclude that UNESCO must afford recognition to alternative values and ways of doing global citizenship such that global citizenship education becomes more socially just.
Central Necrosis in Isolated Hypoxic Human Pancreatic Islets: Evidence for Postisolation Ischemia

A variety of explanations have been provided to elucidate the requirement of the large islet mass that is essential for a successful treatment of patients with type I diabetes by intrahepatic transplantation. The purpose of this study was to investigate islet cell survival under the effect of prolonged hypoxia and/or nutrient withdrawal, which mimics posttransplantation environment of transplanted islets in the liver. We studied the influence of 24 h of hypoxia (1% O2) in intact isolated human and rat islets as well as the effect of combined oxygen/nutrient deprivation in a mouse insulinoma cell line (MIN6). In intact human islets, 24 h of hypoxia led to central necrosis combined with apoptotic features such as nuclear pyknosis and DNA fragmentation. In the course of hypoxic treatment, ultrastructural analysis demonstrated a gradual transition from an apoptotic to a necrotic morphology particularly pronounced in central areas of large islets. In MIN6 cells, on the other hand, hypoxia led to a twofold (p < 0.01) increase in caspase-3 activity, an indicator of apoptosis, but not to necrosis, as determined by release of lactate dehydrogenase (LDH). Only in combination with nutrient/serum deprivation was a marked increase in LDH release observed (sixfold vs. control, p < 0.01). We therefore conclude that, similar to MIN6 cells, central necrosis in isolated hypoxic islets is the result of the combined effects of hypoxia and nutrient/serum deprivation, most likely due to limited diffusion. Provided that transplanted islets undergo a similar fate as shown in our in vitro study, future emphasis will require the development of strategies that protect the islet graft from early cell death and accelerate the revascularization process.
Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: A randomized trial comparing 3‐ and 6‐month periodicities

Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC ≤30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n = 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, ≤30 mm in diameter 74%). Focal‐lesion incidence was not different between Gr3M and Gr6M groups (2‐year estimates, 20.4% versus 13.2%, P = 0.067) but incidence of lesions ≤10 mm was increased (41% in Gr3M versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence (P = 0.13) or in prevalence of tumors ≤30 mm in diameter (79% versus 70%, P = 0.30) was observed between the randomized groups. Conclusion: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures. (HEPATOLOGY 2011;)
Age Related Natural Killer Activity of Peripheral Blood Lymphocytes from Healthy Subjects and Cancer Patients. A Comparative in Vitro Study with Interleukin-2

Aims and Beckground Natural killer (NK) cell activity is known to be depressed in neoplastic diseases, and ageing influences the cytotoxicity of NK cells. However, very little information is available on the responsiveness of NK cells of cancer patients to the stimulating effects of interleukin-2 (IL-2) as a function of age. Methods We assessed in vitro IL-2 induced modulation of NK activity in peripheral blood lymphocytes (PBL) from 7 young (30-50 years) and 9 elderly (55-78 years) male patients with carcinoma of the oral cavity. In these patients generation of lyphokine activated killer (LAK) activity was also studied. NK and LAK activity of PBL were measured in 14 age and sex matched healthy volunteers as who served as conrols. Cytotoxicity of the NK and LAK cells was assayed against NK sensitive K562 and NK resistant Daudi cells in 4-h 51 Cr-release assays. Results NK activity in the cancer patients was significantly lower than that in healthy volunteers. In both groups the younger subjects had higher NK activity than the elderly ones. NK cells of both young and elderly healthy controls responded similarly to 24-hour in vitro exposure to human recombinant IL-2 (rIL-2, 100 u/ml) with highly increased cytotoxicity. Though there was significant enhancement of NK activity with rIL-2 in both young and elderly cancer patients, the rIL-2 induced NK cytotoxicity in the elderly patients was much lower than the basal level of NK activity of the age matched controls. Interestingly, LAK activity, generated by 3-7 days of in vitro exposure of PBL to rlL-2 was comparable in the cancer patients and healthy volunteers Conclusion The data suggest serious impairment of NK function in elderly patients with oral carcinoma. Generation of LAK activity with exogenous IL-2 could be an important modality of treatment in these patients.