Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability, protein binding and clearance studies of [99mTc]DTPA. Evaluation of a commercially available dry-kit.

[99mTc]DTPA has achieved widespread use for the measurement of glomerular filtration rate (GFR) with the single injection plasma clearance technique and for gamma-camera renography. However, the quality of the commercial preparations varies. The purpose of the present investigation was to study the quality of a commercial [99mTc]DTPA preparation (C.I.S., France) with reference to stability, protein binding and accuracy of the determined plasma clearance values as a measure of GFR. The stability of the preparations was studied by thin-layer chromatography, the in vitro protein binding by Sephadex filtration after incubation with human serum albumin and in vivo protein binding by filtration of human plasma. The accuracy of the plasma clearance values was investigated by comparison with the simultaneously measured plasma clearance of [51Cr]EDTA. There was no detectable free pertechnetate or hydrolysed reduced technetium in eight vials five and six hours after the preparation. The in vitro protein binding 10 (20), 120 and 300 min after the preparation of eight vials was 2.3% (0.8%), 0.2% and 0.1%, respectively. The in vivo protein binding in 12 patients 5, 90 and 180 min after the injection was 0.3%, 0.7% and 1.1%, respectively. The plasma clearance of [99mTc]DTPA was on an average 3.7% higher than that of [51Cr]EDTA in 27 patients. It is concluded that the [99mTc]DTPA preparation is reliable for the measurement of GFR. The preparation is stable for at least six hours at room temperature. It is recommended not to use the [99mTc]DTPA until 30 min after the preparation.
The periplasmic domain of the histidine autokinase CitA functions as a highly specific citrate receptor

The two‐component regulatory system CitA/CitB is essential for induction of the citrate fermentation genes in Klebsiella pneumoniae. CitA represents a membrane‐bound sensor kinase consisting of a periplasmic domain flanked by two transmembrane helices, a linker domain and the conserved kinase or transmitter domain. A fusion protein (MalE–CitAC) composed of the maltose‐binding protein and the CitA kinase domain (amino acids 327–547) showed constitutive autokinase activity and transferred the γ‐phosphate group of ATP to its cognate response regulator CitB. The autokinase activity of CitA was abolished by an H350L exchange, and phosphorylation of CitB was inhibited by a D56N exchange, indicating that H‐350 and D‐56 represent the phosphorylation sites of CitA and CitB respectively. In the presence of ATP, CitB–D56N formed a stable complex with MalE–CitAC. To analyse the sensory properties of CitA, the periplasmic domain (amino acids 45–176) was overproduced as a soluble, cytoplasmic protein with a C‐terminally attached histidine tag (CitAPHis). Purified CitAPHis bound citrate, but none of the other tri‐ and dicarboxylates tested, with high affinity (KD ≈ 5 μM at pH 7) in a 1:1 stoichiometry. As shown by isothermal titration calorimetry, the binding reaction was driven by the enthalpy change (ΔH = −76.3 kJ mol−1), whereas the entropy change was opposed (−TΔS = + 46.3 kJ mol−1). The pH dependency of the binding reaction indicated that the dianionic form H‐citrate2− is the citrate species recognized by CitAPHis. In the presence of Mg2+ ions, the dissociation constant increased significantly, suggesting that the Mg–citrate complex is not bound by CitAPHis. This work defines the periplasmic domain of CitA as a highly specific citrate receptor and elucidates the binding characteristics of CitAPHis.
The Impact of Cliometrics on Economics and History

La cliometrie a transforme l’histoire economique en passant d’une approche essentiellement narrative a une approche mathematique, suscitant par la meme beaucoup d’apprehensions et de debats quant a l’equilibre approprie entre l’economie et l’histoire. Le point culminant de cette transformation s’est produit en 1993 lorsque les pionniers de la cliometrie Robert Fogel et Douglass North ont recu le prix Nobel de science economique. La cliometrie a realise un equilibre delicat entre economie et histoire. Elle n’est ni trop « etroitement » economique, c’est-a-dire qu’elle ne se contente pas de mesurer les phenomenes sans les expliquer, ni trop historique (elle ne rejette pas les contacts avec les economistes). En fusionnant l’histoire economique avec les techniques modernes, les cliometriciens n’ont pas mis fin a l’histoire economique, mais ils lui ont donne une autre dimension.
R&D and patents: is it a two way street?

ABSTRACT This paper provides empirical evidence on the link between firms’ R&D expenditure and patent registrations by applying the Granger causality test. We use a panel of Spanish manufacturing firms for the period 1990–2013. We first, examine the R&D-patents relationship in the manufacturing firms as a whole and subsequently, manufacturing was broken down into three groups of firms according to the technological level of the industries to which the firms belonged: high and medium-high (HMHT), low medium (LMT) and low (LT) technology firms. For the entire panel, our results provide support for a bidirectional relationship between R&D and patents, supporting both the traditional view and the reverse causality approach (patents cause R&D). When the sample is split into the three technology levels, we also find strong support for a bidirectional relationship in HMHT firms and weak support in LT ones. We found no evidence of this bidirectional link in LMT firms.
Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer

Purpose: UGT1A1*28 confers a higher risk of toxicity in patients treated with irinotecan. Patients with *1/*1 and *1/*28 genotypes might tolerate higher than standard doses of irinotecan. We aimed to identify the MTD of irinotecan in patients with metastatic colorectal cancer (mCRC) with *1/*1 and *1/*28 genotypes treated with FOLFIRI plus bevacizumab, and to determine whether bevacizumab alters irinotecan pharmacokinetics. Experimental Design: Previously untreated patients with mCRC (25 *1/*1; 23 *1/*28) were given FOLFIRI plus bevacizumab every 2 weeks. The irinotecan dose was escalated using a 3 + 3 design in each genotype group as follows: 260, 310, and 370 mg/m2. The MTD was the highest dose at which <4/10 patients had a dose-limiting toxicity (DLT). Pharmacokinetics of irinotecan and SN-38 were measured on days 1 to 3 (without bevacizumab) and 15 to 17 (with bevacizumab). Results: For *1/*1 patients, 2 DLTs were observed among 10 patients at 310 mg/m2, while 370 mg/m2 was not tolerated (2 DLTs in 4 patients). For *1/*28 patients, 2 DLTs were observed among 10 patients at 260 mg/m2, while 310 mg/m2 was not tolerated (4 DLTs in 10 patients). Neutropenia and diarrhea were the most common DLTs. Changes in the AUCs of irinotecan and SN-38 associated with bevacizumab treatment were marginal. Conclusions: The MTD of irinotecan in FOLFIRI plus bevacizumab is 310 mg/m2 for UGT1A1 *1/*1 patients and 260 mg/m2 for *1/*28 patients. Bevacizumab does not alter the pharmacokinetics of irinotecan. The antitumor efficacy of these genotype-guided doses should be tested in future studies of patients with mCRC treated with FOLFIRI plus bevacizumab. Clin Cancer Res; 23(4); 918–24. ©2016 AACR.
Economic Diplomacy and the Liberal Peace

The purpose of this work is two-fold. The first is to relate the theory of liberal peace to the notion of economic diplomacy. The second objective of this essay is to relate the greater economic globalization outcome of economic diplomacy, and its counterpart liberal peace objective, to the incidence and nature of domestic conflict. Nowadays, civil war has become the dominant form of war, mainly in developing countries. But other forms of social conflict and unrest short of war are also emerging, especially in the wake of the growing global tide of rising inequality and relative deprivation since the current phase of globalization gathered pace after circa 1980. This is also reflected in voting in democratic countries, for example the referendum in favour of Brexit in 2016. A game theoretic model of interaction between the state and a dissident group over the degree of globalization is also presented. This version: 11 January 2016.
The tissue factor–factor VIIa complex: procoagulant activity, regulation, and multitasking

Summary. Greater understanding of the cellular interactions associated with tissue factor (TF), activated factor (F) VII and TF–FVIIa complexes is likely to provide considerable clinical benefit. This article reviews current knowledge on the function and regulation of TF and its role in a range of biological processes, including hemostasis, thrombosis and inflammation.
Volunteer tourists’ perceptions of their impacts on marginalized communities

Abstract Using a phenomenological approach, this study examines the experiences of volunteer tourists in host communities using social representations theory. Semi-structured interviews were conducted with volunteer tourists on perceived impacts on favela (slum) communities of Rio de Janeiro, Brazil. This study was developed to address a need for further research that critically looks at the social impacts of volunteer tourism in marginalized communities. It addresses the following question: How does volunteer tourism influence a marginalized community from the perspective of the volunteers? Notably, the majority of the volunteers in this study had difficulty describing how volunteer tourism has benefited the community beyond their own individual contributions, and it was difficult for them to see broader implications of volunteer tourism in general. Recommendations of management actions that will help to maintain and enhance the benefits and alleviate the negative consequences and obstacles that were perceived by volunteer tourists are given.
Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients.

BACKGROUND The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. METHODS This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). RESULTS Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). CONCLUSIONS Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis.
A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS

Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so‐called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre‐clinical pharmacological testing and large‐scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor‐mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor‐mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short‐term clinical efficacy, set the stage for a large‐scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms. Neurourol. Urodynam. 26:458–463, 2007. © 2007 Wiley‐Liss, Inc.
Glycerol turnover and oxidation in man.

The oxidation and turnover of plasma glycerol has been studied in lean and obese, fed and starving man by means of a long-term infusion of glycerol-(14)C, and the participation of glycerol in gluconeogenesis has been determined. Under none of the experimental conditions did glycerol contribute more than 10% of the total respiratory CO(2). Glycerol turnover in fed lean subjects was 106 mmoles/min. Glycerol levels and turnover were higher in the obese subjects and with all subjects after starvation. There was a direct correlation between plasma levels and turnover values for which a regression equation was derived: y = 1556 x + 33.1, when y = turnover in micromoles per minute and x = glycerol level in micromoles per milliliter. Whereas a direct relation was established between glycerol and FFA levels, the FFA/glycerol turnover ratio was 4.7:1 in the lean group indicating incomplete hydrolysis of adipose tissue triglycerides.During starvation plasma glycerol is nearly or completely converted to glucose in the lean and obese groups, respectively. Of the new glucose formed from protein and glycerol 38% is derived from glycerol in the lean and 79% in the obese. Protein and glycerol have been shown to be adequate as precursors to supply at least as much glucose as is being oxidized per day.
Associations between allergies and risk of hematologic malignancies: Results from the VITamins and lifestyle cohort study

Immune dysregulations associated with allergies may affect cancer cell biology but studies on the relationship between allergies and risk of hematologic malignancies (HM) yielded inconsistent results. Herein, we used the vitamins and Lifestyle (VITAL) cohort to examine this association. From 2000 to 2002, 66,212 participants, aged 50–76, completed a baseline questionnaire on cancer risk factors, medical conditions, allergies, and asthma. Through 2009, incident HMs (n = 681) were identified via linkage to the surveillance, epidemiology, and end results cancer registry. After adjustment for factors possibly associated with HMs, a history of airborne allergy was associated with increased risk of HMs (hazard ratio [HR] = 1.19 [95% confidence interval: 1.01–1.41], P = 0.039) in Cox proportional hazards models. This association was limited to allergies to plants/grass/trees (HR = 1.26 [1.05–1.50], P = 0.011) and was strongest for some mature B‐cell lymphomas (HR = 1.50 [1.14–2.00], P = 0.005). Gender‐stratified analyses revealed that the associations between airborne allergies overall and those to plants, grass, and trees were only seen in women (HR = 1.47 [1.14–1.91], P = 0.004; and HR = 1.73 [1.32–2.25], P < 0.001) but not men (HR = 1.03 [0.82–1.29], P = 0.782; and HR = 0.99 [0.77–1.27], P = 0.960). Together, our study indicates a moderately increased risk of HMs in women but not men with a history of allergies to airborne allergens, especially to plant, grass, or trees. Am. J. Hematol. 88:1050–1054, 2013. © 2013 Wiley Periodicals, Inc.
Temporal weighting of binaural information at low frequencies: Discrimination of dynamic interaural time and level differences.

The importance of sound onsets in binaural hearing has been addressed in many studies, particularly at high frequencies, where the onset of the envelope may carry much of the useful binaural information. Some studies suggest that sound onsets might play a similar role in the processing of binaural cues [e.g., fine-structure interaural time differences (ITD)] at low frequencies. This study measured listeners' sensitivity to ITD and interaural level differences (ILD) present in early (i.e., onset) and late parts of 80-ms pure tones of 250-, 500-, and 1000-Hz frequency. Following previous studies, tones carried static interaural cues or dynamic cues that peaked at sound onset and diminished to zero at sound offset or vice versa. Although better thresholds were observed in static than dynamic conditions overall, ITD discrimination was especially impaired, regardless of frequency, when cues were not available at sound onset. Results for ILD followed a similar pattern at 1000 Hz; at lower frequencies, ILD thresholds did not differ significantly between dynamic-cue conditions. The results support the "onset" hypothesis of Houtgast and Plomp [(1968). J. Acoust. Soc. Am. 44, 807-812] for ITD discrimination, but not necessarily ILD discrimination, in low-frequency pure tones.
The Effects of Terrorism on Turkish Financial Markets

Abstract In this research, we analyzed how Turkish financial markets and foreign investors in the stock market reacted to the terror attacks in Turkey. Our analysis, which was performed using the terror index for the stock market and the foreign exchange market, revealed that returns, abnormal returns, and cumulative abnormal returns were not affected by the terror attacks; however, foreign investors in the stock market were affected. When the geographic regions of the terror attacks were analyzed, the findings showed that foreign investors were negatively affected mainly by the terror attacks that occurred in southeast Anatolia. Attack type and target type were important only for foreign investors. An evaluation of the interaction between the terror attacks and the markets with the involvement of the terrorist organizations indicated that only the foreign investors in the stock market were affected by Al-Qaeda and PKK-linked terror attacks. An evaluation of the effect of terror attacks in foreign countries on Turkish financial markets revealed no effect on the domestic stock market and foreign exchange markets. We also examined the volatility spillovers from the terror index to the stock market and found that terrorist attacks increased the volatility of the stock market.
Anti-catastrophic time

Abstract:One of the dominant features of post-apocalyptic or Anthropocene culture is a ‘this changes everything’ sentiment regarding time. Whatever cultural differences the world may have been able to harbour up until the present, the current feeling of end-times focuses attention on the future. The overwhelming evidence for anthropogenic climate change seems to demand either that we think about humans as a historical agent at the level of the species or that we devalue the human to recognise a temporality beyond that of human concern. This essay questions that exclusive disjunction: it is possible to recognise both the thoroughly ‘human’ nature of the sense ‘we’ make of the world, while also striving to think beyond what has (up until now) counted as human temporality.
Living With Inequality: Neighborhood Income Diversity and Perceptions of the Income Gap

This article explores whether the places where people live—and specifically the diversity of incomes where people live—influence views about income inequality. Using a unique survey of New York City that contains geographic identifiers and questions about attitudes toward inequality, coupled with a rich array of Census data, we assess the degree to which the income diversity within spatially customized neighborhood boundaries influences beliefs about inequality. We find consistent evidence that attitudes about inequality are influenced by the places where people live—those who are exposed to more income diversity near their homes perceive larger gaps between the rich and everybody else, and are more likely to believe that the gap should be smaller. Moreover, this effect appears to be especially pronounced among those with lower educational attainment and at either end of the income spectrum.
Psychosocial aspects of adolescent cancer survival

The purpose of this research was to examine the psychosocial status of adolescent cancer survivors and compare them with healthy peers. It has been suggested in previous research that the majority of survivors display equivalent levels of psychosocial functioning post‐treatment as compared with healthy controls. However, despite successful treatment, survivors may have to adjust to living with a chronic illness and its associated late effects interspersed across the lifespan (e.g. infertility, cognitive deficits, heart complications). Whilst young people appear to have similar levels of psychosocial functioning, avoidance strategies such as denial may result in previous research findings being confounded and in underestimating the true psychosocial status of survivors. It is important to understand the psychosocial status of survivors in order to optimise their quality of life.