Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.

BACKGROUND Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy. METHODS We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression. Overall survival was analyzed with a Cox model adjusted for clinical and pathological factors. RESULTS Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, P=0.009). Adjuvant chemotherapy, as compared with observation, significantly prolonged survival among patients with ERCC1-negative tumors (adjusted hazard ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but not among patients with ERCC1-positive tumors (adjusted hazard ratio for death, 1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to 0.90; P=0.009). CONCLUSIONS Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.
Augmentation of Tendon Healing With Butyric Acid–Impregnated Sutures

Background: Butyric acid (BA) has been shown to be angiogenic and to enhance transcriptional activity in tissue. These properties of BA have the potential to augment biological healing of a repaired tendon. Purpose: To evaluate this possibility both biomechanically and histologically in an animal tendon repair model. Study Design: Controlled laboratory study. Methods: A rabbit Achilles tendon healing model was used to evaluate the biomechanical strength and histological properties at 6 and 12 weeks after repair. Unilateral tendon defects were created in the middle bundle of the Achilles tendon of each rabbit, which were repaired equivalently with either Ultrabraid BA-impregnated sutures or control Ultrabraid sutures. Results: After 6 weeks, BA-impregnated suture repairs had a significantly increased (P < .0001) Young’s modulus and ultimate tensile strength relative to the control suture repairs. At 12 weeks, no statistical difference was observed between these measures. The histological data at 6 weeks demonstrated significantly increased (P < .005) vessel density within 0.25 mm of the repair suture in the BA-impregnated group. There was also an associated 42% increase in the local number of myofibroblasts in the BA samples relative to the controls at this time. By 12 weeks, these differences were not observed. Conclusion: Tendons repaired with BA-impregnated sutures demonstrated improved biomechanical properties at 6 weeks relative to control sutures, suggesting a neoangiogenic mechanism of enhanced healing through an increased myofibroblast presence. Clinical Relevance: These findings demonstrate that a relatively simple alteration of suture material may augment early tendon healing to create a stronger repair construct during this time.
Short introns interrupting the Oct-2 POU domain may prevent recombination between POU family genes without interfering with potential POU domain 'shuffling' in evolution.

Transcription factors are often encoded by gene families that share the same type of DNA binding domain. The POU domain genes are one such paradigm. We compared the genomic DNA encoding the POU domain of the Oct-2 genes in human and mouse. In both species this domain is split into a cluster of four exons by short, highly diverged introns. We postulate that the main role of these introns is to prevent ectopic homologous recombination with other members of the POU gene family, with its potentially deleterious effects in somatic and germline cells. Such rapidly diverging introns may generally promote evolution by facilitating the maintenance of duplicated genes. The use of different codons for the same protein domain among members of a gene family may be a slower process that serves a similar purpose. Introns that split conserved domains such as the POU domain do not conform to the exon shuffling hypothesis originally put forward by W. Gilbert (1978). However, we note that the introns flanking the POU domain are in the same phase, i.e. interrupt codons in the same reading frame. Thus we propose that the entire POU domain, which is encoded by a tight cluster of exons, has been shuffled together during evolution as a functional unit, or 'shufflon'.
A methodology for measuring the gate-drain capacitance of CMOS devices

In this paper, the author presents a new methodology for measuring the gate drain capacitance of CMOS devices using an accelerated dc measurement scheme. The gate-drain capacitance was measured using a floating gate MOS transistor, i.e., an MOS transistor with an additional capacitor placed in series with the gate oxide capacitance. This was implemented within a standard p-well CMOS process using two matched transistors. The top capacitance couples charge onto the gate oxide capacitor and the gate-drain capacitor. The amount of coupling is determined by the ratio of these two capacitors.
Framework Agreements Under Turkish Law

Classical contract law prioritizes certainty over flexibility. In commercial transactions, however, flexibility is as important as certainty. Contractual transactions are also usually expensive in terms of the time, effort and money they require to negotiate, draft and follow up the enforcement of the agreement. To increase flexibility and mitigate the aforementioned problems, non-binding framework agreements that eases the formation of many future binding contracts are becoming more attractive in certain areas of contractual transactions. This article examines the concept of framework agreement under the Turkish law. It focuses on legislations and case laws related with framework agreements in the Turkish Law of Obligation, the Turkish Public Procurement law and Turkish Labour law.
E. A. Wrigley, The Path to Sustained Growth: England’s Transition from an Organic Economy to an Industrial Revolution (New York: Cambridge University Press, 2016), pp. xi + 219, $30 (paperback). ISBN: 9781316504284.

———. 2000. From Our Italian Correspondent: Luigi Einaudi’s Articles in the “Economist” , 1908–1946. Two volumes. edited by R. Marchionatti. Florence: olschki. Faucci, Riccardo. 1986. Luigi Einaudi. Turin: Utet. Heritier, Paolo, and Paolo silvestri, eds. 2012. Good Government, Governance, Human Complexity: Luigi Einaudi’s Legacy and Contemporary Societies. Florence: olschki. silvestri, Paolo. 2008. Il liberalismo di Luigi Einaudi o del Buongoverno. soveria Mannelli: Rubbettino.
Side Chain-oxidized Oxysterols Regulate the Brain Renin-Angiotensin System through a Liver X Receptor-dependent Mechanism*

Disturbances in cholesterol metabolism have been associated with hypertension and neurodegenerative disorders. Because cholesterol metabolism in the brain is efficiently separated from plasma cholesterol by the blood-brain barrier (BBB), it is an unsolved paradox how high blood cholesterol can cause an effect in the brain. Here, we discuss the possibility that cholesterol metabolites permeable to the BBB might account for these effects. We show that 27-hydroxycholesterol (27-OH) and 24S-hydroxycholesterol (24S-OH) up-regulate the renin-angiotensin system (RAS) in the brain. Brains of mice on a cholesterol-enriched diet showed up-regulated angiotensin converting enzyme (ACE), angiotensinogen (AGT), and increased JAK/STAT activity. These effects were confirmed in in vitro studies with primary neurons and astrocytes exposed to 27-OH or 24S-OH, and were partially mediated by liver X receptors. In contrast, brain RAS activity was decreased in Cyp27a1-deficient mice, a model exhibiting reduced 27-OH production from cholesterol. Moreover, in humans, normocholesterolemic patients with elevated 27-OH levels, due to a CYP7B1 mutation, had markers of activated RAS in their cerebrospinal fluid. Our results demonstrate that side chain-oxidized oxysterols are modulators of brain RAS. Considering that levels of cholesterol and 27-OH correlate in the circulation and 27-OH can pass the BBB into the brain, we suggest that this cholesterol metabolite could be a link between high plasma cholesterol levels, hypertension, and neurodegeneration.
Photopolymer Electrolytes for Sustainable, Upscalable, Safe, and Ambient-Temperature Sodium-Ion Secondary Batteries.

The first example of a photopolymerized electrolyte for a sodium-ion battery is proposed herein. By means of a preparation process free of solvents, catalysts, purification steps, and separation steps, it is possible to obtain a three-dimensional polymeric network capable of efficient sodium-ion transport. The thermal properties of the resulting solid electrolyte separator, characterized by means of thermogravimetric and calorimetric techniques, are excellent for use in sustainable energy systems conceived for safe large-scale grid storage. The photopolymerized electrolyte shows a wide electrochemical stability window up to 4.8 V versus Na/Na(+) along with the highest ionic conductivity (5.1 mS cm(-1) at 20 °C) obtained in the field of Na-ion polymer batteries so far and stable long-term constant-current charge/discharge cycling. Moreover, the polymeric networks are also demonstrated for the in situ fabrication of electrode/electrolyte composites with excellent interfacial properties, which are ideal for all-solid-state, safe, and easily upscalable device assembly.
The longterm outcome of osteoarthritis: rates and predictors of joint space narrowing in symptomatic patients with knee osteoarthritis.

OBJECTIVE To determine the rate of progression of radiographic joint space narrowing (JSN) and the factors that predict it in symptomatic clinic patients with knee osteoarthritis (OA). METHODS In total 1,507 patients with knee OA were studied with extended weight-bearing anterior-posterior views of the knee as part of a longitudinal study of longterm outcomes of osteoarthritis (OA). Baseline demographic and severity measurements included body mass index (BMI), pain, global severity, Health Assessment Questionnaire disability, and erythrocyte sedimentation rate. Rates and predictors of progression were obtained by Kaplan-Meier survival analyses and Cox regressions using a JSN score of 3 as "failure. " RESULTS For the 1,232 patients who had not reached the endpoint narrowing score of 3 when first evaluated, the 75th and 50th survival times (time to JSN = 3) were 11.27 and 17.84 years for those with JSN = 0 at onset, 7.41 and 12.03 years for those with JSN = 1 at onset, and 4.49 and 7.44 years for those with JSN = 2 at onset. The corresponding yearly incidence rates for the 3 initial groups were 0.017, 0.032, and 0.077. In multivariate Cox models, initial JSN, BMI, symptom duration, and global severity were predictors of progression, but only JSN was a strong predictor. BMI predicted JSN in those with JSN = 0 at onset, but not in patients with more severe disease. Although contralateral JSN predicted progression, it was only of value with initial homolateral JSN scores of 0. Assessment of homolateral osteophytes aided prediction in patients with initial JSN = 0, but was of much less help when JSN had a higher severity score. CONCLUSION The risk of progression in clinical OA patients with radiographic abnormalities is substantial. Nonradiographic predictors of OA progression (e.g., BMI) are weak predictors of radiographic progression compared to current radiographic status. Rates of progression are greatest in those with established radiographic abnormalities. Osteophytes are of limited additional values once JSN = 2 is present. Contralateral radiographic abnormalities are useful predictors only in those with JSN = 0. Intervention studies to prevent radiographic progression probably should utilize joints where evidence of abnormality already exists. At a clinical level, current radiographic status predicts future status, with 50% of patients with JSN = 1 and 50% of patients with JSN = 2 progressing to complete joint space loss in 12.03 and 7.44 years, respectively.
Ex vivo release of eicosanoids after aneurysmal subarachnoid hemorrhage: a preliminary experience in humans 1

Authors addressed the question whether the byosynthesis and the release of specific eicosanoids may occur in human brain cortex, and if the qualitative pattern of arachidonic acid metabolism is similar to that observed in experimental SAH. Human brain samples from 18 patients operated on for anterior communicating artery aneurysm (5 unruptured aneurysms considered as control cases, 7 patients operated on between Days 1 and 4 after SAH and 6 patients operated on between Days 10 and 14) were studied for the ex vivo release of 4 selected eicosanoids (Prostaglandin D2, E2, 6‐keto‐PGF1a and Leukotriene C4). Levels of arachidonate metabolites were determined by radioimmunoassay technique. PGD2 release is significantly lower in cases operated on delayed phase if compared to both control cases (p < 0.05) and patients operated on in the acute phase, while there is no significant difference between the release of PGD2 in control cases and patients operated on in the acute phase. Release of 6‐keto‐PGF1a is significantly higher in patients operated on in a delayed phase (p < 0.03 vs patients operated on in the acute phase and p < 0.05 versus control cases). The release of LTC4 is significantly enhanced (p < 0.05) in cases operated on in the acute phase if compared with unruptured aneurysms. The release of PGE2 is significantly enhanced in patients operated on in the acute phase (p < 0.05) if compared to patients with unruptured aneurysm. These results firstly confirm that in human brain tissue arachidonate metabolism is significantly enhanced after SAH, and suggest that the enhanced AA metabolism would be considered as an indirect ex vivo demonstration of the increased peroxidative processes caused by SAH.
A MACROECONOMIC BASELINE WITH STRUCTURAL CHANGE

Paper's Objectives : To develop a baseline for examining environmental impacts for a long-term horizon (to 2030). The baseline makes specific assumptions concerning prospects for sectoral labour productivity. The motivation is that in the previous version of the JOBS model, the baseline scenario assumed the same productivity growth in, for instance, manufacturing and service sectors. As a matter of fact historical data does not confirm such an assumption, so as long as the different sectors will be more or less “labour-saving” (or “capital- saving” or “energy-saving”) in the future the impacts on environmental impacts will be different. Methodology : Undertake simulations on a macroeconomic model called “JOBS” which was developed at the OECD. This is a global recursive dynamic computable general equilibrium model that captures international trade. Historically this model is a modified version of the LINKAGE model (World Bank) but with a focus on environmental issues. It is implemented using GAMS software. Database : This version of the model is based on Version 6 of the GTAP dataset. Others databases are used, especially to implement and calibrate prospective scenarios built from population and economic trends and parameters. Among them : United nation population prospects, ILO active population rates, OECD STAN database for sector specifics labour productivity, IEA data for energy efficiency improvements. Anticipated findings : Calculation of endogenous structural change and its implications under assumptions regarding the evolution of sectoral labour productivity.
A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps

In this article, we advance a hypothesis for the rupture of thin fibrous cap atheroma, namely that minute (10-μm-diameter) cellular-level microcalcifications in the cap, which heretofore have gone undetected because they lie below the visibility of current in vivo imaging techniques, cause local stress concentrations that lead to interfacial debonding. New theoretical solutions are presented for the local stress concentration around these minute spherical inclusions that predict a nearly 2-fold increase in interfacial stress that is relatively insensitive to the location of the hypothesized microinclusions in the cap. To experimentally confirm the existence of the hypothesized cellular-level microcalcifications, we examined autopsy specimens of coronary atheromatous lesions using in vitro imaging techniques whose resolution far exceeds conventional magnetic resonance imaging, intravascular ultrasound, and optical coherence tomography approaches. These high-resolution imaging modalities, which include confocal microscopy with calcium-specific staining and micro-computed tomography imaging, provide images of cellular-level calcifications within the cap proper. As anticipated, the minute inclusions in the cap are very rare compared with the numerous calcified macrophages observed in the necrotic core. Our mathematical model predicts that inclusions located in an area of high circumferential stress (>300 kPa) in the cap can intensify this stress to nearly 600 kPa when the cap thickness is <65 μm. The most likely candidates for the inclusions are either calcified macrophages or smooth muscle cells that have undergone apoptosis.
Cognitive-Behavioral Therapy Plus Healthy Lifestyle Enhancement for Depressed, Overweight/Obese Adolescents: Results of a Pilot Trial

The objective of this article was to conduct a treatment development study to examine the feasibility, acceptability, and preliminary efficacy of treating depressed, overweight/obese adolescents using both an exercise regimen and a Cognitive Behavioral Therapy (CBT) protocol modified to address aspects of healthy living and nutrition (CBT plus healthy lifestyle; CBT-HL). A randomized controlled repeated measures design was used to test the hypothesis that CBT-HL would lead to greater reductions in depressed mood and weight compared to CBT for Depression Only (CBT). Participants (n=33; 24 in CBT-HL condition) included 33 adolescents (median age 15, 73% female, 61% white, 36% Hispanic) who met DSM-IV criteria for Current Major Depressive Episode (MDE) and had BMI ≥ 85th percentile. CBT-HL was found to be feasible to implement with most adolescents. Both conditions resulted in improvement in depressed mood. The CBT-HL protocol was more effective in stabilizing weight status as assessed by BMI. Percent time spent in MVPA was increased at 12 weeks for adolescents in CBT-HL compared to those in CBT. The CBT-HL protocol was acceptable to most, but not all, adolescents, and resulted in an improvement in depressed mood as well as stabilization of weight status. A larger study to test efficacy and moderators of treatment outcome is necessary to better understand which adolescents would benefit most from the increased demands of exercise and adhering to nutrition recommendations in addition to standard CBT for depression. Revisions to the treatment protocol to support weight loss, not just stabilization, are also suggested.
Human in vivo study of the renin–angiotensin–aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk

Objective: Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin‐converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk.
Probability predictions of currency movements: Judgement and technical analysis

INTRODUCTION For the effective use of technical analysis in the volatile environment of the world’s financial markets, it is important to realise: 1. the critical role played by human judgement, and 2. the need to enhance the analyst’s ability to express this judgement in a probabilistic form. Chartist techniques, which form the basis for technical analysis, are effectively based on human judgement. Currency movements are heavily influenced by prevailing market sentiments that manifest themselves via varying levels of optimism, pessimism and differing degrees of uncertainty in the minds of market participants. It is this mindset that the Chartist approach aims to capture by examining patterns in the time path of exchange rates. The efficient use of judgement in extracting information from the plethora of pattern swings and volume spikes requires not only an interpretation of the predicted movement (direction of change) but also an associated probability assessment (probability of a rise or fall) which accompanies the prediction. There is, therefore, a need for technical analysis techniques to express financial price movements in a probabilistic form. This can be achieved by calculating moving period estimated probabilities (EPs) from first differences in the logarithms over a specified period. EPs are based on the assumption that for a short number of data points (e.g., less than 50 days for daily data) the changes in the logarithms of currency series will be approximately Normally distributed with a stable mean and standard deviation. Over a longer range of data points, however, the distribution can be subject to changing means and standard deviations due to the influences of optimism, pessimism and uncertainty. In contrast to simple directional predictions or buy and sell statements, probability statements convey much more comprehensive and effective information to the user. Probability statements, provided by analysts, need to be made in a framework that incorporates information on the nature and characteristics of exchange rate series. There are several issues that need to be considered in relation to the making of probability statements regarding currency movements. It is necessary to have a clear structure in the formation of probability statements, that is, to have a clear and appropriate statistical distribution in mind and to be able to form statements regarding the relevant parameters of the distribution. It is also necessary that, when the resulting probability statements have been formed, procedures are available to evaluate the accuracy and validity of probability predictions at the end of the predictive horizon. This provides valuable feedback that can be used to improve future probability predictions. EPs provide a natural method on which an analyst can base his/her judgemental probability predictions in a form that is consistent with the framework. These issues are examined below.