Miracle-dz/UniFAR-FTUs huggingface dataset:
Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer.

PURPOSE Cisplatin concomitantly administered with radiotherapy is increasingly used in locally advanced head and neck squamous cell carcinoma. We aimed to compare the incidence of hearing loss between patients treated with intra-arterial high-dose cisplatin chemoradiation with sodium thiosulfate (CRT-IA) and intravenous high-dose cisplatin chemoradiation without sodium thiosulfate (CRT-IV). PATIENTS AND METHODS We conducted a prospective analysis of hearing thresholds at low and (ultra-) high frequencies obtained before, during, and after treatment in 158 patients. Patients were randomly assigned for either CRT-IA (150 mg/m(2), four courses) with sodium thiosulfate cisplatin neutralization or CRT-IV (100 mg/m(2), three courses) without rescue. All patients received concomitant radiation therapy (RT; 70 Gy). RESULTS CRT-IA resulted in approximately 10% less hearing loss at frequencies vital for speech perception, compared with CRT-IV (P < .001). In CRT-IA, fewer ears qualified for hearing aids (36% v 49%; P = .03). However, in both treatment arms, the incidence expressed in National Cancer Institute Common Terminology Criteria of Adverse Events (version 3) did not deviate (P > .14). Age, cumulative cisplatin dose, cumulative RT dose, and the considered frequency area determine the degree of hearing loss (P < .001). Cisplatin induced increasing hearing loss of 24% to 60% with increasing frequencies. RT induced hearing loss at speech frequencies of 9% to 12%. CONCLUSION Depending on the criteria used to assess hearing loss due to treatment, differences in ototoxicity between CRT-IA and CRT-IV were found in favor of CRT-IA. It is desirable to specify hearing loss criteria toward frequencies vital for speech perception, and to refine grading scales to reveal subtle and clinically relevant dissimilarities in ototoxicity between different treatment protocols.
Identification, Timing, and Signal Specificity of Pseudomonas aeruginosa Quorum-Controlled Genes: a Transcriptome Analysis

ABSTRACT There are two interrelated acyl-homoserine lactone quorum-sensing-signaling systems in Pseudomonas aeruginosa. These systems, the LasR-LasI system and the RhlR-RhlI system, are global regulators of gene expression. We performed a transcriptome analysis to identify quorum-sensing-controlled genes and to better understand quorum-sensing control of P. aeruginosa gene expression. We compared gene expression in a LasI-RhlI signal mutant grown with added signals to gene expression without added signals, and we compared a LasR-RhlR signal receptor mutant to its parent. In all, we identified 315 quorum-induced and 38 quorum-repressed genes, representing about 6% of the P. aeruginosa genome. The quorum-repressed genes were activated in the stationary phase in quorum-sensing mutants but were not activated in the parent strain. The analysis of quorum-induced genes suggests that the signal specificities are on a continuum and that the timing of gene expression is on a continuum (some genes are induced early in growth, most genes are induced at the transition from the logarithmic phase to the stationary phase, and some genes are induced during the stationary phase). In general, timing was not related to signal concentration. We suggest that the level of the signal receptor, LasR, is a critical trigger for quorum-activated gene expression. Acyl-homoserine lactone quorum sensing appears to be a system that allows ordered expression of hundreds of genes during P. aeruginosa growth in culture.
RNA‐DNA hybrid formation at the human mitochondrial heavy‐strand origin ceases at replication start sites: an implication for RNA‐DNA hybrids serving as primers.

Critical elements of a mammalian mitochondrial DNA heavy‐strand replication origin include a promoter and three downstream conserved sequence blocks (CSBIII, CSBII and CSBI). We found recently that a stable and persistent RNA‐DNA hybrid forms during in vitro transcription at Saccharomyces cerevisiae mitochondrial origins; hybrid formation was dependent on the conserved CSBII element. We report here that during in vitro transcription with human mitochondrial RNA polymerase, stable and persistent RNA‐DNA hybrid formation is also evident at the human mitochondrial heavy‐strand origin. As predicted, hybrid formation was dependent on the GC‐rich CSBII element. The human RNA‐DNA hybrids terminate within or downstream of CSBI at locations implicated in initiation of mitochondrial DNA replication. Interestingly, efficient hybrid formation in the human system is influenced by sequence 5′ to the RNA‐DNA hybrid, including the CSBIII element. These results suggest that the RNA‐DNA hybrids formed during transcription across the mitochondrial DNA heavy‐strand origin provide RNA primers for initiation of mitochondrial DNA replication.
Three Essays on Trading by Members of Congress

Three Essays on Trading by Members of Congress Serkan Karadas My dissertation examines the information content of stock trades by members of Congress (politicians) in three separate essays. In my first essay, based on approximately 62,000 common stock transactions over the 2004-2010 period, I present evidence that past firm-level trading activity by politicians predicts future firm-level stock returns, and this prediction is stronger for the pre-recession period and for small firms. By constructing buy-minussell transactions-based portfolios, I document that the portfolios of Republicans outperform those of Democrats. Also, being a powerful member of Congress is associated with substantially higher abnormal returns for Republicans, but not for Democrats. Among powerful Republicans, the portfolios of unsophisticated traders perform significantly better than those of sophisticated ones with abnormal returns exceeding 34% on annual basis under one-week holding period. The abnormal returns in general disappear beyond three-month holding period suggesting that politicians trade on time-sensitive value-relevant information. This study contributes to the literature showing that power, party membership, and investor sophistication are important determinants of the abnormal returns in congressional stock portfolios. In my second essay, I , for the first time in the literature, separately examine the performance of common stock transactions of politicians and their family members (spouses and dependent children). I document that the transactions by both politicians and spouses contain value-relevant information, but the content of information is less time-sensitive for spouses. On the other hand, the transactions in the accounts of the dependent children perform very poorly. I also present evidence that the transactions in tax-deferred accounts such as 401(k)s contain less information than those in taxable trading accounts for both politicians and their spouses. I finally show that the portfolios of the powerful politicians’ spouses outperform those of the non-powerful politicians’ spouses. These results suggest that members of Congress take advantage of their informational advantage trading through the accounts of their spouses. My third essay examines the properties of aggregate congressional trading. I investigate the ability of aggregate trading activity by members of Congress to predict stock market returns using 77,663 stock transactions over the 2004-2010 period. I find that aggregate congressional trading predicts excess market returns 2 to 3 months in advance. These findings imply that politicians, similar to corporate insiders, trade on information containing macroeconomic components.
Catch-up in nanotechnology industry in China from the aspect of process-based innovation

Nanotechnology is frequently heralded as an emerging strategic industry in developed and developing countries. However, little is known about the catch-up of companies in emerging industries like the nanotechnology industry in developing countries, such as China. From the perspective of process-based innovation proposed by Linton and Walsh, this paper explores the catch-up process and role of process-based innovation in nanotechnology companies. The research reveals the catch-up process in emerging industries in developing countries is different from the original Utterback and Abernathy (U–A) model and Kim’s model, the reverse U–A model, and confirms the model proposed by Linton and Walsh. Innovation in the catch-up process in emerging industries in developing countries follows the same stages as that in advanced countries, but there is a time delay in the start of commercialisation. The research showcases a large role for competitiveness derived from owning critical technology in the production process (process-based innovation) in the catch-up process. This research contributes to the catch-up theory and catch-up in emerging industries, such as nanotechnology industry.
White matter changes in healthy elderly persons correlate with attention and speed of mental processing.

OBJECTIVE To evaluate the association between white matter changes (leukoaraiosis [LA]) seen on magnetic resonance imaging and cognitive functions. DESIGN Survey of cohorts of neurologically healthy elderly subjects derived consecutively from a population-based random sample. SETTING General community, the Helsinki (Finland) Aging Brain Study. SUBJECTS Cohorts of neurologically healthy subjects aged 55, 60, 65, 70, 75, 80, and 85 years (n = 20, 18, 19, 18, 17, 17 and 11 subjects, respectively; total N = 120). MEASURES Leukoaraiosis was rated in the periventricular areas (0 to 24) and the centrum semiovale (0 to 24); also, a total LA score was obtained (0 to 48). The neuropsychological test battery covered memory, verbal intellectual and constructional functions, language, speed and attention, and speed of mental processing, as well as simple psychomotor speed. RESULTS Low age-related LA scores and deterioration of cognitive functions were obtained in the normal subjects. When controlling for age, we found that speed and attention, together with the speed of mental processing measured by the Trail Making A and the Stroop tests, correlated with the total LA score. However, there was wide variation between subjects. Comparing groups with and without LA proved the association of LA with Trail Making A time, Stroop test result (words/time and difference/time), and the compound score of speed and attention. Presence of periventricular LA was especially related to speed of mental processing. CONCLUSION Leukoaraiosis could explain some of the intellectual impairment in the elderly, especially that of slowing of distinct motor and attentional functions, as well as slowing of mental processing. Mild LA in normal aged subjects could also signal brain at risk for further cognitive impairment.
TDOA-Based Source Localization With Distance-Dependent Noises

This paper focuses on the problem of source localization using time-difference-of-arrival (TDOA) measurements in both 2-D and 3-D spaces. Different from existing studies where the variance of TDOA measurement noises is assumed to be independent of the associated source-to-sensor distances, we consider the more realistic model where the variance is a function of the source-to-sensor distances, which dramatically complicates TDOA-based source localization. After formulating the distance-dependent noise model, we prove that using the extra information about the source location in the functional variance improves the estimation accuracy of TDOA-based source localization, but contributes little under a sufficiently small noise level. Further, we theoretically analyze the problem of optimal sensor placement, and derive the necessary and sufficient conditions for optimizing localization performance under different circumstances. Then, a localization scheme based on the iteratively reweighted generalized least squares (IRGLS) method is proposed to efficiently exploit the extra source location information. Finally, a simulation analysis confirms our theoretical studies, and shows that the performance of the proposed localization scheme is comparable to the Cramer-Rao lower bound (CRLB) given moderate TDOA measurement noises.
The evolution in theories of the brain drain and the migration of skilled personnel 1

Migrations have ever since been one of the most important phenomenon of human civilisation. It is therefore quite natural that social sciences have been interested in studying them since their origin. Until the end of the Second World War, migrants came from the poorest and less educated classes of their country of origin, and on these people all the first academic surveys were focused. The high qualified migrants were very rare, and often were or very relevant in historical or cultural terms and therefore considered as the topic for a biographical study of a singular case rather then for a wide scientific analysis. After the end of the War the way of production changed dramatically and started to include innovations stemming out of general scientific and technological development; the number and the economic importance of migrations of highly qualified people increased due also to the radical changes of the political and social international picture. These migrations started to get the interest of researchers starting from the first relevant case: the departure from Germany and Italy of scientists persecuted for political and racial reasons during the nazi and fascist dictatorships. It was very evident that this exodus had a strong effect on the economic and military potential both of origin and receiving countries (Huges, 1970). However the changes in socio-economic realities over the past 50 years have brought a strong evolution of the issues surrounding the migration of highly-qualified workers.
Seronegative myasthenia gravis: A plasma factor inhibiting agonist‐induced acetylcholine receptor function copurifies with IgM

Anti—acetylcholine receptor antibodies cannot be detected by standard radioimmunoassay in 10 to 15% of patients with generalized myasthenia gravis (seronegative myasthenia gravis). We investigated the effect of seronegative myasthenia gravis plasma on 22Na+ flux through acetylcholine receptors and voltage‐gated sodium channels in the human rhabdomyosarcoma cell line, TE671. Fourteen of 19 seronegative MG plasmas inhibited acetylcholine receptor 22Na+ flux; none inhibited voltage‐gated sodium channel flux. The inhibitory activity was found in the IgG‐depleted fraction, and copurified with IgM after gel‐filtration chromatography. Inhibitory activity was absent from the plasma of 8 healthy control subjects and of 6 patients with the Lambert‐Eaton myasthenic syndrome, but was present in the IgG‐depleted plasma fraction of 4 of 6 seropositive patients with myasthenia gravis and all 5 patients with demyelinating polyneuropathy. We conclude that a low‐affinity serum factor, probably an IgM antibody, found in a high proportion in patients with seronegative and those with seropositive myasthenia gravis may contribute to the muscle weakness in myasthenia gravis, but its role in these and other neuroimmunological disorders requires further investigation.
Complement C3a-Induced IL-17 Plays a Critical Role in an IgE-Mediated Late-Phase Asthmatic Response and Airway Hyperresponsiveness via Neutrophilic Inflammation in Mice

Allergen-specific IgE plays an essential role in the pathogenesis of allergic asthma. Although there has been increasing evidence suggesting the involvement of IL-17 in the disease, the relationship between IL-17 and IgE-mediated asthmatic responses has not yet been defined. In this study, we attempted to elucidate the contribution of IL-17 to an IgE-mediated late-phase asthmatic response and airway hyperresponsiveness (AHR). BALB/c mice passively sensitized with an OVA-specific IgE mAb were challenged with OVA intratracheally four times. The fourth challenge caused a late-phase increase in airway resistance associated with elevated levels of IL-17+CD4+ cells in the lungs. Multiple treatments with a C3a receptor antagonist or anti-C3a mAb during the challenges inhibited the increase in IL-17+CD4+ cells. Meanwhile, a single treatment with the antagonist or the mAb at the fourth challenge suppressed the late-phase increase in airway resistance, AHR, and infiltration by neutrophils in bronchoalveolar lavage fluid. Because IL-17 production in the lungs was significantly repressed by both treatments, the effect of an anti–IL-17 mAb was examined. The late-phase increase in airway resistance, AHR, and infiltration by neutrophils in bronchoalveolar lavage fluid was inhibited. Furthermore, an anti–Gr-1 mAb had a similar effect. Collectively, we found that IgE mediated the increase of IL-17+CD4+ cells in the lungs caused by repeated Ag challenges via C3a. The mechanisms leading to the IgE-mediated late-phase asthmatic response and AHR are closely associated with neutrophilic inflammation through the production of IL-17 induced by C3a.
Are Investors Rational When Valuing Loss Firms?

ABSTRACT The authors examine whether high valuation of loss firms really exists and can be explained by behavioral factors. This valuation may originate from irrational behavior of optimistic investors who prefer lottery-like stocks, or from rational expectations of firms' profitability. Using a sample of small Canadian firms going public, the authors show that both individual investors and underwriters price loss firms higher than profit firms, everything being equal. Post-IPO 3-year underperformance does not differ statistically between loss and profit firms. Investors thus apparently behave irrationally for all firms, but their irrationality does not seem greater for loss firms.
A Skin Color Mutation of Grapevine, from Black-Skinned Pinot Noir to White-Skinned Pinot Blanc, Is Caused by Deletion of the Functional VvmybA1 Allele

A white-wine grape, Pinot Blanc, is thought to be a white-skinned mutant of a red-wine grape, Pinot Noir. Pinot Noir was heterozygous for VvmybA1. One allele was the non-functional VvmybA1a, and the other was the functional VvmybA1c. In Pinot Blanc, however, only VvmybA1a was observed, and the amount of VvmybA1 DNA in Pinot Blanc was half that in Pinot Noir. These findings suggest that deletion of VvmybA1c from Pinot Noir resulted in Pinot Blanc.
Produce Retail Price Volatility and Perceptions in the Canadian Market: Nutrition Security Variances

ABSTRACT Nutrition security has been studied but rarely in the context of a developed economy. Furthermore, few studies have looked at how fluctuating produce process may influence nutrition security and how consumers cope with abrupt macro-economic changes. Between 2014 and 2015, Canadian consumers saw produce prices jump by more than 25% in a year in some cases. This exploratory survey looks at socioeconomic factors and evaluates how price increases influence produce consumption and substitution. A total of 1007 respondents participated in a cross national survey over a two-week period. Results show that lower income households are more vulnerable than higher income respondents. Results also explore a few more behavioral factors such as where produce shopping occurs and how market data is gathered before purchases. Respondents who consult flyers and use apps are more likely to behave rationally and cope with changing prices. Some limitations are presented. And finally, future research thrusts related to produce price fluctuations and nutrition security are suggested.
Protective effect of L‐carnitine and L‐arginine against busulfan‐induced oligospermia in adult rat

Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L‐carnitine and L‐arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L‐arginine (Bus + L‐arg) and busulfan plus L‐carnitine (Bus + L‐car). After 28 days, the semen was collected from the epididymis and the testes were assessed. Sperm count, motility and velocity were measured by CASA, and smears were prepared for assessment of sperm morphology. Serum and testes supernatants were separated for DNA metabolites, oxidative stress and cell energy parameters. Testes tissues also subjected for caspase‐3. The results showed significant improvement in sperm morphology, motility, velocity and count in the groups treated with L‐arginine and L‐carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in GSH, AMP, ADP, NO and 8‐OHDG also recorded. These results are supported by caspase‐3. Conclusions: Administration of L‐arg and L‐car attenuated the cytotoxic effects of busulfan by improving semen parameters, reducing oxidative stress and maintaining cell energy.
Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia.

Anaesthesia-induced malignant hyperthermia (MH) may be caused by specific gene defects in the skeletal muscle ryanodine receptor. We have studied the frequency of occurrence of the C1840T mutation, analogous to the porcine mutation, and three mutations associated both with MH and central core disease (G7301A, C487T and C1209G). We investigated skeletal muscle specimens from up to 137 patients testing negative and 101 patients testing positive for MH susceptibility by the North American MH Group protocol. The presence or absence of the mutations was determined by polymerase chain reaction and restriction enzyme digestion. The frequencies of occurrence of the C1840T and C487T mutations were 2% and 1%, respectively, in MH-positive subjects and were the only two mutations identified. One subject with central core disease did not have any of the three mutations examined associated with this disorder. Therefore, the porcine and central core disease-associated mutations examined in the ryanodine receptor account for a small proportion (approximately 3%) of MH-positive diagnoses. The mutations examined did not occur in any of the MH-negative patients, supporting an association between defects in the ryanodine receptor and a positive diagnosis for MH. (ABSTRACT TRUNCATED AT 250 WORDS)