Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional response to circumscribed cortical brain ischemia: spatiotemporal patterns in ischemic vs. remote non‐ischemic cortex

Focal brain infarcts are surrounded by extended perilesional zones that comprise the partially ischemic penumbra but also completely non‐ischemic cortex of the remote ipsilateral hemisphere. To delineate the impact of lesion‐associated vs. remote processes on transcriptional programming after focal ischemia, we used cDNA array analysis, quantitative real‐time polymerase chain reaction and immunohistochemistry in the photothrombosis model of circumscribed cortical ischemia in rats. At an early stage of 4 h after ischemia, gene induction occurred to a similar extent in the ischemic infarct and remote non‐ischemic cortex of the ipsilateral hemisphere. Among the genes induced in non‐ischemic cortex we found the NGF‐inducible genes PC3, VGF and Arc, the transcriptional regulators IκB‐α and Stat3, and the β‐chemokine MIP‐1α (CCL3). At 3 days, the spatial pattern of gene expression had changed dramatically with brain fatty acid‐binding protein as the only gene significantly induced in non‐ischemic ipsilateral cortex. In contrast, numerous genes were exclusively regulated at the lesion site, comprising genes involved in cell cycle regulation, proteolysis, apoptosis, lipid homeostasis and anti‐inflammatory counter‐regulation. Cortical spreading depression was identified as the main mechanism underlying gene induction in remote non‐ischemic cortex. Our data demonstrate a dynamic spatiotemporal pattern of gene induction, which may contribute to delayed progression of damage or, alternatively, mediate neuroprotection, tissue remodeling and functional compensation.
Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence.

OBJECTIVE This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence. METHOD Fifty-one treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, choline-containing compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classified as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest. RESULTS Resumers demonstrated significantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest. CONCLUSIONS The significantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite differences between abstainers and light-drinking nonsmoking controls suggests premorbid factors potentially contributed to the baseline brain metabolite abnormalities observed in resumers.
Synergistic effect of rapamycin and cisplatin in endometrial cancer cells

Mammalian target of rapamycin (mTOR) inhibitors modulate signaling pathways involved in cell cycle progression, and phase 2 trials for endometrial cancer are currently being conducted. Because rapamycin is known to enhance the cytotoxicity of chemotherapeutic drugs, the authors' goal was to examine the effects of rapamycin and cisplatin in endometrial cancer cell lines.
The Effect of Glucocorticosteroid Treatment on Dentine Formation in the Lewis Rat, A Histological Study

Abstract Glucocorticosteroids are widely used in the treatment of chronic illnesses and have been reported to cause premature obliteration of the pulp space. During the active stages of dentinogenesis, odontoblasts are growth hormone receptor (GHr) positive. The aims of this study were to determine if the glucocorticosteroid, prednisone, affected the rate of dentine deposition and odontoblast expression of GHr in the rat molar. Following subcutaneous injection of 0.05 mg/kg, 1.0 mg/kg or 5.0 mg/kg prednisone for 20 days, immature and mature molars from rats aged 3 and 6 weeks respectively, were examined histologically. Distribution of GHr expression was determined immunohistochemically. No morphological differences were observed in molars from prednisone treated animals. Prednisone did not appear to enhance dentine deposition in immature molars but in mature molars significantly increased dentine deposition on the roof of the pulp chamber at a dosage of 5.0mg/kg (p > 0.001). In all immature molars, odontoblasts and pulp cells expressed GHr immunoreactivity. In mature molars, odontoblasts and pulpal cells from controls did not show GHr immunoreactivity. However, odontoblasts and pulp cells were GHr immunoreactive in mature molars from animals treated with prednisone.
Identification of an Adeno-Associated Virus Rep Protein Binding Site in the Adenovirus E2a Promoter

ABSTRACT Adeno-associated virus (AAV) and other parvoviruses inhibit proliferation of nonpermissive cells. The mechanism of this inhibition is not thoroughly understood. To learn how AAV interacts with host cells, we investigated AAV's interaction with adenovirus (Ad), AAV's most efficient helper virus. Coinfection with Ad and AAV results in an AAV-mediated inhibition of Ad5 gene expression and replication. The AAV replication proteins (Rep) activate and repress gene expression from AAV and heterologous transcription promoters. To investigate the role of Rep proteins in the suppression of Ad propagation, we performed chromatin immunoprecipitation analyses that demonstrated in vivo AAV Rep protein interaction with the Ad E2a gene promoter. In vitro binding of purified AAV Rep68 protein to the Ad E2a promoter was characterized by electrophoretic mobility shift assays (Kd = 200 ± 25 nM). A 38 bp, Rep68-protected region (5′-TAAGAGTCAGCGCGCAGTATTTACTGAAGAGAGCCT-3′) was identified by DNase I footprint analysis. The 38-bp protected region contains the weak E2a TATA box, sequence elements that resemble the Rep binding sites identified by random sequence oligonucleotide selection, and the transcription start site. These results suggest that Rep binding to the E2a promoter contributes to the inhibition of E2a gene expression from the Ad E2a promoter and may affect Ad replication.
Variations in ocular biometry in an adult Chinese population in Singapore: the Tanjong Pagar Survey.

PURPOSE To describe the variation in ocular biometry in adult Chinese individuals in Singapore. METHODS This study was a population-based, cross-sectional survey of adult Chinese persons aged 40 to 81 years residing in Tanjong Pagar district, Singapore. Axial ocular dimensions, including axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and vitreous chamber depth (VCD) were measured using an A-scan ultrasound device. Corneal curvature (CC) and noncycloplegic refraction were measured with an autorefractor, with refraction further refined subjectively. Lens nuclear opacity (NO) was graded clinically using the modified Lens Opacity Classification System III (LOCS III) score. RESULTS A total of 1717 subjects were eligible for the survey, of whom 1232 (71.8%) participated. Biometric and refraction data were available for 1004 (58.5%) phakic subjects. The AL, ACD, LT, VCD, CC, and LOCS III scores were 23.23 +/- 1.17 mm, 2.90 +/- 0.44 mm, 4.75 +/- 0.47 mm, 15.58 +/- 1.11 mm, 7.65 +/- 0.27 mm, and 3.2 +/- 0.9 (mean +/- SD), respectively. On average, people aged 40 to 49 years, when compared with those 70 to 81 years, had longer ALs (mean difference, +0.58 mm), deeper ACDs (+0.52 mm), longer VCDs (+0.72 mm), but thinner lenses (-0.70 mm) and less severe NO (-1.7 LOCS III score). CCs did not vary significantly with age. After controlling for age, women had shorter ALs and VCDs, shallower ACDs, but thicker lenses and steeper CCs than men. The variation in noncycloplegic refraction with age was nonlinear. Among people aged 40 to 59 years, a higher prevalence of hyperopia was seen in older compared with younger persons (on average, a difference of +1.3 D for every 10-year difference in age, P: < 0.001), explained principally by shorter AL (and VCD) in older persons. Among those 60 to 81 years, this pattern was not obvious (a difference of -0.03 D for every 10-year difference in age, P: = 0.12), as NO became an additional determinant of refraction, with greater degrees of NO in older person's driving refraction in the "minus" direction. CONCLUSIONS Ocular dimensions vary with age and gender in adult Chinese persons in Singapore. The variation in noncycloplegic refraction in people 40 years and older may be explained by differences in axial lengths (principally vitreous chamber depths) between older and younger persons and, from 60 years onwards, differences in lens nuclear opacification as well.
Memory and Metamemory Performance in Older Adults: One Deficit or Two?

In two separate experiments, three groups of older adults (50–80 years old) were shown lists of forename-surname pairs. At test subjects were cued with the surname and asked whether they knew the forename (prospective evaluation). Subjects attempted recall for those items they claimed to know and rated their confidence in their answer (retrospective evaluation). In Experiment 1 subjects saw the name list on 5 successive occasions and attempted recall after each. The older subjects recalled fewer items, but there were no age differences on retrospective memory evaluation. There was a marginally significant age effect on the prospective memory evaluation, which on closer inspection appeared to be a scaling effect related to recall performance. Experiment 2 verified this conclusion in a sample of older adults taking part in a training study extended over many weeks. The main implication of this work is that studies that compare metamemory accuracy in groups that differ in baseline memory performance should be careful before drawing conclusions about metamemory independently of memory performance.
International tourists' risk perception towards terrorism and political instability. The case of Tunisia

INTERNATIONAL TOURISTS’ RISK PERCEPTION TOWARDS TERRORISM AND POLITICAL INSTABILITY: THE CASE OF TUNISIA Ngoc Bich Pham Advisor: University of Guelph, 2016 Professor Marion Joppe The purpose of this study was to find out changes in international tourists’ risk perception towards Tunisia during the period from 2010 to 2015. Content analysis was employed to analyze posts of (potential) tourists in TripAdvisor forum. The findings showed tourists mostly heightened awareness during the time of the Arab Spring Revolution & the three terrorist attacks in 2015, and only during the first month after an incident. Terrorism-related risk received higher attention than political risk did. Risk perception of tourists towards terrorism and political instability in term of travelling to Tunisia was also revealed. The study emphasized the role of social media in influencing and reflecting tourists’ risk perception. The influence of government issued travel advisories on tourist’s risk perception and decision to visit was marked. Practical implication of the study is the suggestions for the Tunisian government and DMOs to mitigate negative impact on tourism industry.
The World Rushed In: The California Gold Rush Experience

Centered around the diaries and letters of William Swain, a New Yorker who sought his fortune in the 1849 California gold rush, this revealing volume is one of the best first-hand accounts recently published. The author devoted nearly thirty years in collecting and editing the materials. He has blended these accounts with scores of others and provides excellent background chapters on the 'origins and development of gold mining in California. Beautifully illustrated with contemporary drawings from the notebooks of J. Goldsborough Bruff (whose diary has also been used), this book should remain as a classic among the literature of the '49er movement.
Effects of cognitive workload on speech production: acoustic analyses and perceptual consequences.

The present investigation examined the effects of cognitive workload on speech production. Workload was manipulated by having talkers perform a compensatory visual tracking task while speaking test sentences of the form "Say hVd again. " Acoustic measurements were made to compare utterances produced under workload with the same utterances produced in a control condition. In the workload condition, some talkers produced utterances with increased amplitude and amplitude variability, decreased spectral tilt and F0 variability and increased speaking rate. No changes in F1, F2, or F3 were observed across conditions for any of the talkers. These findings indicate both laryngeal and sublaryngeal adjustments in articulation, as well as modifications in the absolute timing of articulatory gestures. The results of a perceptual identification experiment paralleled the acoustic measurements. Small but significant advantages in intelligibility were observed for utterances produced under workload for talkers who showed robust changes in speech production. Changes in amplitude and amplitude variability for utterances produced under workload appeared to be the major factor controlling intelligibility. The results of the present investigation support the assumptions of Lindblom's ["Explaining phonetic variation: A sketch of the H&H theory," in Speech Production and Speech Modeling (Klewer Academic, The Netherlands, 1990)] H&H model: Talkers adapt their speech to suit the demands of the environment and these modifications are designed to maximize intelligibility.
Urinary Prostasin: A Possible Biomarker for Renal Pressure Natriuresis in Black Adolescents

Prostasin is a membrane-bound/secretive serine protease interacting with aldosterone and the epithelial sodium channel in the kidney. We and others have previously proposed the concept of stress-induced pressure natriuresis (SIPN) where increased urinary sodium excretion (UNaV) is coupled with elevated blood pressure (BP) in response to behavioral stress in normotensive adolescents. This study thus aimed to test the relationship between prostasin and pressure natriuresis using the SIPN model. A cohort of 102 normotensive black adolescents (mean age: 17.0 ± 1.2 y; 56% females) were placed on a controlled sodium (4000 ± 200 mg/d) and potassium (2600 ± 200 mg/d) diet for three days before testing. The SIPN protocol consisted of a 1-h baseline period, a 1-h stress period (competitive video game), and a 1-h recovery period. During the stress period, BP elevation was coupled with an increase in UNaV. Urinary prostasin concentration had more than a 2-fold reduction from baseline (38.4 ± 32.7 ng/mL) to stress (17.2 ± 16.0 ng/mL), and further declined during recovery (12.1 ± 16.2 ng/mL) (p < 0.001). Urinary prostasin was inversely correlated with UNaV during stress (r = −0.43, p = 0.0001), even after being normalized by urinary creatinine. Our data suggest that urinary prostasin could be a novel biomarker and/or mechanism for renal pressure natriuresis in normotensive black adolescents.
Enhancing Retrieval and Ranking Performance for Media Search Engine by Deep Learning

Deep learning has emerged as a powerful technique to uncover deep structured, nonlinear features for various information processing tasks, such as image processing, speech recognition, and information retrieval. In this paper, we introduce a framework of utilizing a Deep Structured Semantic Model (DSSM) to build similarity features to enhance search engine relevance. To illustrate the effectiveness of the proposed deep learned similarity features, we applied our method to an Xbox Media Search Engine. Specifically, we leverage a large-scale Bing web search log to train a generic DSSM. We then tune the DSSM parameters - making the model specific to media search - by using a training dataset from the Xbox Media Search Engine. Finally, we conduct a series of experiments in building Xbox search engine with and without the proposed DSSM similarity features. Our experiment results show that adding DSSM-based similarity features significantly improves the retrieval and ranking performance.
DNA mismatch repair as an effector for promoting phorbol ester‐induced apoptotic DNA damage and cell killing: Implications in tumor promotion

Phorbol ester was known to activate protein kinase C (PKC) and exert numerous cellular effects, including proliferation, apoptosis, and oncogenic transformation. How phorbol ester stimulates both apoptosis and tumor promotion is not clear. Here DNA mismatch repair (MMR)‐proficient human colon cancer cells (DLD‐1+Ch2; hMSH6+) treated with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) undergo rapid cell death, which is significantly abolished by staurosporine (PKC inhibitor) or antioxidant, compared with the paired MMR‐deficient (DLD‐1; hMSH6−) cells. Induction of reactive oxygen species (ROS) by TPA is shown to be one of downstream effectors required, but not sufficient, for cell killing as it is also observed in DLD‐1 cells. Strikingly, DLD‐1+Ch2 cells selected for resistance to TPA are found to lose the expression of hMSH6. Treatment of TPA‐resistant DLD‐1+Ch2 cells with 5‐aza‐2′‐deoxycytidine, not only restores hMSH6 expression but also resensitizes TPA‐resistant cells to TPA, suggesting that expression of hMSH6 is transcriptionally silenced by cytosine methylation confirmed directly by bisulfite sequencing. Knockdown hMSH6 or hPMS2 with siRNA in DLD‐1+Ch2 cells resulted in more resistant to TPA‐induced cell killing, further suggesting that MMR proteins involve in TPA or ROS‐induced cell killing. Results suggest that deficiency in MMR could promote tumorigenesis by inhibiting apoptotic responses to ROS‐mediated DNA damages as ROS are continuously produced as a byproduct of normal metabolism. © 2006 Wiley‐Liss, Inc.
Neutralization of a Conserved Amino Acid Residue in the Human Na+/Glucose Transporter (hSGLT1) Generates a Glucose-gated H+ Channel*

The role of conserved Asp204 in the human high affinity Na+/glucose cotransporter (hSGLT1) was investigated by site-directed mutagenesis combined with functional assays exploiting the Xenopus oocyte expression system. Substitution of H+ for Na+ reduces the apparent affinity of hSGLT1 for glucose from 0.3 to 6 mm. The apparent affinity for H+ (7 μm) is about three orders of magnitude higher than for Na+ (6 mm). Cation/glucose cotransport exhibits a coupling ratio of 2 Na+ (or 2 H+):1. Pre-steady-state kinetics indicate that similar Na+- or H+-induced conformational changes are the basis for coupled transport. Replacing Asp204 with Glu increases the apparent affinity for H+ by >20-fold with little impact on the apparent Na+ affinity. This implies that the length of the carboxylate side chain is critical for cation selectivity. Neutralization of Asp204 (Asp → Asn or Cys) reveals glucose-evoked H+ currents that were one order of magnitude greater than Na+ currents. These phlorizin-sensitive H+ currents reverse and are enhanced by internal acidification of oocytes. Together with a H+ to sugar stoichiometry as high as 145:1, these results favor a glucose-gated H+ channel activity of the mutant. Our observations support the idea that cotransporters and channels share common features.
Face Animacy is Not All in the Eyes: Evidence from Contrast Chimeras

Observers are capable of distinguishing real faces from artificial faces of various types (eg dolls, computer-generated faces) relatively easily. While a number of diagnostic cues are potentially available to observers to accomplish this task, the appearance of the eyes has been shown to be critically important. However, eye appearance appears to interact with other cues, like the appearance of the skin, in some settings. The ‘uncanny’ appearance of some artificial faces appears to result from multiple visual features and their departure from typical face norms, for example, and recent results investigating how real and artificial features are perceived in chimeric faces also suggest that observers use multiple cues to measure face animacy. Presently, we examined the cues that support real-artificial face discrimination by using contrast negation and so-called ‘contrast chimeras’ to selectively disrupt the appearance of the eyes and the remainder of the face pattern. First, we demonstrate that, like other aspects of face perception, perceived animacy is significantly impacted by contrast negation. Second, by selectively manipulating the contrast of the eyes relative to the rest of the face, we demonstrate that these face regions are of approximately equal use to observers for animacy discrimination.
Detection of molecular markers for chloroquine and pyrimethamine/sulfadoxine resistance in imported cases of Plasmodium falciparum malaria in Poland

The identified mutations in the pfcrt, dhfr and dhps genes of Plasmodium falciparum show a very high correlation with resistance to chloroquine, pyrimethamine and sulfadoxine, the drugs that are still used as malaria chemoprophylaxis or treatment. We undertook a molecular screening of 82 Polish P. falciparum isolates, mainly imported from different countries of sub-Saharan Africa to assess their molecular drug-resistance profiles. Only 4 isolates showed no mutations in the three analyzed gene fragments. In the remaining isolates from one to six mutations in one or more examined genes were found. Different mutations in the pfcrt, dhfr and dhps genes were found in ca. 76%, 80% and 70% of P. falciparum isolates, respectively. About forty our patients used chloroquine or pyrimethamine + sulfadoxine as malaria chemoprophylaxis and/or antimalarial treatment, but without success. In all but 5 of the P. falciparum isolates obtained from these persons, mutations associated to resistance of the parasite to chloroquine and the antifolate drugs were found.