Miracle-dz/UniFAR-FTUs huggingface dataset:
Cobicistat Boosts the Intestinal Absorption of Transport Substrates, Including HIV Protease Inhibitors and GS-7340, In Vitro

ABSTRACT The experimental pharmacoenhancer cobicistat (COBI), a potent mechanism-based inhibitor of cytochrome P450 3A enzymes, was found to inhibit the intestinal efflux transporters P-glycoprotein and breast cancer resistance protein. Consistent with its transporter inhibition, COBI significantly increased the absorptive flux of potential candidates for clinical coadministration, including the HIV protease inhibitors atazanavir and darunavir and the lymphoid cell- and tissue-targeted prodrug of the nucleotide analog tenofovir, GS-7340, through monolayers of Caco-2 cells in vitro.
Rapid stress‐induced corticosterone rise in the hippocampus reverses serial memory retrieval pattern

We previously showed that an acute stress (electric footshocks) induced both a rapid plasma corticosterone rise and a reversal of serial memory retrieval pattern in a contextual serial discrimination (CSD) task. This study is aimed at determining (i) if the rapid stress effects on CSD performance are mediated by the hippocampus; (ii) if hippocampal corticosterone membrane receptor activation is involved in the rapid stress effects on CSD performance. In experiment 1, microdialysis in the dorsal hippocampus (dHPC) was used to measure the stress‐induced corticosterone rise; in parallel, the effect of acute stress on CSD performance was evaluated. In addition, the functional involvement of corticosterone in the behavioral effects of stress was assessed by administering metyrapone, a corticosterone synthesis inhibitor, before stress. In experiment 2, the involvement of hippocampal corticosterone membrane receptors in the stress‐induced reversal of CSD performance was studied by injecting corticosterone‐bovine serum albumin (BSA) (a membrane‐impermeable complex) in the dHPC in non stressed mice. Results showed that (i) the acute stress induced a rapid (15 min) and transitory (90 min) corticosterone rise into the hippocampus dHPC, and a reversal of serial memory retrieval pattern; (ii) both the endocrinal and memory stress‐induced effects were blocked by metyrapone; (iii) corticosterone‐BSA injection into the dHPC in non stressed mice mimicked the effects of stress on serial retrieval pattern. Overall, our study is first to show that (i) a rapid stress‐induced corticosterone rise into the dHPC transitorily reverses serial memory retrieval pattern and (ii) hippocampal corticosterone membrane receptors activation is involved in the rapid effects of acute stress on serial memory retrieval. © 2009 Wiley‐Liss, Inc.
Neural basis of confabulation

we present a case of acute alcohol-induced Korsakoff amnesia. A severe amnestic-confabulatory syndrome characterized the early clinical status. The initial neuropsychological tests demonstrated severe learning deficits plus impaired performance on many, but not all, tests of frontal lobe function. Single-photon emission CT (SPECT) at this stage showed hypoperfusion in the orbital and medial frontal regions and the medial diencephalic area. Four months later, the patient's amnesia remained but there was no confabulation. Repeat neuropsychological tests confirmed an ongoing severe amnesia, but performance on the frontal lobe tests now was normal. Repeat SPECT showed a return to normal perfusion in the frontal brain areas but little improvement in the medial diencephalic region. These findings along with data from the clinical literature suggest that confabulation results from dysfunction of orbital and a medial frontal cortex.
Indian New England Before the Mayflower

In offering here a highly readable yet comprehensive description of New England's Indians as they lived when European settlers first met them, the author provides a well-rounded picture of the natives as neither savages nor heroes, but fellow human beings existing at a particular time and in a particular environment. He dispels once and for all the common notion of native New England as peopled by a handful of savages wandering in a trackless wilderness. In sketching the picture the author has had help from such early explorers as Verrazano, Champlain, John Smith, and a score of literate sailors; Pilgrims and Puritans; settlers, travelers, military men, and missionaries. A surprising number of these took time and trouble to write about the new land and the characteristics and way of life of its native people. A second major background source has been the patient investigations of modern archaeologists and scientists, whose several enthusiastic organizations sponsor physical excavations and publications that continually add to our perception of prehistoric men and women, their habits, and their environment. This account of the earlier New Englanders, of their land and how they lived in it and treated it; their customs, food, life, means of livelihood, and philosophy of life will be of interest to all general audiences concerned with the history of Native Americans and of New England.
Cohort profile: a nationwide cohort of Finnish military recruits born in 1958 to study the impact of lifestyle factors in early adulthood on disease outcomes

Purpose The cohort was set up to study the impact of lifestyle factors in early adulthood on disease outcomes, with a focus on assessing the influence of body composition and physical performance in early adulthood on subsequent cancer risk. Participants Men born in 1958 who performed their military service between the ages of 17 and 30 years were included in this study (n=31 158). They were eligible for military service if they were healthy or had only minor health problems diagnosed at the beginning of their service. Men with chronic illnesses requiring regular medication or treatment were not eligible for service. Comprehensive health data including diagnosed illnesses, anthropometric measures and health behaviour were collected at the beginning and at the end of military service, including data from medical check-ups. Findings to date During the follow-up, 1124 new cancer cases were diagnosed between baseline (ie, end of the military service for each individual) and end of the year 2014. In the end of the follow-up, 91% of the study participants were still alive. Overweight (body mass index (BMI) ≥25 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with an overall increased risk of cancer. A good or excellent physical condition significantly reduced cancer risk. Future plans The dataset offers the possibility of linkage with other databases, such as the Finnish Cancer Registry (eg, primary site of the tumour, morphology, time of detection, spreading and primary treatment), vital statistics (date of emigration or deaths), censuses (socioeconomic indicators), hospital discharge data (comorbidity) and population surveys (life habits).
Towards automotive augmented reality

Projection of virtual presentation schemes into the reality via Augmented Reality (AR) has the potential to equip novel driver assistance systems with more intuitive user interfaces. Information presentation through AR reduces the number of glances towards in-car displays, thus enabling higher degrees of attention towards the environmental events. Spatial relationships between objects in the car’s environment can directly be indicated through AR without enforcing the user to switch between different frames of reference. This thesis examines issues which arise when such assistance systems with AR are developed. The common development process of such assistance systems in driving simulators is analyzed and facilitated with new solutions, which partly incorporate AR technology. A fixed-base driving simulator is extended to serve as a rapid prototyping environment for a broad spectrum of in-car systems. To analyze spatial relationships of the surrounding of the car, a subsystem for context analysis and reasoning on spatial sensor data is implemented and incorporated with the rapid prototyping environment. An additional system enables creation of realistic traffic scenarios in virtual environments using a tracked miniature car. This thesis also develops new approaches for AR presentation schemes and evaluates them in usability studies. An AR presentation scheme showing the physical behavior of the own car minimizes the need for last second collision warnings. For time-critical collision alerts, an AR system guides the attention of a car driver towards imminent dangers. The evaluations of the concepts indicate, among other things, that the application of AR reduces reaction times and that mental workload is not increased. The thesis concludes with another system enabling the examination of AR schemes in real environments. The system also enables porting of AR assistance systems to real cars when Heap-Up Display and sensor technology are able to provide the demanded needs.
Performance Evaluation of Scene Registration and Stereo Matching for Artographic Feature Extraction

Three major areas in the development of competent 3-D scene interpretation system are discussed. First, the importance of accurate automatic scene registration and the difficulty in automated extraction and matching of scene reference points are described. Second, the authors describe two stereo matching algorithms, S1, which is an area-based matcher previously used in the SPAM system, and S2, which is a feature-based matching algorithm based on hierarchical waveform matching. Third, the authors introduce several performance evaluation metrics that made it possible to measure the quality of the overall scene recovery, the building disparity estimate, and the quality and sharpness of the building delineations. Such manually generated scene reference models are critical for understanding strengths and weaknesses of various matching algorithms and in the incremental development of improvements to existing algorithms. Experiments were performed on difficult examples of aerial imagery. >
Isolation, production, and characterization of an extracellular lipase from Trichoderma harzianum isolated from soil

Th is is the fi rst report about the characterization of Trichoderma harzianum lipase. A novel strain of Trichoderma harzianum IDM14D was isolated from soil. Th e isolated strain was cultivated for lipase production in shake fl asks at 30 °C for 7 days. For lipase production, it was determined that the best carbon source was glucose and the best nitrogen source was peptone. Maximum biomass was produced at a concentration of 1.25 g/L, in 7 days. Th e optimum pH and temperature for activity of the enzyme were 8.5 and 40 °C, respectively. Th e lipase was stable at a pH range of 8.0-10.0 and at 40 °C for 60 min. Ca 2+ and Mn 2+ enhanced lipase activity but it was determined that other metallic ions did not aff ect the enzyme activity. Th e K m and V max values of the crude enzyme for p-nitrophenyl butyrate hydrolysis were found to be 7.15 mM and 7.067 mM/min, respectively.
Temperature affects methylation of the myogenin putative promoter, its expression and muscle cellularity in Senegalese sole larvae

Myogenin (myog) encodes a highly conserved myogenic regulatory factor that is involved in terminal muscle differentiation. It has been shown in mammals that methylation of cytosines within the myog promoter plays a major role in regulating its transcription. In the present study, the Senegalese sole (Solea senegalensis) myog putative proximal promoter was identified and found to be highly conserved among teleosts. Therefore, it is plausible that it plays a similar role in controlling myog expression. Cytosine methylation of the myog promoter in skeletal muscle of Senegalese sole larvae undergoing metamorphosis was influenced by rearing temperature. A lower temperature (15°C) significantly increased myog promoter methylation in skeletal muscle, particularly at specific CpG sites, relatively to higher rearing temperatures (18 and 21°C). Myog transcription was downregulated at 15°C, whereas expression of dnmt1 and dnmt3b was upregulated, consistently with the higher myog methylation observed at this temperature. Rearing temperature also affected growth and fast muscle cellularity, producing larger fibers at 21°C. Taken together, our data provide the first evidence of an epigenetic mechanism that may be underlying the temperature-induced phenotypic plasticity of muscle growth in teleosts.
Problem-based Learning Revisited, introduction of Active and Self-directed Learning to reduce fatigue among students

Despite several years of successfully applying problem-based learning at Maastricht University, the Faculty of Medicine observed a slow erosion of problem-based practices and “PBL fatigue” among themselves and students. In response to this fatigue and new research into the development of the young adult brain, Active Self-Directed Learning was introduced through the new bachelor of European Public Health programme in an effort to re-energise the classical PBL model and reduce or eliminate erosion. ASDL is split into a four part learning cycle: 1) sensitisation, 2) exploration, 3) integration, and 4) application. The cycle supports problem-based learning and the developing minds of students through the integration of information, critical thinking and self-evaluation, while also teaching self-responsibility and team management skills. When applied as part of a problem-based learning curriculum, ASDL at Maastricht University helped reduce PBL fatigue and re-energised students’ interest in PBL within the first EPH cohort (2006-2009) according to survey feedback obtained after the 5th semester. The positive student response was tempered by recommendations on how to continue improving the ASDL model.
Center CLICK: A Clustering Algorithm with Applications to Gene Expression Analysis

Novel DNA mlcroarray technologies enable the monitoring of expression levels of thousands of genes simultaneously. This allows a global view on the transcription levels of many (or all) genes when the cell undergoes specific conditions or processes. Analyzing gene expression data requires the clustering of genes into groups with similar expression patterns. We have developed a novel clustering algorithm, called CLICK, which is applicable to gene expression analysis as well as to other biological applications. No prior assumptions are made on the structure or the number of the clusters. The algorithm utilizes graph-theoretic and statistical techniques to identify tight groups of highly similar dements (kernels), which are likely to belong the same true cluster. Several heuristic procedures are then used to expand the kernels into the full clustering. CLICK has been implemented and tested on a variety of biological datasets, ranging from gene expression, eDNA ollgo-fmgerprinting to protein sequence similarity. In all those applications it outperformed extant algorithms according to several common figures of merit. CLICK is also very fast, allowing clustering of thousands of elements in minutes, and over 100,000 elements in a couple of hours on a regular workstation.
A factor analytic study in bipolar depression, and response to lamotrigine

Objective There have been no previous factor analytic studies of the Hamilton Depression Rating Scale (HDRS) in samples with bipolar I depression, and no investigations of the utility of any derived factors in determining treatment response in this condition. This study aimed to identify and compare factors of a 31-item version of the HDRS (HDRS-31) in large samples of patients with bipolar depression and Major Depressive Disorder (MDD), then examine the responsiveness of such factors to lamotrigine compared with placebo in the bipolar depressed sample. Methods This multivariate analytical study was performed on 2 large depressed samples (one bipolar and the other MDD) that had been recruited for separate, contemporaneous, double-blind placebo-controlled trials of lamotrigine. The 2 studies had similar designs and assessment tools, the major measures being the Montgomery–Asberg Depression Rating Scale (MADRS) and HDRS-31. To identify the constructs underlying the scale, exploratory factor analyses were conducted using HDRS-31 baseline scores. Treatment responsiveness in the bipolar depressed sample—as indicated by improvement in the total MADRS and HDRS-31, as well as HDRS factors—were examined using both a mixed-effects analysis and individual time-point t-tests. Results Seven factors of the HDRS-31 were identified: I—“depressive cognitions,” II—“psychomotor retardation,” III—“insomnia,” IV—“hypersomnia,” V—“appetite and weight change,” VI—“anxiety,” and VII—“anergia. ” A significant therapeutic effect of lamotrigine in bipolar depression was found for the “depressive cognitions” factor (from week 3) and “psychomotor retardation” (from week 4). Conclusion This study has identified 7 factors of the HDRS in a large sample of patients with bipolar depression. The results suggest that that the clinical benefits of lamotrigine in acute bipolar depression are primarily upon depressive cognitions and psychomotor slowing.
Simultaneous Analysis of Greenhouse Gases by Gas Chromatography

Two analytical methods based on the Agilent 7890A GC system are developed for simultaneous analysis of methane (CH4), carbon dioxide (CO2), nitrous oxide (N2O) in air samples. Each system has its own features to meet different requirements of greenhouse gases analyses. Both systems can easily be expanded to determine sulfur hexafluoride (SF6). Results from both methods demonstrated high sensitivity and excellent repeatability for the required analyses. Author Chunxiao Wang Agilent Technologies 412 YingLun Road Waigaoqiao Free Trade Zone Shanghai 200131 China Application Environmental
Small-signal characterization of SiGe-HBT f/sub T/-doubler up to 120 GHz

In this brief, small-signal characterizations of selectively implanted collector (SIC) and non-SIC SiGe-heterojunction bipolar transistors (HBT) f/sub T/-doublers up to 120 GHz are measured, analyzed, and compared with those of the corresponding single devices. The measured results confirm a great improvement in transit frequency with almost no considerable decrease in the maximum stable gain/maximum available gain, and maximum oscillation frequency. Since the f/sub T/-doubler can be used easily instead of a single transistor, a much higher transit frequency and RF power can be achieved while using a technology with a moderate f/sub T/.
Personal resources of mastery–optimism, and communal support beliefs, as predictors of posttraumatic stress in uprooted Israelis

Abstract The study aims to assess the personal resources of mastery–optimism, and communal support beliefs, as predictors of posttraumatic stress and adaptation in uprooted Israelis following Israel's disengagement from the Gaza Strip and northern Samaria in the summer of 2005. A telephone interview of a sample of 104 respondents slated to be uprooted was conducted several weeks before the disengagement (T1), and again 9 months after the event (T2). At T1, respondents answered a questionnaire which included assessments of dispositional optimism and mastery, beliefs in the availability of community–family and governmental–societal support, nation-related anxiety, and demographic data. Posttraumatic stress levels were assessed at T2. The main findings showed that high levels of mastery–optimism and low nation-related anxiety at T1 predicted a low severity of total posttraumatic stress scores at T2. A high educational level and a secular identity also predicted low posttraumatic stress. In contrast, communal support beliefs were not related to posttraumatic stress. These findings point to the importance of personal resources and education as protective factors against posttraumatic stress following an event such as forced uprooting.
A Chronological Outline for the Northwest Florida Coast

The northwestern part of Florida is a strip of land about 225 miles long, extending from Pensacola Bay to Apalachee Bay, in which are recognized two physiographic regions, “Flatwoods and Hammock Lands,” along the coast, and “Southern Pine Hills,” inland. The coastal region, in which are located most of the sites to be considered, is quite flat and of uniformly low elevation, and includes several contrasting types of landscape. The greater part of the land is occupied by the flatwoods or open groves of longleaf and other pines interspersed with grassy meadows and the hammock lands, which support a denser vegetation characterized by palmetto and hardwoods. Along the major rivers are swamps through which wind creeks and bayous.
A PATIENT WITH DEPRESSIVE SYMPTOMATOLOGY

cians in behavioral activation methods aimed at palliating depressive symptoms, including graded task assignment, goal setting scheduling, reinforcement of social contact behaviors or performance of gratifying activities (Kanter, Busch, & Rusch, 2009; Lejuez, Hopko, & Hopko, 2002; Martell, Addis, & Jacobson, 2001). In fact, there was always a place for these strategies in the most serious cases, but they were considered as part of an initial approach, and as a preparatory step for the use of cognitive techniques whose procedures, it was believed, would enable solid improvements in depressive conditions and the avoidance of relapses (Beck, Rush, Shaw, & Emery, 1979). However, recent meta-analytical reviews (Cuijpers, van Straten, & Warmerdam, 2007) and experimental studies comparing different therapeutic approaches — antidepressant medication, cognitive therapy and behavioral activation therapy — (Dimidjian et al., 2006) have revealed that purely behavioral interventions are sufficiently effective and efficient for depressive conditions, even in the long term (Dobson et al., 2008). At the same time as the really useful components of cognitive therapy were being studied systematically (Gortner, Gollan, Dobson, & Jacobson, 1998; Jacobson et al., 1996), a clinical approach to depression was being formulated that incorporated the analysis of the factors maintaining it. This approach recovered the explanatory model of Ferster (1973) and Lewinsohn’s (1974) first model, but enlarged on them, stressing the functional character that should guide all case analyses (Hopko, Lejuez, Ruggiero, & Eifert, 2003; Jacobson & Gortner, BEHAVIORAL ACTIVATION INTERVENTION IN A PATIENT WITH DEPRESSIVE SYMPTOMATOLOGY
A Picture of Health?: unmasking the role of appearance in health

Evaluating health requires visual assessment. From the meticulous self-scrutiny of a worried woman in front of the looking glass to the doctor's reaction at the sight of a patient in the examining room, external appearance plays an important role in appraising health above and beyond clinical assessment. However, this dominance of the visual in our image-driven culture has assumed a disproportionately prominent position. Media, businesses, and health care commonly misrepresent appearance as the reality of health. Industry mongers beauty-promoting wares and services as health-protecting products, and physical appearance contributes to clinicians' imperfect heuristics. An explanation for this focus on appearance is persistence of the ancient belief that looks indicate inner character. In this article we unmask the historical origin of this belief and reveal how it contaminates contemporary approaches to health assessment and maintenance.