Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Gi G‐Protein‐Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing

G‐protein‐coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of Gi‐GPCR or activation of Gs‐GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of Gi signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age‐related bone loss in female mice. In addition, activation of Gs signaling by expressing the Gs‐coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the Gi and Gs pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous Gi signaling was inhibited by PTX, or to mice with activated Gs signaling mediated by Rs1. Blockade of endogenous Gi resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous Gi signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that Gi blockade and Gs activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of Gs and Gi‐GPCR activation may be important for optimizing fracture repair. © 2015 American Society for Bone and Mineral Research.
A segmentation clock operating in blastoderm and germband stages of Tribolium development

In Drosophila, all segments form in the blastoderm where morphogen gradients spanning the entire anterior-posterior axis of the embryo provide positional information. However, in the beetle Tribolium castaneum and most other arthropods, a number of anterior segments form in the blastoderm, and the remaining segments form sequentially from a posterior growth zone during germband elongation. Recently, the cyclic nature of the pair-rule gene Tc-odd-skipped was demonstrated in the growth zone of Tribolium, indicating that a vertebrate-like segmentation clock is employed in the germband stage of its development. This suggests that two mechanisms might function in the same organism: a Drosophila-like mechanism in the blastoderm, and a vertebrate-like mechanism in the germband. Here, we show that segmentation at both blastoderm and germband stages of Tribolium is based on a segmentation clock. Specifically, we show that the Tribolium primary pair-rule gene, Tc-even-skipped (Tc-eve), is expressed in waves propagating from the posterior pole and progressively slowing until they freeze into stripes; such dynamics are a hallmark of clock-based segmentation. Phase shifts between Tc-eve transcripts and protein confirm that these waves are due to expression dynamics. Moreover, by tracking cells in live embryos and by analyzing mitotic profiles, we found that neither cell movement nor oriented cell division could explain the observed wave dynamics of Tc-eve. These results pose intriguing evolutionary questions, as Drosophila and Tribolium segment their blastoderms using the same genes but different mechanisms.
Identification of silencing of nine genes in human gastric cancers.

Aberrant methylations in human gastric cancers were searched for by a genome scanning technique, methylation-sensitive representational difference analysis. Nine CpG islands (CGIs) in the 5' regions of nine genes, LOX, HRASLS, bA305P22.2. 3, FLNc (gamma-filamin/ABPL), HAND1, a homologue of RIKEN 2210016F16, FLJ32130, PGAR (HFARP/ANGPTL4/ARP4), and thrombomodulin, were found to be methylated in two gastric cancer cell lines, MKN28 and MKN74, but unmethylated in the normal sample. Their expressions were lost in the two cell lines, and the causal roles of the methylations in gene silencing were shown by treatment with 5-aza-2'-deoxycytidine. In 41 primary gastric cancers, methylations of these CGIs in association with reduced expressions were observed at high incidences (29-41%) for five genes, including LOX and HRASLS, which have been reported to have tumor-suppressive activities. The other four genes were methylated at low incidences (0-7%). By analysis of the numbers of aberrant methylations in individual cancers, a subset of cancers with high prevalence of aberrant methylations was identified, and all of the 11 cancers in the subset were diffuse type. To analyze the possible involvement of decreased fidelity of maintenance methylation in this subset of cancers, aberrant hypomethylations of three normally methylated CGIs were examined. Cancers with high prevalence of hypomethylations of normally methylated CGIs, however, constituted a different subset. It is expected that these nine genes may include important genes in gastric cancer development and would be useful to identify a distinct subset of gastric cancers.
Zur Bedeutung von Hippocampus und Parahippocampus hinsichtlich normaler und gestörter Gedächtnisfunktionen

For decades there have been differing, partly controversial ideas concerning the function of the hippocampus. They were newly stimulated by the discovery of the widespread neocortical connexions of the adjacent parahippocampus, which itself is closely interconnected via its anterior part with the hippocampus. All theories have in common that they conceive these areas to be sites for the integration of complex information. However, some of the observations regarding their role in various memory functions are very contradictory. The present article gives a survey of the current state of knowledge concerning anatomy, physiology and pathophysiology of these cerebral areas. It appears that hippocampus and parahippocampus play a significant part in the regulation of selective attention and expectation. Thus they might also influence the process of comparison and valuation which modulates the access to neocortical associative information stores.
Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever

Background Mice lacking the type I interferon receptor (IFNAR−/− mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR−/− mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus. Methodology/Principal Findings CCHF virus-infected IFNAR−/− mice died 2–6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. Virus-infected and apoptotic hepatocytes clustered in the necrotic areas. Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by ≥3 log units (IC50 0.6–2.8 µg/ml; IC90 1.2–4.7 µg/ml). Ribavirin [100 mg/(kg×d)] did not increase the survival rate of IFNAR−/− mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers. Arbidol [150 mg/(kg×d)] had no efficacy in vivo. Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg×d)] or up to 2 days [300 mg/(kg×d)] post infection survived, showed no signs of disease, and had no virus in blood and organs. Co-administration of ribavirin and T-705 yielded beneficial rather than adverse effects. Conclusions/Significance Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF. Clustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. T-705 is highly potent against CCHF virus in vitro and in vivo. Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin.
The Big Seven model: A cross-cultural replication and further exploration of the basic dimensions of natural language trait descriptors.

The objective of this study was to identify the major lexical dimensions in the Hebrew language and to compare these dimensions with the Big Seven factor structure. A list of 252 trait descriptors was assembled from a Hebrew dictionary, using nonrestrictive criteria similar to those introduced by A. Tellegen and N. G. Waller (1987). The factor structure recovered from these data largely replicates the Big Seven model. In particular, 2 major evaluative factors emerged, Positive and Negative Valence, which are prominent in the Big Seven but are not represented in the Big Five. Four of the remaining 5 factors also clearly correspond to 4 of the Big Seven dimensions and their counterparts in the Big Five.
The nature of the laws of nature

We human beings live in the explanations of our existence as living beings. These explanations of our existence include what we call the ‘laws of nature’. Though we name them laws, we cannot claim that they have an existence independent of us. We human beings do not exist in nature, nature arises with us, and we ourselves arise with it. In this dynamic co-arising, we explain ourselves and our circumstances while operating as observers. The laws of nature are abstractions of the regularities of our operation as living systems that we distinguish as we explain our experiences with the coherences of our experiences. Copyright © 2000 John Wiley & Sons, Ltd.
Analysis of an abbreviated form of the Wisconsin Card Sorting Test.

Abstract The Wisconsin Card Sorting Test (WCST) was administered to 120 subjects in the standardized 128-card format. The standard scoring measures of the traditional administration were compared to those obtained using only the first 64 cards. Rank ordered correlations for all of the measures were significant. T-test comparisons revealed no differences on the measures between the test versions. These results provide preliminary support for an abbreviated administration of the WCST. Suggestions regarding further research are discussed.
From gift to waste: changing policies in biobanking practices

Traditionally the analysis of biomedical discourses surrounding biobanking has focused on the role of donation and gift giving as central aspects related to the procurement and use of tissue samples. More recently, studies have looked at the political underpinnings of building national collections of tissue samples. These national projects draw increasingly on a discourse of waste and efficiency as a way of legitimising activities. This paper draws attention to the way new arguments draw from environmental discourses in an attempt to reframe contentious ethical and legal issues in a more favourable light. Attempts to evoke notions of efficiency draw on a different set of persuasive techniques to foster support for large research and development ventures involving public-private partnerships, but at the same time limit public debate. Copyright , Beech Tree Publishing.
Vicarious traumatization: An empirical study of the effects of trauma work on trauma therapists.

This study examined vicarious traumatization (i.e., the deleterious effects of trauma therapy on the therapist) in 188 self-identified trauma therapists. Participants completed questionnaires about their exposure to survivor clients' trauma material as well as their own psychological well-being. Those newest to the work were experiencing the most psychological difficulties (as measured by the TSI Belief Scale; L. A. Pearlman, in press-a) and Symptom Checklist-90—Revised (L. Derogatis, 1977) symptoms. Trauma therapists with a personal trauma history showed more negative effects from the work than those without a personal history. Trauma work appeared to affect those without a personal trauma history in the area of other-esteem. The study indicates the need for more training in trauma therapy and more supervision and support for both newer and survivor trauma therapists.
Prevalence and Prognosis of Pseudoexfoliation Glaucoma in Western India

PurposeTo investigate the prevalence and reconnoiter treatment modalities for Pseudoexfoliation Glaucoma (PXG) in subjects with Pseudoexfoliation Syndrome (PXF) in a rural scenario of western India. DesignA prospective prevalence study. MethodsOccurrence of PXG in 250 subjects with PXF was studied in the Department of Glaucoma, Shri Ganapati Netralaya, Jalna, India, from 2009 to 2011. The subject pool presented with PXF, having intraocular pressure (IOP) ≥ 20 mm of Hg, and evidencing optic nerve damage and abnormal visual fields were judiciously selected as PXG cohorts. A decision table is formulated to assist the physician in rendering medical or surgical treatment options. ResultsThe prevalence of PXG increased with increasing age at 30% (95% CI: 28.56–33.72) in the 60-year-old and older population. It was predominantly higher in cohorts involved in outdoor physical activities at 46% (95% CI: 41.24–52.38). The eminence and prevalence of nuclear cataract in subjects with PXG was 72 % (95% CI: 65.72–76.34). Visual impairment was highly prevalent in 75% (95% CI: 73.43–78.29) and 10% (95% CI: 6.87–13.21) cohorts with PXG and PXF respectively. In general, linear modelling IOP was 26.37±1.64 in subjects with PXG, which was managed to 16.50±1.32 after rendering our adapted treatment protocols. ConclusionsIncreased IOP, occludable angles, and glaucomatous optic neuropathy occur more frequently in the population with PXF. It is inferred that that treatment protocol of combined cataract and glaucoma surgery gives maximum reduction in IOP.
Effect of voice characteristics on the attended and unattended processing of two concurrent messages

Three experiments using dichotic listening measured the priming effect produced on the detection of a semantically defined target word in an attended list of words by a lexically identical word presented to the opposite ear with an attenuation of 12 dB. Experiment 1 embedded the prime in unattended continuous speech and found a 21 ms priming effect, but only when the voices of the two messages had different pitch ranges. Experiment 2 emphasised and generalised the priming effect to a more natural situation using voices differing both in pitch and timbre. This priming effect did not vary with word frequency. In Experiment 3 the prime was part of a list of isolated words played to the unattended ear. It found a 94 ms priming effect when there was no pitch-range difference between the two messages. This priming effect was larger for high-frequency words than for low. These results extend recent findings by Rivenez, Darwin, and Guillaume (2006) and demonstrate the importance of factors that influence perceptual organisation in determining the extent to which unattended messages can be processed.
Social networking sites and contact risks among Flemish youth

This study investigates how teenagers use social networking sites (SNS) and other online communication applications, to what extent they are exposed to online contact risks related to the use of these online tools and how they cope with these risks. A written survey was administered among 815 Flemish adolescents aged 14–19. The study controls for sociodemographics and psychosocial factors, and it concludes that boys, pupils in technical or vocational education, adolescents living in lower SES families, teens with either low or high self-confidence and those having a bad relationship with their parents are more at-risk.
LOCAL LINEAR PROJECTION (LLP)

Dimensionality reduction has important applications in exploratory data analysis. A method based on Local Linear Projection (LLP) is proposed. The advantage of this method is that it is robust against uncertainty. Statistical analysis is applied to estimate parameters. Simulational results on synthetic data are promising. Some preliminary experiment of applying this method to microarray data is reported. The results show that LLP can identify significant patterns. We propose some future tasks to perfect this method.
Multi-layer protocol tracing in a GPRS network

The paper presents a performance evaluation of GPRS accomplished by a combination of measurement at the end hosts and tracing inside the network. The multi-layer tracing approach allows not only observing, but also understanding of, the network performance. With end-to-end measurements, we assess data rates, latency, and buffering experienced by users in a live GPRS network. Comparing the results to our previous measurements shows a notable improvement in the network and terminals over the previous two years. Mobility tests while driving in an urban environment quantify the interval, duration and data loss caused by cell reselections. In the test lab, multi-layer tracing of radio, link and transport protocols gives a closer picture of GPRS performance. For instance, TCP interacts inefficiently with resource allocation at the RLC (radio link control) layer and fragmentation at the LLC (logical link control) layer. Finally, we illustrate delay spikes and data losses during cell reselection by tracing signaling messages during cell update and routing area update procedures.
Intravitreal bevacizumab for retinal vein occlusion and early growth of epiretinal membrane: a possible secondary effect?

Aims To report the early development of epiretinal membranes (ERM) in eyes with retinal vein occlusions (RVO) treated with intravitreal bevacizumab and to describe possible mechanisms that may be involved in the growth and contraction of these lesions. Methods Retrospective and interventional study that included 25 eyes of 25 patients with RVO (16 eyes with central retinal vein occlusion and nine eyes with branch retinal vein occlusion). After an initial 2.5 mg/0.1 ml intravitreal bevacizumab injection all patients were followed-up every 6 weeks. Re-treatments were based on visual acuity and optical coherence tomography findings. Results Twenty-five eyes were treated with bevacizumab and followed for 8.3 (range 4.5–13.5) months. Four eyes developed an ERM within 6–7 weeks after the administration of bevacizumab. ERM was not associated with further deterioration of visual acuity or metamorphopsia in these patients. A rebound of macular oedema was observed in one patient with ERM and in two other patients. No other side effects were observed. Conclusions Intravitreal bevacizumab may be associated with an early growth of ERM in eyes with RVO, although a causative relationship cannot be established. Future randomised clinical trials are necessary to determine the efficacy and safety profile of this novel therapy.
Candida albicans-Conditioned Medium Protects Yeast Cells from Oxidative Stress: a Possible Link between Quorum Sensing and Oxidative Stress Resistance

ABSTRACT Candida albicans, the most frequent fungal pathogen of humans, encounters high levels of oxidants following ingestion by professional phagocytes and through contact with hydrogen peroxide-producing bacteria. In this study, we provide evidence that C. albicans is able to coordinately regulate the oxidative stress response at the global cell population level by releasing protective molecules into the surrounding medium. We demonstrate that conditioned medium, which is defined as a filter-sterilized supernatant from a C. albicans stationary-phase culture, is able to protect yeast cells from both hydrogen peroxide and superoxide anion-generating agents. Exponential-phase yeast cells preexposed to conditioned medium were able to survive levels of oxidative stress that would normally kill actively growing yeast cells. Heat treatment, digestion with proteinase K, pH adjustment, or the addition of the oxidant scavenger alpha-tocopherol did not alter the ability of conditioned medium to induce a protective response. Farnesol, a heat-stable quorum-sensing molecule (QSM) that is insensitive to proteolytic enzymes and is unaffected by pH extremes, is partly responsible for this protective response. In contrast, the QSM tyrosol did not alter the sensitivity of C. albicans cells to oxidants. Relative reverse transcription-PCR analysis indicates that Candida-conditioned growth medium induces the expression of CAT1, SOD1, SOD2, and SOD4, suggesting that protection may be mediated through the transcriptional regulation of antioxidant-encoding genes. Together, these data suggest a link between the quorum-sensing molecule farnesol and the oxidative stress response in C. albicans.
Deficiency in anterior-posterior connectivity of default-mode network in amnestic mild cognitive impairment: A combined task-related and resting-state fMRI study

Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). Recent functional imaging studies have demonstrated regional deactivation magnitudes changes of default-mode network (DMN) in patients, accompanied by a defect of memory function. However, functional connectivity in the DMN during task performance was rarely investigated. METHODS : 26 amnestic MCI and 27 healthy controls underwent functional magnetic resonance imaging (fMRI) during an episodic memory task. Resting-state fMRI data were also collected. The changes in default-mode networks under both task-related and resting-state fMRI were obtained with a temporal correlation analysis. RESULTS: Significantly decreased functional connectivity was found mainly in anterior-posterior connectivity of DMN in aMCI groups. And a correlation existed between the anterior-posterior functional connectivity and MMSE scores. CONCLUSIONS: This study showed that disconnectivity of DMN could be used as an imaging biomarker for predicting the future cognitive decline of aMCI patients.
The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer

BRG1, a member of the SWI/SNF complex, is mutated in cancer, but it is unclear how it promotes tumourigenesis. We report that re‐expression of BRG1 in lung cancer cells up‐regulates lung‐specific transcripts, restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restores sensitivity. Conversely, in SH‐SY5Y cells, a paradigm of RA‐dependent differentiation, abrogation of BRG1 prevented the response to RA. Further, our data suggest an antagonistic functional connection between BRG1 and MYC, whereby, refractoriness to RA and GC by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, some of these effects are mediated by BRG1 binding to MYC and MYC‐target promoters. The BRG1‐MYC antagonism was also evident in primary tumours. Finally, BRG1 restoration significantly dampened invasion and progression and decreased MYC in lung cancer cells orthotopically implanted in nude mice. Thus, BRG1 inactivation enables cancer cells to sustain undifferentiated gene expression programs and prevent its response to environmental stimuli.
Random trees and general branching processes

We consider a tree that grows randomly in time. Each time a new vertex appears, it chooses exactly one of the existing vertices and attaches to it. The probability that the new vertex chooses vertex x is proportional to w(deg(x)), a weight function of the actual degree of x. The weight function w : ℕ → ℝ+ is the parameter of the model.