Miracle-dz/UniFAR-FTUs huggingface dataset:
The Hominoid-specific Oncogene TBC1D3 Activates Ras and Modulates Epidermal Growth Factor Receptor Signaling and Trafficking*

Hominoid- and human-specific genes may have evolved to modulate signaling pathways of a higher order of complexity. TBC1D3 is a hominoid-specific oncogene encoded by a cluster of eight paralogs on chromosome 17. Initial work indicates that TBC1D3 is widely expressed in human tissues ( Hodzic, D., Kong, C., Wainszelbaum, M. J., Charron, A. J., Su, X., and Stahl, P. D. (2006) Genomics 88, 731-736 ). In this study, we show that TBC1D3 expression has a powerful effect on cell proliferation that is further enhanced by epidermal growth factor (EGF) in both human and mouse cell lines. EGF activation of the Erk and protein kinase B/Akt pathways is enhanced, both in amplitude and duration, by TBC1D3 expression, whereas RNA interference silencing of TBC1D3 suppresses the activation. Light microscopy and Western blot experiments demonstrate that increased signaling in response to EGF is coupled with a significant delay in EGF receptor (EGFR) trafficking and degradation, which significantly extends the life span of EGFR. Moreover, TBC1D3 suppresses polyubiquitination of the EGFR and the recruitment of c-Cbl. Using the Ras binding domain of Raf1 to monitor GTP-Ras we show that TBC1D3 expression enhances Ras activation in quiescent cells, which is further increased by EGF treatment. We speculate that TBC1D3 may alter Ras GTP loading. We conclude that the expression of TBC1D3 generates a delay in EGFR degradation, a decrease in ubiquitination, and a failure to recruit adapter proteins that ultimately dysregulate EGFR signal transduction and enhance cell proliferation. Altered growth factor receptor trafficking and GTP-Ras turnover may be sites where recently evolved genes such as TBC1D3 selectively modulate signaling in hominoids and humans.
SMALL-TIME ASYMPTOTICS FOR FAST MEAN-REVERTING STOCHASTIC VOLATILITY MODELS

In this paper, we study stochastic volatility models in regimes where the maturity is small, but large compared to the mean-reversion time of the stochastic volatility factor. The problem falls in the class of averaging/homogenization problems for nonlinear HJB-type equations where the "fast variable" lives in a noncompact space. We develop a general argument based on viscosity solutions which we apply to the two regimes studied in the paper. We derive a large deviation principle, and we deduce asymptotic prices for out-of-the-money call and put options, and their corresponding implied volatilities. The results of this paper generalize the ones obtained in Feng, Forde and Fouque [SIAM J. Financial Math. 1 (2010) 126-141] by a moment generating function computation in the particular case of the Heston model.
Do Coup Leaders Matter? Leadership Change and Economic Growth in Politically Unstable Countries

We examine the impact of leadership change after a coup d’etat on economic growth. We consider successful coup attempts as our treatment group and use failed coup attempts as controls to condition on political instability. To take account of selection bias, we control for the determinants of coup success. Our main finding is that leadership changes after a coup d’etat have a positive effect on economic growth in the least developed countries, but have a negative effect in other developing countries.
Analysis of Output Pulse Characteristics in $Q$ -Switched Yb-Doped Fiber Laser

Characteristics of the output pulses of a high-peak-power Q-switched Yb-doped fiber laser are presented. A Q-switched fiber laser with 1.3 kW peak power and with typical pulse duration of 240 ns at 20 kHz modulation frequency was realized, variations of pulse duration, average power, peak power, and pulse energy with variation in the modulation frequency were studied. The effect of the modulation duty cycle (DC) on the Q-switched pulse characteristics was analyzed both theoretically and experimentally. It is shown that, for a particular pump power and repetition rate, the DC of modulation needs to be optimized to achieve high-peak-power single-pulse output. If the DC of modulation is long, satellite pulses of low peak power are also observed along with the main peak, when the DC is made short enough, the satellite pulses disappear and single peak pulses appear in the output. Theoretical analysis and simulation to predict the pulse build-up time, output pulse shape, and effect of modulation window time on the output pulse characteristic were carried out. Simulation results show good agreement with experimental results. This paper reported here will be useful in the development of high-peak-power Q -switched fiber lasers.
Deep Neural Generative Model of Functional MRI Images for Psychiatric Disorder Diagnosis

Accurate diagnosis of psychiatric disorders plays a critical role in improving the quality of life for patients and potentially supports the development of new treatments. Many studies have been conducted on machine learning techniques that seek brain imaging data for specific biomarkers of disorders. These studies have encountered the following dilemma: A direct classification overfits to a small number of high-dimensional samples but unsupervised feature-extraction has the risk of extracting a signal of no interest. In addition, such studies often provided only diagnoses for patients without presenting the reasons for these diagnoses. This study proposed a deep neural generative model of resting-state functional magnetic resonance imaging (fMRI) data. The proposed model is conditioned by the assumption of the subject's state and estimates the posterior probability of the subject's state given the imaging data, using Bayes’ rule. This study applied the proposed model to diagnose schizophrenia and bipolar disorders. Diagnostic accuracy was improved by a large margin over competitive approaches, namely classifications of functional connectivity, discriminative/generative models of regionwise signals, and those with unsupervised feature-extractors. The proposed model visualizes brain regions largely related to the disorders, thus motivating further biological investigation.
Scrutiny of Relationship between E-Banking Information Quality Dimensions and Customer Satisfaction

Poor information quality can have a significant negative effect on the success of an organization. This study investigated the relationship between information quality's dimensions, namely accuracy, completeness, timeliness and relevancy, on the satisfaction of customers towards E-banking services in Palestine's banking sector. It also studied the relationship between the intent to use E-banking services and customer satisfaction. The study implemented a quantitative method for data collection using a questionnaire survey. The results revealed that the accuracy, completeness, timeliness and relevancy of information had a positive effect on customer satisfaction towards E-banking services. Consequently, customer satisfaction affects the intention to utilize such services. The study also offered limitations, conclusions and recommendations for further studies in the future.
Hepatoprotective and antioxidant effects of Alnus japonica extracts on acetaminophen‐induced hepatotoxicity in rats

The stem bark of the Betulaceae plant Alnus japonica, which is indigenous to Korea, has been used as a popular folk medicine for hepatitis and cancer. In this study, the antioxidant activity of the crude extract and the hepatoprotective activities on acetaminophen (AAP)‐induced toxicity in the rat liver were evaluated. We investigated the effect of the methanol (AJM) and solvent fracton of the stem bark of Alnus japonica (AJ) on AAP‐induced hepatotoxicity in rats. In rat hepatocyte culture, pretreatment with AJM (50, 100, 150 and 200 µg[sol ]ml) significantly decreased the cytotoxicity of AAP in a dose‐dependent manner. The pretreated with EtOAc and BuOH fraction led to an increase in free radical scavenging activity and a decrease in inhibition of lipid peroxidation, both superoxide dismutase and catalase prevent the hepatotoxicity by AAP in the treatment of A. japonica fraction. We conclude that AJ is an important antioxidant in AAP‐induced live hepatotoxicity and that extract of AJM plays a hepatoprotective effects in the against AAP‐induced cytotoxicity in cultured rat hepatocytes in vitro. Pending more evaluation for safety and efficacy, AJ can potentially be used in mitigating AAP‐induced hepatotoxicity. Copyright © 2004 John Wiley & Sons, Ltd.
Gaucher iPSC‐Derived Macrophages Produce Elevated Levels of Inflammatory Mediators and Serve as a New Platform for Therapeutic Development

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the acid β‐glucocerebrosidase (GCase; GBA) gene. The hallmark of GD is the presence of lipid‐laden Gaucher macrophages, which infiltrate bone marrow and other organs. These pathological macrophages are believed to be the sources of elevated levels of inflammatory mediators present in the serum of GD patients. The alteration in the immune environment caused by GD is believed to play a role in the increased risk of developing multiple myeloma and other malignancies in GD patients. To determine directly whether Gaucher macrophages are abnormally activated and whether their functional defects can be reversed by pharmacological intervention, we generated GD macrophages by directed differentiation of human induced pluripotent stem cells (hiPSC) derived from patients with types 1, 2, and 3 GD. GD hiPSC‐derived macrophages expressed higher levels of tumor necrosis factor α, IL‐6, and IL‐1β than control cells, and this phenotype was exacerbated by treatment with lipopolysaccharide. In addition, GD hiPSC macrophages exhibited a striking delay in clearance of phagocytosed red blood cells, recapitulating the presence of red blood cell remnants in Gaucher macrophages from bone marrow aspirates. Incubation of GD hiPSC macrophages with recombinant GCase, or with the chaperones isofagomine and ambroxol, corrected the abnormal phenotypes of GD macrophages to an extent that reflected their known clinical efficacies. We conclude that Gaucher macrophages are the likely source of the elevated levels of inflammatory mediators in the serum of GD patients and that GD hiPSC are valuable new tools for studying disease mechanisms and drug discovery. Stem Cells 2014;32:2338–2349
Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma

Background—Human chorionic gonadotropin (hCG) is normally produced and secreted by trophoblastic cells during pregnancy and from gestational trophoblastic neoplasms. It is also detected in ovarian, stomach, and colon adenocarcinomas, as well as in squamous cell carcinoma of the oesophagus. Recently, interest in its role in the pathogenesis of tumours has been enlivened after the presence of βhCG in the cell membrane of several malignant cells was shown in vitro. Aims—To investigate the circulating concentrations of βhCG in patients with exocrine pancreatic adenocarcinoma and to examine its potential prognostic value. Patients—Thirty six patients with exocrine pancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and 21 healthy volunteers were studied. Methods—βhCG serum concentrations were detected by the application of a radioimmunoassay technique. Results—Fifteen of 36 patients with pancreatic adenocarcinoma and only one patient with chronic pancreatitis had detectable plasma concentrations of βhCG (p<0.01). The patients with circulating serum titres of βhCG had a worse outcome compared with the group of βhCG negative patients: the difference was statistically significant (p=0.01). Conclusion—More than 40% of pancreatic exocrine tumours produce βhCG and its production is correlated with an adverse effect on outcome.
Bayesian and likelihood phylogenetic reconstructions of 1 morphological traits are not discordant when taking uncertainty into 2 consideration

9 Puttick et al. [1] performed a simulation study to compare accuracy among methods of inferring 10 phylogeny from discrete morphological characters. They report that a Bayesian implementation 11 of the Mk model [2] was most accurate (but with low resolution), while a maximum likelihood 12 (ML) implementation of the same model was least accurate. They conclude by strongly 13 advocating that Bayesian implementations of the Mk model should be the default method of 14 analysis for such data. While we appreciate the authors’ attempt to investigate the accuracy of 15 alternative methods of analysis, their conclusion is based on an inappropriate comparison of the 16 ML point estimate, which does not consider confidence, with the Bayesian consensus, which 17 incorporates estimation credibility into the summary tree. Using simulation, we demonstrate that 18 ML and Bayesian estimates are concordant when confidence and credibility are comparably 19 reflected in summary trees, a result expected from statistical theory. We therefore disagree with 20 the conclusions of PEA and consider their prescription of any default method to be poorly 21 founded. Instead, we recommend caution and thoughtful consideration of the model or method 22 being applied to a morphological dataset. 23
Both LRP5 and LRP6 Receptors Are Required to Respond to Physiological Wnt Ligands in Mammary Epithelial Cells and Fibroblasts*

Background: Mammary stem cells require a specific Wnt signaling receptor, LRP5, despite co-expression of the (better studied) LRP6 receptor. Results: Both LRP5 and LRP6 are required for mammary epithelial cell responsiveness to Wnt1/9b/10b (but not Wnt3a). Conclusion: LRP5 co-expression with LRP6 can confer active Wnt signaling where either receptor alone cannot. Significance: This explains aspects of stem cell regulation and tumorigenesis. A canonical Wnt signal maintains adult mammary ductal stem cell activity, and this signal requires the Wnt signaling reception, LRP5. However, previous data from our laboratory have shown that LRP5 and LRP6 are co-expressed in mammary basal cells and that LRP6 is active, leading us to question why LRP6 is insufficient to mediate canonical signaling in the absence of LRP5. Here, we show that at endogenous levels of LRP5 and LRP6 both receptors are required to signal in response to some Wnt ligands both in vitro (in mouse embryonic fibroblasts and mammary epithelial cells) and in vivo (in mammary outgrowths). This subgroup of canonical ligands includes Wnt1, Wnt9b, and Wnt10b; the latter two are expressed in mammary gland. In contrast, the ligand commonly used experimentally, Wnt3a, prefers LRP6 and requires just one receptor regardless of cellular context. When either LRP5 or LRP6 is overexpressed, signaling remains ligand-dependent, but the requirement for both receptors is abrogated (regardless of ligand type). We have documented an LRP5-6 heteromer using immiscible filtration assisted by surface tension (IFAST) immunoprecipitation. Together, our data imply that under physiological conditions some Wnt ligands require both receptors to be present to generate a canonical signal. We have designed a model to explain our results based on the resistance of LRP5-6 heteromers to a selective inhibitor of E1/2-binding Wnt-LRP6 interaction. These data have implications for stem cell biology and for the analysis of the oncogenicity of LRP receptors that are often overexpressed in breast tumors.
Clinical Pharmacists' Impact on Prescribing in an Acute Adult Psychiatric Facility

An analysis is presented of data collected to evaluate the impact of a clinical pharmacy service on an acute psychiatric admitting unit. Retrospective longitudinal drug utilization reviews (RLDUR) were performed one year apart (pre- and post-implementation of services) on the same treatment team. Process measures significantly affected include (percent reduction): total drugs/patient (33.9), number of antipsychotic drugs/patient (38.0), number of anticholinergics started on admission/patient (53.2), and number of doses/patient/d (42.4). Other drug-use parameters significantly affected include: a 42-percent increase in the mean dosage expressed as chlorpromazine equivalents, and a 47-percent reduction in the number of patients on low potency antipsychotic medications. Beneficial outcome was reflected by a faster rate of discharge or transfer to a less restrictive ward environment in the pharmacy study population. The study population also demonstrated a 55.8-percent decrease in their readmission rate to the facility over a one-year follow-up period. Clinical pharmacy services positively affect both process and outcome health care measures.
ALLOGENEIC HEMOPOIETIC STEM CELL TRANSPLANTATION (HSCT) FOR WISKOTT-ALDRICH SYNDROME: A Report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)

Allogeneic stem cell transplantation is the only curative treatment for Wiskott-Aldrich syndrome. The authors retrospectively analyzed the outcome with this procedure in 13 patients with severe Wiskott-Aldrich syndrome transplanted in 5 Spanish centers from 1989 to 2006. A patient was transplanted twice from the same donor due to a late engraftment failure. Age at transplant ranged from 7 to 192 months (median 30 months). There were 10 matched donors (3 related and 7 unrelated), 2 mismatched unrelated, and 1 haploidentical. Conditioning regimen consisted of busulfan and cyclophosphamide (BuCy) in 11 cases and fludarabine and melfalan (1) or BuCy (1). ATG was added in transplants from non-genetically matched donors. GvHD prophylaxis consisted of cyclosporine and methotrexate in most patients plus T-cell depletion in the haploidentical HSCT. Nine of the 13 transplanted patients are alive with complete clinical, immunologic, and hematologic recovery 8–204 months (median 101 months) after HSCT. Eight surviving patients had been transplanted from matched donors (3 related and 5 unrelated) and 1 from a haploidentical donor. Four patients died, 2 transplanted from matched donors (1 from acute GvHD and organ failure, 1 from a lymphoproliferative disorder after a second transplant), and 2 transplanted from mismatched unrelated donors (1 from acute GvHD and organ failure, 1 from graft failure and infection). Allogeneic hemopoietic stem cell transplantation must be utilized in all patients with severe Wisckott-Aldrich syndrome, using the most suitable graft variant for each patient.
Effects of mild heat stress periods on milk production, milking frequency and rumination time of grazing dairy cows milked by a mobile automatic system.

Grazing dairy cows milked by an automatic system (AS) experienced mild heat stress (HS) periods twice during the summer. The daily temperature humidity index (THI) during these periods were higher than 72. Milk production, as well as milking frequency, rumination time and milk fat to protein ratio (F/P) during these periods were compared with adjacent periods with mean THI of 61. The daily milking frequency, the total number of visits to the AS, and milk production were significantly higher in HS periods (2.12 vs. 1.97, 2.99 vs. 2.69, and 19.7 vs. 18.5 kg milk per cow, respectively). There were significant interactions between times and periods for milking frequency and number of visits, whereas the daily rumination time was significantly lower (339 vs. 419 min) and the F/P in milk tended to be decreased (1.17 vs. 1.23). These results could be explained by changes in cow behaviour during HS periods.
Where Can Colorectal Cancer Screening Interventions Have the Most Impact?

Background: Although colorectal cancer death rates in the United States have declined by half since 1970, large geographic disparities persist. Spatial identification of high-risk areas can facilitate targeted screening interventions to close this gap. Methods: We used the Getis-Ord Gi* statistic within ArcGIS to identify contemporary colorectal cancer “hotspots” (spatial clusters of counties with high rates) based on county-level mortality data from the national vital statistics system. Hotspots were compared with the remaining aggregated counties (non-hotspot United States) by plotting trends from 1970 to 2011 and calculating rate ratios (RR). Trends were quantified using joinpoint regression. Results: Spatial mapping identified three distinct hotspots in the contemporary United States where colorectal cancer death rates were elevated. The highest rates were in the largest hotspot, which encompassed 94 counties in the Lower Mississippi Delta [Arkansas (17), Illinois (16), Kentucky (3), Louisiana (6), Mississippi (27), Missouri (15), and Tennessee (10)]. During 2009 to 2011, rates here were 40% higher than the non-hotspot United States [RR, 1.40; 95% confidence interval (CI), 1.34–1.46], despite being 18% lower during 1970 to 1972 (RR, 0.82; 95% CI, 0.78–0.86). The elevated risk was similar in blacks and whites. Notably, rates among black men in the Delta increased steadily by 3.5% per year from 1970 to 1990, and have since remained unchanged. Rates in hotspots in west central Appalachia and eastern Virginia/North Carolina were 18% and 9% higher, respectively, than the non-hotspot United States during 2009 to 2011. Conclusions: Advanced spatial analysis revealed large pockets of the United States with excessive colorectal cancer death rates. Impact: These well-defined areas warrant prioritized screening intervention. Cancer Epidemiol Biomarkers Prev; 24(8); 1151–6. ©2015 AACR.
Clips versus suture technique: is there a difference?

INTRODUCTION Coronary artery bypass grafting (CABG) is one of the most common procedures performed today, and wound complications are a major source of morbidity and cost. OBJECTIVE To determine whether there is any difference in wound outcome (including cost in a Canadian context) between a subcuticular suture technique and skin stapling technique for closure of sternal and leg incisions in CABG patients. PATIENTS AND METHODS One hundred and sixty-two patients undergoing CABG were prospectively, randomly placed to have their sternal and leg incisions closed with either a subcuticular suture technique or with a skin clip. Data were obtained through chart review, in-hospital assessments and follow-up visits. Nonblinded assessments were made regarding wound leakage, inflammation, infection, necrosis, swelling, dehiscence and cosmesis. Each of the parameters was graded on a scale from 1 to 4. The cost was evaluated in Canadian dollars. RESULTS There were trends toward increased rates of in-hospital sternal (P=0.09) and leg (P=0.17) incision inflammation when the wounds were closed with skin clips. There was a significantly greater (P=0.05) rate of sternal wound infection with clips, as well as a tendency (P=0.15) toward a greater rate of mediastinitis at follow-up assessment. Cosmetic outcome was similar for both groups. The cost incurred was significantly greater when skin clips were used for closure. There was a greater than threefold difference, which translates to a greater than $10,000 difference over one year. CONCLUSIONS Closure with a subcuticular technique achieves better outcomes than the use of skin clips. When factoring in the increased cost incurred by using clips, as well as other intangible factors such as surgical skill acquisition, subcuticular suture closure appears to be a favourable method of wound closure in CABG patients compared with the use of skin stapling techniques.