Miracle-dz/UniFAR-FTUs huggingface dataset:
MAP Kinase‐Dependent RUNX2 Phosphorylation Is Necessary for Epigenetic Modification of Chromatin During Osteoblast Differentiation

RUNX2, an essential transcription factor for osteoblast differentiation and bone formation is activated by ERK/MAP kinase‐dependent phosphorylation. However, relationship between these early events and specific epigenetic modifications of chromatin during osteoblast differentiation have not been previously examined. Here, we explore these relationships using chromatin immunoprecipitation (ChIP) to detect chromatin modifications in RUNX2‐binding regions of Bglap2 and Ibsp. Growth of MC3T3‐E1c4 preosteoblast cells in differentiation conditions rapidly induced Bglap2 and lbsp mRNAs. For both genes, osteogenic stimulation increased chromatin‐bound P‐ERK, P‐RUNX2, p300, and RNA polymerase II as well as histone H3K9 and H4K5 acetylation. The level of H3K4 di‐methylation, another gene activation‐associated histone mark, also increased. In contrast, levels of the gene repressive marks, H3K9 mono‐, di‐, and tri‐methylation in the same regions were reduced. Inhibition of MAP kinase signaling blocked differentiation‐dependent chromatin modifications and Bglap2 and Ibsp expression. To evaluate the role of RUNX2 phosphorylation in these responses, RUNX2‐deficient C3H10T1/2 cells were transduced with adenovirus encoding wild type or phosphorylation site mutant RUNX2 (RUNX2 S301A/S319A). Wild type RUNX2, but not the non‐phosphorylated mutant, increased H3K9 and H4K5 acetylation as well as chromatin‐associated P‐ERK, p300, and polymerase II. Thus, RUNX2 phosphorylation is necessary for subsequent epigenetic changes required for osteoblast gene expression. Taken together, this study reveals a molecular mechanism through which osteogenic genes are controlled by a MAPK and P‐RUNX2‐dependent process involving epigenetic modifications of specific promoter regions. J. Cell. Physiol. 232: 2427–2435, 2017. © 2016 Wiley Periodicals, Inc.
Barriers to antiretroviral adherence in HIV-positive patients receiving free medication in Kayunga, Uganda

Abstract Global and local efforts have been devoted to increase the supply of antiretroviral therapy (ART) in sub-Saharan Africa. Recent qualitative studies suggest that even with free ART, patients may fail to adhere to medication because of socioeconomic barriers such as transportation costs to clinics. The aim of this study was to measure adherence in a population of patients receiving free ART and to examine barriers to adherence. Adherence was measured using the pill count and self-report methods among 140 HIV-positive patients at four PEPFAR-facilitated ART clinics in Kayunga, a rural district in Uganda. Self-report was also used to examine reasons for non-adherence. Pill count adherence estimates revealed that 86.4% of the patients were adherent (≥95%) in the past six months. Self-report estimates showed that all the patients were adherent in the past six months with average adherence of 99.7%±0.6. The main reasons for non-adherence were being away from medication at dose time (29.4%) and forgetting to take pills (27.5%). Lack of access to food and transportation costs accounted for 11.7% and 7.8% of non-adherence, respectively. Patients with 100% adherence reported lack of access to food as the main challenge they had to overcome to stay adherent. Patients attending the rural clinic were significantly less adherent to ART than patients at the Kayunga district capital [OR 0.046 (0.008–0.269)]. The study revealed that the greatest patient-perceived challenge to adherence in this population is the lack of access to food; however, the immediate reasons for non-adherence were found to be forgetfulness and being away from medication at dose's time. These results suggest that interventions tackling lack of access to food are necessary, but interventions addressing forgetfulness and being away from medication at dose's time would be the most effective in enhancing adherence inpatients receiving free ART.
Perspectives on Community Dental Clinics and Oral Health Inequities in British Columbia

Background. This study investigates the expansion of community dental clinics to address oral health inequities in the province of British Columbia (BC) from the perspectives of dental professionals and allied service-providers. Methods. Sixty-three people participated in individual and group interviews with dentists (n=4), dental hygienists (n=30), dental clinic staff (n=17), and other health care and social service providers (n=12). Results. We identified two service-models: a volunteer-charitable (VC) model typically operating part-time mostly to relieve pain and a not-for-profit (NFP) model open full-time usually within a community health centre with paid staff providing basic dental services. Conclusions. Community dental clinics are increasing in number to fill a gap in the oral health care of disadvantaged people in BC. Staff in these clinics raised questions indirectly about distributive justice and health care inequity by suggesting that the unmet dental need of vulnerable people requires political attention and that restricted dentistry for underserved communities is socially unacceptable.
Pineal is required for testicular maintenance in the turkish hamster (mesocricetus brandti).

The effect of pinealectomy on reproductive function was examined in the Turkish hamster, Mesocricetus brandti. Pinealectomy resulted in testicular regression in this species. This result was unexpected since pinealectomy prevents short day-induced regression of the gonads in the closely related Syrian hamster, Mesocricetus auratus. Decentralization of the superior cervical ganglia and exposure to continuous illumination also caused testicular regression in the Turkish hamster. These manipulations are believed to block pineal melatonin synthesis. In each case (i.e. pinealectomy, decentralization of the superior cervical ganglia, exposure to continuous illumination), the testes regressed after approximately 3--9 weeks and underwent recrudescence after approximately 16--28 weeks. This cycle of testicular regression and recrudescence was similar to that observed in Turkish hamsters exposed to a short day photoperiod. In further experiments, the effects of exogenous melatonin were studied in Turkish and Syrian hamsters. The results of these studies suggest that, in Turkish hamsters, pineal melatonin may be involved in both the maintenance of testis function during exposure to a long day photoperiod and also in the suppression of reproductive function in short days. This is in contrast to the Syrian hamster, in which melatonin appears to be important only for inhibition of gonadal function in short days.
Pricing and capacity planning for product-line expansion and reduction

We investigate optimal pricing and capacity planning decisions for product-line settings such as introducing a new product or dropping an existing one. We consider a two-product, two-period model with stochastic demands, where price and capacity decisions are made at the outset. Investment in capacity must be traded-off against the possibility of buying at higher spot market prices due to shortage in capacity or charging a higher price to manage the demand. Prior studies argue that introducing an additional product to the product-line strains capacity, resulting in an increase in the price of an existing product. In contrast, we find that introducing a new product can also result in a drop in price of an existing product, enabling strategic pricing by firms. The necessary condition for this to occur is that the demand uncertainties for the products are of similar magnitude and negatively correlated. Similar insights are obtained for the setting where an existing product is dropped from the product-line. Hence, product-market decisions and contextual factors play a role in capacity planning, capacity cost allocation and pricing.
Reporting Score Distributions Makes a Difference: Performance Study of LSTM-networks for Sequence Tagging

In this paper we show that reporting a single performance score is insufficient to compare non-deterministic approaches. We demonstrate for common sequence tagging tasks that the seed value for the random number generator can result in statistically significant (p < 10^{-4}) differences for state-of-the-art systems. For two recent systems for NER, we observe an absolute difference of one percentage point F₁-score depending on the selected seed value, making these systems perceived either as state-of-the-art or mediocre. Instead of publishing and reporting single performance scores, we propose to compare score distributions based on multiple executions. Based on the evaluation of 50.000 LSTM-networks for five sequence tagging tasks, we present network architectures that produce both superior performance as well as are more stable with respect to the remaining hyperparameters.
Albuterol delivered by metered-dose inhaler to treat acute bronchitis.

BACKGROUND Previous research has suggested that cough associated with acute bronchitis is more likely to subside within 7 days when treated with albuterol than with an antibiotic. This study examines the effectiveness of aerosolized albuterol for the treatment of acute bronchitis in patients treated with erythromycin or placebo. METHODS A double-blind, randomized placebo-controlled trial of albuterol delivered by metered-dose inhaler (MDI) was conducted in a primary care setting with healthy adult patients who presented with a productive cough of fewer than 30 days' duration. In addition to randomization for albuterol, patients were also randomized to receive erythromycin or placebo. Outcomes were assessed at follow-up after 7 days. RESULTS Patients treated with albuterol MDI were less likely to be coughing after 7 days of treatment than were patients using a placebo inhaler (61% still coughing vs 91%, P = .02). When analysis was stratified by cigarette smoking status and the use of erythromycin, the differences observed between albuterol MDI patients and controls persisted. CONCLUSIONS Albuterol appears to reduce the likelihood that patients with acute bronchitis will be coughing after 7 days following initiation of treatment. This effect appears to be independent of cigarette smoking or the concomitant use of antibiotics.
A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) μ‐opioid agonists on cellular markers related to opioid tolerance and dependence

Previous studies established that Tyr‐D‐Ala‐Gly‐N‐Me‐Phe‐Gly‐ol (DAMGO) and (2S,4aR,6aR,7R,9S,10aS,10bR)‐9‐(Benzoyloxy)‐2‐(3‐furanyl)dodecahydro‐6a,10b‐dimethyl‐4,10‐dioxo‐2H‐naphtho‐[2,1‐c]pyran‐7‐carboxylic acid methyl ester (herkinorin) are fully efficacious μ‐agonists. Herkinorin (HERK), unlike DAMGO, does not recruit β‐arrestin and promote μ‐receptor internalization, even in cells that over express β‐arrestin. We hypothesized that chronic HERK and DAMGO treatment will differentially affect cellular markers of tolerance and dependence. CHO cells expressing the cloned human μ‐receptor were treated for 20 h with 10 μM DAMGO, HERK, morphine, or medium. Both DAMGO and HERK acted as full agonists in the [35S]GTP‐γ‐S binding assay with EMAX values of 230% and EC50 values of 12.8 and 92.5 nM, respectively. In the cAMP assay, DAMGO and HERK had similar EMAX values of ∼80% and EC50 values of 3.23 and 48.7 nM, respectively. Chronic exposure to both drugs produced moderate tolerance to both drugs (∼2 to 5 fold) in the [35S]GTP‐γ‐S binding assay. In the cAMP assay, chronic DAMGO produced tolerance to both drugs (∼3 to 4 fold). Chronic HERK eliminated the ability of either drug to inhibit forskolin‐stimulated cAMP accumulation. Chronic DAMGO increased, and chronic HERK decreased, forskolin‐stimulated cAMP accumulation. Naloxone, after chronic HERK (but not DAMGO) induced a large increase in forskolin‐stimulated cAMP accumulation. Viewed collectively with published data, the current data indicate that both internalizing and noninternalizing μ‐agonists produce cellular signs of tolerance and dependence. Synapse 61:166–175, 2007. Published 2006 Wiley‐Liss, Inc.
Empagliflozin (BI 10773), a Potent and Selective SGLT2 Inhibitor, Induces Dose‐Dependent Glucosuria in Healthy Subjects

Empagliflozin is an orally available, selective inhibitor of sodium glucose cotransporter 2. In this study, single oral doses of empagliflozin from 0.5 to 800 mg were not associated with any clinically significant safety concerns in healthy male volunteers. The incidence of adverse events (AEs) was similar in subjects receiving placebo (22.2%) or empagliflozin (25.0%) in the single rising dose part of the study and after 50 mg empagliflozin under fed (28.6%) or fasted (28.6%) conditions. The most frequent AE was headache. No clinically relevant changes in laboratory or electrocardiogram (ECG) measurements were observed. Single oral doses of empagliflozin were rapidly absorbed, reaching peak levels after 1.0–2.1 hours. Increases in empagliflozin exposure were roughly dose‐proportional and a dose‐dependent increase in urinary glucose excretion was observed for empagliflozin doses up to 100 mg. After ingestion of 50 mg empagliflozin in conjunction with a high‐fat, high‐calorie meal, no clinically relevant changes in exposure were found, indicating that empagliflozin can be administered independent of food. Empagliflozin up to 800 mg did not generate clinically significant safety concerns in healthy male subjects. The pharmacokinetic properties of empagliflozin support once daily administration independent of food.
Effects of intracuff dexamethasone on post-extubation reactions

Background: The most common complications after tracheal intubation during general anesthesia are sore throat, hoarseness, and laryngospasm which can cause severe discomfort to patients. Several methods have been suggested to prevent these complications. In this study, the effects of intracuff dexamethasone, lidocaine, and normal saline in reducing post-extubation reactions were compared. Methods: This double-blind clinical trial was performed on 180 men of ASA (American Society of Anesthesiologists) class I or II who underwent general anesthesia for elective inguinal herniation surgery in Imam Reza Hospital, Tehran, Iran during 2008-2010. Depending on the kind of drug used to fill the endotracheal tube (ETT) cuff, patients were randomly allocated into normal saline, lidocaine, and dexamethasone groups. Post-extubation reactions were then evaluated in all groups. Results: The groups were demographically comparable. There were no significant differences between the three groups regarding post-extubation sore throat, hoarseness, or laryngospasm (p > 0.05). However, a significant difference in cough existed between the three groups (p = 0.02). Moreover, the groups were not significantly different in terms of patient satisfaction after 24 hours (p = 0.062). Prolongation of spontaneous ventilation time and time to extubation were observed in the three groups. No significant differences were detected between the three groups regarding hemodynamic variables. Conclusion: The three drugs were not significantly different in attenuating post-extubation reactions such as hoarseness, sore throat, and laryngospasm. However, lidocaine was more effective on cough incidence while dexamethasone had better efficacy in reducing cough severity. In addition, all three drugs could satisfy patients after 24 hours. ETT tolerance was more in the lidocaine group than the other two groups.
Expression of VEGF-C/VEGFR-3 in human laryngeal squamous cell carcinomas and its significance for lymphatic metastasis.

OBJECTIVES Expression of vascular endothelial growth factor C (VEGF-C)and vascular endothelial growth factor receptor-3 (VEGFR-3) in laryngeal squamous carcinoma and its relationship to lymph node metastasis were investigated. METHODS VEGF-C and VEGFR-3 gene expression in 30 cases of normal laryngeal mucosa tissue (NLM), primary laryngeal carcinoma cell carcinomas (PLC) and cervical lymph nodes (CLN) was examined by reverse transcription polymerase chain reaction (RT-PCR). Protein levels of VEGF-C expression were determined by immunohistochemical staining in 60 cases of PLC. RESULTS Expression of VEGF-C and VEGFR-3 different among NLM, PLC and CLN in the same patient. In PLC, expression was significantly higher in lymph node positive group than in the lymph node negative group and associated with histological grade of differentiation; Expression of VEGF-C and VEGFR-3 was not linked with age, sex, site or T stage. CONCLUSIONS A close correlation was found between VEGF-C/VEGFR-3 expression and lymph node metastasis in PLC, suggesting a role in metastasis of laryngeal carcinomas.
Comparison of Prolactin, CA 15–3 and TPA in Breast Carcinomas

Circulating prolactin, CA 15–3 and TPA were assayed pre-therapeutically and sequentially thereafter from 68 breast cancer patients attending the Gujarat Cancer and Research Institute, Ahmedabad — a regional cancer institute in Western India. The three marker values were correlated with the stage, histologic grade and disease status. At least one of the markers was elevated in 82% of patients. CA 15–3 and TPA levels were elevated with the advancement of stage. Prolactin levels were high in poorly differentiated tumors of pre-menopausal patients. The disease status was effectively reflected by the levels of prolactin and CA 15–3. TPA showed high false positivity so was of no use as an indicator of disease status. Recurrence could be predicted early, with a lead time of 3–6 months using prolactin and CA 15–3.
Urinary tract ultrasonography in normal rams and in rams with obstructive urolithiasis.

We determined the position, dimensions, and structure of the kidneys, ureters, bladder, and urethra in 20 healthy, adult rams by use of ultrasonography. The findings were compared with those of seven rams with obstructive urolithiasis, thus establishing criteria for the diagnosis of urolithiasis via ultrasonography. A 5.0 MHz convex transducer was placed over the right paralumbar fossa to examine the kidneys, and a 5.0 MHz linear rectal transducer was used to examine the bladder and urethra transrectally. All examinations were performed on standing rams. The left kidney had a length of 8.4 +/- 0.3 cm (mean +/- SD), a width of 4.7 +/- 0.3 cm, and a depth of 4.4 +/- 0.3 cm. The diameter of the renal sinus of the left kidney was 1.5 +/- 0.2 cm. The circumference of the medullary pyramids measured 2.8 +/- 0.3 cm. Similar ultrasonographic measurements were obtained for the right kidney. The mean diameter of the bladder of 12 rams was 7.5 +/- 2.8 cm. The diameter of the bladder could not be determined in the remaining eight rams because it was greater than 10 cm and therefore beyond the penetration depth of the scanner. The only part of the urethra which could be visualized ultrasonographically was the internal urethral orifice. It had a diameter of 0.2 +/- 0.1 cm.Ultrasonographic examination of seven rams with obstructive urolithiasis revealed a markedly dilated urethra and urinary bladder. Due to severe cystitis, the contents of the urinary bladder appeared as multiple, tiny, uniformly distributed echoes. The renal pelvis and medullary pyramids of both kidneys were dilated in four rams. In two rams, uroperitoneum and accumulation of urine in the abdomen were diagnosed via ultrasonography. In one ram this was due to a ruptured ureter and in one to a ruptured bladder. The results of this study indicate that ultrasonography is a useful aid in the diagnosis of obstructive urolithiasis.
Biosynthetic Studies on Acetosellin and Structure Elucidation of a New Acetosellin Derivative

Abstract Natural products from fungi, especially Ascomycota, play a major role in therapy and drug discovery. Fungal strains originating from marine habitats offer a new avenue for finding unusual molecular skeletons. Here, the marine-derived fungus Epicoccum nigrum (strain 749) was found to produce the azaphilonoid compounds acetosellin and 5′,6′-dihydroxyacetosellin. The latter is a new natural product. The biosynthesis of these polyketide-type compounds is intriguing, since two polyketide chains are assembled to the final product. Here we performed 13C labeling studies on solid cultures to prove this hypothesis for acetosellin biosynthesis.
JTCP: jitter-based TCP for heterogeneous wireless networks

Transmission control protocol (TCP), a widely used transport protocol performs well over the traditional network which is constructed by purely wired links. As wireless access networks are growing rapidly, the wired/wireless mixed internetwork, a heterogeneous environment will get wide deployment in the next-generation ALL-IP wireless networks. TCP which detects the losses as congestion events could not suit the heterogeneous network in which the losses will be introduced by higher bit-error rates or handoffs. There exist some unsolved challenges for applying TCP over wireless links. End-to-end congestion control and fairness issues are two significant factors. To satisfy these two criteria, we propose a jitter-based scheme to adapt sending rates to the packet losses and jitter ratios. The experiment results show that our jitter-based TCP (JTCP) conducts good performance over the heterogeneous network.
Decreasing the knowledge gap among different socioeconomic status groups on the issue of climate change

ABSTRACT Climate change is causing severe negative consequences to small low-lying islands. To mitigate and adapt to climate change, it is important to improve public knowledge on its causes and consequences. As a social issue that needs collective action to address, the knowledge gap among different segments of population would be a barrier to people’s behaviors toward mitigation and adaption to climate change. This study aims to investigate public knowledge acquisition of climate change by revisiting the knowledge gap hypothesis. A nationally representative random computer-assisted telephone interview survey (N = 1093) was conducted in Singapore. Quantitative analyses revealed that both newspaper reading and television viewing could reduce the knowledge gap between high and low socioeconomic status individuals. We recommend that governments and relevant authorities should utilize mass media to disseminate information and cultivate public understanding of climate change.