Miracle-dz/UniFAR-FTUs huggingface dataset:
Repression of breast cancer cell growth by proteasome inhibitors in vitro: impact of mitogen-activated protein kinase phosphatase 1

Mitogen activated protein kinase phosphatase-1 (MKP-1) has emerged as an important protein mediating breast cancer oncogenesis and chemoresistance to cancer chemotherapies, especially proteasome inhibitors. In this in vitro study, we utilized the breast cancer epithelial cell lines MCF-7 and MDA-MB-231, in comparison to MCF-10A control cells, to examine the impact of MKP-1 on breast cancer cell growth and repression by proteasome inhibitors. We confirm that proteasome inhibitors MG-132 and bortezomib induce MKP-1 protein upregulation and we show that one of the ways in which bortezomib increases MKP-1 in breast cancer cells, in addition to inhibition of ubiquitin-proteasome system, is via upregulation of MKP-1 mRNA expression in p38 MAPK-mediated manner. Notably, these effects are specific to cancer cells, as bortezomib activated p38 MAPK and induced MKP-1 in MCF-7 and MDA-MB-231 breast cancer cells, but not in control cells (MCF-10A). We took a dual approach toward targeting MKP-1 to show that bortezomib-induced effects are enhanced. Firstly, treatment with the non-specific MKP-1 inhibitor triptolide reduces breast cancer cell growth and augments proteasome inhibitor-induced effects. Secondly, specific knock-down of MKP-1 with siRNA significantly repressed cell viability by reduced cyclin D1 expression, and enhanced repression of cancer cell growth by proteasome inhibitors. Taken together, these results indicate that removing the unwanted (MKP-1-inducing) effects of bortezomib significantly improves the efficacy of proteasome inhibition in breast cancer cells. Thus, future development of drugs targeting MKP-1 offer promise of combination therapies with reduced toxicity and enhanced cell death in breast cancer.
A physical model scheduler for multi-hop wireless networks based on local information

There is wide consensus that properly taking into account wireless interference is necessary to design high performance link scheduling algorithms for multi-hop networks. However, most approaches in the literature use simplified models, which significantly abstract from the physical behavior of wireless links. Indeed, the main problem in representing the wireless propagation conditions with a proper level of detail is the very large amount of information needed, that includes the wireless link gains between all node pairs. In this paper, we propose a greedy, centralized scheduler which is based on the physical interference model but aims at exploiting local information available at each node, in order to reduce global information exchange and therefore the overhead as well as the computational complexity of the algorithm. We prove the effectiveness of our approach by extensive simulation results. We also show that our system outperforms the most up-to-date benchmark in realistic interference aware schedulers for wireless multi-hop networks.
The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans

Here, Coffill et al. characterize Tp53, Tp63, and Tp73 in a jawless vertebrate, the Japanese lamprey, as well as the Mdm2 and Mdm4 genes using genome analysis. Functional analysis reveals conservation of p63 and p73 compared with p53, which shows substantial variability within the C-terminal and N-terminal domains, and that lamprey Mdm2 degrades human p53 with great efficiency; however, this interaction is not inhibited by currently available small molecule inhibitors of the human HDM2 protein.
PELAPORAN CORPORATE SOCIAL RESPONSIBILITY (CSR) DENGAN MENGGUNAKAN GLOBAL REPORTING INITIATIVE (GRI)

Abstrak Perusahaan adalah organisasi yang didirikan oleh seorang atau sekelompok orang yang aktivitasnya harus memperhatikan lingkungan disekitarnya. Corporate Sosial Responsibility (CSR) merupakan bentuk perhatian perusahaan terhadap masyarakat disekitarnya. Proses pelaksanaan CSR dikenal dengan nama Triple Bottom Lineyang memuat tiga hal yaitu: Planet, People dan Profitdan laporan pelaksanaan atau laporan keberlanjutannya dinamakan sustainability report yang memakai standar yang terdapat dalam Global Reporting Initiative (GRI) terdiri dari yaitu : strategi dan profil, pendekatan manajemen dan implementasi. Metode penelitian ini menggunakan kualitatif deskriptif dengan menggunakan laporan keberlanjutan untuk pemaparannya. Kesimpulannya bahwa dengan pelaporan CSR yang memakai standar GRI, maka laporan tersebut tidak hanya menginformasikan mengenai proses pelaksanaan CSR, namun juga memperkenalkan kepada masyarakat luas mengenai profil dan strategi perusahaan serta pendekatan manajemen yang dilakukan serta manfaat lain yang dapat menghasilkan keuntungan secara ekonomis. Keywords : Corporate Sosial Responsibility, Global Reporting Initiative
Diagnosis and treatment of Clostridium difficile in adults: a systematic review.

IMPORTANCE Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. OBJECTIVE To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years). EVIDENCE REVIEW Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process. FINDINGS Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI). CONCLUSIONS AND RELEVANCE Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.
Informed Trading in the Options Market and Stock Return Predictability

Previous research highlights the importance of two distinct types of informed trading in the options market: trading on the price direction of underlying stocks, and trading on their uncertainty. Surprisingly, however, the studies considering these in a unified framework are scant.This study attempts to fill the gap. We predict that when both directional andvolatility information could motivateoptions trading, the return predictability of options volume hinges onthe shape of the volatility smirk.Consistent with this prediction, we find thatthe negative relationship between options volume and future stock returns is concentrated in stocks exhibiting steep volatility smirks. © 2017 Wiley Periodicals, Inc. Jrl Fut Mark 37:1053–1093, 2017
Imagination of body rotation can induce eye movements

Objective Several studies have shown that spatiotemporal aspects of motion are stored and can be retrieved with the use of vestibular and somatosensory cues. The purpose of this study was to examine whether intentional imagination of body rotation can induce oculomotor activity similar to the typical vestibulo-ocular reflex (VOR). Material and Methods Normal subjects without known vestibular and/or oculometric abnormalities were instructed to imagine a sensation of accelerating body rotation in the horizontal plane (rightward or leftward) while sitting in darkness with closed eyes, using only vestibular and somatosensory cues and not imaginary visual cues. Eye movements were recorded during the imagery session and also during a full, routine electronystagmography (ENG) test. All subjects selected for this study showed normal results in the ENG test, and none of them had gaze-evoked or end-point nystagmus. Results In response to imaginary rotations, horizontal eye movements were found in 91/121 recordings (75%) in 10 subjects. A typical pattern of nystagmus (0.3–3 Hz, 3–30°/s maximal speed of slow component) was recorded in 53% of mental rightward rotations and 49% of leftward rotations. The fast component was always in the direction of the imaginary rotation (similar to a normal VOR). Other types of eye movement comprised either contralateral eye drift (≈17% of trials) or macro square waves. In 25% of the recordings no definite eye movements could be detected during the mental maneuvers. Conclusion These mentally induced eye movements seem to be due to a cortical process which can affect the normal input to the brainstem nuclei. A possible mechanism is discussed. This phenomenon may serve as an objective measurement of mental activity, may be used for testing the cognitive resources of patients and can probably be used for enhancing the rehabilitation process after acute vestibular insult.
Comparison of homologous and heterologous formats in nanocolloidal gold-based immunoassays for parathion residue determination

The effectiveness of homologous and heterologous formats in a nanocolloidal gold-based immunoassay for pesticide residue determination was investigated. Parathion, one of the most toxic organophosphorus pesticides, was used as the target analyte. One-step homologous and heterologous test strips based on a nanocolloidal gold-labeled monoclonal antibody were developed for the rapid detection of parathion residues. The results showed that the heterologous format was more effective than the homologous format, being more sensitive, more specific to parathion and more tolerant of matrix interferences. The best competitive hapten was found to have a moderate heterology and the opposite electronic distribution to the immunizing hapten. The detection limits for parathion using the preferred heterologous strip were 1 μg/L in water samples and 5 μg/kg in soil and food samples.
Long Wavelength Pass Filters Designed for the Management of Color Vision Deficiencies

This study reports on the effectiveness of long wavelength pass filters dispensed as tinted spectacles as an aid for individuals with congenital red-green color vision deficiencies. The effectiveness of the filters was evaluated by the performance on a series of clinical color vision tests and a questionnaire after the subjects had tried the lenses for 1 week. The lenses improved performance on color vision tests that required discrimination between large color differences, particularly between red and green hues. However, performance was degraded on tests which required fine color discrimination or used colors that were located parallel to the tritan confusion axis. The improved performance on certain tests was primarily based on brightness artifacts induced by the filters, whereas the degraded performance on the other tests was due to the absorption of short- to midwavelength light by the filters. A slight majority (56%) of the subjects rated the filters as being moderate to highly effective in improving their color discrimination. Nevertheless, only 17% were interested in actually purchasing a pair. Common reasons for rejecting the filters were the color distortions produced by the red filters and fewer colors were actually perceived when wearing the filters.
Glutathione‐S‐transferase polymorphisms and risk of squamous‐cell carcinoma of the head and neck

Differences in genetic susceptibility to tobacco‐induced carcinogenesis appear to modulate an individual's risk of squamous‐cell carcinoma of the head and neck (SCCHN). Risk for SCCHN may be associated with the null alleles of the carcinogen‐metabolizing genes glutathione‐S‐transferase (GST) T1 and GSTM1. In this study, we evaluated the association between GSTM1 and GSTT1 null genotypes and risk of SCCHN in a matched case‐control study of 162 patients with SCCHN and 315 healthy controls. Our results showed that 53.1% of cases and 42.9% of controls were null for GSTM1, whereas 32.7% of cases and 17.5% of controls were null for GSTT1 (p < 0.05 and p < 0.001, respectively). Furthermore, 19.8% of cases but only 7.9% of controls were null for both genes (p < 0.001). Multivariate analysis using logistic regression models, including age, sex, ethnicity, smoking status, alcohol status and GST genotypes, showed that both of these genotypes remained independent risk factors for disease [adjusted odds ratios (ORs) = 1.50 and 2.27, respectively; 95% confidence intervals (CIs) = 1.01–2.23 and 1.43–3.60, respectively). When the genotypes were divided into neither null, either null or both null, there was a dose‐response relationship (adjusted OR = 1.50, 95% CI = 0.98–2.30) for the either‐null group and (adjusted OR = 3.64, 95% CI = 1.94–6.84) for the both‐null group (p < 0.001, trend test). Our findings suggest that the GSTM1 and GSTT1 null genotypes are independent risk factors for SCCHN and markers for genetic susceptibility to tobacco‐induced carcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:220–224, 1999. © 1999 Wiley‐Liss, Inc.
Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.
Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma

Background: The present study observed the expression levels of epidermal growth factor receptor (EGFR), p53, Bcl2, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (cox-2), cyclin D1, human epidermal receptor-2 (HER-2) and Ki-67 in gallbladder carcinoma (GBC) and their association with clinicopathological profiles and disease outcomes. Materials and Methods: Fifty consecutive samples of cholecystectomy/biopsies from GB bed (archived formalin fixed paraffin embedded tissue blocks of different stages of GBC) were included, and patient details related to their demographic profile, investigations, tumor profile, treatment, and follow-up were recorded. Immunohistochemistry was performed to study the expression levels. Results: Overexpression of EGFR, p53, Bcl2, VEGF, cox-2, cyclin D1 and HER-2 was observed as 74%, 44%, 8%, 34%, 66%, 64%, and 4%, respectively. Association of Bcl2 overexpression in mucinous morphology (40%, P = 0.045), cox-2 overexpression in early stage (I/II) tumors (87.5%, P = 0.028) and VEGF overexpression in alive patients (47.1%, P = 0.044) was observed. Co-expression of EGFR and p53 were statistically significant (P = 0.033). Ki-67 labeling index was significantly higher in patients in age group <40 years (P = 0.027), and poorly differentiated tumors (P = 0.023). Advanced disease and poorly differentiated tumors showed a significantly poor median survival (P < 0.05). Conclusion: EGFR, cox-2 and cyclin D1 were largely overexpressed. Advanced tumor stages and poorly differentiated tumors are predictors of poor survival.
Can HRM alleviate the negative effects of the resource curse on firms? Evidence from Brunei

Purpose The resource curse literature suggests that firms operating in non-oil and non-gas industries in petrostates face considerable challenges in securing competitiveness and sustaining themselves. Based on a firm-level survey within a micro-petrostate, Brunei, the purpose of this paper is to explore the relationship between specific HR policies and practices and organisational performance; analyse, compare, and contrast oil and gas with non-oil and non-gas sectors; and draw out the comparative lessons for understanding the potential and performance consequences of HR interventions in resource-centred national economies. Design/methodology/approach Data for this study were generated from a primary survey administered amongst the HR directors in companies operating in all sectors in Brunei. A statistically representative sample size of 214 was selected. Findings The authors confirmed that firms in the oil and gas sector indeed performed better than other sectors. However, the authors found that the negative effects associated with operating outside of oil and gas could be mitigated through strategic choices: the strategic involvement of HR directors in the affairs of the company reduced employee turnover and added positively to financial returns across sectors. Practical implications Developing and enhancing the role of people management is still very much easier than bringing about structural institutional reforms: the study confirms that at least part of the solution to contextual difficulties lies within, and that the firm-level consequences of the resource curse can be ameliorated through a strategic choice. Originality/value The nature of the present investigation is one of few studies conducted in South East Asia in general and in the context of Brunei, in particular. It also contributes to the authors’ understanding whether HR interventions can ameliorate the challenges of operating in a non-resource sector in a resource-rich country.
A Corpus-based Comparative Study of Ideational Grammatical Metaphor in Marine Engineering and Maritime Legal Regulation English

Grammatical metaphor is one of the language phenomena introduced by Halliday (2004) in the framework of functional grammar. This paper used Halliday’s metafunctional framework in marine engineering and maritime legal regulation English discourses under Prichard’s category (2003) of English for occupational purposes and English for academic purposes respectively. The analysis of data was conducted through a description of English occupational and academic texts, based on grammatical metaphor. The researcher conducted some statistical analysis, including frequency and percentage of ideational grammatical metaphor and its different processes of transitivity in both genres. Finally, two genres of English texts were compared statistically to show in what aspect they are significantly different or similar. The results obtained indicate that the two genres bear more similarities than differences in terms of using the nominalization of ideational grammatical metaphor. In other words, while indicating genre differences, the study proves their functional similarities in using the material process types more than other process types to convey meaning, however marine engineering English applies a little less frequency of material and relational process. Some behavior process types were found in marine engineering English texts but no behavior processes were found in marine legal English. Maritime legal English applies small amount of existential process and mental process while in marine engineering English these two types of process were not found. Both genres apply ideational metaphor to condense the information and increase the complexity of sentence structure.
Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke

Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.