Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations of microRNAs and their targets are associated with acquired resistance of MCF‐7 breast cancer cells to cisplatin

Cancer cells that develop resistance to chemotherapeutic agents are a major clinical obstacle in the successful treatment of breast cancer. Acquired cancer chemoresistance is a multifactorial phenomenon, involving various mechanisms and processes. Recent studies suggest that chemoresistance may be linked to drug‐induced dysregulation of microRNA function. Furthermore, mounting evidence indicates the existence of similarities between drug‐resistant and metastatic cancer cells in terms of resistance to apoptosis and enhanced invasiveness. We studied the role of miRNA alterations in the acquisition of cisplatin‐resistant phenotype in MCF‐7 human breast adenocarcinoma cells. We identified a total of 103 miRNAs that were overexpressed or underexpressed (46 upregulated and 57 downregulated) in MCF‐7 cells resistant to cisplatin. These differentially expressed miRNAs are involved in the control of cell signaling, cell survival, DNA methylation and invasiveness. The most significantly dysregulated miRNAs were miR‐146a, miR‐10a, miR‐221/222, miR‐345, miR‐200b and miR‐200c. Furthermore, we demonstrated that miR‐345 and miR‐7 target the human multidrug resistance‐associated protein 1. These results suggest that dysregulated miRNA expression may underlie the abnormal functioning of critical cellular processes associated with the cisplatin‐resistant phenotype.
Towards an Islamic Stock Exchange in a Transitional Stage

The paper deals with the structure and operation of an Islamic stock exchange. Several issues have been discussed. The first of these is related to speculation. Though speculation is often blamed for the volatility of share prices, the paper contends that a reasonable degree of speculation is still required in an Islamic stock exchange. To regulate speculation in an Islamic stock exchange, an aim that the paper advocates, several methods have been suggested. The second major question which has been addressed in the paper is related to price mechanism. Although some writers have suggested price ceiling in an Islamic stock exchange, the paper argues that price fixation should be avoided. The paper also discusses the organizational structure of an Islamic stock market and the code of conduct appropriate to it.
Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation

In the G protein-coupled receptor rhodopsin, the conserved NPxxY(x)5,6F motif connects the transmembrane helix VII and the cytoplasmic helix 8. The less geometrically constrained retinal analogue 9-demethyl-retinal prevents efficient transformation of rhodopsin to signaling metarhodopsin (Meta) II after retinal photoisomerization. Here, we demonstrate that Ala replacement mutations within the NPxxY(x)5,6F domain, which eliminate an interaction between aromatic residues Y306 and F313, allow formation of Meta II despite the presence of 9-demethyl-retinal. Also a disulfide bond linking residues 306 and 313 in the 9-demethyl-retinal-reconstituted mutant Y306C/F313C/C316S prevented Meta II formation, whereas the reduced form of the mutant readily transformed to Meta II after illumination. These observations suggest that the interaction between residues 306 and 313 is disrupted during the Meta I/Meta II transition. However, this enhancement in Meta II formation is not reflected in the G protein activation, which is dramatically reduced for these mutants, suggesting that changes in the Y306–F313 interaction also lead to a proper realigning of helix 8 after photoisomerization. The E134Q mutation, located in the second conserved motif, D(E)RY, rescues activity in 9-demethyl-retinal-reconstituted mutants to different degrees, depending on the position of the Ala replacement in the NPxxY(x)5,6F motif, thus revealing distinct roles for the NP and Y(x)5,6F portions. Our studies underscore the importance of the NPxxY(x)5,6F and D(E)RY motifs in providing structural constraints in rhodopsin that rearrange in response to photoisomerization during formation of the G protein-activating Meta II. The dual control of the structural rearrangements secures reliable transformation of quiescent rhodopsin to activating Meta II.
Characterization of phycobilisome glycoproteins in the cyanobacterium Anacystis nidulans R2

Concanavalin A-reactive linker and anchor subunits of phycobilisomes from Anacystis nidulans R2 (H. C. Riethman, T. P. Mawhinney, and L. A. Sherman, FEBS Lett. 215:209-214, 1987) were purified electrophoretically and analyzed for carbohydrate composition and quantity. Different quantities of glucose and N-acetylgalactosamine were found on the concanavalin A-reactive subunits analyzed. Proteolytic analysis of the purified subunits suggested that small regions of the 33- and 27-kilodalton linker polypeptides previously shown to be important for in vitro phycobilisome assembly contained the concanavalin A-reactive carbohydrates present on these subunits. The linker and anchor subunits from the morphologically different phycobilisome of Synechocystis sp. strain PCC6714 were also shown to be concanavalin A reactive. Membranes from iron-starved Anacystis nidulans, which lack assembled phycobilisomes and are associated with glycogen deposits, were shown to be depleted of linker and anchor proteins and to accumulate very large quantities of a concanavalin A-reactive, extrinsic membrane glycoprotein. We suggest that this iron stress-induced glycoprotein is associated with the glycogen deposits on the thylakoid surface and that the glycosylation of phycobilisome linker and anchor subunits is involved in the physiological regulation of phycobilisome assembly and degradation.
Body-Tied Germanium FinFETs Directly on a Silicon Substrate

We fabricated body-tied Ge p-channel fin field-effect transistors (p-FinFETs) directly on a Si substrate with a high-κ/metal gate stack. This scheme is fully compatible with Si standard processing. The FinFET structure has excellent control on the channel potential and thus can improve the short-channel effect. The diode with p<sup>+</sup>-Ge/n-Si heterojunctions illustrates a remarkably high I<sub>ON</sub>/I<sub>OFF</sub> >; 10<sup>6</sup> despite the presence of misfit dislocations at the interface. The high-hole-mobility body-tied Ge p-FinFETs with a fin width <i>W</i><sub>Fin</sub> of ~ 40 nm and a mask channel length <i>L</i><sub>Mask</sub> of 120 nm depict a driving current of 22 μA/μm at <i>VG</i> = -2V and a low off-current of 3 nA/μm at <i>VG</i> = 2V. The subthreshold characteristics with a swing of 228 mV/dec and drain-induced barrier lowering of 288 mV/V are demonstrated.
Measuring the financial sustainability and its influential factors in local governments

ABSTRACT The economic crisis has led international organizations and previous research to point out the need for measuring and controlling financial sustainability in governments. Based on the main international pronouncements, this article seeks to contribute to the measurement and management of the financial sustainability, analysing the income statement evolution and identifying its influential factors. An empirical study of Spanish municipalities is then undertaken to test the relationship between the measure of the financial sustainability and three dimensions proposed by International Federation of Accountants (IFAC) (revenues, debt and services). Our findings indicate that the income statement is a good approach for the financial sustainability assessment, because it reveals relevant information about its three dimensions, allowing to identify the specific factors which could provoke sustainability problems on public services.
Exploring the modular nature of riboswitches and RNA thermometers

Abstract Natural regulatory RNAs like riboswitches and RNA thermometers (RNAT) have considerable potential in synthetic biology. They are located in the 5′ untranslated region (UTR) of bacterial mRNAs and sense small molecules or changes in temperature, respectively. While riboswitches act on the level of transcription, translation or mRNA stability, all currently known RNATs regulate translation initiation. In this study, we explored the modularity of riboswitches and RNATs and obtained regulatory devices with novel functionalities. In a first approach, we established three riboswitch-RNAT systems conferring dual regulation of transcription and translation depending on the two triggers ligand binding and temperature sensing. These consecutive fusions control gene expression in vivo and can even orchestrate complex cellular behavior. In another approach, we designed two temperature-controlled riboswitches by the integration of an RNAT into a riboswitch aptamer domain. These ‘thermoswitches’ respond to the cognate ligand at low temperatures and are turned into a continuous on-state by a temperature upshift. They represent the first RNATs taking control of transcription. Overall, this study demonstrates that riboswitches and RNATs are ideal for engineering synthetic RNA regulators due to their modular behavior.
Seizure Detection by a Novel Wavelet Packet Method

We describe a novel wavelet-based method for the detection of seizure in patients with temporal lobe epilepsy. This method uses local discriminant bases and cross- data entropy algorithms to identify nodes of a wavelet packet dictionary that best discriminate preictal from ictal EEG signals. The algorithms are based on relative entropy criterion as a measure of discrepancy between different classes of signals. The frequency bands associated with these nodes were in the range of interest for seizure events. After selecting two bands, we determined the ratio of energies at the level of wavelet packet chosen by the cross-data entropy algorithm. Preliminary results demonstrate that the wavelet packet energy ratio could serve as a robust criterion in seizure detection
Association of preoperative plasma levels of insulin-like growth factor I and insulin-like growth factor binding proteins-2 and -3 with prostate cancer invasion, progression, and metastasis.

PURPOSE We tested the hypothesis that preoperative plasma levels of insulin-like growth factor (IGF) binding protein (BP)-2 or IGFBP-3 would predict cancer stage and prognosis in patients undergoing radical prostatectomy. MATERIAL AND METHODS Plasma levels of IGF-I, IGFBP-2, and IGFBP-3 were measured preoperatively in 120 consecutive patients who underwent radical prostatectomy for clinically localized disease, postoperatively in 51 of these patients, in 44 healthy men, in 19 patients with metastases to regional lymph nodes, and in 10 patients with bone metastases. RESULTS Plasma IGFBP-3 levels were lowest in patients with bone metastases (P < or = .043). IGFBP-2 levels were elevated in prostate cancer patients compared with healthy subjects (P < or = .006). However, within the group of prostatectomy patients, preoperative plasma IGFBP-2 levels were lower in patients with advanced disease (P < or = .033), were inversely correlated with prostatic tumor volume (P =.037), and declined after prostate removal (P =.044). Lower preoperative IGFBP-2 and IGFBP-3 levels and biopsy Gleason score were independent predictors of biochemical progression (P =.043, P =.040, and P =.020, respectively). In patients with disease progression, preoperative plasma IGFBP-3 levels were lower in those with aggressive than in those with nonaggressive failure (P =.042). CONCLUSION Elevation of plasma IGFBP-2 levels in prostate cancer patients apparently is due to increased release directly from the prostate. For patients with clinically localized prostate cancer, preoperative plasma IGFBP-2 levels are inversely associated with biologically aggressive disease and disease progression. Preoperative plasma IGFBP-3 levels were decreased in patients with prostate cancer metastases and were an independent predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
Evaluation of Anticonvulsant, Sedative, Anxiolytic, and Phytochemical Profile of the Methanol Extract from the Aerial Parts of Swertia corymbosa (Griseb.) Wight ex C.B. Clarke

The objective of the present study was to evaluate the anxiolytic, antidepressant, and anticonvulsant activity of the methanolic extract of Swertia corymbosa (SCMeOH). After acute toxicity test, oral treatment with SCMeOH at doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus-maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal electroshock induced seizure models were utilized. In open field test, SCMeOH (125, 250, and 500 mg/kg) (P < 0.01, P < 0.001) increased the number of rearings. However, the number of central motor and ambulation (P < 0.01, P < 0.001) were reduced. Likewise, the number of entries and the time spent in open arm were increased while the number of locomotion was decreased (P < 0.001) in elevated-plus-maze and actophotometer test, respectively. SCMeOH (125–500 mg/kg) protected the mice against the pentylenetetrazole and isoniazid induced convulsions; it causes significant (P < 0.01 and P < 0.001) dose dependent increase in latency of convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb extension induced by electroshock. Two major compounds such as gentiopicroside and swertianin were analyzed by HPLC system.
A Lexical Decision Tree Scheme for Supporting Schema Matching

To manipulate semantic web and integrate different data sources efficiently, automatic schema matching plays a key role. A generic schema matching method generally includes two phases: the linguistic similarity matching phase and the structural similarity matching phase. Since linguistic matching is an essential step for effective schema matching, developing a high accurate linguistic similarity matching scheme is required. In this paper, a schema matching approach called Similarity Yield Matcher (SYM) is proposed. In SYM, a lexical decision tree is presented to determine the linguistic similarity matching of the first phase. A structural matching algorithm is then proposed to find the structure similarity between two tree schemas. The proposed schema matching approach was evaluated by testing on several benchmarks of real schemas and comparing with other methods. The experimental results show that the proposed lexical decision tree substantially improves the linguistic similarity matching effectively and efficiently. The proposed SYM algorithm also performs high effectiveness on 1–1 schema matching.
Familial risks for cancer as the basis for evidence-based clinical referral and counseling.

OBJECTIVE Reliable, clinically useful data on familial risks have not been available for all types of cancer, and familial aggregations of cancers, which are not known to belong to an inherited cancer syndrome, are often overlooked by medical referral systems. We provide uniform data on familial risks in all common cancers. METHODS The nationwide Swedish Family-Cancer Database includes 11.5 million individuals, born in 1932 and later, along with their parents. Standardized incidence ratios (SIRs) were calculated for age-specific familial risks in offspring. RESULTS The familial risks for offspring cancer were increased at 24 of 25 sites when a parent was diagnosed with concordant cancer, at 20 of 24 sites when a sibling was affected, and at 14 of 16 sites when a parent and at least one other sibling were affected. Among the offspring of affected parents, testicular cancer showed the highest risk, 4.52, followed by Hodgkin's disease (3.95) and esophageal cancer (3.36). At many sites, the risks between siblings were higher than those between offspring and affected parents, probably in part because of childhood environmental effects. CONCLUSIONS The data show convincingly that familial clustering is a common feature for all cancer sites. The results will be helpful in implementing evidence-based guidelines for clinical genetic counseling and in facilitating the recognition of familial risk at all levels of the general medical referral system.
Enduring Reversal of Neuropathic Pain by a Single Intrathecal Injection of Adenosine 2A Receptor Agonists: A Novel Therapy for Neuropathic Pain

Previous studies of peripheral immune cells have documented that activation of adenosine 2A receptors (A2ARs) decrease proinflammatory cytokine release and increase release of the potent anti-inflammatory cytokine, interleukin-10 (IL-10). Given the growing literature supporting that glial proinflammatory cytokines importantly contribute to neuropathic pain and that IL-10 can suppress such pain, we evaluated the effects of intrathecally administered A2AR agonists on neuropathic pain using the chronic constriction injury (CCI) model. A single intrathecal injection of the A2AR agonists 4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)prop-2-ynyl)piperidine-1-carboxylic acid methyl ester (ATL313) or 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamido adenosine HCl (CGS21680), 10–14 d after CCI versus sham surgery, produced a long-duration reversal of mechanical allodynia and thermal hyperalgesia for at least 4 weeks. Neither drug altered the nociceptive responses of sham-operated controls. An A2AR antagonist [ZM241385 (4-(2-[7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a)(1,3,5)triazin-5-ylamino]ethyl)phenol)] coadministered intrathecally with ATL313 abolished the action of ATL313 in rats with neuropathy-induced allodynia but had no effect on allodynia in the absence of the A2AR agonist. ATL313 attenuated CCI-induced upregulation of spinal cord activation markers for microglia and astrocytes in the L4–L6 spinal cord segments both 1 and 4 weeks after a single intrathecal ATL313 administration. Neutralizing IL-10 antibodies administered intrathecally transiently abolished the effect of ATL313 on neuropathic pain. In addition, IL-10 mRNA was significantly elevated in the CSF cells collected from the lumbar region. Activation of A2ARs after intrathecal administration may be a novel, therapeutic approach for the treatment of neuropathic pain by increasing IL-10 in the immunocompetent cells of the CNS.
Selective serotonin reuptake inhibitors in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a complex psychiatric condition, which can be triggered by a variety of traumatic events. Lifetime prevalence rates range from 1.3% to 10.4%, with women twice as likely as men to be affected. The clinical management of this condition is complex, since PTSD is associated with high rates of comorbid psychiatric disorders, particularly major depression, other anxiety and panic disorders, substance abuse and antisocial behaviour. Broadly, there are two main approaches to treatment: pharmacotherapy and cognitive or behavioural therapy. This paper reviews available pharmacological approaches for the treatment of PTSD and comorbid disorders. Although the optimal pharmacological approach has yet to be established, there is increasing evidence to support the use of antidepressants, and particularly selective serotonin reuptake inhibitors (SSRIs), as first-line therapy. In addition to alleviating the core symptoms of PTSD, some SSRIs are also effective for the treatment of common comorbidities, such as depression, panic disorder and social anxiety disorder; a fact which would appear to have important implications for patient management.
Association of incident dementia with hospitalizations.

CONTEXT Dementia is associated with increased rates and often poorer outcomes of hospitalization, including worsening cognitive status. New evidence is needed to determine whether some admissions of persons with dementia might be potentially preventable. OBJECTIVE To determine whether dementia onset is associated with higher rates of or different reasons for hospitalization, particularly for ambulatory care-sensitive conditions (ACSCs), for which proactive outpatient care might prevent the need for a hospital stay. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of hospitalizations among 3019 participants in Adult Changes in Thought (ACT), a longitudinal cohort study of adults aged 65 years or older enrolled in an integrated health care system. All participants had no dementia at baseline and those who had a dementia diagnosis during biennial screening contributed nondementia hospitalizations until diagnosis. Automated data were used to identify all hospitalizations of all participants from time of enrollment in ACT until death, disenrollment from the health plan, or end of follow-up, whichever came first. The study period spanned February 1, 1994, to December 31, 2007. MAIN OUTCOME MEASURES Hospital admission rates for patients with and without dementia, for all causes, by type of admission, and for ACSCs. RESULTS Four hundred ninety-four individuals eventually developed dementia and 427 (86%) of these persons were admitted at least once; 2525 remained free of dementia and 1478 (59%) of those were admitted at least once. The unadjusted all-cause admission rate in the dementia group was 419 admissions per 1000 person-years vs 200 admissions per 1000 person-years in the dementia-free group. After adjustment for age, sex, and other potential confounders, the ratio of admission rates for all-cause admissions was 1.41 (95% confidence interval [CI], 1.23-1.61; P < .001), while for ACSCs, the adjusted ratio of admission rates was 1.78 (95% CI, 1.38-2.31; P < .001). Adjusted admission rates classified by body system were significantly higher in the dementia group for most categories. Adjusted admission rates for all types of ACSCs, including bacterial pneumonia, congestive heart failure, dehydration, duodenal ulcer, and urinary tract infection, were significantly higher among those with dementia. CONCLUSION Among our cohort aged 65 years or older, incident dementia was significantly associated with increased risk of hospitalization, including hospitalization for ACSCs.
Surgical Menopause, Estrogen, and Cognitive Function in Women: What Do the Findings Tell Us?

Abstract: Randomized, controlled trials of estrogen treatment found protective effects of estrogen therapy (ET) on verbal memory in healthy, 45‐year‐old surgically menopausal women given 17‐β estradiol immediately after surgery. However, no effect was found when conjugated equine estrogens were given to older women years after their surgical menopause. These findings suggest that there is a critical time for the initiation of estrogen following the menopause with regard to its protective effect on memory as well as a specificity of the effect on verbal memory. These factors may explain why no protective effect of ET on cognitive aging was found in the Women's Health Initiative Memory Study.