Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of Sprouty1 and Jagged1 With Aggressive Prostate Cancer Cells With Different Sensitivities to Androgen Deprivation

Prostate cancer is a heterogeneous disease and thus, it is important to understand whether among the heterogeneous collection of cell types, androgen‐deprivation insensitive cells exist prior to hormonal manipulation. We established several LNCaP subclones with distinct insensitivities to androgen deprivation from a parental LNCaP cell line. In the resulting clones, the sensitivity to androgen‐deprivation negatively correlated with their PSA expression levels. In two of these clones, an androgen insensitive clone, LNCaP‐cl1, and an androgen sensitive clone, LNCaP‐cl5, the DNA copy number differed significantly, indicating that these clones contain genetically distinct cells. LNCaP‐cl1 had higher PSA expression but lower invasiveness and tumor growth potential than LNCaP‐cl5. The expression levels of two genes that are known to be regulated by miR‐21, an androgen‐regulated microRNA, Sprouty1 (SPRY1) and Jagged1 (JAG1) were significantly lower in LNCaP‐cl1 than in LNCaP‐cl5. Knocking down SPRY1 in LNCaP cells enhanced PSA expression and cell proliferation. JAG1 administration in LNCaP cells enhanced cell invasion and JAG1 knockdown in PC3 cells suppressed cell invasion and tumor formation. These results indicated that the expression differences in SPRY1 and JAG1 may contribute to the phenotypic differences between the LNCaP‐cl1 and LNCaP‐cl5 clones. In tissue samples, SPRY1 expression levels were significantly lower in prostate cancer patients with PSA recurrence after surgical treatment (P = 0.0076) and JAG1 expression levels were significantly higher in Gleason sum (GS) 8–9 disease than in GS 5–6 (P = 0.0121). In summary a random population of LNCaP cells comprises a heterogeneous group of cells with different androgen‐deprivation sensitivities and potential for invasiveness. J. Cell. Biochem. 115: 1505–1515, 2014. © 2014 Wiley Periodicals, Inc.
Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors.

OBJECTIVE Inflammatory and immune reactions raised in response to periodontopathogens are thought to trigger periodontal tissue destruction. We therefore investigated the expression of matrix metalloproteinases (MMPs) and the osteoclastogenic factor RANKL (receptor activator of nuclear factor-kappaB ligand), their respective inhibitors TIMPs (tissue inhibitors of metalloproteinases) and OPG (osteoprotegerin) and their possible correlation with the expression of inflammatory and regulatory cytokines in the course of experimental periodontal disease in mice. METHODS We characterized the time course of leukocyte migration and alveolar bone loss in C57BL/6 mice infected with Actinobacillus actinomycetemcomitans. Quantitative polymerase chain reaction (RealTime PCR) and ELISA were performed to determine the expression of MMPs, TIMPs, RANKL, OPG and cathepsin K, interleukin-1beta, tumor necrosis factor-alpha, interferon-gamma, interleukin-12, interleukin-4 and interleukin-10 in periodontal tissue samples harvested throughout the course of experimental disease. RESULTS Oral inoculation of A. actinomycetemcomitans results in an intense and widespread migration of leukocytes to the gingival tissues, besides marked alveolar bone resorption. Our data also demonstrate two distinct patterns of MMP/TIMP and RANKL/OPG expression in the course of experimental periodontal disease. The expression of MMPs (MMP-1, 2 and 9) and RANKL was correlated with the expression of interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma, in a time period characterized by the intense increase of inflammatory reaction and alveolar bone loss. On the other hand, interleukin-4 and interleukin-10 were associated with higher expression of TIMPs (TIMP 1, 2 and 3) and OPG, with a lower expression of MMPs and RANKL, and with reduced rates of increase of cellular infiltration in periodontal tissues and alveolar bone loss. CONCLUSIONS It is possible that the pattern of cytokines produced in periodontal tissues determines the progression and the severity of experimental periodontal disease, controlling the breakdown of soft and bone tissues through the balance between MMPs/TIMP and RANKL/OPG expression in gingival tissues.
Job Openings Continue to Grow in 2012, Hires and Separations Less So

Data from the Bureau of Labor Statistics Job Openings and Labor Turnover Survey (JOLTS) indicate that the job openings level and rate continued to grow during 2012. On an annual basis, data that are not seasonally adjusted show that the average monthly number of job openings increased from 3.2 million in 2011 to 3.6 million in 2012. The average monthly job openings rate rose from 2.3 percent to 2.6 percent. The increases in average monthly hires and separations, however, were not as large. From 2011 to 2012, the average monthly number of hires ticked up from 4.1 million to 4.3 million while the rate held steady at 3.2 percent. Besides illustrating the preceding data, the following tabulation shows that the average monthly number of separations increased from 4.0 million in 2011 to 4.1 million in 2012 while the average monthly rate rose from 3.0 percent to 3.1 percent between the 2 years (data not seasonally adjusted): May 2013
In Vitro and In Vivo Antifungal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum

ABSTRACT TAK-456 is a novel oral triazole compound with potent and broad-spectrum in vitro antifungal activity and strong in vivo efficacy against Candida albicans and Aspergillus fumigatus. TAK-456 inhibited sterol synthesis of C. albicans and A. fumigatus by 50% at 3 to 11 ng/ml. TAK-456 showed strong in vitro activity against clinical isolates of Candida spp. , Aspergillus spp. , and Cryptococcus neoformans, except for Candida glabrata. The MICs at which 90% of the isolates tested were inhibited byTAK-456, fluconazole, itraconazole, voriconazole, and amphotericin B were 0.25, 4, 0.5, 0.13, and 0.5 μg/ml, respectively, for clinical isolates of C. albicans and 1, >64, 0.5, 0.5, and 0.5 μg/ml, respectively, for clinical isolates of A. fumigatus. Therapeutic activities of TAK-456 and reference triazoles against systemic lethal infections caused by C. albicans and A. fumigatus in mice were investigated by orally administering drugs once daily for 5 days, and efficacies of the compounds were evaluated by the prolongation of survival. In normal mice, TAK-456 and fluconazole were effective against infection caused by fluconazole-susceptible C. albicans at a dose of 1 mg/kg. In transiently neutropenic mice, therapeutic activity of TAK-456 at 1 mg/kg of body weight against infection with the same strain was stronger than those at 1 mg/kg of fluconazole. TAK-456 was effective against infections with two strains of fluconazole-resistant C. albicans at a dose of 10 mg/kg. TAK-456 also expressed activities similar to or higher than those of itraconazole against the infections caused by two strains of A. fumigatus in neutropenic mice at a dose of 10 mg/kg. These results suggest that TAK-456 is a promising candidate for development for the treatment of candidiasis and aspergillosis in humans.
Costing children's speech, language and communication interventions.

BACKGROUND There are few economic evaluations of speech and language interventions. Such work requires underpinning by an accurate estimate of the costs of the intervention. This study seeks to address some of the complexities of this task by applying existing approaches of cost estimation to interventions described in published effectiveness studies. AIMS The study has two aims: to identify a method of estimating unit costs based on the principle of long-run marginal opportunity costs; and to illustrate the challenges in estimating unit costs for speech and language interventions. METHOD & PROCEDURES Descriptions of interventions were extracted from eight papers and combined with information on the unit cost of speech and language therapists to identify information requirements for a full-cost estimation of an intervention. OUTCOMES & RESULTS Four challenges were found relating to the level of detail about the therapists, the participants, the scope of activities and parents. Different assumptions made about any of these elements will have a marked effect on the cost of the intervention. CONCLUSIONS & IMPLICATIONS Nationally applicable unit cost data for speech and language therapists can be used as a reference point, but sufficient descriptive data about delivery and receipt of the intervention are key to accuracy.
Innovation and geographical spillovers: new approaches and empirical evidence

ABSTRACT Innovation and geographical spillovers: new approaches and empirical evidence. Regional Studies. This special issue concerns the generation of knowledge and geographical spillovers, and it includes a selection of papers that cover existent research gaps with respect to the role of space in the promotion of knowledge spillovers and innovation. These papers analyse different typologies of innovation processes carried out in several geographical areas and highlight heterogeneities of these processes, after focusing on several determinants in innovation. Empirical results indicate the positive role of geographical spillovers and the importance of accurate matching among firms, in industry and with regard to regional characteristics, in order to ensure the generation of knowledge and innovation.
Dilution of Urine Drug Tests: Is It Random?

Background:The purpose of this study was to determine whether the act of in vivo urine dilution is a random phenomenon. Methods:The sample population was divided into 4 groups for each of the drugs tested. The groups are precreatinine normalization laboratory positive, precreatinine normalization laboratory negative, and postcreatinine normalization laboratory drug positive, and postcreatinine normalization laboratory drug negative. The nonparametric Kruskal-Wallis 1-way ANOVA by ranks with post hoc Mann-Whitney U testing Bonferroni adjustment was used to compare the mean urine creatinine concentration of each group. Results:The Kruskal-Wallis test revealed that each drug had a statistically significant difference in group comparisons. Post hoc testing found that cocaine demonstrated no statistically significant difference between the prenormalization drug positive and negative groups. Amphetamines, marijuana, and opiates did confirm statistically significant differences between the prenormalization drug positive and negative groups. The examination of phencyclidine was limited by the lack of a prenormalization drug positive group; therefore, no definitive findings can be presented. Statistically significant differences were found between the postnormalization drug positive and negative groups for each drug tested. Conclusions:This study supports the theory that urine dilution is not a random happening and it may adversely affect the integrity of the drug-testing process.
Design and development of de-blur/de-noising filter using multiple image captures on a massively parallel architecture

Now a days mobile devices are capable of performing more operations in less amount of time. More number of GPU and CPU cores are added to the mobile devices. Due to increase in processing power various image processing algorithms are targeted at mobile devices. The users of these devices demand quality that is similar to that of a professional camera. There are definite limitations on the sensors that can be used in a smart phone. However, with the increase in computing power of smart phones/tablets, better software can be developed to compensate for these shortcomings. The image capture in low light condition can be enhanced by using guided filter. In this paper, we present the implementation of the Guided filter on Nexus 4. It has been observed that the speedup increases with respect to increase in size of image and size of window.
Digital assistant current sensor for PWM DC-DC converter with segmented output stage

A digital assistant sensor in PWM converter with segmented output stage is proposed in this paper. The output stage is segmented according to the load current, especially segmented in light loads condition. Conversional current sensor in a power integrated converter is not accurate enough for the light loads. A segmented current sensor (SCS) allying a time digital converter (TDC) is proposed to sensor the load current at light load condition in discontinuous current mode (DCM) in this paper. The SCS detects the load current in continuous current mode (CCM). Hence, refined segmented output stage can be obtained for optimized efficiency. The structure of the proposed digital assistant current sensor is described in this paper. And the PWM converter with the adaptive segmented output stage is designed and simulated in a 0. 13μm standard CMOS process. The simulation results show that the maximum efficiency improvement of the proposed converter reaches 8% compared to converter without segment.
Plasmodium falciparum Malaria in the Peruvian Amazon, a Region of Low Transmission, Is Associated with Immunologic Memory

ABSTRACT The development of clinical immunity to Plasmodium falciparum malaria is thought to require years of parasite exposure, a delay often attributed to difficulties in developing protective antibody levels. In this study, we evaluated several P. falciparum vaccine candidate antigens, including apical membrane antigen 1 (AMA-1), circumsporozoite protein (CSP), erythrocyte binding antigen 175 (EBA-175), and the 19-kDa region of merozoite surface protein 1 (MSP119). After observing a more robust antibody response to MSP119, we evaluated the magnitude and longevity of IgG responses specific to this antigen in Peruvian adults and children before, during, and after P. falciparum infection. In this low-transmission region, even one reported prior infection was sufficient to produce a positive anti-MSP119 IgG response for >5 months in the absence of reinfection. We also observed an expansion of the total plasmablast (CD19+ CD27+ CD38high) population in the majority of individuals shortly after infection and detected MSP1-specific memory B cells in a subset of individuals at various postinfection time points. This evidence supports our hypothesis that effective antimalaria humoral immunity can develop in low-transmission regions.
Nonmotor symptoms are independently associated with impaired health‐related quality of life in Chinese patients with Parkinson's disease

We performed a cross‐sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18‐month period using a clinical interview to assess the prevalence of nonmotor symptoms (NMS), the association with disease severity and motor status, and the impact on patients' health‐related quality of life (Hr‐QoL). The patients' NMS, Hr‐QoL, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), the 39‐item Parkinson's Disease Questionnaire (PDQ‐39), the modified Hoehn and Yahr staging scale (H&Y) and the Unified Parkinson's Disease Rating Scale part III (UPDRS III), respectively. We found that 100% of patients with PD presented with NMS. The NMSS significantly correlated with disease duration (Spearman's rS = 0.276, P = 0.012), H&Y (rS = 0.230, P = 0.038), and UPDRS III (rS = 0.350, P = 0.001). Similarly, the PDQ‐39 SI significantly associated with the disease duration (rS = 0.258, P = 0.019), H&Y (rS = 0.340, P = 0.002), and UPDRS III (rS = 0.453, P < 0.001). NMS domains that influenced the PDQ‐39 SI were sleep/fatigue, mood, gastrointestinal, urinary, and miscellaneous symptoms. This strongly suggested that the five domains played a key role in the manifestation of Hr‐QoL. NMSS explains more of the variability in Hr‐QoL than UPDRS III, when both are the model (stepwise multiple linear regression analysis R2 change, 47.8% vs. 5.87%, respectively). Therefore, these findings demonstrate that NMS are independently and negatively associated with Hr‐QoL in PD and that improving NMS should be viewed as an important part in the management of PD. © 2010 Movement Disorder Society
Osteoclast precursors, RANKL/RANK, and immunology

Summary: Rapid progress has been made in recent years in our understanding of the mechanisms regulating the formation, activation, and survival of osteoclasts, which are derived from precursor cells in the myeloid lineage. In contrast, study of the regulation of osteoclast precursors (OCPs) has been relatively slow, in part because it has been hard to accurately identify them. However, following the discovery of cell‐surface markers that facilitated purification of OCPs, recent studies have demonstrated that peripheral blood OCP numbers are increased in tumor necrosis factor (TNF)‐mediated arthritis, both in animals and humans, and these numbers correlate with serum TNF levels. The increase can be reversed by anti‐TNF therapy. Furthermore, the precursor cells that give rise to osteoclasts can also differentiate into other cell types, including dendritic cells. Receptor activator nuclear factor‐κB ligand (RANKL) stimulates OCPs to produce pro‐inflammatory cytokines and chemokines, and RANKL blockade prevents joint inflammation in a murine model of inflammatory arthritis. These findings suggest that OCPs may serve as a source for both osteoclasts and other effector cells and participate actively in the pathogenesis of diseases. Here, we review our current understanding of the regulation of OCP formation and differentiation and provide a model of a vicious cycle in which pro‐inflammatory cytokines produced in inflamed joints feedback on the bone marrow to promote the generation and release of OCPs. The OCPs then home to the inflamed joints to differentiate into mature osteoclasts or to produce more inflammatory factors in the presence of RANKL. Disruption of this cycle could provide a new strategy for the development of drugs to treat inflammatory arthritis and other disorders associated with elevated OCP/myeloid progenitors.
Colective and individual analytical competences as a contemporary foundations of organizaction’s development

The aim of the article is to present the concept of analytical competences and its 19 importance for the development of contemporary enterprises. In the first part of the article, the 20 role of business analytics is presented in a concise manner. The following sections consider the 21 most important categories of analytical competence in their dual understanding – as the 22 collective competences of the organization and as the individual competences of specialists. 23 The article is based on a narrative literature review and secondary sources, and its main goal is 24 to indicate the need to discuss the importance of new competences and their potential for 25 development of organizations. 26
Twenty-eight-day efficacy and phamacokinetics of the sirolimus-eluting stent

BackgroundIn-stent restenosis is caused by neointimal hyperplasia. Sirolimus (rapamycin; Wyeth Research, Radnor, Pennsylvania, USA) inhibits vascular smooth muscle cell proliferation and we evaluated the efficacy of sirolimus in reducing neointimal formation in a rabbit iliac model and in-vivo pharmacokinetics in the porcine coronary model. DesignRandomized, blinded, prospective animal study. MethodsBilateral rabbit iliac artery stent implantation was performed using crossflex stents (Cordis Corporation, Warren, New Jersey, USA) coated with sirolimus incorporated in a nonerodable polymer. Arteries were randomized to one of four stent groups: uncoated stents (n = 8); polymer control stents (n = 10); low-dose sirolimus-eluting stents (n = 9); and high-dose sirolimus-eluting stents (n = 10). Histomorphometry was performed at 28 days. Arterial tissue and stents were retrieved at 8, 14 and 28 days and blood samples were obtained daily during the first week. ResultsTreatment with low-dose sirolimus was associated with a 23% (P = NS) reduction in neointimal area and treatment with high-dose sirolimus with a 45% (P < 0.05) reduction. Sustained drug release from the stent and prolonged intramural arterial deposition were confirmed for up to 28 days. No detectable sirolimus was found in the blood after 2 days. ConclusionControlled-release local delivery of a cell-cycle inhibitor from a nonerodable polymer-coated stent reduced neointimal formation in rabbit iliac arteries in a dose-dependent manner and represents a promising strategy for preventing restenosis.
Casein Kinase II Sites in the Intracellular C-terminal Domain of the Thyrotropin-releasing Hormone Receptor and Chimeric Gonadotropin-releasing Hormone Receptors Contribute to β-Arrestin-dependent Internalization*

We have previously shown that the mammalian gonadotropin-releasing hormone receptor (GnRHR), a unique G-protein-coupled receptor (GPCR) lacking an intracellular carboxyl tail (C-tail), does not follow a β-arrestin-dependent internalization pathway. However, internalization of a chimeric GnRHR with the thyrotropin-releasing hormone receptor (TRHR) C-tail does utilize β-arrestin. Here, we have investigated the sites within the intracellular C-tail domain that are important for conferring β-arrestin-dependent internalization. In contrast to the chimeric GnRHR with a TRHR C-tail, a chimeric GnRHR with the catfish GnRHR C-tail is not β-arrestin-dependent. Sequence comparisons between these chimeric receptors show three consensus phosphorylation sites for casein kinase II (CKII) in the TRHR C-tail but none in the catfish GnRHR C-tail. We thus investigated a role for CKII sites in determining GPCR internalization via β-arrestin. Sequential introduction of three CKII sites into the chimera with the catfish C-tail (H354D,A366E,G371D) resulted in a change in the pattern of receptor phosphorylation and β-arrestin-dependence, which only occurred when all three sites were introduced. Conversely, mutation of the putative CKII sites (T365A,T371A,S383A) in the C-tail of a β-arrestin-sensitive GPCR, the TRHR, resulted in decreased receptor phosphorylation and a loss of β-arrestin-dependence. Mutation of all three CKII sites was necessary before a loss of β-arrestin-dependence was observed. Visualization of β-arrestin/GFP redistribution confirmed a loss or gain of β-arrestin sensitivity for receptor mutants. Internalization of receptors without C-tail CKII sites was promoted by a phosphorylation-independent β-arrestin mutant (R169E), suggesting that these receptors do not contain the necessary phosphorylation sites required for β-arrestin-dependent internalization. Apigenin, a specific CKII inhibitor, blocked the increase in receptor internalization by β-arrestin, thus providing further support for the involvement of CKII. This study presents evidence of a novel role for C-tail CKII consensus sites in targeting these GPCRs to the β-arrestin-dependent pathway.