Miracle-dz/UniFAR-FTUs huggingface dataset:
A mouse model of Rubinstein-Taybi syndrome: Defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4

Mice carrying a truncated form of cAMP-responsive element binding protein (CREB)-binding protein (CBP) show several developmental abnormalities similar to patients with Rubinstein-Taybi syndrome (RTS). RTS patients suffer from mental retardation, whereas long-term memory formation is defective in mutant CBP mice. A critical role for cAMP signaling during CREB-dependent long-term memory formation appears to be evolutionarily conserved. From this observation, we reasoned that drugs that modulate CREB function by enhancing cAMP signaling might yield an effective treatment for the memory defect(s) of CBP+/− mice. To this end, we designed a cell-based drug screen and discovered inhibitors of phosphodiesterase 4 (PDE4) to be particularly effective enhancers of CREB function. We extend previous behavioral observations by showing that CBP+/− mutants have impaired long-term memory but normal learning and short-term memory in an object recognition task. We demonstrate that the prototypical PDE4 inhibitor, rolipram, and a novel one (HT0712) abolish the long-term memory defect of CBP+/− mice. Importantly, the genetic lesion in CBP acts specifically to shift the dose sensitivity for HT0712 to enhance memory formation, which conveys molecular specificity on the drug's mechanism of action. Our results suggest that PDE4 inhibitors may be used to treat the cognitive dysfunction of RTS patients.
Analysis and Improvement of Maximum Power Point Tracking Algorithm Based on Incremental Conductance Method for Photovoltaic Array

Photovoltaic (PV) array in the photovoltaic power system (PVPS) has the nonlinear current-voltage characteristic which is affected by the panels temperature and irradiance conditions. To improve the energy converter efficiency of the PVPS, the maximum power point tracking algorithm should be adopted to maximize the yield of the PV array. The incremental conductance (INC) method is widely used in the PVPS due to its succinctness and high tracking efficiency. The conventional INC algorithm using a fixed iteration step-size is impossible to achieve rapid dynamic response and good steady tracking accuracy simultaneously, because if the step-size is increased for rapid dynamic response, the tracking accuracy is decreased and vice versa. An improved algorithm with variable step- size is proposed to solve the problem in this paper. The contrastive experimental results between the improved and the conventional INC algorithm are presented to demonstrate its effectiveness.
Reaction Mechanism of Glutathione Synthetase from Arabidopsis thaliana

Glutathione is essential for maintaining the intracellular redox environment and is synthesized from γ-glutamylcysteine, glycine, and ATP by glutathione synthetase (GS). To examine the reaction mechanism of a eukaryotic GS, 24 Arabidopsis thaliana GS (AtGS) mutants were kinetically characterized. Within the γ-glutamylcysteine/glutathione-binding site, the S153A and S155A mutants displayed less than 4-fold changes in kinetic parameters with mutations of Glu-220 (E220A/E220Q), Gln-226 (Q226A/Q226N), and Arg-274 (R274A/R274K) at the distal end of the binding site resulting in 24-180-fold increases in the Km values for γ-glutamylcysteine. Substitution of multiple residues interacting with ATP (K313M, K367M, and E429A/E429Q) or coordinating magnesium ions to ATP (E148A/E148Q, N150A/N150D, and E371A) yielded inactive protein because of compromised nucleotide binding, as determined by fluorescence titration. Other mutations in the ATP-binding site (E371Q, N376A, and K456M) resulted in greater than 30-fold decreases in affinity for ATP and up to 80-fold reductions in turnover rate. Mutation of Arg-132 and Arg-454, which are positioned at the interface of the two substrate-binding sites, affected the enzymatic activity differently. The R132A mutant was inactive, and the R132K mutant decreased kcat by 200-fold; however, both mutants bound ATP with Kd values similar to wild-type enzyme. Minimal changes in kinetic parameters were observed with the R454K mutant, but the R454A mutant displayed a 160-fold decrease in kcat. In addition, the R132K, R454A, and R454K mutations elevated the Km value for glycine up to 11-fold. Comparison of the pH profiles and the solvent deuterium isotope effects of A. thaliana GS and the Arg-132 and Arg-454 mutants also suggest distinct mechanistic roles for these residues. Based on these results, a catalytic mechanism for the eukaryotic GS is proposed.
[Total disc prosthesis for painful degenerative lumbar disc disease].

OBJECTIVES We evaluated clinical and radiographic results of patients treated by the ProDisc II total disc prosthesis (TDP) for painful degenerative lumbar disc disease. METHODS The study included 34 patients (25 females, 9 males; mean age 44 years; range 37 to 54 years) who underwent a total of 62 lumbar TDP procedures for degenerative lumbar disc disease. Lumbar disc replacement involved one level in 12 cases, two levels in 17 cases, three levels in four cases, and four levels in one case. Clinical and radiographic assessments were made preoperatively and at 3, 6, 12, and 24 months postoperatively. Clinical evaluations were made with a visual analog scale (VAS) and the Oswestry Disability Index (ODI). Radiographic parameters included lumbar lordotic angle, the height and flexion-extension range of the affected discs. The mean follow-up period was 29.3 months (range 24 to 39 months). RESULTS Low back pain and lower extremity pain showed near-complete improvement up to the third postoperative month. At the end of the 24th month, preoperative ODI and VAS scores of 59.6 and 7.8 decreased to 19.8 and 1.0, respectively. Preoperative and postoperative lumbar lordotic angles were 52.6 degrees and 57.1 degrees , respectively. The mean disc height of implanted discs increased from 4.6 mm to 12.1 mm postoperatively. The mean flexion-extension angle increased from 2.8 degrees to 8.4 degrees at L5-S1, and from 2.6 degrees to 9.8 degrees at L4-5. The overall improvement in the mean flexion-extension angle was 7.2 degrees . CONCLUSION Lumbar disc prosthesis offers significant advantages in terms of functional improvement and increased quality of life in the surgical treatment of degenerative disc disease.
Childhood Hyperactivity as a Predictor of Carotid Artery Intima Media Thickness Over a Period of 21 Years: The Cardiovascular Risk in Young Finns Study

Objective: We investigated whether childhood temperament was able to predict carotid artery intima media thickness (IMT) and/or its risk factors in adulthood 21 years later. Methods: The subjects were the three youngest age cohorts of the population-based sample of the Cardiovascular Risk in Young Finns study, i.e., those who were aged 3 to 9 years (n = 708) at the baseline. IMT was assessed by ultrasound, and temperament in terms of negative emotionality, hyperactivity, and sociability (following Buss and Plomin). In addition, the levels of traditional risk factors for atherosclerosis were measured in both childhood and adulthood. Results: Childhood temperament was found to predict adulthood risk factors such as smoking in both genders and body mass index (BMI), systolic blood pressure (SBP), and educational level in women. In women, childhood hyperactivity predicted adulthood IMT after adjustment for childhood and adulthood risk factors for atherosclerosis. Conclusion: These findings suggest that temperament may contribute to the development of IMT in two ways: indirectly through risk factors in both genders and in women directly through a mechanism that is not considered in the present study. There were no significant gender-related differences in temperament, but it seemed to play different roles in different genders. Hyperactivity was a greater risk for girls than for boys. BMI = body mass index; LDL = low-density lipoprotein; IMT = intima media thickness; CHD = coronary heart disease; SBP = systolic blood pressure.
[Angiotensin(1-7) attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy].

OBJECTIVE To investigate the effect of Angiotensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy (ADR-DCM). METHODS Weight-matched adult male Wistar rats were randomly divided into 3 groups: (1) the ADR-DCM group (n = 25), in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks. (2) Ang(1-7) group (n = 25), in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 µg×kg(-1)×h(-1), ip. ) for 12 weeks. (3) normal control group (n = 10). Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde (MDA) was measured by TBA methods. The plasma concentration of AngII was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and anti-apoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot. RESULTS Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16% vs. 40%, P < 0.01). Compared to the control group, left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group (all P < 0.01) while fractional shorting (FS), +dp/dtmax and -dp/dtmax were significantly reduced in ADR-DCM group (all P < 0.01). LVEDD, LVESD and LVEDP were significantly reduced while FS, +dp/dtmax and -dp/dtmax were significantly higher in Ang(1-7) group compared to the ADR-DCM group, but still higher than the control group (all P < 0.01). The concentrations of AngII and MDA were higher in the ADR-DCM group than in the control group (P < 0.01), which were significantly reduced by Ang(1-7) treatment (P < 0.01). The TUNEL-positive cells and apoptosis index, the expression of pro-apoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P < 0.01) which could all be partially reversed by Ang(1-7) treatment (all P < 0.01). CONCLUSION Ang(1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.
Impacts of strategic planning and management in municipal government: an analysis of subjective survey and objective production and efficiency measures in Norway

ABSTRACT This article analyses impacts of formal strategic planning, strategic types, stakeholder involvement, and their interactions on performance in Norwegian municipalities. Internal stakeholders often overstate their organization’s performance. Therefore, the analysis complements subjective survey data on strategic planning, strategy content and the senior officials’ perceptions of the impacts of the strategic planning, with more objective administrative data of municipal production, efficiency and change in efficiency. Moderated multiple regression analyses show that strategic planning and a defender strategy had positive perceived impacts. The analyses with administrative data for performance showed little significant positive impacts of strategic planning, strategy content and stakeholder involvement.
Protective Effect of Erdosteine against Cisplatin-Induced Ototoxicity in a Guinea Pig Model

Objective. Cisplatin is a commonly used chemotherapeutic agent. One of its major dose-limiting side effects is ototoxicity. No treatment has yet been approved for this condition. The objective of this study was to determine the potential protective effect of a systemic administration of erdosteine against cisplatin-induced ototoxicity. Study Design. A prospective controlled trial conducted in an animal model. Setting. Animal care research facilities of The Montreal Children’s Hospital Research Institute. Subjects and Methods. A total of 27 guinea pigs were assigned to 4 groups, each receiving a different concentration of intraperitoneal erdosteine: group 1 (control group; n = 9) did not receive erdosteine, group 2 (n = 6) received 100 mg/kg/d, group 3 (n = 6) received 200 mg/kg/d, and group 4 (n = 6) received 500 mg/kg/d. The animals in the experimental groups received the erdosteine injection daily for 4 days. All of the animals received 12 mg/kg of intraperitoneal cisplatin. Auditory brainstem response threshold shifts were measured at 4 frequencies (8, 16, 20, and 25 kHz) for all groups. Scanning electron microscopy and outer hair cell counts were performed to assess the protective effect of erdosteine. Results. Significant protection was observed in groups 3 and 4 at 25 kHz. These findings are supported by outer hair cell counts by scanning electron microscopy. Conclusion. A systemic administration of erdosteine appears to provide an otoprotective effect at high frequencies for cisplatin-induced ototoxicity.
Evidence of Recombinant Strains of Porcine Epidemic Diarrhea Virus, United States, 2013

To investigate the evolutionary process by which porcine epidemic diarrhea virus (PEDV) in the United States hypothetically descended from strains in China, we analyzed PEDV-positive samples collected in China during January 2012–July 2013. Recombination in 2 strain sublineages was likely associated with identification of PEDV in the United States in 2013.
Human Serotonin Transporter: Regulation by the Neuroprotective Agent Aurintricarboxylic Acid and by Epidermal Growth Factor

Abstract: The influence of aurintricarboxylic acid (ATA), a neuroprotective compound, on the serotonin transporter expressed in JAR human placental choriocarcinoma cells was investigated. Treatment of the cells with ATA for 16 h led to a significant stimulation of the serotonin transporter activity. This effect was not observed, however, when the treatment was done for 1–2 h. The stimulatory effect was associated with an increase in the maximal velocity of the transport process with no significant change in the Michaelis‐Menten constant. Northern blot hybridization revealed that ATA treatment caused a marked increase in the steady‐state levels of serotonin transporter‐specific transcripts. Treatment of the cells with ATA was found to increase tyrosine phosphorylation of a 180‐kDa protein. The phosphotyrosine content of a protein of a similar molecular size increased dramatically when the cells were exposed to epidermal growth factor (EGF), suggesting that this protein may be the EGF receptor. Treatment of the cells with EGF for 24 h could reproduce the stimulatory effects of ATA on the serotonin transporter activity, the maximal velocity of the transport process, and the steady‐state levels of the transporter‐specific mRNAs. Genistein, a tyrosine kinase inhibitor, was able to block the stimulatory effect of ATA and EGF. It is concluded that EGF increases the serotonin transporter expression in JAR cells and that the neuroprotective compound ATA produces similar effects on the transporter most likely by activating the EGF receptor through tyrosine phosphorylation.
STRengthening Analytical Thinking for Observational Studies: the STRATOS initiative

The validity and practical utility of observational medical research depends critically on good study design, excellent data quality, appropriate statistical methods and accurate interpretation of results. Statistical methodology has seen substantial development in recent times. Unfortunately, many of these methodological developments are ignored in practice. Consequently, design and analysis of observational studies often exhibit serious weaknesses. The lack of guidance on vital practical issues discourages many applied researchers from using more sophisticated and possibly more appropriate methods when analyzing observational studies. Furthermore, many analyses are conducted by researchers with a relatively weak statistical background and limited experience in using statistical methodology and software. Consequently, even ‘standard’ analyses reported in the medical literature are often flawed, casting doubt on their results and conclusions. An efficient way to help researchers to keep up with recent methodological developments is to develop guidance documents that are spread to the research community at large.
College Students’ Values for Self-Expression, their Facebook Use, and Bridging Social Capital

Emerging adults are coming of age in social worlds permeated by social media. Communication with others on social media can provide access to bridging social capital, defined as social resources embedded in relationships with acquaintances which promote access to new information. Grooming ties through self-expression and masspersonal communication in networked publics is important for acquiring bridging social capital, behaviors complicated by context collapse. When engaging in masspersonal communication, social media users must balance their desire to express themselves with their desire to maintain positive impressions to multiple audiences. Recent research suggests an important strategy for navigating context collapse is the use of privacy controls. However, using privacy controls could inhibit relational maintenance with acquaintances who offer novel information. The current study investigates how college students are adapting to masspersonal communication on Facebook by examining their bridging social capital, privacy control behaviors, values for self-expression, and network diversity. Confirming previous research, bridging social capital was associated with frequency of Facebook use and relationship maintenance behaviors, however, it was not associated with privacy control behaviors or network diversity. Value for self-expression, relationship maintenance behaviors, Facebook use, and network size each uniquely predicted bridging social capital. Further, strength of self-expression endorsements differed across masspersonal communication topics. Qualitative analysis of college students’ reasoning about the appropriateness of various masspersonal communication topics provides insights into the values and priorities young people are bringing into their social constructions of online norms in response to new tensions created by context collapse. Implications of findings are discussed.
Hierarchical Role of Fetuin-A and Acidic Serum Proteins in the Formation and Stabilization of Calcium Phosphate Particles*

The serum protein fetuin-A is a potent systemic inhibitor of soft tissue calcification. Fetuin-A is highly effective in the formation and stabilization of protein-mineral colloids, referred to as calciprotein particles (CPPs). These particles ripen in vitro in a two-step process, indicated by a morphological conversion from spheres to larger prolate ellipsoids. Using a combined light scattering and electron microscopic imaging approach we determined that the second-stage particles resulted from a highly anisotropic outgrowth of the first-stage particles. Electron microscopy of ascites fluid from a patient with calcifying peritonitis revealed particles reminiscent of secondary CPPs. Thus, CPPs form in the body and undergo the two-step ripening at least in pathological conditions. Unlike in vitro generated CPPs, ascites-derived CPPs contained little fetuin-A but large amounts of albumin. This prompted us to study the role of fetuin-A combined with other serum proteins in CPP formation. Fetuin-A was indispensable for primary CPP formation. Albumin and acidic proteins in general greatly enhanced the fetuin-A triggered formation of secondary CPPs and, thus, substituted substantial amounts of fetuin-A without loss of inhibition of calcium phosphate precipitation. Thus, direct mineral deposition from solute in the body is unlikely even at low fetuin-A serum levels as long as sufficient bulk acidic protein is available. Collectively fetuin-A and other acidic bulk plasma proteins may be considered as mineral chaperones mediating the stabilization, safe transport, and clearance in the body of calcium and phosphate as colloidal complexes, thus, preventing ectopic calcification.
The association between psoriasis and hypertension: a systematic review and meta-analysis of observational studies

Population-based observational studies have suggested a relationship between psoriasis and hypertension. We performed a systematic review and meta-analysis to better understand the association between psoriasis and hypertension. We systematically searched MEDLINE, EMBASE, and the Cochrane Central Register from 1 January 1980 to 1 January 2012. Two authors independently assessed trial eligibility and quality. We applied the Meta-Analysis of Observational Studies in Epidemiology guidelines in the conduct of this study. We identified 24 observational studies with a total of approximately 2.7 million study participants fulfilling our inclusion criteria. Among them, 309 469 were patients with psoriasis. On the basis of random effects modeling of case–control and cross–sectional studies, the odds ratio (OR) for hypertension among patients with psoriasis was 1.58 [95% confidence interval (CI) 1.42–1.76] compared with the controls. The OR for hypertension among patients with mild psoriasis was 1.30 (95% CI 1.15–1.47) and the OR for hypertension among patients with severe psoriasis was 1.49 (95% CI 1.20–1.86) compared with the controls. Two cohort studies examining incidence of hypertension found that psoriasis was associated with a hazard ratio of 1.09 (95% CI 1.05–1.14) and 1.17 (95% CI 1.06–1.30) for development of hypertension. In a subgroup analysis, patients with psoriatic arthritis also had an increased prevalence of hypertension (OR 2.07, 95% CI 1.41–3.04). Psoriasis and psoriatic arthritis are associated with greater prevalence of hypertension. Patients with severe psoriasis have greater odds of hypertension than those with mild psoriasis.
Dose-Dependent Protection against or Exacerbation of Disease by a Polylactide Glycolide Microparticle-Adsorbed, Alphavirus-Based Measles Virus DNA Vaccine in Rhesus Macaques

ABSTRACT Measles remains an important cause of vaccine-preventable child mortality. Development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. DNA vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. In the current study, we evaluated the use of a layered alphavirus DNA/RNA vector encoding measles virus H (SINCP-H) adsorbed onto polylactide glycolide (PLG) microparticles. In mice, antibody and T-cell responses to PLG-formulated DNA were substantially improved compared to those to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5 mg) or intradermally (0.5 or 0.1 mg). Antibody and T-cell responses were induced but not sustained. On challenge, the intramuscularly vaccinated monkeys did not develop rashes and had lower viremias than vector-treated control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. Monkeys vaccinated intradermally with the low dose developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia, and higher viremia compared to vector-treated control monkeys. Protection after challenge correlated with gamma interferon-producing T cells and with early production of high-avidity antibody that bound wild-type H protein. We conclude that PLG/SINCP-H is most efficacious when delivered intramuscularly but does not provide an advantage over standard DNA vaccines for protection against measles.