Miracle-dz/UniFAR-FTUs huggingface dataset:
The universe of Hsp 90

Molecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Among the ATPdependent chaperones, heat shock proteins (Hsp90) proteins play a special role. While Hsp90s can interact with unfolded and misfolded proteins, their main (and in eukaryotic cells essential) function appears to involve interactions with a limited number of protein clients at late steps of maturation or in ‘ alter-native ’ conformations for regulating their stability and activity. Because Hsp90 clients are hubs of diverse signaling networks and participate in nearly every cellular function, Hsp90s interconnect many regulatory circuits and link them to environmental impacts. The availability and activity of Hsp90 may thus infl uence complex physiological and pathophysiological processes, such as differentiation, development, aging, cancer, neurodegeneration, and infectious diseases. Furthermore, through homeostatic effects on differentiation and development, Hsp90s act as capacitors of phenotypic evolution. In this review, we discuss recent insights in the structure and chaperone cycle of Hsp90s, the mechanisms underlying Hsp90 binding to clients, and potential reasons why client proteins specifi cally require the assistance of Hsp90s. Moreover, the current views on Hsp90-cochaperone interactions and regulation of Hsp90 proteins via posttranslational modifi cations are summarized. The second half of this article is devoted to the role of Hsp90 proteins in health and disease, aging, and evolution.
Reply: To PMID 23503339.

To the Editor: We read with interest the article by Cho et al entitled “Healing of conjunctival wounds after 23-gauge sutureless vitrectomy. ” The authors evaluated the healing process of conjunctival wounds in sutureless vitrectomy, not sclerotomy wounds. It is clinically practical. We have two issues that we would like to share with the authors. First, the relationships between the surgical factors such as concomitant cataract surgery and the healing time of the conjunctival wound were assessed using Mann–Whitney test. However, because the evaluation of conjunctival wound was done postoperatively on Days 1, 4, 8, and 15, the variable was not continuous. Therefore, cross tabulation and correlation analyses should have been used. Furthermore, the sample size was too small (only 11 vs. 23 eyes). Second, we agree with the authors about the need for further prospective and large sample studies, which compare the incidence of endophthalmitis after combined surgery or vitrectomy alone. In sutureless diabetic vitrectomy studies, however, the incidence of early postoperative hypotony was lower in combined surgery than in vitrectomy alone. We suppose that sclerotomy wound leak and related endophthalmitis may be less in the combined surgery. It is more important in the early postoperative period before the conjunctival wound is completely healed. In addition, we recommend minimal or partial air tamponade for the prevention of hypotony in sutureless vitrectomy.
Human Population Genetic Structure and Diversity Inferred from Polymorphic L1(LINE-1) and Alu Insertions

Background/Aims: The L1 retrotransposable element family is the most successful self-replicating genomic parasite of the human genome. L1 elements drive replication of Alu elements, and both have had far-reaching impacts on the human genome. We use L1 and Alu insertion polymorphisms to analyze human population structure. Methods: We genotyped 75 recent, polymorphic L1 insertions in 317 individuals from 21 populations in sub-Saharan Africa, East Asia, Europe and the Indian subcontinent. This is the first sample of L1 loci large enough to support detailed population genetic inference. We analyzed these data in parallel with a set of 100 polymorphic Alu insertion loci previously genotyped in the same individuals. Results and Conclusion: The data sets yield congruent results that support the recent African origin model of human ancestry. A genetic clustering algorithm detects clusters of individuals corresponding to continental regions. The number of loci sampled is critical: with fewer than 50 typical loci, structure cannot be reliably discerned in these populations. The inclusion of geographically intermediate populations (from India) reduces the distinctness of clustering. Our results indicate that human genetic variation is neither perfectly correlated with geographic distance (purely clinal) nor independent of distance (purely clustered), but a combination of both: stepped clinal.
Green School Based Management Model as A Powerful Alternative Solution to Overcome Global Climate Change: A Need Assessment Survey Analysis of Teacher in Lampung, Indonesia

The roles and responsibilities of schools in dealing with 21st-century problems, especially those related to global climate change which treats the entire world, become a challenge for school communities to take part to overcome this problem we proposed Green School Based Management Model (Green SBM Model). Green SBM Model is a new model that has been proposed to be conducted in all schools in Lampung. Just because the existed SBM Model focused on school improvement plans / learning outcomes only (management of human resources, materials, finance, strategic planning, program management, and marketing oriented). Before conducting Green SBM Model, we do need assessment surve for the teacher in Lampung Indonesia to know teacher perception about global warming and its solution. The design of this study is a cross-sectional non-experimental descriptive survey approach using a questionnaire to 107 teachers in Lampung, Indonesia. Based on data analysis, it can be concluded that all of the teachers realized the negative impact of global warming and they should take a part in overcoming the negative impact of global warming. Besides that, teachers also believed that Green School Based Management Model is a powerful model which can be a solution to overcome the negative impact of global warming.
Landmark-based navigation in complex buildings

Growing numbers of mobile devices in our daily life and their capability to fulfill challenging computational tasks raise the question about new application fields beyond well-established tasks. While outdoor navigation became a standard task for many mobile devices, indoor positioning and navigation is still in the research and development stage. Even though complex buildings require aided guidance for visitors, today's mobile hardware is not able to deliver a reliable indoor navigation system. In this paper we describe a novel information system for indoor navigation in complex buildings. Users are guided through the building by using images of the surroundings and textual instructions. We avoid hardware-based user positioning due to its known drawbacks. Instead, users are involved into the navigation process and complete missing information through recognized context and logical constrains of their surroundings. The human navigation process based on recognition of certain unique locations and visual clues is the foundation of this work. The proposed system is universally applicable without restrictions on navigation devices or existing hardware in the building.
Comparison of Anterior Segment Measurements With a Dual Scheimpflug Placido Corneal Topographer and a New Partial Coherence Interferometer in Keratoconic Eyes

Purpose: To evaluate the repeatability and agreement of the anterior segment measurements obtained using the Galilei dual Scheimpflug analyzer (Galilei DSA; Ziemer) and Nidek AL Scan (Nidek CO, Aichi, Japan) biometry in keratoconic and normal eyes. Methods: Three consecutive measurements were performed by the same examiner using both devices in 62 healthy and 88 keratoconic eyes. Central corneal thickness (CCT), anterior chamber depth, keratometry readings (K) [in flattest meridian (Kf), in steepest meridian (Ks), and mean (Km)], and white-to-white distance were evaluated. Repeatability was assessed by calculating the within-subject SD and coefficient of variation. The agreement between both devices was assessed using the Bland–Altman method. Results: Both devices achieved excellent repeatability for all parameters in each group. The 95% limits of agreement (LoA) between both devices were also very narrow and acceptable for all parameters in normal corneas. However, the 95% LoA for agreement was large for CCT and measurements related to K (Kf, Ks, and Km) using both 2.4 and 3.3 mm in keratoconic eyes. In addition, compared with the Galilei DSA, K values of the Nidek AL Scan using a diameter of 3.3 mm showed slightly closer 95% LoA than those obtained using a diameter of 2.4 mm. Conclusions: In normal eyes, the Galilei DSA and Nidek AL Scan can be used interchangeably for anterior segment measurements. In keratoconic eyes, both devices yielded interchangeable anterior chamber depth and white-to-white distance measurements, whereas CCT and keratometry measurements showed clinically significant differences.
Multiplicité des tests, et calculs de taille d'échantillon en recherche clinique

Ce travail a eu pour objectif de repondre aux problematiques inherentes aux tests multiples dans le contexte des essais cliniques. A l’heure actuelle un nombre croissant d’essais cliniques ont pour objectif d’observer l’effet multifactoriel d’un produit, et necessite donc l’utilisation de co-criteres de jugement principaux. La significativite de l’etude est alors conclue si et seulement si nous observons le rejet d’au moins r hypotheses nulles parmi les m hypotheses nulles testees. Dans ce contexte, les statisticiens doivent prendre en compte la multiplicite induite par cette pratique. Nous nous sommes consacres dans un premier temps a la recherche d’une correction exacte pour l’analyse des donnees et le calcul de taille d’echantillon pour r = 1. Puis nous avons travaille sur le calcul de taille d’´echantillon pour toutes valeurs de r, quand les procedures en une etape, ou les procedures sequentielles sont utilisees. Finalement nous nous sommes interesses a la correction du degre de signification engendre par la recherche d’un codage optimal d’une variable explicative continue dans un modele lineaire generalise
RB1 gene mutations in retinoblastoma

Mutations in both alleles of the RB1 gene are causal for the development of retinoblastoma, a childhood tumor of the eye. The spectrum of somatic and germline mutations in this gene is dominated by small mutations. Data on small mutations are listed in a locus specific database available at http://www.d‐lohmann.de/Rb/mutations.html. Analysis of 368 reported small mutations reveals considerable heterogeneity. A notable recurrence of transitions is observed at 13 CpG‐dinucleotides that are part of CGA codons or splice donor sites. Most mutations create a premature termination codon. With few exceptions, patients heterozygous for mutations of this kind develop bilateral retinoblastoma. Missense mutations and inframe deletions are rare. Some of these mutations are associated with a distinct phenotype marked by incomplete penetrance and reduced expressivity. Hum Mutat 14:283–288, 1999. © 1999 Wiley‐Liss, Inc.
DYNAMICS OF MEASLES EPIDEMICS: SCALING NOISE, DETERMINISM, AND PREDICTABILITY WITH THE TSIR MODEL

Two key linked questions in population dynamics are the relative importance of noise vs. density-dependent nonlinearities and the limits on temporal predictability of population abundance. We propose that childhood microparasitic infections, notably mea- sles, provide an unusually suitable empirical and theoretical test bed for addressing these issues. We base our analysis on a new mechanistic time series model for measles, the TSIR model, which captures the mechanistic essence of epidemic dynamics. The model, and parameter estimates based on short-term fits to prevaccination measles time series for 60 towns and cities in England and Wales, is introduced in a companion paper. Here, we explore how well the model predicts the long-term dynamics of measles and the balance between noise and determinism, as a function of population size. The TSIR model captures the basic dynamical features of the long-term pattern of measles epidemics in large cities remarkably well (based on time and frequency domain analyses). In particular, the model illustrates the impact of secular increases in birth rates, which cause a transition from biennial to annual dynamics. The model also captures the observed increase in epidemic irregularity with decreasing population size and the onset of local extinction below a critical community size. Decreased host population size is shown to be associated with an increased impact of demographic stochasticity. The interaction between nonlinearity and noise is explored using local Lyapunov exponents (LLE). These testify to the high level of stability of the biennial attractor in large cities. Irregularities are due to the limit cycle evolving with changing human birth rates and not due to complex dynamics. The geometry of the dynamics (sign and magnitude of the LLEs across phase space) is similar in the cities and the smaller urban areas. The qualitative difference in dynamics between small and large host communities is that demographic and extinction-recolonization stochasticities are much more influential in the former. The regional dynamics can therefore only be understood in terms of a core-satellite metapopulation structure for this host-enemy system. We also make a preliminary exploration of the model's ability to predict the dynamic consequences of measles vaccination.
Identification and Expression of a Rat Fatty Acid Elongase Involved in the Biosynthesis of C18 Fatty Acids

A major part of the palmitic acid (C16:0) generated by fatty acid synthase is converted into stearic acid (C18:0) via carbon chain elongation. Here, we describe the cloning and expression of a rat hepatic enzyme, rELO2, responsible for the elongation of C16:0, presumably at the condensing reaction. Heterologous expression experiments in a yeast, Saccharomyces cerevisiae, demonstrated the elongation activity of rELO2 on C16:0 and to a lesser extent, C18:0 and fatty acids with low desaturation degree. This was distinct from that rELO1, a rat homolog of HELO1, which preferably catalyzed the elongation of mono- and polyunsaturated fatty acids of C16–C20. The Northern analysis showed that the expression of rELO2, but not rELO1, in hepatocytes was activated by the cycles of fasting and refeeding rats on a fat-free diet. Under these conditions, the rELO1 was expressed constitutively in various tissues but the rELO2 transcripts were detected predominantly in liver.
Molecular Circuitry of the SUMO (Small Ubiquitin-like Modifier) Pathway in Controlling Sumoylation Homeostasis and Suppressing Genome Rearrangements*

Small ubiquitin-like modifier (SUMO) E3 ligases are known to have a major role in preventing gross chromosomal rearrangements (GCRs); however, relatively little is known about the role of SUMO isopeptidases in genome maintenance and their role in controlling intracellular sumoylation homeostasis. Here we show the SUMO isopeptidase Ulp2 in Saccharomyces cerevisiae does not prevent the accumulation of GCRs, and interestingly, its loss causes subunit-specific changes of sumoylated minichromosome maintenance (MCM) helicase in addition to drastic accumulation of sumoylated nucleolar RENT and inner kinetochore complexes. In contrast, loss of Ulp1 or its mis-localization from the nuclear periphery causes substantial accumulations of GCRs and elevated sumoylation of most proteins except for Ulp2 targets. Interestingly, the E3 ligase Mms21, which has a major role in genome maintenance, preferentially controls the sumoylation of Mcm3 during DNA replication. These findings reveal distinct roles for Ulp1 and Ulp2 in controlling homeostasis of intracellular sumoylation and show that sumoylation of MCM is controlled in a subunit-specific and cell cycle dependent manner.
Evaluation of the effect of three growth regulators in the germination of comparettia falcata seeds under in vitro conditions

SummaryThe effect of 3-indoleacetic acid (IAA), 6-furfurylaminopurine (kinetin), and gibberellic acid (GA3) on germination of the orchid Comparettia falcata was evaluated in a factorial experiment (4×4×4) with Murashige and Skoog (1962) basal medium. It was established that seeds of this orchid could be maintained under aseptic conditions as long as the necessary nutrients and appropriate concentrations of growth regulators were provided. Of the three growth regulators used, IAA significantly decreased seed germination of Comparettia falcata. There was a synergistic effect in the kinetin:GA3 combination that produced a positive response in both percentage seed germination and development of seedlings. This study describes a single medium-based protocol able to achieve more than 160000 seedlings within 21 wk, starting from a single capsule, sufficient for both large-scale propagation and in vitro conservation of this threatened orchid.
Measuring autonomy in disabled people: validation of a new scale in a UK population

Objective: To evaluate the validity and reliability of an English version of the Impact on Participation and Autonomy Questionnaire (IPA). The original Dutch IPA has been shown to load onto five factors. Design: A validation study. Setting: Outpatients clinics and people’s homes. Subjects: Two hundred and thirteen people with multiple sclerosis, rheumatoid arthritis, spinal cord injury, and general practice attendees, stratified by level of disability (median age 54, 42% male, 58% female). Inclusion criteria: English as first language, aged 18-75, Mental Status Questionnaire score >6. Interventions: Self- and interviewer-administered outcome measures. Main measures: IPA, including one new item (66 participants completed the IPA on a second occasion). Other measures: Short Form-36 Health Survey (SF-36), London Handicap Scale, three domains of the Functional Limitations Profile (FLP): household management, social integration, emotion. Results: Confirmatory factor analysis confirmed the construct validity of the IPA (Normal Fit Index=0.98, Comparative Fit Index=0.99), indicating a good fit to the model. Convergent and discriminant validity were confirmed by the predicted associations, or lack of, with the exception of a poor association between the ‘social life/relationships’ IPA subscale and FLP-emotion. Internal reliability of the IPA was confirmed (Cronbach alphas >0.8; item-total correlations for all subscales >0.5). Test-retest reliability was confirmed for all items (weighted kappas >0.6) and subscales (intraclass correlation coefficients >0.90). Conclusions: The English IPA is a valid, reliable and acceptable measure of participation and autonomy in people with a range of conditions and can make a unique and fundamental contribution to outcome assessment. Further research is required to examine the responsiveness of the IPA to change over time, its clinical utility and suitability for use with people from ethnic minorities and with older people.
Hyperlocation in the Chilean pharmacy market: Its influence in consumer purchasing decisions

Factors influencing purchasing decisions in a competitive market experiencing hyperlocation are explored. Hyperlocation is a new term in the retailing literature, which is coined in this study. The term illustrates the presence of two or more branches of the same brand located within relatively close walking distance in high traffic pedestrian streets. Results indicate that price perception and discounts, proximity, brand preference, and loyalty cards are among the most important factors influencing consumers ́ purchasing decisions when hyperlocation is present. These factors importance were found to vary by gender and age group.
Sentiweb: French communicable disease surveillance on the world wide web

For 12 years the French Sentinel system has collected about 330 000 cases of eight communicable diseases in France from a sample of about 1% of the country's general practitioners (see box). 1 These sentinel general practitioners use a PC with a modem or a videotex home terminal to transmit data to a front server.2 Case records are automatically stored in a relational database (Oracle), and the incidence of each disease, expressed in cases per 100 000 inhabitants, is calculated weekly. Incidences are calculated for each administrative district (96 departments and 22 regions in metropolitan France). Weekly electronic bulletins give feedback to the sentinel general practitioners and public health authorities. Since September 1995 the results of this communicable disease surveillance have been available on a worldwide web site called Sentiweb (http://www.b3e. jussieu.fr/sentiweb). Sentiweb also provides an …
Curcumin Implants, Not Curcumin Diet, Inhibit Estrogen-Induced Mammary Carcinogenesis in ACI Rats

Curcumin is widely known for its antioxidant, anti-inflammatory, and antiproliferative activities in cell-culture studies. However, poor oral bioavailability limited its efficacy in animal and clinical studies. Recently, we developed polymeric curcumin implants that circumvent oral bioavailability issues, and tested their potential against 17β-estradiol (E2)–mediated mammary tumorigenesis. Female Augustus Copenhagen Irish (ACI) rats were administered curcumin either via diet (1,000 ppm) or via polymeric curcumin implants (two 2 cm; 200 mg each; 20% drug load) 4 days before grafting a subcutaneous E2 silastic implant (1.2 cm, 9 mg E2). Curcumin implants were changed after 4.5 months to provide higher curcumin dose at the appearance of palpable tumors. The animals were euthanized after 3 weeks, 3 months, and after the tumor incidence reached >80% (∼6 months) in control animals. The curcumin administered via implants resulted in significant reduction in both the tumor multiplicity (2 ± 1 vs. 5 ± 3; P = 0.001) and tumor volume (184 ± 198 mm3 vs. 280 ± 141 mm3; P = 0.0283); the dietary curcumin, however, was ineffective. Dietary curcumin increased hepatic CYP1A and CYP1B1 activities without any effect on CYP3A4 activity, whereas curcumin implants increased both CYP1A and CYP3A4 activities but decreased CYP1B1 activity in the presence of E2. Because CYP1A and CYP3A4 metabolize most of the E2 to its noncarcinogenic 2-OH metabolite, and CYP1B1 produces potentially carcinogenic 4-OH metabolite, favorable modulation of these CYPs via systemically delivered curcumin could be one of the potential mechanisms. The analysis of plasma and liver by high-performance liquid chromatography showed substantially higher curcumin levels via implants versus the dietary route despite substantially higher dose administered. Cancer Prev Res; 7(4); 456–65. ©2014 AACR.