Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermal and chemical denaturation of Colocasia esculenta tuber agglutinin from α2β2 to unfolded state

The major tuber storage protein of Colocasia esculenta, is a monocot mannose-binding, widely used dietary lectin, containing two polypeptides of 12.0 and 12.4 kDa. By both gel filtration and dynamic light scattering at pH 7.2, the lectin has a α2β2 form of apparent molecular mass of 48.2 kDa and a hydrodynamic radius of 6.1 ± . 2 nm; however, at pH 3, it migrates as αβ and has a reduced hydrodynamic radius of 4.6 ± . 3 nm. Our circular dichroism spectroscopy studies show that the lectin retains approximately 100% of its secondary structure between pH 2–8, going down to ~90% for extreme acidic/alkaline conditions. The fluorescence emission maxima of 346 to 350 nm for pH 4 to 10 show that the tryptophan residues are relatively exposed. The unfolding is a simple two-state process, N4 ↔ 4U, as seen in our denaturation scan profiles. These denaturation profiles, monitored separately by fluorescence, far-UV CD, and near-UV CD, are completely super imposable. Analyses of these profiles provide an estimate of several thermodynamic parameters at each guanidinium chloride concentration, including the melting temperature Tg, which is 346.9 K in 0 M, but lowers to 321.8 K in 3.6 M. Dimeric and tetrameric interfaces observed in the crystal structure for the same protein are used to rationalize solution data in some detail.
Nucleocapsid and Matrix Protein Contributions to Selective Human Immunodeficiency Virus Type 1 Genomic RNA Packaging

ABSTRACT The nucleocapsid protein (NC) of retroviruses plays a major role in genomic RNA packaging, and some evidence has implicated the matrix protein (MA) of certain retroviruses in viral RNA binding. To further investigate the role of NC in the selective recognition of genomic viral RNA and to address the potential contribution of MA in this process, we constructed chimeric and deletion human immunodeficiency virus type 1 (HIV-1) mutants that alter the NC or MA protein. Both HIV and mouse mammary tumor virus (MMTV) NC proteins have two zinc-binding domains and similar basic amino acid compositions but differ substantially in total length, amino acid sequence, and spacing of the zinc-binding motifs. When the entire NC coding sequence of HIV was replaced with the MMTV NC coding sequence, we found that the HIV genome was incorporated into virions at 50% of wild-type levels. Viruses produced from chimeric HIV genomes with complete NC replacements, or with the two NC zinc-binding domains replaced with MMTV sequences, preferentially incorporated HIV genomes when both HIV and MMTV genomes were simultaneously present in the cell. Viruses produced from chimeric MMTV genomes in which the MMTV NC had been replaced with HIV NC preferentially incorporated MMTV genomes when both HIV and MMTV genomes were simultaneously present in the cell. In contrast, viruses produced from chimeric HIV genomes containing the Moloney NC, which contains a single zinc-binding motif, were previously shown to preferentially incorporate Moloney genomic RNA. Taken together, these results indicate that an NC protein with two zinc-binding motifs is required for specific HIV RNA packaging and that the amino acid context of these motifs, while contributing to the process, is less crucial for specificity. The data also suggest that HIV NC may not be the exclusive determinant of RNA selectivity. Analysis of an HIV MA mutant revealed that specific RNA packaging does not require MA protein.
Genome-Wide Testing of Exonic Variants and Breast Cancer Risk in the California Teachers Study

Background: Few studies have focused on the relationship of exonic variation with breast cancer and subtypes defined by tumor markers: estrogen receptor (ER), progesterone receptor (PR), and HER2. Methods: We genotyped 1,764 breast cancer patients and 1,400 controls from the California Teachers Study cohort using the Infinium HumanExome Beadchip. Individual variant and gene-based analyses were conducted for overall breast cancer and by individual tumor marker subtype. Results: No exonic variants or gene-based analyses were statistically significantly associated with breast cancer overall or by ER-, PR-, or HER2-defined subtype. Conclusions: We did not detect any novel statistically significant exonic variants with overall breast cancer risk or by subtype. Impact: Exonic variants in the exome chip may not be associated with overall breast cancer or subtype susceptibility. Cancer Epidemiol Biomarkers Prev; 26(9); 1462–5. ©2017 AACR.
Occupational risk for Legionella infection among dental healthcare workers: meta-analysis in occupational epidemiology

Objective The occupational risk for Legionella infection among dental healthcare workers (DHCWs) is conjectured because of the risk of routine inhalation of potentially contaminated aerosols produced by the dental instruments. Nevertheless, occupational epidemiology studies are contrasting. This meta-analysis assessed the level of scientific evidence regarding the relative occupational risk for Legionella infection among DHCWs. Methods Literature search was performed without time and language restrictions, using broad data banks (PubMed, Scopus, Web of Science, GOOGLE Scholar) and generic keywords (‘legionella’ AND ‘dent*’). Analytical cross-sectional studies comparing prevalence of high serum Legionella antibody levels in DHCWs and occupationally unexposed individuals were considered. The relative occupational risk was assessed through prevalence ratio (PR) with 95% CI. Between-study heterogeneity was assessed (Cochran’s Q test) and was used to choose the meta-analytic method. Study quality (modified Newcastle-Ottawa Scale) and publication bias (Begg and Mazumdar’s test, Egger and colleagues’ test, trim and fill R0 method) were assessed formally and considered for the sensitivity analysis. Sensitivity analysis to study inclusion, subgroup analyses (dental staff categories; publication year, before vs after 1998, ie, 5 years after the release by the Centers for Disease Control and Prevention of the infection control guidelines in dental healthcare setting) were performed. Results Seven studies were included (2232 DHCWs, 1172 occupationally unexposed individuals). No evidence of publication bias was detected. The pooled PR estimate was statistically non-significant at 95% level (1.7; 95% CI 0.8 to 3.2), study-quality adjustment did not change the PR considerably (PR, 1.5; 95% CI 0.5 to 4.1). PR was statistically significant before 1998 and no longer significant after 1998. Subgroup analysis according to DHCW categories was inconclusive. Conclusions There is no scientific evidence that DHCWs are at high occupational risk. The differences between former and recent studies could be due to different characteristics of municipal water systems and the infection control guideline dissemination.
Intratumoral Payload Concentration Correlates with the Activity of Antibody–Drug Conjugates

Antibody–drug conjugates (ADC) have become important scaffolds for targeted cancer therapies. However, ADC exposure–response correlation is not well characterized. We demonstrated that intratumor payload exposures correlated well with the corresponding efficacies of several disulfide-linked ADCs, bearing an DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2-expressing xenograft models. The correlation suggests that a threshold concentration of intratumor payload is required to support sustained efficacy and an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy (“Plateau” effect). In contrast to tumor PBD concentrations, related assessments of systemic exposures, plasma stability, and drug-to-antibody ratio changes of related ADCs did not consistently rationalize the observed ADC efficacies. A minimal efficacious dose could be determined by ADC dose-fractionation studies in the xenograft models. Mechanistic investigations revealed that both linker immolation and linker disulfide stability are the key factors that determine intratumor PBD concentrations. Overall, this study demonstrates how a linker design can impact ADC efficacy and that the intratumor exposure of a payload drug as the molecular mechanism quantitatively correlate with and predict the antitumor efficacy of ADCs. Mol Cancer Ther; 17(3); 677–85. ©2018 AACR.
Chemical Genomics Approach Leads to the Identification of Hesperadin, an Aurora B Kinase Inhibitor, as a Broad-Spectrum Influenza Antiviral

Influenza viruses are respiratory pathogens that are responsible for annual influenza epidemics and sporadic influenza pandemics. Oseltamivir (Tamiflu®) is currently the only FDA-approved oral drug that is available for the prevention and treatment of influenza virus infection. However, its narrow therapeutic window, coupled with the increasing incidence of drug resistance, calls for the next generation of influenza antivirals. In this study, we discovered hesperadin, an aurora B kinase inhibitor, as a broad-spectrum influenza antiviral through forward chemical genomics screening. Hesperadin inhibits multiple human clinical isolates of influenza A and B viruses with single to submicromolar efficacy, including oseltamivir-resistant strains. Mechanistic studies revealed that hesperadin inhibits the early stage of viral replication by delaying the nuclear entry of viral ribonucleoprotein complex, thereby inhibiting viral RNA transcription and translation as well as viral protein synthesis. Moreover, a combination of hesperadin with oseltamivir shows synergistic antiviral activity, therefore hesperadin can be used either alone to treat infections by oseltamivir-resistant influenza viruses or used in combination with oseltamivir to delay resistance evolution among oseltamivir-sensitive strains. In summary, the discovery of hesperadin as a broad-spectrum influenza antiviral offers an alternative to combat future influenza epidemics and pandemics.
Prostate carcinoma risk subsequent to diagnosis of benign prostatic hyperplasia

Pathologically, benign prostatic hyperplasia (BPH) is not considered a precursor for prostate carcinoma. However, because the two conditions share not only a similar hormonal environment within the prostate but also several common risk factors, it is possible that men with BPH may be at increased risk of prostate carcinoma due to these shared factors.
The Genus Alnus, A Comprehensive Outline of Its Chemical Constituents and Biological Activities

The genus Alnus (Betulaceae) is comprised of more than 40 species. Many species of this genus have a long history of use in folk medicines. Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds. Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are the dominant constituents in the genus, whose anticancer effect has been brought into focus. Pure compounds and crude extracts from the genus exhibit a wide spectrum of pharmacological activities both in vitro and in vivo. This paper compiles 273 naturally occurring compounds from the genus Alnus along with their structures and pharmacological activities, as reported in 138 references.
Effect of Troglitazone on Leptin Production: Studies In Vitro and in Human Subjects

Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese and lose weight when given leptin, but little is known about the physiological role of leptin in humans. Obese subjects have higher concentrations of leptin than lean subjects, the strongest correlation being with percentage body fat. Thus, it appears that obese subjects are resistant to the effects of endogenously secreted leptin. We have also shown that insulin stimulates leptin production, chronically but not acutely, presumably through its trophic effect on adipocytes. Troglitazone is an insulinsensitizing thiazolidinedione, which improves hepatic and skeletal muscle insulin resistance in NIDDM and obesity. This study was undertaken to investigate the effects of troglitazone on leptin production in vitro and in vivo. In the presence and absence of 100 nmol/l insulin and 10 umol/L troglitazone, 72-h primary cultures of isolated abdominal adipocytes were studied. Insulin led to an almost twofold increase in leptin in vitro, and this increase was completely abolished by coincubation with troglitazone. Incubation with troglitazone alone led to a 40% decrease in leptin production. In obese patients administered troglitazone 200 mg twice daily for 12 weeks, there was no significant change in fasting plasma leptin concentrations, despite a 40–50% reduction in fasting and postmeal plasma insulin concentrations. Troglitazone treatment led to a significant increase in insulin sensitivity, and there was a positive correlation between the change in insulin sensitivity and the change in plasma leptin concentration in these subjects. In conclusion, troglitazone treatment had no net effect on plasma leptin concentrations, possibly because of improvement in insulin sensitivity and reduction in plasma insulin concentrations.
Dynamic Relationship Between Oil Price And Inflation In South Africa

The oil price-inflation relationship has been at the center of attention among economists and policy analysts, especially after 1970's oil shocks that resulted in a significant increase in the rate of inflation in number of countries around the world. However in the recent years, a number of empirical study, mostly in developed economies, has found that the effect of oil price shocks on inflation has weakened; mainly due to a reduction in oil intensity in production process and lower inflation environment. Moreover, some empirical evidences have shown the response of inflation from a negative and a positive oil shock to differ. This study aims to investigate the evolving relationship between oil price and inflation in South Africa, using time series data of inflation and oil price starting from January, 1922 to July, 2013. The study has a policy relevance on monetary policy reaction to oil shocks as South Africa is a small open economy with higher dependency on oil import and a floating exchange rate system. We fit both symmetric and asymmetric dynamic conditional correlation GARCH (DCC-GARCH) to the data. The results reveal the oil price to have a positive relationship with inflation, however the correlation is low and ranges between 0.07-0.08. The time-series patterns show a tendency of temporary upward shift in the pair-wise conditional correlations during predominant oil crisis. We also observe an upward shift in correlation in the year 1986, which can be attributed to South Africa's oil embargo. Further, the asymmetric-DCC model, based on the DCC exponential GARCH (DCC-EGARCH) framework, which fits the data better than the symmetric DCC-GARCH, show that the positive shocks have higher effect on inflation than negative shocks of the same magnitude. Finally, we observe that the correlation has been decreasing gradually over time for both symmetric and asymmetric specification of DCC model. The weaker oil price-inflation relationship, observed in recent years, could be attributed to the South African Reserve Bank's commitment to stabilize inflation expectation in the presence of external shocks. The study highlights the relative importance of oil shocks on inflation, and recommends that the Reserve Bank needs to remain attentive to oil price shocks, especially the positive ones.
Effects of cognitive remediation on negative symptoms dimensions: exploring the role of working memory

Background Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement. Method Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests. Results Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = −0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation. Conclusions The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.
Two Sides to the Story: An Interactionist Perspective on Identifying Potential

PETER G. DOMINICKStevens Institute of TechnologyALLISON S. GABRIELThe University of AkronTreat people as if they were what theyoughttobeandyouhelpthemtobecomewhat they are capable of being. —Johann Wolfgang Von GoetheSilzer and Church (2009) rightly point outthat the identiﬁcation of potential mustbegin with a clear and contextually rele-vant deﬁnition of the construct. As theynote, across varying ﬁelds of practice andresearch, one will ﬁnd a wide array ofvariables emphasized as critical to that def-inition. Their article makes a signiﬁcantcontribution toward the integration andsynthesis of those divergent perspectives.Yet, in today’s global workplace wherethe competition for a qualiﬁed workforceis ever increasing (e.g., Farrell et al., 2005;Gandossy&Effron,2003),perhapsthemorepressing challenges organizations face cen-ter on what they can do not just to identifyhigh potential but also to optimize and,perhaps in some cases, create potentialamong the workforce they possess.
Rethinking Wine Investment in the UK and Australia

This article presents three arguments as to why the value of wine as an investment good has typically been understated and argues that wine investment in the UK and Australia represents a value proposition. It is argued that general all vintage wine indexes understate the return the typical investor receives; that comparisons using pre-tax returns overstate the value of standard financial assets relative to wine; and that wine investment provides value in terms of allowing portfolio risk to be reduced.
Price Formation and the Measurement of Market Power on the International Dairy Markets

In the recent years, the international dairy markets have become more and more the focus of public attention. This was primarily due to a higher degree of price volatility that also spilled over to the prices in the European Union after the export subsidies were suspended. Under these circumstances, it is increasingly important to understand the price formation on the international dairy markets. Since the international supply side on these markets is highly concentrated, the price formation can be expected to be influenced by market power. In this context, especially New Zealand is worth mentioning. The New Zealand dairy co-operative Fonterra is the most important player on the dairy markets holding world market shares of more than fifty percent in some cases. In this PhD thesis – that is composed of three papers – the pricing-to-market and the residual demand approach are used to analyze the New Zealand dairy exports with regard to market power. In doing so, both approaches are extended or modified. In the first paper, simulated data is used to show that the empirical pricing-to-market model proposed by Knetter can be expected to provide biased estimates of the prevailing degree of pricing-to-market. This is because the way of how the model controls for the export country’s overall marginal cost implicitly assumes that changes in the marginal cost affect prices equally across destination countries. However, since the destination-specific pass-through of cost and exchange rates are equal for a profit-maximizing firm, the pricing-to-market coefficients of the Knetter model can be expected to be biased toward the average coefficient in the sample – around fifty percent under realistic conditions. Therefore, in the second paper, an alternative approach to control for the marginal cost is proposed – the usage of the so-called “stochastic” marginal cost; this procedure also allows the inference of pricing-to-market through changes in the marginal cost. At the same time, the Knetter model is extended to an oligopolistic model of pricing-to-market that a) provides an index of product differentiation and additionally b) identifies the source of pricing-to-market – a task that had not been solved until now. In the third paper, the concept of the stochastic marginal cost is applied to the residual demand approach in order to replace cost shifting variables that often reflect only a small proportion of the marginal cost. The results of both approaches show that Fonterra has a moderate degree of market power on the international dairy markets with estimated markups that amount to nine percent on average. These markups vary much more across destination countries than across the products analyzed. As the pattern can hardly be explained by observable factors, the prevailing degrees of market power seem to be caused by unobservable and qualitative factors. The results also show that Fonterra uses its markup in order to smooth out changes in the marginal cost – on average 40% – in order to maintain its market share in the destination countries.
A CANDIDATE YOUNG MASSIVE PLANET IN ORBIT AROUND THE CLASSICAL T TAURI STAR CI TAU

The ∼2 Myr old classical T Tauri star CI Tau shows periodic variability in its radial velocity (RV) variations measured at infrared (IR) and optical wavelengths. We find that these observations are consistent with a massive planet in a ∼9 day period orbit. These results are based on 71 IR RV measurements of this system obtained over five years, and on 26 optical RV measurements obtained over nine years. CI Tau was also observed photometrically in the optical on 34 nights over ∼one month in 2012. The optical RV data alone are inadequate to identify an orbital period, likely the result of star spot and activity-induced noise for this relatively small data set. The infrared RV measurements reveal significant periodicity at ∼9 days. In addition, the full set of optical and IR RV measurements taken together phase coherently and with equal amplitudes to the ∼9 day period. Periodic RV signals can in principle be produced by cool spots, hotspots, and reflection of the stellar spectrum off the inner disk, in addition to resulting from a planetary companion. We have considered each of these and find the planet hypothesis most consistent with the data. The RV amplitude yields an of ∼8.1 MJup; in conjunction with a 1.3 mm continuum emission measurement of the circumstellar disk inclination from the literature, we find a planet mass of ∼11.3 MJup, assuming alignment of the planetary orbit with the disk.