Miracle-dz/UniFAR-FTUs huggingface dataset:
A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone.

OBJECTIVE Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks. METHOD After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [(11)C]raclopride PET to measure D(2) occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone. RESULTS Mean post- and preinjection D(2) occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration associated with 50% D(2) occupancy (ED(50)) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D(2) occupancy. CONCLUSIONS All three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.
Rapid Development of gp120-Focused Neutralizing B Cell Responses during Acute Simian Immunodeficiency Virus Infection of African Green Monkeys

ABSTRACT The initial phases of acute human immunodeficiency virus type 1 (HIV-1) infection may be critical for development of effective envelope (Env)-specific antibodies capable of impeding the establishment of the latent pool of HIV-1-infected CD4+ T cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical virus transmission. However, the initial systemic HIV-1 Env-specific antibody response targets gp41 epitopes and fails to control acute-phase viremia. African-origin, natural simian immunodeficiency virus (SIV) hosts do not typically progress to AIDS and rarely postnatally transmit virus to their infants, despite high milk viral loads. Conversely, SIV-infected rhesus macaques (RMs), Asian-origin nonnatural SIV hosts, sustain pathogenic SIV infections and exhibit higher rates of postnatal virus transmission. In this study, of acute SIV infection, we compared the initial systemic Env-specific B cell responses of AGMs and RMs in order to probe potential factors influencing the lack of disease progression observed in AGMs. AGMs developed higher-magnitude plasma gp120-specific IgA and IgG responses than RMs, whereas RMs developed more robust gp140-directed IgG responses. These gp120-focused antibody responses were accompanied by rapid autologous neutralizing responses during acute SIV infection in AGMs compared to RMs. Moreover, acute SIV infection elicited a higher number of circulating Env-specific memory B cells in peripheral blood of AGMs than in the blood of RMs. These findings indicate that AGMs have initial systemic Env-specific B cell responses to SIV infection distinct from those of a nonnatural SIV host, resulting in more functional SIV-specific humoral responses, which may be involved in impairing pathogenic disease progression and minimizing postnatal transmission. IMPORTANCE Due to the worldwide prevalence of HIV-1 infections, development of a vaccine to prevent infection or limit the viral reservoir remains an important goal. HIV-1-infected humans, as well as SIV-infected nonnatural SIV hosts, develop pathogenic infections and readily transmit the virus to their infants. Conversely, natural SIV hosts do not develop pathogenic infections and rarely transmit the virus to their infants. The immunologic factors contributing to these favorable outcomes in natural SIV hosts could prove invaluable for directing HIV-1 vaccine and therapy design. This study identified distinctions in the specificity and function of the initial systemic SIV envelope-specific B cell response that developed during acute SIV infection in natural and nonnatural SIV host species. Identification of distinct acute B cell responses in natural SIV hosts may inform vaccine strategies seeking to elicit similar responses prior to or during the initial phases of acute HIV-1 infection.
Wearable Privacy: Skeletons in The Data Closet

Equipped with sensors that are capable of collecting physiological and environmental data continuously, wearable technologies have the potential to become a valuable component of personalized healthcare and health management. However, in addition to the potential benefits of wearable devices, the widespread and continuous use of wearables also poses many privacy challenges. In some instances, users may not be aware of the risks associated with wearable devices, while in other cases, users may be aware of the privacy-related risks, but may beunable to negotiate complicated privacy settings to meet their needs and preferences. This lack of awareness could have an adverse impact on users in the future, even becoming a "skeleton in the closet. " In this work, we conducted 32 semi-structured interviews to understand how users perceive privacy in wearable computing. Results suggest that user concerns toward wearable privacy have different levels of variety ranging from no concern to highly concerned. In addition, while user concerns and benefits are similar among participants in our study, these variablesshould be investigated more extensively for the development of privacy enhanced wearable technologies.
Ethnic differences in weight retention after pregnancy: the ABCD study.

BACKGROUND Postpartum weight retention contributes to the development of overweight and obesity in women of childbearing age and is more pronounced in ethnic minority groups. This study examined ethnic differences in postpartum weight retention and the explanatory role of socio-economic status (SES), mental health and lifestyle. METHODS In the Amsterdam Born Children and their Development (ABCD) study, a large multi-ethnic cohort study conducted in The Netherlands, women filled out questionnaires in the first trimester of pregnancy and 3-5 months postpartum. A total of 4213 women provided data on weight gain, ethnicity, SES, mental health and lifestyle during and after pregnancy. Postpartum weight retention was defined as a difference of ≥5 kg between self-reported pre-pregnancy and postpartum weight. The influence of ethnicity on postpartum weight retention was assessed in logistic regression analyses. Whether the role of ethnicity was attenuated by adding SES, mental health and lifestyle factors were subsequently investigated. RESULTS Marked differences in weight change during and after pregnancy were found between ethnic groups. Turkish women had significantly more weight retention than Dutch women. This difference could not be explained by other factors. CONCLUSION In the prevention of postpartum weight retention, no single approach seems applicable to all ethnic groups. During pregnancy, health professionals should focus on Turkish women in particular, as they appear to have the highest risk of weight retention.
Mutations within the ADP (E3-11.6K) Protein Alter Processing and Localization of ADP and the Kinetics of Cell Lysis of Adenovirus-Infected Cells

ABSTRACT ADP (also known as E3-11.6K protein) is synthesized abundantly in late adenovirus infection and is required for efficient lysis of infected cells and release of viral progeny at the end of the viral replication cycle. ADP is a type III bitopic NendoCexo nuclear membrane and Golgi glycoprotein that is produced at high levels in late adenovirus infection (>24 h postinfection). We show pulse-chase and other studies indicating that ADP undergoes a complex process of N- and O-linked glycosylation and proteolytic cleavage. In order to further characterize ADP, a series of 23 deletion and point mutations has been constructed in the adenovirus serotype 2 adp gene and then built into a wild-type adenovirus background. These mutants were analyzed for processing and intracellular localization of ADP. Mutation of the single predicted N glycosylation site eliminated N glycosylation. Deletion of a region in ADP rich in serine and threonine residues reduced O glycosylation. In general, mutations within the lumenal domain of ADP resulted in lower protein stability; immunofluorescence assays indicated that these ADPs were primarily present in the Golgi apparatus. Viruses with mutations within the cytoplasmic-nucleoplasmic domain of ADP showed normal glycosylation patterns and protein abundance for ADP, but the protein was often found throughout cellular membranes rather than being localized specifically to the nuclear membrane and Golgi apparatus. The ADP virus mutants were analyzed by cell viability assays to determine the kinetics of cell lysis following infection of human A549 cells. In general, viruses with mutations within the lumenal domain of ADP display greatly reduced efficiencies of cell lysis. Viruses with large deletions in the cytoplasmic-nucleoplasmic domain of ADP retain much of their ability to lyse infected cells.
Optimal Loading Range for the Development of Peak Power Output in the Hexagonal Barbell Jump Squat

Abstract Turner, TS, Tobin, DP, and Delahunt, E. Optimal loading range for the development of peak power output in the hexagonal barbell jump squat. J Strength Cond Res 29(6): 1627–1632, 2015—Recent studies indicate that the utilization of the hexagonal barbell jump squat (HBJS) compared with the traditional barbell jump squat may offer a superior method of developing peak power. The notion that a single optimal load may be prescribed in training programs aiming to develop peak power is subject to debate. The purpose of this study was to identify the optimal load corresponding with peak power output during the HBJS in professional rugby union players. Seventeen professional rugby union players participated in this study. Participants performed 3 unloaded countermovement jumps on a force plate and 3 HBJS at each of the following randomized loads: 10, 20, 30, and 40% of box squat 1 repetition maximum (1RM). Peak power output was the dependent variable of interest. A one-way repeated measures analysis of variance was conducted to compare peak power output across each load. Peak power output was the dependent variable of interest. A significant main effect for load was observed (Wilk's Lambda = 0.11, F(4,13) = 18.07, p < 0.01, partial &eegr;2 = 0.88). Results of the Bonferroni-adjusted pairwise comparisons indicated that peak power output in the HBJS is optimized at a load range between 10 and 20% of box squat 1RM. The results of this study indicate that the use of the HBJS with a training load between 10 and 20% of box squat 1RM optimizes peak power output in professional rugby union players.
Gender differences in long‐term outcome after primary percutaneous intervention for ST‐segment elevation myocardial infarction

Previous studies on gender differences in outcome in patients with ST segment elevation myocardial infarction (STEMI) have been performed, but most of those are from before the current era of PCI technique and medical therapy and have a short duration of follow‐up. The objective of our study is to assess the influence of gender on long‐term outcome in patients with STEMI who underwent primary percutaneous intervention (PCI) between January 2006 and May 2008.
Correlations of cell cycle regulators (p53, p21, pRb and mdm2) and c‐erbB‐2 with biological markers of proliferation and overall survival in breast cancer

Aim: The biological impact of cell cycle regulatory proteins on breast cancer progression is widely recognised, although mostly unclear. The aim of this preliminary study was to investigate the correlations of several cell cycle modulators (p53, p21, pRb, and mdm2) and c‐erbB‐2 expression with cell proliferation markers (S‐phase fraction [SPF] and Ki‐67) and overall survival in breast cancer. Methods: The series comprised 50 women with stage I‐II invasive ductal breast carcinoma (median follow‐up 87 months), who were selected for their tumour proliferative characteristics (15 low, 15 high, and 20 intermediate proliferative tumours). Tumour differentiation was assessed following the Nottingham grading criteria. Cell cycle regulators, oestrogen receptor status, and Ki‐67 index were analysed by immunohistochemistry on paraffin embedded material (cut‐offs 10%). c‐erbB‐2 was evaluated according to a standardised immunohistochemical assay and borderline cases were confirmed by FISH analysis. Ploidy and SPF were determined by DNA flow cytometry on frozen samples. Chi‐square test and Fisher's exact test were applied to analyse the statistical significance of data. Results: Positive immunostaining was observed in nine (18%) p53+, 30 (60%) p21+, 13 (26%) pRb+, and one (2%) mdm2+ cases. c‐erbB‐2 expression was considered positive in 11 (22%) cases. In the subset of patients dead of the disease, a high incidence of c‐erbB‐2 over‐expression (7/10, 70%) was verified. In general, no significant correlations among cell cycle regulators or between the latter and histopathological or proliferative characteristics were found. Only the p53−/p21+ phenotype significantly correlated with low SPF (p=0.048), and p21 positivity showed a trend to be associated with low SPF (p=0.083). No statistically significant correlations between cell cycle inhibitors and clinical outcome were found. On the contrary, c‐erbB‐2 over‐expression showed significant correlations with DNA aneuploidy (p<0.001), high SPF (p<0.001), high tumour grading (p=0.008), lack of oestrogen receptors (p=0.036), and poor overall survival (p<0.001). Conclusions: The results seem to indicate the lack of correlations of cell cycle regulatory proteins with cell proliferation markers and overall survival in breast cancer, in contrast to c‐erbB‐2 over‐expression which was found to be associated with increased proliferation rate and worse prognosis.
Multi‐site Study of Incidence of Pressure Ulcers and the Relationship Between Risk Level, Demographic Characteristics, Diagnoses, and Prescription of Preventive Interventions

OBJECTIVE: To determine the incidence of pressure ulcers in varied populations, and whether demographic characteristics (age, gender, race) and primary diagnosis are factors in pressure ulcer development when the level of risk for developing ulcers is considered. To determine if there is a difference in the type of preventive services prescribed for persons who do or do not develop pressure ulcers when risk is controlled and whether differences can be related to demographic characteristics.
The investment horizon problem: a possible resolution

In the conventional model of investments, the optimal fractions in the risky assets do not depend on the time horizon. This is against empirical evidence, and against the typical recommendations of portfolio managers. We demonstrate that if the intertemporal coefficient of relative risk aversion is allowed to depend on time, or the age of the investor, the investment horizon problem can be resolved. Accordingly, the only standard assumption in applied economics/finance that we relax in order to obtain our conclusion, is the state and time separability of the intertemporal felicity index in the investor’s utility function. We include a random, idiosyncratic horizon of the consumer, which is essential when there is no intermediate consumption, we consider bequest, and also demonstrate that preferences aggregate.
Inactivation by gamma irradiation of animal viruses in simulated laboratory effluent

Several animal viruses were treated with gamma radiation from a 60Co source under conditions which might be found in effluent from an animal disease laboratory. Swine vesicular disease virus, vesicular stomatitis virus, and blue-tongue virus were irradiated in tissues from experimentally infected animals. Pseudorabies virus, fowl plague virus, swine vesicular disease virus, and vesicular stomatitis virus were irradiated in liquid animal feces. All were tested in animals and in vitro. The D10 values, that is, the doses required to reduce infectivity by 1 log10, were not apparently different from those expected from predictions based on other data and theoretical considerations. The existence of the viruses in pieces of tissue or in liquid feces made no difference in the efficacy of the gamma radiation for inactivating them. Under the "worst case" conditions (most protective for virus) simulated in this study, no infectious agents would survive 4.0 Mrads.
The Effect of Variation in the Interval Between Right and Left Ventricular Activation on Paced QRS Duration

O'COCHLAIN, B. , et al.: The Effect of Variation in the Interval Between Right and Left Ventricular Activation on Paced QRS Duration. Pacing of the RV and LV is a promising technique for treating patients with dilated cardiomyopathy and bundle branch block. The salutary effects of biventricular pacing may be due to resynchronization of LV activation. Currently, available biventricular pacemakers and implanted defibrillators produce simultaneous ventricular output pulses. The purpose of the current study was to assess the effects of variation in the timing of RV and LV activation, using the paced QRS duration as a marker of resynchronization. Twenty‐six patients undergoing transvenous biventricular pacemaker implantation were studied. After stable lead positions were achieved, activation of the LV and RV was varied over a range of ± 50 ms and the QRS duration measured on a 12‐lead ECG. Only 6 (23%) of the 26 patients had maximal shortening of the paced QRS with simultaneous activation of the LV and RV. The shortest paced QRS duration was most often produced by an LV to RV interval of – 30 ms (LV activation preceding RV activation). Optimization of LV to RV interval resulted in an additional 13% shortening of the paced QRS compared to simultaneous activation (P < 0.0001). Patients with leads located on the lateral or anterolateral walls of the LV were more likely to benefit from preexcitation of the LV than did patients with leads in the posterior position. Results of this study suggest that the ability to program the LV to RV interval may be useful to optimize the benefit of biventricular pacing.
Role of technology entrepreneurship in the development of innovativeness of small and medium-sized enterprises

Summary Technology entrepreneurship is an interesting concept for transforming the potential of the scientific and research and development fields (including a wider impact of the so-called business environment sphere) into innovative products and services. In consequence, it might become a key factor in building the innovation potential of modern enterprises, especially SME sector enterprises, which due to their resource shortages have limited ability to carry out independent research and development operations. Taking the above into account, the aim of the article is to identify and evaluate the role of entrepreneurship in the development of innovativeness of SMEs. To achieve this aim, a survey was conducted on a sample of 300 SMEs based in ithe łódzkie province.
Random Walk, Ergodicity versus Predictability – The Case of the Budapest Stock Exchange

In financial markets, the term 'random walk' is frequently used in relation to price movement over a period of time. This highly expressive term simply means that prices do not follow a predictable trend, and so previous movements are unsuitable as a basis for speculation regarding future price changes. There exists, however, another model which is based on the ergodic theorem, and this says that past and present probability distribution define the probability distribution which will dictate future market prices. Clearly, the 'random walk' hypothesis and the ergodic theorem are polar opposites, and, whilst the concept of uncertainty is closely linked to the former, the latter suggests that forecasting is, in fact, possible. This paper examines how the theory of efficient markets and the efficiency of the market itself provide the means to resolve this contradiction. We provide empirical proof concerning the 'random walk' theory, for both the recession and post-recession periods in the case of the stock index of the Hungarian stock market.
Expression Analysis of Genes Associated with the Induction of the Carbon-Concentrating Mechanism in Chlamydomonas reinhardtii1[W][OA]

Acclimation to varying CO2 concentrations and light intensities is associated with the monitoring of environmental changes by controlling genetic and physiological responses through CO2 and light signal transduction. While CO2 and light signals are indispensable for photosynthesis, and these environmental factors have been proposed as strongly associated with each other, studies linking these components are largely limited to work on higher plants. In this study, we examined the physiological characteristics of a green alga, Chlamydomonas reinhardtii, exposed to various light intensities or CO2 concentrations. Acclimation to CO2-limiting conditions by Chlamydomonas requires the induction of a carbon-concentrating mechanism (CCM) to allow the uptake of inorganic carbon (Ci) and increase the affinity for Ci. We revealed that the induction of the CCM is not solely dependent on absolute environmental Ci concentrations but is also affected by light intensity. Using a cDNA array containing 10,368 expressed sequence tags, we also obtained global expression profiles related to the physiological responses. The induction of several CCM-associated genes was strongly affected by high light as well as CO2 concentrations. We identified novel candidates for Ci transporters and CO2-responsive regulatory factors whose expression levels were significantly increased during the induction of the CCM.
Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase

Cells respond to DNA double-strand breaks by recruiting factors such as the DNA-damage mediator protein MDC1, the p53-binding protein 1 (53BP1), and the breast cancer susceptibility protein BRCA1 to sites of damaged DNA. Here, we reveal that the ubiquitin ligase RNF8 mediates ubiquitin conjugation and 53BP1 and BRCA1 focal accumulation at sites of DNA lesions. Moreover, we establish that MDC1 recruits RNF8 through phosphodependent interactions between the RNF8 forkhead-associated domain and motifs in MDC1 that are phosphorylated by the DNA-damage activated protein kinase ataxia telangiectasia mutated (ATM). We also show that depletion of the E2 enzyme UBC13 impairs 53BP1 recruitment to sites of damage, which suggests that it cooperates with RNF8. Finally, we reveal that RNF8 promotes the G2/M DNA damage checkpoint and resistance to ionizing radiation. These results demonstrate how the DNA-damage response is orchestrated by ATM-dependent phosphorylation of MDC1 and RNF8-mediated ubiquitination.
How are Income and Wealth Linked to Health and Longevity

The greater one? s income, the lower one? s likelihood of disease and premature death. Americans at all income levels are less healthy than those with higher incomes. Not only is income associated with better health, but wealth affects health as well. Though it is easy to imagine how health is tied to income for the very poor or the very rich, the relationship between income and health is a gradient: discrepancies exist at every level of the economic ladder. Middle-class Americans are healthier than those living in or near poverty, but they are less healthy than the upper class.