Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy. PATIENTS AND METHODS Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy. RESULTS High-level MDR transduction of erythroid burst-forming unit (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM) derived from transduced CD34+ cells was shown posttransduction and prereinfusion. However, only two of the five patients showed evidence of MDR transduction of their marrow at a low level at 10 weeks and 3 weeks, respectively, posttransplantation. The cytokine-stimulated transduced cells may be out-competed in repopulation by unmanipulated normal cells that are reinfused concomitantly. The MDR retroviral supernatant that was used was shown to be free of replication-competent retrovirus (RCR) before use, and all tests of patients' samples posttransplantation were negative for RCR. In addition, no adverse events with respect to marrow engraftment or other problems related to marrow transplantation were encountered. CONCLUSION These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.
The effect of dimethyl sulfoxide on hepatic differentiation of mesenchymal stem cells

Introduction Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are suitable choices in autologous stem cell treatment of liver-associated diseases due to their hepatic differentiation potential. Dimethyl sulfoxide (DMSO) is an amphipathic molecule with potential of delivering both lipophilic and hydrophilic agents into cells, also a common cryoprotectant for freezing of the cells. DMSO was used in some protocols for induction of AT-MSCs towards hepatocyte like cells. However, the effect of DMSO on hepatogenic differentiation of AT-MSCs were not surveyed, previously. In the present study, we aimed at evaluation of the effect of DMSO on differentiation of AT-MSCs into hepatic lineage. Methods We isolated mesenchymal stem cells (MSCs) from adipose tissue, and then verifies multi-potency and surface markers of AT-MSCs . Isolated AT-MSCs randomly dispensed in four groups including Group 1: HGF treated, 2: HGF+ DMSO treated, 3: HGF+ DMSO+ OSM treated, and group control for a period of 3 weeks in the expansion medium without serum; EGF and bFGF were also included in the first days of inductions. The morphologic changes during induction period was observed with microscopy. The secretion of albumin (ALB) of the differentiating MSCs was investigated using ELISA, and urea production was evaluated using colorimetric assay. The qRT-PCR was performed for quantitation of hepatocyte marker genes including AFP, ALB, CK18, HNF4a, and HNF6. The glycogen storage of differentiated cells was visualized by periodic-acid Schiff‘s staining. Results The results demonstrate that DMSO speeds up hepatic differentiation of AT-MSCs characterized by rapid changes in morphology; higher expression of hepatic marker gene (ALB) in both mRNA and protein level (P < 0.05); also increased transcriptional levels of other liver genes including CK18, HNF4a, and HNF6 (P < 0.01); and moreover, greater percentage of glycogen storage(p < 0.05) in DMSO-treated groups. Conclusion DMSO catalyzes hepatic differentiation; therefore, using DMSO for acceleration of the hepatogenic protocols of AT-MSCs appears advantageous.
Designing and Engineering Methylorubrum extorquens AM1 for Itaconic Acid Production

Methylorubrum extorquens (formerly Methylobacterium extorquens) AM1 is a methylotrophic bacterium with a versatile lifestyle. Various carbon sources including acetate, succinate and methanol are utilized by M. extorquens AM1 with the latter being a promising inexpensive substrate for use in the biotechnology industry. Itaconic acid (ITA) is a high-value building block widely used in various industries. Given that no wildtype methylotrophic bacteria are able to utilize methanol to produce ITA, we tested the potential of M. extorquens AM1 as an engineered host for this purpose. In this study, we successfully engineered M. extorquens AM1 to express a heterologous codon-optimized gene encoding cis-aconitic acid decarboxylase. The engineered strain produced ITA using acetate, succinate and methanol as the carbon feedstock. The highest ITA titer in batch culture with methanol as the carbon source was 31.6 ± 5.5 mg/L, while the titer and productivity were 5.4 ± 0.2 mg/L and 0.056 ± 0.002 mg/L/h, respectively, in a scaled-up fed-batch bioreactor under 60% dissolved oxygen saturation. We attempted to enhance the carbon flux toward ITA production by impeding poly-β-hydroxybutyrate accumulation, which is used as carbon and energy storage, via mutation of the regulator gene phaR. Unexpectedly, ITA production by the phaR mutant strain was not higher even though poly-β-hydroxybutyrate concentration was lower. Genome-wide transcriptomic analysis revealed that phaR mutation in the ITA-producing strain led to complex rewiring of gene transcription, which might result in a reduced carbon flux toward ITA production. Besides poly-β-hydroxybutyrate metabolism, we found evidence that PhaR might regulate the transcription of many other genes including those encoding other regulatory proteins, methanol dehydrogenases, formate dehydrogenases, malate:quinone oxidoreductase, and those synthesizing pyrroloquinoline quinone and thiamine co-factors. Overall, M. extorquens AM1 was successfully engineered to produce ITA using acetate, succinate and methanol as feedstock, further supporting this bacterium as a feasible host for use in the biotechnology industry. This study showed that PhaR could have a broader regulatory role than previously anticipated, and increased our knowledge of this regulator and its influence on the physiology of M. extorquens AM1.
Inter-individual Variability for High Fat Diet Consumption in Inbred C57BL/6 Mice

Since inbred C57BL/6 mice are known to show inter-individual phenotypic variability for some traits, we tested the hypothesis that inbred C57BL/6 mice display a different tendency to consume a high fat (HF) diet. For this purpose, we used a compilation of HF intake data from an experimental protocol in which satiated mice were exposed to a HF pellet every morning for 2-h over 4 consecutive days. We found that mice displayed a large degree of variability in HF intake. Since day 1 HF intake significantly correlated with HF intake in successive days, we applied a hierarchical clustering algorithm on HF intake measurements in days 2, 3, and 4 in order to classify mice into “low” or “high” HF intake groups. “Low” HF intake group showed a day 1 HF intake similar to that seen in mice exposed to regular chow, while “high” HF intake group showed a higher day 1 HF intake as compared to “low” HF intake group. Both groups of mice increased HF consumption over the successive days, but “high” HF intake group always displayed a higher HF consumption than the “low” HF intake group. As compared to “low” HF intake group, “high” HF intake group showed a higher number of dopamine neurons positive for c-Fos in the VTA after the last event of HF intake. Thus, inbred C57BL/6 mice show inter-individual variability for HF intake and such feature may be linked to a different response to the rewarding properties of the HF diet.
How a Nuclear Power Plant Accident Influences Acceptance of Nuclear Power: Results of a Longitudinal Study Before and After the Fukushima Disaster

Major nuclear accidents, such as the recent accident in Fukushima, Japan, have been shown to decrease the public's acceptance of nuclear power. However, little is known about how a serious accident affects people's acceptance of nuclear power and the determinants of acceptance. We conducted a longitudinal study (N= 790) in Switzerland: one survey was done five months before and one directly after the accident in Fukushima. We assessed acceptance, perceived risks, perceived benefits, and trust related to nuclear power stations. In our model, we assumed that both benefit and risk perceptions determine acceptance of nuclear power. We further hypothesized that trust influences benefit and risk perceptions and that trust before a disaster relates to trust after a disaster. Results showed that the acceptance and perceptions of nuclear power as well as its trust were more negative after the accident. In our model, perceived benefits and risks determined the acceptance of nuclear power stations both before and after Fukushima. Trust had strong effects on perceived benefits and risks, at both times. People's trust before Fukushima strongly influenced their trust after the accident. In addition, perceived benefits before Fukushima correlated with perceived benefits after the accident. Thus, the nuclear accident did not seem to have changed the relations between the determinants of acceptance. Even after a severe accident, the public may still consider the benefits as relevant, and trust remains important for determining their risk and benefit perceptions. A discussion of the benefits of nuclear power seems most likely to affect the public's acceptance of nuclear power, even after a nuclear accident.
The Predictive Properties of Violence Risk Instruments May Increase by Adding Items Assessing Sleep

Background: The psychometric instruments developed for short-term prediction of violence in psychiatric inpatients do not include variables assessing sleep. Disturbances in sleep may precede aggression in this setting. We investigated whether adding information on sleep improved the predictive properties of the Brøset Violence Checklist (BVC). Methods: The study population consists of all patients admitted to a psychiatric intensive care unit (PICU) over a 6-month period who were hospitalized for at least one night (n = 50). Sleep observed by staff (521 nights), behavior assessed with the BVC (433 days), and aggressive incidents recorded by the Staff Observation Scale-Revised (n = 14) were included in the analysis. Results: The ability of the BVC to predict aggressive incidents improved from AUCROC 0.757 to AUCROC 0.873 when a combined sleep variable including both sleep duration and night-to-night variations of sleep duration was added to the BVC recordings. The combined sleep variable did not significantly predict aggressive incidents (AUCROC 0.653, p = 0.051). Conclusions: A sleep disturbance variable improves the predictive properties of the BVC in PICUs. Further studies of sleep duration, night-to-night variations in duration of sleep, and aggression are needed.
Antecedents and Outcomes of Parental Homework Involvement: How Do Family-School Partnerships Affect Parental Homework Involvement and Student Outcomes?

Recent studies have demonstrated that parental homework involvement may not always foster students’ desired school outcomes. Such studies have also concluded that the quality of parental homework involvement matters, rather than the quantity. Most importantly, previous studies have shown that strong family-school partnerships (FSPs) may help to improve parental involvement. However, there is little research on how FSP is related to homework involvement. The aim of the present study is to examine the link between an effective family-school communication (EFSC) – as one aspect of FSP – and the quality of parental homework involvement in the German context. For this purpose, we developed a new measure of EFSC. Taking a self-determination theory perspective on parental need support, the quality of parental homework involvement was differentiated into two dimensions of parental supportive behavior: autonomy support and competence support. We analyzed the data of 309 parents (82% mothers) of school students (52% girls) who participated in an online survey. The structural equation model revealed a positive relation between EFSC and the quality of parental homework involvement, which in turn was positively associated with school performance and well-being. Moreover, we found that the quality of parental homework involvement mediated the relations of EFSC with achievement and well-being. The results of our study highlight the role of EFSC as a key performance factor that helps to improve the quality of parental homework involvement, thereby promoting student achievement and well-being.
Honey Bee Parasitic Mite Contains the Sensilla-Rich Sensory Organ on the Foreleg Tarsus Expressing Ionotropic Receptors With Conserved Functions

Honey bee parasitic mites (Tropilaelaps mercedesae and Varroa destructor) detect temperature, humidity, and odor but the underlying sensory mechanisms are poorly understood. To uncover how T. mercedesae responds to environmental stimuli inside a hive, we first identified the sensilla-rich sensory organ on the foreleg tarsus. The organ appeared to correspond to Haller’s organ in ticks and contained four types of sensilla, which may respond to different stimuli based on their morphology. We searched for differentially expressed genes between the forelegs and hindlegs to identify mRNAs potentially associated with the sensory organ. The forelegs were enriched with mRNAs encoding sensory proteins such as ionotropic receptors (IRs) and gustatory receptors, as well as proteins involved in ciliary transport. We also found that T. mercedesae IR25a and IR93a were capable of rescuing temperature and humidity preference defects in Drosophila melanogaster IR25a and IR93a mutants. These results demonstrate that the structures and physiological functions of ancient IRs have been conserved during arthropod evolution. Our study provides insight into the sensory mechanisms of honey bee parasitic mites, as well as potential targets for methods to control the most serious honey bee pest.
SR : A Language for Parallel and Distributed Programming March 9 , 1992

This paper introduces the newest version of the SR concurrent programming language and illustrates how it provides support for different execution environments, ranging from shared-memory multiprocessors to distributed systems. SR uses a few well-integrated mechanisms for concurrency to provide flexible, yet efficient, support for parallel and distributed programming. This paper gives several realistic examples to illustrate these language mechanisms.
Squeaky Wheels and Troop Loyalty

This article considers how domestic protests influence coups. Protests signal regime illegitimacy, which incentivizes coups and provides a favorable climate for postcoup reforms. Protests also ease coordination obstacles among coup plotters and make international actors less likely to punish coup leaders. We expect these signaling processes to be strongest when protests take place near the capital or are nonviolent. Our empirical analyses introduce event-level protest data from the Social, Political, and Economic Event Database project into the coup literature. Examining a global sample of coup attempts from 1951 to 2005, we find strong support for our theoretical expectations. Our discussion provides implications for scholars studying coups and nonviolent movements more generally. It also speaks to the influence of external actors on social uprisings and highlights the importance of geographical disaggregation in the study of dissident behavior.
Electronic calendars in the office: an assessment of user needs and current technology

Manufacturers of integrated electronic office systems have included electronic versions of the calendar in almost every system they offer. This paper describes a survey of office workers, carried out to examine their use both of paper calendars and of electronic calendars that are commercially available as part of integrated office systems. It assesses the degree to which electronic calendars meet the needs of users. Our survey shows that the simple paper calendar is a tool whose power and flexibility is matched by few, if any, of the current commercially available electronic calendars. Recommendations for features that should be included in electronic calendars and automatic schedulers are included.
Representation and incorporation of clinical information in outpatient oncology prognosis using Bayesian networks and Naïve Bayes

Many studies have focused on prognosis for oncology patients with the following characteristics: an inpatient setting (uniform sampling), binary outcomes, and predictor variables of patient demographics and tumor characteristics. This paper examines the problem of predicting prognosis in an outpatient setting (non-uniform sampling), discrete outcomes, and predictor variables of clinical observations. In particular, we consider how to represent the clinical observational data and reason over the prognosis using Bayesian networks (BN) and Naíve Bayes (NB). Different representations include trend behaviors using splines and differences over a time period and the clinical observations themselves. The best models were able to outperform the majority classifier with 8.5% (BN) and 10.2% (NB) higher accuracies in predicting a patient's length of survival. The models with highest predictive performance both include a temporal behavioral representation.
Hemoglobin A1c Levels and Aortic Arterial Stiffness: The Cardiometabolic Risk in Chinese (CRC) Study

Objective The American Diabetes Association (ADA) recently published new clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT). Research Design and Methods The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV) and HbA1c were measured in 5,098 men and women. Results After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend <0.0001). The associations remained significant after further adjustment for blood pressure, heart rate, and lipids (P = 0.004), and the difference in cfPWV between the highest and the lowest quintiles of HbA1c was 0.31 m/s. Fasting glucose and 2 h OGTT were not associated with cfPWV in the multivariate analyses. HbA1c showed additive effects with fasting glucose or 2 h OGTT on cfPWV. In addition, age and blood pressure significantly modified the associations between HbA1c and cfPWV (P for interactions <0.0001 for age; and = 0.019 for blood pressure). The associations were stronger in subjects who were older (≥60 y; P for trend = 0.004) and had higher blood pressure (≥120 [systolic blood pressure]/80 mmHg [diastolic blood pressure]; P for trend = 0.028) than those who were younger and had lower blood pressure (P for trend >0.05). Conclusions HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.
Changes in cardiovascular health score and atherosclerosis progression in middle-aged and older persons in China: a cohort study

Objectives The American Heart Association (AHA) proposed a definition of 4 cardiovascular health behaviours and 3 health factors. On the basis of the 7 metrics, the cardiovascular health score (CHS) was used to estimate individual-level changes in cardiovascular health status. The aim of this study was to investigate whether changes in CHS (⊿CHS) at different time-points are associated with atherosclerosis progression in middle-aged and older persons. Design Prospective cohort study in China. Settings We defined 8 groups (≤−4, −3, −2, −1, 0, 1, 2 and ≥3) according to ⊿CHS. The impact of ⊿CHS on the change of brachial–ankle pulse wave velocity (⊿baPWV) and atherosclerosis progression was analysed. Participants A total of 3951 individuals met the inclusion criteria (≥40 years old; no history of stroke, transient ischaemic attack or myocardial infarction) and had complete information. Results ⊿baPWV decreased gradually (126.46±355.91, 78.4±343.81, 69.6±316.27, 49.59±287.57, 57.07±261.17, 40.45±264.27, 37.45±283.26 and 21.66±264.17 cm/s, respectively) with increasing ⊿CHS (p for trend<0.05). Multivariate linear regression analysis suggested a negative relationship between these 2 variables, which persisted after adjustment for other risk factors. Each increase in CHS was associated with a reduced baPWV for 15.22 cm/s (B value −15.22, p<0.001). Conclusions ⊿CHS were negatively related to ⊿baPWV, which proved to be an independent predictor of the progression of atherosclerosis in middle-aged and older persons. Trial registration number Kailuan study (ChiCTR-TNC-11001489).
Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters.