Miracle-dz/UniFAR-FTUs huggingface dataset:
ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases

ONC201 triggers an apoptotic cellular stress response in both solid and blood tumors. Stressing cancer cells to death The anticancer drug ONC201 triggers cell death in various tumor types. A pair of papers (see also the Focus by Greer and Lipkowitz) show that ONC201 activated cell stress pathways that depended on the activation of the transcription factor ATF4. Kline et al. showed this stress response to ONC201 occurred in cells derived from various types of solid tumors, in which ATF4 activation led to an increase in the abundance of the proapoptotic protein TRAIL and its receptor DR5. Ishizawa et al. demonstrated that in acute myeloid leukemia and mantle cell lymphoma, ONC201 triggered apoptosis and inhibited mTORC1 signaling, a pathway that promotes cell growth and proliferation. The findings reveal more details about ONC201’s mechanism of action, potentially enabling patient stratification and future development to improve its efficacy. ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation– and cell survival–promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway.
The acquisition of noun and verb inflections.

This research describes the acquisition of 5 noun and verb inflections by 3 subjects of a longitudinal study. Criteria were established for asserting that inflections were required in particular utterances, and the proportion of supplied to omitted inflections was charted over time. Plurals appear before possessives, and each appears first in particular linguistic contexts. Present progressives appear before pasts and present indicatives. When rate of acquisition is compared across children, different results are obtained if chronological age or mean length of utterance is held constant. These findings, and a categorization of errors of commission according to the levels of generative grammar, are discussed.
BDNF and HSP gene polymorphisms and their influence on the progression of primary open-angle glaucoma in a Polish population

Introduction Glaucoma is a neurodegenerative disease that is often associated with high intraocular pressure (IOP). One of the effects of elevated IOP is disorder of neurotrophic molecules transport, including brain-derived neurotrophic factor (BDNF) and recruit specific cellular proteins called “heat shock proteins” (HSPs). The aim of this study was to evaluate a relationship between the BDNF and HSP70-1 gene polymorphisms with risk occurrence of primary open-angle glaucoma (POAG). Material and methods The study consisted of 167 patients with POAG (mean age: 73 ±9) and 193 healthy subjects (mean age: 64 ±13). Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP, using the following restriction enzymes: NlaIII (rs6265) and BsrBI (rs1043618). The Heidelberg retinal tomography (HRT) clinical parameters were also analyzed. The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. Results Comparison of the distributions of genotypes and alleles of the 196G/A polymorphism of the BDNF gene as well as 190G/C polymorphism of the HSP70-1 gene and analysis of the odds ratio (OR) showed no statistically significant differences between POAG patients and controls (p > 0.05). However, there was a statistically significant association of the 196G/A of BDNF and 190G/C of HSP70-1 gene polymorphisms with progression of POAG depending on values of clinical parameters. 196G/A of BDNF correlated with the parameters GDx and RA (p = 0.03; p = 0.002, respectively), while 190G/C of HSP70-1 correlated with c/d and RA (p = 0.014, p = 0.024, respectively). Conclusions The BDNF 196G/A and HSP70-1 190G/C gene polymorphisms may be related to progression of POAG.
Gifts Differing? Psychological Type Among Stipendiary And Non-Stipendiary Anglican Clergy

This chapter tests the idea that clergy in different kinds of ministry have different psychological profiles that relate to the kinds of jobs they may be required to do. Psychological type preferences of 529 male and 518 female clergy ordained in the Anglican Church in the United Kingdom from 2004 to 2007 were assessed using the Francis Psychological Type Scales. Overall, clergy showed a preference for introversion over extraversion, feeling over thinking, and judging over perceiving, but they showed no preference between sensing and intuition. After allowing for differences between the sexes and between clergy of different church tradition, theological orientation, and charismatic practice, there were significant differences in the psychological profiles of stipendiary ministers (SMs), Non-Stipendiary Ministers (NSMs), and Ordained Local Ministers (OLMs). Keywords: Anglican Church; Non-Stipendiary Ministers (NSMs); psychological type; stipendiary ministers (SMs)
Pioglitazone Attenuates Atherosclerosis in Diabetic Mice by Inhibition of Receptor for Advanced Glycation End-Product (RAGE) Signaling

Background Peroxisome proliferator-activated receptor-γ (PPAR-γ) exhibits anti-inflammatory and anti-diabetic properties, and is protective against cardiovascular diseases. This study aimed to determine the effects of a PPAR-γ agonist pioglitazone on atherogenesis in an ApoE knockout mouse (ApoE−/−) diabetic mouse model and in a cultured vascular smooth muscle cells (VSMCs) model. Material/Methods Male ApoE−/− mice were rendered diabetic by 5 daily intraperitoneal injections of streptozotocin. Pioglitazone (20 mg/kg/d) or PPAR-γ inhibitor GW9662 (1 mg/kg/d) were administered for 12 weeks. At the end of treatment, mice were killed and the aortae were isolated. Oil Red O staining was used to evaluate atherosclerotic plaque area. H&E staining was used to evaluate the number of complicated plaques. Western blotting and immunohistochemistry were used to determine the expression of advanced glycation end-products (RAGE) and PPAR-γ. The effects of pioglitazone and GW9662 on RAGE and PPAR-γ expression were examined in cultured primary mouse VSMCs in hyperglycemic conditions. Results Administration of pioglitazone in diabetic ApoE−/− mice successfully reduced atherosclerotic plaque area and the number of complicated plaques. Moreover, pioglitazone inhibited RAGE and stimulated PPAR-γ protein expression in atherosclerotic plaques of diabetic ApoE−/− mice. In cultured VSMCs upon high-glucose challenge, pioglitazone downregulated RAGE mRNA and protein expression. Blockade of PPAR-γ activity by GW9662 remarkably attenuated the inhibitory actions of pioglitazone on atherogenesis, both in diabetic ApoE−/− mice and in cultured VSMCs, upon high-glucose challenge. Conclusions Pioglitazone has a therapeutic effect on atherosclerosis in diabetes, and inhibition of RAGE signaling plays a critical role in mediating the beneficial effects of pioglitazone.
Smartphone Enabled Dangerous Driving Report System

This paper proposes a novel dangerous driving report system using a smart phone platform. By collecting a stream of data through built-in GPS receiver, a time series of speed profile can be obtained for a given journey. An algorithm is proposed to detect anomaly in speed profile in order to detect whether a vehicle is speeding. As well as the ability to alert passengers in real-time in the case of speeding, the proposed system also records the journey data to be used as evidence when making a report. This is a feature which is not yet possible in the traditional dangerous driving report deployed in Thailand. A case study using three different smart phones in the proposed framework is performed. The findings reveal that the data from Smart phone is as accurate as the values from car's speedometer with a speed offset of approximately 4km/hr.
On computing the complex passivity radius

We characterize the complex passivity radius of a rational transfer matrix G(s):=C(sIn−A)−1B+D and propose an approach to compute it. The method depends on computing the smallest structured indefinite perturbation to a Hermitian matrix that makes it singular. We consider both additive and multiplicative perturbations, giving details for the additive case. In both cases, the smallest indefinite perturbation can be efficiently computed by solving a unimodal optimization problem in a real parameter. The passivity radius can be computed by minimizing the smallest singularity-inducing multiplicative indefinite perturbation of a frequency-dependent matrix over the imaginary axis.
Lifetime Extension of Wireless Sensor Networks Using Probabilistic Transmission Control for Distributed Estimation

This paper presents a novel network lifetime extension technique that uses probabilistic transmission control for distributed estimation in wireless sensor networks. In conventional techniques, only a few sensors are selected to transmit messages, and the remaining sensors are not used for measurement. Furthermore, as measurements cannot be carried out when the batteries of the selected sensors are exhausted, network lifetimes strongly depend on the battery capacity of the selected sensors. The presented technique increases the number of available sensors relative to conventional techniques. Sensors that are not selected in conventional techniques can be incorporated into the presented technique to obtain final estimates. As a result, the number of potentially usable sensors in networks increases. These newly available sensors are partitioned into several sensor sets to maintain the same estimation performance. Since observation and transmission for each sensor set are not carried out for every observation period, the network lifetime can be expected to be extended for a given estimation performance. Numerical examples are presented to validate the effectiveness of the presented technique.
A Self-Organized Neural Comparator

Abstract Learning algorithms need generally the ability to compare several streams of information. Neural learning architectures hence need a unit, a comparator, able to compare several inputs encoding either internal or external information, for instance, predictions and sensory readings. Without the possibility of comparing the values of predictions to actual sensory inputs, reward evaluation and supervised learning would not be possible. Comparators are usually not implemented explicitly. Necessary comparisons are commonly performed by directly comparing the respective activities one-to-one. This implies that the characteristics of the two input streams (like size and encoding) must be provided at the time of designing the system. It is, however, plausible that biological comparators emerge from self-organizing, genetically encoded principles, which allow the system to adapt to the changes in the input and the organism. We propose an unsupervised neural circuitry, where the function of input comparison emerges via self-organization only from the interaction of the system with the respective inputs, without external influence or supervision. The proposed neural comparator adapts in an unsupervised form according to the correlations present in the input streams. The system consists of a multilayer feedforward neural network, which follows a local output minimization (anti-Hebbian) rule for adaptation of the synaptic weights. The local output minimization allows the circuit to autonomously acquire the capability of comparing the neural activities received from different neural populations, which may differ in population size and the neural encoding used. The comparator is able to compare objects never encountered before in the sensory input streams and evaluate a measure of their similarity even when differently encoded.
Good Automatic Authentication Question Generation

We explore a novel application of Question Generation (QG) for authentication use, where questions are widely used to verify user identity for online accounts. In our approach, we prompt users to provide a few sentences about their personal life events. We transform user-provided input sentences into a set of simple fact-based authentication questions. We compared our approach with previous QG systems, and evaluation results show that our approach yielded better performance and the promise of future personalized authentication question generation.
Taste reactivity in alcohol preferring and nonpreferring rats.

Taste reactivity tests were used to examine the orofacial responses of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats to the taste of alcohol. In the initial exposure, naive rats were tested for reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40% v/v), water, and one solution each of sucrose and quinine. A two-bottle consumption test was then given for a 3-week period to allow the rats access to 10% alcohol. After the preference test, a second taste reactivity test was done using the same solutions as in the initial reactivity test. The results indicated no significant differences in taste reactivity between P rats and NP rats on the initial exposure, except that NP rats made significantly more mouth movements. During the two-bottle tests, consumption of alcohol by P rats was consistently higher than that of NP rats across all test days. On the second taste reactivity test, P rats showed an increase in the number of ingestive responses and a decrease in the number of aversive responses to alcohol. NP rats' taste reactivity to alcohol remained unchanged from Exposure 1 to Exposure 2. P rats' and NP rats' responses to sucrose and quinine did not change from Exposure 1 to Exposure 2. It was concluded that there were no innate taste response differences between P and NP rats to alcohol but that following alcohol experience, P rats showed a significant increase in ingestive responses and a concomitant decrease in aversive responses to the taste of alcohol. (ABSTRACT TRUNCATED AT 250 WORDS)
Childhood residential mobility and multiple health risks during adolescence and adulthood: the hidden role of adverse childhood experiences.

BACKGROUND Throughout US history, US society has been characterized by its high degree of residential mobility. Previous data suggest a relationship between mobility and increased health risk, but this relationship might be confounded by unmeasured adverse childhood experiences (ACEs). OBJECTIVES To examine the relationship of childhood residential mobility to health problems during adolescence and adulthood and to determine how much these apparent relationships may result from underlying ACEs. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 8116 adults who completed a survey that included childhood residential mobility, ACEs (childhood abuse, childhood neglect, and household dysfunction), and multiple health problems. MAIN OUTCOME MEASURES Number of childhood residential moves and number of ACEs (ACE score) were assessed for relationships to depressed affect, attempted suicide, alcoholism, smoking, early sexual initiation, and teenaged pregnancy. RESULTS After adjustment for demographic variables, the risk of high residential mobility during childhood (> or = 8 moves) was 1.7- to 3.1-fold for each ACE, and increased with the number of ACEs. Compared with respondents who never moved, the odds of health risk for respondents with high mobility during childhood ranged from 1.3 (for smoking) to 2.5 (for suicide). However, when the number of ACEs was entered into multivariate models, the relationship between mobility and health problems was greatly reduced. CONCLUSIONS Adverse childhood experiences are strongly associated with frequent residential mobility. Moreover, the apparent relationship between childhood mobility and various health risks is largely explained by ACEs. Thus, previous studies showing a relationship between residential mobility and negative outcomes were likely confounded by unmeasured ACEs.
Osteocutaneous free flaps for mandibular reconstruction: systematic review of their frequency of use and a preliminary quality of life comparison

Abstract Objectives: To determine whether the fibula free flap is the most frequently used osteocutaneous flap for mandible reconstruction, and whether it provides quality of life, depression and anxiety advantages. Methods: A systematic review of the public Medline database was conducted. Thirteen patients who underwent mandibular reconstruction at our hospital centre completed questionnaires to evaluate quality of life, depression and anxiety outcomes. Results: The most frequently used free flaps are those of the fibula (n = 982), radial forearm (n = 201), iliac crest (n = 113), subscapular system (n = 50) and rib–serratus (n = 7). In our patient population, there was a trend towards a better quality of life in those with a fibula free flap. However, patients in this group were significantly younger than patients with other flap types (p = 0.025). Patients with a subscapular system free flap were more depressed (p = 0.031); however, they had large through-and-through defects. Conclusion: The flap used most frequently in the literature is the fibula free flap. Comparative quality of life data are lacking, and homogeneous populations should be used to reach significant conclusions.
Prevalence of Malnutrition in Orally and Tube-Fed Elderly Nursing Home Residents in Germany and Its Relation to Health Complaints and Dietary Intake

Objective. To investigate the prevalence of malnutrition in orally and tube-fed nursing home (NH) residents in Germany and its relation to common health complaints and dietary intake. Methods. In 350 NH residents, subjects' characteristics, Mini Nutritional Assessment (MNA), and several health problems were inquired with the nursing staff using standardised interviews. In a subset of 122 residents, dietary intake was assessed by 3-day weighing records. Results. 7.7% of the participants were tube fed. 24.1% of orally nourished and 57.7% of tube-fed residents were malnourished (MNA < 17 p.). Malnutrition was significantly related to nausea/vomiting, constipation, pressure ulcers, dehydration, infections, antibiotic use, and hospitalisation. Mean daily energy intake was 1535 ± 413 kcal and mean protein intake was 54.2 ± 0.9 g/d irrespective of the nutritional state. Conclusion. In Germany, malnutrition is widespread among NH residents and is related to common health problems. The MNA rather reflects health condition than currently reduced dietary intake.
Induction of chondroitin sulfate proteoglycan synthesis and secretion in lymphocytes and monocytes

The ability of mononuclear leukocytes to synthesize and secrete proteoglycans was evaluated. Using radiolabeling with H2 35SO4, it is shown that peripheral blood mononuclear cells (PBMC) and their major subpopulations (B cells, T cells, and monocytes), as well as mouse spleen cells, all secreted easily detectable proteoglycan. After 24-h labeling periods, 90% of macromolecular 35S could be detected in culture media. This material was primarily (greater than 95%) chondroitin-4-sulfate proteoglycan (CSPG). Production and secretion of CSPG could be stimulated more than 200% in PBMC and 300% in T cell populations by high concentrations of concanavalin A and phorbol 12- myristate-13-acetate; lipopolysaccharide induced a small (twofold) but reproducible increase in CSPG secretion by adherent mononuclear leukocytes. The CSPG secreted by PBMC was relatively small in size compared to chondrocyte CSPG (130,000 daltons vs. 2-4 million daltons) but possessed similar sizes of glycosaminoglycan chains and greater solubility in low ionic strength solutions. This sulfated polyanion, which was produced endogenously by leukocytes and was actively secreted, might function as a co-mediator or "second messenger" in certain immune responses.
A non‐randomised dose‐escalating phase II study of thalidomide for the treatment of patients with low‐risk myelodysplastic syndromes: the Thal‐SMD‐2000 trial of the Groupe Français des Myélodysplasies

Patients (n = 47) with low‐risk myelodysplastic syndrome were treated with thalidomide [200 mg/d, increased by 200 mg/d/4 weeks up to week 16]. Responses were evaluated according to the International Working Group criteria at week 16 for 39 patients who received at least 8 weeks of treatment. Twenty‐three (59%) patients showed haematological improvement (HI): four major erythroid response (HI‐EM), 15 minor erythroid response, six major neutrophil response, two major platelet response. Side effects caused 22/39 to stop thalidomide before week 16. Nine of 23 responders continued thalidomide after week 16 [19% of trial patients] with sustained response in eight of nine. Six reached week 56, including the four HI‐EM patients [13% of trial patients]. Nineteen of 36 red blood cell transfusion‐dependent patients (53%) showed erythroid response, but only four became transfusion‐independent. Among the 23 responders, the median duration of response was 260 d (range 30–650). Responses were sustained in all patients except one, and were observed between week 4 and week 8 in 85% of patients, at doses ranging from 200 to 400 mg. Only two patients responded at 600 mg/d and none at 800 mg/d. No clinical characteristics of responding versus non‐responding patients were identified. The erythroid response rate was identical in all cytogenetic subgroups, including 5q31.1 deletions. Pretreatment vascular endothelial growth factor levels were lower in responders compared with non‐responders (P = 0·004). Microvessel density (MVD) increased and apoptosis decreased in four of six and in all six responders studied respectively whereas MVD and apoptosis were unchanged in three non‐responders.
Academic performance of male in comparison with female undergraduate medical students in Pharmacology examinations.

OBJECTIVE To compare the academic performance of male and female medical students in Pharmacology examinations. METHODS The comparative study was conducted at Rehman Medical College, Peshawar, Pakistan, from March to August 2015. For evaluating the students' academic performance, male and female students of academic sessions 2013-14 and 2014-15 were divided into 4 groups. Group 1: < 50% marks; Group 2: 50-69% marks; Group 3: 70-79% marks; and Group 4: >80% marks. SPSS 20 was used for data analysis. RESULTS Of the 200 medical students enrolled, 102(51%) were male and 98(41%) were female. There was no significant difference in the academic performance in terms of gender in multiple choice questions (p=0.811) and short essay questions (p=0.515). The effect of attendance was also insignificant (p=0.130). Significant difference was found between the academic records of urban male and female students compared to rural students (p=0.038). Boarder students' results were insignificantly different from those of day scholars (p=0.887). CONCLUSIONS There was no significant difference between the academic performance of male and female students.