Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of the South East Asian Nutrition Survey (SEANUTS): a four-country multistage cluster design study

Nutrition is a well-known factor in the growth, health and development of children. It is also acknowledged that worldwide many people have dietary imbalances resulting in over- or undernutrition. In 2009, the multinational food company FrieslandCampina initiated the South East Asian Nutrition Survey (SEANUTS), a combination of surveys carried out in Indonesia, Malaysia, Thailand and Vietnam, to get a better insight into these imbalances. The present study describes the general study design and methodology, as well as some problems and pitfalls encountered. In each of these countries, participants in the age range of 0·5–12 years were recruited according to a multistage cluster randomised or stratified random sampling methodology. Field teams took care of recruitment and data collection. For the health status of children, growth and body composition, physical activity, bone density, and development and cognition were measured. For nutrition, food intake and food habits were assessed by questionnaires, whereas in subpopulations blood and urine samples were collected to measure the biochemical status parameters of Fe, vitamins A and D, and DHA. In Thailand, the researchers additionally studied the lipid profile in blood, whereas in Indonesia iodine excretion in urine was analysed. Biochemical data were analysed in certified laboratories. Study protocols and methodology were aligned where practically possible. In December 2011, data collection was finalised. In total, 16 744 children participated in the present study. Information that will be very relevant for formulating nutritional health policies, as well as for designing innovative food and nutrition research and development programmes, has become available.
Timed-Elastic-Bands for time-optimal point-to-point nonlinear model predictive control

This contribution presents a novel approach for nonlinear time-optimal model predictive control (MPC) based on Timed-Elastic-Bands (TEB). The TEB merges the states, control inputs and time intervals into a joint trajectory representation which enables planning of time-optimal trajectories in the context of model predictive control. Model predictive control integrates the planning of the optimal trajectory with state feedback in the control loop. The TEB approach formulates the fixed horizon optimal control problem for point-to-point transitions as a nonlinear program. The comparative analysis of the TEB approach with state-of-the-art approaches demonstrates its computational efficiency. The TEB approach generates a trajectory that approximates the analytical time-optimal trajectory in few iterations. This efficiency enables the refinement of the planned state and control sequence within the underlying closed-loop control during runtime.
Transmitter modulation of spike‐evoked calcium transients in arousal related neurons: muscarinic inhibition of SNX‐482‐sensitive calcium influx

Nitric oxide synthase (NOS)‐containing cholinergic neurons in the laterodorsal tegmentum (LDT) influence behavioral and motivational states through their projections to the thalamus, ventral tegmental area and a brainstem ‘rapid eye movement (REM)‐induction’ site. Action potential‐evoked intracellular calcium transients dampen excitability and stimulate NO production in these neurons. In this study, we investigated the action of several arousal‐related neurotransmitters and the role of specific calcium channels in these LDT Ca2+‐transients by simultaneous whole‐cell recording and calcium imaging in mouse (P14–P30) brain slices. Carbachol, noradrenaline and adenosine inhibited spike‐evoked Ca2+‐transients, while histamine, t‐ACPD, a metabotropic glutamate receptor agonist, and orexin‐A did not. Carbachol inhibition was blocked by atropine, was insensitive to blockade of G‐protein‐coupled inward rectifier (GIRK) channels and was not inhibited by nifedipine, ω‐conotoxin GVIA or ω‐agatoxin IVA, which block L‐, N‐ and P/Q‐type calcium channels, respectively. In contrast, SNX‐482 (100 nm), a selective antagonist of R‐type calcium channels containing the alpha1E (Cav2.3) subunit, attenuated carbachol inhibition of the somatic spike‐evoked calcium transient. To our knowledge, this is the first demonstration of muscarinic inhibition of native SNX‐482‐sensitive R‐channels. Our findings indicate that muscarinic modulation of these channels plays an important role in the feedback control of cholinergic LDT neurons and that inhibition of spike‐evoked Ca2+‐transients is a common action of neurotransmitters that also activate GIRK channels in these neurons. Because spike‐evoked calcium influx dampens excitability, our findings suggest that these ‘inhibitory’ transmitters could boost firing rate and enhance responsiveness to excitatory inputs during states of high firing, such as waking and REM sleep.
Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real‐time PCR

Minimal (i.e. submicroscopic) residual disease (MRD) predicts outcome in childhood acute lymphoblastic leukaemia (ALL). To be used clinically, MRD assays must be reliable and accurate. Two well‐established techniques, flow cytometry (FC) and polymerase chain reaction (PCR), can detect leukaemic cells with a sensitivity of 0·01% (10−4). We analysed diagnostic samples of 45 ALL‐patients (37 B‐lineage ALL, eight T‐lineage ALL) by four‐colour FC and real‐time PCR. Leukaemia‐associated immunophenotypes, at a sensitivity of MRD detection by FC at the 0·01% level, were identified in 41 cases (91%); antigen‐receptor gene rearrangements suitable for MRD detection with a sensitivity of 0·01% or better by PCR were identified in 38 cases (84%). The combined use of FC and PCR allowed MRD monitoring in all 45 patients. In 105 follow‐up samples, MRD estimates by both methods were highly concordant, with a deviation factor of <5 by Bland–Altman analysis. Importantly, the concordance between FC and PCR was also observed in regenerating bone marrow samples containing high proportions of CD19+ cells, and in samples studied 24 h after collection. We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false‐negative results due to clonal evolution or phenotypic shifts.
Complete mutation analysis panel of the 39 human HOX genes.

BACKGROUND The HOX gene family consists of highly conserved transcription factors that specify the identity of the body segments along the anteroposterior axis of the embryo. Because the phenotypes of mice with targeted disruptions of Hox genes resemble some patterns of human malformations, mutations in HOX genes have been expected to be associated with a significant number of human malformations. Thus far, however, mutations have been documented in only three of the 39 human HOX genes (HOXD13, HOXA13, and HOXA11) partly because current knowledge on the complete coding sequence and genome structure is limited to only 20 of the 39 human HOX genes. METHODS Taking advantage of the human and mouse draft genome sequences, we attempted to characterize the remaining 19 human HOX genes by bioinformatic analysis including phylogenetic footprinting, the probabilistic prediction method, and comparison of genomic sequences with the complete set of the human anonymous cDNA sequences. RESULTS We were able to determine the full coding sequences of 19 HOX genes and their genome structure and successfully designed a complete set of PCR primers to amplify the entire coding region of each of the 39 HOX genes from genomic DNA. CONCLUSIONS Our results indicate the usefulness of bioinformatic analysis of the draft genome sequences for clinically oriented research projects. It is hoped that the mutation panel provided here will serve as a launchpad for a new discourse on the genetic basis of human malformations.
Identification and management of inconsistencies in dynamically adaptive software systems

Computing devices now enable access to rich information about their surrounding execution environment gathered through sensor networks or system monitors. This ability allows software systems to be conceived with context in mind, instead of being created in isolation as in traditional approaches for software development. Services provided by software systems can be adapted to sensed conditions rendering such services more appropriate to the surrounding execution environment. Adaptations to the system's behavior take place unannounced over time. However, if not dealt with carefully, the behavior provided by such adaptations could lead to inconsistencies in the system's behavior. In order to avoid such inconsistencies, dependencies between adaptations must be carefully managed so that interactions gathered for the surrounding execution environment are not rendered incompatible. This dissertation investigates how to provide more guarantees about the predictability of the system's behavior when it is adapted dynamically at run time. Based on the observation of different dynamically adaptive software systems, we put forward a set of requirements that software systems should satisfy to ensure consistency of its behavioral adaptations. We propose a formal basis to support the development of consistent software systems in the presence of dynamic behavioral adaptations, called context Petri nets. This formal basis complies with the requirements for consistent dynamically adaptive software systems, and in particular context-oriented programming, on three levels: formalization, execution, and analysis. Context Petri nets offer a formalization for the definition of adaptations, the interactions between them, and the notion of consistency of a system in the presence of dynamic behavioral adaptations. Interactions between adaptations are formalized by a well-defined set of rules that capture the intention of programmers at a high-level, while enabling the low-level representation and automatic verification of those rules. Consistency verification of the system is provided at two levels. At design-time, system properties can be analyzed for the identification of possible incoherence in the definition of interactions between adaptations. At run-time the satisfiability of all interaction rules between adaptations is verified, hence, it can be ensured that no inconsistencies occur. Based on the proposed formal basis, we offer a tool for the design, manipulation, and simulation of adaptations and their interactions. This work is validated by demonstrating its usefulness in analyzing existing context-aware applications, its appropriateness in broadening the frontiers of context-oriented programming, and its extensibility by expanding the formal basis itself.
Older people and falls: health status, quality of life, lifestyle, care networks, prevention and views on service use following a recent fall.

AIM AND OBJECTIVE This study has investigated older people's experiences of a recent fall, its impact on their health, lifestyle, quality of life, care networks, prevention and their views on service use. BACKGROUND Falls are common in older people and prevalence increases with age. Falls prevention is a major policy and service initiative. DESIGN An exploratory, qualitative design involving two time points. METHOD A convenience sample of 27 older people from two primary care trusts who had a recent fall. Taped semi structured qualitative interviews were conducted and repeated at follow up to detect change over time and repeat falls. Data were collected on their experience of falls, health, activities of living, lifestyle, quality of life, use of services, prevention of falls, informal care and social networks. Content analysis of transcribed interviews identified key themes. RESULTS The majority of people fell indoors (n = 23), were repeat fallers (n = 22) with more than half alone when they fell (n = 15). For five people it was their first ever fall. Participants in primary care trust 1 had a higher mean age than those in primary care trust 2 and had more injurious falls (n = 12, mean age 87 years vs. n = 15, mean age 81 years). The majority of non-injurious falls went unreported to formal services. Falls can result in a decline in health status, ability to undertake activities of living, lifestyle and quality of life. CONCLUSIONS Local informal care and support networks are as important as formal care for older people at risk of falls or who have fallen. Access to falls prevention programmes and services is limited for people living in more rural communities. RELEVANCE TO PRACTICE Falls prevention initiatives and services should work with local communities, agencies and informal carers to ensure equitable access and provision of information, resources and care to meet the needs of older people at risk or who have fallen.
The Design and Implementation of the RUA Protocol in the Home Node B

Femtocell is an effective solution to improve indoor coverage for mobile/cellular network and to enhance the system capacity. 3GPP has proposed Femtocell Network Architecture (FNA) to integrate Home Node B (HNB) and Node B with Radio Network Controller (RNC). In this paper, we describe 3GPP FNA and its related Iuh protocols. Specifically, we focus on the RANAP User Adaptation (RUA) protocol, which is a lightweight mechanism to replace the SCCP and M3UA protocols in RNC. We describe the design and implementation of the RUA protocol through Message Queue (MQ) method and primitive flow model, which can work on different platforms. We also develop simulation experiments to investigate performance improvement with SCCP/M3UA protocols. This study indicates that the RUA protocol can improve the processing time by 20-40%.
[Hepatitis B virus X protein-regulated expression of Plk1].

OBJECTIVE To investigate the ability and underlying mechanism of hepatitis B virus X protein (HBx) regulation of Polo-like kinase 1 (Plk1) expression. METHODS The human HCC cell line HepG2 was transfected (transiently and stably) with an HBx plasmid expression vector (pCMV-HA-HBx) or empty plasmid vector (control), with and without expression plasmids with the Plk1 promoter. Effects on Plk1 expression were assessed by western blotting. Functional effects on the Plk1 promoter were assessed by luciferase reporter assay. Effects on the mRNA level of Plk1 in S phase HepG2 cells were assessed by quantitative real-time reverse transcriptase polymerase chain reaction. After blocking protein synthesis by treatment with cycloheximide (CHX), the turnover rate of Plk1 was assessed by western blotting. Lastly, the effect of HBx on cell cycle was assessed by flow cytometry. RESULTS HBx did not increase the protein expression of Plk1 in non-synchronized HepG2 cells, but did significantly up-regulate the Plk1 protein level in the synchronized S phase cells (P = 0.026 and P = 0.003, respectively). Ectopic expression of HBx did not increase the mRNA level of Plk1 in HepG2 cells, but did inhibit the degradation of Plk1, as evidenced by an increased half-life of Plk1 protein (from 30 to 90 minutes). The HBx-expressing HepG2 cells showed more frequent entry into the S or G(2)/M phase than the control cells (31.65% vs. 24.56% or 9.43% vs. 4.47%, respectively) and less in the G(0)/G(1) phase (decrease from 70.97% to 58.92% for the HBx-expressing HepG2 cells). CONCLUSION HBx is able to up-regulate the expression of Plk1 in HepG2 cells by a mechanism involving stabilization of the Plk1 protein primarily in the S phase of the cell cycl.
Self-Induced Patched Receptor Down-Regulation Modulates Cell Sensitivity to the Hedgehog Morphogen Gradient

A self-regulating receptor allows cells to maintain the appropriate balance of ligand-bound and unbound receptors. Receptor Rheostat The Hedgehog signaling pathway plays essential roles in cell fate specification and tissue patterning during development. The cellular response to this morphogen is complex because cells respond both to the absence of the ligand Hedgehog and to the presence of Hedgehog, with the cellular response a function of both the concentration of Hedgehog and the ratio of the Hedgehog-bound and unbound receptor Patched. Using the fly wing imaginal disc as a model system, Casali identified a mechanism by which Patched, which is transcriptionally induced in response to Hedgehog signaling, triggers its own down-regulation to maintain the appropriate balance of bound and unbound receptors. The mechanism did not require Hedgehog signaling per se, because both constitutively active and dominant-negative forms of the receptor induced the down-regulation. However, the Patched-induced decrease in abundance did require a ubiquitination motif in the C-terminal domain and the presence of internalization-competent receptors. Morphogens form signaling gradients that control patterning processes during development. Responding cells must perceive and interpret the concentration-dependent information provided by the morphogen to generate precise patterns of gene expression and cell differentiation in developing tissues. Generally, the absolute number of activated, ligand-bound receptors determines cell perception of the morphogen. In contrast, cells interpret the morphogen Hedgehog (Hh) by measuring the ratio of bound to unbound molecules of its receptor Patched (Ptc). This ratio depends on both the Hh concentration and the absolute number of Ptc molecules. Here, I describe a posttranscriptional process that controls the absolute amount of Ptc present in a cell, which regulates gradient interpretation, wherein self-induced receptor down-regulation that is independent of ligand binding dictates the cell response to a morphogen gradient.
Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients.

We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guérin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value.
Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation

We investigated whether Rad51 overexpression plays a role in soft tissue sarcoma (STS) chemoresistance as well as the regulatory mechanisms underlying its expression. The studies reported here show that Rad51 protein is overexpressed in a large panel of human STS specimens. Human STS cell lines showed increased Rad51 protein expression, as was also observed in nude rat STS xenografts. STS cells treated with doxorubicin exhibited up-regulation of Rad51 protein while arrested in the S-G2 phase of the cell cycle. Treatment with anti-Rad51 small interfering RNA decreased Rad51 protein expression and increased chemosensitivity to doxorubicin. Because we previously showed that reintroduction of wild-type p53 (wtp53) into STS cells harboring a p53 mutation led to increased doxorubicin chemosensitivity, we hypothesized that p53 participates in regulating Rad51 expression in STS. Reintroduction of wtp53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression. Using luciferase reporter assays, we showed that reconstitution of wtp53 function decreased Rad51 promoter activity. Deletion constructs identified a specific Rad51 promoter region containing a p53-responsive element but no p53 consensus binding site. Electrophoretic mobility shift assays verified activator protein 2 (AP2) binding to this region and increased AP2 binding to the promoter in the presence of wtp53. Mutating this AP2 binding site eliminated the wtp53 repressive effect. Furthermore, AP2 knockdown resulted in increased Rad51 expression. In light of the importance of Rad51 in modulating STS chemoresistance, these findings point to a potential novel strategy for molecular-based treatments that may be of relevance to patients burdened by STS. [Mol Cancer Ther 2007;6(5):1650–60]
A videotape intervention to enhance the informed consent process for medical and psychiatric treatment research.

OBJECTIVE This study evaluated a brief educational video designed to enhance the informed consent process for people with serious mental and medical illnesses who are considering participating in treatment research. METHOD Individuals with schizophrenia who were being recruited for ongoing clinical trials, medical patients without self-reported psychiatric comorbidity, and university undergraduates were randomly assigned to view either a highly structured instructional videotape about the consent process in treatment research or a control videotape that presented only general information about bioethical issues in human research. Knowledge about informed consent was measured before and after viewing. RESULTS Viewing the experimental videotape resulted in larger gains in knowledge about informed consent. Standardized effect sizes were large in all groups. CONCLUSIONS The videotape was thus an effective teaching tool across diverse populations, ranging from individuals with severe chronic mental illness to university undergraduates.
Fuzzy clustering based traffic pattern identification

Automatic anomaly detection is of great importance in the big data era because the large volume of raw data can be accessed easily and the automatic method to analyze the data is desirable. This paper uses a framework based on fuzzy c-means clustering to detect anomaly in temporal traffic data. In this framework the sliding window is employed first to generate a collection of segments or subsequences of the time series. Then the fuzzy clustering is applied on those segments to reveal the outliers or abnormal segments in the series. The abnormal score for each segment is calculated according to the clustering results. To obtain the best setting of parameters and more meaningful abnormal scores, we design one novel performance index. The proposed approach is tested on the temporal traffic data set collected from Beijing, China, and the results demonstrate that the proposed approach can identify many valuable traffic patterns in the data.