Computational Complexity of interacting electrons and fundamental limitations of Density Functional Theory

One of the central problems in quantum mechanics is to determine the ground state properties of a system of electrons interacting via the Coulomb potential. Since its introduction by Hohenberg, Kohn, and Sham, Density Functional Theory (DFT) has become the most widely used and successful method for simulating systems of interacting electrons, making their original work one of the most cited in physics. In this letter, we show that the field of computational complexity imposes fundamental limitations on DFT, as an efficient description of the associated universal functional would allow to solve any problem in the class QMA (the quantum version of NP) and thus particularly any problem in NP in polynomial time. This follows from the fact that finding the ground state energy of the Hubbard model in an external magnetic field is a hard problem even for a quantum computer, while given the universal functional it can be computed efficiently using DFT. This provides a clear illustration how the field of quantum computing is useful even if quantum computers would never be built.Comment: 8 pages, 3 figures. v2: Version accepted at Nature Physics; differs significantly from v1 (including new title). Includes an extra appendix (not contained in the journal version) on the NP-completeness of Hartree-Fock, which is taken from v

Using a model of group psychotherapy to support social research on sensitive topics

This article describes the exploratory use of professional therapeutic support by social researchers working on a sensitive topic. Talking to recently bereaved parents about the financial implications of their child's death was expected to be demanding work, and the research design included access to an independent psychotherapeutic service. Using this kind of professional support is rare within the general social research community, and it is useful to reflect on the process. There are likely to be implications for collection and interpretation of data, research output and the role and experience of the therapist. Here, the primary focus is the potential impact on researcher well-being

Inboard and outboard radial electric field wells in the H- and I-mode pedestal of Alcator C-Mod and poloidal variations of impurity temperature

We present inboard (HFS) and outboard (LFS) radial electric field (E[subscript r]) and impurity temperature (T[subscript z]) measurements in the I-mode and H-mode pedestal of Alcator C-Mod. These measurements reveal strong Er wells at the HFS and the LFS midplane in both regimes and clear pedestals in T[subscript z], which are of similar shape and height for the HFS and LFS. While the H-mode E[subscript r] well has a radially symmetric structure, the E[subscript r] well in I-mode is asymmetric, with a stronger ExB shear layer at the outer edge of the E[subscript r] well, near the separatrix. Comparison of HFS and LFS profiles indicates that impurity temperature and plasma potential are not simultaneously flux functions. Uncertainties in radial alignment after mapping HFS measurements along flux surfaces to the LFS do not, however, allow direct determination as to which quantity varies poloidally and to what extent. Radially aligning HFS and LFS measurements based on the T[subscript z] profiles would result in substantial inboard-outboard variations of plasma potential and electron density. Aligning HFS and LFS E[subscript r] wells instead also approximately aligns the impurity poloidal flow profiles, while resulting in a LFS impurity temperature exceeding the HFS values in the region of steepest gradients by up to 70%. Considerations based on a simplified form of total parallel momentum balance and estimates of parallel and perpendicular heat transport time scales seem to favor an approximate alignment of the E[subscript r] wells and a substantial poloidal asymmetry in impurity temperature.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)Swiss National Science Foundatio

A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicum in 50 irrigated and rain-fed villages in Samar Province, the Philippines

BACKGROUND: Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines. METHODS: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis. RESULTS: A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21). DISCUSSION: We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants

SICTIN: Rapid footprinting of massively parallel sequencing data

BACKGROUND: Massively parallel sequencing allows for genome-wide hypothesis-free investigation of for instance transcription factor binding sites or histone modifications. Although nucleotide resolution detailed information can easily be generated, biological insight often requires a more general view of patterns (footprints) over distinct genomic features such as transcription start sites, exons or repetitive regions. The construction of these footprints is however a time consuming task. METHODS: The presented software generates a binary representation of the signals enabling fast and scalable lookup. This representation allows for footprint generation in mere minutes on a desktop computer. Several different input formats are accepted, e.g. the SAM format, bed-files and the UCSC wiggle track. CONCLUSIONS: Hypothesis-free investigation of genome wide interactions allows for biological data mining at a scale never before seen. Until recently, the main focus of analysis of sequencing data has been targeted on signal patterns around transcriptional start sites which are in manageable numbers. Today, focus is shifting to a wider perspective and numerous genomic features are being studied. To this end, we provide a system allowing for fast querying in the order of hundreds of thousands of features

Pesticides in house dust from urban and farmworker households in California: an observational measurement study

<p>Abstract</p> <p>Background</p> <p>Studies report that residential use of pesticides in low-income homes is common because of poor housing conditions and pest infestations; however, exposure data on contemporary-use pesticides in low-income households is limited. We conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion.</p> <p>Methods</p> <p>In 2006, we collected up to two dust samples 5-8 days apart from each of 13 urban homes in Oakland, California and 15 farmworker homes in Salinas, California, an agricultural community (54 samples total). We measured 22 insecticides including organophosphates (chlorpyrifos, diazinon, diazinon-oxon, malathion, methidathion, methyl parathion, phorate, and tetrachlorvinphos) and pyrethroids (allethrin-two isomers, bifenthrin, cypermethrin-four isomers, deltamethrin, esfenvalerate, imiprothrin, permethrin-two isomers, prallethrin, and sumithrin), one phthalate herbicide (chlorthal-dimethyl), one dicarboximide fungicide (iprodione), and one pesticide synergist (piperonyl butoxide).</p> <p>Results</p> <p>More than half of the households reported applying pesticides indoors. Analytes frequently detected in both locations included chlorpyrifos, diazinon, permethrin, allethrin, cypermethrin, and piperonyl butoxide; no differences in concentrations or loadings were observed between locations for these analytes. Chlorthal-dimethyl was detected solely in farmworker homes, suggesting contamination due to regional agricultural use. Concentrations in samples collected 5-8 days apart in the same home were strongly correlated for the majority of the frequently detected analytes (Spearman ρ = 0.70-1.00, p < 0.01). Additionally, diazinon and chlorpyrifos concentrations in Salinas farmworker homes were 40-80% lower than concentrations reported in samples from Salinas farmworker homes studied between 2000-2002, suggesting a temporal reduction after their residential phase-out. Finally, estimated non-dietary pesticide intake for resident children did not exceed current U.S. Environmental Protection Agency's (U.S. EPA) recommended chronic reference doses (RfDs).</p> <p>Conclusion</p> <p>Low-income children are potentially exposed to a mixture of pesticides as a result of poorer housing quality. Historical or current pesticide use indoors is likely to contribute to ongoing exposures. Agricultural pesticide use may also contribute to additional exposures to some pesticides in rural areas. Although children's non-dietary intake did not exceed U.S. EPA RfDs for select pesticides, this does not ensure that children are free of any health risks as RfDs have their own limitations, and the children may be exposed indoors via other pathways. The frequent pesticide use reported and high detection of several home-use pesticides in house dust suggests that families would benefit from integrated pest management strategies to control pests and minimize current and future exposures.</p

HALT (Hernia Active Living Trial): protocol for a feasibility study of a randomised controlled trial of a physical activity intervention to improve quality of life in people with bowel stoma with a bulge/parastomal hernia

Background Parastomal hernia (PSH) can be repaired surgically, but results to date have been disappointing, with reported recurrence rates of 30 to 76%. Other types of intervention are therefore needed to improve the quality of life of people with PSH. One potential intervention is physical activity. We hypothesise that the intervention will increase core activation and control across the abdominal wall at a site of potential weakness and thus reduce the risk of PSH progression. Increases in physical activity will improve body image and quality of life (QoL). Methods Subjects and sample There were approximately 20 adults with a bowel stoma and PSH. People with previous PSH repair will be excluded as well as people who already do core training. Study design This is a feasibility study of a randomised controlled trial with 2 months follow-up, in 2 sites using mixed methods. Stage 1 involves intervention development and in stage 2, intervention and trial parameters will be assessed. Intervention A theoretically informed physical activity intervention was done, targeting people with PSH. Main outcome of feasibility study The main outcome is the decision by an independent Study Steering Committee whether to proceed to a full randomised controlled trial of the intervention. Other outcomes We will evaluate 4 intervention parameters—fidelity, adherence, acceptability and safety and 3 trial parameters (eligible patients’ consent rate, acceptability of study design and data availability rates for following endpoints): I. Diagnosis and classification of PSH II. Muscle activation III. Body composition (BMI, waist circumference) IV. Patient reported outcomes: QoL, body image and physical functioning V. Physical activity; VI. Psychological determinants of physical activity Other data Included are other data such as interviews with all participants about the intervention and trial procedures. Data analysis and statistical power As this is a feasibility study, the quantitative data will be analysed using descriptive statistics. Audio-recorded qualitative data from interviews will be transcribed verbatim and analysed thematically. Discussion The feasibility and acceptability of key intervention and trial parameters will be used to decide whether to proceed to a full trial of the intervention, which aims to improve body image, quality of life and PSH progression. Trial registration ISRCTN1520759

ApoB siRNA-induced Liver Steatosis is Resistant to Clearance by the Loss of Fatty Acid Transport Protein 5 (Fatp5)

The association between hypercholesterolemia and elevated serum apolipoprotein B (APOB) has generated interest in APOB as a therapeutic target for patients at risk of developing cardiovascular disease. In the clinic, mipomersen, an antisense oligonucleotide (ASO) APOB inhibitor, was associated with a trend toward increased hepatic triglycerides, and liver steatosis remains a concern. We found that siRNA-mediated knockdown of ApoB led to elevated hepatic triglycerides and liver steatosis in mice engineered to exhibit a human-like lipid profile. Many genes required for fatty acid synthesis were reduced, suggesting that the observed elevation in hepatic triglycerides is maintained by the cell through fatty acid uptake as opposed to fatty acid synthesis. Fatty acid transport protein 5 (Fatp5/Slc27a5) is required for long chain fatty acid (LCFA) uptake and bile acid reconjugation by the liver. Fatp5 knockout mice exhibited lower levels of hepatic triglycerides due to decreased fatty acid uptake, and shRNA-mediated knockdown of Fatp5 protected mice from diet-induced liver steatosis. Here, we evaluated if siRNA-mediated knockdown of Fatp5 was sufficient to alleviate ApoB knockdown-induced steatosis. We determined that, although Fatp5 siRNA treatment was sufficient to increase the proportion of unconjugated bile acids 100-fold, consistent with FATP5's role in bile acid reconjugation, Fatp5 knockdown failed to influence the degree, zonal distribution, or composition of the hepatic triglycerides that accumulated following ApoB siRNA treatment

Conservation, Variability and the Modeling of Active Protein Kinases

The human proteome is rich with protein kinases, and this richness has made the kinase of crucial importance in initiating and maintaining cell behavior. Elucidating cell signaling networks and manipulating their components to understand and alter behavior require well designed inhibitors. These inhibitors are needed in culture to cause and study network perturbations, and the same compounds can be used as drugs to treat disease. Understanding the structural biology of protein kinases in detail, including their commonalities, differences and modes of substrate interaction, is necessary for designing high quality inhibitors that will be of true use for cell biology and disease therapy. To this end, we here report on a structural analysis of all available active-conformation protein kinases, discussing residue conservation, the novel features of such conservation, unique properties of atypical kinases and variability in the context of substrate binding. We also demonstrate how this information can be used for structure prediction. Our findings will be of use not only in understanding protein kinase function and evolution, but they highlight the flaws inherent in kinase drug design as commonly practiced and dictate an appropriate strategy for the sophisticated design of specific inhibitors for use in the laboratory and disease therapy

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program