Multiscale continuum modeling of protein dynamics

Two multiscale continuum models for simulating protein dynamics are developed which allow for resolution of protein peptide planes in a beam-like finite element. A curvature and strain based finite element formulation is utilized. This formulation is advantageous in simulating proteins since amino acid chains may be described by a single element, even when the protein segment considered exhibits large curvature and twist such as the alpha-helical shapes prominent in many proteins. Specifically, concurrent and hierarchical multiscale models are developed for the curvature and strain based beam formulation. The hierarchical multiscale continuum model utilizes a novel shooting method to calculate the deformed configuration of the protein. An optimization algorithm determines the requisite stiffness parameters by varying the beam stiffness used in the shooting method until deformed configurations of test cases correspond to those produced by the LAMMPS molecular dynamics software. Additionally, a concurrent multiscale method is detailed for evaluating protein inter-atomic potential parameters from the curvature and strain degrees of freedom employed in the model. This allows internal forces and moments to be calculated using nonlinear protein potentials. Proof of concept testing and model verification for both models includes comparing the multiscale techniques to all-atom molecular dynamics solutions. Specifically, the models are verified by simulating a polypeptide in a vacuum and comparing the predicted results to those computed using LAMMPS.MSCommittee Chair: Leamy, Michael; Committee Member: Ferri, Aldo; Committee Member: Lipkin, Harve

Quantum teleportation of EPR pair by three-particle entanglement

Teleportation of an EPR pair using triplet in state of the Horne-Greenberger-Zeilinger form to two receivers is considered. It needs a three-particle basis for joint measurement. By contrast the one qubit teleportation the required basis is not maximally entangled. It consists of the states corresponding to the maximally entanglement of two particles only. Using outcomes of measurement both receivers can recover an unknown EPR state however one of them can not do it separately. Teleportation of the N-particle entanglement is discussed.Comment: 7 pages, LaTeX, 3 figure

Gravid Anopheles gambiae sensu stricto avoid ovipositing in Bermuda grass hay infusion and it's volatiles in two choice egg-count bioassays.

BACKGROUND: A number of mosquito species in the Culex and Aedes genera prefer to lay eggs in Bermuda grass (Cynodon dactylon) hay infusions compared to water alone. These mosquitoes are attracted to volatile compounds from the hay infusions making the infusions effective baits in gravid traps used for monitoring vectors of arboviral and filarial pathogens. Since Bermuda grass is abundant and widespread, it is plausible to explore infusions made from it as a potential low cost bait for outdoor monitoring of the elusive malaria vector Anopheles gambiae s.s. METHODS: This study investigated preferential egg laying of individual An. gambiae s.s. in hay infusion or in tap water treated with volatiles detected in hay infusion headspace compared to tap water alone, using two-choice egg-count bioassays. Infusions were prepared by mixing 90 g of dried Bermuda grass (hay) with 24 L of unchlorinated tap water in a bucket, and leaving it for 3 days at ambient temperature and humidity. The volatiles in the headspace of the hay infusion were sampled with Tenax TA traps for 20 h and analysed using gas chromatography coupled to mass spectrometry. RESULTS: In total, 18 volatiles were detected in the infusion headspace. Nine of the detected compounds and nonanal were selected for bioassays. Eight of the selected compounds have previously been suggested to attract/stimulate egg laying in An. gambiae s.s. Gravid females were significantly (p < 0.05) less likely to lay eggs in hay infusion dilutions of 25, 50 and 100 % and in tap water containing any of six compounds (3-methylbutanol, phenol, 4-methylphenol, nonanal, indole, and 3-methylindole) compared to tap water alone. The oviposition response to 10 % hay infusion or any one of the remaining four volatiles (4-hepten-1-ol, phenylmethanol, 2-phenylethanol, or 4-ethylphenol) did not differ from that in tap water. CONCLUSIONS: Anopheles gambiae s.s. prefers to lay eggs in tap water rather than Bermuda grass hay infusion. This avoidance of the hay infusion appears to be mediated by volatile organic compounds from the infusion. It is, therefore, unlikely that Bermuda grass hay infusion as formulated and used in gravid traps for Culex and Aedes mosquitoes will be suitable baits for monitoring gravid An. gambiae s.s

Why are the oldest old less generous? Explanations for the unexpected age-related drop in charitable giving

ABSTRACT Previous research has demonstrated that the generally positive relationship between age and the presence of charitable giving becomes negative at the oldest ages. We investigate potential causes of this drop in charitable giving among the oldest old including changes in health, cognition, egocentric networks, religious attendance, and substitution of charitable bequest planning. A longitudinal analysis of data from the United States Health and Retirement Survey indicates that the drop in charitable giving is mediated largely by changes in the frequency of church attendance, with only modest influences from changes in health and cognition

On the polarization properties of the charmed baryon Lambda^+_c in the Lambda^+_c -> p + K^- + pi^+ + pi^0 decay

The polarization properties of the charmed Lambda^+_c baryon are investigated in weak non-leptonic four-body Lambda^+_c -> p + K^- + pi^+ + pi^0 decay. The probability of this decay and the angular distribution of the probability are calculated in the effective quark model with chiral U(3)XU(3) symmetry incorporating Heavy Quark Effective theory (HQET) and the extended Nambu-Jona-Lasinio model with a linear realization of chiral U(3)XU(3) symmetry. The theoretical value of the probability of the decay Lambda^+_c -> p + K^- + pi^+ + pi^0 relative to the probability of the decay Lambda^+_c -> p + K^- + pi^+ does not contain free parameters and fits well experimental data. The application of the obtained results to the analysis of the polarization of the Lambda^+_c produced in the processes of photo and hadroproduction is discussed.Comment: 10 pages, no figures, Late

Influence of Spin Wave Excitations on the Ferromagnetic Phase Diagram in the Hubbard-Model

The subject of the present paper is the theoretical description of collective electronic excitations, i.e. spin waves, in the Hubbard-model. Starting with the widely used Random-Phase-Approximation, which combines Hartree-Fock theory with the summation of the two-particle ladder, we extend the theory to a more sophisticated single particle approximation, namely the Spectral-Density-Ansatz. Doing so we have to introduce a `screened` Coulomb-interaction rather than the bare Hubbard-interaction in order to obtain physically reasonable spinwave dispersions. The discussion following the technical procedure shows that comparison of standard RPA with our new approximation reduces the occurrence of a ferromagnetic phase further with respect to the phase-diagrams delivered by the single particle theories.Comment: 8 pages, 9 figures, RevTex4, accepted for publication in Phys. Rev.

Thromboprophylaxis Is Associated With Reduced Post-hospitalization Venous Thromboembolic Events in Patients With Inflammatory Bowel Diseases

Background & Aims Patients with inflammatory bowel diseases (IBDs) have increased risk for venous thromboembolism (VTE); those who require hospitalization have particularly high risk. Few hospitalized patients with IBD receive thromboprophylaxis. We analyzed the frequency of VTE after IBD-related hospitalization, risk factors for post-hospitalization VTE, and the efficacy of prophylaxis in preventing post-hospitalization VTE. Methods In a retrospective study, we analyzed data from a multi-institutional cohort of patients with Crohn's disease or ulcerative colitis and at least 1 IBD-related hospitalization. Our primary outcome was a VTE event. All patients contributed person-time from the date of the index hospitalization to development of VTE, subsequent hospitalization, or end of follow-up. Our main predictor variable was pharmacologic thromboprophylaxis. Cox proportional hazard models adjusting for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results From a cohort of 2788 patients with at least 1 IBD-related hospitalization, 62 patients developed VTE after discharge (2%). Incidences of VTE at 30, 60, 90, and 180 days after the index hospitalization were 3.7/1000, 4.1/1000, 5.4/1000, and 9.4/1000 person-days, respectively. Pharmacologic thromboprophylaxis during the index hospital stay was associated with a significantly lower risk of post-hospitalization VTE (HR, 0.46; 95% CI, 0.22–0.97). Increased numbers of comorbidities (HR, 1.30; 95% CI, 1.16–1.47) and need for corticosteroids before hospitalization (HR, 1.71; 95% CI, 1.02–2.87) were also independently associated with risk of VTE. Length of hospitalization or surgery during index hospitalization was not associated with post-hospitalization VTE. Conclusions Pharmacologic thromboprophylaxis during IBD-related hospitalization is associated with reduced risk of post-hospitalization VTE.National Institutes of Health (U.S.) (U54-LM008748

Improving Case Definition of Crohnʼs Disease and Ulcerative Colitis in Electronic Medical Records Using Natural Language Processing

available in PMC 2014 June 01Background: Previous studies identifying patients with inflammatory bowel disease using administrative codes have yielded inconsistent results. Our objective was to develop a robust electronic medical record–based model for classification of inflammatory bowel disease leveraging the combination of codified data and information from clinical text notes using natural language processing. Methods: Using the electronic medical records of 2 large academic centers, we created data marts for Crohn’s disease (CD) and ulcerative colitis (UC) comprising patients with ≥1 International Classification of Diseases, 9th edition, code for each disease. We used codified (i.e., International Classification of Diseases, 9th edition codes, electronic prescriptions) and narrative data from clinical notes to develop our classification model. Model development and validation was performed in a training set of 600 randomly selected patients for each disease with medical record review as the gold standard. Logistic regression with the adaptive LASSO penalty was used to select informative variables. Results: We confirmed 399 CD cases (67%) in the CD training set and 378 UC cases (63%) in the UC training set. For both, a combined model including narrative and codified data had better accuracy (area under the curve for CD 0.95; UC 0.94) than models using only disease International Classification of Diseases, 9th edition codes (area under the curve 0.89 for CD; 0.86 for UC). Addition of natural language processing narrative terms to our final model resulted in classification of 6% to 12% more subjects with the same accuracy. Conclusions: Inclusion of narrative concepts identified using natural language processing improves the accuracy of electronic medical records case definition for CD and UC while simultaneously identifying more subjects compared with models using codified data alone.National Institutes of Health (U.S.) (NIH U54-LM008748)American Gastroenterological AssociationNational Institutes of Health (U.S.) (NIH K08 AR060257)Beth Isreal Deaconess Medical Center (Katherine Swan Ginsburg Fund)National Institutes of Health (U.S.) (NIH R01-AR056768)Burroughs Wellcome Fund (Career Award for Medical Scientists)National Institutes of Health (U.S.) (NIH U01-GM092691)National Institutes of Health (U.S.) (NIH R01-AR059648

Normalization of Plasma 25-Hydroxy Vitamin D Is Associated with Reduced Risk of Surgery in Crohn’s Disease

available in PMC 2014 August 01AB Background: Vitamin D may have an immunologic role in Crohn's disease (CD) and ulcerative colitis (UC). Retrospective studies suggested a weak association between vitamin D status and disease activity but have significant limitations. Methods: Using a multi-institution inflammatory bowel disease cohort, we identified all patients with CD and UC who had at least one measured plasma 25-hydroxy vitamin D (25(OH)D). Plasma 25(OH)D was considered sufficient at levels >=30 ng/mL. Logistic regression models adjusting for potential confounders were used to identify impact of measured plasma 25(OH)D on subsequent risk of inflammatory bowel disease-related surgery or hospitalization. In a subset of patients where multiple measures of 25(OH)D were available, we examined impact of normalization of vitamin D status on study outcomes. Results: Our study included 3217 patients (55% CD; mean age, 49 yr). The median lowest plasma 25(OH)D was 26 ng/mL (interquartile range, 17-35 ng/mL). In CD, on multivariable analysis, plasma 25(OH)D =30 ng/mL. Similar estimates were also seen for UC. Furthermore, patients with CD who had initial levels <30 ng/mL but subsequently normalized their 25(OH)D had a reduced likelihood of surgery (odds ratio, 0.56; 95% confidence interval, 0.32-0.98) compared with those who remained deficient. Conclusion: Low plasma 25(OH)D is associated with increased risk of surgery and hospitalizations in both CD and UC, and normalization of 25(OH)D status is associated with a reduction in the risk of CD-related surgery. (C) Crohn's & Colitis Foundation of America, Inc

A Lin28 homologue reprograms differentiated cells to stem cells in the moss Physcomitrella patens

Both land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3′-untranslated region (3′-UTR). Removal of the 3′-UTR stabilizes PpCSP1 transcripts, results in accumulation of PpCSP1 protein and enhances reprogramming. A quadruple deletion mutant of PpCSP1 and three closely related PpCSPgenes exhibits attenuated reprogramming indicating that the PpCSP genes function redundantly in cellular reprogramming. Taken together, these data demonstrate a positive role of PpCSP1 in reprogramming, which is similar to the function of mammalian Lin28