Discrete adjoint approximations with shocks

This paper is concerned with the formulation and discretisation of adjoint equations when there are shocks in the underlying solution to the original nonlinear hyperbolic p.d.e. For the model problem of a scalar unsteady one-dimensional p.d.e. with a convex flux function, it is shown that the analytic formulation of the adjoint equations requires the imposition of an interior boundary condition along any shock. A 'discrete adjoint' discretisation is defined by requiring the adjoint equations to give the same value for the linearised functional as a linearisation of the original nonlinear discretisation. It is demonstrated that convergence requires increasing numerical smoothing of any shocks. Without this, any consistent discretisation of the adjoint equations without the inclusion of the shock boundary condition may yield incorrect values for the adjoint solution

Do community medicine residency trainees learn through journal club? An experience from a developing country

BACKGROUND: Journal clubs are an internationally recognized teaching tool in many postgraduate medical education fields. In developing countries lack of funds for current print materials may have limited journal club use. But with advancing information technology trainees in developing countries increasingly have more access to high quality journals online. However, we are aware of no studies describing journal club existence and effectiveness in postgraduate medical training in Pakistan. Also we have found no published effectiveness studies of this teaching modality in Community Medicine (Public Health) in any country. This study evaluated the effectiveness of Community Medicine (Public Health) Resident Journal Club (CMR-JC) in Aga Khan University, Pakistan using international criteria for successful journal clubs (2 years continuous existence and more than 50% attendance) and examining resident and alumni satisfaction. METHODS: Journal club effectiveness criteria were searched using electronic search databases. Departmental records were reviewed from September1999–September 2005. Ninety percent of residents and alumni of Community Medicine Residency Programme participated voluntarily in a confidential survey. RESULTS: The CMR-JC was regularly conducted. More than 95% of residents attended. (Total residents in the CMR-Programme: 32). Twenty-seven out of 29 current residents/alumni responded to the anonymous questionnaire. Acquisition of critical appraisal skills (23 respondents) and keeping up with current literature (18 respondents) were the two most important objectives achieved. Respondents recommended improved faculty participation and incorporating a structured checklist for article review. CONCLUSION: CMR-JC fulfils criteria for effective journal clubs. Residents and alumni agree CMR-JC meets its objectives. Incorporating suggested recommendations will further improve standards. The journal club learning modality should be included in residency training programs in developing countries. Effective use of online resources to support journal clubs is demonstrated as a successful alternative to excessive expenditure for obtaining print journals. Those trying to start or improve journal clubs can benefit from our experience

Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.</p> <p>Methods</p> <p>Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. <it>In vivo </it>effect of EGCG on tumor growth was examined in a xenograft model.</p> <p>Results</p> <p>Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H₂O₂, 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.</p> <p>Conclusions</p> <p>Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.</p

The Chop Gene Contains an Element for the Positive Regulation of the Mitochondrial Unfolded Protein Response

We have previously reported on the discovery of a mitochondrial specific unfolded protein response (mtUPR) in mammalian cells, in which the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional activation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ, and ClpP, but not those encoding stress proteins of the endoplasmic reticulum (ER) or the cytosol. Analysis of the chaperonin 60/10 bidirectional promoter showed that the CHOP element was required for the mtUPR and that the transcription of the chop gene is activated by mtUPR. In order to investigate the role of CHOP in the mtUPR, we carried out a deletion analysis of the chop promoter. This revealed that the transcriptional activation of the chop gene by mtUPR is through an AP-1 (activator protein-1) element. This site lies alongside an ERSE element through which chop transcription is activated in response to the ER stress response (erUPR). Thus CHOP can be induced separately in response to 2 different stress response pathways. We also discuss the potential signal pathway between mitochondria and the nucleus for the mtUPR

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Validation of the ADAMO Care Watch for step counting in older adults

Background: Accurate measurement devices are required to objectively quantify physical activity. Wearable activity monitors, such as pedometers, may serve as affordable and feasible instruments for measuring physical activity levels in older adults during their normal activities of daily living. Currently few available accelerometer-based steps counting devices have been shown to be accurate at slow walking speeds, therefore there is still lacking appropriate devices tailored for slow speed ambulation, typical of older adults. This study aimed to assess the validity of step counting using the pedometer function of the ADAMO Care Watch, containing an embedded algorithm for measuring physical activity in older adults. Methods: Twenty older adults aged ≥ 65 years (mean ± SD, 75±7 years; range, 68–91) and 20 young adults (25±5 years, range 20–40), wore a care watch on each wrist and performed a number of randomly ordered tasks: walking at slow, normal and fast self-paced speeds; a Timed Up and Go test (TUG); a step test and ascending/descending stairs. The criterion measure was the actual number of steps observed, counted with a manual tally counter. Absolute percentage error scores, Intraclass Correlation Coefficients (ICC), and Bland–Altman plots were used to assess validity. Results: ADAMO Care Watch demonstrated high validity during slow and normal speeds (range 0.5–1.5 m/s) showing an absolute error from 1.3% to 1.9% in the older adult group and from 0.7% to 2.7% in the young adult group. The percentage error for the 30-metre walking tasks increased with faster pace in both young adult (17%) and older adult groups (6%). In the TUG test, there was less error in the steps recorded for older adults (1.3% to 2.2%) than the young adults (6.6% to 7.2%). For the total sample, the ICCs for the ADAMO Care Watch for the 30-metre walking tasks at each speed and for the TUG test were ranged between 0.931 to 0.985. Conclusion: These findings provide evidence that the ADAMO Care Watch demonstrated highly accurate measurements of the steps count in all activities, particularly walking at normal and slow speeds. Therefore, these data support the inclusion of the ADAMO Care Watch in clinical applications for measuring the number of steps taken by older adults at normal, slow walking speeds