Self-assembled nanoparticle spirals from two-dimensional compositional banding in thin films

A self-assembly process is reported in which spiral patterns of goldnanoparticles form on siliconsurfaces during the epitaxial crystallization of thin gold-silicon alloy layers. This behavior is observed only for gold concentrations above a critical value and is shown to result from two-dimensional compositional banding of a liquid alloy layer during the crystallization process. The compositional banding consists of alternate gold-rich and silicon-rich alloy bands, which are shown to be a direct consequence of free energy minimization, the band spacing being that which gives the maximum diffusive composition-separation rate. Goldnanoparticles subsequently form by Ostwald ripening on the surface of the gold-rich bands to give rise to the observed spiral patterns.We thank P. Evans and D. Button for MEVVA implantation at Australian Nuclear Science Technology Organization under an AINSE Grant No. AINGRA05155P. We thank S.K. Bhargava at RMIT University for the financial support to D.K.V. to carry out initial stages of this research

Isolation of a Collagenase cDNA Clone and Measurement of Changing Collagenase mRNA Levels during Induction in Rabbit Synovial Fibroblasts.

To facilitate our studies on the mechanisms controlling collagenase production at a molecular level in rabbit synovial fibroblasts, we have constructed a cDNA library using mRNAs isolated from cells induced with crystals of monosodium urate monohydrate. We have screened this library with cDNA probes made from induced and control mRNA populations. From among 30 clones that hybridized preferentially to the induced-cell probe, 4 contained collagenase sequences. The largest, a clone of 650 base pairs, was identified by its ability to hybrid select a mRNA that could be translated in a cell-free system into a product that was precipitable with monospecific antibody to collagenase. Using this clone to probe blots of RNA from induced cells, we detected the appearance of a collagenase mRNA of 2.7 kilobases within 5 hr of addition of urate. The level of collagenase mRNA continued to increase for 35-40 hr, when it was 60 to 90 times more abundant in induced cells than in control cells. The increase in mRNA levels correlated with an increase in immunoreactive collagenase protein that was detectable in culture medium by 10 hr

Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma

Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132). Given MG-132's strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS

Measuring access to effective care among elderly medicare enrollees in managed and fee-for-service care: a retrospective cohort study

BACKGROUND: Our aim was to compare access to effective care among elderly Medicare patients in a Staff Model and Group Model HMO and in Fee-for-Service (FFS) care. METHODS: We used a retrospective cohort study design, using claims and automated medical record data to compare achievement on quality indicators for elderly Medicare recipients. Secondary data were collected from 1) HMO data sets and 2) Medicare claims files for the time period 1994–95. All subjects were Medicare enrollees in a defined area of New England: those enrolled in two divisions of a managed care plan with different physician payment arrangements: a staff model, and a group model; and the Medicare FFS population. We abstracted information on indicators covering several domains: preventive, diagnosis-specific, and chronic disease care. RESULTS: On the indicators we created and tested, access in the single managed care plan under study was comparable to or better than FFS care in the same geographic region. Percent of Medicare recipients with breast cancer screening was 36 percentage points higher in the staff model versus FFS (95% confidence interval 34–38 percentage points). Follow up after hospitalization for myocardial infarction was 20 percentage points higher in the group model than in FFS (95% confidence interval 14–26 percentage points). CONCLUSION: According to indicators developed for use in both claims and automated medical record data, access to care for elderly Medicare beneficiaries in one large managed care organization was as good as or better than that in FFS care in the same geographic area

The mechanism of resistance to favipiravir in influenza.

Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance

A multilevel intervention to promote colorectal cancer screening among community health center patients: results of a pilot study

Background: Colorectal cancer screening rates are low among poor and disadvantaged patients. Patient navigation has been shown to increase breast and cervical cancer screening rates, but few studies have looked at the potential of patient navigation to increase colorectal cancer screening rates. Methods: The objective was to determine the feasibility and effectiveness of a patient navigator-based intervention to increase colorectal cancer screening rates in community health centers. Patients at the intervention health center who had not been screened for colorectal cancer and were designated as "appropriate for outreach" by their primary care providers received a letter from their provider about the need to be screened and a brochure about colorectal cancer screening. Patient navigators then called patients to discuss screening and to assist patients in obtaining screening. Patients at a demographically similar control health center received usual care. Results: Thirty-one percent of intervention patients were screened at six months, versus nine percent of control patients (p < .001). Conclusion: A patient navigator-based intervention, in combination with a letter from the patient's primary care provider, was associated with an increased rate of colorectal cancer screening at one health center as compared to a demographically similar control health center. Our study adds to an emerging literature supporting the use of patient navigators to increase colorectal cancer screening in diverse populations served by urban health centers

Parkinson’s disease: an inquiry into the etiology and treatment

Parkinson’s disease affects over one million people in the United States. Although there have been remarkable advances in uncovering the pathogenesis of this disabling disorder, the etiology is speculative. Medical treatment and operative procedures provide symptomatic relief only. Compression of the cerebral peduncle of the midbrain by the posterior cerebral artery in a patient with Parkinson’s Disease (Parkinson’s Disease) was noted on magnetic resonance imaging (MRI) scan and at operation in a patient with trigeminal neuralgia. Following the vascular decompression of the trigeminal nerve, the midbrain was decompressed by mobilizing and repositioning the posterior cerebral artery The patient's Parkinson's signs disappeared over a 48-hour period. They returned 18 months later with contralateral peduncle compression. A blinded evaluation of MRI scans of Parkinson's patients and controls was performed. MRI scans in 20 Parkinson's patients and 20 age and sex matched controls were evaluated in blinded fashion looking for the presence and degree of arterial compression of the cerebral peduncle. The MRI study showed that 73.7 percent of Parkinson's Disease patients had visible arterial compression of the cerebral peduncle. This was seen in only 10 percent of control patients (two patients, one of whom subsequently developed Parkinson’s Disease); thus 5 percent. Vascular compression of the cerebral peduncle by the posterior cerebral artery may be associated with Parkinson’s Disease in some patients. Microva-scular decompression of that artery away from the peduncle may be considered for treatment of Parkinson’s Disease in some patients

The statistical mechanics of complex signaling networks : nerve growth factor signaling

It is becoming increasingly appreciated that the signal transduction systems used by eukaryotic cells to achieve a variety of essential responses represent highly complex networks rather than simple linear pathways. While significant effort is being made to experimentally measure the rate constants for individual steps in these signaling networks, many of the parameters required to describe the behavior of these systems remain unknown, or at best, estimates. With these goals and caveats in mind, we use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. To establish the usefulness of our approach, we have applied our methods towards modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. Using our approach, we are able to extract predictions that are highly specific and accurate, thereby enabling us to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. We show that extracting biologically relevant predictions from complex signaling models appears to be possible even in the absence of measurements of all the individual rate constants. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems wherein particular ''soft'' combinations of parameters can be varied over wide ranges without impacting the final output and demonstrating that a few ''stiff'' parameter combinations center around the paramount regulatory steps of the network. We refer to this property -- which is distinct from robustness -- as ''sloppiness.''Comment: 24 pages, 10 EPS figures, 1 GIF (makes 5 multi-panel figs + caption for GIF), IOP style; supp. info/figs. included as brown_supp.pd