Preliminary Evaluation of Lectins as Fluorescent Probes of Seed Structure and Composition

Several commercially available fluoresceinisothiocyanate and rhodamine isothiocyanateconjugated plant lectins have been applied to cereal and oilseed tissues to permit identification and localization of specific structures and carbohydrates by fluorescence microscopy . Ulex europeaus Agglutinin I (UEAl) and Ricinis communis Agglutinin I (RCA I) showed specificity for the amyloids in rapeseed cotyledonary cell walls . Wheat Germ Agglutinin (WGA) bound to rapeseed coat mucilage, as well as fungal hyphae in infected wheat . Lens culinaris Agglutinin (LCA) bound only to starch in cereal sections, and at higher magnifications of isolated starch granules , the annular structure was clearly visible

Dynamics of An Underdamped Josephson Junction Ladder

We show analytically that the dynamical equations for an underdamped ladder of coupled small Josephson junctions can be approximately reduced to the discrete sine-Gordon equation. As numerical confirmation, we solve the coupled Josephson equations for such a ladder in a magnetic field. We obtain discrete-sine-Gordon-like IV characteristics, including a flux flow and a ``whirling'' regime at low and high currents, and voltage steps which represent a lock-in between the vortex motion and linear ``phasons'', and which are quantitatively predicted by a simple formula. At sufficiently high anisotropy, the fluxons on the steps propagate ballistically.Comment: 11pages, latex, no figure

Infant mental health home visiting therapists- reflective supervision self- efficacy in community practice settings

In recent years, there has been an increase in the research on reflective supervision, including the development of tools designed to measure reflective practice in the context of reflective supervision. The Reflective Supervision Self- Efficacy Scale for Supervisees (RSSESS) is a self- report measure that has been used in previous evaluations and is designed to assess perceived reflective practice self- efficacy for Infant Mental Health- Home Visiting (IMH- HV) therapists. Properties of the RSSESS including factor structure and reliability are explored in a first study that lays the foundation for the use of the RSSESS in an IMH- HV evaluation in the State of Michigan. IMH- HV therapists completed the RSSESS at 4 time points over a 12- month period and also completed a Clinician Profile Form that included questions about their IMH background and their work experience, including job satisfaction and burnout. Results indicated that the RSSESS is a reliable tool to measure change in reflective practice skills. IMH- HV therapists demonstrated growth in their use of reflective practice skills with families and their observational skills over the 12- month period. In addition, results indicated correlations between reflective supervision self- efficacy and job satisfaction as well as burnout.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154909/1/imhj21834.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154909/2/imhj21834_am.pd

Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks

Enhanced efficacy and increased long-term toxicity of CNS-directed, AAV-based combination therapy for Krabbe disease

Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a demyelinating disease caused by the deficiency of the lysosomal enzyme galactosylceramidase (GALC) and the progressive accumulation of the toxic metabolite psychosine. We showed previously that central nervous system (CNS)-directed, adeno-associated virus (AAV)2/5-mediated gene therapy synergized with bone marrow transplantation and substrate reduction therapy (SRT) to greatly increase therapeutic efficacy in the murine model of Krabbe disease (Twitcher). However, motor deficits remained largely refractory to treatment. In the current study, we replaced AAV2/5 with an AAV2/9 vector. This single change significantly improved several endpoints primarily associated with motor function. However, nearly all (14/16) of the combination-treated Twitcher mice and all (19/19) of the combination-treated wild-type mice developed hepatocellular carcinoma (HCC). 10 out of 10 tumors analyzed had AAV integrations within the Rian locus. Several animals had additional integrations within or near genes that regulate cell growth or death, are known or potential tumor suppressors, or are associated with poor prognosis in human HCC. Finally, the substrate reduction drug L-cycloserine significantly decreased the level of the pro-apoptotic ceramide 18:0. These data demonstrate the value of AAV-based combination therapy for Krabbe disease. However, they also suggest that other therapies or co-morbidities must be taken into account before AAV-mediated gene therapy is considered for human therapeutic trials

Energy Landscape and Global Optimization for a Frustrated Model Protein

The three-color (BLN) 69-residue model protein was designed to exhibit frustrated folding. We investigate the energy landscape of this protein using disconnectivity graphs and compare it to a Go model, which is designed to reduce the frustration by removing all non-native attractive interactions. Finding the global minimum on a frustrated energy landscape is a good test of global optimization techniques, and we present calculations evaluating the performance of basin-hopping and genetic algorithms for this system.Comparisons are made with the widely studied 46-residue BLN protein.We show that the energy landscape of the 69-residue BLN protein contains several deep funnels, each of which corresponds to a different β-barrel structure

Mood instability, mental illness and suicidal ideas : results from a household survey

Purpose: There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. Methods: We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. Results: There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95 % confidence interval (CI) 7.51–15.13] and PTSD by 8.69 (95 % CI 5.90–12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95 % CI 3.39–6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. Conclusions: MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required

Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.

BACKGROUND: There is evidence of under-detection and poor management of pain in patients with dementia, in both long-term and acute care. Accurate assessment of pain in people with dementia is challenging and pain assessment tools have received considerable attention over the years, with an increasing number of tools made available. Systematic reviews on the evidence of their validity and utility mostly compare different sets of tools. This review of systematic reviews analyses and summarises evidence concerning the psychometric properties and clinical utility of pain assessment tools in adults with dementia or cognitive impairment. METHODS: We searched for systematic reviews of pain assessment tools providing evidence of reliability, validity and clinical utility. Two reviewers independently assessed each review and extracted data from them, with a third reviewer mediating when consensus was not reached. Analysis of the data was carried out collaboratively. The reviews were synthesised using a narrative synthesis approach. RESULTS: We retrieved 441 potentially eligible reviews, 23 met the criteria for inclusion and 8 provided data for extraction. Each review evaluated between 8 and 13 tools, in aggregate providing evidence on a total of 28 tools. The quality of the reviews varied and the reporting often lacked sufficient methodological detail for quality assessment. The 28 tools appear to have been studied in a variety of settings and with varied types of patients. The reviews identified several methodological limitations across the original studies. The lack of a 'gold standard' significantly hinders the evaluation of tools' validity. Most importantly, the samples were small providing limited evidence for use of any of the tools across settings or populations. CONCLUSIONS: There are a considerable number of pain assessment tools available for use with the elderly cognitive impaired population. However there is limited evidence about their reliability, validity and clinical utility. On the basis of this review no one tool can be recommended given the existing evidence

Perturbations of Noise: The origins of Isothermal Flows

We make a detailed analysis of both phenomenological and analytic background for the "Brownian recoil principle" hypothesis (Phys. Rev. A 46, (1992), 4634). A corresponding theory of the isothermal Brownian motion of particle ensembles (Smoluchowski diffusion process approximation), gives account of the environmental recoil effects due to locally induced tiny heat flows. By means of local expectation values we elevate the individually negligible phenomena to a non-negligible (accumulated) recoil effect on the ensemble average. The main technical input is a consequent exploitation of the Hamilton-Jacobi equation as a natural substitute for the local momentum conservation law. Together with the continuity equation (alternatively, Fokker-Planck), it forms a closed system of partial differential equations which uniquely determines an associated Markovian diffusion process. The third Newton law in the mean is utilised to generate diffusion-type processes which are either anomalous (enhanced), or generically non-dispersive.Comment: Latex fil

Net Charge Fluctuations in Au + Au Interactions at sqrt(s_NN) = 130 GeV

Data from Au + Au interactions at sqrt(s_NN) = 130 GeV, obtained with the PHENIX detector at RHIC, are used to investigate local net charge fluctuations among particles produced near mid-rapidity. According to recent suggestions, such fluctuations may carry information from the Quark Gluon Plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.Comment: 6 pages, RevTeX 3, 3 figures, 307 authors, submitted to Phys. Rev. Lett. on 21 March, 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm