Particle-in-cell Simulations of Ion Dynamics in a Pinched-beam Diode

article-in-cell simulations of a 1.6 MV, 800 kA, and 50 ns pinched-beam diode have been completed with emphasis placed on the quality of the ion beams produced. Simulations show the formation of multiple regions in the electron beam flow characterized by locally high charge and current density (“hot spots”). As ions flow through the electron-space-charge cloud, these hot spots electrostatically attract ions to produce a non-uniform ion current distribution. The length of the cavity extending beyond the anode-to-cathode gap (i.e., behind the cathode tip) influences both the number and amplitude of hot spots. A longer cavity length increases the number of hot spots yet significantly reduces the amplitude producing a smoother, more uniform ion beam than for shorter cavities. The net current and the ion bending angles are also significantly smaller with long cavities

Microcanonical rates, gap times, and phase space dividing surfaces

The general approach to classical unimolecular reaction rates due to Thiele is revisited in light of recent advances in the phase space formulation of transition state theory for multidimensional systems. We analyze in detail the gap time distribution and associated reactant lifetime distribution for the isomerization reaction HCN $\rightleftharpoons$ CNH. Both algebraic (power law) and exponential decay regimes have been identified. Statistical estimates of the isomerization rate are compared with the numerically determined decay rate. Examination of the decay properties of subsensembles of trajectories that exit the HCN well through either of 2 available symmetry related product channels shows that the complete trajectory ensemble effectively attains the full symmetry of the system phase space on a short timescale $t \lesssim 0.5$ ps, after which the product branching ratio is 1:1, the "statistical" value. At intermediate times, this statistical product ratio is accompanied by nonexponential (nonstatistical) decay. We point out close parallels between the dynamical behavior inferred from the gap time distribution for HCN and nonstatistical behavior recently identified in reactions of some organic molecules.Comment: 44 pages, 9 figure

A 115-bp MethyLight assay for detection of p16 (CDKN2A) methylation as a diagnostic biomarker in human tissues

<p>Abstract</p> <p>Background</p> <p><it>p16 </it>Methylation is a potential biomarker for prediction of malignant transformation of epithelial dysplasia. A probe-based, quantitative, methylation-specific PCR (MSP) called MethyLight may become an eligible method for detecting this marker clinically. We studied oral mucosa biopsies with epithelial dysplasia from 78 patients enrolled in a published 4-years' followup cohort, in which cancer risk for patients with <it>p16 </it>methylation-positive dysplasia was significantly higher than those without <it>p16 </it>methylation (by 150-bp MSP and bisulfite sequencing; +133 ~ +283, transcription starting site, +1). The <it>p16 </it>methylation status in samples (<it>N </it>= 102) containing sufficient DNA was analyzed by the 70-bp classic (+238 ~ +307) and 115-bp novel (+157 ~ +272) MethyLight assays, respectively.</p> <p>Results</p> <p><it>p16 </it>Methylation was detectable in 75 samples using the classic MethyLight assay. The methylated-<it>p16 </it>positive rate and proportion of methylated-<it>p16 </it>by the MethyLight in MSP-positive samples were higher than those in MSP-negative samples (positive rate: 37/44 vs. 38/58, <it>P</it>=0.035, two-sided; proportion [median]: 0.78 vs. 0.02, <it>P <</it>0.007). Using the published results of MSP as a golden standard, we found sensitivity, specificity, and accuracy for this MethyLight assay to be 70.5%, 84.5%, and 55.0%, respectively. Because amplicon of the classic MethyLight procedure only partially overlapped with the MSP amplicon, we further designed a 115-bp novel MethyLight assay in which the amplicon on the sense-strand fully overlapped with the MSP amplicon on the antisense-strand. Using the 115-bp MethyLight assay, we observed methylated-<it>p16 </it>in 26 of 44 MSP-positive samples and 2 of 58 MSP-negative ones (<it>P </it>= 0.000). These results were confirmed with clone sequencing. Sensitivity, specificity, and accuracy using the 115-bp MethyLight assay were 59.1%, 98.3%, and 57.4%, respectively. Significant differences in the oral cancer rate were observed during the followup between patients (≥60 years) with and without methylated-<it>p16 </it>as detected by the 115-bp MethyLight assay (6/8 vs. 6/22, P = 0.034, two-sided).</p> <p>Conclusions</p> <p>The 115-bp MethyLight assay is a useful and practical assay with very high specificity for the detection of <it>p16 </it>methylation clinically.</p

Infant observation research: What have we learned so far?

This paper reviews published literature in the field of psychoanalytic infant observation research, and asks, how much has so far been achieved by this work? It identifies themes, theoretical ideas, techniques, and applications which have been explored and developed in this literature. How far has the distinctive method which characterises naturalistic infant observation proved capable of generating new hypotheses, or locating hitherto unrecognised phenomena in the field of mother-infant relationships, and family dynamics more generally? The writer identifies a number of areas where significant development has taken place. His view is that a greater measure of reflection and review of research publication in infant observation and indeed child psychotherapy, would strengthen these research programmes. It would also support writing being increasingly undertaken for doctoral and masters programmes

Reclaiming the humanity in personality Disorder.

This paper provides a commentary upon the nursing care of individuals diagnosed with personality disorder and associated education courses. The discussion focuses upon recent policy trends in the UK as a point of departure. This policy discourse is critical of mainstream mental health services in previously operating to exclude such individuals. One of the consequences has been a recent growth in interest in relevant training courses, many of which devote significant attention to staff attitudes regarding this client group. Various previous researchers and commentators have remarked upon the implications for practice of a perceived negative attitude among care staff. We reflect upon our own anecdotal experience of developing and delivering new university-based courses for practitioners working in the field of personality disorder to offer a particular critique of the UK context, in which this policy, training, and practice is framed. Social constructionist theories are drawn on to offer insights into public and practitioner discourse and the possible effects on therapeutic relationships. The available discourse constructs individuals with a diagnosis of personality disorder as essentially different from other people. We argue that staff training and practice development initiatives are likely to be more successful if such discourse is challenged, and attempts are made in therapeutic encounters to recognize shared characteristics and positive attributes as much as perceived difference and negative attributes. We refer to this as a re-engagement with common humanity. Despite the singular national context, the discursive themes explored are not necessarily restricted to the UK

Epigenetic reprogramming of breast cancer cells with oocyte extracts

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.</p> <p>Results</p> <p>We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts.</p> <p>Conclusions</p> <p>This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.</p

The Bile Acid Synthesis Pathway Is Present and Functional in the Human Ovary

Background: Bile acids, end products of the pathway for cholesterol elimination, are required for dietary lipid and fat-soluble vitamin absorption and maintain the balance between cholesterol synthesis in the liver and cholesterol excretion. They are composed of a steroid structure and are primarily made in the liver by the oxidation of cholesterol. Cholesterol is also highly abundant in the human ovarian follicle, where it is used in the formation of the sex steroids. Methodology/Principal Findings: Here we describe for the first time evidence that all aspects of the bile acid synthesis pathway are present in the human ovarian follicle, including the enzymes in both the classical and alternative pathways, the nuclear receptors known to regulate the pathway, and the end product bile acids. Furthermore, we provide functional evidence that bile acids are produced by the human follicular granulosa cells in response to cholesterol presence in the culture media. Conclusions/Significance: These findings establish a novel pathway present in the human ovarian follicle that has the capacity to compete directly with sex steroid synthesis