Simulation of electron transport in quantum well devices

Double barrier resonant tunneling diodes (DBRTD) have received much attention as possible terahertz devices. Despite impressive experimental results, the specifics of the device physics (i.e., how the electrons propagate through the structure) are only qualitatively understood. Therefore, better transport models are warranted if this technology is to mature. In this paper, the Lattice Wigner function is used to explain the important transport issues associated with DBRTD device behavior

Influence of TP53 and CDH1 genes in hepatocellular cancer spheroid formation and culture: a model system to understand cancer cell growth mechanics

BACKGROUND: Spheroid based culture methods are gaining prominence to elucidate the role of the microenvironment in liver carcinogenesis. Additionally, the phenomenon of epithelial-mesenchymal transition also plays an important role in determining the metastatic potential of liver cancer. Tumor spheroids are thus important models to understand the basic biology of liver cancer. METHODS: We cultured, characterized and examined the formation of compact 3-D micro-tumor spheroids in five hepatocellular carcinoma (HCC) cell lines, each with differing TP53 mutational status (wt vs mutant vs null). Spheroid viability and death was systematically measured over a course of a 10 day growth period using various assays. We also examined the TP53 and E-cadherin (CDH1) mRNA and protein expression status in each cell line of the 2-D and 3-D cell models. RESULTS: A novel finding of our study was the identification of variable 3-D spheroid morphology in individual cell lines, ranging from large and compact, to small and unstable spheroid morphologies. The observed morphological differences between the spheroids were robust and consistent over the duration of spheroid culture growth of 10 days in a repeatable manner. Highly variable CDH1 expression was identified depending on the TP53 mutational status of the individual HCC cell line, which may explain the variable spheroid morphology. We observed consistent patterns of TP53 and CDH1 expression in both 2-D and 3-D culture models. CONCLUSIONS: In conclusion, we show that 3-D spheroids are a useful model to determine the morphological growth characteristics of cell lines which are not immediately apparent in routine 2-D culture methods. 3-D culture methods may provide a better alternative to study the process of epithelial-mesenchymal transition (EMT) which is important in the process of liver cancer metastasis

Working Memory in Attention Deficit/Hyperactivity Disorder is Characterized by a Lack of Specialization of Brain Function

Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD) and create problems along numerous functional dimensions. The present study utilized the Visual Serial Addition Task (VSAT) and functional magnetic resonance imaging (fMRI) to explore working memory processes in thirteen typically developing (TD) control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA) was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6) and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity

Outcome of pterygium surgery: analysis over 14 years

Aim: To report the outcome of pterygium surgery performed at a tertiary eye care centre in South India. Methods: Retrospective analysis of medical records of 920 patients (989 eyes) with primary and recurrent pterygia operated between January 1988 and December 2001. The demographic variables, surgical technique (bare sclera, primary closure, amniotic membrane transplantation (AMT), conjunctival autograft (CAG), conjunctival-limbal autograft (CLAG), or surgical adjuvants), recurrences and postoperative complications were analysed. Results: A total of 496 (53.9%) were male and 69 (7.5%) had bilateral pterygia. Bare sclera technique was performed in 267 (27.0%) eyes, primary conjunctival closure in 32 (3.2%), AMG in 123 (12.4%), CAG in 429 (43.4%), and CLAG in 70 (7.1%). Adjuvant mitomycin C was used in 44 (4.4%) cases. The mean duration of follow-up was 8.917.0 and 5.98.8 months for unilateral primary and recurrent pterygia, respectively. The overall recurrence rate was 178 (18.0%). Following primary and recurrent unilateral pterygium excision respectively, recurrences were noted in 46 (19.4%) and 1 (33.3%) eyes after bare sclera technique, five (16.7%) and 0 after primary closure, 28 (26.7%) and 0 with AMG, 42 (12.2%) and five (31.3%) with CAG, and nine (17.3%) and two (40%) with CLAG. Recurrences were significantly more in males with primary (23.3 vs10.7%, P<0.0001) and recurrent (26.7 vs0%, P=0.034) pterygia, and in those below 40 years (25.2 vs14.8%, P=0.003). Conclusion: CAG appears to be an effective modality for primary and recurrent pterygia. Males and patients below 40 years face greater risk of recurrence. Bare sclera technique has an unacceptably high recurrence. Prospective studies comparing CAG, CLAG, and AMG for primary and recurrent pterygia are needed

MR-guided focused ultrasound thalamotomy modulates cerebello-thalamo-cortical tremor network in essential tremor patients

ObjectivesTo advance the mechanistic understanding of changes occurring to brain connectivity after successful MR-guided Focused Ultrasound ventral intermediate nucleus (VIM) thalamotomy for essential tremor (ET).MethodsThis retrospective study included fifteen right-handed ET patients, who underwent successful unilateral VIM ablation and experienced improved hand tremor on their dominant hand. Resting-state fMRI scans were conducted both before and 1-year post-treatment for all participants. A seed-based whole brain resting-state functional connectivity (FC) analysis was performed, centering on tremor-related regions within the cerebello-thalamo-cortical (CTC) network, including the left and right ventral intermediate nucleus (VIM), primary motor cortex (M1H), and dentate nucleus (DN). The study examined both the changes in FC and their correlation with clinical outcomes evaluated using the Clinical Rating Scale for Tremor (CRST) at the 1-year post-treatment.ResultsET patients demonstrated significant tremor improvement at the treated hand, which persisted throughout the 1-year study period. Compared with the baseline, FC of both left VIM and right VIM decreased in precentral gyrus and postcentral gyrus; FC of left M1 hand area increased in premotor cortex and supplemental motor area (SMA); and FC of left DN also increased in premotor cortex, SMA, M1, and anterior cingulate cortex (ACC). Association analysis between changes in left VIM functional connectivity and contralateral hand tremor scores revealed a significant negative correlation in the bilateral precentral gyrus, superior parietal lobule, precuneus, occipital cortex, and middle prefrontal cortex. Conversely, a significant positive correlation was observed in the frontal orbital cortex, right insular cortex, temporal pole, hippocampus, left lingual gyrus, right cerebellar lobules IV/V, left cerebellar lobule VI, and vermis IV/V.ConclusionOur findings of altered functional connectivity within the cerebello-thalamo-cortical network, encompassing regions involved in motor, sensory, attention, visual, and visuospatial functions, and its association with hand tremor improvement suggest that targeting functional connectivity abnormalities may be a potential approach for alleviating tremor symptoms in ET patients

Rapid assessment of visual impairment (RAVI) in marine fishing communities in South India - study protocol and main findings

<p>Abstract</p> <p>Background</p> <p>Reliable data are a pre-requisite for planning eye care services. Though conventional cross sectional studies provide reliable information, they are resource intensive. A novel rapid assessment method was used to investigate the prevalence and causes of visual impairment and presbyopia in subjects aged 40 years and older. This paper describes the detailed methodology and study procedures of Rapid Assessment of Visual Impairment (RAVI) project.</p> <p>Methods</p> <p>A population-based cross-sectional study was conducted using cluster random sampling in the coastal region of Prakasam district of Andhra Pradesh in India, predominantly inhabited by fishing communities. Unaided, aided and pinhole visual acuity (VA) was assessed using a Snellen chart at a distance of 6 meters. The VA was re-assessed using a pinhole, if VA was < 6/12 in either eye. Near vision was assessed using N notation chart binocularly. Visual impairment was defined as presenting VA < 6/18 in the better eye. Presbyopia is defined as binocular near vision worse than N8 in subjects with binocular distance VA of 6/18 or better.</p> <p>Results</p> <p>The data collection was completed in <12 weeks using two teams each consisting of one paramedical ophthalmic personnel and two community eye health workers. The prevalence of visual impairment was 30% (95% CI, 27.6-32.2). This included 111 (7.1%; 95% CI, 5.8-8.4) individuals with blindness. Cataract was the leading cause of visual impairment followed by uncorrected refractive errors. The prevalence of blindness according to WHO definition (presenting VA < 3/60 in the better eye) was 2.7% (95% CI, 1.9-3.5).</p> <p>Conclusion</p> <p>There is a high prevalence of visual impairment in marine fishing communities in Prakasam district in India. The data from this rapid assessment survey can now be used as a baseline to start eye care services in this region. The rapid assessment methodology (RAVI) reported in this paper is robust, quick and has the potential to be replicated in other areas.</p

VPS29 Is Not an Active Metallo-Phosphatase but Is a Rigid Scaffold Required for Retromer Interaction with Accessory Proteins

VPS29 is a key component of the cargo-binding core complex of retromer, a protein assembly with diverse roles in transport of receptors within the endosomal system. VPS29 has a fold related to metal-binding phosphatases and mediates interactions between retromer and other regulatory proteins. In this study we examine the functional interactions of mammalian VPS29, using X-ray crystallography and NMR spectroscopy. We find that although VPS29 can coordinate metal ions Mn2+ and Zn2+ in both the putative active site and at other locations, the affinity for metals is low, and lack of activity in phosphatase assays using a putative peptide substrate support the conclusion that VPS29 is not a functional metalloenzyme. There is evidence that structural elements of VPS29 critical for binding the retromer subunit VPS35 may undergo both metal-dependent and independent conformational changes regulating complex formation, however studies using ITC and NMR residual dipolar coupling (RDC) measurements show that this is not the case. Finally, NMR chemical shift mapping indicates that VPS29 is able to associate with SNX1 via a conserved hydrophobic surface, but with a low affinity that suggests additional interactions will be required to stabilise the complex in vivo. Our conclusion is that VPS29 is a metal ion-independent, rigid scaffolding domain, which is essential but not sufficient for incorporation of retromer into functional endosomal transport assemblies

Mapping the Interactions between a RUN Domain from DENND5/Rab6IP1 and Sorting Nexin 1

Eukaryotic cells have developed a diverse repertoire of Rab GTPases to regulate vesicle trafficking pathways. Together with their effector proteins, Rabs mediate various aspects of vesicle formation, tethering, docking and fusion, but details of the biological roles elicited by effectors are largely unknown. Human Rab6 is involved in the trafficking of vesicles at the level of Golgi via interactions with numerous effector proteins. We have previously determined the crystal structure of Rab6 in complex with DENND5, alternatively called Rab6IP1, which comprises two RUN domains (RUN1 and RUN2) separated by a PLAT domain. The structure of Rab6/RUN1-PLAT (Rab6/R1P) revealed the molecular basis for Golgi recruitment of DENND5 via the RUN1 domain, but the functional role of the RUN2 domain has not been well characterized. Here we show that a soluble DENND5 construct encompassing the RUN2 domain binds to the N-terminal region of sorting nexin 1 by surface plasmon resonance analyses