Pumped double quantum dot with spin-orbit coupling

We study driven by an external electric field quantum orbital and spin dynamics of electron in a one-dimensional double quantum dot with spin-orbit coupling. Two types of external perturbation are considered: a periodic field at the Zeeman frequency and a single half-period pulse. Spin-orbit coupling leads to a nontrivial evolution in the spin and orbital channels and to a strongly spin- dependent probability density distribution. Both the interdot tunneling and the driven motion contribute into the spin evolution. These results can be important for the design of the spin manipulation schemes in semiconductor nanostructures

Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia

Abstract Background Base deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples. Methods We conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry, serum albumin (Alb) and lactate(Lac) levels measured from the same sample. We assessed the capacity of AG, BD, and ACAG to diagnose HL and severe hyperlactatemia (SHL). HL was defined as Lac > 2.5 mmol/L. SHL was defined as a Lac of > 4.0 mmol/L. Results From 143 patients we identified 497 series of lab values that met our study criteria. Mean age was 62.2 ± 15.7 years. Mean Lac was 2.11 ± 2.6 mmol/L, mean AG was 9.0 ± 5.1, mean ACAG was 14.1 ± 3.8, mean BD was 1.50 ± 5.4. The area under the curve for the ROC for BD, AG, and ACAG to diagnose HL were 0.79, 0.70, and 0.72, respectively. Conclusion AG and BD failed to reliably detect the presence of clinically significant hyperlactatemia. Under idealized conditions, ACAG has the capacity to rule out the presence of hyperlactatemia. Lac levels should be obtained routinely in all patients admitted to the ICU in whom the possibility of shock/hypoperfusion is being considered. If an AG assessment is required in the ICU, it must be corrected for albumin for there to be sufficient diagnostic utility.</p

Transmission Heterogeneity and Control Strategies for Infectious Disease Emergence

The control of emergence and spread of infectious diseases depends critically on the details of the genetic makeup of pathogens and hosts, their immunological, behavioral and ecological traits, and the pattern of temporal and spatial contacts among the age/stage-classes of susceptible and infectious host individuals.We show that failing to acknowledge the existence of heterogeneities in the transmission rate among age/stage-classes can make traditional eradication and control strategies ineffective, and in some cases, policies aimed at controlling pathogen emergence can even increase disease incidence in the host. When control strategies target for reduction in numbers those subsets of the population that effectively limit the production of new susceptible individuals, then control can produce a flush of new susceptibles entering the population. The availability of a new cohort of susceptibles may actually increase disease incidence. We illustrate these general points using Classical Swine Fever as a reference disease.Negative effects of culling are robust to alternative formulations of epidemiological processes and underline the importance of better assessing transmission structure in the design of wildlife disease control strategies

Combined analysis of transcriptome and metabolite data reveals extensive differences between black and brown nearly-isogenic soybean (Glycine max) seed coats enabling the identification of pigment isogenes

<p>Abstract</p> <p>Background</p> <p>The <it>R </it>locus controls the color of pigmented soybean (<it>Glycine max</it>) seeds. However information about its control over seed coat biochemistry and gene expressions remains limited. The seed coats of nearly-isogenic black (<it>iRT</it>) and brown (<it>irT</it>) soybean (<it>Glycine max</it>) were known to differ by the presence or absence of anthocyanins, respectively, with genes for only a single enzyme (anthocyanidin synthase) found to be differentially expressed between isolines. We recently identified and characterized a UDP-glycose:flavonoid-3-<it>O</it>-glycosyltransferase (<it>UGT78K1</it>) from the seed coat of black (<it>iRT</it>) soybean with the aim to engineer seed coat color by suppression of an anthocyanin-specific gene. However, it remained to be investigated whether <it>UGT78K1 </it>was overexpressed with anthocyanin biosynthesis in the black (<it>iRT</it>) seed coat compared to the nearly-isogenic brown (<it>irT</it>) tissue.</p> <p>In this study, we performed a combined analysis of transcriptome and metabolite data to elucidate the control of the R locus over seed coat biochemistry and to identify pigment biosynthesis genes. Two differentially expressed late-stage anthocyanin biosynthesis isogenes were further characterized, as they may serve as useful targets for the manipulation of soybean grain color while minimizing the potential for unintended effects on the plant system.</p> <p>Results</p> <p>Metabolite composition differences were found to not be limited to anthocyanins, with specific proanthocyanidins, isoflavones, and phenylpropanoids present exclusively in the black (<it>iRT</it>) or the brown (<it>irT</it>) seed coat. A global analysis of gene expressions identified <it>UGT78K1 </it>and 19 other anthocyanin, (iso)flavonoid, and phenylpropanoid isogenes to be differentially expressed between isolines. A combined analysis of metabolite and gene expression data enabled the assignment of putative functions to biosynthesis and transport isogenes. The recombinant enzymes of two genes were validated to catalyze late-stage steps in anthocyanin biosynthesis <it>in vitro </it>and expression profiles of the corresponding genes were shown to parallel anthocyanin biosynthesis during black (<it>iRT</it>) seed coat development.</p> <p>Conclusion</p> <p>Metabolite composition and gene expression differences between black (<it>iRT</it>) and brown (<it>irT</it>) seed coats are far more extensive than previously thought. Putative anthocyanin, proanthocyanidin, (iso)flavonoid, and phenylpropanoid isogenes were differentially-expressed between black (<it>iRT</it>) and brown (<it>irT</it>) seed coats, and <it>UGT78K2 </it>and <it>OMT5 </it>were validated to code UDP-glycose:flavonoid-3-<it>O</it>-glycosyltransferase and anthocyanin 3'-<it>O</it>-methyltransferase proteins <it>in vitro</it>, respectively. Duplicate gene copies for several enzymes were overexpressed in the black (<it>iRT</it>) seed coat suggesting more than one isogene may have to be silenced to engineer seed coat color using RNA interference.</p

Prognostic and therapeutic relevance of FLIP and procaspase-8 overexpression in non-small cell lung cancer

Non-small cell lung carcinoma remains by far the leading cause of cancer-related deaths worldwide. Overexpression of FLIP, which blocks the extrinsic apoptotic pathway by inhibiting caspase-8 activation, has been identified in various cancers. We investigated FLIP and procaspase-8 expression in NSCLC and the effect of HDAC inhibitors on FLIP expression, activation of caspase-8 and drug resistance in NSCLC and normal lung cell line models. Immunohistochemical analysis of cytoplasmic and nuclear FLIP and procaspase-8 protein expression was carried out using a novel digital pathology approach. Both FLIP and procaspase-8 were found to be significantly overexpressed in tumours, and importantly, high cytoplasmic expression of FLIP significantly correlated with shorter overall survival. Treatment with HDAC inhibitors targeting HDAC1-3 downregulated FLIP expression predominantly via post-transcriptional mechanisms, and this resulted in death receptor- and caspase-8-dependent apoptosis in NSCLC cells, but not normal lung cells. In addition, HDAC inhibitors synergized with TRAIL and cisplatin in NSCLC cells in a FLIP- and caspase-8-dependent manner. Thus, FLIP and procaspase-8 are overexpressed in NSCLC, and high cytoplasmic FLIP expression is indicative of poor prognosis. Targeting high FLIP expression using HDAC1-3 selective inhibitors such as entinostat to exploit high procaspase-8 expression in NSCLC has promising therapeutic potential, particularly when used in combination with TRAIL receptor-targeted agents

Diurnal Variation in Urodynamics of Rat

In humans, the storage and voiding functions of the urinary bladder have a characteristic diurnal variation, with increased voiding during the day and urine storage during the night. However, in animal models, the daily functional differences in urodynamics have not been well-studied. The goal of this study was to identify key urodynamic parameters that vary between day and night. Rats were chronically instrumented with an intravesical catheter, and bladder pressure, voided volumes, and micturition frequency were measured by continuous filling cystometry during the light (inactive) or dark (active) phases of the circadian cycle. Cage activity was recorded by video during the experiment. We hypothesized that nocturnal rats entrained to a standard 12:12 light:dark cycle would show greater ambulatory activity and more frequent, smaller volume micturitions in the dark compared to the light. Rats studied during the light phase had a bladder capacity of 1.44±0.21 mL and voided every 8.2±1.2 min. Ambulatory activity was lower in the light phase, and rats slept during the recording period, awakening only to urinate. In contrast, rats studied during the dark were more active, had a lower bladder capacities (0.65±0.18 mL), and urinated more often (every 3.7±0.9 min). Average bladder pressures were not significantly different between the light and dark (13.40±2.49 and 12.19±2.85 mmHg, respectively). These results identify a day-night difference in bladder capacity and micturition frequency in chronically-instrumented nocturnal rodents that is phase-locked to the normal circadian locomotor activity rhythm of the animal. Furthermore, since it has generally been assumed that the daily hormonal regulation of renal function is a major driver of the circadian rhythm in urination, and few studies have addressed the involvement of the lower urinary tract, these results establish the bladder itself as a target for circadian regulation

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

<p>Abstract</p> <p>Background</p> <p>While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile.</p> <p>Methods</p> <p>RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes.</p> <p>Results</p> <p><it>In silico </it>models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells).</p> <p>Conclusion</p> <p>Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.</p

Magnetic Resonance Water Proton Relaxation in Protein Solutions and Tissue: T1ρ Dispersion Characterization

BACKGROUND: Image contrast in clinical MRI is often determined by differences in tissue water proton relaxation behavior. However, many aspects of water proton relaxation in complex biological media, such as protein solutions and tissue are not well understood, perhaps due to the limited empirical data. PRINCIPAL FINDINGS: Water proton T(1), T(2), and T(1rho) of protein solutions and tissue were measured systematically under multiple conditions. Crosslinking or aggregation of protein decreased T(2) and T(1rho), but did not change high-field T(1). T(1rho) dispersion profiles were similar for crosslinked protein solutions, myocardial tissue, and cartilage, and exhibited power law behavior with T(1rho)(0) values that closely approximated T(2). The T(1rho) dispersion of mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5 kHz that was sensitive to changes in pH. The T(1rho) dispersion of crosslinked BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5 kHz but showed decreased dispersion below 5 kHz. CONCLUSIONS: Proton exchange is a minor pathway for tissue T(1) and T(1rho) relaxation above 5 kHz. Potential models for relaxation are discussed, however the same molecular mechanism appears to be responsible across 5 decades of frequencies from T(1rho) to T(1)