N=2 Sigma Models for Ramond-Ramond Backgrounds

Using the U(4) hybrid formalism, manifestly N=(2,2) worldsheet supersymmetric sigma models are constructed for the Type IIB superstring in Ramond-Ramond backgrounds. The Kahler potential in these N=2 sigma models depends on four chiral and antichiral bosonic superfields and two chiral and antichiral fermionic superfields. When the Kahler potential is quadratic, the model is a free conformal field theory which describes a flat ten-dimensional target space with Ramond-Ramond flux and non-constant dilaton. For more general Kahler potentials, the model describes curved target spaces with Ramond-Ramond flux that are not plane-wave backgrounds. Ricci-flatness of the Kahler metric implies the on-shell conditions for the background up to the usual four-loop conformal anomaly.Comment: 19 pages harvma

Robotic therapy : Cost, accuracy, and times. New challenges in the neonatal intensive care unit

Background: The medication process in the Neonatal Intensive Care Unit (NICU), can be challenging in terms of costs, time, and the risk of errors. Newborns, especially if born preterm, are more vulnerable to medication errors than adults. Recently, robotic medication compounding has reportedly improved the safety and efficiency of the therapeutic process. In this study, we analyze the advantages of using the I.V. Station\uae system in our NICU, compared to the manual preparation of injectable drugs in terms of accuracy, cost, and time. Method: An in vitro experimental controlled study was conducted to analyze 10 injectable powdered or liquid drugs. Accuracy was calculated within a 5% difference of the bottle weight during different stages of preparation (reconstitution, dilution, and final product). The overall cost of manual and automated preparations were calculated and compared. Descriptive statistics for each step of the process are presented as mean \ub1 standard deviation or median (range). Results: The median error observed during reconstitution, dilution, and final therapy of the drugs prepared by the I.V. Station\uae ranged within \ub15% accuracy, with narrower ranges of error compared to those prepared manually. With increasing preparations, the I.V. Station\uae consumed less materials, reduced costs, decreased preparation time, and optimized the medication process, unlike the manual method. In the 10 drugs analyzed, the time saved from using the I.V. Station\uae ranged from 16 s for acyclovir to 2 h 57 min for teicoplanin, and cost savings varied from 8% for ampicillin to 66% for teicoplanin. These advantages are also capable of continually improving as the total amount of final product increases. Conclusions: The I.V. Station\uae improved the therapeutic process in our NICU. The benefits included increased precision in drug preparation, improved safety, lowered cost, and saved time. These advantages are particularly important in areas such as the NICU, where the I.V. Station\uae could improve the delivery of the high complexity of care and a large amount of intravenous therapy typically required. In addition, these benefits may lead to the reduction in medication errors and improve patient and family care; however, additional studies will be required to confirm this hypothesis

Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with nonsyndromic mental retardation

Mental retardation (MR) is displayed by 57% of NF1 patients with microdeletion syndrome as a result of 17q11.2 region haploinsufficiency. We considered the cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) and oligodendrocyte-myelin glycoprotein (OMG) genes, mapping in the NF1 microdeleted region, as candidate genes for MR susceptibility. CDK5R1 encodes for a neurone-specific activator of cyclin-dependent kinase 5 (CDK5) involved in neuronal migration during central nervous system development. OMG encodes for an inhibitor of neurite outgrowth by the binding to the Nogo-66 receptor (RTN4R). CDK5R1 and OMG genes are characterized by large 3\u2032 and 5\u2032 untranslated regions (UTRs), where we predict the presence of several transcription/ translation regulatory elements. We screened 100 unrelated Italian patients affected by unspecific MR for mutations in CDK5R1 and OMG coding regions and in their 3\u2032 or 5\u2032 UTRs. Four novel mutations and two novel polymorphisms for CDK5R1 and three novel mutations for OMG were detected, including two missense changes (c.323C>T; A108V in CDK5R1 and c.1222A>G; T408A in OMG), one synonymous codon variant (c.532C>T; L178L in CDK5R1), four variants in CDK5R1 3\u2032UTR and two changes in OMG 5\u2032UTR. All the mutations were absent in 370 chromosomes from normal subjects. The allelic frequencies of the two novel polymorphisms in CDK5R1 3\u2032UTR were established in both 185 normal and 100 mentally retarded subjects. Prediction of mRNA and protein secondary structures revealed that two changes lead to putative structural alterations in the mutated c.2254C>G CDK5R1 3\u2032UTR and in OMG T408A gene product

Molecular Etiology Disclosed by Array CGH in Patients With Silver–Russell Syndrome or Similar Phenotypes

Introduction: Silver-Russell syndrome (SRS) is an imprinting disorder primarily caused by genetic and epigenetic aberrations on chromosomes 11 and 7. SRS is a rare growth retardation disorder often misdiagnosed due to its heterogeneous and non-specific clinical features. The Netchine-Harbison clinical scoring system (NH-CSS) is the recommended tool for differentiating patients into clinical SRS or unlikely SRS. However, the clinical diagnosis is molecularly confirmed only in about 60% of patients, leaving the remaining substantial proportion of SRS patients with unknown genetic etiology. Materials and Methods: A cohort of 34 Italian patients with SRS or SRS-like features scored according to the NH-CSS and without any SRS-associated (epi)genetic alterations was analyzed by high-resolution array-based comparative genomic hybridization (CGH) in order to identify potentially pathogenic copy number variants (CNVs). Results and Discussion: In seven patients, making up 21% of the initial cohort, five pathogenic and two potentially pathogenic CNVs were found involving distinct genomic regions either previously associated with growth delay conditions (1q24.3-q25.3, 17p13.3, 17q22, and 22q11.2-q11.22) and with SRS spectrum (7p12.1 and 7p15.3-p14.3) or outlined for the first time (19q13.42), providing a better definition of reported and as yet unreported SRS overlapping syndromes. All the variants involve genes with a defined role in growth pathways, and for two genes mapping at 7p, IGF2BP3 and GRB10, the association with SRS turns out to be reinforced. The deleterious effect of the two potentially pathogenic variants, comprising GRB10 and ZNF331 genes, was explored by targeted approaches, though further studies are needed to validate their pathogenic role in the SRS etiology. In conclusion, we reconfirm the utility of performing a genome-wide scan to achieve a differential diagnosis in patients with SRS or similar features and to highlight novel chromosome alterations associated with SRS and growth retardation disorders

2d Stringy Black Holes and Varying Constants

Motivated by the recent interest on models with varying constants and whether black hole physics can constrain such theories, two-dimensional charged stringy black holes are considered. We exploit the role of two-dimensional stringy black holes as toy models for exploring paradoxes which may lead to constrains on a theory. A two-dimensional charged stringy black hole is investigated in two different settings. Firstly, the two-dimensional black hole is treated as an isolated object and secondly, it is contained in a thermal environment. In both cases, it is shown that the temperature and the entropy of the two-dimensional charged stringy black hole are decreased when its electric charge is increased in time. By piecing together our results and previous ones, we conclude that in the context of black hole thermodynamics one cannot derive any model independent constraints for the varying constants. Therefore, it seems that there aren't any varying constant theories that are out of favor with black hole thermodynamics.Comment: 12 pages, LaTeX, to appear in JHE

4-point effective actions in open and closed superstring theory

Recently the effective action for the 4-point functions in abelian open superstring theory has been derived, giving an explicit construction of the bosonic and fermionic terms of this infinite $\alpha'$ series. In the present work we generalize this result to the nonabelian case. We test our result, at ${\alpha'}^3$ and ${\alpha'}^4$ order, with several existing versions for these terms, finding agreement in most of the cases. We also apply these ideas to derive the effective action for the 4-point functions of the NS-NS sector of closed superstring theory, to all order in $\alpha'$.Comment: 26 pages, 1 figure. To appear in JHE

Quintessential Maldacena-Maoz Cosmologies

Maldacena and Maoz have proposed a new approach to holographic cosmology based on Euclidean manifolds with disconnected boundaries. This approach appears, however, to be in conflict with the known geometric results [the Witten-Yau theorem and its extensions] on spaces with boundaries of non-negative scalar curvature. We show precisely how the Maldacena-Maoz approach evades these theorems. We also exhibit Maldacena-Maoz cosmologies with [cosmologically] more natural matter content, namely quintessence instead of Yang-Mills fields, thereby demonstrating that these cosmologies do not depend on a special choice of matter to split the Euclidean boundary. We conclude that if our Universe is fundamentally anti-de Sitter-like [with the current acceleration being only temporary], then this may force us to confront the holography of spaces with a connected bulk but a disconnected boundary.Comment: Much improved exposition, exponent in Cai-Galloway theorem fixed, axionic interpretation of scalar explained, JHEP version. 33 pages, 3 eps figure

Giant Gravitons - with Strings Attached (III)

We develop techniques to compute the one-loop anomalous dimensions of operators in the ${\cal N}=4$ super Yang-Mills theory that are dual to open strings ending on boundstates of sphere giant gravitons. Our results, which are applicable to excitations involving an arbitrary number of open strings, generalize the single string results of hep-th/0701067. The open strings we consider carry angular momentum on an S$^3$ embedded in the S$^5$ of the AdS$_5\times$S$^5$ background. The problem of computing the one loop anomalous dimensions is replaced with the problem of diagonalizing an interacting Cuntz oscillator Hamiltonian. Our Cuntz oscillator dynamics illustrates how the Chan-Paton factors for open strings propagating on multiple branes can arise dynamically.Comment: 66 pages; v2: improved presentatio

Resolution of dark matter problem in f(T) gravity

In this paper, we attempt to resolve the dark matter problem in f(T) gravity. Specifically, from our model we successfully obtain the flat rotation curves of galaxies containing dark matter. Further, we obtain the density profile of dark matter in galaxies. Comparison of our analytical results shows that our torsion-based toy model for dark matter is in good agreement with empirical data-based models. It shows that we can address the dark matter as an effect of torsion of the space.Comment: 14 pages, 3 figure

Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short-term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns. Evidence from several studies has suggested that in schizophrenia and bipolar disorder, mRNA of the reelin gene (RELN), which encodes a protein necessary for neuronal migration, axonal branching, synaptogenesis, and cell signaling, is severely reduced in post-mortem brains. Therefore, we investigated the methylation status of the RELN promoter region in schizophrenic patients and normal controls as a potential mechanism for down regulation of its expression. Ten post-mortem frontal lobe brain samples from male schizophrenic patients and normal controls were obtained from the Harvard Brain Tissue Resources Center. DNA was extracted using a standard phenol-chloroform DNA extraction protocol. To evaluate differences between patients and controls, we applied methylation specific PCR (MSP) using primers localized to CpG islands flanking a potential cyclic AMP response element (CRE) and a stimulating protein-1 (SP1) binding site located in the promoter region. For each sample, DNA extraction, bisulfite treatment, and MSP were independently repeated at least four times to accurately determine the methylation status of the target region. Forty-three PCR trials were performed on the test and control samples. MSP analysis of the RELN promoter revealed an unmethylated signal in all reactions (43 of 43) using DNA from the frontal brain tissue, derived from either the schizophrenic patients or normal controls indicating that this region of the RELN promoter is predominantly unmethylated. However, we observed a distinct methylated signal in 73 of the trials (16 of 22) in schizophrenic patients compared with 24 (5 of 21) of controls. Thus, the hypermethylation of the CpG islands flanking a CRE and SP1 binding site observed at a significantly higher level (t = -5.07, P = 0.001) may provide a mechanism for the decreased RELN expression, frequently observed in post-mortem brains of schizophrenic patients. We also found an inverse relationship between the level of DNA methylation using MSP analysis and the expression of the RELN gene using semi-quantitative RT-PCR. Despite the small sample size, these studies indicate that promoter hypermethylation of the RELN gene could be a significant contributor in effecting epigenetic alterations and provides a molecular basis for the RELN gene hypoactivity in schizophrenia. Further studies with a larger sample set would be required to validate these preliminary observations. © 2005 Wiley-Liss, Inc