SWAS and Arecibo observations of H2O and OH in a diffuse cloud along the line-of-sight to W51

Observations of W51 with the Submillimeter Wave Astronomy Satellite (SWAS) have yielded the first detection of water vapor in a diffuse molecular cloud. The water vapor lies in a foreground cloud that gives rise to an absorption feature at an LSR velocity of 6 km/s. The inferred H2O column density is 2.5E+13 cm-2. Observations with the Arecibo radio telescope of hydroxyl molecules at ten positions in W51 imply an OH column density of 8E+13 cm-2 in the same diffuse cloud. The observed H2O/OH ratio of ~ 0.3 is significantly larger than an upper limit derived previously from ultraviolet observations of the similar diffuse molecular cloud lying in front of HD 154368. The observed variation in H2O/OH likely points to the presence in one or both of these clouds of a warm (T > 400) gas component in which neutral-neutral reactions are important sources of OH and/or H2O.Comment: 15 pages (AASTeX) including 4 (eps) figures. To appear in the Astrophysical Journa

Photoinduced charge transport over branched conjugation pathways: donor–acceptor substituted 1,1-diphenylethene and 2,3-diphenylbutadiene

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence (http://creativecommons.org/licenses/by-nc/3.0/)Photoinduced charge transport in 1,1-diphenylethene and 2,3-diphenylbutadiene functionalized with an electron donating dimethylamino group and an electron accepting cyano group is reported. UV-spectroscopy reveals that in these compounds, which incorporate a cross-conjugated spacer, a direct charge transfer transition is possible. It is shown by application of the generalized Mulliken–Hush approach that introduction of an additional branching point in the π-electron spacer (i.e., when going from the 1,1-diphenylethene to the 2,3-diphenylbutadiene) leads to only a moderate reduction (68–92%) of the electronic coupling between the ground and the charge separated state. The σ-electron system is however likely to be dominant in the photoinduced charge separation process

Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli

Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffnesschondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process

The Ionization Fraction in Dense Molecular Gas II: Massive Cores

We present an observational and theoretical study of the ionization fraction in several massive cores located in regions that are currently forming stellar clusters. Maps of the emission from the J = 1-> O transitions of C18O, DCO+, N2H+, and H13CO+, as well as the J = 2 -> 1 and J = 3 -> 2 transitions of CS, were obtained for each core. Core densities are determined via a large velocity gradient analysis with values typically 10^5 cm^-3. With the use of observations to constrain variables in the chemical calculations we derive electron fractions for our overall sample of 5 cores directly associated with star formation and 2 apparently starless cores. The electron abundances are found to lie within a small range, -6.9 < log10(x_e) < -7.3, and are consistent with previous work. We find no difference in the amount of ionization fraction between cores with and without associated star formation activity, nor is any difference found in electron abundances between the edge and center of the emission region. Thus our models are in agreement with the standard picture of cosmic rays as the primary source of ionization for molecular ions. With the addition of previously determined electron abundances for low mass cores, and even more massive cores associated with O and B clusters, we systematically examine the ionization fraction as a function of star formation activity. This analysis demonstrates that the most massive sources stand out as having the lowest electron abundances (x_e < 10^-8).Comment: 35 pages (8 figures), using aaspp4.sty, to be published in Astrophysical Journa

Discovering schizophrenia endophenotypes in randomly ascertained pedigrees

Background Although case-control approaches are beginning to disentangle schizophrenia’s complex polygenic burden, other methods will likely be necessary to fully identify and characterize risk genes. Endophenotypes, traits genetically correlated with an illness, can help characterize the impact of risk genes by providing genetically relevant traits that are more tractable than the behavioral symptoms that classify mental illness. Here we present an analytic approach for discovering and empirically validating endophenotypes in extended pedigrees with very few affected individuals. Our approach indexes each family member’s risk as a function of shared genetic kinship with an affected individual, often referred to as the coefficient of relatedness. To demonstrate the utility of this approach, we search for neurocognitive and neuroanatomic endophenotypes for schizophrenia in large unselected multigenerational pedigrees. Methods A fixed effect test within the variance component framework was performed on neurocognitive and cortical surface area traits in 1,606 Mexican-American individuals from large, randomly ascertained extended pedigrees who participate in the “Genetics of Brain Structure and Function” study. As affecteds are excluded from analyses, results are not influenced by disease state or medication usage. Results Despite having sampled just 6 individuals with schizophrenia, our sample provided 233 individuals at various levels of genetic risk for the disorder. We identified three neurocognitive measures (digit-symbol substitution, facial memory, and emotion recognition) and six medial temporal and prefrontal cortical surfaces associated with liability for schizophrenia. Conclusions With our novel analytic approach one can discover and rank endophenotypes for schizophrenia, or any heritable disease, in randomly ascertained pedigrees

Development of Phenalenone-Triazolium Salt Derivatives for aPDT: Synthesis and Antibacterial Screening

The increasing number of hospital-acquired infections demand the development of innovative antimicrobial treatments. Antimicrobial photodynamic therapy (aPDT) is a versatile technique which relies on the production of reactive oxygen species (ROS) generated by light-irradiated photosensitizers (PS) in the presence of oxygen (O2). 1H-Phenalen-1-one is a very efficient photosensitizer known for its high singlet oxygen quantum yield and its antimicrobial potential in aPDT when covalently bound to quaternary ammonium groups. Triazolium salts are stable aromatic quaternary ammonium salts that recently appeared as interesting moieties endowed with antimicrobial activities. The coupling between phenalenone and triazolium groups bearing various substituents was realized by copper-catalyzed azide-alkyne cycloaddition followed by alkylation with methyl iodide or 2-(bromomethyl)-1H-phenalen-1-one. As expected, most of the compounds retained the initial singlet oxygen quantum yield, close to unity. Minimum inhibitory concentrations (MIC) of 14 new phenalenone-triazolium salt derivatives and 2 phenalenone-triazole derivatives were determined against 6 bacterial strains (Gram-negatives and Gram-positives species). Most of these PS showed significant photoinactivation activities, the strongest effects being observed against Gram-positive strains with as low as submicromolar MIC values.EU Framework Programme Horizon 202

Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families

Objective: While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D. Methods: Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes. Results: Decreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment--insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals. Conclusion: Serum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D

The interplay between statins, caveolin-1, and aldosterone

Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin’s aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1–43.2) lower aldosterone level (P=0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels (P=0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant (P=0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin’s aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation

The effects of RF coils and SAR supervision strategies for clinically applicable nonselective parallel-transmit pulses at 7 T

Purpose: To investigate the effects of using different parallel-transmit (pTx) head coils and specific absorption rate (SAR) supervision strategies on pTx pulse design for ultrahigh-field MRI using a 3D-MPRAGE sequence. Methods: The PTx universal pulses (UPs) and fast online-customized (FOCUS) pulses were designed with pre-acquired data sets (B0, B1+ maps, specific absorption rate [SAR] supervision data) from two different 8 transmit/32 receive head coils on two 7T whole-body MR systems. For one coil, the SAR supervision model consisted of per-channel RF power limits. In the other coil, SAR estimations were done with both per-channel RF power limits as well as virtual observation points (VOPs) derived from electromagnetic field (EMF) simulations using three virtual human body models at three different positions. All pulses were made for nonselective excitation and inversion and evaluated on 132 B0, B1+, and SAR supervision datasets obtained with one coil and 12 from the other. At both sites, 3 subjects were examined using MPRAGE sequences that used UP/FOCUS pulses generated for both coils. Results: For some subjects, the UPs underperformed when simulated on a different coil from which they were derived, whereas FOCUS pulses still showed acceptable performance in that case. FOCUS inversion pulses outperformed adiabatic pulses when scaled to the same local SAR level. For the self-built coil, the use of VOPs showed reliable overestimation compared with the ground-truth EMF simulations, predicting about 52% lower local SAR for inversion pulses compared with per-channel power limits. Conclusion: FOCUS inversion pulses offer a low-SAR alternative to adiabatic pulses and benefit from using EMF-based VOPs for SAR estimation