The Origin of Chalcogen-Bonding Interactions

Favorable molecular interactions between group 16 elements have been implicated in catalysis, biological processes, and materials and medicinal chemistry. Such interactions have since become known as chalcogen bonds by analogy to hydrogen and halogen bonds. Although the prevalence and applications of chalcogen-bonding interactions continues to develop, debate still surrounds the energetic significance and physicochemical origins of this class of σ-hole interaction. Here, synthetic molecular balances were used to perform a quantitative experimental investigation of chalcogen-bonding interactions. Over 160 experimental conformational free energies were measured in 13 different solvents to examine the energetics of O···S, O···Se, S···S, O···HC, and S···HC contacts and the associated substituent and solvent effects. The strongest chalcogen-bonding interactions were found to be at least as strong as conventional H-bonds, but unlike H-bonds, surprisingly independent of the solvent. The independence of the conformational free energies on solvent polarity, polarizability, and H-bonding characteristics showed that electrostatic, solvophobic, and van der Waals dispersion forces did not account for the observed experimental trends. Instead, a quantitative relationship between the experimental conformational free energies and computed molecular orbital energies was consistent with the chalcogen-bonding interactions being dominated by n → σ* orbital delocalization between a lone pair (n) of a (thio)­amide donor and the antibonding σ* orbital of an acceptor thiophene or selenophene. Interestingly, stabilization was manifested through the same acceptor molecular orbital irrespective of whether a direct chalcogen···chalcogen or chalcogen···H–C contact was made. Our results underline the importance of often-overlooked orbital delocalization effects in conformational control and molecular recognition phenomena

RNA-seq and metabolomic analyses of Akt1-mediated muscle growth reveals regulation of regenerative pathways and changes in the muscle secretome

A schematic representation of gene expression changes in the oxidative phosphorylation pathway. (PDF 590 kb

Rollover Risk and Tax Avoidance

This study examines the association between rollover risk and tax avoidance. Rollover risk, also referred to as refinancing risk, is the risk that firms are not able to obtain new debt to refinance their existing debt. On the one hand, firms may avoid taxes to generate cash internally. On the other hand, tax avoidance can increase the cost of debt. Our findings suggest that, in general, a positive relationship exists between rollover risk and tax avoidance. In cross-sectional analyses, we find that the positive association between rollover risk and tax avoidance is more (less) pronounced for firms with financial constraints (alternative financing sources). Additional analyses reveal that this positive association is attenuated when the market interest rates are higher. Furthermore, financially constrained firms operating in a higher market interest rates environment exhibit a further reduction in the positive association between rollover risk and tax avoidance. Finally, we find that firms engage in tax avoidance in anticipation of debt maturing in the following year. The findings are informative to shareholders and policy makers who have an interest in shaping firms’ tax avoidance activities

Nestin Is Essential for Zebrafish Brain and Eye Development through Control of Progenitor Cell Apoptosis

BACKGROUND: Nestin is expressed in neural progenitor cells (NPC) of developing brain. Despite its wide use as an NPC marker, the function of nestin in embryo development is unclear. METHODOLOGY/PRINCIPAL FINDINGS: As nestin is conserved in zebrafish and its predicted sequence is clustered with the mammalian nestin orthologue, we used zebrafish as a model to investigate its role in embryogenesis. Injection of nestin morpholino (MO) into fertilized eggs induced time- and dose-dependent brain and eye developmental defects. Nestin morphants exhibited characteristic morphological changes including small head, small eyes and hydrocephalus. Histological examinations show reduced hind- and mid-brain size, dilated ventricle, poorly organized retina and underdeveloped lens. Injection of control nestin MO did not induce brain or eye changes. Nestin MO injection reduced expression of ascl1b (achaete-scute complex-like 1b), a marker of NPCs, without affecting its distribution. Nestin MO did not influence Elavl3/4 (Embryonic lethal, abnormal vision, Drosophila-like 3/4) (a neuronal marker), or otx2 (a midbrain neuronal marker), but severely perturbed cranial motor nerve development and axon distribution. To determine whether the developmental defects are due to excessive NPC apoptosis and/or reduced NPC proliferation, we analyzed apoptosis by TUNEL assay and acridine orange staining and proliferation by BrdU incorporation, pcna and mcm5 expressions. Excessive apoptosis was noted in hindbrain and midbrain cells. Apoptotic signals were colocalized with ascl1b. Proliferation markers were not significantly altered by nestin MO. CONCLUSION/SIGNIFICANCE: These results suggest that nestin is essential for zebrafish brain and eye development probably through control of progenitor cell apoptosis

A correlation study between in-brace correction, compliance to spinal orthosis and health-related quality of life of patients with Adolescent Idiopathic Scoliosis

BACKGROUND: It has been proposed that in-brace correction is the best guideline for prediction of the results of brace treatment for patients with Adolescent Idiopathic Scoliosis (AIS). However, bracing may be a stressful experience for patients and bracing non-compliance could be psychologically related. The purpose of this study was to assess the correlation between brace compliance, in-brace correction and QoL of patients with AIS. METHODS: Fifty-five patients with a diagnosis of AIS were recruited. All were female and aged 10 years or above when a brace was prescribed, none had undergone prior treatment, and all had a Risser sign of 0–2 and a Cobb angle of 25-40°. The patients were examined in three consecutive visits with 4 to 6 months between each visit. The Chinese translated Trunk Appearance Perception Scale (TAPS), the Chinese translated Brace Questionnaires (BrQ) and the Chinese translated SRS-22 Questionnaires were used in the study. The in-brace Cobb angle, vertebral rotation and trunk listing were also measured. Patients’ compliance, in-brace correction and patients’ QoL were assessed. To identify the relationship among these three areas, logistic regression model and generalized linear model were used. RESULT: For the compliance measure, a significant difference (p = 0.008) was detected on TAPS mean score difference between Visit 1 and Visit 2 in the least compliant group (0–8 hours) and the most compliant group (17–23 hours). In addition, a significant difference (p = 0.000) was detected on BrQ mean score difference between Visit 2 and Visit 3 in the least compliant group (0–8 hours) and the most compliant group (17–23 hours). For the orthosis effectiveness measure, no significant difference was detected between the three groups of bracing hours (0–8 hours, 9–16 hours, 17–23 hours) on in-brace correction (below 40% and 40% or above). For the QoL measure, no significant difference was detected between the two different in-brace correction groups (below 40% and 40% or above) on QoL as reflected by the TAPS, BrQ and SRS-22r mean scores. CONCLUSION: The results showed a positive relationship between patients’ brace wear compliance and patients’ QoL. Poor compliance would cause a lower QoL

Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen

Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp²-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C–H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C–H arylation/Cu­(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls

Eikonal Approximation for Coupled Equations for Multichannel Scattering

It is well known that the Glauber approximation for scattering amplitudes is obtained by applying the eikonal approximation to the Fourier transform of the transition operator. The eikonal approximation can also be applied to the coupled equations of scattering obtained by the expansion of the state function in terms of a suitable set of functions. The scattering amplitude can thus be obtained by solving the set of eikonal coupled equations. The latter approach is analyzed for a special class of channel-coupling potentials. The first-order approximation to the derived eikonal coupled equations is the eikonal Born approximation. Numerical illustrations in this approximation are given for the 1s-2s and 1s-2p excitations of hydrogen atoms by electron and positron impact. The results are compared with those obtained in the Glauber eikonal approximation and with experimental measurements

Gender effects on cytidine analogue metabolism and myelodysplastic syndrome treatment outcomes

In vivo, half-lives of cytidine analogues such as 5-azacytidine and decitabine, used to treat myelodysplastic syndromes (MDS), are determined largely by cytidine deaminase (CDA), an enzyme that rapidly metabolizes these drugs into inactive uridine counterparts. Genetic factors influence CDA activity, and hence, could impact 5-azacytidine/decitabine levels and efficacy, a possibility requiring evaluation. Using an HPLC assay, plasma CDA activity was confirmed to be decreased in individuals with the CDA SNP A79C. More interestingly, there was an even larger decrease in females. Explaining the decrease in enzyme activity, liver CDA expression was significantly lower in female versus male mice. As expected, decitabine plasma levels, measured by mass-spectrometry, were significantly higher in females. In mathematical modeling, the detrimental effect of shortening half-life of S-phase specific therapy was amplified in low S-phase fraction disease (e.g., MDS). Accordingly, in multivariate analysis of MDS patients treated with 5-azacytidine/decitabine, overall survival was significantly worse in males

Control of Formation-Flying Multi-Element Space Interferometers with Direct Interferometer-Output Feedback

The long-baseline space interferometer concept involving formation flying of multiple spacecrafts holds great promise as future space missions for high-resolution imagery. A major challenge of obtaining high-quality interferometric synthesized images from long-baseline space interferometers is to accurately control these spacecraft and their optics payloads in the specified configuration. Our research focuses on the determination of the optical errors to achieve fine control of long-baseline space interferometers without resorting to additional sensing equipment. We present a suite of estimation tools that can effectively extract from the raw interferometric image relative x/y, piston translational and tip/tilt deviations at the exit pupil aperture. The use of these error estimates in achieving control of the interferometer elements is demonstrated using simulated as well as laboratory-collected interferometric stellar images

Management of tracheobronchial obstruction in infants using metallic stents: long-term outcome

© 2015, Springer-Verlag Berlin Heidelberg. Results: Twelve balloon-expandable metallic stents were placed in the trachea (n = 10) and/or bronchi (n = 2) of 5 patients with a median age of 13 months (range 5–30 months). Etiology of the airway obstruction included congenital tracheal stenosis (n = 4), giant cervical and superior mediastinal lymphatic malformation with tracheobronchomalacia (n = 1). Seven complications were reported (3 patients developed granulation tissue, 2 patients had re-stenosis, 1 stent migrated, 1 stent fractured). All patients survived and were in good condition with a median follow-up of 16 years (range 11–18 years). Three patients weaned off ventilator and oxygen. Conclusions: Endoscopic stenting with metallic stent has satisfactory long-term outcome in treating infants with tracheobronchial obstruction. Introduction: Tracheobronchial obstruction, although uncommon in the pediatric age group, remains a challenging problem. We review the long-term outcome of endoscopic metallic stenting in infants with tracheobronchial obstruction. Materials and methods: Medical records of all pediatric surgical patients who underwent tracheobronchial metallic stenting in our center were reviewed retrospectively from 1996 to 2014. Patients’ demographic data, including etiology, associated anomalies and nature of obstruction were reviewed. Outcome measures include complications such as re-stenosis, granulation tissue, stent migration, fractured stent, maximal tracheal diameter achieved, weaning of ventilator and growth at interval follow-up.postprin