Searching and fixating: scale-invariance vs. characteristic timescales in attentional processes

In an experiment involving semantic search, the visual movements of sample populations subjected to visual and aural input were tracked in a taskless paradigm. The probability distributions of saccades and fixations were obtained and analyzed. Scale-invariance was observed in the saccadic distributions, while the fixation distributions revealed the presence of a characteristic (attentional) time scale for literate subjects. A detailed analysis of our results suggests that saccadic eye motions are an example of Levy, rather than Brownian, dynamics.Comment: Accepted to Europhysics Letters (2011

PRELIMINARY STUDIES ON BRAIN TARGETING OF INTRANASAL ATOMOXETINE LIPOSOMES

Objective: The objective of the present study was to evaluate the enhancement in brain uptake of liposomes containing atomoxetine (ATX-Lipo) for intranasal delivery in the management of Attention Deficit Hyperactivity Disorder (ADHD).Methods: ATX-Lipo and ATX mucoadhesive liposomes (ATX-Muco Lipo) with and without a vasoconstrictor phenylephrine (PHE) were prepared by lipid film hydration method and characterized for physicochemical parameters. Biodistribution and pharmacokinetic evaluation of ATX-Lipo in the brain and blood of Sprague Dawley rats following intranasal (i. n.) and intravenous (i. v.) administrations were examined using optimized technetium-labeled ([99]m Tc-labeled) atomoxetine formulations. Gamma scintigraphy imaging was performed in Sprague Dawley rats.Results: ATX-Lipo and ATX-Muco Lipo were found to be stable with average particle size of 404.35±1.86 nm and 510.50±1.22 nm respectively.[99]mTc tagged ATX-Lipo, ATX-Muco Lipo, ATX+PHE-Muco Lipo and ATX solution were found to be stable and suitable for in vivo studies. On comparing ATX concentrations after i. n. administrations of ATX-Lipo, ATX-Muco Lipo and ATX+PHE-Muco Lipo and i. v. administration of ATX-Lipo, brain/blood uptake ratios (BBR) at 30 min were found to be 0.161, 1.255, 0.331, and 0.003 respectively. These results revealed effective brain targeting following i. n. administration of mucoadhesive ATX liposomes. Higher drug targeting efficiency (% DTE) and direct transport percentage (%DTP) for mucoadhesive liposomes indicated considerable brain targeting from ATX-Muco liposomes. Gamma scintigraphy imaging of the rat brain conclusively demonstrated the greater extent of transport of atomoxetine by ATX+PHE-Muco Lipo (i. n.), when compared with ATX solution (i. n.) into the rat brain.Conclusion: This preliminary investigation demonstrates a considerable extent of transport of ATX into the brain through i. n. ATX+PHE-Muco Lipo, which may prove to be a new platform for better management of ADHD.Keywords: Intranasal delivery, Brain targeting, Mucoadhesive liposomes, Vasoconstrictor, Radiolabeling, Drug targeting efficiency, Direct transport percentage, Gamma scintigraphy

Scaffold Diversity through a Branching Double Annulation Cascade Strategy: An Iminium Induced One-pot Synthesis of Diverse Fused Tetrahydroisoquinoline (THIQ) Scaffolds

A branching double annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium induced one-pot double cyclization sequence involving Pictect-Spengler type cyclization has been developed for the first time. The salient features of this protocol are direct and rapid access to unprecedented diverse fused THIQ skeletons, metal/catalyst free, cleaner reaction profile, good to excellent yields and convenient approach. This catalyst-free domino process facilitates the double annulation with variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bonds formation in a single step, under uniform reaction conditions. Furthermore, we reveal an unusual dual BDAC sequence leading to N-N linked isoquinoline dimer

Combinatorial screening yields discovery of 29 metal oxide photoanodes for solar fuel generation

Combinatorial synthesis combined with high throughput electrochemistry enabled discovery of 29 ternary oxide photoanodes, 15 with visible light response for oxygen evolution. Y₃Fe₅O₁₂ and trigonal V₂CoO₆ emerge as particularly promising candidates due to their photorepsonse at sub-2.4 eV illumination

Comparative study of chlorhexidine dressings versus simple gauze dressings in midline laparotomy wound

Background: Wound infections are the most common complication of surgery that adds significantly to the morbidity of the patient and the cost of the treatment. Most of the surgical site infections are preventable. Dressing is an active element of wound management, designed to control infection and promote healing. This study was done to compare clinical efficacy of normal gauze dressings versus chlorhexidine dressings in midline laparotomy wounds.Methods: Patients with midline laparotomy incision were randomized to receive either gauze or chlorhexidine dressings. Bacterial colonization, post- operative fever, frequency of infection, change of dressings, hospital stay and postoperative pain were assessed at the start of treatment and at weekly intervals until full healing occurred.Results: A total of 128 patients were enrolled in the study and divided into 2 groups viz chlorhexidine group (Group A) and Simple gauze group (Group B) with 64 patients each. Wound cultures, change of antibiotics, post-operative soakage, median hospital stay duration, postoperative pain, post- operative wound infection, and follow up visits for wound healing were compared between two groups A and B and statistical significance established.Conclusions: The analysis of wound culture, fever incidence and frequency of infection on Chlorhexidine dressings showed decreasing trends compared to traditional dressings

To assess the role of multisite instillation of bupivacaine-xylocaine combination for reducing post-operative pain after elective laparoscopic cholecystectomy

Background: Pain following laparoscopic surgery is multifactorial, arising from trocar sites (somatic pain), operative site (visceral pain) and shoulder pain (referred from diaphragmatic irritation because of pneumo-peritoneum). Currently no standard of care exists to reduce post-operative pain by use of local analgesia in laparoscopic cholecystectomy. Despite many studies, there are contradictory results. Aim of the study was to assess whether instillation of local anaesthetics at trocar sites and intraperitoneally, reduces the amount of pain experienced in the immediate postoperative period after laparoscopic cholecystectomy.Methods: This prospective study was carried out in the Department of General Surgery in a tertiary medical Centre in Mumbai. 75 subjects were randomized into 2 groups. Group A consisting of 38 patients were subjected to multisite instillation of LA combination (bupivacaine+xylocaine) at trocar site, gall bladder fossa, sub diaphragmatic space. Group B, (control group) consisting of 37 patients was given no such LA. Post operatively, pain was assessed by VAS scale (0-100) at 1,4,24 hours. Both the groups were compared and analysed.Results: Group A showed significantly reduced pain scores at 1, 4 and 24 hours post operatively as compared to group B.Conclusions: Our results indicate that multisite infiltration of local anesthetic combination (bupivacaine+xylocaine) after laparoscopic cholecystectomy surgery significantly reduces pain at 1, 4 and 24 hours postoperatively

Heterosis for economic traits in coconut (Cocos nucifera L.)

Field studies conducted for a period of 12 years to assess the traits responsible for yield performance and heterosis of twelve coconut hybrids in comparison with three varieties showed that among the hybrids, GBGD x ECT recorded the highest mean yield of 127.6 nuts palm-1 year-1 and was on par with ECT x GBGD (106.9 nuts palm-1 year-1), COD x LCT (108.0 nuts palm-1 year-1) and WCT x MYD (107.6 nuts palm-1 year-1). Hybrid GBGD x PHOT recorded the highest fruit length (23.9 cm) followed by ECT x GBGD (23.3 cm). The hybrid ECT x GBGD recorded the highest values for most of the fruit characteristics viz., fruit breadth (17.3 cm), fruit weight (1180.0 g), husked fruit weight (758.0 g) and copra weight (231.1 g). The variety ‘Laccadive Ordinary’ recorded higher oil content (71.1%) compared to its hybrids, LCT x GBGD (70.8%), COD x LCT (70.0%) and LCT x COD (69.8%). Hybrids displayed substantial differences in their heterotic response for nut characters. The highest yielding hybrid, GBGD x ECT excelled its standard check by 40.8 per cent followed by LCT x COD (39.4%)

Can radiosensitivity associated with defects in DNA repair be overcome by mitochondrial-targeted antioxidant radioprotectors

Radiation oncologists have observed variation in normal tissue responses between patients in many instances with no apparent explanation. The association of clinical tissue radiosensitivity with specific genetic repair defects (Wegner's syndrome, Ataxia telangiectasia, Bloom's syndrome, and Fanconi anemia) has been well established, but there are unexplained differences between patients in the general population with respect to the intensity and rapidity of appearance of normal tissue toxicity including radiation dermatitis, oral cavity mucositis, esophagitis, as well as differences in response of normal tissues to standard analgesic or other palliative measures. Strategies for the use of clinical radioprotectors have included modalities designed to either prevent and/or palliate the consequences of radiosensitivity. Most prominently, modification of total dose, fraction size, or total time of treatment delivery has been necessary in many patients, but such modifications may reduce the likelihood of local control and/or radiocurability. As a model system in which to study potential radioprotection by mitochondrial-targeted antioxidant small molecules, we have studied cell lines and tissues from Fanconi anemia (Fancd2-/-) mice of two background strains (C57BL/6NHsd and FVB/N). Both were shown to be radiosensitive with respect to clonogenic survival curves of bone marrow stromal cells in culture and severity of oral cavity mucositis during single fraction or fractionated radiotherapy. Oral administration of the antioxidant GS-nitroxide, JP4-039, provided significant radioprotection, and also ameliorated distant bone marrow suppression (abscopal effect of irradiation) in Fancd2-/- mice. These data suggest that radiation protection by targeting the mitochondria may be of therapeutic benefit even in the setting of defects in the DNA repair process for irradiation-induced DNA double strand breaks. © 2014 Greenberger, Berhane, Shinde, Han Rhieu, Bernard, Wipf, Skoda and Epperly

In-situ Magnesium Diboride Superconducting Thin Films grown by Pulsed Laser Deposition

Superconducting thin films of MgB2 were deposited by Pulsed Laser Deposition on magnesium oxide and sapphire substrates. Samples grown at 450C in an argon buffer pressure of about 10-2 mbar by using a magnesium enriched target resulted to be superconducting with a transition temperature of about 25 K. Film deposited from a MgB2 sintered pellet target in ultra high vacuum conditions showed poor metallic or weak semiconducting behavior and they became superconducting only after an ex-situ annealing in Mg vapor atmosphere. Up to now, no difference in the superconducting properties of the films obtained by these two procedures has been evidenced.Comment: 10 pages, 4 figure

De novo variants disturbing the transactivation capacity of POU3F3 cause a characteristic neurodevelopmental disorder

POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder