1,902 research outputs found

    Projectile-shape dependence of impact craters in loose granular media

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    We report on the penetration of cylindrical projectiles dropped from rest into a dry, noncohesive granular medium. The cylinder length, diameter, density, and tip shape are all explicitly varied. For deep penetrations, as compared to the cylinder diameter, the data collapse onto a single scaling law that varies as the 1/3 power of the total drop distance, the 1/2 power of cylinder length, and the 1/6 power of cylinder diameter. For shallow penetrations, the projectile shape plays a crucial role with sharper objects penetrating deeper.Comment: 3 pages, 3 figures; experimen

    Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

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    YesObjectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM:4-ASA cocrystals with different habits in order to investigate the effect on dissolution, and the derived powder properties of flow and compaction. Methods: Cocrystals were prepared in a 1:1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray-drying (habit IV). Key findings: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr’s compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. Conclusions: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behavior.Science Foundation Ireland. Grant Number: SFI/12/RC/227

    Neural Representations of Food-Related Attributes in the Human Orbitofrontal Cortex during Choice Deliberation in Anorexia Nervosa

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    Decisions about what to eat recruit the orbitofrontal cortex (OFC) and involve the evaluation of food-related attributes such as taste and health. These attributes are used differently by healthy individuals and patients with disordered eating behavior, but it is unclear whether these attributes are decodable from activity in the OFC in both groups and whether neural representations of these attributes are differentially related to decisions about food. We used fMRI combined with behavioral tasks to investigate the representation of taste and health attributes in the human OFC and the role of these representations in food choices in healthy women and women with anorexia nervosa (AN). We found that subjective ratings of tastiness and healthiness could be decoded from patterns of activity in the OFC in both groups. However, health-related patterns of activity in the OFC were more related to the magnitude of choice preferences among patients with AN than healthy individuals. These findings suggest that maladaptive decision-making in AN is associated with more consideration of health information represented by the OFC during deliberation about what to eat. SIGNIFICANCE STATEMENT An open question about the OFC is whether it supports the evaluation of food-related attributes during deliberation about what to eat. We found that healthiness and tastiness information was decodable from patterns of neural activity in the OFC in both patients with AN and healthy controls. Critically, neural representations of health were more strongly related to choices in patients with AN, suggesting that maladaptive overconsideration of healthiness during deliberation about what to eat is related to activity in the OFC. More broadly, these results show that activity in the human OFC is associated with the evaluation of relevant attributes during value-based decision-making. These findings may also guide future research into the development of treatments for AN

    Synthesis of a protected keto-lysidine analogue via improved preparation of arabino-isocytosine nucleosides

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    Anhydrouridines react with aliphatic amines to give N-alkyl isocytosines, but reported procedures often demand very long reaction times and can be low yielding, with narrow scope. A modified procedure for such reactions has been developed, using microwave irradiation, significantly reducing reaction time and allowing facile access to a diverse range of novel nucleosides on the gram scale. The method has been used to prepare a precursor to a novel analogue of lysidine, a naturally occurring iminonucleoside found in (t)RNA

    Unexpected Sources of Strontium to the Neuse and Cape Fear River Basins, North Carolina: Implications for the Global Strontium Isotope Budget in Seawater

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    Water, bedrock, and saprolite samples from the Neuse and Cape Fear River basins, North Carolina, were analyzed for 87Sr/86Sr and [Sr] to evaluate the control of exposed bedrock on fluvial Sr isotopic compositions and the influence of geology on Sr delivered to the ocean. The 87Sr/86Sr and [Sr] of the two rivers start low and rise downstream, eventually approximating recent ocean isotopic compositions before entering their estuaries. Groundwater samples from the headwaters have 87Sr/86Sr ratios that are lower than expected from the dominant exposed bedrock. The isotopic compositions of bedrock and saprolite samples vary predictably with rock type and age and show no correlation with degree of weathering. The data indicate that dominant surficial bedrock is not the primary source of Sr to the headwaters of the rivers. Rather, mafic dikes that focus groundwater flow and are more easily weathered than their silicic hosts impact the 87Sr/86Sr of the waters more than their limited exposure might suggest. Furthermore, the Sr isotopic composition of the water delivered to the marine environment is buffered by groundwater from coastal plain sedimentary rocks, leaving no evidence of upstream geology. The data suggest that rock type and structure exert significant control on the Sr isotope geochemistry of groundwater that enters into streams. Considering the global fluvial Sr budget, these results emphasize that, in some settings, (1) rock exposure area can be a poor indication of the geologic influence on Sr isotopic compositions of surface waters, and (2) downstream Sr isotopic compositions may not reflect upstream geology

    Perceived benefits of complementary and alternative medicine: A whole systems research perspective

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    The purpose of this study was to examine the benefits associated with complementary and alternative medicine (CAM) treatments from the patients’ perspective using a whole systems research approach as a guiding framework. We conducted five focus groups of six to eight participants each, with users of CAM recruited through experienced CAM providers and clinics. Eligible participants were aged 21 or older, had used CAM in the last 12 months, and believed the treatment to be beneficial. The focus group discussions were digitally recorded, transcribed, and analyzed through a qualitative content analysis. Responses were inductively coded for common themes, and then placed into broader conceptual categories reflecting the CAM outcome domains suggested by Verhoef and colleagues. Participants described physical health benefits including symptom relief and improved function, and positive psychological benefits such as improved coping and resilience. Social health benefits that arose from the positive aspects of the patient-practitioner relationship were also reported, including support and advocacy. In addition, participants identified empowerment, increased hope and spiritual growth as results of receiving CAM treatments. A new behavioral health outcome domain emerged as participants reported that CAM use had fostered behavioral changes such as increased exercise, smoking cessation and improving their diets. These patient-reported benefits of CAM treatment are consistent with the outcome model proposed by Verhoef and colleagues, and extend this model by identifying a new outcome domain—behavioral health outcome. The findings provide insight and direction for the development of outcome and process measures to evaluate CAM treatment effects

    CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy

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    SummaryObjectiveThe role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA.DesignOA was induced in 10 weeks old male wild type (WT), Ccl2−/− and Ccr2−/− mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6 h and 7 days post-surgery and examined by reverse transcription polymerase chain reaction (RT-PCR). Gene expression changes between naïve and DMM-operated mice were compared. Chondropathy scores, from mice at 8, 12, 16 and 20 weeks post DMM were calculated using modified Osteoarthritis Research Society International (OARSI) grading systems. Changes in hind paw weight distribution, as a measure of pain, were assessed by Linton incapacitance.ResultsAbsence of CCL2 strongly suppressed (>90%) selective inflammatory response genes in the joint 6 h post DMM, including arginase 1, prostaglandin synthase 2, nitric oxide synthase 2 and inhibin A. IL6, MMP3 and tissue inhibitor of metalloproteinase 1 were also significantly suppressed. Similar trends were also observed in the absence of CCR2. A lower average chondropathy score was observed in both Ccl2−/− and Ccr2−/− mice at 12, 16 and 20 weeks post DMM compared with WT mice, but this was only statistically significant at 20 weeks in Ccr2−/− mice. Pain-related behaviour in Ccl2−/− and Ccr2−/− mice post DMM was delayed in onset.ConclusionThe CCL2/CCR2 axis plays an important role in the development of pain in murine OA, but contributes little to cartilage damage
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