Flank solar wind interaction

This report summarizes the results of the first 12 months of our program to study the interaction of the Earth's magnetosphere with the solar wind on the far flanks of the bow shock. This study employs data from the ISEE-3 spacecraft during its traversals of the Earth's magnetotail and correlative data from spacecraft monitoring the solar wind upstream. Our main effort to date has involved assembling data sets and developing new plotting programs. Two talks were given at the Spring Meeting of the American Geophysical Union describing our initial results from analyzing data from the far flank foreshock and magnetosheath. The following sections summarize our results

Change in the magnitude of meiotic drive due to increased temperature

While major changes to chromosomal form is generally deleterious, karyotypes are not static. Major chromosomal rearrangements contribute to genetic isolation and divergence within and between species. As mechanisms that drive these divergences have not been fully elucidated. We hypothesize that meiotic drive, ie. bias transmission from parent to offspring, has contributed to the reshaping of karyotypes. Drosophila americana and Drosophila novamexicana are sister species that are an excellent model to study such evolutionary forces. Since diverging from D. novamexicana, D. americana has had two major chromosomal rearrangements: centromere fusions between the 2nd and 3rd chromosomes and the X and 4th chromosome. The X-4 chromosome has remained polymorphic. It is found in a latitudinal gradient along the Mississippi River. Northern populations contain more of the fused arrangement while southern populations have more of the unfused arrangement. With meiotic drive favoring the X-4 chromosome, it should fix in the population. There are two leading hypotheses explaining the polymorphic nature of the X-4 fused chromosome. First, the meiotic drive is only activated in times of stress, which is more consistent in Northern populations. Second, Meiotic drive occurs in all flies, but selection against the fused X-4 chromosome is high in climates that are more associated with the Southern United States. This study was intended to identify if increased temperature affects meiotic drive. We measured inheritance patterns from heterozygous females to offspring at an increased temperature. Then the offspring’s DNA was extracted. PCR and Gel electrophoresis was done to identify which chromosome was inherited

Assessment of quality of life in HAART-treated HIV-positive subjects with body fat redistribution in Rwanda

<p>Abstract</p> <p>Background</p> <p>The introduction of HAART has initially improved the quality of life (QoL) of HIV-positive (HIV+) patients, however body fat redistribution (BFR) and metabolic disorders associated with long-term HAART use may attenuate this improvement. As access to treatment improves in sub-Saharan Africa, the disfiguring nature of BFR (peripheral atrophy and/or central adiposity) may deter treatment adherence and initiatives and decrease QoL. We examined the relationship between BFR and domains of QoL in HAART-treated HIV+ African men and women with (HIV+BFR, n = 50) and without (HIV+noBFR, n = 50) BFR in Rwanda.</p> <p>Results</p> <p>HIV+ subjects with BFR were less satisfied with their body image (4.3 ± 0.1 versus 1.5 ± 0.2; p < .001), self-esteem and social life (4.1 ± 1.4 versus 2.1 ± 0.3; p = 0.003). HIV+BFR were more ashamed in public (4.5 ± 1.2 versus 1.1 ± 1.1), reported less confident about their health (4.6 ± 1.4 versus 1.5 ± 1.2) and were frequently embarrassed due to body changes (4.1 ± 1.1 versus 1.1 ± 0.9) (p < .001) than HIV+noBFR. HIV+ Rwandan women with BFR reported more dissatisfaction with psychological (8.3 ± 2.9 versus 13.7 ± 1.9), social relationships (6.9 ± 2.3 versus 11.1 ± 4.1) and HIV HAART-specific domain of wellbeing (3.1 ± 4.8 versus 6.3 ± 3.6) (p < .001). Age was associated with independence (r²= 0.691; <it>p </it>= 0.009) and marital status was associated with psychological (r²= 0.593; <it>p </it>= 0.019) and social relationships (r²= 0.493; <it>p </it>= 0.007). CD4 count (r²= 0.648; <it>p </it>= 0.003) and treatment duration (r²= 0.453; <it>p </it>= 0.003) were associated with HIV HAART-specific domain of wellbeing. HIV+ Rwandan women with BFR were significantly more affected by abdominal adiposity (p < .001), facial and buttocks atrophy (p < .05) than HIV+ men with BFR.</p> <p>Conclusion</p> <p>Body fat alterations negatively affect psychological and social domains of quality of life. These symptoms may result in stigmatization and marginalization mainly in HAART-treated African women, adversely affecting HAART adherence and treatment initiatives. Efforts to evaluate self-perceived body fat changes may improve patients' wellbeing, HAART adherence and treatment outcomes and contribute towards stability in quality of life continuum.</p

Intravenous meloxicam for the treatment of moderate to severe acute pain: a pooled analysis of safety and opioid-reducing effects.

BACKGROUND AND OBJECTIVES: To describe the safety and tolerability of intravenous meloxicam compared with placebo across all phase II/III clinical trials. METHODS: Safety data and opioid use from subjects with moderate to severe postoperative pain who received ≥1 dose of intravenous meloxicam (5-60 mg) or placebo in 1 of 7 studies (4 phase II; 3 phase III) were pooled. Data from intravenous meloxicam 5 mg, 7.5 mg and 15 mg groups were combined (low-dose subset). RESULTS: A total of 1426 adults (86.6% white; mean age: 45.8 years) received ≥1 dose of meloxicam IV; 517 (77.6% white; mean age: 46.7 years) received placebo. The incidence of treatment-emergent adverse events (TEAEs) in intravenous meloxicam and placebo-treated subjects was 47% and 57%, respectively. The most commonly reported TEAEs across treatment groups (intravenous meloxicam 5-15 mg, 30 mg, 60 mg and placebo, respectively) were nausea (4.3%, 20.8%, 5.8% and 25.3%), headache (1.5%, 5.6%, 1.6% and 10.4%), vomiting (2.8%, 4.6%, 1.6% and 7.4%) and dizziness (0%, 3.5%, 1.1% and 4.8%). TEAE incidence was generally similar in subjects aged \u3e65 years with impaired renal function and the general population. Similar rates of cardiovascular events were reported between treatment groups. One death was reported (placebo group; unrelated to study drug). There were 35 serious adverse events (SAEs); intravenous meloxicam 15 mg (n=5), intravenous meloxicam 30 mg (n=15) and placebo (n=15). The SAEs in meloxicam-treated subjects were determined to be unrelated to study medication. Six subjects withdrew due to TEAEs, including three treated with intravenous meloxicam (rash, localized edema and postprocedural pulmonary embolism). In trials where opioid use was monitored, meloxicam reduced postoperative rescue opioid use. CONCLUSIONS: Intravenous meloxicam was generally well tolerated in subjects with moderate to severe postoperative pain. TRIAL REGISTRATION NUMBERS: NCT01436032, NCT00945763, NCT01084161, NCT02540265, NCT02678286, NCT02675907 and NCT02720692

Selective Targeting of the TPX2 Site of Importin-α Using Fragment-Based Ligand Design.

Protein-protein interactions are difficult therapeutic targets, and inhibiting pathologically relevant interactions without disrupting other essential ones presents an additional challenge. Herein we report how this might be achieved for the potential anticancer target, the TPX2-importin-α interaction. Importin-α is a nuclear transport protein that regulates the spindle assembly protein TPX2. It has two binding sites--major and minor-to which partners bind. Most nuclear transport cargoes use the major site, whereas TPX2 binds principally to the minor site. Fragment-based approaches were used to identify small molecules that bind importin-α, and crystallographic studies identified a lead series that was observed to bind specifically to the minor site, representing the first ligands specific for this site. Structure-guided synthesis informed the elaboration of these fragments to explore the source of ligand selectivity between the minor and major sites. These ligands are starting points for the development of inhibitors of this protein-protein interaction.This work was supported by the University of Cambridge Cancer Research UK Medicinal Chemistry training program and Medical Research Council grant U105178939 (to M.S.).This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201500014/abstrac

Oral and intravenous bretylium disposition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109931/1/cptclpt1980190.pd

The Ursinus Weekly, March 5, 1951

Helfferich retains MAC title; Voted outstanding • Music Club lists HMS Pinafore as Spring production • Community Chest receives support • MSGA holds discussion on guests\u27 meal prices • Brownback receives material for May 4, 5 grad record exam • Dr. McClure to view Ursinus problems at YM-YWCA meeting • Group presentation of Condemned scores hit • DuPont lecturer shows new super light plastic • Larry Livingston, DuPont manager, to speak here • Dr. Yost to read poetry of Edna St. Vincent Millay • Administration receives additional data on draft • Seniors\u27 original Speak Easy ready for production • Lantern staff prepares issue; Meeting called • Notecrackers lose coin-tossing finals • Charles Lachman donates rug for Library faculty room • Red Cross drive begins • Rushing starts Monday • Editorial: Participation makes spirit; Support Red Cross; Lenten thoughts • L-shaped office is language office, where all is congeniality, cooperation, cordiality • Star gazers view sky, map moon through telescope atop Pfahler Hall • Staff grinds out The Weekly midst daily confusion • Swarthmore knocks Ursinus quintet from league contention in 78-56 win • Jerry Seeders awaits word on call to Army; Was captain in last war • Quintet winds up season in 95-62 loss to Blue Hens • Bear matmen rally, tie Drexel 14-14 • Belles defeat Penn to stay unbeaten • Mermaids capture fourth place in district intercollegiate meet • Club holds supperhttps://digitalcommons.ursinus.edu/weekly/1561/thumbnail.jp

Exercise training reduces central adiposity and improves metabolic indices in HAART-treated HIV-positive subjects in Rwanda: A randomized controlled trial

As HAART becomes more accessible in sub-Saharan Africa, metabolic syndromes, body fat redistribution (BFR), and cardiovascular disease may become more prevalent. We conducted a 6-month, randomized controlled trial to test whether cardiorespiratory exercise training (CET), improves metabolic, body composition and cardiorespiratory fitness parameters in HAART-treated HIV(+) African subjects with BFR. Six months of CET reduced waist circumference (−7.13 ± 4.4 cm, p < 0.0001), WHR (−0.10 ± 0.1, p < 0.0001), sum skinfold thickness (−6.15 ± 8.2 mm, p < 0.0001) and % body fat mass (−1.5 ± 3.3, p < 0.0001) in HIV(+)BFR(+)EXS. Hip circumference was unchanged in non-exercise control groups. CET reduced fasting total cholesterol (−0.03 ± 1.11 mM, p < 0.05), triglycerides (−0.22 ± 0.48 mM, p < 0.05) and glucose levels (−0.21 ± 0.71 mM, p < 0.05) (p < 0.0001). HDL-, LDL-cholesterol and HOMA values were unchanged after CET. Interestingly, HIV(+) subjects randomized to non-exercising groups experienced increases in fasting plasma glucose levels, whereas HIV seronegative controls did not (p < 0.001). Predicted VO(2) peak increased more in the HIV(+)BFR(+)EXS than in all other groups (4.7 ± 3.9 ml/kg/min, p < 0.0001). Exercise training positively modulated body composition and metabolic profiles, and improved cardiorespiratory fitness in HAART-treated HIV(+) Africans. These beneficial adaptations imply that exercise training is a safe, inexpensive, practical, and effective treatment for evolving metabolic and cardiovascular syndromes associated with HIV and HAART exposure in resource-limited sub-Saharan countries, where treatment is improving, morbidity and mortality rates are declining, but where minimal resources are available to manage HIV- and HAART-associated cardiovascular and metabolic syndromes