Nox2 redox signaling maintains essential cell populations in the brain.

Reactive oxygen species (ROS) are conventionally classified as toxic consequences of aerobic life, and the brain is particularly susceptible to ROS-induced oxidative stress and damage owing to its high energy and oxygen demands. NADPH oxidases (Nox) are a widespread source of brain ROS implicated in seizures, stroke and neurodegeneration. A physiological role for ROS generation in normal brain function has not been established, despite the fact that mice and humans lacking functional Nox proteins have cognitive deficits. Using molecular imaging with Peroxyfluor-6 (PF6), a new selective fluorescent indicator for hydrogen peroxide (H(2)O(2)), we show that adult hippocampal stem/progenitor cells (AHPs) generate H(2)O(2) through Nox2 to regulate intracellular growth signaling pathways, which in turn maintains their normal proliferation in vitro and in vivo. Our results challenge the traditional view that brain ROS are solely deleterious by demonstrating that controlled ROS chemistry is needed for maintaining specific cell populations

Second-generation PLINK: rising to the challenge of larger and richer datasets

PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.Comment: 2 figures, 1 additional fil

Management of Elbow Dislocations in the National Football League.

Background: Although much literature exists regarding the treatment and management of elbow dislocations in the general population, little information is available regarding management in the athletic population. Furthermore, no literature is available regarding the postinjury treatment and timing of return to play in the contact or professional athlete. Purpose: To review the clinical course of elbow dislocations in professional football players and determine the timing of return to full participation. Study Design: Case series; Level of evidence, 4. Methods: All National Football League (NFL) athletes with elbow dislocations from 2000 through 2011 who returned to play during the season were identified from the NFL Injury Surveillance System (NFL ISS). Roster position, player activity, use of external bracing, and clinical course were reviewed. Mean number of days lost until full return to play was determined for players with elbow dislocations who returned in the same season. Results: From 2000 to 2011, a total of 62 elbow dislocations out of 35,324 injuries were recorded (0.17%); 40 (64.5%) dislocations occurred in defensive players, 12 (19.4%) were in offensive players; and 10 (16.1%) were during special teams play. Over half of the injuries (33/62, 53.2%) were sustained while tackling, and 4 (6.5%) patients required surgery. A total of 47 (75.8%) players who sustained this injury were able to return in the same season. For this group, the mean number of days lost in players treated conservatively (45/47) was 25.1 days (median, 23.0 days; range, 0.0-118 days), while that for players treated operatively (2/47) was 46.5 days (median, 46.5 days; range, 29-64 days). Mean return to play based on player position was 25.8 days for defensive players (n = 28; median, 21.5 days; range, 3.0-118 days), 24.1 days for offensive players (n = 11; median, 19 days; range, 2.0-59 days), and 25.6 days for special teams players (n = 8; median, 25.5 days; range, 0-44 days). Conclusion: Elbow dislocations comprise less than a half of a percent of all injuries sustained in the NFL. Most injuries occur during the act of tackling, with the majority of injured athletes playing a defensive position. Players treated nonoperatively missed a mean of 25.1 days, whereas those managed operatively missed a mean of 46.5 days

Chemistry and radiative shielding in star forming galactic disks

To understand the conditions under which dense, molecular gas is able to form within a galaxy, we post-process a series of three-dimensional galactic-disk-scale simulations with ray-tracing based radiative transfer and chemical network integration to compute the equilibrium chemical and thermal state of the gas. In performing these simulations we vary a number of parameters, such as the ISRF strength, vertical scale height of stellar sources, cosmic ray flux, to gauge the sensitivity of our results to these variations. Self-shielding permits significant molecular hydrogen (H2) abundances in dense filaments around the disk midplane, accounting for approximately ~10-15% of the total gas mass. Significant CO fractions only form in the densest, n>~10^3 cm^-3, gas where a combination of dust, H2, and self-shielding attenuate the FUV background. We additionally compare these ray-tracing based solutions to photochemistry with complementary models where photo-shielding is accounted for with locally computed prescriptions. With some exceptions, these local models for the radiative shielding length perform reasonably well at reproducing the distribution and amount of molecular gas as compared with a detailed, global ray tracing calculation. Specifically, an approach based on the Jeans Length with a T=40K temperature cap performs the best in regards to a number of different quantitative measures based on the H2 and CO abundances.Comment: 21 Pages, 15 figures. Submitted to MNRAS. Comments welcom

Magneto-optic Kerr effect in a spin-polarized zero-moment ferrimagnet

The magneto-optical Kerr effect (MOKE) is often assumed to be proportional to the magnetisation of a magnetically ordered metallic sample; in metallic ferrimagnets with chemically distinct sublattices, such as rare-earth transition-metal alloys, it depends on the difference between the sublattice contributions. Here we show that in a highly spin polarized, fully compensated ferrimagnet, where the sublattices are chemically similar, MOKE is observed even when the net moment is strictly zero. We analyse the spectral ellipsometry and MOKE of Mn 2 Ru x Ga, and show that this behaviour is due to a highly spin-polarized conduction band dominated by one of the two manganese sublattices which creates helicity-dependent reflectivity determined by a broad Drude tail. Our findings open new prospects for studying spin dynamics in the infra-red.Comment: 7 pages, 7 figure

Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens

Purpose Hydrogen peroxide (H2O2) is an endogenously produced reactive oxygen species (ROS) present in a variety of mammalian systems. This particular ROS can play dichotomous roles, being beneficial in some cases and deleterious in others, which reflects the level and location of H2O2 production. While much is known about the redox regulation of ROS by antioxidant and repair systems in the lens, little is known about the endogenous production of H2O2 in embryonic lens tissue or the physiologic relevance of endogenous H2O2 to lens development. This gap in knowledge exists primarily from a lack of reagents that can specifically detect endogenous H2O2 in the intact lens. Here, using a recently developed chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6-AM), which selectively detects H2O2 over related ROS, we examined the endogenous H2O2 signals in the embryonic lens. Methods: Embryonic day 10 chick whole lenses in ex vivo organ culture and lens epithelial cells in primary culture were loaded with the H2O2 probe PF6-AM. To determine the relationship between localization of mitochondria with active membrane potential and the region of H2O2 production in the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks generation of intracellular ROS production, was used to confirm that the signal from PF6-AM was due to endogenous ROS production. All imaging was performed by live confocal microscopy. Results: PF6-AM detected endogenous H2O2 in lens epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells grown in primary culture. No endogenous H2O2 signal could be detected in differentiating lens fiber cells with this probe. Treatment with DPI markedly attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the lens epithelium, suggesting that basal generation of ROS occurs in this region. The lens epithelial cells producing an endogenous H2O2 signal were also rich in actively respiring mitochondria. Conclusions: PF6-AM can be used as an effective reagent to detect the presence and localization of endogenous H2O2 in live lens cells

ABA Triblock Brush Polymers: Synthesis, Self-Assembly, Conductivity, and Rheological Properties

The synthesis, self-assembly, conductivity, and rheological properties of ABA triblock brush polymers (BBCPs) with grafted polystyrene (A block, N_(PS) = 21) and poly(ethylene oxide) (B block, N_(PEO) = 45) side chains are reported. Two backbone molecular weights (N_A:N_B:N_A = 11:78:11 and 15:119:15) were investigated with lithium bis(trifluoromethane)sulfonimide (LiTFSI) doping ratios 2 ≤ [EO]:[Li+] ≤ 20. Blends with 2 ≤ [EO]:[Li+] ≤ 10 suppress PEO crystallization and self-assemble into hexagonally packed cylinders of the minority gPS component. Conductivity is on the order of 10^(–3) S/cm at 105 °C with a corresponding elastic modulus ca. 10^4 Pa. The optimum conductivity occurs at a blend ratio near 10:1 [EO]:[Li+], similar to that reported for linear block copolymer analogues

Transhiatal esophagectomy in the profoundly obese: implications and experience.

BACKGROUND: Historically, obesity contraindicated an abdominal approach to the esophagogastric junction. The technique of transhiatal esophagectomy (THE) evolved without specific regard to body habitus. The dramatic increase in obese patients requiring an esophagectomy for complications of reflux disease prompted this evaluation of the impact of obesity on the outcomes of esophagectomy to determine whether profound obesity should contraindicate the transhiatal approach. METHODS: We used our Esophagectomy Database to identify 133 profoundly obese patients (body mass index [BMI] > or = 35 kg/m2) from among 2176 undergoing a THE from 1977 to 2006. This group was matched to a randomly selected, non-obese (BMI, 18.5 to 30 kg/m2) control population of 133 patients. Intraoperative, postoperative, and long-term follow-up results were compared retrospectively. RESULTS: Profoundly obese patients had significantly greater intraoperative blood loss (mean, 492.2 mL versus 361.8 mL, p = 0.001), need for partial sternotomy (18 versus 3, p = 0.001), and frequency of recurrent laryngeal nerve injury (6 versus 0, p = 0.04). The two groups did not differ significantly in the occurrence of chylothorax, wound infection, or dehiscence rate; length of hospital stay or need for intensive care unit stay; or hospital or operative mortality. Follow-up results for dysphagia, dumping, regurgitation, and overall functional score were also comparable between the two groups. CONCLUSIONS: With appropriate instrumentation, transhiatal esophagectomy in obese patients has similar morbidity and outcomes as in non-obese patients. Obesity, even when profound, does not contraindicate a transhiatal esophagectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/6/Scipione 2007.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/5/Benign BMI Control.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/4/Benign BMI CS07.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/3/CA BMI Control no pt id.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/2/CA BMI 35 CS.tx