Chipping away at gamma-H2AX foci

The mammalian histone H2AX protein functions as a dosage-dependent genomic caretaker and tumor suppressor. Phosphorylation of H2AX to form gamma-H2AX in chromatin around DNA double strand breaks (DSBs) is an early event following induction of these hazardous lesions. For a decade, mechanisms that regulate H2AX phosphorylation have been investigated mainly through two-dimensional immunofluorescence (IF). We recently used chromatin immunoprecipitation (ChIP) to measure gamma-H2AX densities along chromosomal DNA strands broken in G(1) phase mouse lymphocytes. Our experiments revealed that (1) gamma-H2AX densities in nucleosomes form at high levels near DSBs and at diminishing levels farther and farther away from DNA ends, and (2) ATM regulates H2AX phosphorylation through both MDC1-dependent and MDC1-independent means. Neither of these mechanisms were discovered by previous if studies due to the inherent limitations of light microscopy. Here, we compare data obtained from parallel gamma-H2AX ChIP and three-dimensional IF analyses and discuss the impact of our findings upon molecular mechanisms that regulate H2AX phosphorylation in chromatin around DNA breakage sites

The Erratic Equity Position May Be Caused by FAS 52: An Investigation of the Results of Unrecognized Gains and Losses from Foreign Currency Translations

Financial Accounting Standards Board Statement No. 52 (FAS 52) replaced FAS 8 in 1981 and the new guidelines have been accepted widely for providing noncontroversial and adequate disclosure of foreign currency matters. The nine years since the adoption of FAS 52 have seen erratically fluctuating exchange rates, however, and the equity positions of many firms have responded accordingly. This article provides an investigation into the erratic equity positions and recommends actions that can be taken currently that may avoid future embarrassments for the profession

Excimer laser-facilitated balloon angioplasty of a nondilatable lesion

AbstractPreliminary clinical experience with excimer laser coronary angioplasty shows that it is a safe and effective means of achieving nonsurgical coronary revascularization in selected patients but specific indications for its use are as yet undefined. In the present report a specific indication is proposed for the use of the excimer laser: to facilitate balloon inflation in a rigid stenosis that fails to dilate despite high balloon inflation pressures

Effects of Hypovolemia on Cerebral Blood Velocity and Autoregulation During Upright Tilt: Implications for Post-Spaceflight Orthostasis

Orthostatic stability depends on maintenance of adequate cerebral blood flow. Orthostatic instability experienced by returning astronauts is associated with microgravity-induced hypovolemia, suggesting that hypovolemia may disrupt the ability of the cerebral vasculature to regulate blood flow. PURPOSE: To test the hypothesis that hypovolemia reduces cerebral blood velocity and impairs cerebral autoregulation (CA) during upright tilt. METHODS: Nine males (age 23 ± .5 yrs; height 172 ± 2 cm; weight 87 ± 3 kg; mean ± SE) were tilted head-up to 70° on two occasions separated by at least 5 days under euhydration (EUH) and dehydration (DEH) conditions. Dehydration was induced with 40 mg Furosemide and 8 h water restriction. Plasma volumes (PV) and blood volumes (BV) were estimated from venous hemoglobin and hematocrit. ECG, beat-by-beat finger arterial pressures, and cerebral blood velocity (CBV) were measured during a five min supine baseline, and during the first (T1) and last (T2) five min of upright tilt. Dynamic CA was assessed in the frequency domain with cross-spectral analysis of mean arterial pressure (MAP) and mean CBV within the frequency range of 0.07-0.2 Hz. RESULTS: Furosemide reduced PV by 10 ± 2 % and BV by 6 ± 2 % (P = .005 and P = .07). MAP decreased during tilt (P \u3c .007), but the reduction was similar between hydration conditions. CBV during DEH was lower during the entire 10-min tilt by about 7 cm/s (P \u3c .004) compared with EUH. Low frequency coherence was higher during DEH T1 compared with EUH T1 (.67 ± .04 vs .51 ± .04; P = .02), but coherence decreased as tilt continued, and was similar to EUH during T2 (P = 0.7). CONCLUSIONS: Increased coherence during the first 5 min of tilt suggests that reductions of CBV with hypovolemia might be explained by a reduced autoregulatory capacity. However, maintenance of lower CBV despite reduced coherence during the second 5 min of tilt suggests that disruptions of autoregulatory capacity with hypovolemia are transient. Our results provide evidence that hypovolemic astronauts may be at greatest risk for orthostatic intolerance immediately upon assumption of upright posture

Bostonia. Volume 15

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

1863-12-08 C.H. Sanborn inquires about George Holt who was wounded at Gettysburg

https://digitalmaine.com/cw_me_22nd_regiment_corr/1088/thumbnail.jp

Evaluation of automated decisionmaking methodologies and development of an integrated robotic system simulation, appendix A

A generic computer simulation for manipulator systems (ROBSIM) was implemented and the specific technologies necessary to increase the role of automation in various missions were developed. The specific items developed were: (1) Capability for definition of a manipulator system consisting of multiple arms, load objects, and an environment; (2) Capability for kinematic analysis, requirements analysis, and response simulation of manipulator motion; (3) Postprocessing options such as graphic replay of simulated motion and manipulator parameter plotting; (4) Investigation and simulation of various control methods including manual force/torque and active compliance control; (5) Evaluation and implementation of three obstacle avoidance methods; (6) Video simulation and edge detection; and (7) Software simulation validation. This appendix is the user's guide and includes examples of program runs and outputs as well as instructions for program use

Evaluation of automated decisionmaking methodologies and development of an integrated robotic system simulation

A generic computer simulation for manipulator systems (ROBSIM) was implemented and the specific technologies necessary to increase the role of automation in various missions were developed. The specific items developed are: (1) capability for definition of a manipulator system consisting of multiple arms, load objects, and an environment; (2) capability for kinematic analysis, requirements analysis, and response simulation of manipulator motion; (3) postprocessing options such as graphic replay of simulated motion and manipulator parameter plotting; (4) investigation and simulation of various control methods including manual force/torque and active compliances control; (5) evaluation and implementation of three obstacle avoidance methods; (6) video simulation and edge detection; and (7) software simulation validation

Ovarian Hormones and Cerebral Hemodynamics During Upright Tilt

The cerebral vasculature is a specific target for ovarian hormones. Estrogens in particular activate endothelial factors that decrease vessel tone and increase blood flow. Changes in cerebral blood flow across the menstrual cycle could underlie the observation that women experience orthostatic instability more often than men, but the influence of ovarian hormone levels on cerebral hemodynamics in the upright posture is unclear. PURPOSE: To test the hypothesis that cerebral blood velocity and cerebral autoregulatory capacity change in parallel with ovarian hormone concentrations. METHODS: Nine healthy eumenorrheic women (mean age 24 ± 1 yr, height 166 ± 3 cm, weight 68 ± 2 kg; mean ± SE) were studied during the early and late follicular (EF and LF) and early and late luteal (EL and LL) phases of the menstrual cycle. We recorded the ECG, beat-by-beat arterial pressure, end-tidal CO2, and cerebral blood velocity from the middle cerebral artery (transcranial Doppler). Plasma ovarian hormone concentrations were assessed with high performance liquid chromatography. Subjects breathed in time to a metronome for 10 min (15 breaths/min) in the supine position, and were then tilted head-up to 70° for an additional 10 min of controlled breathing. Cerebral autoregulation was assessed in the frequency domain with cross-spectral analysis of mean arterial pressure (MAP) and mean CBV within the frequency range of 0.07-0.2 Hz. RESULTS: Upright tilt decreased CBV (supine 74 ± 1.7; tilt 65 ± 1.8 cm ∙ s-1; P=.005 pooled across phases) and end-tidal CO2 (P\u3c.001) but did not affect MAP. Coherence increased from .45 ± .02 to .67 ± .03 with tilt (P\u3c .001 pooled across phases) and was significantly higher during LF (.61 ± .03) compared with LL (.48 ± .03; P = .04). Lower coherence during LL compared with LF was associated with higher concentrations of progesterone (P \u3c .001). CONCLUSIONS: Upright tilt decreases CBV, and the magnitude of reduction is not related to ovarian hormone concentrations. Lower coherence during LL compared with LF suggests improved autoregulatory capacity mediated by higher concentrations of progesterone. These results have implications for orthostatic stability in women