New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

Compound A, a Dissociated Glucocorticoid Receptor Modulator, Inhibits T-bet (Th1) and Induces GATA-3 (Th2) Activity in Immune Cells

Background: Compound A (CpdA) is a dissociating non-steroidal glucocorticoid receptor (GR) ligand which has antiinflammatory properties exerted by down-modulating proinflammatory gene expression. By favouring GR monomer formation, CpdA does not enhance glucocorticoid (GC) response element-driven gene expression, resulting in a reduced side effect profile as compared to GCs. Considering the importance of Th1/Th2 balance in the final outcome of immune and inflammatory responses, we analyzed how selective GR modulation differentially regulates the activity of T-bet and GATA-3, master drivers of Th1 and Th2 differentiation, respectively. Results: Using Western analysis and reporter gene assays, we show in murine T cells that, similar to GCs, CpdA inhibits T-bet activity via a transrepressive mechanism. Different from GCs, CpdA induces GATA-3 activity by p38 MAPK-induction of GATA-3 phosphorylation and nuclear translocation. CpdA effects are reversed by the GR antagonist RU38486, proving the involvement of GR in these actions. ELISA assays demonstrate that modulation of T-bet and GATA-3 impacts on cytokine production shown by a decrease in IFN-c and an increase in IL-5 production, respectively. Conclusions: Taken together, through their effect favoring Th2 over Th1 responses, particular dissociated GR ligands, fo

Yeast Screens Identify the RNA Polymerase II CTD and SPT5 as Relevant Targets of BRCA1 Interaction

BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1. These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1) to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, NUP188, POM34) and cytoplasmic mRNA decay at P-bodies (CCR4, DHH1). Strikingly, BRCA1 interacted with the phosphorylated RNA polymerase II (RNAPII) carboxy terminal domain (P-CTD), phosphorylated in the pattern specified by the CTDK-I kinase, to induce DEF1-dependent cleavage and accumulation of a RNAPII fragment containing the P-CTD. Significantly, breast cancer associated BRCT domain defects in BRCA1 that suppressed P-CTD cleavage and lethality in yeast also suppressed the physical interaction of BRCA1 with human SPT5 in breast epithelial cells, thus confirming SPT5 as a relevant target of BRCA1 interaction. Furthermore, enhanced P-CTD cleavage was observed in both yeast and human breast cells following UV-irradiation indicating a conserved eukaryotic damage response. Moreover, P-CTD cleavage in breast epithelial cells was BRCA1-dependent since damage-induced P-CTD cleavage was only observed in the mutant BRCA1 cell line HCC1937 following ectopic expression of wild type BRCA1. Finally, BRCA1, SPT5 and hyperphosphorylated RPB1 form a complex that was rapidly degraded following MMS treatment in wild type but not BRCA1 mutant breast cells. These results extend the mechanistic links between BRCA1 and transcriptional consequences in response to DNA damage and suggest an important role for RNAPII P-CTD cleavage in BRCA1-mediated cancer suppression

Observation of magnetic order in the heavy-fermion superconductor UBe13.

We have measured the magnetostriction L(H) of a single crystal of the heavy-fermion superconductor UBe13 using an all-silicon high-precision capacitance dilatometer. We find clear evidence for a transition to an antiferromagnetic state at TN 8.8 K, which is suppressed in a field by dTN/dH 0.36 K/T. At low temperatures we observe pronounced magnetostrictive oscillations, which we believe are de Haasvan Alphen oscillations due to an unusual aspect of the Fermi surface. © 1990 The American Physical Society

Observation of magnetic order in the heavy fermion superconductor UBe13

We have measured the magnetostriction, L(H), of a single crystal of the Heavy Fermion superconductor, UBe13, using an all silicon high precision capacitance dilatometer. We find clear evidence for a transition to an antiferromagnetic state at TN ∼ 8.8K, which is suppressed in a field by dTN/dH ∼ 0.36K/T. At low temperatures we observe pronounced magnetostrictive oscillations, which we believe are de Haas-van Alphen oscillations due to an unusual aspect of the Fermi surface. © 1990

Observation of magnetic order in the heavy-fermion superconductor UBe13.

We have measured the magnetostriction L(H) of a single crystal of the heavy-fermion superconductor UBe13 using an all-silicon high-precision capacitance dilatometer. We find clear evidence for a transition to an antiferromagnetic state at TN 8.8 K, which is suppressed in a field by dTN/dH 0.36 K/T. At low temperatures we observe pronounced magnetostrictive oscillations, which we believe are de Haasvan Alphen oscillations due to an unusual aspect of the Fermi surface. © 1990 The American Physical Society

Intubated Patients in a Neuroscience Intensive Care Unit Oral Health, Ventilator-Associated Pneumonia, and Intracranial Pressure in Email alerts

Background Although oral health affects systemic health, studies of oral health during intubation among critically ill neuroscience patients are lacking. Furthermore, the effect of oral care on intracranial pressure among critically ill patients in a neuroscience intensive care unit is unknown. Objectives To describe changes in oral health and development of ventilatorassociated pneumonia during intubation among patients in a neuroscience intensive care unit and to assess the influence of oral care on intracranial pressure. Methods Data on 45 consecutive intubated patients admitted to a neuroscience intensive care unit during 1 year were collected by using oral cultures and the Oral Assessment Guide throughout intubation and 48 hours after extubation. Occurrence of ventilator-associated pneumonia and intracranial pressures associated with oral care were recorded. Results Oral health, assessed by the Oral Assessment Guide, deteriorated significantly during intubation and improved to almost baseline levels 48 hours after extubation. During intubation, occurrence of oral gram-negative bacteria and yeast increased. The incidence of ventilator-associated pneumonia was 24% among patients enrolled for 4 to 10 days. During or after 879 instances of oral care, overall intracranial pressure did not increase. Among 30 instances in which intracranial pressure was greater than 20 mm Hg before oral care, pressure decreased during and 30 minutes after the procedure (P < .001). Conclusions Intubation may contribute to worsening of oral health among patients in neuroscience intensive care units. Execution of oral care does not seem to affect intracranial pressure adversely. Oral care should be explored further to promote good oral and systemic health in patients in neuroscience intensive care units and to determine its effect on ventilator-associated pneumonia