Approaching Free Fall on Two Degrees of Freedom: Simultaneous Measurement of Residual Force and Torque on a Double Torsion Pendulum.

A torsion pendulum with 2 soft degrees of freedom (DOFs), realized by off-axis cascading two torsion fibers, has been built and operated. This instrument helps characterize the geodesic motion of a test mass for LISA Pathfinder or any other free-fall space mission, providing information on cross talk and other effects that cannot be detected when monitoring a single DOF. We show that it is possible to simultaneously measure both the residual force and the residual torque acting on a quasifree test mass. As an example of the investigations that a double pendulum allows, we report the measurement of the force-to-torque cross talk, i.e., the amount of actuation signal, produced by applying a force on the suspended test mass, that leaks into the rotational DOF, detected by measuring the corresponding (unwanted) torque.

Sub-Femto-g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results.

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1 fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15} g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3) fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5 mHz we observe a low-frequency tail that stays below 12 fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

Thiol functionalised silica microsphere loaded polymeric hydrogel: Development of a novel hybrid sorbent for removal of lead and cadmium.

Current study presents a facile synthesis method for thiol functionalised silica microsphere loaded polymeric hydrogel. Silica microspheres were synthesised as core shell particles by sol-gel method followed by hydrolysis and condensation reaction to form the silica core. The silica was functionalised with thiol and the functionalised silica microsphere was subsequently impregnated into polymeric alginate matrix to form thiol functionalised silica microspheres loaded alginate hydrogel beads (SH-SiO2MS-Ca-Alg). The developed components and final products were characterised by BET, FTIR, DLS, SEM-EDS. The developed SH-SiO2MS-Ca-Alg hydrogel beads were used for efficient removal of Pb and Cd [72-97 % for Pb; 60-85 % for Cd at concentration range of 0.1-100 µg mL-1 and optimum pH 5-7] from aquatic medium. The sorption capacities evaluated for Pb and Cd from Langmuir isotherm were 127.99 and 70.68 mgg-1 respectively. Uptake kinetics, isotherm, thermodynamics, intraparticle diffusion studies were carried out for both Pb (II) and Cd (II). Mechanism of Pb (II) and Cd (II) removal by SH-SiO2MS-Ca-Alg hydrogel hybrid beads was proposed with the help of zeta potentials of SH-SiO2MS at different pH along with fraction diagram of Pb and Cd.

Development of a topical bacteriophage gel targeting Cutibacterium acnes for acne prone skin and results of a phase 1 cosmetic randomized clinical trial.

Background: Topical antibiotics are frequently used to treat acne vulgaris. Their prolonged use, often for longer durations than recommended, has led to antibiotic resistance in Cutibacterium acnes (C. acnes), a bacterium implicated in acne pathophysiology. Bacteriophage (phage), which specifically target C. acnes by a different mechanism of action and do not harm potentially beneficial bacteria, may offer an alternative approach for improvement of the appearance of acne prone skin. Objectives: To identify and characterize C. acnes targeting phage, carry out a comprehensive preclinical safety evaluation of phages selected for further development and examine their safety, tolerability and ability to target facial C. acnes when applied topically in a cosmetic clinical study including participants with mild-to-moderate acne. Methods: Phages were isolated by conventional microbiological methods also used to examine their breadth of host range on different C. acnes strains and specificity to this bacterial species. Safety assessment of three selected phages was carried out by complete genomic analysis to assure the absence of undesired sequences and by ex vivo models employed to evaluate the safety, irritability and potential systemic bioavailability of phage applied topically. A randomized, controlled clinical study assessed safety, tolerability and efficacy in targeting facial C. acnes. Results: Wide host range phages that also target antibiotic resistant C. acnes were identified. Their genomes were shown to be free of undesired genes. The three-phage cocktail, BX001, was not irritant to human skin or ocular tissues in ex vivo models and did not permeate through human epidermis. In a cosmetic clinical study, topically applied BX001 was safe and well tolerated and reduced the facial burden of C. acnes. Conclusions: Combined in silico and ex vivo approaches successfully predicted the observed safety and efficacy of C. acnes targeting phage when these were topically administered in a well-controlled cosmetic clinical study.

Design of the collection optics for the Core Plasma Thomson Scattering (CPTS) in ITER.

In the ITER Core Plasma Thomson Scattering, the scattered light collection optics system is installed both inside and outside the diagnostic port under vacuum. The length of the optical path (∼6 m) and the need to shield the neutron and γ radiation increased the complexity of the system with the inclusion of multiple dog-legs, forcing the use of many elements with optical power. Multiple rounds of design have been required in order to satisfy iteratively the system requirements in terms of resolution, aberration, and shielding. The adoption of quasi-free-form reflective surfaces for several mirrors eventually allowed the correct compromise between all conflicting requirements.

The level of urokinase-type plasminogen activator receptor is increased in serum of ovarian cancer patients.

Ascites and serum of patients with ovarian carcinoma contain a soluble form of urokinase-type plasminogen activator receptor (uPAR). We now report that pro-uPA-Sepharose-purified uPAR from ascites of patients with ovarian carcinoma is the full-length molecule missing the glycosyl-phosphatidylinositol anchor, as determined by its amino acid composition. We next examined the significance of determining serum soluble uPAR (suPAR) levels in ovarian cancer patients using a specific ELISA and compared the results with serum concentrations of CA-125, an established diagnostic marker. Serum from pre- and postoperative ovarian cancer patients was assayed for suPAR and CA-125. The majority of the patients with ovarian cancer had enhanced preoperative serum levels of suPAR compared with healthy controls, but suPAR concentrations decreased after operation. Although uPAR was associated with most ovarian carcinomas, it appeared to be a less specific indicator for ovarian cancer than CA-125. On the other hand, suPAR was more specific for other types of solid tumors. Moreover, we have observed some cases of ovarian cancer that showed increase of suPAR but not of CA-125. The prognostic significance of serum suPAR assay for survival of ovarian carcinoma patients was evaluated using Cox's proportional hazards analysis. Our preliminary data show that high preoperative levels of suPAR were associated with worse survival of the patients, whereas CA-125 had no prognostic implications. This is the first report evaluating the assay of serum suPAR levels in ovarian cancer and analyzing its value as a tumor or prognostic marker.

The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate.

Three times daily administration of isosorbide dinitrate may avoid much of the tolerance seen with more frequent dosing. To determine the daylong pattern of the antianginal effect of three times daily isosorbide dinitrate, eight men with stable exertional angina and a positive exercise test were studied. The subjects had demonstrated increased exercise duration in response to oral isosorbide dinitrate therapy and absence of complete tolerance to long-term three times daily isosorbide dinitrate. Treadmill exercise to onset of angina was performed over 2 days at 8 AM, 9 AM, 11 AM, 1 PM, 2 PM, 4 PM, 6 PM and 7 PM. On one day each patient received isosorbide dinitrate at 8 AM, 1 PM and 6 PM in a previously titrated dose (mean 27.5 mg), which had been taken three times daily for at least 2 weeks. On the other day at the same hours each patient received double blind a placebo identical in appearance to isosorbide dinitrate. One hour after the 8 AM dose of isosorbide dinitrate, mean systolic blood pressure at rest had fallen by 19 mm Hg and mean exercise time to angina increased by 200 s. However, by 11 AM exercise time had returned to control level. One hour after the 1 PM dose of isosorbide dinitrate, exercise time increased by a mean of 150 s but was again at control level 2 h later.(ABSTRACT TRUNCATED AT 250 WORDS)

Symptomatic sick sinus syndrome due to guanethidine. Case report.

A patient is described who developed symptomatic sinus bradycardia as low as 20 beats per minute and sinus arrest of up to 4.4 seconds while receiving guanethidine, 75 mg daily. The bradycardia resolved following discontinuation of the drug and reappeared upon challenge with it. Intrinsic disease of the sinoatrial and atrioventricular nodes was evidenced 3 weeks following discontinuation of the guanethidine by a borderline abnormally prolonged sinus node recovery time of 1500 msec and a PR interval of 0.28 seconds. Although sinus bradycardia is a known and not infrequent side effect of guanethidine, such an extreme form as seen in our patient appears to be quite rare, and may be related to the pre-existing disease of the conduction system.

Defining the proper role for self-administered sublingual nitroglycerin. A survey of physicians and patients.

Within a half-year period, we encountered six cases of patients harmed by the adverse effects of self-administered nitroglycerin--syncope, delayed definitive medical care, and the worsening of nonischemic symptoms. We therefore surveyed 112 patients after a remote myocardial infarction, and 121 cardiologists and internists, regarding the use of sublingual nitroglycerin. Of the physicians, 84 percent routinely prescribed nitroglycerin to patients after a myocardial infarction, and 79 percent of the patients had the tablets available (83 percent of these, at all times). Most patients used the tablets less than once per month, and 37 percent of the patients who always carried nitroglycerin had not used it at all during the preceding year. Although 89 percent of the patients claimed to know when to use the drug, 57 percent had used it or would use it for symptoms such as dizziness, rapid heartbeat, or presyncope. All patients having nitroglycerin claimed it relieved their symptoms, even if the relief was only partial, the time elapsed until relief could not be specified, and the symptoms were of a type unlikely to be relieved by the drug. We suggest that the practice of routinely prescribing nitroglycerin to patients after a myocardial infarction should be reassessed.

The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration.

This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical.

Prevention of lidocaine-infusion phlebitis by heparin and hydrocortisone.

Previous reports have suggested that infusions of lidocaine (lignocaine) cause a high incidence of phlebitis. We investigated the possibility of reducing this high incidence by the addition of small amounts of heparin or hydrocortisone (or both) to the infusate of lidocaine. One hundred patients with acute myocardial infarction who were to receive a 48-hour prophylactic infusion of lidocaine (2.25 mg/min) were randomized to have one of the following added to their infusate in double-blind fashion: (1) placebo; (2) heparin (4,000 units/24 hr); (3) hydrocortisone (20 mg/24 hr); or (4) heparin and hydrocortisone. After 48 hours the incidence of phlebitis was 94 percent in the control group but only 41 percent in the group receiving heparin and hydrocortisone (p less than 0.005). Had the infusion been stopped after 24 hours, the incidence of phlebitis would have been 56 percent in the group receiving placebo, but only 19 percent in the drug-treated groups (p less than 0.01). We conclude that infusion of lidocaine causes a high incidence of phlebitis which can be markedly reduced by adding heparin or hydrocortisone (or both) to the infusate and limiting the duration of the infusion in a given vein to 24 hours.

The additive antianginal action of oral isosorbide dinitrate in patients receiving propranolol. Magnitude and duration of effect.

Ten men with stable angina not completely relieved by full doses of propranolol (mean, 218 mg daily) were given double-blind, on alternate mornings, a placebo or an oral dose (5 to 30 mg) of isosorbide dinitrate (ISDN) previously titrated to lower sitting systolic blood pressure by 20 mm Hg. Patients had been trained in a protocol which precipitated angina after three to six minutes of bicycle exercise. On test days, with propranolol continued, bicycle exercise was performed until the appearance of angina before ISDN or placebo administration, and hourly thereafter for eight hours. Mean exercise duration was greater one hour after ISDN than after placebo by 182 sec (423 +/- 39 vs 241 +/- 13, p less than 0.001), and a difference of 63 sec was still present at six hours (p less than 0.002). At one hour, ISDN lowered resting systolic blood pressure by 26 mm Hg (from 114 +/- 5 mm Hg to 88 +/- 4 mm Hg; p less than .001) without appreciably changing heart rate. We conclude that ISDN is a very effective and reasonably long-acting antianginal supplement to propranolol.

Pericardial tamponade due to perforation with a permanent endocardial pacing catheter.

A case is presented in which shock developed suddenly during implantation of a permanent pacemaker. The cause proved to be pericardial tamponade secondary to catheter perforation. Analysis of this case and the 6 similar cases reported in the literature reveals that although perforation occurs not infrequently from immediately to many months after implantation, tamponade is quite rare and is invariably closely related temporally to catheter manipulation. Tamponade has occurred with different catheter sizes and makes. It is more likely related to local myocardial factors than to faulty technique. Closed pericardiocentesis is generally unsuccessful in relieving the tamponade, and prompt open drainage through the subxiphoid approach is recommended.

The effect upon coronary blood flow of coronary ostial intubation with an angiographic catheter.

Fifty-two patients undergoing cardiac catheterization were studied to determine whether intubation of the coronary ostium in the course of coronary angiographic studies interferes with coronary blood flow. Pressure at the tip of the catheter and coronary sinus blood flow were measured continuously during insertion of a No. 7.2 French Judkins' catheter into the left coronary ostium and during withdrawal of the catheter from it. In 48 of the 52 patients, there was no change in blood flow related to manipulation of the catheter. In four patients, either a drop in flow following insertion of the catheter or a rise following withdrawal or both were recorded. Two of these four patients had high-grade obstruction of the main left coronary artery, and in the other two the catheter inadvertently advanced and became wedged. In all four cases, reduction in coronary flow was indicated by a drop in or "ventricularization" of the catheter-tip pressure. It is concluded that in the large majority of instances, intubation of the coronary ostium during coronary angiographic studies causes no interference with resting coronary blood flow, but that monitoring of catheter-tip pressure is an important, as well as a valid, procedure for detecting such an interference if it should occur.

Cosmic rays observed by the resonant gravitational wave detector NAUTILUS

The passage of cosmic rays has been observed to excite mechanical vibrations in the resonant gravitational wave detector NAUTILUS operating at temperature of 100 mK. A very significant correlation (more than 10 standard deviations) is found.

First search for gravitational wave bursts with a network of detectors

We report the initial results from a search for bursts of gravitational radiation by a network of five cryogenic resonant detectors during 1997 and 1998. This is the first significant search with more than two detectors observing simultaneously. No gravitational wave burst was detected. The false alarm rate was lower than 1 per 10(4) yr when three or more detectors were operating simultaneously. The typical threshold was H approximately 4x10(-21) Hz-1 on the Fourier component at approximately 10(3) Hz of the gravitational wave strain amplitude. New upper limits for amplitude and rate of gravitational wave bursts have been set.

A novel VIP responsive gene. Activity dependent neuroprotective protein.

Activity dependent neuroprotective protein (ADNP, 828 amino acids, pI 5.99) is a glial-derived protein that contains a femtomolar active neuroprotective peptide, NAPVSIPQ (NAP). VIP induces a two- to threefold increase in ADNP mRNA in astrocytes, suggesting that ADNP is a VIP-responsive gene. ADNP is widely distributed in the mouse hippocampus, cerebellum, and cerebral cortex. VIP has been shown to possess neuroprotective activity that may be exerted through the activation of glial proteins. We suggest that ADNP may be part of the VIP protection pathway through the femtomolar-acting NAP and through putative interaction with other macromolecules.

Vasoactive intestinal peptide. Link between electrical activity and glia-mediated neurotrophism.

Vasoactive intestinal peptide has neurotrophic and neuroprotective properties that influence the survival of activity-dependent neurons in the central nervous system. Investigations of the mechanism of this neurotrophic peptide indicated that these actions are contingent on interactions with astroglia. The complex mixture of neurotrophic mediators released from astroglia include cytokines, a protease inhibitor, and activity-dependent neurotrophic factor, a protein with apparent structural similarities to hsp60. Investigations of ADNF resulted in the discovery of active peptides of extraordinary potency and broad neuroprotective properties. These studies indicate that a nine-amino acid core peptide of ADNF had significantly greater neuroprotective properties in comparison to the parent growth factor and these advantages identify ADNF-9 as an attractive lead compound for drug development.