Liposomes containing lipid A serve as an adjuvant for induction of antibody and cytotoxic T-cell responses against RTS,S malaria antigen

Encapsulation of soluble protein antigens in liposomes was previously shown to result in processing of antigen via the major histocompatibility complex class I pathway, as evidenced by costaining of the trans-Golgi region of murine bone marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or liposome-encapsulated RTS,S, a particulate malaria antigen consisting of hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum circumsporozoite protein, also was localized in the trans-Golgi after incubation with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T-lymphocyte (CTL) response was detected, however, only after immunization with RTS,S encapsulated in liposomes containing lipid A and not after immunization with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A. Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi of BMs does not necessarily result in a CTL response in vivo unless an additional adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose-dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody response compared to that of free RTS,S. The IgG1 and IgG2a subclasses predominated after immunization with RTS,S encapsulated in liposomes containing MPL. These results demonstrate that encapsulation of a lipid-containing particulate antigen, such as RTS, S, in liposomes containing lipid A can enhance both humoral and cellular immune responses.     

Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units

OBJECTIVE: To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews. DESIGN: Randomised single blind controlled trial with obstetric units allocated to an educational visit or control group. SETTING: 25 of the 26 district general obstetric units in two former NHS regions. SUBJECTS: The senior obstetrician and midwife from each intervention unit participated in educational visits. Clinical practices of all staff were assessed in 4508 pregnancies. INTERVENTION: Single informal educational visit by a respected obstetrician including discussion of evidence based obstetrics, guidance on implementation, and donation of Cochrane database and other materials. MAIN OUTCOME MEASURES: Rates of perineal suturing with polyglycolic acid, ventouse delivery, prophylactic antibiotics in caesarean section, and steroids in preterm delivery, before and 9 months after visits, and concordance of guidelines with review evidence for same marker practices before and after visits. RESULTS: Rates varied greatly, but the overall baseline mean of 43% (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse delivery increased significantly in intervention units but not in control units; there was no difference between the two types of units in uptake of other practices. Pooling rates from all 25 units, use of antibiotics in caesarean section and use of polyglycolic acid sutures increased significantly over the period, but use of steroids in preterm delivery was unchanged. Labour ward guidelines seldom agreed with evidence at baseline; this hardly improved after visits. Educational visits cost pound860 each (at 1995 prices). CONCLUSIONS: There was considerable uptake of evidence into practice in both control and intervention units between 1994 and 1995. Our educational visits added little to this, despite the informal setting, targeting of senior staff from two disciplines, and donation of educational materials. Further work is needed to define cost effective methods to enhance the uptake of evidence from systematic reviews and to clarify leadership and roles of senior obstetric staff in implementing the evidence.     

Molecular and geographic patterns of tuberculosis transmission after 15 years of directly observed therapy

Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound.     

Non-isotopic in situ hybridization of HPV types in cervical intraepithelial lesions in patients with AIDS

Naturally produced methane shows different delta 13C-values with respect to its origin, e.g., geological or biological. Methane-production of ruminants is considered to be the dominant source from the animal kingdom. Isotopic values of rumen methane--given in literature--range between -80/1000 and -50/1000 and are related to feed composition and also sampling techniques. Keeping cows, camels and sheep under identical feed conditions and sampling rumen gases via implanted fistuale we compared delta PDB 13C-values of methane and CO2 between the species. Referring to mean values obtained from 4 or 5 samples at different times of 11 animals (n = 47) we calculated delta PDB 13C-medians resulting in small but not significant differences within and significant differences between the species for CO2 and methane. The delta PDB 13C-differences between methane and CO2 were statistically equal within and also between the species. Therefore a linear regression of methane values on CO2 is appropriate and leads to: delta PDB 13C(methane)/1000 = 1.57 * delta PDB 13C(CO2)/1000 - 47/1000 with a correlation coefficient of r = 0.87.     

Experimental occlusal interferences. Part IV. Mandibular rotations induced by a pliable interference

In 12 subjects, a pliable, yet unbreakable, intercuspal interference (aluminum shim onlay splint; uniform height of 0.25 mm) was placed between either the right or left maxillary and mandibular second premolars and first molars. During brief and forceful biting (dynamic chewing stroke of about 20 kg force) the interference emulated a semisoft food bolus, and at the end of biting (subsequent static clenching stroke of about 20 kg force) it emulated a rigid metal interference. During dynamic/static biting, rotational electrognathography measured maximum frontal and horizontal plane torque of the right and left mandibular condyles. Eleven subjects (92%) showed frontal plane upward rotation (mean of 1.0 degree) of the condyle contralateral to the interference, and one subject (8%) showed frontal plane upward rotation (0.4 degree) of the condyle ipsilateral to the interference. Two subjects (17%) showed no horizontal plane rotation; seven subjects (58%) showed backward rotation (mean of 0.4 degree) of the condyle contralateral to the interference; and three subjects (25%) showed backward rotation (mean of 0.3 degree) of the condyle ipsilateral to the interference. It is suggested that, in the presence of an occlusal interference, mastication may have both short- and long-term detrimental effects.     

Vectorized garbage collection

Garbage collection can be done in vector mode on supercomputers like the CRAY-2 and the Cyber 205. Both copying collection and mark-and-sweep can be expressed as breadth-first searches in which the queue can be processed in parallel. We have designed a copying garbage collector whose inner loop works entirely in vector mode. We give performance measurements of the algorithm as implemented for Lisp CONS cells on the Cyber 205. Vector-mode garbage collection performs up to nine times faster than scalar-mode collection-a worthwhile improvement.Supported in part by NSF Grants DCR-8603543 and CCR-8806121, and by a Digital Equipment Corp. Faculty Incentive Grant.Supported by the NSF Research Experiences for Undergraduates program.     

Loop headers in λ-calculus or CPS

The introduction of a loop header block facilitates the hoisting of loop-invariant code from a loop. In a -calculus intermediate representation, which has a notion of scope, this transformation is particularly useful. Loop headers with scope also solve a problem with in-line expansion of recursive functions or loops: if done naively, only the first iteration is inlined. A loop header can encapsulate the loop or recursion for better in-line expansion. This optimization improves performance by about 5% in Standard ML of New Jersey.     

Effect of Berezinskii-Kosterlitz-Thouless vortex fluctuations on the nuclear spin relaxation rate

In this work we examine the influence of the diffusive motion of vortices in highly anisotropic high-T_c superconductors near the Berezinskii-Kosterlitz-Thouless (BKT) transition temperature T _bkt on the spin-lattice relaxation rate T ₁ ^–1 .We find a jump in T ₁ ^–1 at the temperature T _bkt .