Blood-to-brain glucose transport and cerebral glucose metabolism are not reduced in poorly controlled type 1 diabetes

Clinical and epidemiological studies suggest that thiazide diuretics can prevent bone loss and decrease the incidence of hip fractures. However, the mechanism of the effect of diuretics on bone is not clearly established. Indapamide (IDP), a sulfonamide diuretic related to thiazides, is used to treat hypertension. Sixty spontaneously hypertensive rats (SHRs) were divided into four groups and treated with or without IDP (1.5 mg/kg/day) during 8 weeks in the presence or absence of a high sodium load (8% NaCl supplementation in the diet). Sodium and calcium excretions were increased in the rats receiving the high sodium load (SHR + 8% NaCl) comparatively with control rats (SHR). IDP decreased and increased, respectively, calcium and sodium excretions. Serum parathyroid hormone (PTH) was unchanged in any group. Bone density was measured at the femur, tibia, and vertebrae, and bone morphometry was performed at the metaphysis of the femur to evaluate bone architecture. Rats fed a high sodium diet had an average 5.5% decreased bone density at every site except the femoral diaphysis. The trabecular bone volume was also decreased (SHR + 8% NaCl vs. SHR, 11.99+/-0.78 vs. 17.51+/-1.5%, p < 0.05). An increase in trabecular separation suggested that these changes were due to increased bone resorption. In the SHR + 8% NaCl + IDP group, IDP increased bone density and trabecular bone volume (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 16.52+/-1.04 vs. 11.99+/-0.78%, p < 0.05). Trabecular separation and pyridinoline/creatinine excretion (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 136.39+/-9.62 vs. 195.18+/-22.34 nmol/mmol, p < 0.05) were also decreased by IDP. These results show that in rats receiving a high sodium diet, IDP can reverse sodium-induced bone loss and increased bone resorption independently of changes in serum PTH.     

Poly(lactide-co-glycolide) microencapsulation of vaccine antigens

Fimbriae from Bordetella pertussis have been encapsulated in poly(lactide-co-glycolide) (PLG) microspheres of a size appropriate for oral administration. The binding of antibodies which react with conformational or linear fimbrial epitopes, to fimbriae released from microspheres, suggested that the process of was not detrimental to the native integrity of the protein. Mice were immunised by oral gavage with a single dose of microencapsulated fimbriae, or with fimbriae adsorbed onto alhydrogel and administered by intraperitoneal injection. The resulting immune responses in serum were comparable but only oral administration of microencapsulated fimbriae elicited specific immune responses in external secretions. Six weeks after immunisation, both groups of immunised animals were protected against challenge with live B. pertussis.     

cis-acting RNA elements required for replication of bovine viral diarrhea virus-hepatitis C virus 5'' nontranslated region chimeras

Pestiviruses, such as bovine viral diarrhea virus (BVDV), share many similarities with hepatitis C virus (HCV) yet are more amenable to virologic and genetic analysis. For both BVDV and HCV, translation is initiated via an internal ribosome entry site (IRES). Besides IRES function, the viral 5' nontranslated regions (NTRs) may also contain cis-acting RNA elements important for viral replication. A series of chimeric RNAs were used to examine the function of the BVDV 5' NTR. Our results show that: (1) the HCV and the encephalomyocarditis virus (EMCV) IRES element can functionally replace that of BVDV; (2) two 5' terminal hairpins in BVDV genomic RNA are important for efficient replication; (3) replacement of the entire BVDV 5' NTR with those of HCV or EMCV leads to severely impaired replication; (4) such replacement chimeras are unstable and efficiently replicating pseudorevertants arise; (5) pseudorevertant mutations involve deletion of 5' sequences and/or acquisition of novel 5' sequences such that the 5' terminal 3-4 bases of BVDV genome RNA are restored. Besides providing new insight into functional elements in the BVDV 5' NTR, these chimeras may prove useful as pestivirus vaccines and for screening and evaluation of anti-HCV IRES antivirals.     

Design synthesis in VLSI and software engineering

In this paper we present the results of the Working Group on Design Synthesis and Measurement. This group explored the issues that separate and bind software engineering and VLSI design. The issues on which we comment are design views and tradeoff, levels of abstraction and their importance, and design methodologies and their effect on decisions. We also examine the support environments needed to facilitate design in VLSI and software engineering, state-of-the-art of silicon compilation today, and the types of problems that are best suited to silicon compilation.     

On Optimum Sampled-Data FM Demodulation

Since the introduction of large-scale integration (LSI) techniques, there has been a continuing effort to develop digitalization techniques for communication equipment amenable to LSI implementation. Hopefully, this will permit expanded capability in the equipment while taking advantage of the cost reliability attributed of LSI. In this paper, a digitalized or sampled-data FM demodulator recursive algorithm is synthesized and its signal-to-noise ratio performance compared with the optimum analog demodulator and the conventional limiter discriminator demodulator. The demodulator is shown to exhibit threshold extension capability and automatic time-varying gain (bandwidth) adjustments from acquisition through tracking of the incoming modulated signal.     

Self-infusion of GABAA antagonists directly into the ventral tegmental area and adjacent regions.

This study used an intracerebral self-administration paradigm in rats to determine if blockade of GABAA receptors in the ventral tegmental area (VTA) has a reinforcing effect. Rats quickly learned to self-infuse a picrotoxin solution into the anterior VTA; rats discriminated the lever that produced picrotoxin infusions from the lever without consequences; and when the response requirement was increased, rats increased response levels for picrotoxin infusion. The reinforcing effect of picrotoxin was site-specific: Anterior VTA regions supported vigorous self-infusions, but not the posterior VTA, substantia nigra, or lateral hypothalamus. Muscimol, a GABAA agonist, disrupted picrotoxin self-infusion, but bicuculline, a GABAA antagonist, was self-infused into the VTA. The results suggest that blockade of GABAA receptors in the anterior VTA is reinforcing and that functional organization of the GABA systems within the VTA is heterogeneous. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implications of N and C-terminal proximity for protein folding

We have investigated the proximity of the N and C termini in protein structures, and developed a model to test the theoretical possibility that proteins fold with their termini closely associated. On average, the distance between the termini is not significantly different from what would be expected based on chance. However, the theoretical model indicated that it is possible to greatly decrease the N-to-C terminal distance by allowing small (approximately six amino acid residues) solvent-accessible terminal fragments to move. Subsequent to this distance minimization method, more than 90% of the proteins studied had smaller-than-expected N-to-C distances, but only minor structural modification.     

Social experience with siblings fosters species specific responsiveness to maternal visual cues in bobwhite quail chicks (Colinus virginianus).

Examined the role of visual and social experience with siblings in the development of bobwhite quail chicks' preference for species-specific maternal visual cues. Chicks were reared in 1 of 4 conditions: group, isolation, partial isolation, and heterospecific group. They were tested in simultaneous choice tests with species-typical and species-atypical audiovisual stimuli. Results revealed that only Ss that were reared in a group with same-aged conspecifics preferred the visual features of a bobwhite hen model. Ss in the other 3 conditions did not exhibit species-specific visual preference. Findings suggest that visual experience and direct social interaction with siblings facilitate the development of bobwhite chicks' species-specific responsiveness to static maternal visual cues and illustrate the important influence of experience with conspecifics in the development of early perceptual preferences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Further observations on tissue heating patterns using an invasive ground probe with radiofrequency hyperthermia system

Critical modifications have been made in the grounded elements of a previously reported hybrid radiofrequency heating system with inductive, capacitive, and grounded elements designed for deep focal heating. These modifications facilitate introduction of the ground probe, the single invasive element of the system, into animals and humans. The modified grounded elements also enable monitoring and optimization of ground point current, thereby improving control of heating rate, and greatly increase the volume of tissue that can be heated using a single invasive grounding element, embedded in a lossy dielectric field in the near field of the radiofrequency hyperthermia system.