Macro-to-micro porous special bioactive glass and ceftriaxone-sulbactam composite drug delivery system for treatment of chronic osteomyelitis: an investigation through in vitro and in vivo animal trial

A systematic and extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis in animal model were made using antibiotic loaded special bioactive glass porous scaffolds. After thorough characterization for porosity, distribution, surface charge, a novel drug composite were infiltrated by using vacuum infiltration and freeze-drying method which was subsequently analyzed by SEM-EDAX and studied for in vitro drug elution in PBS and SBF. Osteomyelitis in rabbit was induced by inoculation of Staphylococcus aureus and optimum drug-scaffold were checked for its efficacy over control and parenteral treated animals in terms of histopathology, radiology, in vivo drug concentration in bone and serum and implant-bone interface by SEM. It was optimized that 60P samples with 60-65% porosity (bimodal distribution of macro- to micropore) with average pore size ~60 μm and higher interconnectivity, moderately high antibiotic adsorption efficiency (~49%) was ideal. Results after 42 days showed antibiotic released higher than MIC against S. aureus compared to parenteral treatment (2 injections a day for 6 weeks). In vivo drug pharmacokinetics and SEM on bone-defect interface proved superiority of CFS loaded porous bioactive glass implants over parenteral group based on infection eradication and new bone formation.     

An immunity-based technique to characterize intrusions in computernetworks

This paper presents a technique inspired by the negative selection mechanism of the immune system that can detect foreign patterns in the complement (nonself) space. In particular, the novel pattern detectors (in the complement space) are evolved using a genetic search, which could differentiate varying degrees of abnormality in network traffic. The paper demonstrates the usefulness of such a technique to detect a wide variety of intrusive activities on networked computers. We also used a positive characterization method based on a nearest-neighbor classification. Experiments are performed using intrusion detection data sets and tested for validation. Some results are reported along with analysis and concluding remarks     

In vitro displacement of phenytoin from protein binding by nonsteroidal antiinflammatory drugs tolmetin, ibuprofen, and naproxen in normal and uremic sera

Displacement of phenytoin (90% bound to albumin) by other highly albumin-bound drugs like salicylate has been well documented. Other widely used nonsteroidal antiinflammatory drugs like tolmetin, ibuprofen, and naproxen are also strongly bound to albumin and can potentially displace phenytoin. However, phenytoin-ibuprofen interaction has been poorly studied in the past, and interaction of phenytoin with tolmetin or naproxen has not been studied before. For normal serum pool (albumin 3.7 g/dl), we observed significant increases in free phenytoin concentrations only with antiinflammatory drug concentrations at the upper end of therapeutic or above therapeutic concentrations. However, for the uremic pool (albumin 2.9 g/dl), displacement of phenytoin was significant even at the lower end of therapeutic concentrations of those antiinflammatory drugs. Of the three antiinflammatory drugs we studied, ibuprofen caused the highest displacement of phenytoin.     

Convergence of the signed output error adaptive identifier

This paper considers an adaptive output error identifier with a signum function in its update kernel. It is shown that the classical strict positive real (SPR) condition required for the convergence of traditional adaptive identifiers does not suffice for the convergence of this signed identifier. Instead, what is needed is a stronger operator condition called the strict dominant passive (SDP) condition. We give an analog of the Kalman-Yakubovic-Popov Lemma for the SDP conditions and, using it, give a convergence proof under the assumptions of persistent excitation and SDP     

Pre-labour rupture of membrane: the histological study of membrane and bacteriological profile

One hundred two (102) cases of pre-labour rupture of membrane (PROM) were studied and special attention was given to the histological study of the amniotic membrane as well as to the bacteriological study of high vaginal flora, cervical flora and flora of amniotic fluid, in search of probable causes or factors leading to PROM. The incidence was found to be 3.16% in the age group of 20-25 years without any relation to parity; and the duration of gestation was 38 to 40 weeks in most of the cases. The histological study revealed: (a) Focally denuded amniotic epithelium, focally separated amniotic epithelium from chorion layer, lesser density of focal squamoid change of the epithelium and thicker chorion layer probably indicating focal immaturity of the chorio-amnion, (b) lesser thickness of collagen layer, focal hydropic degeneration and mild cellular infiltrate, (c) presence of focal hyaline degeneration and focal calcification of chorio-amnion. Microbial culture revealed: (a) Higher rate of positive culture in high vaginal swab, cervical swab and amniotic fluid showing presence predominantly of Esch coli, Strept haemolyticus, klebseilla species, Staph aureus, Strept non-haemolyticus, proteus species and pseudomonas species against that of positive cultures in the control cases, (b) no anaerobic bacteria from high vaginal swab, cervical swab or from amniotic fluid. It was presumed that focal immaturity of chorio-amnion or focal irregularity in the chorio-amnion at the microscopical level, focal degeneration of collagen superadded with bacterial infection, however mild, could be the factors leading to weakness in the tensile strength of chorio-amnion, again leading to PROM, in the face of stress factors of foetal origin.     

Cleavage of transcriptional activator Oct-1 by poliovirus encoded protease 3Cpro

To understand the regulation of receptor-mediated endocytosis in hepatocytes, we have used two specific inhibitors of serine-threonine protein phosphatases (PP), microcystin (MCYST) and okadaic acid (OKA) as probes to alter protein phosphorylation in hepatocytes. We have then examined the impact of these changes on the specific binding and uptake of transferrin (Tf) in hepatocytes. The measurement of PP activity in hepatocyte lysates showed that OKA and MCYST shared a common inhibition of protein phosphatase 2A (PP2A). Our results showed that both OKA (250 nmol/L) and MCYST (500 nmol/L) significantly reduced Tf uptake at steady state (P < or = .05). The measurement of Tf internalization after 15 minutes in protein phosphatase inhibitor-pretreated cells revealed that the initial uptake was also significantly reduced. Binding studies showed that pretreatment with either of the phosphatase inhibitors did not result in significant changes in the K(d) for Tf binding to transferrin receptor (TfR). Additionally, no significant changes in the number of TfR in the plasma membrane were observed in phosphatase inhibitor-pretreated cells. The treatment of hepatocytes with nocodazole (NOC), which results in microtubule disassembly and inhibition of microtubule-based vesicle transport, caused comparable reductions in initial and steady state levels of transferrin accumulation. The changes in transferrin accumulation by both phosphatase inhibitors and nocodazole were accompanied by redistribution of the microtubule-anchored Golgi apparatus and lysosomal network from the perinuclear region to the cell periphery. Our data show that the regulation of Tf uptake by receptor-mediated endocytosis is mediated by PP2A and additionally may occur through regulation of microtubule-based vesicle transport.     

Differential solubilization of membrane lipids by detergents: coenrichment of the sheep brain serotonin 5-HT1A receptor with phospholipids containing predominantly saturated fatty acids

It is a widely held belief that the inactive X-chromosome (Xi) in female cell nuclei is strongly condensed as compared to the largely decondensed active X-chromosome (Xa). We have reconsidered this problem and painted X-chromosome domains in nuclei of subconfluent, female and male human amniotic fluid cell cultures (46,XX and 46,XY) by chromosomal in situ suppression (CISS) hybridization with biotinylated human X-chromosome specific library DNA. FITC-conjugated avidin was used for probe detection and nuclei were counterstained with propidium iodide (PI). The shape of these nuclei resembling flat ellipsoids or elliptical cylinders makes them suitable for both two-dimensional (2D) and three-dimensional (3D) analyses. 2D analyses of Xi- and Xa-domains were performed in 34 female cell nuclei by outlining of the painted domains using a camera lucida. Identification of the sex chromatin body in DAPI-stained nuclei prior to CISS-hybridization was confirmed by its colocalization with one of the two painted X-domains. In 31 of the 34 nuclei the area AXi for the inactive X-domain was smaller than the area AXa for the active domain (mean ratio AXa/AXi = 1.9 +/- 0.8 SD, range 1.0-4.3). The signed rank test showed a highly significant (P < .0001) difference both between AXa and AXi and between the ratios r(Xa) and r(Xi), calculated by dividing the maximum length L of each X-domain by its maximum width W. In most nuclei (26/34) we found r(Xa) > r(Xi) demonstrating a generally more elongated structure of Xa. For 3D analysis a confocal scanning laser fluorescence microscope (CSLFM) was used. Ten to 20 light optical sections (PI-image, FITC-image) were registered with equal spacings (approx. 0.4 microns). A thresholding procedure was applied to determine the PI-labeled nuclear and FITC-labeled X-domain areas in each section. Estimated slice volumes were used to compute total nuclear and X-domain volumes. In a series of 35 female nuclei most domains extended from the top to the bottom nuclear sections. The larger of the two X-chromosome domains comprised (3.7 +/- 1.7 S.D.)% of the nuclear volume. A mean ratio of 1.2 +/- 0.2 SD (range 1.1-2.3) was found for the volumes of the larger and the smaller X-domains in these female nuclei. In a series of 27 male amniotic fluid cell nuclei the relative X-chromosome domain volume comprised (4.0 +/- 2.6 S.D.)%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Understanding design: Artificial intelligence as an explanatory paradigm

A substantial part of the intellectual content of what H A Simon called the ‘sciences of the artificial’ is contained in the activity we calldesign. A central aim ofdesign theory is to construct testable, explanatory models of the design process that will serve to enhance our understanding of how artifacts are, or can be, designed. In this paper, we discuss how some of the basic concepts underlying the discipline ofartificial intelligence (ai) can serve to provide anexplanatory paradigm for understanding design. We present an AI-based model of the design process and describe some of the implications of this model for our understanding of design — including that aspect of it we call ‘invention’.