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The changes in the tensile toughness (U), degree of crystallinity (%C), melting temperature (Tm), lamella thickness, and lamella alignment of uncrosslinked and unaged GUR 1150HP ultra-high-molecular-weight polyethylene specimens, following different sterilization treatments (none, gamma-irradiation in air, gamma-irradiation in a nitrogen-rich atmosphere, ethylene oxide gas, and gas plasma) were determined. For each of the properties - U, %C, and Tm - the only significant difference in the mean value was found between the set of specimens gamma-irradiated in air, on the one hand, and each of the other sets, on the other hand. It was found that lamella thickness showed little change between the groups of specimens but there was a significant difference in the lamella orientation between the set of specimens that had been gamma-irradiated in air, on the one hand, and each of the other sets, on the other. It thus appears that the changes seen in the physical and mechanical properties determined may be a reflection of the change in the polymer's lamella alignment.

The exact mechanism by which mechanical stimulus regulates the healing process of a bone fracture is not understood. This has led to the development of several hypotheses that predict the pattern of differentiation of tissue during healing that may arise from characteristic fields of stress or strain at the fracture. These have so far remained unproved because data on stress fields in actual fracture tissue have been unavailable until recently. Thus the present study examines the predictive performance of the hypothesis proposed in J Orthop Res 6 (1988) 736, against measured and calculated data reported in J Biomech 33 (2000) 415, using a 2D FEM of a clinical fracture. The hypothesis was used to predict the influence of stress fields present in the Gardner et al. tissues at four temporal stages during healing. These predictions were then correlated with callus-size, rate of endochondral ossification and ossification pattern subsequently observed by Gardner et al. in the clinical fracture. Results corroborate the hypothesis that high octahedral shear stresses may increase the size of the callus during the initial phase of healing, and they also suggest that this may be true during the later stages of the fracture fixation period. However, compressive dilatational stresses were not found to inhibit endochondral ossification, as suggested by the hypothesis. Although high shear stresses were found in regions indicative of fibrous tissue as postulated by the hypothesis, this was not found to be the case for high tensile dilatational stresses. Also, contour diagrams of Osteogenic index (I) indicated only limited correlation with callus maturation and the pattern of healing. Therefore, the hypothesis was not wholly successful in predicting healing pattern.

Ranjan et al. [Phys. Rev. B 65, 060102(R) (2002)] have recently presented results of a powder neutron-diffraction study of the high-temperature monoclinic ${(F}_{M}^{\mathrm{HT}})$ to low-temperature monoclinic ${(F}_{M}^{\mathrm{LT}})$ phase transition in $\mathrm{Pb}({\mathrm{Ti}}_{1\ensuremath{-}x}{\mathrm{Zr}}_{x}){\mathrm{O}}_{3}$ discovered by Ragini et al. [Phys. Rev. B 64, 054101 (2001)]. They attribute the presence of superlattice reflections in the diffraction data to tilting of oxygen octahedra and propose a monoclinic space group $\mathrm{Pc}$ for the ${F}_{M}^{\mathrm{LT}}$ phase. It is shown that for the model proposed by Ranjan et al., the correct space group of the ${F}_{M}^{\mathrm{LT}}$ phase should be $\mathrm{Cc}.$ This has also been corroborated by a group-theoretical approach to the problem. A different set of refined structural parameters for the $\mathrm{Cc}$ space group obtained from the Rietveld analysis of the powder neutron-diffraction data of Ranjan et al. is also presented.

Results of a powder neutron diffraction study of the high-temperature monoclinic ${(F}_{M}^{\mathrm{HT}})$ to a low-temperature monoclinic ${(F}_{M}^{\mathrm{LT}})$ phase transition in $\mathrm{Pb}({\mathrm{Ti}}_{1\ensuremath{-}x}{\mathrm{Zr}}_{x}){\mathrm{O}}_{3}$ discovered recently by Ragini et al. are presented for $x=0.520.$ The powder neutron diffraction pattern of the ${F}_{M}^{\mathrm{LT}}$ phase contains superlattice reflections which have all odd hkl $(h\ensuremath{\ne}k\ensuremath{\ne}l)$ Miller indices with respect to a doubled elementary perovskite cell, characteristic of antiphase tilting of oxygen octahed\ifmmode \acute{r}\else \'{r}\fi{}a. In analogy to other perovskite systems, the appearance of these superlattice reflections is attributed to an instability at the R point of the cubic Brillouin zone. We show that the most plausible space group of the ${F}_{M}^{\mathrm{LT}}$ phase is Pc. Results of Rietveld refinement for this space group are presented to show that the oxygen octahedra indeed undergo antiphase rotations about [001] direction.

Results of dielectric and resonance frequency (f r ) measurements below room temperature are presented for Pb(Zr x Ti 1-x )O 3 , x=0.515 and 0.520. It is shown that the temperature coefficient of f r changes sign from negative to positive around 210 and 265 K for x=0.520 and 200 and 260 K for x=0.515. Anomalies in the real part of the dielectric constant (e') are observed around the same temperatures at which the temperature coefficient of f r changes sign because of the electrostrictive coupling between the elastic and dielectric responses. Low-temperature powder x-ray-diffraction (XRD) data, however, reveal only one transition from the tetragonal to monoclinic phase similar to that reported by Noheda et al. [Phys. Rev. B, 61, 8687 (2000)]. Electron-diffraction data, on the other hand, reveal yet another structural transition at lower temperatures corresponding to the second anomaly in the e' vs T and f r vs T curves. This second transition is shown to be a cell-doubling transition not observed by Noheda et al. in their XRD studies. The observation of superlattice reflections raises doubts about the correctness of the Cm space group proposed by Noheda et al. for the monoclinic phase of Pb(Zr x Ti 1-x )O 3 below the second transition temperature.

Polygalacturonase isoenzyme 3 (PG-3) was purified to homogeneity with a specific activity of 0.7 mu katal mg-1 protein from banana fruit pulp. The purified enzyme was a glycoprotein with ca. 8% carbohydrate. The molecular weight of the native enzyme was found to be 90 +/- 10 kDa with a subunit molecular weight of 29 +/- 2 kDa. The enzyme exhibited optimum activity at pH 4.3 and temperature 40 degrees C with activation energy 35.4 kJ mol-1. A unique property of the enzyme was the requirement of -SH groups for the enzyme activity. The enzyme was inhibited by p-CMB and activated by 2-ME and DTT. The inhibition of p-CMB could be reversed by DTT. The enzyme contained eight free -SH groups. The Km of the enzyme was 0.15% for polygalacturonic acid.

Data from a number of laboratories support a potential role for tumor necrosis factor-alpha (TNF-alpha) in the loss of insulin sensitivity and the pathogenesis of insulin resistance (IR) in diabetic animal models and human patients. We designed experiments to establish a dose-response relationship for TNF-alpha and IR in H-411E cells in culture. IR was measured by inhibition of the ability of graded amounts of insulin to stimulate expression of calmodulin (CaM) mRNA in these cells. This was assessed by autoradiographs of Northern blot(s) of CaM mRNA probed with labeled oligonucleotide cDNA for rat CaM. We found that TNF-alpha at 0.1, 1.0, and 10.0 ng/ml opposed 10,000 microU/ml insulin (i.e., %IR = 20%, 67%, and 88%, respectively). At 1.0 ng/ml TNF-alpha, insulin at the concentration of 1000 microU/ml (0.006 micromol/L) stimulated CaM mRNA at a 41% level and at 10,000 microU/ml (0.06 micromol/L) at a 63% level. Furthermore, oligopeptide TNF-alpha homologs (at 1000 x the molar concentration of TNF-alpha) TNF-alpha 69-100 and TNF-alpha 133-157 conferred 66% and 101% IR, respectively, while all other peptide fragments of TNF-alpha were essentially without effect. Studies done with both monoclonal and polyclonal antibodies to the TNF-alpha receptor demonstrated blocking activity by polyclonal but not by monoclonal anti TNF-alpha receptor antibody. This supports the concept that the activity of the peptide fragments occurs through the TNF-alpha receptor and not through nonspecific translocation across the plasma membrane. These data suggest that the epitopes on TNF-alpha that mediate IR reside in two regions of the molecule spanning amino acid residues 69-100 and 133-157.

Chloroma, also called granulocytic sarcoma or myeloid sarcoma, is a rare malignant extramedullary neoplasm of myeloid precursor cells that occurs usually in association with acute myeloid leukaemia or blast phase of chronic myeloid leukaemia (CML). The chloromas are regarded as an early herald of a systemic relapse, rather than as a localised process. The author reports a rare case of multiple skin chloromas in the chronic phase of CML. The patient was treated initially with hydroxyurea and chloromas disappeared. Patient has been followed for around three and half years and maintained in chronic stable phase on imatinib therapy.

Visceral leishmaniasis (VL) is prevalent worldwide. In the past there has been steep rise in the incidence of VL in southern Europe and Africa. Factors attributed for this are economic development, a shift of the reservoir of Leishmania, immunodeficiency due to HIV infection and intravenous drug abuse. The co-infection of VL and HIV is common in southern European-African countries and is proposed that it should be included as an AIDS-defining illness. VL is not only considered to be an opportunistic infection in HIV-infected individuals but it may also reactivate latent infection. This case is worth reporting as it highlights increasing incidence of VL-HIV co-infection and its sparse literature from India, changing ecology and possible evolving epidemic in the Indian subcontinent. Additionally an atypical presentation such as lymphadenopathy in VL should arouse suspicion of HIV co-infection and vice versa.

Amit Kumar Srivastava,1 Priyanka Bhatnagar,2 Madhulika Singh,1 Sanjay Mishra,1 Pradeep Kumar,2 Yogeshwer Shukla,1 Kailash Chand Gupta1,2 1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), Lucknow, India; 2Nucleic Acid Research Laboratory, Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, India Abstract: In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF]) and green (epigallocatechin-3-gallate [EGCG]) tea in poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA)-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically) of mouse skin with either TF or EGCG (100 µg/mouse) doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk), 57.63% (1/10th of bulk), and 63.14% (1/5th of bulk) prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3) and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2) as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior ability to prevent DMBA-induced DNA damage at much lower concentrations, thus opening a new dimension in chemoprevention research. Keywords: DNA alkaline unwinding assay, mouse skin, DNA repair

Laser beam percussion drilling is used for the rapid fabrication of small diameter hole in a wide variety of engineering materials. A computational thermal model to predict the material removal rate will help to enhance the cost effectiveness of LBPD process especially for material like aluminium which has very low machinability during laser beam machining due to its adverse optical and thermal properties. An axisymmetric finite element method-based thermal model incorporating the temperature dependent thermal and optical properties as well as the phase change phenomena has been developed to determine the transient temperature distribution in thin aluminium sheet, which is further used to obtain the material removal rate (MRR). The predicted values of MRR have been compared with the self conducted experimental results. It was found that the peak power has the dominant effect on MRR followed by thickness of sheet, pulse width and pulse frequency.

The novel HIV-1 integrase inhibitor 1, discovered in our laboratory, exhibits potent anti-HIV activity against a diverse set of HIV-1 isolates and also against HIV-2 and SIV. In addition, this compound displays low cellular cytotoxicity and possesses a favorable in vitro drug interaction profile with respect to isozymes of cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT). However, the total synthesis of this significant HIV integrase inhibitor has not been reported. This contribution describes an optimized, reproducible, multi-step, synthetic route to inhibitor 1. The yield for the separate steps averaged about 80%. The methodologies utilized in the synthesis were, among others, a palladium-catalyzed cross-coupling reaction, a crossed-Claisen condensation, and a hydrazino amide synthesis step. Successful alternative synthetic methodologies for some of the steps are also described.

The goal of this paper is to examine the use of TETRAD to generate attitude formation models from data. We review the controversy regarding models of attitude formation in the psychology literature, and we re-analyze the data using different subroutines from TETRAD to shed further light on this controversy.

Results: We investigated 64 institutionalized children aged 2 to 12 years. Parasitic infections were identified in 44 cases (68.7%). Hymenolepis nana (31.2%), Giardia lamblia (28.1%), Blastocytis hominis (7.8%), Entamoeba coli (4.7%), Ascaris lumbricoides (4.7%), and Trichuris trichiura (3.1%) were diagnosed. We have determined associations of two (45.4%) and more than two parasites (18.2%) among the infected children; of the 20 with hymenolepiasis, 11 (55%) had multiple parasitic infections. Clinical and laboratory examinations were conducted to investigate the presence of symptoms and eosinophilia in patients with parasitic infections. Diarrhoea (38.6%), weight loss (47.7%), abdominal pain (25%), nervous disorders (34.1%), cutaneous manifestations (22.7%), fever (9.1%) and respiratory infections (59.1%) were reported in the infected children. Eosinophilia was noted in 27 (61%) of the 44 patients with parasitosis. High eosinophil values were mostly observed among those diagnosed with helminth infections. Conclusion: Hymenolepis nana infection was reported with an increased frequency among Romanian institutionalized children. The majority of the patients with hymenolepiasis were diagnosed with multiple parasitic infections.

X-ray diffraction studies on Sr1-x Cax TiO3 in the temperature range 12 to 300 K reveal cubic to tetragonal (I4/mcm) antiferrodistortive and tetragonal to orthorhombic (Ic2m) polar phase transitions at ∼170 and 225, 32, 34 K, respectively, for x=0.02 and 0.04. It is shown that the polarization in the orthorhombic phase is along the ⟨110⟩ pseudocubic direction, in agreement with the experimentally reported easy polarization direction by Bednorz and Muller. However, in disagreement with them the moments are found to be ferrielectrically coupled in the neighboring (001) planes that is responsible for the anomalously low values of the spontaneous polarization in the polar phase.

Site-directed spin labeling and electron paramagnetic resonance were used to investigate the structure and conformational dynamics of the small multidrug resistance transporter EmrE from Escherichia coli. The data set consists of the mobilities, solvent accessibilities of 110 spin labeled residues as well as selected pairwise distances. These parameters were interpreted as constraints on the local steric environment, the orientation of helices in the lipid phase and packing of the transmembrane helices in each monomer as well as across the dimer interface. The data collectively suggest that in liposomes, ligand-free EmrE average structure is not compatible with the crystal structure and an EM-based model. Spin label pairs at the dimer interface located at opposite sides of helix 3 reveal dipolar interaction between the spins separated by less than 15A which contradicts their inverted relative orientation in the crystal structure. Furthermore, distances between spin labels along helix 4 are not consistent with its tight packing at the dimer interface. The spectroscopic data is supported by an expanded topological analysis of EmrE-GFP chimeras which reveals that the previous interpretation of Rapp et al is not unequivocal. Binding of tetraphenyl phosphonium (TPP+) to EmrE increases the structural order as manifested by a narrowing of spin label distance distributions but does not lead to major conformational rearrangements. The EPR-based constraints are being used to generate a model of EmrE in liposomes.

Many researchers have demonstrated the existence of an attraction effect that increases the choice probability of an existing “target” brand by the introduction of a relatively inferior “decoy” brand. This study develops a causal model that links antecedent variables with the attraction effect. We find that the attraction effect is explained to a considerable extent by changes in the following seven variables: (1) information relevance or stimulus meaningfulness, (2) product class knowledge, (3) task involvement, (4) perceived similarity between decoy and target, (5) relative brand preference, (6) share captured by decoy brand, and (7) perceived decoy popularity. The overall results were consistent across product classes studied, which included beer, cars, and TV sets. The popularity explanation for attraction effect, alluded to by Huber, Payne, and Puto (1982), was tested and found to hold true.

Research efforts on the human immunodeficiency virus (HIV) integrase have resulted in two approved drugs. However, co-infection of HIV with Mycobacterium tuberculosis and other microbial and viral agents has introduced added complications to this pandemic, requiring favorable drug-drug interaction profiles for antiviral therapeutics targeting HIV. Cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT) are pivotal determining factors in the occurrence of adverse drug–drug interactions. For this reason, it is important that anti-HIV agents, such as integrase inhibitors, possess favorable profiles with respect to CYP and UGT. We have discovered a novel HIV integrase inhibitor (compound 1) that exhibits low nM antiviral activity against a diverse set of HIV-1 isolates, and against HIV-2 and the simian immunodeficiency virus (SIV). Compound 1 displays low in vitro cytotoxicity and its resistance and related drug susceptibility profiles are favorable. Data from in vitro studies revealed that compound 1 was not a substrate for UGT isoforms and that it was not an inhibitor or activator of key CYP isozymes.

Clathrin is a trimeric protein involved in receptor-mediated-endocytosis, but can function as a non-trimer outside of endocytosis. We have discovered that the subcellular distribution of a clathrin cysteine mutant we previously studied is altered and a proportion is also localized to nuclear spaces. MALS shows C1573A hub is a mixture of trimer-like and detrimerized molecules. The X-ray structure of the trimerization domain reveals that without light chains, a helix harboring cysteine-1573 is reoriented. We propose clathrin has a detrimerization switch, which suggests clathrin topology can be altered naturally for new functions.

To test the hypothesis that α-crystallin chaperone activity plays a central role in maintenance of lens transparency, we investigated its interactions with γ-crystallin mutants that cause congenital cataract in mouse models. Although the two substitutions, I4F and V76D, stabilize a partially unfolded γD-crystallin intermediate, their affinities to α-crystallin are marginal even at relatively high concentrations. Detectable binding required further reduction of γD-crystallin stability which was achieved by combining the two mutations. Our results demonstrate that mutants and possibly age-damaged γ-crystallin can escape quality control by lens chaperones rationalizing the observation that they nucleate protein aggregation and lead to cataract.Structured summary of protein interactionsgammaD Crystallin and alphaB Crystallin bind by molecular sieving (View interaction)gammaD Crystallin and alphaB Crystallin bind by fluorescence technology (View interaction)gammaD Crystallin and alphaA Crystallin bind by fluorescence technology (View interaction)gammaD Crystallin and alphaA Crystallin bind by molecular sieving (View interaction)

Bone tissue health depends largely on efficient fluid and solute transport between the blood supply and cells that are the living component of the tissue. We hypothesized that the lacunocanalicular hydraulic network, which is defined by the pericellular fluid space that is common to all bone tissue, is optimized to transport fluid and solutes between the blood supply and bone cells. An analytical study was carried out to evaluate the effect of osteonal architecture, including the osteon diameter, number of annular lamellar regions, and number and length of canalicular channels, on fluid transport between the blood supply and bone cells. On the basis of this analysis, we conclude that osteon size is limited to the distance over which fluid and solutes can be transported efficiently between the blood supply and cells. This analytic model suggests that hydraulic conductivity is highest in lamellar regions closest to the Haversian canal (HC) and decreases with increasing distance from the blood supply, reaching a plateau after the fifth lamella (169 micro m radius). Furthermore, an increase in the diameter of the HC, or a decrease in the length of canaliculi, reduces the hydraulic conductivity within the lacunocanalicular network. Applying the principle of minimal expenditure of energy to this analysis, the path distance comprising five or six lamellar regions represents an effective limit for fluid and solute transport between the blood supply and cells; beyond this threshold, hydraulic resistance in the network increases and additional energy expenditure is necessary for further transportation. This suggests that transport is optimized to meet metabolic demands concomitant with a minimal expenditure of energy. This fundamental new insight into bone structure and physiology may provide a new basis of understanding for tissue engineering, bone physiology in health and disease, and evolutionary biology.