Achieving excellent microformability in aluminum by engineering a unique ultrafine-grained microstructure.

During microforming of conventional materials, specimen and microstructural length-scales are close to each other. This leads to an abnormal deformation behavior of the material and reduces microformability. Engineering ultrafine-grained (UFG) microstructure in the material is a possible solution. However, micro-scale deformation behavior of UFG material is not fully understood. Present work attempts to comprehensively investigate the micro-scale deformation of four distinctly engineered microstructures: UFG with residual dislocations and elongated grains, UFG free of residual dislocation with equiaxed grains, bimodal-grained and coarse-grained. The deformation behavior is captured via micro-scale uniaxial tensile test and micro-deep drawing operation. Micro-cups generated from UFG material with equiaxed grains show excellent surface quality, form-accuracy and minimal process scatter. Postmortem microscopy of the formed micro-cups attributes this improved microformability to the activation of grain boundary-mediated plasticity in the material which results in synergetic grain migration and rotation. Presence of residual dislocations and elongated grains hinders the grain migration and rotation leading to strain localization and thinning. In case of bimodal and coarse-grained material, cross-slip based deformation mode progressively dominates over grain migration and rotation, which results in a reduction in microformability due to the influence of size-effect.

Relationship between Dislocation Density and Antibacterial Activity of Cryo-Rolled and Cold-Rolled Copper.

In the present work, cold rolling and cryo-rolling were performed on 99% commercially pure copper substrates. Both cold and cryo-rolling processes caused severe plastic deformation that led to an increase in dislocation density by 14× and 28× respectively, as compared to the pristine material. Increases in average tensile strengths, by 75% (488 MPa) and 150% (698 MPa), were observed in the two rolled materials as the result of the enhancement in dislocation density. In addition to strength, enhanced antibacterial property of cryo-rolled copper was observed in comparison to cold rolled and pristine copper. Initial adhesion and subsequent proliferation of bio-film forming Gram-positive bacteria Staphylococcus aureus was reduced by 66% and 100% respectively for cryo-rolled copper. Approximately 55% protein leakage, as well as ethidium bromide (EtBr) uptake, were observed confirming rupture of cell membrane of S. aureus. Inductively coupled plasma-mass spectroscopy reveals higher leaching of elemental copper in nutrient broth media from the cryo-rolled copper. Detailed investigations showed that increased dislocation led to leaching of copper ions that caused damage to the bacterial cell wall and consequently killing of bacterial cells. Cryo-rolling enhanced both strength, as well as antibacterial activity, due to the presence of dislocations.

Comparative therapeutic efficacy of levofloxacin, ornidazole and alpha tocopherol combination with prostaglandin F2α on IL-6 and IL-10 transcript level in longstanding cases of endometritis in crossbreed Jersey cows.

This study compared the therapeutic efficacy of levofloxacin, ornidazole and alpha tocopherol combination and prostaglandin F2α (PGF2α) in longstanding cases of endometritis and evaluated their impact on Interleukin-6 (IL-6) and Interleukin-10 (IL-10) transcript level in peripheral blood leukocytes. Eighteen endometritic crossbred Jersey cows were randomly allotted to three groups (six in each) viz. Group I (levofloxacin combo treatment I/U), group II (PGF2α treatment I/M), group III (no treatment, control), and group IV (six non-endometritic healthy cyclic) was taken for comparison study. The clinical efficacy was assessed by haematological study (TLC: Total leukocyte count; DC: Differential count), polymorphonuclear leukocytes (PMN) count in uterine cytology and relative mRNA expression of IL-6 and IL-10 in peripheral blood leukocytes before and after treatment with respect to conception rate following single and second inseminations. Group I and II registered significant increase in TLC and neutrophil count. PMN cytology was increased two and three fold in group I and II, respectively. The IL-6 transcript level was increased by 2.5 and 4.6 fold while that of IL-10 increased by 3.7 and 5.2 fold in group I and II, respectively. Conception rate across group I to IV following single insemination was found to be 66.67%, 50%, 16.67%, and 83.33% and their corresponding values following second insemination were 66.67%, 83.33%, 16.67%, and 83.33%, respectively. Thus, the administration of levofloxacin combo and PGF2α might have better conception rate following first and second insemination, respectively. Our study also reveals that PGF2α could register better clearance of bacteria through stronger PMN cell and cytokine activity in post-treatment period.

To evaluate and compare the efficacy of combined sucrose and non-nutritive sucking for analgesia in newborns undergoing minor painful procedure: a randomized controlled trial.

OBJECTIVE: The objective of this study was to evaluate and compare the efficacy of combined sucrose and non-nutritive sucking (NNS) for analgesia in newborn infants undergoing heel-stick procedures. STUDY DESIGN: This randomized control trial was conducted in the neonatal intensive care unit of a tertiary care hospital over a period of 1 year. One hundred and eighty full-term neonates with birth weight >2200 g and age >24 h were randomized to one of four interventions administered 2 min before the procedure: 2 ml of 30% sucrose (group I, n=45) or NNS (group II, n=45) or both (group III, n=45) or none (group IV, n=45). Primary outcome was composite score based on Premature Infant Pain Profile (PIPP) score. RESULT: Baseline variables were comparable among the groups. Median (interquartile range) PIPP score was 3 (2 to 4) in group III as compared with 7 (6.5 to 8) in group I, 9 (7 to 11) in group II and 13 (10.5 to 15) in group IV. Group III had significant decrease in the median PIPP score compared with other groups (P=0.000). Median PIPP score also decreased significantly with any intervention as compared with no intervention (P=0.000). CONCLUSION: Sucrose and/or NNS are effective in providing analgesia in full-term neonates undergoing heel-stick procedures, with the combined intervention being more effective compared with any single intervention.

Phosphorus speciation in the marine sediment of Kalpakkam coast, southeast coast of India.

A study was carried out at Kalpakkam coast to find out the distribution of various fractions of phosphorus (P) in the marine sediment during pre-northeast monsoon period. Samples were collected from ten locations covering ~80 km(2) of the inner-shelf region. Sedimentary parameters such as sand, silt, clay, and organic carbon percentage were analyzed in order to find out their relation with various P fractions. The sediment was found to be predominantly sandy in nature with low silt and clay content. Among all the fractions (loosely bound (LoP), calcium bound (CaP), iron bound (FeP), aluminum bound (AlP), and organic (OP)), CaP fraction constituted the largest portion (68.7%) followed by organic fraction (16.3%). The bioavailable P fractions ranged from 5 to 44% of the total P (TP) content. Relatively high LoP content was observed at the offshore locations with comparatively high mud percentage as compared with the near-shore locations. As FeP and AlP concentrations were directly proportional to the amount of fine-grain sediment, the low levels of these fractions found in this coastal area were therefore attributed to the sandy nature of the sediments. The order of abundance of the major forms of P in the surface sediments of Kalpakkam coast was as follows: CaP > OP > LoP > AlP > FeP.

Nutrient dynamics and seasonal variation of phytoplankton assemblages in the coastal waters of southwest Bay of Bengal.

In order to understand the phytoplankton community structure and its relationship with the environmental variables in the near shore waters of Kalpakkam, east coast of India, observations were carried out during 2008-2009. Phytoplankton population was comprised of 219 species, and the density was higher during the southwest monsoon (SWM) and inter-monsoon seasons than that of north east monsoon (NEM) season. The nutrient status on a temporal and spatial scale indicated the impact of point sources carrying anthropogenic runoff. Comparison of ambient nutrient ratios with the Redfield ratio (N/P/Si = 16:1:16) showed a clear temporal variation in the factors that regulate the phytoplankton growth. SWM and inter-monsoon season was evident to have an acute N-limitation of algal growth (~76%) whereas P-limitation was encountered during the NEM season (~75%). Interestingly, a sizable population of cyanobacteria (Trichodesmium erythraeum) were noticed during NEM season when there was an exponential increase in nitrogen concentration, probably due to nitrogen fixation. No significant impact of temperature on phytoplankton proliferation was observed in situ during the study period.

Novel aspects of Kindlin-3 function in humans based on a new case of leukocyte adhesion deficiency III.

BACKGROUND: Kindlin-3 is a novel integrin activator in hematopoietic cells, and its deficiency leads to immune problems and severe bleeding, known as leukocyte adhesion deficiency III (LAD-III). Our current understanding of Kindlin-3 function primarily relies on analysis of animal models or cell lines. OBJECTIVES: To understand the functions of Kindlin-3 in human primary blood cells. PATIENTS/METHODS: We analyzed primary and immortalized hematopoietic cells obtained from a new LAD-III patient with immune problems, bleeding, a history of anemia, and abnormally shaped red blood cells. RESULTS: The patient's white blood cells (WBCs) and platelets showed defects in agonist-induced integrin activation and botrocetin-induced platelet agglutination. Primary leukocytes from this patient exhibited abnormal activation of ß(1) integrin. Integrin activation defects were responsible for the observed deficiency in the botrocetin-induced platelet response. Analysis of patient genomic DNA revealed a novel mutation in the Kindlin3 gene. The mutation abolished Kindlin-3 expression in primary WBCs and platelets, owing to abnormal splicing. Kindlin-3 is expressed in red blood cells (RBCs), and its deficiency is proposed to lead to abnormally shaped RBCs. Immortalized patient WBCs expressed a truncated form of Kindlin-3 that was not sufficient to support integrin activation. Expression of Kindlin-3 cDNA in immortalized patient WBCs rescued integrin activation defects, whereas overexpression of the truncated form did not. CONCLUSIONS: Kindlin-3 deficiency impairs integrin function, including activation of ß(1) integrin. Abnormalities in glycoprotein Ib-IX function in Kindlin-3-deficient platelets are secondary to integrin defects. The region of Kindlin-3 encoded by exon 11 is crucial for its ability to activate integrins in humans.

Virtual screening of 4-anilinoquinazoline analogues as EGFR kinase inhibitors: importance of hydrogen bonds in the evaluation of poses and scoring functions.

Virtual Screening (VS) is a computational technique that allows selection and ranking of possible hits from a library of compounds. We have carried out VS on 128 selected EGFR kinase inhibitors with GOLD and LigandFit. From the experimental crystal structure of the erlotinib-EGFR complex, three key hydrogen bonds were identified as responsible for anchoring the ligand in the active site. These are of the N-H...N, O(w)-H...N, and C-H...O types. Failure to include the hydrogen-bonded water molecule that forms the O(w)-H...N bond leads to incorrect results. Of the three interactions, the C-H...O formed by an activated C-H group is the best conserved. On the basis of the efficacy of these hydrogen bonds, the poses were classified into one of three categories: close, shifted, and misoriented. In the VS context, all three interactions need to be modeled correctly so that correct poses and affinities are obtained, and this happens in ligands of the close variety. Cross scoring wherein the poses from one software are input into another for scoring and consensus scoring wherein the scores from various software packages are weighted are also helpful in obtaining better agreements.

Nonmyeloablative stem cell transplantation for the treatment of cancer and life-threatening nonmalignant disorders: past accomplishments and future goals.

Allogeneic bone marrow transplantation (BMT) or blood stem cell transplantation represents an important therapeutic tool for the treatment of otherwise incurable malignant and nonmalignant diseases. Until recently. autologous and allogeneic BMT or mobilized blood stem cell transplantation was used primarily to replace a malignant, genetically abnormal, or deficient immunohematopoietic compartment, and therefore highly toxic myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies have indicated that more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT. Thus eradication of blood cancer cells, especially in patients with chronic myelogenous leukemia and less frequently in patients with other hematologic malignancies, can frequently be achieved despite complete resistance of such tumor cells to the maximum tolerated doses of chemoradiotherapy. Our cumulative experience suggests that graft vs leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. Based on the cumulative clinical experience and experimental data in animal models of human diseases, it appears that induction of host vs graft tolerance as the first step may allow durable engraftment of immunocompetent donor lymphocytes, which may be used for induction of effective biologic warfare against host-type immunohematopoietic cells that need to be replaced, whether they are malignant, genetically abnormal, or self-reactive. Based on this rationale, we speculate that the therapeutic benefit of BMT may be increased by using safer conditioning as part of the transplantation procedure, with the goal of inducing host vs graft tolerance to enable subsequent induction of GVL, possibly graft vs tumor, or even graft vs autoimmunity effects, rather than attempting to eliminate host cells with hazardous myeloablative chemoradiotherapy. Our hypothesis suggests that effective BMT procedures might be accomplished without lethal conditioning of the host, using new, well-tolerated nonmyeloablative regimens, possibly minimizing immediate and late side effects related to myeloablative procedures. Recent clinical data suggest that effective BMT procedures may be accomplished with nonmyeloablative stem cell transplantation (NST) regimens, with no major toxicity. Thus new NST approaches may make BMT procedures safer for a spectrum of clinical indications in children and elderly individuals without lower or upper age limits, while minimizing procedure-related toxicity and mortality. Our cumulative data suggest that high-dose chemotherapy and radiation therapy may be successively replaced by more effective alloreactive donor lymphocytes, thus setting the stage for innovative therapeutic procedures with safer and more effective treatment of patients requiring BMT.

Non-myeloablative allogeneic stem cell transplantation focusing on immunotherapy of life-threatening malignant and non-malignant diseases.

Allogeneic bone marrow transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion (DLI) following BMT. Thus, eradication of blood cancer cells, especially in patients with CML can be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. The latter working hypothesis suggested that effective BMT procedures may be accomplished without lethal conditioning of the host, using new well tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that safe non-myeloablative stem cell transplantation (NST), with no major toxicity can replace the conventional BMT. Thus, NST may provide an option for cure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality.

Indolent aspergillus arthritis complicating fludarabine-based non-myeloablative stem cell transplantation.

Fungal arthritis and osteomyelitis are rare and documented mainly in immunocompromised or neutropenic patients. Patients receiving therapeutic immunosuppression for organ transplants have also reported to suffer from aspergillus osteoarthritis. We describe two patients with aspergillus arthritis of the knee joint following fludarabine-based non-myeloablative stem cell transplantation. Both were suffering from acute and chronic GVHD and treated with heavy immunosuppression including steroids and cyclosporine. Interestingly in one of our patients, the arthritis was almost asymptomatic and did not spread to other organs. Heavy pre- and post-transplant immunosuppression is a major risk factor for invasive fungal infection, which can involve remote organs and manifest in an indolent and atypical manner.

Moisture prediction from simple micrometeorological data.

ABSTRACT Four linear regression methods and a generalized regression neural network (GRNN) were evaluated for estimation of moisture occurrence and duration at the flag leaf level of wheat. Moisture on a flat-plate resistance sensor was predicted by time, temperature, relative humidity, wind speed, solar radiation, and precipitation provided by an automated weather station. Dew onset was estimated by a classification regression tree model. The models were developed using micrometeorological data measured from 1993 to 1995 and tested on data from 1996 and 1997. The GRNN outperformed the linear regression methods in predicting moisture occurrence with and without dew estimation as well as in predicting duration of moisture periods. Average absolute error for prediction of moisture occurrence by GRNN was at least 31% smaller than that obtained by the linear regression methods. Moreover, the GRNN correctly predicted 92.7% of the moisture duration periods critical to disease development in the test data, while the best linear method correctly predicted only 86.6% for the same data. Temporal error distribution in prediction of moisture periods was more highly concentrated around the correct value for the GRNN than linear regression methods. Neural network technology is a promising tool for reasonably precise and accurate moisture monitoring in plant disease management.

The nutritive value of stackburned yellow maize for livestock: tests in vitro and in broiler chicks.

Difference in the nutritive value of four grades of stackburned yellow maize, obtained from a single storage unit in Mozambique, were examined. Samples were analysed for chemical composition, and subjected to the following in vitro assays for estimating digestibility: total dietary fibre and pancreatin for non-ruminants, and gas production using sheep rumen fluid for ruminant livestock. Samples were also fed to broiler chicks at 600 g/kg diet in a growth trial. There were no significant differences in crude protein contents of the maize samples, but there was evidence for the development of Maillard reaction products. Detectable amino acids were lower in discoloured maize, with decreases of 52% in lysine, 35% in arginine, and 15% in glycine concentration in the most severely discoloured sample compared with control. Total starch, reducing sugar, acid-detergent fibre and amylase-neutral-detergent fibre values increased, while total non-reducing sugar content decreased with increased discolouration. Total dietary fibre and pancreatin assays indicated a lowering in digestibility of maize with increasing discolouration. Weight gain of chicks (P = 0.0228), efficiency of feed utilization (P = 0.0009) and the metabolizable energy value of diets decreased (P < 0.0001) with increasing stackburn discolouration. There were no significant effects on N retention of diets. In vitro fermentation using sheep rumen fluid showed a linear decrease in gas production with increasing maize discolouration, indicating a reduction in rumen degradability with stackburn.

Effects on dietary phosphorus of treating cottonseed meal with crystalline ferrous sulphate for the prevention of brown yolk discolouration.

1. Two experiments were carried out to examine whether the adverse effects on laying hen performance of treating cottonseed meal (CSM) with crystalline ferrous sulphate heptahydrate (FSH) to prevent brown yolk discolouration, was a consequence of iron reducing the availability of dietary phosphorus. Two batches of CSM, with different free gossypol and cyclopropenoid fatty acid contents, were treated with FSH at a 4:1 weight ratio of iron to free gossypol, and incorporated into diets at 300 g/kg with or without supplementation with sodium dihydrogen phosphate (SHP), and fed to hens. 2. FSH treatment of CSM reduced food intake and egg production. Although performance was improved by supplementing the FSH-treated CSM diets with SHP, it was still poorer than that achieved by hens fed a non-CSM control diet. 3. Brown yolk discolouration was prevented by treatment of CSM with FSH. Additional phosphorus did not produce any significant effects on brown colour development in yolks, indicating that the bioavailable gossypol content of the diets had not been altered; however, chemical analyses showed an apparent increase in the free gossypol content of the diets with the inclusion of SHP, suggesting that the assay gives misleading results.

Effects of oven-drying tubers of two high-protein sweet potato varieties at different temperatures on their feeding value in broilers.

1. Unpeeled tubers from 2 high-protein varieties of sweet potato (white-fleshed Bosbok, and orange-fleshed Carmel) were chipped and oven-dried at 40, 60, or 80 degrees C, to examine the effects on nutritive value. The dried ground chips were substituted for maize at 500 g/kg and the diets fed to day-old, Ross-1 broiler chicks for 3 weeks. 2. Compared with Carmel, Bosbok had a lower crude protein content (90 V. 138 g/kg DM) and trypsin inhibitor activity (TIA) (3 v. 5 mg of trypsin inhibited per g flour). Processing did not significantly affect TIA, but the lysine and cystine contents were lowered and the starch content raised as the drying temperature increased. However, whereas this was reflected in increased reducing sugars in Carmel, there was no trend in Bosbok. 3. The results of in vitro pancreatin digestibility and total dietary fibre assays showed variety and processing temperature to be significant factors influencing the nutritive value of sweet potato tubers, with a variety temperature interaction also being indicated. The interaction was also observed for weight gain, dry matter intake, water: food intake ratios, excreta water content, presence of bile in excreta and liver weights. The best growth was obtained with Bosbok dried at 60 degrees C , for which liveweights at 21 d were 11% lower than for the maize controls.

Bioassay of mycotoxins using terrestrial and aquatic, animal and plant species.

The role of bioassay in the diagnosis of mycotoxicoses in farm animals is discussed. Methods for detecting mycotoxin contamination of animal feeds using biological species (aquatic and terrestrial animals and plants but excluding bacteria and yeast) are reviewed. Factors that need to be considered when choosing and using particular bioassay procedures in a feed-screening programme are discussed in relation to the occurrence of false positives and false negatives.