Influence of interleukin-1 beta on platelet-poor plasma clot formation: A potential impact on early bone healing

Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition

Laskowski inhibitors regulate serine proteases by an intriguing mode of action that involves deceiving the protease into synthesizing a peptide bond. Studies exploring naturally occurring Laskowski inhibitors have uncovered several structural features that convey the inhibitor's resistance to hydrolysis and exceptional binding affinity. However, in the context of Laskowski inhibitor engineering, the way that various modifications intended to fine-tune an inhibitor's potency and selectivity impact on its association and dissociation rates remains unclear. This information is important as Laskowski inhibitors are becoming increasingly used as design templates to develop new protease inhibitors for pharmaceutical applications. In this study, we used the cyclic peptide, sunflower trypsin inhibitor-1 (SFTI-1), as a model system to explore how the inhibitor's sequence and structure relate to its binding kinetics and function. Using enzyme assays, MD simulations and NMR spectroscopy to study SFTI variants with diverse sequence and backbone modifications, we show that the geometry of the binding loop mainly influences the inhibitor's potency by modulating the association rate, such that variants lacking a favourable conformation show dramatic losses in activity. Additionally, we show that the inhibitor's sequence (including both the binding loop and its scaffolding) influences its potency and selectivity by modulating both the association and the dissociation rates. These findings provide new insights into protease inhibitor function and design that we apply by engineering novel inhibitors for classical serine proteases, trypsin and chymotrypsin and two kallikrein-related peptidases (KLK5 and KLK14) that are implicated in various cancers and skin diseases.

Stereochemical analysis of the antigenic tip of the V3 loop peptide of HIV-1 gp120

A novel multiple turn conformation has been observed for a segment GPGRAFY in the crystal structure of a complex of HIV-1 gp120 V3 loop peptide with the Fab fragment of a neutralizing antibody [Ghiara ct al. (1994) Science 264, 82-85]. A structural motif has been defined for the peptide segment, employing idealized backbone conformations characterized by ranges of virtual C-alpha torsion angles and bond angles. A search of 122 high-resolution protein crystal structures has permitted identification of 24 examples of similar structural motifs. Two major conformational families have been identified, which differ primarily in the conformation at residue 3. The observed conformation at residue 3 in family 1 is left-handed helical (alpha(L)) and that in family 2 is right-handed helical (alpha(R)). Of the 10 examples in family 1, 9 examples have Gly residues at position 3. Of the 12 examples in family 2, 7 examples have Asn/Asp at position 3. Computer modeling of the V3 loop tip sequence using the two backbone conformational families as starting points leads to minimum-energy conformations in which antigenically important side-chains occupy similar spatial arrangements. This stereochemical analysis of the V3 loop tip sequence suggests a rational basis for the design of synthetic analog peptides for use as viral antagonists or synthetic antigens. (C) Munksgaard 1995.

Exame da compatibilidade e adequação orçamentária e financeira da emenda apresentada na CFT AO PL 6.243/2014 : Cria Funções Comissionadas do Departamento de Polícia Rodoviária Federal - FCPRF; e cria e extingue cargos em comissão do Grupo-Direção e Assessoramento Superiores - DAS e Funções Gratificadas

Avalia a compatibilidade e adequação orçamentária e financeira da Emenda 1/2013, de autoria do Deputado Arnaldo Jordy, apresentada na Comissão de Finanças e Tributação : CFT ao Projeto de Lei nº 6.243, de 2013

Studies on the complex formation of iron with humic substances [Translation from: Vom Wasser 53, 243-247, 1979]

Most of the humic substances which occur in natural waters have an iron content of a few percent, indicated by the mg/1 content of organically-bonded carbon. This iron is apparently bound in a complex with the humic substances, for it quite plainly differs in its chemical and physico-chemical properties from what one would expect from the purely inorganic iron-water system. The deviations range from the solubility to the redox behaviour, and thus are frequently the basis of analytical and technical difficulties. The key to the solution of most of this problem lies in a better understanding of the aforementioned bonds between the iron and the humic substances. This paper studies the iron content of the humic substance concentration from a bog lake sample and the complexing of iron by humic substances from the surface of the bog lake.

Linefish resources annual report for the year 2000. Part 1: fisheries assessment

This work reflects the activities of line and trap fishing in Southern Mozambique in 2000. The catch in line fishing has been estimated at 441 mt, according to the DNAP records. The same sources indicated that 1767 days were spent at sea and the estimated catch rate was 250 Kg per boaticlay. Most of the line fishing effort shifted away from Maputo and moved to Inhambane region. The monthly analysis of fishing vessels, stricter controls over catch and effort data submission, development of long-term research programme and the continuation of the on board sampling to improve the data collection are the recommendation for line fishing. The catch of trap vessels increases from 30mt in 1997 to 172 mt in 2000, during which the total number of traps increased from 25 to 300. During this time the number of fishing days has remained relatively constant, as well the soak time. These data sets are thus not compatible with each other, reflecting an increase in daily catch from 243 Kg to 791 kg. The species composition is mainly dominated by P. coeruleopunctatus, C. puniceus, C. nufar and E. andersoni.

Alpha-momorcharin inhibits HIV-1 replication in acutely but not chronically infected T-lymphocytes

AIM: To identify the anti-human immunodeficiency virus type 1 (HIV-1) activities of alpha-momorcharin ( alpha-MMC) from Momordica charantia in acutely and chronically infected lymphocytes. METHODS: The anti-HIV activities of alpha-MMC were examined by 1) the inhibition of syncytia formation induced by HIV-1 III B; 2) reduction of p24 core antigen expression level and decrease in numbers of HIV antigen positive cells in acutely and chronically infected cultures. The cytotoxic effects of alpha-MMC was tested by trypan blue dye exclusion or colorimetric MTT assay. RESULTS: alpha-MMC was found to obviously inhibit HIV-1 III B-inducing C8166 syncytia formation and markedly reduced both expression of p24 core antigen and the numbers of HIV antigen positive cells in acutely but not chronically HTV-1-infected culture. The median effective concentration (EC50) in these assays were 0.016, 0.07, and 0.32 mg.L-1, respectively. CONCLUSION: alpha-MMC is a unique component of momorcharin with anti-HIV activity, and markedly inhibited HIV-1 replication in acutely but not chronically HIV-1-infected T-lymphocytes.

Dependence of optical properties on the structure of multi-layer self-organized InAs quantum dots emitting near 1.3 mu m

Self-organized InAs quantum dots (QDs) have been fabricated by molecular beam epitaxy and characterized by photoluminescence (PL). For both single- and multi-layer QDs, PL intensity of the first excited state is larger than that of the ground state at 15 K. Conversely, at room temperature (RT), PL intensity of the first excited state is smaller than that of the ground state. This result is explained by the phonon bottleneck effect. To the ground state, the PL intensities of the multi-layer QDs are larger than that of the single-layer QDs at 15 K, while the intensities are smaller than that of the single-layer QDs at RT. This is due to the defects in the multi-layer QD samples acting as the nonradiative recombination centers. The inter-diffusion of Ga and In atoms in the growth process of multi-layer QDs results in the PL blueshift of the ground state and broadening of the full-width at half-maximum (FWHM), which can be avoided by decreasing the spacers' growth temperature. At the spacers' growth temperature of 520degreesC, we have prepared the 5-layer QDs which emit near 1.3 mum with a FWHM of 31.7 meV at RT, and 27.9 meV at 77 K. (C) 2002 Published by Elsevier Science B.V.

Isolation and Characterization of a Methomyl-Degrading Paracoccus sp mdw-1

Methomyl, an extremely toxic pesticide, is widely used in agriculture. A strain named mdw-1 capable of degrading methomyl rapidly was successfully isolated from activated sludge in this study. It could utilize methomyl as the sole carbon or nitrogen source. The optimal temperature and medium pH for its growth and methomyl biodegradation were 30 degrees C and 7.0, respectively. It was identified as a Paracoccus sp. according to its morphological features, physiological and biochemical characteristics, and phylogenetic analysis based on the sequence of 16S rDNA. Gas chromatography-mass spectrometry (GC-MS) analysis showed that methomyl could be completely transformed to S-methyl-N-hydroxythioacetamidate in 10 h of incubation with the isolate mdw-1.

分子镀法制备厚镅(~(241,243)Am)靶

研究了异丙醇 -硝酸介质中镅 ( 2 4 1,2 4 3Am)的分子镀过程和实验条件。在保持电压为 550 V、电流密度为 4～ 6m A/ cm2 的条件下电镀 1h,通过一次分子镀过程就能在薄铝箔 (厚度 7μm)衬底材料上制备出厚度为 0 .6～ 1.2 mg/ cm2的 2 4 1,2 4 3Am靶。

IMPLEMENTATION OF SIGNAL PROCESSING FUNCTIONS USING 1-BIT SYSTOLIC ARRAYS.

The use of systolic arrays of 1-bit cells to implement a range of important signal processing functions is demonstrated. Two examples, a pipelined multiplier and a pipelined bit-slice transform circuit, are given. This approach has many important implications for silicon technology, and these are outlined.

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies

Aims/hypothesis The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.

Methods A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.

Results In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors’ adjustments for potential confounding made a substantial difference to the pooled ORs.

Conclusions/interpretation This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.