150 research outputs found

    An empirical formula for predicting the depth of hardness durign induction hardening

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    The prediction of the depth of hardness in terms of power density and scanning rate has been one of the central problems of interest in induction hardening of cylindrical parts like Axel Shafts, Piston Pins, Torsion Bars and King Pins. In this thesis an empirical relationship is developed that can be used to predict the depth of hardness for AISI C 1045 normalized steel once the hardening conditions have been selected and without the necessity of conducting a trial hardening operation, thus saving electrical power, generator and scanning machine time

    In situ synthesis of nanoclay filled polyethylene using polymer supported metallocene catalyst system

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    In situ ethylene polymerizations were performed using bis(cyclopentadiene)titanium dichloride supported on polyethersulfone as catalyst. The bis(cyclopentadiene)titanium dichloride supported on polyethersulfone catalyst activity estimated by ethylene polymerization was 360 kgPE/molTi/h. During polymerization the fillers used were montmorillionite nanoclays having surface modifications with 35-45 wt% dimethyl dialkyl(14-18)amine (FA) and 25-30 wt% trimethyl stearyl ammonium (FB). These fillers were pretreated with methylaluminoxine (MAO; cocatalyst) for better dispersion onto the polymer matrix. The formation of polyethylene within the whole matrix was confirmed by FTIR studies. It was found that the nature of nanofiller did not have any remarkable effect on the melting characteristics of the polymer. TGA study indicates that nanoclay FB filled polyethylene has higher thermal stability than nanoclay FA filled polyethylene. The melting temperature of the obtained polyethylenes was 142 ºC, which corresponds to that synthesized by the polyether sulfone supported catalyst

    The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions

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    Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9, an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to diminish expression of these genes. The mechanism involved interactions between CTCF and class II transactivator (CIITA), the master regulator of major histocompatibility complex class II (MHC-II) gene expression, and the formation of long-distance chromatin loops between XL9 and the proximal promoter regions of these MHC-II genes. The interactions were inducible and dependent on the activity of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations show that both genes can be expressed simultaneously from the same chromosome. Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci can interact simultaneously with XL9, and describe a new regulatory mechanism for these MHC-II genes involving the alteration of the general chromatin conformation of the region and their regulation by CTCF

    Choroba Mikulicza-Radeckiego z zapaleniem przysadki — nowe zaburzenie związane z IgG4

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      Introduction: We present a case of Mikulicz’s Disease with hypophysitis. This is a rare clinical association as part of the group of IgG4- related diseases, a group of disorders which can have multiorgan involvement. Methods: A 55-year-old male patient was diagnosed with Mikulicz’s disease. He was treated with oral steroids for six months with complete resolution. After two years the patient presented with fatigue, generalised weakness, and weight loss of 11 kg over six months. On evaluation he was found to have panhypopituitarism. MRI pituitary revealed homogeneously enlarged, well enhancing pituitary with thickening of the stalk. Serum IgG4 levels were significantly elevated. The patient was treated with methyl prednisolone pulse therapy followed by oral steroids for three months. He developed diabetes insipidus after starting steroid therapy. There was a significant resolution in the enlargement of the pituitary and stalk thickening at three months. Results: The clinical, biochemical, and radiological findings of hypophysitis associated with Mikulicz’s disease are presented with a brief review of literature. Conclusions: IgG4-related diseases are rare and have recently been recognised as a cause of hypophysitis. They can have multiorgan involvement. A high index of suspicion is required for clinching this rare diagnosis, which can be confirmed by measurement of serum levels of IgG4. Steroid therapy can reverse the inflammatory changes in IgG4 hypophysitis. (Endokrynol Pol 2016; 67 (6): 622–626)    Wstęp: W pracy przedstawiono przypadek choroby Mikulicza-Radeckiego z zapaleniem przysadki. Jest to rzadko występujące połączenie zaburzeń należących do grupy chorób związanych z IgG4, które mogą obejmować wiele narządów. Metody: U mężczyzny w wieku 55 lat rozpoznano chorobę Mikulicza-Radeckiego. Stosowano doustne steroidy przez 6 miesięcy, uzyskując całkowite ustąpienie choroby. Po 2 latach chory zaczął odczuwać zmęczenie i ogólne osłabienie, a ponadto w ciągu 6 miesięcy schudł 11 kg. Badanie wykazało wielohormonalną niedoczynność przysadki. Badanie rezonansu magnetycznego przysadki uwidoczniło równomiernie powiększoną, ulegającą wzmocnieniu po podaniu kontrastu, z pogrubioną szypułą. Stężenie IgG4 w surowicy było istotnie podwyższone. U pacjenta zastosowano najpierw terapię pulsacyjną metylprednizolonem, a następnie 3-miesięczne leczenie steroidami podawanymi doustnie. Po rozpoczęciu leczenia steroidami u chorego rozwinęła się moczówka prosta. Po 3 miesiącach nastąpiło istotne zmniejszenie powiększonej przysadki i pogrubionej szypuły. Wyniki: Przedstawiono kliniczne, biochemiczne i radiologiczne objawy niedoczynności przysadki związanej z chorobą Mikulicza-Radeckiego oraz krótki przegląd literatury. Wnioski: Choroby związane z IgG4 występują rzadko. W ostatnim czasie wykazano, że mogą powodują one niedoczynność przysadki. Mogą one obejmować wiele narządów. Rozpoznanie tej rzadkiej choroby można potwierdzić, oznaczając stężenie IgG4 w surowicy. Można potwierdzić diagnozę, mierząc stężenie IgG4 w surowicy. Leczenie steroidami może spowodować ustąpienie zmian zapalnych z niedoczynności przysadki związanej z IgG4. (Endokrynol Pol 2016; 67 (6): 622–626)

    Shaped Charge Jet Penetration of Alon® Ceramic Assessed by Proton Radiography and Computational Simulations

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    AbstractThis work describes the use of proton radiography and continuum simulations to investigate the mechanics of a copper jet penetrating unconfined ALON® transparent ceramic. Use of proton radiography enabled characterization of the jet and ceramic material at 21 time steps, in situ, throughout the penetration process. These radiographs provide time-evolution data pertaining to the material densities, cavity growth, and material failure. The data were compared to legacy analytical penetration models and to a simulation of the event computed using a continuum multi-physics code. These comparisons revealed additional insights into the penetration mechanics as well as strengths and weaknesses of the computational algorithms and material models used in the simulations

    Research for practice in small human service organisations: doing and disseminating smallscale research

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    A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives were designed, synthesized and evaluated in vitro as potential inhibitors of chorismate mutase (CM). All these compounds were prepared via a multi-component reaction (MCR) involving sequential I2-mediated Biginelli reaction followed by Cu-free Sonogashira coupling. Some of them showed promising inhibitory activities when tested at 30 μM. One compound showed dose dependent inhibition of CM with IC50 value of 14.76 ± 0.54 μM indicating o-alkynylphenyl substituted DHPM as a new scaffold for the discovery of promising inhibitors of CM

    Establishment of Systems to Enable Isolation of Porcine Monoclonal Antibodies Broadly Neutralizing the Porcine Reproductive and Respiratory Syndrome Virus

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    The rapid evolution of porcine reproductive and respiratory syndrome viruses (PRRSV) poses a major challenge to effective disease control since available vaccines show variable efficacy against divergent strains. Knowledge of the antigenic targets of virus-neutralizing antibodies that confer protection against heterologous PRRSV strains would be a catalyst for the development of next-generation vaccines. Key to discovering these epitopes is the isolation of neutralizing monoclonal antibodies (mAbs) from immune pigs. To address this need, we sought to establish systems to enable the isolation of PRRSV neutralizing porcine mAbs. We experimentally produced a cohort of immune pigs by sequential challenge infection with four heterologous PRRSV strains spanning PRRSV-1 subtypes and PRRSV species. Whilst priming with PRRSV-1 subtype 1 did not confer full protection against a subsequent infection with a PRRSV-1 subtype 3 strain, animals were protected against a subsequent PRRSV-2 infection. The infection protocol resulted in high serum neutralizing antibody titers against PRRSV-1 Olot/91 and significant neutralization of heterologous PRRSV-1/-2 strains. Enriched memory B cells isolated at the termination of the study were genetically programmed by transduction with a retroviral vector expressing the Bcl-6 transcription factor and the anti-apoptotic Bcl-xL protein, a technology we demonstrated efficiently converts porcine memory B cells into proliferating antibody-secreting cells. Pools of transduced memory B cells were cultured and supernatants containing PRRSV-specific antibodies identified by flow cytometric staining of infected MARC-145 cells and in vitro neutralization of PRRSV-1. Collectively, these data suggest that this experimental system may be further exploited to produce a panel of PRRSV-specific mAbs, which will contribute both to our understanding of the antibody response to PRRSV and allow epitopes to be resolved that may ultimately guide the design of immunogens to induce cross-protective immunity

    Calcium/Calmodulin Dependent Protein Kinase II Bound to NMDA Receptor 2B Subunit Exhibits Increased ATP Affinity and Attenuated Dephosphorylation

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    Calcium/calmodulin dependent protein kinase II (CaMKII) is implicated to play a key role in learning and memory. NR2B subunit of N-methyl-D-aspartate receptor (NMDAR) is a high affinity binding partner of CaMKII at the postsynaptic membrane. NR2B binds to the T-site of CaMKII and modulates its catalysis. By direct measurement using isothermal titration calorimetry (ITC), we show that NR2B binding causes about 11 fold increase in the affinity of CaMKII for ATPγS, an analogue of ATP. ITC data is also consistent with an ordered binding mechanism for CaMKII with ATP binding the catalytic site first followed by peptide substrate. We also show that dephosphorylation of phospho-Thr286-α-CaMKII is attenuated when NR2B is bound to CaMKII. This favors the persistence of Thr286 autophosphorylated state of CaMKII in a CaMKII/phosphatase conjugate system in vitro. Overall our data indicate that the NR2B- bound state of CaMKII attains unique biochemical properties which could help in the efficient functioning of the proposed molecular switch supporting synaptic memory

    Werner Protein Is a Target of DNA-dependent Protein Kinase in Vivo and in Vitro , and Its Catalytic Activities Are Regulated by Phosphorylation

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    Human Werner Syndrome is characterized by early onset of aging, elevated chromosomal instability, and a high incidence of cancer. Werner protein (WRN) is a member of the recQ gene family, but unlike other members of the recQ family, it contains a unique 3'-->5' exonuclease activity. We have reported previously that human Ku heterodimer interacts physically with WRN and functionally stimulates WRN exonuclease activity. Because Ku and DNA-PKcs, the catalytic subunit of DNA-dependent protein kinase (DNA-PK), form a complex at DNA ends, we have now explored the possibility of functional modulation of WRN exonuclease activity by DNA-PK. We find that although DNA-PKcs alone does not affect the WRN exonuclease activity, the additional presence of Ku mediates a marked inhibition of it. The inhibition of WRN exonuclease by DNA-PKcs requires the kinase activity of DNA-PKcs. WRN is a target for DNA-PKcs phosphorylation, and this phosphorylation requires the presence of Ku. We also find that treatment of recombinant WRN with a Ser/Thr phosphatase enhances WRN exonuclease and helicase activities and that WRN catalytic activity can be inhibited by rephosphorylation of WRN with DNA-PK. Thus, the level of phosphorylation of WRN appears to regulate its catalytic activities. WRN forms a complex, both in vitro and in vivo, with DNA-PKC. WRN is phosphorylated in vivo after treatment of cells with DNA-damaging agents in a pathway that requires DNA-PKcs. Thus, WRN protein is a target for DNA-PK phosphorylation in vitro and in vivo, and this phosphorylation may be a way of regulating its different catalytic activities, possibly in the repair of DNA dsb
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