Search

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Electronic signals shift valves precisely to control flow and pressure - and thus acceleration, deceleration, velocity, and force - in open- and closed-loop circuits Advances in hardware and software for [...]

What's available in pneumatic quick-acting couplings A look at some of the handy connectors available in the marketplace Originally developed to connect and disconnect air hoses to hand-held pneumatic tools [...]

Copyright of Tijdschrift voor Consumentenrecht en Handelspraktijken is the property of Uitgeverij Paris and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A look at hydraulic manifolds This quick study spotlights several of the advantages that manifolds offer designers and users The growing diversity and resultant popularity of cartridge valves has spurred [...]

Stringent performance requirements challenge these engineered connectors A major manufacturer of hydraulic hose and couplings once estimated that fittings and connectors accounted for more than half of its reported field [...]

OSHA lockout/tagout rule affects most industrial equipment The following is the official summary of the OSHA lockout/tagout standard*, as it appeared in the Federal Register, September 1, 1989, Rules and [...]

Purpose: Accumulation of water within airspaces causes impairment of gas exchange in edematous lungs. Recent reports suggest that some [CO.sub.2] exchange across cellular membranes of frog oocytes occurs through water [...]

We explored how addressing culture may improve patient-provider relationships and reduce health disparities for racial and ethnic individuals with limited English proficiency (LEP). We analyzed qualitative data collected to explore health disparities in preventive cancer screenings for Hmong and Spanish-speaking LEP patients in a large Midwest healthcare system. We interviewed 20 participants (10 from each group) and the audiotaped interviews were transcribed verbatim, then back translated focusing on meaning. Data was analyzed using content analysis. Two themes are: conversation is relational and quality time is valued. Good communication skills involve the amount of conversation, clear explanations, and engaging with the patient. Quality of time meant physical time spent with patient and the task-oriented nature of the encounter. Cultural literacy in healthcare practice helps to understand the whole patient rather than focusing on the symptoms of illness. Patients should not be treated in isolation of their culture. A patient-centered approach to care means physicians should not remain culturally neutral but be more culturally sensitive. We propose steps to reduce disparities by increasing the awareness of cultural literacy for physicians to improve patient-provider relationship.

Here are examples of unusual non-special pump controls At first thought, the term distinctive, off-the shelf/out-of a-catalog controls for variable-displacement pumps would seem ambiguous. However, as the examples of pump [...]

Effective sealing is essential to efficient performance by fluid power systems. And the perception - sometimes real - of fluid power systems as leakage-prone has been a major detriment to [...]

T3, the first commercial robot, has direct hydraulic drive for high torque, and one cylinder and five actuators to provide high repeatability. It is designed to operate in difficult conditions for long periods.

Background: Early recognition of neonatal seizures secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications, but respond well to sodium-channel blockers. We report a unique aEEG pattern in neonatal seizures caused by SCN2Aand KCNQ3pathogenic variants, as well as adding regular EEG description. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and conventional EEG findings of 10 newborns with seizures due to pathogenic SCN2Aand KCNQ3gene variants. Results: Seizures started in the first postnatal week. Seizure semiology typically included tonic posturing with apnea and desaturation. The aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral attenuation in the EEG at onset, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. The majority of patients became seizure free upon initiation of a sodium-channel blocker. Conclusions: Neonatal seizures caused by SCN2Aand KCNQ3mutations can be recognized by a characteristic ictal aEEG pattern and clinical semiology. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium-channel blockers even before genetic test results are available.

A look at airline drains A variety of products are available to remove liquids from compressed-air systems Almost all atmospheric air contains some amount of water vapor. When this water [...]

Air preparation combinations are convenient, attractive, and get the one Almost every pneumatically powered machine or tool benefits from having its supply air filtered, regulated, and lubricated. The components that [...]

Through the monitoring of the auto-fluorescent mitochondrial metabolic coenzymes, NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavoprotein Adenine Dinucleotide), the redox state of metabolism can be probed in real time in many intact organs, but its use has not been fully developed in lungs. The ratio of these fluorophores, (NADH/FAD), referred to as the mitochondrial redox ratio (RR), can be used as a quantitative metabolic marker of tissue. We have designed a fluorometer that can be used to monitor lung surface NADH and FAD fluorescence in isolated perfused lungs. Surface fluorescence NADH and FAD signals were acquired in the absence (control) and presence of pentachlorophenol (PCP), rotenone, and potassium cyanide (KCN). Rotenone, an inhibitor of complex I, increased RR by 18%, predominantly due to an increase in NADH signal. KCN, an inhibitor of complex IV reduced the chain and resulted in an increase of 33% in RR, as a result of 23% increase in NADH and 8% in FAD . PCP, an uncoupler which oxidizes the respiratory chain, decreased RR by 18% as a result of 14% decrease in NADH signal and 4% increase in FAD signal. These results demonstrate the ability of surface fluorometry to detect changes in lung tissue mitochondrial redox state in isolated perfused lungs.

This paper presents the experimental study of fibre Bragg grating sensors for measuring strain inside composite laminates during fatigue loading. The optical fibres are imbedded inside thermoplastic CFRP test-coupons which have an ultimate strain of about 1.1%. Tension – tension fatigue cycling at a rate of 5Hz is been carried out at 314MPa with a maximum strain of 0.51%. At such extreme strain levels the use of high strength sensors becomes inevitable. Neither the sensor nor the composite test-coupons showed any significant degradation even after more than 500000 cycles. Fibre optic Bragg grating sensors are known to be very accurate strain sensors but one should be very careful interpreting their response once they are imbedded inside composite materials. In this study high strength fibre Bragg grating sensors with coating are imbedded in composite test coupons and a pretty good correlation was found between the strain measurements of an electrical extensometer and the imbedded sensor during the complete cycling. The high strength sensor show to be very feasible for extreme and long term strain measurements.

This paper presents the experimental study of fibre Bragg grating sensors for measuring strain inside composite laminates during fatigue loading. The optical fibres are imbedded inside thermoplastic CFRP test-coupons which have an ultimate strain of about 1.1%. Tension – tension fatigue cycling at a rate of 5Hz is been carried out at 314MPa with a maximum strain of 0.51%. At such extreme strain levels the use of high strength sensors becomes inevitable. Neither the sensor nor the composite test-coupons showed any significant degradation even after more than 500000 cycles. Fibre optic Bragg grating sensors are known to be very accurate strain sensors but one should be very careful interpreting their response once they are imbedded inside composite materials. In this study high strength fibre Bragg grating sensors with coating are imbedded in composite test coupons and a pretty good correlation was found between the strain measurements of an electrical extensometer and the imbedded sensor during the complete cycling. The high strength sensor show to be very feasible for extreme and long term strain measurements.

The two charge exchange reactions 14N(d, 2He)14C and 14N(3He, t)14O were studied with high resolution in order to identify the Gamow–Teller (GT) strength distribution starting from the ground state (g.s.) of 14N in the β− and β+ directions. The isospin symmetry in the A = 14 mass system is investigated. An overview of the main features of the experimental investigation is summarized here.

In order to study the Gamow–Teller (GT) transitions in the fp-shell nucleus 64Cu, the 64Ni(3He, t)64Cu charge-exchange reaction was investigated at MeV/nucleon [1]. The outgoing tritons were momentum analysed by the Grand Raiden spectrometer at 0. The very high energy resolution of 35 keV (FWHM) allowed the separation of individual levels in the excitation energy region from 0 to 3.5 MeV. An angular distribution analysis was performed for the observed transitions to these states. In addition to the ground state (g.s.), known to be a Jπ = 1+ GT state, several excited states showed L = 0 nature, making them candidates of GT states. At higher excitation energies, the level density becomes very high and a bump-like structure, the so-called GT Giant Resonance, dominates the spectrum.

Neisseria meningitidis serogroup B infections are among the major causes of fulminant septicemia and meningitis, especially severe in young children, and no broad vaccine is available yet. Because of poor immunogenicity of the serogroup B capsule, many efforts are now devoted to the identification of protective protein antigens. Among those are PorA and, more recently, transferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidis was genetically fused to the N-terminal domain of the Bordetella pertussis filamentous hemagglutinin (FHA), and the fha-tbpB hybrid gene was expressed in B. pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the recombinant strains, despite its large size, and was recognized by both anti-FHA and anti-TbpB antibodies. A single intranasal administration of recombinant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (IgG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of the IgG1, IgG2a, and IgG2b isotypes and were found to express complement-mediated bactericidal activity against N. meningitidis. These observations indicate that recombinant B. pertussis may be a promising vector for the development of a mucosal vaccine against serogroup B meningococci.

The 1992 evaluation on mass A = 103 has been revised, taking into account all data available before July 2000. Detailed experimental information is presented from the neutron rich nucleus 103Sr to the neutron deficient 103Sb nucleus.

J.H. HELBIG, P.C. LÜCK, M. STEINERT, E. JACOBS AND M. WITT. 2001. The macrophage infectivity potentiator (Mip) protein is an important factor in the optimal intracellular survival of Legionella pneumophilain protozoa and human cell lines. In this study we have localized the Mip protein in Legionellagrown on buffered charcoal yeast extract (BCYE) agar as well as in Legionellawhich were ingested by Acanthamoeba castellanii. Immunogold techniques have shown that Mip is exposed on the cell surface of extracellularly grown bacteria. In A. castellaniiinfected with Legionellathe Mip protein was also detected on host membranes which exhibited a multilamellar structure. The morphology of these structures is similar to that of respirable vesicles of amoebas by which live legionellas may be transmitted to humans. It can be assumed that the accumulation of Mip protein in the multilamellar host membranes increases the infection potential.

The hydroxyl end groups of Pluronic®F108 {a triblock copolymer surfactant of poly(ethylene glycol) and poly(propylene glycol) [PEG-PPG-PEG]} were modified into primary amine, sulfonic acid, and quaternary ammonium equivalents for use in affinity chromatography. NMR was used for monitoring the efficacy of modifications on intermediaries and final products. The primary amine equivalents were prepared via conversion of the hydroxyl groups to a tosylate, its displacement with an azide, followed by reduction to the primary amine. The sulfonic acid equivalents were prepared via hydroxyl group tosylation, the displacement of tosylate with thiol, and its oxidation to sulfonic acid. The conversion to trimethyl ammonium was achieved via hydroxyl group tosylation, tosylate displacement by halide, and halide displacement with trimethylamine. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 109–117, 2000

In previous studies we showed that the wild-type histamine H(2) receptor stably expressed in Chinese hamster ovary cells is constitutively active. Because constitutive activity of the H(2) receptor is already found at low expression levels (300 fmol/mg protein) this receptor is a relatively unique member of the G-protein-coupled receptor (GPCR) family and a useful tool for studying GPCR activation. In this study the role of the highly conserved DRY motif in activation of the H(2) receptor was investigated. Mutation of the aspartate 115 residue in this motif resulted in H(2) receptors with high constitutive activity, increased agonist affinity, and increased signaling properties. In addition, the mutant receptors were shown to be highly structurally instable. Mutation of the arginine 116 residue in the DRY motif resulted also in a highly structurally instable receptor; expression of the receptor could only be detected after stabilization with either an agonist or inverse agonist. Moreover, the agonist affinity at the Arg-116 mutant receptors was increased, whereas the signal transduction properties of these receptors were decreased. We conclude that the Arg-116 mutant receptors can adopt an active conformation but have a decreased ability to couple to or activate the G(s)-protein. This study examines the pivotal role of the aspartate and arginine residues of the DRY motif in GPCR function. Disruption of receptor stabilizing constraints by mutation in the DRY motif leads to the formation of active GPCR conformations, but concomitantly to GPCR instability.

The 1992 evaluation on mass A = 110 has been revised, taking into account all data available before January 1999. Detailed experimental information is presented from the neutron rich nucleus 110Zr to the neutron deficient 110Xe nucleus.

The family of variable surface lipoproteins (Vsps) of the bovine pathogen Mycoplasma bovis includes some of the most immunogenic antigens of this microorganism. Vsps were shown to undergo high-frequency phase and size variations and to possess extensive reiterated coding sequences extending from the N-terminal end to the C-terminal end of the Vsp molecule. In the present study, mapping experiments were conducted to detect regions with immunogenicity and/or adhesion sites in repetitive domains of four Vsp antigens of M. bovis, VspA, VspB, VspE, and VspF. In enzyme-linked immunosorbent assay experiments, sera obtained from naturally infected cattle showed antibodies to different repeating peptide units of the Vsps, particularly to units R(A)1, R(A)2, R(A)4.1, R(B)2.1, R(E)1, and R(F)1, all of which were found to contain immunodominant epitopes of three to seven amino acids. Competitive adherence trials revealed that a number of oligopeptides derived from various repeating units of VspA, VspB, VspE, and VspF partially inhibited cytoadhesion of M. bovis PG45 to embryonic bovine lung cells. Consequently, putative adherence sites were identified in the same repeating units (R(A)1, R(A)2, R(A)4.1, R(B)2.1, R(E)1, and R(F)1) and in R(F)2. The positions and lengths of the antigenic determinants were mostly identical to those of adhesion-mediating sites in all short repeating units, whereas in the considerably longer R(F)1 unit (84 amino acid residues), there was only one case of identity among four immunogenic epitopes and six adherence sites. The identification of epitopes and adhesive structures in repetitive domains of Vsp molecules is consistent with the highly immunogenic nature observed for several members of the Vsp family and suggests a possible function for these Vsp molecules as complex adherence-mediating regions in pathogenesis.

ABSTRACTThe family of variable surface lipoproteins (Vsps) of the bovine pathogen Mycoplasma bovisincludes some of the most immunogenic antigens of this microorganism. Vsps were shown to undergo high-frequency phase and size variations and to possess extensive reiterated coding sequences extending from the N-terminal end to the C-terminal end of the Vsp molecule. In the present study, mapping experiments were conducted to detect regions with immunogenicity and/or adhesion sites in repetitive domains of four Vsp antigens of M. bovis, VspA, VspB, VspE, and VspF. In enzyme-linked immunosorbent assay experiments, sera obtained from naturally infected cattle showed antibodies to different repeating peptide units of the Vsps, particularly to units RA1, RA2, RA4.1, RB2.1, RE1, and RF1, all of which were found to contain immunodominant epitopes of three to seven amino acids. Competitive adherence trials revealed that a number of oligopeptides derived from various repeating units of VspA, VspB, VspE, and VspF partially inhibited cytoadhesion ofM. bovisPG45 to embryonic bovine lung cells. Consequently, putative adherence sites were identified in the same repeating units (RA1, RA2, RA4.1, RB2.1, RE1, and RF1) and in RF2. The positions and lengths of the antigenic determinants were mostly identical to those of adhesion-mediating sites in all short repeating units, whereas in the considerably longer RF1 unit (84 amino acid residues), there was only one case of identity among four immunogenic epitopes and six adherence sites. The identification of epitopes and adhesive structures in repetitive domains of Vsp molecules is consistent with the highly immunogenic nature observed for several members of the Vsp family and suggests a possible function for these Vsp molecules as complex adherence-mediating regions in pathogenesis.

Abstract: The clastogenic potential of the phytoestrogens coumoestrol (COUM), genistein (GEN) and daidzein (DAI) has been studied in human peripheral blood lymphocytes in vitro. After exposure of the cultured lymphocytes to 50 or 75 μM COUM or 25 μM GEN for 6 h, a clear induction of structural chromosomal aberrations was observed by cytogenetic analysis. The major alterations were chromatid breaks, gaps and interchanges. In contrast, DAI did not induce chromosome aberrations even at 100 μM. These results, together with previously published reports on the induction of micronuclei and DNA strand breaks in cultured Chinese hamster V79 cells by COUM and GEN, but not DAI, suggest that some but not all phytoestrogens have the potential for genetic toxicity.