Optimal mechanical impact absorbers are reusable and exhibit high specific energy absorption. The forced intrusion of liquid water in hydrophobic nanoporous materials, such as zeolitic imidazolate ...frameworks (ZIFs), presents an attractive pathway to engineer such systems. However, to harness their full potential, it is crucial to understand the underlying water intrusion and extrusion mechanisms under realistic, high-rate deformation conditions. Here, we report a critical increase of the energy absorption capacity of confined water-ZIF systems at elevated strain rates. Starting from ZIF-8 as proof-of-concept, we demonstrate that this attractive rate dependence is generally applicable to cage-type ZIFs but disappears for channel-containing zeolites. Molecular simulations reveal that this phenomenon originates from the intrinsic nanosecond timescale needed for critical-sized water clusters to nucleate inside the nanocages, expediting water transport through the framework. Harnessing this fundamental understanding, design rules are formulated to construct effective, tailorable and reusable impact energy absorbers for challenging new applications.
Molecular separation of carbon dioxide (CO2) and methane (CH4) is of growing interest for biogas upgrading, carbon capture and utilization, methane synthesis and for purification of natural gas. ...Here, we report a new zeolitic-imidazolate framework (ZIF), coined COK-17, with exceptionally high affinity for the adsorption of CO2 by London dispersion forces, mediated by chlorine substituents of the imidazolate linkers. COK-17 is a new type of flexible zeolitic-imidazolate framework Zn(4,5-dichloroimidazolate)2 with the SOD framework topology. Below 200 K it displays a metastable closed-pore phase next to its stable open-pore phase. At temperatures above 200 K, COK-17 always adopts its open-pore structure, providing unique adsorption sites for selective CO2 adsorption and packing through van der Waals interactions with the chlorine groups, lining the walls of the micropores. Localization of the adsorbed CO2 molecules by Rietveld refinement of X-ray diffraction data and periodic density functional theory calculations revealed the presence and nature of different adsorption sites. In agreement with experimental data, grand canonical Monte Carlo simulations of adsorption isotherms of CO2 and CH4 in COK-17 confirmed the role of the chlorine functions of the linkers and demonstrated the superiority of COK-17 compared to other adsorbents such as ZIF-8 and ZIF-71.
Pathogenic sequence variants (PSV) in
or
(
) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in
were associated with risk of overall prostate cancer or ...high grade (Gleason 8+) prostate cancer using an international sample of 65
and 171
male PSV carriers with prostate cancer, and 3,388
and 2,880
male PSV carriers without prostate cancer. PSVs in the 3' region of
(c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 HR = 1.78; 95% confidence interval (CI), 1.25-2.52;
= 0.001, as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95;
= 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68;
= 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54;
= 0.0002). No genotype-phenotype associations were detected for PSVs in
. These results demonstrate that specific
PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
This study presents biochemical, histochemical, morphological and immunological evidence that part of the high molecular weight alkaline phosphatase observed in the serum of patients with liver ...disease and particularly in cases of intrahepatic cholestasis or focal‐, extrahepatic obstruction originates from the liver plasma membrane.
The high molecular weight protein alkaline phosphatase complex contains several plasma membrane enzymes and behaves like a plasma membrane fragment after isopycnic density gradient ultracentrifugation in sucrose, cesium chloride and metrizamide. Electron microscopic examination revealed a triple‐layered vesicle which retained alkaline phosphatase activity. Incubation of human liver cells with anti‐serum against purified high molecular weight multienzyme complex resulted in fixation of antibodies on the plasma membrane as shown by positive plasma membrane fluorescence. These plasma membrane fragments in the serum are not of biliary origin.
Myalgias are common in patients treated with electroconvulsive therapy (ECT). The mechanism of this side effect is unknown. Two commonly postulated etiologies are the motor activity during the ...convulsion and the fasciculations induced by succinylcholine. If the former phenomenon accounts for most of themyalgias, then the appropriate strategy will be to increase the succinylcholine dose at subsequent treatments. If, on the other hand, the latter phenomenon is more important in inducing myalgias, then the appropriate strategy may be to decrease succinylcholine dosages (on the theory that lower doses result in less fasciculating). On the other hand, if neither of these factors accounts for myalgias, then succinylcholine dose adjustments may be irrelevant to myalgias in the ECT situation. In this study, we assessed the degree of convulsive movements during the seizure as well as strength of fasciculations caused by succinylcholine to see which, if either, correlates with ultimate complaints of myalgias. The results indicated that neither of these factors, nor dose of succinylcholine, correlated with myalgias. We conclude that dose adjustments to succinylcholine are unlikely to affect complaints of myalgias in ECT patients.
We compared three current methods (immunoinhibition, "Isomune-CK" immunoprecipitation, and the Tandem-E CKMB II immunoenzymometric assay) for determination of creatine kinase (CK; EC 2.7.3.2) ...isoenzyme MB in serum. Although results inter-correlated well, the immunoinhibition assay gave higher activity values. Atypical CK forms did not interfere with the immunoprecipitation and immunoenzymometric methods. In acute myocardial infarction the catalytic properties of CK decreased with the enzyme's age, as reflected by a steady increase in activation energy of the catalyzed reaction. In septicemia patients with very low CK and CK-MB catalytic activity, mean CK-MB mass concentration exceeded the upper reference limit, suggesting an increased rate of loss of activity concentration in these patients' sera. Because of the assay's lesser susceptibility to conformational changes at the active site of the enzyme, we suggest that measurement of CK-MB mass concentration is better suited for infarct sizing than measurement of catalytic activity.
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes
,
,
,
, and
are associated with breast cancer risk.
, which encodes for a ...DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants
:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of
or
. These three variants were also studied functionally by measuring survival and chromosome fragility in
patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that
:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44,
= 0.034 and OR = 3.79;
= 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for
:p.Arg658* and found that also
:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96;
= 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with
:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare
deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat
-associated tumors.
A 5% (m/m) premix for animal use was quantitatively characterized for the polymorph composition of its benzimidazole drug substance. Raman spectra of reference samples (pure polymorphs A, B and C in ...lactose at a concentration of 5%, m/m) were compared with the spectra of benzimidazole samples with a known polymorph composition and with the spectra of uncharacterized premixes. The raw intensities of 78 selected wavenumbers were vector-normalized and application of stepwise linear regression models estimated the relative quantities of the benzimidazole-drug polymorphs A, B and C in the different samples. Modelling results of the samples with known polymorph composition were in compliance with the expected concentrations, validating the proposed methodology. The benzimidazole drug substance in the premixes was predominantly polymorph B. Although statistically not significant, some traces of polymorph A could not be ruled out. Similar analyses were performed to evaluate the solid-state stability of the benzimidazole drug substance in another drug formulation, i.e. a suspension-emulsion. Suspension-emulsions originally determined as containing polymorph B benzimidazole drug substance were stored for 12 months at 25
°C/60%RH. FT-Raman spectroscopy revealed that no polymorph transformations occurred during this storage.
A sensitive and highly specific ELISA assay was developed to determine the anti-myosin humoral immune response (AMA) in various heart diseases: acute viral myocarditis, infective endocarditis, acute ...myocardial infarction, and valve and coronary bypass surgery. The mean study entry AMA titer of each patient group was already significantly increased compared with age matched controls. During further follow-up (90 d) all the groups except for endocarditis showed a significant increase of AMA titer compared with their entry titer. Anti-myosin antibody titer were higher after cardiac surgery than after myocardial infarction or inflammatory heart disease. These results suggest that anti-myosin immune response is not limited to infectious processes in which the pathogen induces antibodies which cross-react with heart constituents but is merely caused by direct cardiac injury. Myosin as a major compound of heart cellular proteins turned out to be a good candidate to trigger immune response after cardiac injury.
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