Activity Of Ca2 Research Articles

Properties and Microstructure of Na2CO3-Activated Binders Modified with Ca(OH)2 and Mg(OH)2.

Delayed strength development and long setting times are the main disadvantageous properties of Na2CO3-activated slag cements. In this work, combined auxiliary activators of Ca(OH)2 and Mg(OH)2 were incorporated in one-part Na2CO3-activated slag binders to accelerate the kinetics of alkali activation. The properties and microstructure evolution were investigated to clarify the reaction mechanism. The results showed that the additions of auxiliary activators promoted the hardening of the pastes within 2 h. The 28 days compressive strengths were in the range of 39.5–45.5 MPa, rendering the binders practical cementitious materials in general construction applications. Ca(OH)2 was more effective than Mg(OH)2 in accelerating the kinetics of alkali activation. The dissolution of Ca(OH)2 released more OH− and Ca2+ ions in the aqueous phase to increase alkalinity in the aqueous phase and promote the formation of the main binding gel phase of calcium-aluminosilicate hydrate (C-A-S-H). An increase in the Ca(OH)2/Mg(OH)2 ratios increased autogenous shrinkage and decreased drying shrinkage of the binders. The formation of a compact pore structure restricted the water evaporation from the binders during the drying procedure.

STUDY OF BIOCHEMICAL MARKERS OF OSTEOGENESIS IN CASE OF BONE ALLOGRAFTS INCORPORATION IN RATS WITH FOLLOWED AFTER SURGERY ADMINISTRATION OF CISPLATIN AT THE DIFFERENT METHODS OF IMPLANT STERILIZATION

Bone allografts are commonly used for surgical treatment of cancer patients. However, such complications as violation of allograft fusion, its lysis and fractures, infection lead to additional research in this field of medicine. Objective. To study changes in biochemical osteogenesis markers under the action of cytostatics on the process of incorporation of bone allografts. Methods. The work was performed on 20 male white rats (age at the beginning of the experiment 5–6 months). All animals have a perforated defect in the distal metaphysis of the femur filled with bone allograft (diameter 2 mm, height 3 mm), γ-radiation sterilized (Control-1 and Experiment-1) or saturation of the antibiotics sterilized (Control-2 and Experiment-2). In groups «Control» 14 days after implantation intraperitoneally injected 2.0–2.4 ml of 0.9 % sodium chloride solution, in the groups «Experiment» — cisplatin at a dose of 2.5 mg/ kgonce. 30 days after surgery, blood glycoproteins, total protein, Ca, chondroitin sulfates, acidic and alkaline phosphatase activity were evaluated. The index of mineralization (ratio of alkaline to acid phosphatases), degree is analyzed mineralization (ratio of calcium to protein). Results. In the experimental groups, compared with the control, a significant decrease in total protein and values was determined: total calcium, which indicates the suppression of processes mineralization during remodeling of bone tissue of the recipient and allograft. The highest indicators of activity acid phosphatase were recorded in groups Experiment-1 and Experiment-2, reflecting the predominance of resorption over bone formation. The degree of mineralization in the experimental groups was higher than in the control, and the mineralization index was significantly smaller. Conclusions. The detected changes in the values of biochemical markers of bone metabolism reflect the negative effect of cisplatin on osteogenesis under the conditions of allograft implantation, which leads to the lack of their fusion with the recipient bone.

Enhancing translocation and remobilization of zinc in wheat by the application of plant growth regulators

Abstract A pot experiment was carried out to evaluate the impact of plant growth regulators (PGRs) on translocation and accumulation of zinc (Zn) in grains of four wheat varieties of varying Zn sensitivities. Different concentrations of two (gibberellic acid and cytokinin) PGRs viz., control, 10 ppm gibberellic acid (GA), 20 ppm gibberellic acid (GA), 10 ppm cytokinin (kinetin), 20 ppm cytokinin (kinetin), 10 ppm gibberellic acid (GA) + cytokinin (kinetin), 20 ppm gibberellic acid (GA) + cytokinin (kinetin) were applied under different Zn regimes (control), soil application of 5 mg Zn kg-1 soil and soil application of 5 mg Zn kg-1 soil + foliar applications of 0.5% ZnSO4.7H2O + 0.25% lime). Four contrasting wheat varieties i.e., UP262 & PBW175 (Zn inefficient), UP2628 & UP2554 (Zn efficient); were tested for enzyme activities, yield attributes and Zn content in various plant parts. Regarding influence of PGR levels, the maximum CA and SOD activities were recorded under 20 ppm GA and control respectively. The grain yield, straw yield and grain Zn content was found to be the maximum under 10 ppm GA+cytokinin, 20 ppm GA and 20 ppm cytokinin respectively. Among all the methods used, soil along with foliar spray (Zn S+F) was found to be the most effective in improving all the crop parameters. Among varieties, the efficient sets of varieties (UP2628 & UP2554) performed better than Zn inefficient varieties. The use of plant growth regulators along with efficient delivery method could enhance the transport and accumulation of Zn in grains of wheat.

Activating the oxygen electrocatalytic activity of layer-structured Ca0.5CoO2 nanofibers by iron doping.

The development of low-cost, highly efficient and stable electrocatalysts for the oxygen evolution reaction (OER) is of great significance for many promising energy storage and conversion applications, including metal-air batteries and water splitting technology. Here we report a layer-structured Ca0.5CoO2 nanofibers composed of interconnected ultrathin nanoplates, synthesized using an electrospinning process. The OER activity of Ca0.5CoO2 can be dramatically improved by iron doping, and the overpotential of Ca0.5Co1-xFexO2 (x = 0.25) is only 346 mV at a current density of 10 mA cm-2. The mass activity and intrinsic activity of Ca0.5Co0.75Fe0.25O2 at 1.6 V are, respectively, ∼18.7 and ∼11.4 times higher than those of Ca0.5CoO2. Iron doping modifies the electronic structure of Ca0.5CoO2, resulting in partial oxidation of the surface cobalt and increased amount of highly oxidative species (O22-/O2). Consequently, Ca0.5Co0.75Fe0.25O2 nanofibers with tuned electronic states have shown great potential as cost-effective and efficient electrocatalysts for OER.

Microglia-triggered hypoexcitability plasticity of pyramidal neurons in the rat medial prefrontal cortex

Lipopolysaccharide (LPS), an outer component of Gram-negative bacteria, induces a strong response of innate immunity via microglia, which triggers a modulation of the intrinsic excitability of neurons. However, it is unclear whether the modulation of neurophysiological properties is similar among neurons. Here, we found the hypoexcitability of layer 5 (L5) pyramidal neurons after exposure to LPS in the medial prefrontal cortex (mPFC) of juvenile rats. We recorded the firing frequency of L5 pyramidal neurons long-lastingly under in vitro whole-cell patch-clamp, and we found a reduction of the firing frequency after applying LPS. A decrease in the intrinsic excitability against LPS-exposure was also found in L2/3 pyramidal neurons but not in fast-spiking interneurons. The decrease in the excitability by immune-activation was underlain by increased activity of small-conductance Ca2+-activated K+ channels (SK channels) in the pyramidal neurons and tumor necrosis factor (TNF)-α released from microglia. We revealed that the reduction of the firing frequency of L5 pyramidal neurons was dependent on intraneuronal Ca2+ and PP2B. These results suggest the hypoexcitability of pyramidal neurons caused by the upregulation of SK channels via Ca2+-dependent phosphatase during acute inflammation in the mPFC. Such a mechanism is in contrast to that of cerebellar Purkinje cells, in which immune activation induces hyperexcitability via downregulation of SK channels. Further, a decrease in the frequency of spontaneous inhibitory synaptic transmission reflected network hypoactivity. Therefore, our results suggest that the directionality of the intrinsic plasticity by microglia is not consistent, depending on the brain region and the cell type.

Measurement of Calcium Deoxidation and Desulfurization Equilibria of Molten Iron by Controlling Ca Activity Using Ca-Pb Alloys

Measurement of Calcium Deoxidation and Desulfurization Equilibria of Molten Iron by Controlling Ca Activity Using Ca-Pb Alloys

Phosphorus equivalency of phytase with various evaluation indicators of duck in starter.

This study was conducted to evaluate phosphorus (P) equivalency of phytase with various evaluation indicators of ducks in starter (0-14days). Three hundred and twenty 1-day-old Cherry Valley ducks were randomly assigned to eight groups. The dietary treatments were four levels of available phosphorus (aP) with 0.25%, 0.32%, 0.39%, and 0.46% (treatments I-IV) and four levels of phytase added to low-aP basal diet (treatment I) with 300, 600, 900, and 1200 units (U) per kg (treatments V-VIII). The results were that compared to treatment I, increasing aP and supplementary phytase significantly (p<0.05) improved body weight (BW), BW gain (BWG), feed intake (FI), live BW, carcass weight, semieviscerated weight, eviscerated weight, leg muscle weight, and decreased feed conversion ratio (FCR). Treatments V and VI did not significantly increase tibia ash, tibia calcium, and tibia P of 14-day-old ducks (p>0.05). Following the increase of aP level (treatments I-IV), apparent utilization of Ca and P of ducks increased with varying degrees. With the increase of dietary phytase level (treatments V-VIII), the apparent utilization of Ca and P showed no significant difference (p>0.05) but an increasing trend. Serum P reached the highest level when adding 600U/kg phytase (treatment VI). Serum Ca and serum alkaline phosphatase activity showed no significant difference among treatments V-VIII (p>0.05). Based on corn-soybean-rapeseed meal diet, with the evaluation indexes of FI, BWG, tibia ash, tibia Ca, tibia P, and apparent utilization of Ca and P, the addition of 500U/kg phytase could release aP of 0.03%, 0.04%, 0.02%, 0.01%, 0.02%, 0.08%, and 0.07%, respectively. On the same way, the addition of 1000U/kg phytase could release aP of 0.07%, 0.09%, 0.06%, 0.02%, 0.07%, 0.09%, and 0.09%, respectively.

Comprehensive insight into the role of HCl on arsenic capture by CaO during coal combustion: A combined experimental and theoretical study

Influence of HCl on As capture capability of CaO during coal combustion was studied in this work. Experimental results have confirmed the dramatic suppression role of HCl on As capture by CaO, and demonstrated the potential contributions of CaO chlorination to the inhibition role of HCl on As capture. Meanwhile, the clogging impact of HCl on CaO was omitted. For comprehensive understanding of inhibition mechanism of HCl, theoretical adsorption behaviors of As2O3(g) and AsCl3(g) on CaO (001) slab and CaCl2 (001) slab were investigated. It was concluded that chlorination of As2O3(g) and CaO both contributed to the inhibition effect of HCl, and the inhibition role of As2O3(g) chlorination was stronger than that of CaO chlorination. Comparing with the excellent activity of Ca and O sites in CaO (001) surface for As2O3(g) adsorption, CaO chlorination abolished the function of surface O, while As2O3 chlorination limited the activity of surface Ca. Moreover, interactions between AsCl3(g) and CaCl2 induced the offsetting effect of HCl on As capture capability of CaO. Correspondingly, the validity of As2O3(g) chlorination during coal combustion was verified. Moreover, it was also clarified that the suppression role of HCl on arsenic capture by CaO was better than that of SO2.

Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?

The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.

Geochemistry of the trace and rare earth elements mineralisations in the lower member of Um Bogma Formation in the area east of Wadi Baba, southwestern Sinai, Egypt

ABSTRACT The exposures of the lower member of Um Bogma Formation (Early Carboniferous) in a vast area east of Wadi Baba were studied in six localities. The member is dominated by argillaceous rocks in the western and southwestern occurrences, carbonates in the central sector of the area and sandstones at the east.These rock types, especially the carbonates in Allouga locality, consist of large assemblages of non-radioactive, radioactive and REEs- and base metals- bearing minerals of a mixed allogenic-authigenic and primary-secondary origin. Most of the allogenic minerals were inherited from unaltered and altered precursors in felsic igneous rocks. The results of extensive geochemical studies confirmed varying enrichment of the studied rocks in many trace and rare earth elements as well as base metals. The rocks in Allouga locality and, to a lesser extent, those in Talet Seliem and Abu Zarab have the highest potential as possible resources of these elements. Sequential extraction of Mn, Cu, Fe, Pb, U, Th, Y, La and Dy from five fractions revealed that these elements are exchangeable, bound to carbonates, iron and manganese oxides and organic matter and/or residual. The distributions of trace elements and REEs among the different rock types show variation based on their affinities to specific lithologies. The REEs generally show enriched patterns and negative Eu anomalies. U enrichment in rocks of this member is correlated with the occurrence of several types of uranyl silicate minerals. The co-existence of these minerals reflects variations in the activities of Ca, Mg, Cu and Pb. The hydrothermal activities related to the Red Sea extension were responsible for the oxidation of sulphides, alteration of primary minerals and genesis of Mn oxides, surficial uranyl and REEs mineralisations. Based on the obtained data, certain localities are recommended for future prospecting plans.

Tuning the p-Orbital Electron Structure of s-Block Metal Ca Enables a High-Performance Electrocatalyst for Oxygen Reduction.

Most previous efforts are devoted to developing transition metals as electrocatalysts guided by the d-band center model. Themetalsofthes-blockoftheperiodic table have so far received little attention in the application of oxygen reduction reactions (ORR). Herein, a carbon catalyst with calcium (Ca) single atom coordinated with N and O is reported, which displays exceptional ORR activities in both acidic condition (E1/2 = 0.77 V,0.1 mHClO4 )and alkaline condition (E1/2 = 0.90 V,0.1 mKOH).The CaN, O/C exhibits remarkable performance in zinc-air battery with a maximum power density of 218mW cm-2 , superior to a series of catalysts reported so far. X-ray absorption near-edge structure (XANES) characterization confirms the formation of N- and O-atom-coordinated Ca in the carbon matrix. Density functional theory (DFT) calculations reveal that the high catalytic activity of main-group Ca is ascribed to the fact that its p-orbital electron structure is regulated by N and O coordination so that the highest peak (EP ) of the projected density of states (PDOS) for the Ca atom is moved close to the Fermi level, thereby facilitating the adsorption of ORR intermediates and electron transfer.

Zirconium-bearing accessory minerals in UK Paleogene granites: textural, compositional, and paragenetic relationships

Abstract. The mineral occurrences, parageneses, textures, and compositions of Zr-bearing accessory minerals in a suite of UK Paleogene granites from Scotland and Northern Ireland are described. Baddeleyite, zirconolite, and zircon, in that sequence, formed in hornblende + biotite granites (type 1) and hedenbergite–fayalite granites (type 2). The peralkaline microgranite (type 3) of Ailsa Craig contains zircon, dalyite, a eudialyte-group mineral, a fibrous phase which is possibly lemoynite, and Zr-bearing aegirine. Hydrothermal zircon is also present in all three granite types and documents the transition from a silicate-melt environment to an incompatible element-rich aqueous-dominated fluid. No textures indicative of inherited zircon were observed. The minerals crystallized in stages from magmatic through late-magmatic to hydrothermal. The zirconolite and eudialyte-group mineral are notably Y+REE-rich (REE signifies rare earth element). The crystallization sequence of the minerals may have been related to the activities of Si and Ca, to melt peralkalinity, and to local disequilibrium.

THE STRUGGLE OF THE SOVIET AUTHORITY AGAINST THE «REMNANTS OF UNIAT» IN THE UKRAINIAN SSR AT THE BREAK OF THE 1970s – 1980s

The key methods of the Ukrainian SSR party authorities to counter the attempts of reviving the Ukrainian Greek Catholic Church in the western Ukrainian regions at the break of the 80s-90s of the XX century were considered. It was noted that in the late 1970s in this region, particularly in Galicia, Greek-Catholic believers and the clergy measurably intensified their activity, which was evident mainly in houses of worship attendance, traditional rites observance, letters issued to the Council for Religious Affairs of the Soviet Union Ministers with the requirement to register religious communities, clandestine ordination of the clergy, etc. It was stated that in order to counter the religious influence intensification of the Russian Orthodox Church on the population, as well as to prevent negative anti-social manifestations of «remnants of Uniat», local Communist Party committees and Soviet authorities carried out a number of propaganda and mass political events to expose anti-Soviet religious ideology, in particular, «the reactionary role of the Uniat Church in the history of the Ukrainian people». It was noted that the Communist Party of Ukraine took concrete measures to step up anti-religious propaganda in Western Ukrainian regions, as well as to promote the advantages of the Soviet mode of life. It was alleged that the activities of Greek Ca¬tholic believers were discussed at the Council for Religious Affairs of the Soviet Union Ministers sessions of the Ukrainian SSR in the regions of Western Ukraine, party rallies at different levels, meetings of the ideological activists of the regions, seminars of cultural and educational wor¬kers, district and regional atheist conferences. It was noted that the Communist Party of Ukraine paid considerable attention to the media, which should have covered the historical aspects of the «anti-popular backbone of Uniat Church».

Antibacterial Activity of Copper Nanoparticles (CuNPs) against a Resistant Calcium Hydroxide Multispecies Endodontic Biofilm.

Endodontic treatment reduces the amount of bacteria by using antimicrobial agents to favor healing. However, disinfecting all of the canal system is difficult due to its anatomical complexity and may result in endodontic failure. Copper nanoparticles have antimicrobial activity against diverse microorganisms, especially to resistant strains, and offer a potential alternative for disinfection during endodontic therapy. This study evaluated the antibacterial action of copper nanoparticles (CuNPs) on an ex vivo multispecies biofilm using plaque count compared to the antibacterial activity of calcium hydroxide Ca(OH)2. There were significant differences between the Ca(OH)2 and CuNPs groups as an intracanal dressing compared with the CuNPs groups as an irrigation solution (p < 0.0001). An increase in the count of the group exposed to 7 days of Ca(OH)2 was observed compared to the group exposed to Ca(OH)2 for 1 day. These findings differ from what was observed with CuNPs in the same period of time. Antibacterial activity of CuNPs was observed on a multispecies biofilm, detecting an immediate action and over-time effect, gradually reaching their highest efficacy on day 7 after application. The latter raises the possibility of the emergence of Ca(OH)2-resistant strains and supports the use of CuNPs as alternative intracanal medication.

Bi-component HlgC/HlgB and HlgA/HlgB γ-hemolysins from S. aureus: Modulation of Ca2+ channels activity through a differential mechanism

Staphylococcal bi-component leukotoxins known as *pore-forming toxins* induce upon a specific binding to membrane receptors, two independent cellular events in human neutrophils. First, they provoke the opening of pre-existing specific ionic channels including Ca2+ channels. Then, they form membrane pores specific to monovalent cations leading to immune cells death. Among these leukotoxins, HlgC/HlgB and HlgA/HlgB γ-hemolysins do act in synergy to induce the opening of different types of Ca2+ channels in the absence as in the presence of extracellular Ca2+. Here, we investigate the mechanism underlying the modulation of Ca2+-independent Ca2+ channels in response to both active leukotoxins in human neutrophils. In the absence of extracellular Ca2+, the Mn2+ has been used as a Ca2+ surrogate to determine the activity of Ca2+-independent Ca2+ channels. Our findings provide new insights about different mechanisms involved in the staphylococcal γ-hemolysins activity to regulate three different types of Ca2+-independent Ca2+ channels. We conclude that (i) HlgC/HlgB stimulates the opening of La3+-sensitive Ca2+ channels, through a cholera toxin-sensitive G protein, (ii) HlgA/HlgB stimulates the opening of Ca2+ channels not sensitive to La3+, through a G protein-independent process, and (iii) unlike HlgA/HlgB, HlgC/HlgB toxins prevent the opening of a new type of Ca2+ channels by phosphorylation/de-phosphorylation-dependent mechanisms.

The effects of warming on red blood cell carbonic anhydrase activity and respiratory performance in a marine fish

Measures of fitness are valuable tools to predict species' responses to environmental changes, like increased water temperature. Aerobic scope (AS) is a measure of an individual's capacity for aerobic processes, and frequently used as a proxy for fitness. However, AS is complicated by individual variation found not only within a species, but within similar body sizes as well. Maximum metabolic rate (MMR), one of the factors determining AS, is constrained by an individual's ability to deliver and extract oxygen (O2) at the tissues. Recently, data has shown that red blood cell carbonic anhydrase (RBC CA) is rate-limiting for O2 delivery in red drum (Sciaenops ocellatus). We hypothesized increased temperature impacts MMR and RBC CA activity in a similar manner, and that an individual's RBC CA activity drives individual variation in AS. Red drum were acutely exposed to increased temperature (+6 °C; 22 °C to 28 °C) for 24 h prior to exhaustive exercise and intermittent-flow respirometry at 28 °C. RBC CA activity was measured before temperature exposure and after aerobic performance. Due to enzymatic thermal sensitivity, acute warming increased individual RBC CA activity by 36%, while there was no significant change in the control (22 °C) treatment. Interestingly, average MMR of the acute warming treatment was 36% greater than that of control drum. However, we found no relationships between individual RBC CA activity and their respective MMR and AS at either temperature. While warming similarly affects RBC CA activity and MMR, RBC CA activity is not a predictor of individual MMR.

Evolution of pyrochlore in carbonatites of the Amba Dongar complex, India.

AbstractPyrochlore-group minerals are common accessory rare-metal bearing minerals in the calcite and ankerite carbonatites of the Amba Dongar complex (India). Pyrochlore from the Amba Dongar carbonatites differs from that in other Indian complexes in Ta, Zr, Ti, rare earth element (REE) and Pb contents, but is similar with respect to Ca, Ba and Sr abundances. The evolution of pyrochlore composition was studied to understand the alteration processes and the formation of late-stage pyrochlores enriched in REE and Pb. The early magmatic pyrochlore are calcio- and niobium-dominant types and were replaced by secondary cation-deficient varieties as a consequence of the action of hydrothermal fluids and supergene weathering. These processes produce changes mainly at theAsite, rarely at theBsite, and the original F is replaced by OH–groups. Calcium and Na can be extracted from the structure at the alteration stage and charge balance is achieved by the introduction of REE, Th, U, Ba or Sr. At the latest supergene stages, marginal and fractured zones of pyrochlore grains are altered to Pb-rich, Si-rich and cation-deficient hydrated varieties. The magmatic pyrochlore was crystallised in a highly alkaline environment at a high activity of Ca and at temperatures near 600°C, the alteration of pyrochlore began in a hydrothermal environment at temperatures below 350°C. The major compositional changes that are associated with the alteration are summarised by the following reactions: Ca2++ Nb5+→REE3++ Ti4+; Nb5++ Fe3+→ Ti4++ Zr4+; and 2Nb5++ Ca2+→ Ti4++ Si4++ U4+.

Monitoring C-reactive protein facilitates early discontinuation of immune oncology without compromising outcomes in stage IV non-small cell lung cancer.

e21107 Background: C-Reactive Protein (CRP) is a non-specific inflammatory marker and reflects tissue destruction seen in metastatic cancer (ca). We have observed a tight correlation with CRP trends mirroring ca activity, hence it may prove to be a valuable marker to monitor response to Immuno-Oncology (IO) in non-small cell lung cancer (NSCLC) patients (pts). Once CRP levels stabilized, IO discontinuation was offered, and consenting pts were closely observed. This strategy resulted in shortened IO duration and impressive treatment-free progression-free survival (tf-PFS). We sought to examine the validity of this strategy using the rate of return to any form of ca therapy within 6 months after stopping IO. Methods: We analyzed all pts of a single provider since 2016 with stage IV NSCLC who had CRP checked while on IO, totaling 23 pts. We excluded pts who stopped IO for reasons besides stable CRP values (5 progressed on IO, 3 died while on IO, 1 had side effects, 1 stopped for a clinical trial, 1 opted to complete 2 years of IO, and 2 are still on IO). Of the remaining 10 patient cohort, all pts were males treated at the VA with ages between 56-75 years at diagnosis. 50% of the cohort had adenocarcinoma and 50% had squamous cell carcinoma. Results: Using the CRP trend to shorten the duration of IO resulted in durable drug-free holidays with none of the cohort returning to any form of ca therapy within 6 months and comparable rates of overall survival (OS) despite shorter IO duration. In KEYNOTE-042, the median OS for pts on the pembrolizumab arm was 16.7 months in the overall population and 20 months in the TPS ≥50% subgroup. Pts were treated for up to 35 months. In our cohort, median OS was 38 months, with all pts currently still alive, and median number of doses of IO was 9 cycles, or approximately 7 months. Our pts had ongoing progression free survival (PFS) after stopping treatment, which we report as tf-PFS. The median tf-PFS of our cohort was 23.5 months. Conclusions: In pts with stage IV NSCLC treated with IO, CRP appears promising as a marker to tailor IO therapy addressing tumor and clinical heterogeneity. Responding pts with stable CRP levels can be safely taken off IO. CRP should be monitored with stable values indicating continued PFS. tf-PFS rather than PFS may serve as a surrogate for cure and carries significant impact for pts financially, socially, and psychologically. [Table: see text]

Abnormal setting of Portland cement

It is proposed to distinguish the false setting from the abnormal one, considering the false as a variety of the latter. With false setting, the start of setting occurs in a short time, but then it spontaneously disappears, reappearing after a while. Such cements, in which the beginning of setting occurs faster than 50 minutes, and the end – after 5-12 hours, are proposed to be called abnormal cements. It is shown that when the start time of setting is more than 50 ∼ 60 minutes, the probability of abnormal setting decreases sharply. The kinetics of structure formation of cements with different setting patterns is considered. Methods for the identification of abnormal setting by the setting interval (τfinal – τstart)/τstart > 3, the kinetics of structure formation, heat release, and changes in the activity of calcium ions in the liquid phase of cement paste of normal density are proposed. It is shown that the measurement of the kinetics of heat release and the activity of Ca 2+ ions in the liquid phase of cement paste is of great interest for the development of automated and rapid control of the presence of anomalies during setting. It is established that the mixture of the inhibitor and the booster of the setting acts according to the rule of additivity, the use of mineral additives of acidic composition weakens the abnormal properties of cement systems. To combat the belated anomaly, it is necessary to monitor the properties of the cement 1-2 days before its application.

A Highlight on the Inhibition of Fungal Carbonic Anhydrases as Drug Targets for the Antifungal Armamentarium.

Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons. Opportunistic and pathogenic fungi can sense the environmental CO2 levels, which influence their virulence or environmental subsistence traits. The fungal CO2-sensing is directly stimulated by HCO3− produced in a CA-dependent manner, which directly activates adenylyl cyclase (AC) involved in the fungal spore formation. The interference with CA activity may impair fungal growth and virulence, making this approach interesting for designing antifungal drugs with a novel mechanism of action: the inhibition of CAs linked to the CO2/HCO3−/pH chemosensing and signaling. This review reports that sulfonamides and their bioisosteres as well as inorganic anions can inhibit in vitro the β- and α-CAs from the fungi, suggesting how CAs may be considered as a novel “pathogen protein” target of many opportunistic, pathogenic fungi.