Apparent Loss Research Articles

Automated magnetic resonance imaging quantification of cerebral parenchymal and ventricular volume following subarachnoid hemorrhage: associations with cognition

This study aims to investigate cerebral parenchymal and ventricular volume changes after subarachnoid hemorrhage (SAH) and their potential association with cognitive impairment. 17 patients with aneurysmal SAH (aSAH) and 21 patients with angiographically negative SAH (anSAH) without visually apparent parenchymal loss on conventional magnetic resonance imaging (MRI) were included, along with 76 healthy controls. Volumetric analyses were performed using an automated clinical segmentation and quantification tool. Measurements were compared to on-board normative reference database (n = 1923) adjusted for age, sex, and intracranial volume. Cognition was assessed with tests for psychomotor speed, attentional control, (working) memory, executive functioning, and social cognition. All measurements took place 5 months after SAH. Lower cerebral parenchymal volumes were most pronounced in the frontal lobe (aSAH: n = 6 [35%], anSAH n = 7 [33%]), while higher volumes were most substantial in the lateral ventricle (aSAH: n = 5 [29%], anSAH n = 9 [43%]). No significant differences in regional brain volumes were observed between both SAH groups. Patients with lower frontal lobe volume exhibited significantly lower scores in psychomotor speed (U = 81, p = 0.02) and attentional control (t = 2.86, p = 0.004). Additionally, higher lateral ventricle volume was associated with poorer memory (t = 3.06, p = 0.002). Regional brain volume changes in patients with SAH without visible parenchymal abnormalities on MRI can still be quantified using a fully automatic clinical-grade tool, exposing changes which may contribute to cognitive impairment. Therefore, it is important to provide neuropsychological assessment for both SAH groups, also including those with clinically mild symptoms.

Deterioration of interfacial bonding performance between metal mortar and concrete under the coupling effect of freeze-thaw cycle and abrasion

In cold regions, hydraulic concrete structures are often severely damaged by the combined effects of freeze-thaw cycle and hydraulic abrasion, and it is critical for safe operation of the structure to repair the damage. The actions of freeze-thaw cycles (0, 25, 50, 75, 100, 125, and 150 cycles), abrasion (24, 48, 72, 96, 120, and 144 h), and the coupled action of freeze-thaw cycles and abrasion on the metal mortar-concrete interface were investigated. The apparent damage, mass loss, abrasion resistance, and interfacial splitting tensile and shear strengths of metal mortar-concrete are discussed. The changes in the bond properties of metal mortar-concrete interface were also investigated from a microscopic point of view. The results showed that the alternating action of freeze-thaw cycles and abrasion resulted in more apparent damage and mass loss, and the coupling damage became more pronounced as the number of alternations increased. The interfacial bond strength was reduced by 33.7 %–50.06 % under a single freeze-thaw or abrasion action. And interfacial bond strength decreases by 54.94 %–66.33 % under coupled freeze-thaw and abrasion. The interfacial splitting tensile and shear strengths have a good linear relationship under various actions (the correlation coefficients are higher than 0.97). The microscopic tests showed that the maximum width of the interface under the coupled action of freeze-thaw cycles and abrasion reaches 80–110 μm, which is significantly higher than the single action (30–45 μm).

Water meter inaccuracy assessment and operation control considering customer information

Water Meter Inaccuracy (WMI) is one of the apparent loss components contributing to an increase in non-revenue water. The estimation of the volume of water lost due to WMI and control within a utility is still a challenge; thus, the current study investigated its field operation using customer consumption records. A few studies estimated WMI using data obtained in a controlled experimental environment; however, WMI assessment requires a significant computation that includes unforeseen field fault operating environment. This study is of the view that experimental results are necessary for meter type selection, based on the designed flow characteristics and proposes a WMI assessment and control approach in which the field under- or over-registering meters are identified in a billing system. The analysis of this study reveals that a utility operation environment, economic factor and social trust can be efficiently improved using customers water consumption records.

Modeling apparent Pb loss in zircon U–Pb geochronology

Abstract. The loss of radiogenic Pb from zircon is known to be a major factor that can cause inaccuracy in the U–Pb geochronological system; hence, there is a need to better characterize the distribution of Pb loss in natural samples. Treatment of zircon by chemical abrasion (CA) has become standard practice in isotope dilution–thermal ionization mass spectrometry (ID-TIMS), but CA is much less commonly employed prior to in situ analysis via laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) or secondary ionization mass spectrometry (SIMS). Differentiating the effects of low levels of Pb loss in Phanerozoic zircon with relatively low-precision in situ U–Pb dates, where the degree of Pb loss is insufficient to cause discernible discordance, is challenging. We show that U–Pb isotopic ratios that have been perturbed by Pb loss may be modeled by convolving a Gaussian distribution that represents random variations from the true isotopic value stemming from analytical uncertainty with a distribution that characterizes Pb loss. We apply this mathematical framework to model the distribution of apparent Pb loss in 10 igneous samples that have both non-CA LA-ICP-MS or SIMS U–Pb dates and an estimate of the crystallization age, either through CA U–Pb or 40Ar/39Ar geochronology. All but one sample showed negative age offsets that were unlikely to have been drawn from an unperturbed U–Pb date distribution. Modeling apparent Pb loss using the logit–normal distribution produced good fits with all 10 samples and showed two contrasting patterns in apparent Pb loss; samples where most zircon U–Pb dates undergo a bulk shift and samples where most zircon U–Pb dates exhibited a low age offset but fewer dates had more significant offset. Our modeling framework allows comparison of relative degrees of apparent Pb loss between samples of different age, with the first and second Wasserstein distances providing useful estimates of the total magnitude of apparent Pb loss. Given that the large majority of in situ U–Pb dates are acquired without the CA treatment, this study highlights a pressing need for improved characterization of apparent Pb-loss distributions in natural samples to aid in interpreting non-CA in situ U–Pb data and to guide future data collection strategies.

Culprits of Medication-Induced Telogen Effluvium, Part 2.

Telogen effluvium (TE) is a common mechanism underlying medication-related alopecia. The inciting cause of TE may be difficult to identify due to delays in clinically apparent hair loss. Because medication-induced TE is a nonscarring alopecia that typically is reversible, appropriate management requires identification of the underlying trigger and cessation of potential culprit medications. In part 2 of this 2-part series on medication-induced TE, we focus on anticoagulant and antihypertensive medications.

An overview of the Scottish National Adder Survey 2022-24

A study was commissioned by NatureScot to analyse changes in the status of the adder (Vipera berus) and other native reptiles at 16 sites across mainland Scotland, the Isle of Skye and the Isle of Arran over a 30-year period from 1992-93 to 2022-24. In 2022-24, volunteer surveyors revisited sites that were previously surveyed in 1992-93 to identify changes in occupancy. Visual surveys recorded adder, common lizard (Zootoca vivipara), slow-worm (Anguis fragilis), common frog (Rana temporaria), common toad (Bufo bufo), smooth newt (Lissotriton vulgaris), and palmate newt (Lissotriton helveticus). Adders were observed in comparable or even greater numbers at eight sites (seven of the original sites surveyed in 1992-93), but an apparent loss of adders at three of the original sites, and major declines at a previously favourable site on the Scottish Borders are cause for concern. Of the other reptiles, common lizards were the most widespread, recorded at 12 sites; and slow-worms were least often recorded, in low numbers at only four sites, though this could be expected in visual surveys for this cryptic species. This publication reviews the factors most likely to be affecting adders in Scotland, particularly the loss of suitable habitat, the likely historic impact of persecution and the potential effects of disturbance by recreational site users. It highlights the importance of sympathetic habitat management, with a particular focus on maintaining favourable micro-habitats for reptiles.

Magnetically recoverable Fe3O4@SiO2@SBA-3@2-ATP-Cu: an improved catalyst for the synthesis of 5-substituted 1H-tetrazoles.

Functionalization of Fe3O4@SiO2@SBA-3 with double-charged 3-chloropropyltrimethoxysilane (CPTMS) and 2-aminophenol, followed by mechanical mixing of the solid product with copper(i) chloride produces a new, greener and efficient Fe3O4@SiO2@SBA-3@2-ATP-Cu catalyst for the synthesis of 5-substituted 1H-tetrazoles. XRD, SEM, atomic absorption, TGA, N2 adsorption-desorption, and VSM analyses were performed for the characterization of the Fe3O4@SiO2@SBA-3@2-ATP-Cu structure. Nitrogen adsorption-desorption analysis revealed that Fe3O4@SiO2@SBA-3@2-ATP-Cu has a surface area of 242 m2 g-1 and a total pore volume of 55.72 cm3 g-1. In synthesizing 5-substituted 1H-tetrazoles, Fe3O4@SiO2@SBA-3@2-ATP-Cu shows superior yields in short reaction times at 120 °C. This catalyst also showed high thermal stability and recyclability at least for 4 runs without apparent loss of efficiency.

Functional performance of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold: a pre-clinical in vitro tribological study.

Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus.

Unraveling the Effects of Carbon Corrosion on Oxygen Transport Resistance in Low Pt Loading Proton Exchange Membrane Fuel Cells.

Cost and durability have become crucial hurdles for the commercialization of proton exchange membrane fuel cells (PEMFCs). Although a continuous reduction of Pt loading within the cathode catalyst layers (CCLs) can lead to cost savings, it also increases the oxygen transport resistance, which is further compounded by key material degradation. Hence, a further understanding of the mechanism of significant performance loss due to oxygen transport limitations at the triple phase boundaries (TPBs) during the degradation process is critical to the development of low Pt loading PEMFCs. The present study systematically investigates the impact of carbon corrosion in CCLs on the performance and oxygen transport process of low Pt loading PEMFCs through accelerated stress tests (ASTs) that simulate start-up/shutdown cycling. A decline in peak power density from 484.3 to 251.6 mW cm-2 after 1500 AST cycles demonstrates an apparent performance loss, especially at high current densities. The bulk and local oxygen transport resistances (rbulk and Rlocal) of the pristine cell and after 200, 600, 1000, and 1500 AST cycles are quantified by combining the limiting current method with a dual-layer CCL design. The results show that rbulk increased from 1527 to 1679 s cm-2, Rlocal increased from 0.38 to 0.99 s cm-1, and the local oxygen transport resistance with the normalized Pt surface area (rlocal) exhibited an increase from 18.5 to 32.0 s cm-1, indicating a crucial impact on the structure collapse and changes in the chemical properties of the carbon supports in the CCLs. Further, the interaction between the ionomer and carbon supports during the carbon corrosion process is deeply studied via electrochemical quartz crystal microbalance and molecular dynamics simulations. It is concluded that the oxygen-containing functional groups on the carbon surface could impede the adsorption of ionomers on carbon supports by creating an excessively water-rich layer, which in turn aggravates the formation of ionomer agglomerations within the CCLs. This process ultimately leads to the destruction of the TPBs and hinders the transport of oxygen through the ionomer.

A novel apparent power loss based distributed generator siting and sizing method considering dependent loads

In the present paper, it is first established that even though the standard Active Power Loss Sensitivity Factor (APLSF) based technique for Renewable Energy based Distributed Generation (REDG) system excels with respect to many available technical assessment indicators, its performance falls short in case of line loss reduction and power transfer capacity improvement indicators. On further investigation through Dynamic Fault Tree Analysis technique, it is found that the unsatisfactory performance of APLSF stem from neglecting reactive power loss and line reactance. Therefore, a novel apparent power loss augmented technique coined as Dynamic Loss Evaluation Indicator (DLEI) method is proposed here. The suitability of the proposed method is validated on IEEE 33 and 85 bus distribution systems for both voltage and voltage and frequency dependent load models and it is shown that the aforementioned indicators are improved along with the other indicators like voltage profile and voltage stability to name a few. For further validation, contingency and power quality analysis are also carried out and improved performance is observed in DLEI method when compared against the APLSF based method.

Effect of polypropylene fiber and nano-silica on the compressive strength and frost resistance of recycled brick aggregate concrete

Abstracts Wasted clay bricks as coarse aggregate of recycled concrete is an effective solution to save energy and reduce CO2 emissions in the construction industry. However, the mechanical properties and frost resistance of recycled brick aggregate (RBA) concrete are inferior to those of ordinary concrete, which limits its widespread application. In this research, the effects of RBA, polypropylene fiber (PPF) and nano-silica (NS) on the mechanical properties and frost resistance of concrete were investigated. The effect of RBA, PPF, and NS on the compressive strength was quantitatively analyzed, and microstructural analysis and fractal dimension calculation of the concrete were performed. The results show that the concrete compressive strength decreased with the increase in RBA replacement rate, and it was effectively improved by adding PPF and NS (PPF-NS). The compressive strength first increased and then decreased with the increase in PPF and NS. The improvement effect of 0.12% PPF and 2% NS on the compressive strength of 50% replacement rate of RBA concrete was most effective. The gray relational degrees between the compressive strength and RBA, PPF, and NS were 0.6578, 0.8297, and 0.5941, respectively. The frost resistance of PPF-NS modified concrete was better than that of ordinary concrete, mainly manifested in its superior apparent phenomena, mass loss, and strength loss. Compared with normal concrete, the microstructure was denser and the fractal dimension of the cross-section was higher for RBA concrete modified with PPF-NS before and after freeze–thaw cycles.

Molecular and phylogenetic evidence of parallel expansion of anion channels in plants.

Aluminum-activated malate transporters (ALMTs) and slow anion channels (SLACs) are important in various physiological processes in plants, including stomatal regulation, nutrient uptake, and in response to abiotic stress such as aluminum toxicity. To understand their evolutionary history and functional divergence, we conducted phylogenetic and expression analyses of ALMTs and SLACs in green plants. Our findings from phylogenetic studies indicate that ALMTs and SLACs may have originated from green algae and red algae, respectively. The ALMTs of early land plants and charophytes formed a monophyletic clade consisting of three subgroups. A single duplication event of ALMTs was identified in vascular plants and subsequent duplications into six clades occurred in angiosperms, including an identified clade, 1-1. The ALMTs experienced gene number losses in clades 1-1 and 2-1 and expansions in clades 1-2 and 2-2b. Interestingly, the expansion of clade 1-2 was also associated with higher expression levels compared to genes in clades that experienced apparent loss. SLACs first diversified in bryophytes, followed by duplication in vascular plants, giving rise to three distinct clades (I, II, and III), and clade II potentially associated with stomatal control in seed plants. SLACs show losses in clades II and III without substantial expansion in clade I. Additionally, ALMT clade 2-2 and SLAC clade III contain genes specifically expressed in reproductive organs and roots in angiosperms, lycophytes, and mosses, indicating neofunctionalization. In summary, our study demonstrates the evolutionary complexity of ALMTs and SLACs, highlighting their crucial role in the adaptation and diversification of vascular plants.

Iron, Nickel, Copper, Zinc, and their stable isotopes along a salinity gradient in the Pearl River Estuary, southeastern China

Although the crucial role that dissolved trace metals (dTMs) play in both carbon cycling and climate have been revealed over the past three decades, much about the oceanic budgets of dTMs remains unknown. Rivers are one of the most important dTM sources to the ocean, and estuaries are a key interface between land and ocean. However, our understanding of how dTMs behave as they pass through the estuarine transition is limited, leading to uncertainties in estimating fluvial metal fluxes to the ocean and balancing oceanic dTM budgets. Alongside concentrations, metal stable isotopes offer an additional dimension to constrain estuarine processes, but data on metal isotopes in estuaries are scarce. Here we present dTM concentrations and their stable isotope ratios along a full salinity gradient in the Pearl River Estuary (PRE), southeastern China. Concentration data show a large apparent loss of dFe (86%) during estuarine mixing, moderate losses of dNi (13%) and dZn (36%), and nearly conservative behavior for dCu. However, examination of metal isotope data (δ56Fe, δ60Ni, δ65Cu, and δ66Zn) reveals more complex biogeochemistry, requiring either a two-stage scenario or a three-endmember mixing process. The two-stage process involves fractionation of dTM isotopes at low salinities, likely driven by particle adsorption and colloidal flocculation, followed by conservative mixing between intermediate-salinity estuarine waters and South China Sea waters. Alternatively, the three-endmember mixing process includes influences from riverine, oceanic endmembers, and external sources such as benthic flux and industrial activities, shaping dTM isotope distributions. Specifically, capturing δ56Fe fully proves challenging, yet it appears strongly influenced by inputs of benthic Fe within the PRE, characterized by dFe > 13 nmol kg−1 and δ56Fe < −0.80‰. δ60Ni and δ66Zn can be described by either two-stage or there-endmember mixing processes. In the former, the Rayleigh fractionation with αd-p of 1.00004 for δ60Ni and 1.0001 for δ66Zn, or the steady state fractionation with αd-p of 1.00005 for δ60Ni and 1.0002 for δ66Zn, could be derived to explain their patterns at low salinity, likely driven by colloidal flocculation. Additionally, a third source with dNi > 33 nmol kg−1 and δ60Ni > +1.26‰ and a third source with dZn > 13 nmol kg−1 and δ66Zn > +0.96‰, both influenced by human activities, could also shape the δ60Ni and δ66Zn patterns in the PRE, respectively. The description of δ65Cu is best achieved by a three-endmember mixing process, with the external source having dCu > 20 nmol kg−1 andδ65Cu < +1.3‰, indicative of processes like organic matter remineralization or discharge from wastewater treatment plant. Our study highlights the need for more extensive and detailed studies on estuarine settings to elucidate their potentially crucial role in global dTMs budgets.

Morphological description of spontaneous pelvic fin loss in a neotropical cichlid fish.

Pelvic finsare a characteristic structure of the vertebrate Bauplan. Yet, pelvic fin loss has occurred repeatedly across a wide diversity of other lineages of tetrapods and at least 48 times in teleost fishes. This pelvic finless condition is often associated with other morphological features such as body elongation, loss of additional structures, and bilateral asymmetry. However, despite the remarkable diversity in the several thousand cichlid fish species, none of them are characterized by the complete absence of pelvic fins. Here, we examined the musculoskeletal structure and associated bilateral asymmetry in Midas cichlids (Amphilophus cf. citrinellus) that lost their pelvic fins spontaneously in the laboratory. Due to this apparent mutational loss of the pelvic girdle and fins, the external and internal anatomy are described in a series of "normal" Midas individuals and their pelvic finless sibling tankmates. First, other traits associated with teleost pelvic fin loss, the genetic basis of pelvic fin loss, and the potential for pleiotropic effects of these genes on other traits in teleosts were all reviewed. Using these traits as a guide, we investigated whether other morphological differences were associated with the pelvic girdle/fin loss. The mean values of the masses of muscle of the pectoral fin, fin ray numbers in the unpaired fins, and oral jaw tooth numbers did not differ between the two pelvic fin morphotypes. However, significant differences in meristic values of the paired traits assessed were observed for the same side of the body between morphotypes. Notably, bilateral asymmetry was found exclusively for the posterior lateral line scales. Finally, we found limited evidence of pleiotropic effects, such as lateral line scale numbers and fluctuating asymmetry between the Midas pelvic fin morphotypes. The fast and relatively isolated changes in the Midas cichlids suggest minor but interesting pleiotropic effects could accompany loss of cichlid pelvic fins.

Robust Molecular Anodes for Electrocatalytic Water Oxidation Based on Electropolymerized Molecular Cu Complexes.

A multistep synthesis of a new tetra-amidate macrocyclic ligand functionalized with alkyl-thiophene moieties, 15,15-bis(6-(thiophen-3-yl)hexyl)-8,13-dihydro-5H-dibenzo[b,h][1,4,7,10]tetraazacyclotridecine-6,7,14,16(15H,17H)-tetraone, H4 L, is reported. The reaction of the deprotonated ligand, L4- , and Cu(II) generates the complex [LCu]2- , that can be further oxidized to Cu(III) with iodine to generate [LCu]- . The H4 L ligand and their Cu complexes have been thoroughly characterized by analytic and spectroscopic techniques (including X-ray Absorption Spectroscopy, XAS). Under oxidative conditions, the thiophene group of [LCu]2- complex polymerizes on the surface of graphitic electrodes (glassy carbon disks (GC), glassy carbon plates (GCp ), carbon nanotubes (CNT), or graphite felts (GF)) generating highly stable thin films. With CNTs deposited on a GC by drop casting, hybrid molecular materials labeled as GC/CNT@p-[LCu]2- are obtained. The latter are characterized by electrochemical techniques that show their capacity to electrocatalytically oxidize water to dioxygen at neutral pH. These new molecular anodes achieve current densities in the range of 0.4mAcm-2 at 1.30V versus NHE with an onset overpotential at ≈250mV. Bulk electrolysis experiments show an excellent stability achieving TONs in the range of 7600 during 24h with no apparent loss of catalytic activity and maintaining the molecular catalyst integrity, as evidenced by electrochemical techniques and XAS spectroscopy.

Investigating the rheological properties and 3D printability of tomato-starch paste with different levels of xanthan gum

Tomato is an inexpensive vegetable with high nutritional value，but it does not have the suitable self-supporting ability for 3D printing. Xanthan gum (XG) is a common thickener that may improve 3D printability of tomatoes paste. This study evaluated the printability of tomato-starch paste (TSP) by examining its rheological and textural properties and microstructure of 3D samples. The rheological results showed that apparent viscosity, recovery rate, storage modulus, loss modulus, initial and average rheological forces, and shear stress increased significantly (P < 0.05) with increase of XG levels in tomato-starch paste. The low-field NMR results showed that T21 and T22 of the TSP decreased with increase of XG levels (P < 0.05). With increase of XG levels, a dense network structure in the TSP was formed as observed in the microstructural images. The TSP with 5 g/kg XG had the highest printing accuracy, and the textural property showed that the addition of 5 g/kg of XG significantly improved the hardness, elasticity, and chewability of TSP (P < 0.05). Overall, with increase of XG levels the fluidity of the pseudoplastic gel formed by the tomato-starch system and increased the density of the structure, resulting in improved extrudability, shape stability, and self-supporting property.

Evolutionary degeneration of septins into pseudoGTPases: impacts on a hetero-oligomeric assembly interface.

The septin family of eukaryotic proteins comprises distinct classes of sequence-related monomers that associate in a defined order into linear hetero-oligomers, which are capable of polymerizing into cytoskeletal filaments. Like actin and ⍺ and β tubulin, most septin monomers require binding of a nucleotide at a monomer-monomer interface (the septin "G" interface) for assembly into higher-order structures. Like ⍺ and β tubulin, where GTP is bound by both subunits but only the GTP at the ⍺-β interface is subject to hydrolysis, the capacity of certain septin monomers to hydrolyze their bound GTP has been lost during evolution. Thus, within septin hetero-oligomers and filaments, certain monomers remain permanently GTP-bound. Unlike tubulins, loss of septin GTPase activity-creating septin "pseudoGTPases"-occurred multiple times in independent evolutionary trajectories, accompanied in some cases by non-conservative substitutions in highly conserved residues in the nucleotide-binding pocket. Here, we used recent septin crystal structures, AlphaFold-generated models, phylogenetics and in silico nucleotide docking to investigate how in some organisms the septin G interface evolved to accommodate changes in nucleotide occupancy. Our analysis suggests that yeast septin monomers expressed only during meiosis and sporulation, when GTP is scarce, are evolving rapidly and might not bind GTP or GDP. Moreover, the G dimerization partners of these sporulation-specific septins appear to carry compensatory changes in residues that form contacts at the G interface to help retain stability despite the absence of bound GDP or GTP in the facing subunit. During septin evolution in nematodes, apparent loss of GTPase activity was also accompanied by changes in predicted G interface contacts. Overall, our observations support the conclusion that the primary function of nucleotide binding and hydrolysis by septins is to ensure formation of G interfaces that impose the proper subunit-subunit order within the hetero-oligomer.

The Effect of Polypropylene Fiber and Glass Fiber on the Frost Resistance of Desert Sand Concrete

To study the influence of polypropylene (PP) fibers and glass fibers on the frost resistance of desert sand concrete (DSC), the fast-freezing tests were carried out to investigate the freeze-thaw damage law using the apparent damage, mass loss, and relative dynamic elastic modulus as indicators; Based on the mercury intrusion method (MIP) and scanning electron microscopy (SEM), the microstructure evolution was analyzed to reveal the mechanism of fiber frost resistance enhancement. Fit the freeze-thaw damage process of fiber reinforced DSC (FRDSC) and predict the frost resistance life. The results show that fibers can greatly improve the freezing resistance of DSC. The hybrid fiber had the highest enhancing effect, followed by PP fiber and glass fiber. The dynamic elastic modulus of the DSC with 0.15% PP fiber and 0.05% glass fiber is as high as 95%. The pore distribution ratio of FRDSC changes faster, but it is still better than that of reference DSC after freeze-thaw. PP fiber and glass fiber can play a full role in the micro and macro stages of crack development of DSC respectively. The freeze-thaw damage model has high fitting accuracy and the DSC mixed with fibers can significantly improve the service life of buildings in northern China.

Targeting the JAK2V617F Hematopoietic Stem Cell through Beta1 Integrin

The major barrier to progress in treatment of primary myelofibrosis (PMF) is the lack of effective therapies targeting the malignant JAK2 V617F hematopoietic stem cell (HSC), the source of disease progression and relapse. Expression of JAK2 V617F induces abnormal proliferation and differentiation of HSC, affecting all blood lineages but most prominently the erythro-megakaryocytic lineage, leading to clonal megakaryocyte proliferation, erythrocytosis and thrombocytosis. In our previously published work ( Matsuura et al, Blood 2020) we identified elevated expression of the α5 subunit of the α5β1 integrin receptor as a driver of JAK2 V617F megakaryocyte proliferation. Expression of β1 integrin subunit was similar in wild-type (WT) and JAK2 V617F megakaryocytes, but activation of β1 integrin, detected by the conformation-specific 9EG7 antibody, was elevated in JAK2 V617F megakaryocytes. Following up on those findings, we detected elevated β1 integrin activation in long-term hematopoietic stem cells (HSC LT, LSKCD48-CD150+) from JAK2 V617F transgenic mice ( Xing et al, Blood 2008) when compared to WT controls. To determine whether inhibition of β1 integrin in vivo reduces the number of HSC LT in JAK2 V617F transgenic mice, we examined HSC LT 24 hours after intravenous administration of 2mg/Kg of anti-β1 integrin inhibitory antibody HMβ1-1. This regimen led to a sharp reduction in number and percentage of HSC LT in JAK2 V617F transgenic mice, to 45% of control antibody-treated animals. The effect on WT HSC LT was negligible. HSC ST (LSKCD48-CD150-) and MPP2 (LSKCD48+CD150+) were also reduced, but the reduction was not statistically significant. MPP3/4 (LSKCD48+CD150-) and LSK were not affected. Megakaryocyte progenitors (LKCD41+CD150+) were significantly reduced. Inhibition of β1 integrin also sharply reduced peripheral blood platelet numbers in WT animals. The reduction in JAK2 V617F transgenic mice was not statistically significant. A longer observation time of 7 days demonstrated that while WT animals were able to mount a robust regenerative response with slight but significant increases in HSC LT and normalization of platelet numbers, in JAK2 V617F transgenic mice the number of HSC LT remained depressed, as did downstream stem/progenitor populations at various significance levels. To gain insight into the mechanisms that lead to reduction in HSC LT, we examined apoptosis, cell cycle and HSC mobilization, all processes known to be affected by β1 integrin. Although basal expression of the apoptotic marker annexin V was decreased in JAK2 V617F HSC LT compared to WT, no differences were detected upon administration of HMβ1-1 in both genotypes at 4 hours post-administration. Similarly, peripheral blood colony assays revealed a basally higher level of stem/progenitor mobilization in JAK2 V617F, which did not significantly increase upon HMβ1-1 administration. In contrast, the cell cycle profile, examined at 4 hours post-administration to account for the earliest effects, demonstrated a decrease in G0 phase cells and increase in S/G2/M cells indicating cell cycle induction and exit from quiescence in both WT and JAK2 V617F HSC LT. The results indicate that inhibition of β1 integrin disrupts the adhesion-mediated cell cycle suppression in both WT and JAK2 V617F HSC LT leading to exit from quiescence. However, the downstream consequences of cell division in HSC LT differ significantly, with an apparent loss of regenerative potential in JAK2 V617F HSC LT, at least at the observed timepoints. Longer observation times are required to determine whether continuous β1 integrin inhibition can lead to JAK2 V617F HSC LT exhaustion. More sensitive assays to monitor mobilization are warranted to quantify possible minute amounts of mobilized HSC LT. Our preclinical studies indicate that β1 integrin is an attractive target to specifically reduce the number of JAK2 V617F HSC LTin vivo. The role of β1 integrin in HSC LT has not been thoroughly studied due to lack of phenotype in β1 integrin-deficient HSC ( Brakebush et al, Immunity 2002). Our studies using the anti-β1 integrin antibody in WT HSC LT confirm previous findings. However, β1 integrin seems to be critical for maintenance of JAK2 V617F HSC LT, offering a possible therapeutic window. Understanding how β1 integrin supports quiescence in HSC LT will bring us a step closer to understanding the mechanisms that drive malignancy and fitness in JAK2 V617F HSC LT.

Enzymatic approach to the synthesis of chiral intermediate of Rodatristat ethyl

Ketoreductases are widely explored for the reduction of prochiral ketones for the preparation of chiral alcohols. Though, the chiral Ir(III) catalyst has been used for the asymmetric reduction of keto intermediate of Rodatristat ethyl, an enzymatic approach for its preparation has not yet been reported. In this regard, we report, for the first time the preparation of enantiopure secondary alcohols (R-3) and (S-3) from 1-(5-chloro-[1,1’-biphenyl]-2-yl)-2,2,2-trifluoroenthan-1-one (2) using commercially available ketoreductases at 30 °C in the presence of 125 mM sodium phosphate buffer pH 6 over 24 h. This enzymatic approach provides the (R)-3 and (S)-3 chiral alcohols in >99% enantiomeric excess (ee) with >99% conversion using KRED-244 and KRED-101 respectively. Furthermore, the KRED-244 and KRED-101 enzymes have been successfully immobilized with sodium alginate, which makes them recyclable and reusable in subsequent reactions. The reusability experiments were carried out over 15 cycles without any apparent loss of activity even after 10 cycles. It is a sustainable approach to the synthesis of enantiopure intermediates of rodatristat ethyl, contributing to the advancement of green chemistry.