KSI

The influence of tempering temperature on the microstructure of 0.5Cr0.4W steels was investigated by scanning electron microscope, and the roles of grain boundary character, dislocation, and Taylor factor in sulfide stress cracking (SSC) resistance were interpreted using the election backscattered diffraction technique. The 0.5Cr0.4W steels tempered at 690 °C, 700 °C, and 715 °C all showed tempered martensites. The specimen tempered at 715 °C exhibited a higher critical stress intensity factor (KISSC ) of 34...

Introduction: Increasing levels of active travel in the population brings many public health benefits, but may also change the risks of road injury for different road users. We examined changes in rates of pedestrian injuries resulting from collisions with pedal cycles and motor vehicles in England during 2005-2015, a period of increased cycling activity, and described the gender, age distribution and locations of pedestrians injured in collisions with pedal cycles and motor vehicles...

Cold temperature is prevalent across the biosphere and slows the rates of chemical reactions. Increased catalysis has been predicted to be a dominant adaptive trait of enzymes to reduced temperature, and this expectation has informed physical models for enzyme catalysis and influenced bioprospecting strategies. To systematically test rate enhancement as an adaptive trait to cold, we paired kinetic constants of 2223 enzyme reactions with their organism's optimal growth temperature ( T Growth ) and analyzed trends of rate constants as a function of T Growth ...

PURPOSE: To determine the normative and the cut-off values of various indices available in the MS 39 Anterior Segment Optical Coherence Tomography (MS-39 AS-OCT) for keratoconus (KC) diagnosis, and to detect the accuracy of the variable available parameters. METHODS: This cross sectional observational study was conducted at Dr Rifay Ophthalmology Center, Rabat, Morocco, on 172 eyes with KC (group 1) and 248 eyes of healthy controls (group 2). Participants were screened using MS-39 AS-OCT (CSO, Firenze, Italy)...

Ticagrelor is the first reversibly binding, direct-acting, oral P2Y12 receptor inhibitor. The contribution of UDP-glucuronosyltransferases (UGTs) enzymes to the metabolism of ticagrelor to its glucuronide conjugation, ticagrelor-O-glucuronide, in human liver microsomes (HLM) and human intestinal microsomes (HIM), was well characterized in the current study. The inhibition potential of human major UGTs by ticagrelor and ticagrelor-O-glucuronide was explored. The inhibitory effects of ticagrelor-O-glucuronide on cytochrome P450s (CYPs) enzymes were investigated as well...

Despite the great attention paid to Internet literacy research, little has been done to overcome the problems stemming from the heterogeneity of Internet literacy nomenclature and the use of non-standardized measurement tools, especially for adolescents in developing countries. Considering junior students are the high-risk groups of Internet addiction and have wide access to the Internet, the aim of this study is to develop a new scale to assess Chinese junior students' Internet literacy (JIL). In the psychometric study ( n = 1099 junior students), an 18-item scale was developed using the exploratory and confirmatory factor analyses, which includes five subscales: knowledge and skills for the Internet (KSI), Internet self-management (ISM), awareness and cognition of Internet (ACI), Internet interactions (II), and autonomous learning on the Internet (ALI)...

Age-related macular degeneration (AMD) is the most common cause of legal blindness in developed countries. Neovascular (ie, wet) AMD is currently managed with intravitreal therapy. Traditional treatments (ie, bevacizumab, ranibizumab, aflibercept) provide high-efficacy therapy but can also require frequent dosing. Newer and future anti-VEGF therapies aim to decrease injection frequency through eitherlonger half life or port-delivery systems (brolucizumab, conbercept, KSI-301, ranibizumab). This review outlines current anti-VEGF treatments and ways by which their duration might be extended...

Age related macular degeneration (AMD) is the most common cause of vision loss in the elderly population. Neovascular AMD comprises 10% of all cases and can lead to devastating visual loss due to choroidal neovascularization (CNV). There are various cytokine pathways involved in the formation and leakage from CNV. Prior treatments have included focal laser therapy, verteporfin (Visudyne, Bausch and Lomb, Rochester, New York) ocular photodynamic therapy, transpupillary thermotherapy, intravitreal steroids and surgical excision of choroidal neovascular membranes...

Sulfide stress corrosion cracking (SSCC) has been of particular concern in high strength low alloyed (HSLA) steels used in the oil industry, and the non-metallic inclusions are usually considered as a detrimental factor to the SSCC resistance. In the present work, continuous casting (CC) and electroslag remelting (ESR) were adopted to fabricate a 125 ksi grade steel in order to evaluate the effect of microstructure with and without primary NbC carbides (inclusions) on the SSCC resistance in the steel. It was found that ESR could remove the primary NbC carbides, and hence, slightly increase the strength without deteriorating the SSCC resistance...

The corrosivity of bitumen at 60 and 120 °C was examined by exposing American Petroleum Institute (API) X100 (yield strength 100 ksi, 690 MPa) pipeline steel to bitumen in an autoclave for 30 days. Prior to the autoclave measurements, the inclusion types in the API-X100 pipeline steel were characterized by scanning electron microscopy (SEM), and four types of inclusions were identified, according to their elemental compositions. The four types of inclusions and the surrounding matrix were characterized by ex situ SEM before and after exposure to bitumen...

The treatment and outcomes of diabetic macular oedema (DMO) have improved with the introduction of intravitreal injections. However, real-world data reveal that the burden of DMO treatment causes large gaps in outcomes between randomized clinical trials and daily clinical practice. Long-lasting intravitreal drugs and devices for DMO might reduce this disparity by achieving optimal treatment due to more feasible injection regimens. In this manuscript, we cover pharmacodynamics, preliminary results from clinical trials, and safety behavior about brolucizumab, faricimab, conbercept, KSI-301, and port-delivery system WR42221...

A study was carried out on the solvolysis of 1-adamantyl chlorothioformate (1-AdSCOCl, 1 ) in hydroxylic solvents. The rate constants of the solvolysis of 1 were well correlated using the Grunwald-Winstein equation in all of the 20 solvents (R = 0.985). The solvolyses of 1 were analyzed as the following two competing reactions: the solvolysis ionization pathway through the intermediate (1-AdSCO)+ (carboxylium ion) stabilized by the loss of chloride ions due to nucleophilic solvation and the solvolysis-decomposition pathway through the intermediate 1-Ad+ Cl- ion pairs (carbocation) with the loss of carbonyl sulfide...

KSI-301 is a new intravitreal anti-vascular endothelial growth factor (VEGF) antibody biopolymer conjugate under investigation for the treatment of age-related macular degeneration (AMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). Preclinical and early clinical trials so far have shown promising results in retinal vascular diseases. When using anti-VEGF agents for treatment of retinal disorders, the frequency of injections and follow-up visits has increased the treatment burden, greatly affecting the treatment outcome...

Neovascular age-related macular degeneration (nAMD) treatment has been revolutionized by the introduction of vascular endothelial growth factor antagonists (anti-VEGF), but the need for frequent intravitreal injections poses a heavy burden to patients and physicians. Evolving anti-VEGF therapies include longer duration agents, approaches that target multiple pathways, topical anti-VEGF agents, sustained-release, and genetic therapies. Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation...

AIM: We aimed (i) to study the effects of genetic polymorphism of cytochrome P450 3A4 (CYP3A4) and drug interactions on acalabrutinib (ACA) metabolism and (ii) to investigate the mechanisms underlying the effects of CYP3A4 variants on the differential kinetic profiles of ACA and ibrutinib. METHOD: Recombinant human CYP3A4 and variants were expressed using a Bac-to-Bac baculovirus expression system. The cell microsome was prepared and subjected to kinetic study. The analyte concentrations were determined by UPLC-MS/MS...

Phosphoproteomics and proteomics experiments capture a global snapshot of the cellular signaling network, but these methods do not directly measure kinase state. Kinase Enrichment Analysis 3 (KEA3) is a webserver application that infers overrepresentation of upstream kinases whose putative substrates are in a user-inputted list of proteins. KEA3 can be applied to analyze data from phosphoproteomics and proteomics studies to predict the upstream kinases responsible for observed differential phosphorylations...

The Kemp elimination reaction, involving the ring-opening of benzoxazole and its derivatives under the action of natural enzymes or chemical catalysts, has been of interest to researchers since its discovery. Because this reaction does not exist in all currently known metabolic pathways, the computational design of Kemp eliminases has provided valuable insights into principles of enzymatic catalysis. However, it was discovered that the naturally occurring promiscuous enzymes ydbC, xapA and ketosteroid isomerase also can catalyze Kemp elimination...

Pyrenophora tritici-repentis is a causative agent of tan spot in wheat. In recent years, there has been an increasing spread and harmfulness of wheat tan spot. The aim of the research was to study the racial composition of the P. tritici-repentis population in the Republic of Kazakhstan. A collection of 30 common wheat accessions, including promising lines and cultivars from Kazakhstan and CIMMYT-ICARDA, was assessed for resistance to P. tritici- repentis in a greenhouse and characterized using the Xfcp623 molecular marker, diagnostic for the Tsn1 gene...

p-Cresol sulfate, the primary metabolite of p-cresol, is a uremic toxin that has been associated with toxicities and mortalities. The study objectives were to i) characterize the contributions of human sulfotransferases (SULT) catalyzing p-cresol sulfate formation using multiple recombinant SULT enzymes (including the polymorphic variant SULT1A1*2), pooled human liver cytosols, and pooled human kidney cytosols; and ii) determine the potencies and mechanisms of therapeutic inhibitors capable of attenuating the production of p-cresol sulfate...

The main objective of this paper was to analyse the roadway, environmental, and driver-related factors associated with an overrepresentation of frequency and severity of run-off-the-road (ROR) crashes. The data used in this study refer to the 6167 crashes occurred in the section Naples-Candela of A16 motorway, Italy in the period from 2001 to 2011. The analysis was carried out using the rule discovery technique due to its ability of extracting knowledge from large amounts of data previously unknown and indistinguishable by investigating patterns that occur together in a given event...