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For a detailed examination of the interaction of rhamnose containing derivatives with recombinant horseshoe crab plasma lectin (rHPL), two di-rhamno-di-lipids (an α-1,2- and an α-1,3-linked) were synthesized via a new simple method. The N-iodosuccinimide/triflic acid mediated glycosylation of the methyl (R)-3-hydroxydecanoate with phenyl-1-thio-rhamnobioside donors afforded the mono-lipid disaccharides. Removal of the methyl ester group followed by esterification of the mono-lipids with a second (R)-3-hydroxydecanoate unit resulted in fully protected di-lipid derivatives, transformation of which into the target compounds was accomplished in two steps. This method allows the synthesis of both regioisomers in only 6 steps starting from the corresponding free disaccharides. Both synthetic di-rhamnolipids were biologically active for lectin binding differential binding preference between two isomeric di-rhamno-di-lipids. The rHPL lectin favours the α-1,3-linked di-rhamno-di-lipids over its α-1,2-linked regioisomer., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cosmeceutical peptides have become an important topic in recent decades in both academic and industrial fields. Many natural or synthetic peptides with different biological functions including anti-ageing, anti-oxidation, anti-infection and anti-pigmentation have been developed and commercialized. Current cosmeceutical peptides have already satisfied most market demand, remaining: "cargos carrying skin penetrating peptide with high safety" still an un-met need. To this aim, a cell-penetrating peptide, CPP AIF , which efficiently transported cargos into epithelial cells was exanimated. CPP AIF was evaluated with cell model and 3D skin model following OECD guidelines without using animal models. As a highly stable peptide, CPP AIF neither irritated nor sensitized skin, also did not disrupt skin barrier. In addition, such high safety peptide had anti-inflammation activity without allergic effect. Moreover, cargo carrying activity of CPP AIF was assayed using HaCaT cell model and rapid CPP AIF penetration was observed within 30 min. Finally, CPP AIF possessed transepidermal activity in water in oil formulation without disruption of skin barrier. All evidences indicated that CPP AIF was an ideal choice for skin penetrating and its anti-inflammatory activity could improve skin condition, which made CPP AIF suitable and attractive for novel cosmeceutical product development., Competing Interests: The authors declare no conflict of interest.

More than 80% of infectious bacteria form biofilm, which is a bacterial cell community surrounded by secreted polysaccharides, proteins and glycolipids. Such bacterial superstructure increases resistance to antimicrobials and host defenses. Thus, to control these biofilm-forming pathogenic bacteria requires antimicrobial agents with novel mechanisms or properties. Pseudomonas aeruginosa , a Gram-negative opportunistic nosocomial pathogen, is a model strain to study biofilm development and correlation between biofilm formation and infection. In this study, a recombinant hemolymph plasma lectin (rHPL OE ) cloned from Taiwanese Tachypleus tridentatus was expressed in an Escherichia coli system. This rHPL OE was shown to have the following properties: (1) Binding to P. aeruginosa PA14 biofilm through a unique molecular interaction with rhamnose-containing moieties on bacteria, leading to reduction of extracellular di-rhamnolipid (a biofilm regulator); (2) decreasing downstream quorum sensing factors, and inhibiting biofilm formation; (3) dispersing the mature biofilm of P. aeruginosa PA14 to improve the efficacies of antibiotics; (4) reducing P. aeruginosa PA14 cytotoxicity to human lung epithelial cells in vitro and (5) inhibiting P. aeruginosa PA14 infection of zebrafish embryos in vivo. Taken together, rHPL OE serves as an anti-biofilm agent with a novel mechanism of recognizing rhamnose moieties in lipopolysaccharides, di-rhamnolipid and structural polysaccharides (Psl) in biofilms. Thus rHPL OE links glycan-recognition to novel anti-biofilm strategies against pathogenic bacteria.

Background: The most common conservative treatment for Adolescent Idiopathic Scoliosis (AIS) is bracing. However, several papers questioned the effectiveness of bracing for curves between 40° and 50° Cobb: the effectiveness in preventing curve progression could be as low as 35%. Seriate casting is considered a standard approach in early onset scoliosis; however, in the setting of AIS, cast treatment is seldom utilized, with only few studies reporting on its effectiveness. Aim of the study: The main aim of the study is to determine whether a seriate casting with Risser casts associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. Furthermore, the secondary endpoints were: (1) is there a difference in effectiveness of casting between Thoracic (T) and Thoracolumbar/Lumbar (TL/L) curves? (2) Does the 'in cast' correction predicts the treatment outcome? (3) What is the effect on thoracic kyphosis of casting? Methods: This is a retrospective monocentric case–control study; through an Institutional Database search we identified all the patients treated at our institution between 1 January 2017 and 31 December 2020, with a diagnosis of AIS, Risser grade between 0 and 4 at the beginning of the treatment, at least one curve above 40° Cobb and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Standing full spine X-rays in AP and LL are obtained before and after the cast treatment; only AP standing full spine X-rays 'in-cast' are obtained for each cast made. Patients were stratified according to the curve behavior at the end of treatment (Risser 5): progression was defined as ≥6° increase in the curve magnitude or fusion needed; stabilization is defined as a change in curve by ±5°; and improvement was defined as ≥6° reduction in the curve. Results: For the final analysis, 55 compliant patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 27 (4 M, 23 F, mean age 13.6 ± 1.6) in the CG. Eight (14.5%) patients in the SG failed the conservative treatment while 14 (51.3%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1, 3–2.6, p = 0.001), and the Number Needed to Treat was 2,4. No significant difference was found between the T and TL/L curves concerning the 'progressive' endpoint (z-score 0.263, p = 0.79). The mean percentage of 'in cast' curve reduction was 40.1 ± 15.2%; no significant correlation was found between the percentage of correction and the outcome (Spearman Correlation Coefficient 0.18). Finally, no significant differences between baseline and end of FU TK were found (32° ± 16.2 vs. 29.6 ± 15.8, p = ns). Discussion: Seriate Risser casting for AIS with larger curves (>40° Cobb) is effective in reducing curve progression when compared with full time bracing alone in treatment compliant patients. The treatment is equally effective in controlling T and TL/L curves; furthermore, a slight but non-significant decrease in TK was observed in patients treated with casting. This type of treatment should be considered for AIS patients who present with large curves to potentially reduce the percentage of surgical cases. Short Abstract: The aim of the study is to determine whether seriate Risser casting associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. This is a retrospective monocentric case–control study; we identified all the patients treated at our institution with a diagnosis of AIS, Risser grade 0–4 at the beginning of the treatment, at least one curve above 40° Cobb (35° if treated with bracing alone) and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Fifty-five patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 30 (5 M, 25 F, mean age 13.9 ± 1.7) in the CG. Eight (14,5%) patients in the SG failed the conservative treatment while fifteen (50%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1.3–2.6, p = 0.001), and the Number Needed to Treat was 2,4. Seriate Risser casting for AIS with larger curves (>40°) is effective in reducing curve progression when compared with full time bracing alone. This type of treatment should be considered for AIS patients who present with large curves. [ABSTRACT FROM AUTHOR]

Objective: Pericallosal artery aneurysms are not common clinically. The microsurgery and endovascular therapy are surgically challenging operations. The objective of the study is to summarize their clinical symptoms and optimal treatment strategies of pericallosal artery aneurysms., Methods: Nine cases of pericallosal artery aneurysms detected by digital subtraction angiography (DSA) were reviewed. The clinical manifestation, brain imaging characteristics, and optimal treatment methods were summarized., Results: Patients with spontaneous aneurysm had good clinical outcomes after endovascular coiling or microsurgical clipping treatment. There were no any neurological function deficits in five patients. One patient suffered from permanent neurological function deficits. Patients with traumatic aneurysm pericallosal had relatively poor outcomes, including two patients showing disturbed consciousness and the paralysis of the lower limbs with slow recovery, and one patient was dead after the surgery., Conclusion: Spontaneous subarachnoid hemorrhage and interhemispheric fissure hematoma suggest spontaneously pericallosal aneurysm, while traumatic corpus callosum hematoma as well the accompanying embryo of intraventricular hemorrhage suggest traumatic pericallosal aneurysm. Endovascular embolization is the primary surgical treatment for pericallosal aneurysm, while patients with pericallosal aneurysm are not suitable for surgical treatment. Microsurgical clipping treatment may be a choice. However, both of these treatment strategies have high risk., (Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.)

(R)-Phenylephrine [(R)-PE] is an α1-adrenergic receptor agonist and is widely used as a nasal decongestant to treat the common cold without the side effects of other ephedrine adrenergic drugs. We identified a short-chain dehydrogenase/reductase (SM_SDR) from Serratia marcescens BCRC 10948 that was able to convert 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) into (R)-PE. The SM_SDR used NADPH and NADH as cofactors with specific activities of 17.35±0.71 and 5.57±0.07mU/mg protein, respectively, at 30°C and pH 7.0, thereby indicating that this enzyme could be categorized as an NADPH-preferring short-chain dehydrogenase/reductase. Escherichia coli strain BL21 (DE3) expressing SM_SDR could convert HPMAE into (R)-PE with more than 99% enantiomeric excess. The productivity and conversion yield were 0.57mmolPE/lh and 51.06%, respectively, using 10mM HPMAE. Fructose was the most effective carbon source for the conversion of HPMAE to (R)-PE., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In the present paper, soluble Ca content in banana pulp was analyzed with pretreatment of digestion model in vitro. All the samples were digested by strong acid (perchloric acid and nitric acid with 1 : 4 ratio) and determined by AA700 flame atomic absorption spectrophotometry (FAAS). Meanwhile, the reproducibility of the analytical method was investigated. The results showed that (1) Content of Ca was 1.479 mg x g(-1) x DW in eighty percent maturity banana pulp. And the relative standard deviation was 4.12%. (2) Contents of Ca in the soluble and insoluble fractions were 1.108 and 0.412 mg x g(-1) x DW, respectively in eighty percent maturity banana pulp with pretreatment of digestion model in vitro. The extraction rate was 74.9% and the residue rate was 27.8%. (3) The relative standard deviations of the analytical results of Ca contents in those two fractions were 2.56% and 9.10%, respectively, in the reproducibility tests. It was showed that the digestion model in vitro did not affect the reproduction quality significantly. Moreover, the deviation between the theoretical value and the summation value of the extraction and the residue rates was only 2.7%, which showed good availability of the digestion model in vitro to be used as a pretreatment method in mineral element analysis process. (4) Relative standard deviation and recovery yield in the determination procedure were 0.11% (n = 9) and 99.2%, respectively.

Aims: This study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales., Methods: Experimental and in silico ADME, physicochemical and pharmacological data were collected for antimuscarinic activity, blood-brain barrier penetration, bioavailability, chemical structure and P-glycoprotein (P-gp) substrate profile. These five drug properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The model performance was evaluated through 10-fold cross-validation and compared with the clinical Anticholinergic Cognitive Burden (ACB) scale and nonclinical Anticholinergic Toxicity Scores (ATS) scale, which is based primarily on muscarinic binding affinity., Results: In silico software (ADMET Predictor) used for screening drugs for their blood-brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean area under the curve for the unsupervised and ACB scale based on the five selected variables was 0.76 and 0.64, respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (49 of 88) agreed on the classification of less than half the drugs in the ATS scale (12 of 25)., Conclusions: Our findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. By contrast, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering other drug properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The clastogenic effects of imipramine on chromosomes have been investigated in leukocyte cultures from seven healthy blood donors (2 mlae and 5 female), repeat cultures being initiated at intervals of 6 to 12 weeks. At various times prior to harvesting nine different doses of imipramine were added in vitro, the three lowest concentrations being within the range of plasma levels reported in psychiatric patients reveiving the drug therapeutically. In addition, streptonigrin was used as a positive control. No increase in chromosome breaks was found at any concentration for any duration of exposure even in those cultures where high concentration and/or long duration of exposure significantly suppressed cell growth. Only cultures to which streptonigrin had been added showed a significant increase in chromosome breaks.

Chromosomes of peripheral leukocytes were examined in 28 addicts participating in a Veterans Administration-Special Action Office for Drug Abuse Prevention (SAODAP) cooperative study of methadyl acetate vs methadone. Blood samples for 72-hour leukocyte cultures were drawn after nearly 40 weeks of maintenance therapy while subjects were receiving active medication. For comparison, ten nondrug users were also studied. The frequency of chromosome damage was not greater in subjects maintained on methadyl acetate or methadone than in nondrug users.

The philothermal response, i.e., the tendency of polymorphonuclear leukocytes (PMNs) to migrate along a temperature gradient toward warmer temperatures, was evaluated in 11 patients with a clinical diagnosis of dementia of the Alzheimer type (DAT) and compared to 11 age and sex-matched mentally normal individuals. While the total number of migrating PMNs did not differ significantly between these two groups, there was a significant difference in the spatial distribution of the responding cell population. The numerical parameter, R, has been introduced to provide a quantitative measure of the distribution of populations characterized by differences in motile behavior. This R value was unusually high for 10 of the DAT patients but only one of the comparison individuals. No relation between R and duration of illness, age, or sex was detected. These preliminary findings, based on a small number of clinically diagnosed DAT patients, suggest that the philothermal response may represent a biological marker with diagnostic usefulness for at least one subgroup of DAT patients.

The cytogenetic effects of subacute oral administration of delta-9-tetrahydrocannabinol, cannabidiol, cannabinol, and placebo were assessed in 27 subjects in a prospective double-blind study. Both conventional chromosome aberration analysis and sister chromatid exchange were considered. A comparison group of 5 nondrug users was also investigated. The aneuploidy frequency decreased significantly following delta-9-tetrahydrocannabinol administration. By contrast, the frequencies of chromosome aberrations increased slightly for all three drug groups and decreased in the placebo and comparison groups although none of the predrug versus postdrug comparisons were statistically significant. No increase in the sister chromatid exchange frequency was found in any of the groups when predrug versus postdrug comparisons were made. The present study is the fourth short term prospective investigation failing to demonstrate a statistically significant increase in chromosome damage due to cannabinoid usage. However, it must be kept in mind that to date only gross chromosomal aberrations have been identified so that the more subtle chromosomal as well as molecular genetic damage has not been ruled out.

The role of microtubules in the philothermal response of polymorphonuclear leukocytes (PMNs) was examined using colchicine, a known microtubule disrupting agent. Colchicine inhibited PMN migration in a dose dependent fashion. Spatial distribution analysis of the responding cell population revealed a preferential inhibition of distal cell migration, a pattern similar to that found for PMNs obtained from patients with dementia of the Alzheimer type (DAT). The result is consistent with the known role of microtubules in directed cell migration and the hypothesized microtubular defect in DAT. Further investigations of microtubules may provide insight into the etiology and pathogenesis of DAT.

The effects of imipramine hydrochloride on cell proliferation were investigated in leukocyte cultures derived from normal volunteers. Nine different doses of imipramine were added in vitro at random for 4, 24, 48, and 68 hours, the three lowest concentrations being within the range of plasma levels reported in psychiatric patients receiving the drug therapeutically. Cell proliferations, as measured by mitotic index, was affected by both the concentration and the duration of drug exposure; the higher the dose and/or the longer the drug in culture, the lower the mitotic index. Imipramine concentrations corresponding to therapeutic plasma levels had no effect on mitotic index regardless of the length of exposure.

Sister chromatid exchange (SCE) analysis was carried out on ten patients with the clinical diagnosis of dementia of the Alzheimer type (DAT) and 11 cognitively-intact controls of a comparable age. There was no significant difference between patient and control groups in either the mean baseline SCE frequency or the SCE frequency following in vitro exposure to mitomycin-C. The present results, based on the largest sample (n = 21) published to date, fail to confirm the single positive report in the literature of an increased baseline SCE frequency in DAT patients compared to controls.

This first longitudinal study on aged subjects confirms previous cross-sectional observations of increasing aneuploidy with advancing age in women but not in men. In this study of 17 aged twins (mean age 89.7 years), 11 women and 6 men, spanning an interval of approximately 6 years between examinations, only women showed a significant increase in hypodiploidy (also hyperdiploidy and monosomy C). This increase in hypodiploidy was not due to a high frequency of chromosome loss in a few subjects but rather was exhibited by most of the subjects. While men showed a loss in G-group chromosomes during this 6-year interval, that loss was not statistically significant. These findings confirm for the first time by means of longitudinal follow-up that women and not men, even in the ninth decade of life, show a significant increase in hypodiploidy.

Sequential chromosome examinations of peripheral lymphocte cultures were carried out on 21 adult male volunteers who smoked natural blend marijuana cigarettes containing about 1%, 2%, or no delta9-THC. For a limited number of subjects, blood samples from a single venipuncture were cultured independently in two cytogenetic laboratories, and later the slides were exchaged for re-analysis. There were significant differences between laboratories in the absolute break frequencies recorded. These inter-laboratory differences were demonstrated for both techniques of cell culture and metaphase analysis. Neither laboratory found a statistically significant increase in break frequencies asssociated with marijuana smoking. The present study, therefore, failed to detect a measurable effect of marijuana smoking on chromosomal aberrations in subjects experienced in the use of the drug.

A newly developed technique for quantitating the locomotion of polymorphonuclear leukocyte (PMN) populations in temperature gradients has revealed that PMNs accumulate toward higher temperatures. The experiments yield measurements of the numbers of cells that adhere to glass and migrate from a cell suspension through a liquid/gel meniscus into a glass/agarose interface, and of their spatial distribution at subsequent time intervals. Cell locomotion was investigated as a function of the magnitude, sign, and temporal variation of the temperature gradient, the cell concentration in the source suspension, and the presence or absence of chemoattractant gradients. It was found (1) that a temperature gradient stimulates crossing of the meniscus toward higher temperatures, (2) that only a portion of the cells reverses direction of locomotion in response to reversal of the temperature gradient after the cells have traversed the meniscus, and (3) that the distribution of cells in the migration space depends on cell concentration, suggesting that the dynamics of PMN locomotion depend on cell-cell interactions.

Telocentrics for the beta arm of chromosome 4A and the long arm of 6B were used as cytological markers for the determination of chiasma frequency. In concomitant studies of recombination, terminal segments of rye and T. umbellulatum chromatin carrying Hp (Hairy peduncle) and Lr9 (Leaf-rust resistance), respectively, marked 4A and 6B. Two temperatures, 21 degrees and 32 degrees , were used for both the 4A and 6B experiments.-Only one chiasma was observed in each heteromorphic bivalent. Because there was a substantial reduction in pairing between diakinesis and metaphase I, all determinations of chiasma frequency were made at diakinesis. In the 21 degrees experiments, agreement was good between genetic recombination and cytological prediction on the basis of the partial chiasmatypy hypothesis that each chiasma represents a crossover. At 32 degrees both chiasma frequency and crossing over, but particularly the latter, were strongly reduced. The fewer crossovers than expected are explained in part by stickiness of chromosomes at the high temperature, sometimes resulting in adjacent chromosomes being wrongly scored as having a chiasma, and in part by premetaphase disjunction of some recombined bivalents and subsequent independent behavior of the two resulting univalents.-Male transmission of the 4A telocentric from the heteromorphic bivalent was unusually high: 51% at 21 degrees and 31% at 32 degrees .

The design of efficient helical pile structures is complicated because existing design standards lack clarity. In this work, we discuss a method for determining the ultimate bearing capacity of a pile using the screwing torque recorded during its sinking. The parameters of the corresponding correlation dependence and a method for determining the soil contact friction along the cylinder and tapered lateral surfaces of the screwed pile shaft were determined. [ABSTRACT FROM AUTHOR]

Despite being added to numerous products, little is known about cannabidiol. Drowsiness is a self‐reported side effect, which could impact cognitive functioning. To determine whether cannabidiol impacts cognition and psychomotor function, a volunteer sample of healthy, college students were recruited for this randomized, parallel‐group, double‐blind, feasibility trial from April–November 2021. Participants completed a baseline survey, the Stanford Sleepiness Scale, Visual Analog Mood Scale, Digit Symbol Substitution Test, Trail Making Test, Psychomotor Vigilance Test, and Simple Reaction Time Tests. Participants were then randomized and allocated to receive 300 mg cannabidiol oil (N = 21) or placebo (N = 19). After 120 min, participants retook the tests. Performance between groups was compared using Analysis of Covariance and multi‐level Negative Binomial regression. Participants averaged 21 ± 3 years of age, and 52% were female. Self‐reported anxiety did not change posttreatment. Performances on the Stanford Sleepiness Scale, Visual Analog Mood Scale, and Psychomotor Vigilance Test increased for both groups. After accounting for baseline scores, attention lapse duration significantly increased for those receiving cannabidiol compared to placebo in the Psychomotor Vigilance Test (76 vs. 66 ms; p = 0.02). Auditory reaction time improved in the cannabidiol group versus placebo for one sound emitted during the Simple Reaction Time Test (241 vs. 245 ms; p = 0.02), but the number of early responses increased from 0.3 to 0.8 for those receiving cannabidiol. While performance on most tests was similar between those receiving cannabidiol and placebo, cannabidiol might affect certain aspects of vigilance. More research and larger trials are needed. [ABSTRACT FROM AUTHOR]

Given a Banach space X, a w^*-compact subset of X^*, and 1

Cell migration plays an essential role in wound healing and inflammatory processes inside the human body. Peripheral blood neutrophils, a type of polymorphonuclear leukocyte (PMN), are the first cells to be activated during inflammation and subsequently migrate toward an injured tissue or infection site. This response is dependent on both biochemical signaling and the extracellular environment, one aspect of which includes increased temperature in the tissues surrounding the inflammation site. In our study, we analyzed temperature-dependent neutrophil migration using differentiated HL-60 cells. The migration speed of differentiated HL-60 cells was found to correlate positively with temperature from 30 to 42 °C, with higher temperatures inducing a concomitant increase in cell detachment. The migration persistence time of differentiated HL-60 cells was higher at lower temperatures (30–33 °C), while the migration persistence length stayed constant throughout the temperature range. Coupled with the increased speed observed at high temperatures, this suggests that neutrophils are primed to migrate more effectively at the elevated temperatures characteristic of inflammation. Temperature gradients exist on both cell and tissue scales. Taking this into consideration, we also investigated the ability of differentiated HL-60 cells to sense and react to the presence of temperature gradients, a process known as thermotaxis. Using a two-dimensional temperature gradient chamber with a range of 27–43 °C, we observed a migration bias parallel to the gradient, resulting in both positive and negative thermotaxis. To better mimic the extracellular matrix (ECM) environment in vivo, a three-dimensional collagen temperature gradient chamber was constructed, allowing observation of biased neutrophil-like differentiated HL-60 migration toward the heat source. [ABSTRACT FROM AUTHOR]

Previously, impulses were used to model abrupt changes in dynamic biological systems. This paper introduces a hybrid-index model that can characterize instantaneity of the impulsive behavior more effectively, compared with the existing impulsive Boolean network models. Using the hybrid-index model, we investigate the set stabilization of Boolean control networks with state-triggered impulses in the hybrid-domain and the time-domain. We establish necessary and sufficient conditions for set stabilizability in the hybrid and time domains, using the methods of k-domain and quotient mapping, respectively. Further, we obtain algorithms for constructing all hybrid-optimal and time-optimal set stabilizers by partitioning the state space into layers. The relationships between different set stabilizabilities are summarized. In addition, we have shared two examples to demonstrate the main results. [ABSTRACT FROM AUTHOR]

Background: The Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer's disease. Methods: The concentration of proteins in plasma covers a vast range of 12 orders of magnitude. Therefore, to search for medium to low abundant biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL. Results: We report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent on APOE ε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a preliminary validation study, on unique individual samples compared to the discovery cohort, using a targeted LC-MS/MS assay on a subset of discovered biomarkers. We found that targets that displayed a high degree of isoform specific changes in the 2D gels were not changed in the targeted MS assay which reports on the total level of the biomarker. Conclusions: This demonstrates that further development of mass spectrometry assays is needed to capture the isoform complexity that exists in theses biological samples. However, this study indicates that a peripheral protein signature has potential to aid in the characterization of AD. [ABSTRACT FROM AUTHOR]

Next point-of-interest (POI) recommendation, also known as a natural extension of general POI recommendation, is recently proposed to predict user's next destination and has attracted considerable research interest. It focuses on learning users’ sequential patterns of check-in behavior and on training personalized recommendation models using different types of contextual information. Unfortunately, most of the previous studies failed to incorporate the spatiotemporal contextual information, which plays a critical role in analyzing user check-in behavior, into recommending the next POI. In recent years, embedding learning and recurrent neural network (RNN) based approaches show promising performance for modeling sequential patterns of check-in behavior in next POI recommendation. However, not all of the historical check-in records contribute equally to the next-step check-in behavior. To provide better next POI recommendation performance, we first proposed a spatiotemporal long and short-term memory (ST-LSTM) network. By feeding the spatiotemporal contextual information into the LSTM network in each step, ST-LSTM can model the spatial and temporal information better. Also, we developed an attention-based spatiotemporal LSTM (ATST-LSTM) network for next POI recommendation. By using the attention mechanism, ATST-LSTM can focus on the relevant historical check-in records in a check-in sequence selectively using the spatiotemporal contextual information. Besides, we conducted a comprehensive performance evaluation using large-scale real-world datasets collected from two popular location-based social networks, namely Gowalla and Brightkite. Experimental results indicated that the proposed ATST-LSTM network outperformed two state-of-the-art next POI recommendation approaches regarding three commonly-used evaluation metrics. [ABSTRACT FROM AUTHOR]

Background: Although a few studies have investigated a possible association between maternal age and fetal sex chromosome aneuploidies (SCAs), most of these studies were limited to advanced maternal age (AMA) women and the results were conflicting. This study aimed to investigate the correlation between maternal age and common fetal SCAs (including 45,X, 47,XXY, 47,XXX and 47,XYY) in pregnant women of different ages that not only limited to AMA women. We retrospectively investigated a 8-year experience of prenatal diagnosis for fetal chromosome aberrations by second-trimester amniocentesis at a university teaching hospital in China. 20,409 amniotic fluid specimens collected at 19–22+6 gestational weeks were included in this study. The women were categorized into five age groups (≤ 23, 24–28, 29–33, 34–38, 39+ years) based on maternal age at the time of amniocentesis and entered as a categorical variable in all samples. The correlation between fetal SCAs and maternal age was determined using the logistic regression analysis. A chi-square test was performed to compare the incidence of fetal SCAs among age groups. Results: A total of 179 cases of fetal SCAs were detected, and the incidence was 8.77‰ (about 1/114). The incidence of fetal SCAs increased significantly with advancing maternal age (SE, 0.014; odds ratio, 1.044; P = 0.002). Specifically, the incidence of 45,X (SE, 0.037; odds ratio, 0.916; P = 0.017) and 47,XXY (SE, 0.024; odds ratio, 1.127; P = 0.000) had significant correlation with maternal age, while the incidence of 47,XXX and 47,XYY had no correlation with maternal age (P = 0.473; P = 0.272, respectively). The incidence of fetal SCAs was also significantly different among age groups (χ2 = 10.197, P = 0.037 < 0.05), from 5.81 per 1000 fetuses at the 24–28 years to 10.92 per 1000 at the 39+ years. Conclusions: Maternal age was ascertained to be a strong risk factor for fetal SCAs. [ABSTRACT FROM AUTHOR]

The Wills functional 𝒲 (K) of a convex body K , defined as the sum of its intrinsic volumes V i (K) , turns out to have many interesting applications and properties. In this paper, we make profit of the fact that it can be represented as the integral of a log-concave function, which, furthermore, is the Asplund product of other two log-concave functions, and obtain new properties of the Wills functional (indeed, we will work in a more general setting). Among others, we get upper bounds for 𝒲 (K) in terms of the volume of K , as well as Brunn–Minkowski and Rogers–Shephard-type inequalities for this functional. We also show that the cube of edge-length 2 maximizes 𝒲 (K) among all 0 -symmetric convex bodies in John position, and we reprove the well-known McMullen's inequality 𝒲 (K) ≤ e V 1 (K) using a different approach. [ABSTRACT FROM AUTHOR]

Background: The most common conservative treatment for Adolescent Idiopathic Scoliosis (AIS) is bracing. However, several papers questioned the effectiveness of bracing for curves between 40° and 50° Cobb: the effectiveness in preventing curve progression could be as low as 35%. Seriate casting is considered a standard approach in early onset scoliosis; however, in the setting of AIS, cast treatment is seldom utilized, with only few studies reporting on its effectiveness. Aim of the study: The main aim of the study is to determine whether a seriate casting with Risser casts associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. Furthermore, the secondary endpoints were: (1) is there a difference in effectiveness of casting between Thoracic (T) and Thoracolumbar/Lumbar (TL/L) curves? (2) Does the ‘in cast’ correction predicts the treatment outcome? (3) What is the effect on thoracic kyphosis of casting? Methods: This is a retrospective monocentric case–control study; through an Institutional Database search we identified all the patients treated at our institution between 1 January 2017 and 31 December 2020, with a diagnosis of AIS, Risser grade between 0 and 4 at the beginning of the treatment, at least one curve above 40° Cobb and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Standing full spine X-rays in AP and LL are obtained before and after the cast treatment; only AP standing full spine X-rays ‘in-cast’ are obtained for each cast made. Patients were stratified according to the curve behavior at the end of treatment (Risser 5): progression was defined as ≥6° increase in the curve magnitude or fusion needed; stabilization is defined as a change in curve by ±5°; and improvement was defined as ≥6° reduction in the curve. Results: For the final analysis, 55 compliant patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 27 (4 M, 23 F, mean age 13.6 ± 1.6) in the CG. Eight (14.5%) patients in the SG failed the conservative treatment while 14 (51.3%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1, 3–2.6, p = 0.001), and the Number Needed to Treat was 2,4. No significant difference was found between the T and TL/L curves concerning the ‘progressive’ endpoint (z-score 0.263, p = 0.79). The mean percentage of ‘in cast’ curve reduction was 40.1 ± 15.2%; no significant correlation was found between the percentage of correction and the outcome (Spearman Correlation Coefficient 0.18). Finally, no significant differences between baseline and end of FU TK were found (32° ± 16.2 vs. 29.6 ± 15.8, p = ns). Discussion: Seriate Risser casting for AIS with larger curves (>40° Cobb) is effective in reducing curve progression when compared with full time bracing alone in treatment compliant patients. The treatment is equally effective in controlling T and TL/L curves; furthermore, a slight but non-significant decrease in TK was observed in patients treated with casting. This type of treatment should be considered for AIS patients who present with large curves to potentially reduce the percentage of surgical cases. Short Abstract: The aim of the study is to determine whether seriate Risser casting associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. This is a retrospective monocentric case–control study; we identified all the patients treated at our institution with a diagnosis of AIS, Risser grade 0–4 at the beginning of the treatment, at least one curve above 40° Cobb (35° if treated with bracing alone) and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Fifty-five patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 30 (5 M, 25 F, mean age 13.9 ± 1.7) in the CG. Eight (14,5%) patients in the SG failed the conservative treatment while fifteen (50%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1.3–2.6, p = 0.001), and the Number Needed to Treat was 2,4. Seriate Risser casting for AIS with larger curves (>40°) is effective in reducing curve progression when compared with full time bracing alone. This type of treatment should be considered for AIS patients who present with large curves.

The Jin-Neelin model for the El Niño-Southern Oscillation (ENSO for short) is considered for which the authors establish existence and uniqueness of global solutions in time over an unbounded channel domain. The result is proved for initial data and forcing that are sufficiently small. The smallness conditions involve in particular key physical parameters of the model such as those that control the travel time of the equatorial waves and the strength of feedback due to vertical-shear currents and upwelling; central mechanisms in ENSO dynamics.From the mathematical view point, the system appears as the coupling of a linear shallow water system and a nonlinear heat equation. Because of the very different nature of the two components of the system, the authors find it convenient to prove the existence of solution by semi-discretization in time and utilization of a fractional step scheme. The main idea consists of handling the coupling between the oceanic and temperature components by dividing the time interval into small sub-intervals of length k and on each sub-interval to solve successively the oceanic component, using the temperature T calculated on the previous sub-interval, to then solve the sea-surface temperature (SST for short) equation on the current sub-interval. The passage to the limit as k tends to zero is ensured via a priori estimates derived under the aforementioned smallness conditions. [ABSTRACT FROM AUTHOR]

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A major factor associated with poor prognostic outcome after a first psychotic break is cannabis misuse, which is prevalent in schizophrenia and particularly common in individuals with recent-onset psychosis. Behavioral interventions aimed at reducing cannabis use have been unsuccessful in this population. Cannabidiol (CBD) is a phytocannabinoid found in cannabis, although at low concentrations in modern-day strains. CBD has a broad pharmacological profile, but contrary to Δ9-tetrahydrocannabinol (THC), CBD does not activate CB1 or CB2 receptors and has at most subtle subjective effects. Growing evidence indicates that CBD acts as an antipsychotic and anxiolytic, and several reports suggest neuroprotective effects. Moreover, CBD attenuates THC's detrimental effects, both acutely and chronically, including psychotogenic, anxiogenic, and deleterious cognitive effects. This suggests that CBD may improve the disease trajectory of individuals with early psychosis and comorbid cannabis misuse in particular--a population with currently poor prognostic outcome and no specialized effective intervention. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this work was to develop and evaluate a T1-weighted dynamic contrast enhanced (DCE) MRI methodology where tracer-kinetic (TK) parameter maps are directly estimated from undersampled (k,t)-space data. Theory and Methods The proposed reconstruction involves solving a nonlinear least squares optimization problem that includes explicit use of a full forward model to convert parameter maps to (k,t)-space, utilizing the Patlak TK model. The proposed scheme is compared against an indirect method that creates intermediate images by parallel imaging and compressed sensing before to TK modeling. Thirteen fully sampled brain tumor DCE-MRI scans with 5-second temporal resolution are retrospectively undersampled at rates R = 20, 40, 60, 80, and 100 for each dynamic frame. TK maps are quantitatively compared based on root mean-squared-error (rMSE) and Bland-Altman analysis. The approach is also applied to four prospectively R = 30 undersampled whole-brain DCE-MRI data sets. Results In the retrospective study, the proposed method performed statistically better than indirect method at R ≥ 80 for all 13 cases. This approach provided restoration of TK parameter values with less errors in tumor regions of interest, an improvement compared to a state-of-the-art indirect method. Applied prospectively, the proposed method provided whole-brain, high-resolution TK maps with good image quality. Conclusion Model-based direct estimation of TK maps from k,t-space DCE-MRI data is feasible and is compatible up to 100-fold undersampling. Magn Reson Med 78:1566-1578, 2017. © 2016 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Alcohol dehydrogenases (ADHs), which belong to the oxidoreductase superfamily, catalyze the interconversion between alcohols and aldehydes or ketones with high stereoselectivity under mild conditions. ADHs are widely employed as biocatalysts for the dynamic kinetic resolution of racemic substrates and for the preparation of enantiomerically pure chemicals. This review provides an overview of biotechnological applications for ADHs in the production of chiral pharmaceuticals and fine chemicals. [ABSTRACT FROM AUTHOR]

We investigate the problem of learning an evolution equation directly from some given data. This work develops a learning algorithm to identify the terms in the underlying partial differential equations and to approximate the coefficients of the terms only using data. The algorithm uses sparse optimization in order to perform feature selection and parameter estimation. The features are data driven in the sense that they are constructed using nonlinear algebraic equations on the spatial derivatives of the data. Several numerical experiments show the proposed method's robustness to data noise and size, its ability to capture the true features of the data, and its capability of performing additional analytics. Examples include shock equations, pattern formation, fluid flow and turbulence, and oscillatory convection. [ABSTRACT FROM AUTHOR]

Background: Ethyl (R)-4-chloro-3-hydroxybutyrate ((R)-CHBE) is a versatile chiral precursor for many pharmaceuticals. Although several biosynthesis strategies have been documented to convert ethyl 4-chloro-3-oxobutanoate (COBE) to (R)-CHBE, the catalytic efficiency and stereoselectivity are still too low to be scaled up for industrial applications. Due to the increasing demand of (R)-CHBE, it is essential to explore more robust biocatalyst capable of preparing (R)-CHBE efficiently. Results: A stereoselective carbonyl reductase toolbox was constructed and employed into the asymmetric reduction of COBE to (R)-CHBE. A robust enzyme designed as BgADH3 from Burkholderia gladioli CCTCC M 2012379 exhibited excellent activity and enantioselectivity, and was further characterized and investigated in the asymmetric synthesis of (R)-CHBE. An economical and satisfactory enzyme-coupled cofactor recycling system was created using recombinant Escherichia coli cells co-expressing BgADH3 and glucose dehydrogenase genes to regenerate NADPH in situ. In an aqueous/octanol biphasic system, as much as 1200 mmol COBE was completely converted by using substrate fed-batch strategy to afford (R)-CHBE with 99.9% ee at a space-time yield per gram of biomass of 4.47 mmol·L-1·h-1·g DCW-1. Conclusions: These data demonstrate the promising of BgADH3 in practical synthesis of (R)-CHBE as a valuable chiral synthon. This study allows for the further application of BgADH3 in the biosynthesis of chiral alcohols, and establishes a preparative scale process for producing (R)-CHBE with excellent enantiopurity. [ABSTRACT FROM AUTHOR]

306I.306II.307III.312IV.317V.318319References319 Summary: Meiosis is essential for the fertility of most eukaryotes and its structures and progression are conserved across kingdoms. Yet many of its core proteins show evidence of rapid or adaptive evolution. What drives the evolution of meiosis proteins? How can constrained meiotic processes be modified in response to challenges without compromising their essential functions? In surveying the literature, we found evidence of two especially potent challenges to meiotic chromosome segregation that probably necessitate adaptive evolutionary responses: whole‐genome duplication and abiotic environment, especially temperature. Evolutionary solutions to both kinds of challenge are likely to involve modification of homologous recombination and synapsis, probably via adjustments of core structural components important in meiosis I. Synthesizing these findings with broader patterns of meiosis gene evolution suggests that the structural components of meiosis coevolve as adaptive modules that may change in primary sequence and function while maintaining three‐dimensional structures and protein interactions. The often sharp divergence of these genes among species probably reflects periodic modification of entire multiprotein complexes driven by genomic or environmental changes. We suggest that the pressures that cause meiosis to evolve to maintain fertility may cause pleiotropic alterations of global crossover rates. We highlight several important areas for future research. [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of tumor suppressor genes may correspond to the abnormal cell development and tumorigenesis. Rbl2/p130, a member of retinoblastoma family of proteins, has growth suppressive properties. Numerous studies reported de-regulation of Rbl2/p130 in various types of cancer as a consequence of a number of genetic alterations. However, role of epigenetic mechanisms like DNA methylation in Rbl2/p130 expression remains elusive. Methods: In the current study, 76 breast cancer tumors along with normal tissues (n = 76), blood (n = 76) of respective individuals and control blood (n = 50) were analyzed. Rbl2/p130 expression was analyzed by quantitative real time PCR (syber green method). Promoter methylation status was studied through methylation specific PCR of bisulfite converted genomic DNA. Data was analyzed using various statistical tests. Results: We report significantly reduced Rbl2/p130 expression (P = 0.001) in tumors tissues as compared to control samples. Similarly, Rbl2/p130 expression varies with age and disease stages (P = 0.022), which suggest its involvement in tumor progression. Aberrant promoter methylation (Δmeth) was found in almost all the diseased samples and that was significantly different (P<0.001) with control samples. Similarly, methylation status varies significantly with tumor progression stages (P = 0.022). Hyper-methylation was observed at -1, +3, +15 and +75 of Rbl2/p130 promoter flanking around the TSS. Statistical analysis revealed that Rbl2/p130 expression negatively correlates to its promoter methylation (r = -0.412) in tumor tissues. Our results reflect an epigenetic regulation of Rbl2/p130 expression in breast cancer. This highlights the importance of Rbl2/p130 promoter methylation in breast cancer pathogenesis. [ABSTRACT FROM AUTHOR]

An essay on the of patent licensing and secondary markets in the U.S. is presented. Topics discussed include views of economist Zorina Khan on history of the patent licensing and secondary markets in the U.S., provisions in the American patent system for securing property rights, and the need of a patent licensing business model for the commercialization of patented innovation.

Remeron (Mirtazapine) is an antidepressant drug which exerts its action by blocking presynaptic α-2-adrenergic receptors and postsynaptic serotonin types 2 and 3 receptors. In thisin vitroanalysis, human peripheral blood lymphocytes was treated by remeron (10, 25, 40 and 55 μg/mL) for 24 hours and 48 hours periods, then it was attempted to study of genotoxic and cytotoxic effects of the substance on human peripheral blood lymphocytes by some tests such as sister chromatid exchange (SCE), chromosomal abnormalities (CA) and micronucleus (MN) tests. Also proliferating effect of the substance was investigated. Remeron didn’t significantly cause chromosomal abnormalities and sister chromatid exchange while caused micronucleus at 40 μg/mL concentration and 24 h periodic time and increased proliferation index of the both 24 and 48 hours treated cells was decreased in a concentration manner. Also, exposing to the remeron for 24 and 48 hours leaded to a decrease in mitotic index and nucleus division index in the cells by concentration dependent manner. These findings showed that remeron did not have significantly genotoxic effects on human peripheral blood lymphocytes while it showed cytotoxic effects on the cells, which is the first report on genotoxic and cytotoxic properties of remeron. [ABSTRACT FROM PUBLISHER]

We prove existence and uniqueness of stochastic representations for solutions to elliptic and parabolic boundary value and obstacle problems associated with a degenerate Markov diffusion process. In particular, our article focuses on the Heston stochastic volatility process, which is widely used as an asset price model in mathematical finance and a paradigm for a degenerate diffusion process where the degeneracy in the diffusion coefficient is proportional to the square root of the distance to the boundary of the half-plane. The generator of this process with killing, called the elliptic Heston operator, is a second-order, degenerate, elliptic partial differential operator whose coefficients have linear growth in the spatial variables and where the degeneracy in the operator symbol is proportional to the distance to the boundary of the half-plane. In mathematical finance, solutions to terminal/boundary value or obstacle problems for the parabolic Heston operator correspond to value functions for American-style options on the underlying asset. [ABSTRACT FROM AUTHOR]