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Activating leucine-rich repeat kinase 2 (LRRK2) mutations cause Parkinson's and phosphorylation of Rab10 by pathogenic LRRK2 blocks primary ciliogenesis in cultured cells. In the mouse brain, LRRK2 blockade of primary cilia is highly cell type specific: For example, cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2-pathway mutant mice. We show here that the cell type specificity of LRRK2-mediated cilia loss is also seen in human postmortem striatum from patients with LRRK2 pathway mutations and idiopathic Parkinson's. Single nucleus RNA sequencing shows that cilia loss in mouse cholinergic interneurons is accompanied by decreased glial-derived neurotrophic factor transcription, decreasing neuroprotection for dopamine neurons. Nevertheless, LRRK2 expression differences cannot explain the unique vulnerability of cholinergic neurons to LRRK2 kinase as much higher LRRK2 expression is seen in medium spiny neurons that have normal cilia. In parallel with decreased striatal dopaminergic neurite density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion protein expression; glial cells show significant loss of ferritin heavy chain. These data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson's. [ABSTRACT FROM AUTHOR]

This study presents experimental and numerical studies of the initiation and propagation of interface debonding between the substrate and thin-bonded cement-based overlay under fatigue testing. The overlay material is mortar incorporating amorphous metallic fibres (30 kg/m 3 ) and/or rubber aggregates (30%), while the substrate is a plain mortar. Uniaxial tensile tests were carried out on overlay materials and substrate-overlay interface to obtain a residual normal stress-crack opening relationship (σ-w law) and residual normal stress and substrate-overlay interface debonding relation respectively. Three-point bending fatigue tests were carried out on the composite beam to analyse the structural behaviour of repaired beam. The propagation of debonding along the substrate-overlay interface was monitored by using the Digital 3D Image Correlation (DIC) technique. Three-point bending fatigue test was modelled by finite element method (FEM) using CAST3M, developed by French Atomic Energy Commission. Direct tension test results show reduction in tensile strength and improvement in strain capacity (1.5 times of control mortar) for rubberised mortars. For fibre-reinforced mortars, post-peak residual tensile strength is significantly enhanced. Rubberised fibre-reinforced mortars show positive synergetic effects both in the improvement of residual post-peak strength and strain capacity (3.5 times than control mortar). Results show that the rubberised fibre-reinforced thin-bonded cement-based overlay proved to be very effective in restraining crack opening, by transferring stresses through the crack, and enhancing the fatigue resistance of repair system, by limiting interface debonding propagation upto 50%. Experimental results of composite beams are in good agreement with modelling results. [ABSTRACT FROM AUTHOR]

The subsurface structure analysis of the Southern North Sea through the interpretation of 2D seismic data set (SNSTI-NL-87 and SNST-NL-83) is carried out. The subsurface structural geometry of the research area is presented by several interpreted seismic lines, time structure maps, and isopach maps. The rocks presented beneath the Zechstein (Permian) are considered as the basement for the current study. The area was tectonically active in Permian, as the basement was faulted at several locations before the deposition of salt in Late Permian. The dominant fault trends of the area are NW‒SE and NE‒SW. Two main periods are believed to control development of structural elements, i.e. in Late Jurassic‒Early Cretaceous (extension) and Late Cretaceous‒Early Tertiary (inversion). Thick Triassic and Jurassic sediments are observed in the graben areas and due to possible erosion, these sediments are thin or not present on the structural highs. The compressional period and observed thickness variation of sediments are due to tectonic inversion and salt movement in Late Cretaceous. [ABSTRACT FROM AUTHOR]

Activating LRRK2 mutations cause Parkinson's disease, and pathogenic LRRK2 kinase interferes with ciliogenesis. Previously, we showed that cholinergic interneurons of the dorsal striatum lose their cilia in R1441C LRRK2 mutant mice (Dhekne et al., 2018). Here, we show that cilia loss is seen as early as 10 weeks of age in these mice and also in two other mouse strains carrying the most common human G2019S LRRK2 mutation. Loss of the PPM1H phosphatase that is specific for LRRK2-phosphorylated Rab GTPases yields the same cilia loss phenotype seen in mice expressing pathogenic LRRK2 kinase, strongly supporting a connection between Rab GTPase phosphorylation and cilia loss. Moreover, astrocytes throughout the striatum show a ciliation defect in all LRRK2 and PPM1H mutant models examined. Hedgehog signaling requires cilia, and loss of cilia in LRRK2 mutant rodents correlates with dysregulation of Hedgehog signaling as monitored by in situ hybridization of Gli1 and Gdnf transcripts. Dopaminergic neurons of the substantia nigra secrete a Hedgehog signal that is sensed in the striatum to trigger neuroprotection; our data support a model in which LRRK2 and PPM1H mutant mice show altered responses to critical Hedgehog signals in the nigrostriatal pathway. [ABSTRACT FROM AUTHOR]

A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72+ (C9+) ALS patients to derive neuronal progenitor cells. We demonstrated that C9+ and neurotypic neuronal progenitor cells differentiate into neurons. The C9+ neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9+ neurons. Moreover, C9+ neurons expressed high levels of mRNA for CXCL8, a chemokine overexpressed by senescent cells, while media from C9+ neurons contained significant levels of CXCL8, CXCL1, IL13, IP10, CX3CL1, and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia. • Neurotypic and C9+ NPCs can be differentiated in two- and three-dimensional models. • C9+ NPCs spontaneously expressed cyclin D1 protein in three-dimensional culture. • Expression profiling showed increases in genes associated with cellular senescence. • C9+ neurons expressed factors of the senescence-associated secretory phenotype. [ABSTRACT FROM AUTHOR]

With the purpose of investigating a linear elastic solid containing a dilute distribution of cylindrical and prismatic holes parallel to the torsion axis, the full-field solution for an infinite elastic plane containing a single void and subject to torsion is derived. The obtained solution is exploited to derive the analytic expressions for the stress concentration factor related to the presence of an elliptical hole, the stress intensity factor for hypocycloidal holes and star-shaped cracks and the notch stress intensity factor for star-shaped polygons. Special sets of the void location are obtained for which peculiar mechanical behaviours are displayed, such as stress annihilation at some points along the boundary of elliptical voids and stress singularity removal at the cusps or points of hypocycloidal or isotoxal star-shaped polygonal voids. By means of finite-element simulations, it is finally shown that the presented closed-form expressions for the stress intensification provide reliable predictions, even for finite-domain realizations; in particular, the infinite-plane solution remains highly accurate when the the smooth and non-smooth external boundaries are larger than twice and five times the void dimension, respectively. Under these geometrical conditions, the derived analytical expressions represent a valid 'guide tool' in mechanical design. [ABSTRACT FROM AUTHOR]

α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson’s disease, Lewy body dementia, and Alzheimer’s disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory. It also increased extracellular amyloid-β oligomers (AβOs), αSyn oligomers, exacerbated tau conformational and phosphorylation variants associated with AD, and enhanced neuronal cell cycle re-entry (CCR), a frequent prelude to neuron death in AD. Conversely, ablation of the SNCA gene encoding for αSyn in APP mice improved memory retention in spite of increased plaque burden. Reminiscent of the effect of MAPT ablation in APP mice, SNCA deletion prevented premature mortality. Moreover, the absence of αSyn decreased extracellular AβOs, ameliorated CCR, and rescued postsynaptic marker deficits. In summary, this complementary, bidirectional genetic approach implicates αSyn as an essential mediator of key phenotypes in AD and offers new functional insight into αSyn pathophysiology. [ABSTRACT FROM AUTHOR]

Highlights • An analytic solution with the stress concentration factor is derived for an infinite plane. • The analytical solution is shown to work as an accurate approximation for finite planes. • The numerical evaluation of stress intensity factors is discussed. • Thumb rules and tables for the purposes of engineering design are provided. • A three-dimensional model validation is presented via the finite element method. Abstract An elliptical inclusion (covering both void and rigid inclusions) embedded in an infinite and finite elastic plane subject to uniform or nonuniform (m-th order polynomial) anti-plane loading conditions is analyzed. An analytical solution in terms of the stress field for an infinite plane is developed through the method of analytic function and conformal mapping. Closed-form complex potentials and analytical expressions for Stress Concentration Factors (SCFs) are obtained. The results show that (i.) the SCF value decreases with an increasing loading order, so that the influence of the non-uniformity of the anti-plane loads on the SCF is revealed to be beneficial from the failure point of view; (ii.) decrease in the SCF value for an infinite plane is monotonic, which does not hold true for a finite plane. The results for an infinite plane are confirmed and extended for finite planes by exploiting the well-known heat–stress analogy and the finite element method. It is worth mentioning that the comparison between the analytical solution for an infinite plane and the numerical solution for finite plane is provided, showing that the analytical solution of an infinite plane can be used as an accurate approximation to the case of a finite plane. Moreover, the proposed heat–stress analogy can be exploited to study the crack–inclusion interaction or multiply connected bodies. The computational efficiency of the proposed methodology makes it an attractive analysis tool for anti-plane problems with respect to the full scale three-dimensional analysis. [ABSTRACT FROM AUTHOR]

Analytical displacement and stress fields with stress concentration factors (SCFs) are derived for linearly elastic annular regions subject to inhomogeneous boundary conditions: an infinite class of the mth order polynomial antiplane tractions or displacements. The solution of the Laplace equation governing the out-of-plane problem covers both rigid and void circular inclusions forming the core of the annulus. The results show first that the SCF and the loading order are inversely proportional. In particular, the SCF approaches value 2 when either the outer boundary of the annulus tends to infinity or the order of the polynomial loading increases. Second, the number of peculiar points on the inner contour having null stress increases with the increasing loading order. The analytical solution is confirmed and extended to noncircular enclosures via finite element analysis by exploiting the heat-stress analogy. The results show that the closed-form solution for a circular annulus can be used as an accurate approximation for noncircular enclosures. Altogether, the results shown can be exploited for analyzing complex loading conditions and/or multiple rigid or void inclusions for enhancing the design of hollow and reinforced composites materials. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the photochemistry of Luffa cylindrica (L.) Roem in fungal biocontrol interacting treatments. Healthy plants were infected with Pythium aphanidermatum before the biocontrol application. Biocontrol agents were selected in preliminary Petri-plate experiment evaluation against causative agent P. aphanidermatum. Photosynthetic performance traits were studied. We found that P. aphanidermatum infection caused significant reduction in photosynthetic performance, pigments, and in maximum quantum yield of primary photochemistry, photochemical quenching, and electron transport rate with increase in nonphotochemical quenching as compared with non-infected control. However, application of biocontrol agents substantially improved maximum quantum yield of PSII, performance index, and total content of photosynthetic pigments in infected plants. The fluorescence intensity was used for quantifying the antagonist effect of biocontrol agents on infected plant leaves. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has affected people, especially in developing countries. There are problems and shocks from its rapid proliferation and fears of further growth. The situation demands that Pakistan's government deeply engage in planning, consultations, and fixing constitutional breaches to develop a comprehensive national health policy. The issues of a compromised healthcare system need to be urgently addressed. The best way to save lives is to have quality protective gear. It is also crucial to create international health partnerships to save lives. The policy should also focus on the growing problem of fake news. Every effort should include creating investment opportunities in digital platforms and managing external economic domains to achieve growth. Policymakers must also ensure that small businesses stay operating while health emergencies arise. This study examines the entire range of rescue operations, management, and planning but concentrates on specific factors that affect the Pakistani government's ability to enact far-reaching policies for the people's benefit. Considering how pervasive the impacts of the COVID-19 epidemic are, studying what could happen next is inherently more probabilistic. Related perspectives and concerned subjects may be explored in a study of the present outbreak and the policies and efforts to end it. This study uses an analytical approach to take an insight into the health governance of Pakistan and the challenges it faces. [ABSTRACT FROM AUTHOR]

Gwadar is becoming a key factor in bolstering Pakistan's ailing economy. It is astonishing that Gwadar, a small fishing village in Pakistan, is swiftly becoming a smart deep-sea port city. Considering the significance of the region, the Pakistani government has designated Gwadar as a duty-free port and a free economic zone. This has increased its commercial significance and accelerated its rate of development to an incredible degree. When the city's development projects, recreational programs, and special economic zonescomplete, it will be comparable to Singapore, Hong Kong, and Dubai due to its advantageous strategic location. The western port city of Gwadar has already attracted the attention of the global martitime communities. It is highly likely that the port city of Gwadar will be economically more successful than anyone can evaluate. [ABSTRACT FROM AUTHOR]

Karachi harbor has an immense operational infrastructure of Pakistan National Shipping Corporation (PNSC), Pakistan Navy (PN), and Pakistan Maritime Security Agency (PMSA). It is significant for the readiness of PN and PMSA for peace and wartime operations. Although the Government of Pakistan has declared Karachi Port Complex a National Vulnerable Area, Karachi's coast receives massive pollutants from various land and sea sources. The primary sources include liquid discharge from industry and solid effluents of the municipality. The non-availability of disposal facilities and the absence of effluent treatment plants add to the misery. Toxic liquids and solid pollutants remain in the harbor for extended intervals. This pollution threatens the marine environment and ocean life and degrades water quality. These pollutants also affect the life of assets and infrastructures, including incoming and parked ships, which deteriorate fast. This paper includes the sources of pollution and the current state of Karachi h rbor. Also, possible outcomes of the growing pollution fall into the domain of this study. [ABSTRACT FROM AUTHOR]

An infinite class of nonuniform antiplane shear fields is considered for a linear elastic isotropic space and (non-intersecting) isotoxal star-shaped polygonal voids and rigid inclusions perturbing these fields are solved. Through the use of the complex potential technique together with the generalized binomial and the multinomial theorems, full-field closed-form solutions are obtained in the conformal plane. The particular (and important) cases of star-shaped cracks and rigid-line inclusions (stiffeners) are also derived. Except for special cases (addressed in Part II), the obtained solutions show singularities at the inclusion corners and at the crack and stiffener ends, where the stress blows-up to infinity, and is therefore detrimental to strength. It is for this reason that the closed-form determination of the stress field near a sharp inclusion or void is crucial for the design of ultra-resistant composites. [ABSTRACT FROM AUTHOR]

Notch stress intensity factors and stress intensity factors are obtained analytically for isotoxal star-shaped polygonal voids and rigid inclusions (and also for the corresponding limit cases of star-shaped cracks and stiffeners), when loaded through remote inhomogeneous (self-equilibrated, polynomial) antiplane shear stress in an infinite linear elastic matrix. Usually these solutions show stress singularities at the inclusion corners. It is shown that an infinite set of geometries and loading conditions exist for which not only the singularity is absent, but the stress vanishes (‘annihilates’) at the corners. Thus the material, which even without the inclusion corners would have a finite stress, remains unstressed at these points in spite of the applied remote load. Moreover, similar conditions are determined in which a star-shaped crack or stiffener leaves the ambient stress completely unperturbed, thus reaching a condition of ‘quasi-static invisibility’. Stress annihilation and invisibility define optimal loading modes for the overall strength of a composite and are useful for designing ultra-resistant materials. [ABSTRACT FROM AUTHOR]

A numerical study is carried out for two dimensional steady incompressible mixed convective flow of electrically conductive micro nanofluid in a stretchable channel. The flow is generated due to the stretching walls of the channel immersed in a porous medium. The magnetic field is applied perpendicular to the walls. The impact of radiation, viscous dissipation, thermophoretic and Brownian motion of nanoparticles appear in the energy equation. A numerical technique based on Runge-Kutta-Fehlberg fourth-fifth order (RFK45) method is used to express the solutions of velocity, microrotation, temperature and concentration fields. The dimensionless physical parameters are discussed both in tabular and graphical forms. The results are also found in a good agreement with previously published literature work. [ABSTRACT FROM AUTHOR]

Aim: To investigate factors influencing complementary and alternative medicines (CAM) use among patients on warfarin. Method: Cross-sectional study of randomly selected patients at a hospital-based anticoagulation clinic in Malaysia. A 38- item validated data collection form was used to interview patients and investigate the reasons, perceived efficacy and adverse drug events experienced. Data were also collected on potential drug interactions and the international normalised ratio (INR). Results: Of the 138 randomly selected patients, 76 (55%) reported using CAM - 46 (61%) used biologically based practices such as herbal products, vitamins and supplements. Monthly household income (p = 0.05, rs = 0.13) and family history of CAM use (p = 0.001, rs = 0.32) were significantly associated and positively correlated with CAM use. 19 patients reported adverse events with warfarin use while none reported adverse events with CAM use. 19 and 58 patients, respectively, were identified as being at risk of potential interactions between warfarin-CAM and warfarin-conventional medicines. No significant difference in the mean INR was found between CAM and non-CAM users. Conclusion: A large number of patients attending the anticoagulation clinic reported using CAM. Socioeconomic factors such as monthly household income, education level and family history of CAM use were significantly related with CAM use. Routine medication interviews should include questions about concomitant CAM use. [ABSTRACT FROM AUTHOR]

Abstract: Alkylidenation of lactones with functionalised titanium carbenoid reagents (Schrock carbenes) followed by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of [4.4], [4.5] and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxaspiro[5.5]undecanes, respectively, sometimes termed 5,5-, 5,6- and 6,6-spiroketals). The titanium carbenoids are easily generated from readily available thioacetals. [Copyright &y& Elsevier]

Abstract: High throughput screening led to the discovery of a novel series of 1,3-diaminopropan-2-ol sulfonamides as selective GlyT-1 inhibitors. Structure–activity relationships of this novel series and optimisation of the initial hit that led to the identification of (2), a potent and selective GlyT-1 inhibitor, are also presented. [Copyright &y& Elsevier]

In the northern area of New Jersey along the Hackensack and Hudson Rivers exists a vast marsh known locally as the “Meadowlands.” The geologic history and land formations of these areas provide subsurface conditions that have lead to difficulties in design and construction, resulting in a number of problems with structures. In the past, these less suitable areas may not have been considered because of their poor subsurface characteristics, but the scarcity of prime development sites has made the use of the Meadowland areas desirable. Problems, such as excessive settlement, low bearing capacity, high water level, frost heave, and corrosion potential are associated with construction in these areas. This paper presents the findings of a literature review regarding foundation design and construction in marshy areas and provides examples of problems associated with structures in the Meadowlands area of Kearny, N.J. It concludes with recommendations for dealing with these issues in future construction. [ABSTRACT FROM AUTHOR]

Presents information on the infrared and Raman spectra relating to the a single resin bead for the analysis of solid-phase reactions, referencing to the use of the encoding combinatorial libraries. Identification of six lysine compounds and the unfunctionalized lysine template; Use of the Fourier transform infrared (FTIR) and Raman microspectrometry to analyze randomly select beads of unknown identity; Separation of the polymer-bound compounds.

1/16 patients (6.2%) had PE with YA score 0 and d-dimer >1000, 18/121 (14.9%) had PE with unlikely SWS and 34/166 (20.4%) had PE with unlikely OWS. 79/180 patients (43.8%) had PE with YA score >=1 and d-dimer >500, 84/232 (36.2%) had PE with likely SWS and 68/187 (36.3%) had PE with likely OWS. [Extracted from the article]

Early Failure of the Biotronik Linox Introduction The Linox and Durata implantable cardioverter defibrillator (ICD) leads were introduced to British Columbia (BC) in 2008. We determined their performance and the potential risk factors for lead failure in a large population-based patient registry. Methods and Results We used the BC Cardiac Registry, a mandatory Governmental database of ICD implants, to identify all recipients of Linox and Durata leads in BC between October 2008 and April 2012, and those subsequently undergoing reoperation. Lead failure was defined as recurrent nonphysiological high-rate sensing unrelated to external electromagnetic interference or T-wave oversensing; a sudden rise in impedance unrelated to perforation or lead dislodgement; or abnormal lead parameters with definite evidence of lead fracture or insulation failure. We determined the estimated cumulative lead survival by the Kaplan-Meier method, and the risk factors for lead failure in a proportional hazards model. Over a median of 39 (27-50) months, the Linox failed more frequently than the Durata (16/477 [3.4%] vs. 4/838 [0.4%]; P < 0.001), and had a significantly lower estimated cumulative survival (91.6 [80.6-96.5]% vs. 99.4 [98.4-99.8]% at 5 years; P < 0.0001). Linox failure was characterized by high-rate nonphysiological sensing (11 cases), and/or a sudden impedance rise (7 cases). Insulation failure was clearly confirmed in 6 cases of Linox failure. Female sex was a significant risk factor for Linox failure (adjusted HR = 2.1[1.3-3.4]; P = 0.004). Conclusions This multicenter registry indicates a high rate of Linox lead failure, particularly in female patients. Ongoing surveillance of the Linox ICD lead performance is recommended. [ABSTRACT FROM AUTHOR]

Nine organic substrates viz., rice grains, sorghum grains, wheat grains, millet grains, wheat straw, rice husk, cow dung, sawdust, and poultry manure were used for mass multiplication of Trichoderma harzianum. Of these, sorghum grains followed by millet grains were the best substrates. The poultry manure appeared to be the most unsuitable substrate, whereas rice grains, wheat grains, wheat straw, and rice husk performed moderately well. Sucrose was the best carbon source and supported the highest colony growth of T. harzianum on Czapek's Agar plates. Similarly, ammonium nitrate at 3,000 ppm appeared to be the most suitable nitrogen source and produced the highest colony growth as well as abundant conidia. A combined use of sucrose at 30,000 ppm as carbon source, and ammonium nitrate at 3,000 ppm as nitrogen source significantly enhanced the mycelial growth and conidial production by T. harzianum in wheat straw, rice husk, and millet grains, whereas, in sorghum grains and rice grains, the addition of carbon and nitrogen sources showed negative effect on sporulation of T. harzianum. Studies on shelf life of the inocula multiplied on various substrates showed that the populations of T. harzianum on all the substrates achieved the peak at 60-75 days incubation period and declined gradually thereafter. However, even after 330 days, the populations were greater than the population at 0-day. At 345-360 days interval, population was found to be less than the initial population at 0-day. [ABSTRACT FROM AUTHOR]

Highlights: [•] Photoelasticity is employed to investigate the stress state near stiff inclusions. [•] Magnification of stress near a corner is found up to 5.3. [•] Rigid inclusion model is experimentally validated. [ABSTRACT FROM AUTHOR]

Abstract: A titanium benzylidene complex bearing a boronate group converted resin-bound esters into enol ethers. Suzuki cross-coupling with aryl iodides followed by cleavage with acid completed the solid-phase synthesis of 2,5-disubstituted N-Boc-indoles. Also reported is the use of tert-butyllithium and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane to convert an aryl bromide into an arylboronate in the presence of a dithiane, with simultaneous reduction of an aryl azide to an amine. [Copyright &y& Elsevier]

Catecholamine neurons of the locus coeruleus (LC) in the dorsal pontine tegmentum innervate the entire neuroaxis, with signaling actions implicated in the regulation of attention, arousal, sleep–wake cycle, learning, memory, anxiety, pain, mood, and brain metabolism. The co‐release of norepinephrine (NE) and dopamine (DA) from LC terminals in the hippocampus plays a role in all stages of hippocampal‐memory processing. This catecholaminergic regulation modulates the encoding, consolidation, retrieval, and reversal of hippocampus‐based memory. LC neurons in awake animals have two distinct firing modes: tonic firing (explorative) and phasic firing (exploitative). These two firing modes exert different modulatory effects on post‐synaptic dendritic spines. In the hippocampus, the firing modes regulate long‐term potentiation (LTP) and long‐term depression, which differentially regulate the mRNA expression and transcription of plasticity‐related proteins (PRPs). These proteins aid in structural alterations of dendritic spines, that is, structural long‐term potentiation (sLTP), via expansion and structural long‐term depression (sLTD) via contraction of post‐synaptic dendritic spines. Given the LC's role in all phases of memory processing, the degeneration of 50% of the LC neuron population occurring in Alzheimer's disease (AD) is a clinically relevant aspect of disease pathology. The loss of catecholaminergic regulation contributes to dysfunction in memory processes along with impaired functions associated with attention and task completion. The multifaceted role of the LC in memory and general task performance and the close correlation of LC degeneration with neurodegenerative disease progression together implicate it as a target for new clinical assessment tools. [ABSTRACT FROM AUTHOR]

Abstract Background Reference measurement procedures (RMP) have rigorous accuracy specifications. For total 25-hydroxyvitamin D, 25(OH)D, bias ≤1.7% and CV ≤5% are recommended. These quality specifications are impractical for minor analytes, such as 25(OH)D 2. Furthermore, documentation on RMP quality performance specifications for the individual 25(OH)D metabolites and their daily application are missing. Methods To assess accuracy, we used zeta-scores. Daily, 5–10 specimens (duplicate) and 3 reference materials (singleton or duplicate) were measured for 25(OH)D 3 and 25(OH)D 2 using JCTLM-accepted LC-MS/MS RMPs. Protocols were repeated on 3–4 occasions to generate campaign results. We used separate zeta-score acceptability criteria for daily (≤|2|) and campaign (≤|1|) evaluations. Allowable imprecision was determined experimentally. Results Across 7 campaigns, unacceptable daily zeta-scores required repeating 2 runs for 25(OH)D 3 and 5 runs for 25(OH)D 2. Hence, the zeta-scores of acceptable reference material results indicated high accuracy. The allowable imprecision for the RMPs was ≤5% (daily) and ≤ 3% (campaign) for 25(OH)D 3 and ≤ 7% (daily) and ≤ 4% (campaign) for 25(OH)D 2 , respectively. Conclusions Using zeta-scores and experimentally derived imprecision, we developed a straightforward approach to assess the acceptability of individual 25(OH)D reference measurements, providing also much-needed practical accuracy specifications for 25(OH)D 2. Highlights • RM & candidate RM analyzed together in 3 independent measurement series. • Procedures to accept daily & campaign reference measurements detailed • Zeta-score used for accuracy of reference measurements for each 25(OH)D metabolite. • First-time separate accuracy criteria for reference 25(OH)D 3 & 25(OH)D 2 measurements [ABSTRACT FROM AUTHOR]

Mal de Meleda ( MDM) is a palmoplantar keratoderma ( PPK), characterized by hyperkeratosis of the palms and soles, and keratotic skin lesions. Patients with MDM can develop perioral erythema, keratotic and lichenoid plaques over the joints (including the elbows and knees), nail abnormalities, joint contractures and stiffness, brachydactyly, sclerodactyly, pseudoainhum, and malodorous maceration. MDM is associated with mutations in the SLURP1 gene. We report a consanguineous family in which MDM was inherited in an autosomal recessive manner. Genotyping using microsatellite markers established linkage in the family to the SLURP1 gene, which has been mapped previously to chromosome 8q24.3. Sequence analysis revealed a homozygous missense mutation (c.2T>C, p.Met1Thr) in affected family members. Molecular docking studies using a ZDOCK server predicted disruption of binding of the mutant variant to its target α7-nAChR. This study further supports the previously reported findings that homozygous mutations in the SLURP1 gene cause MDM. [ABSTRACT FROM AUTHOR]

The present paper examines the hydromagnetic three-dimensional flow induced by a stretched surface. An incompressible material saturates the porous medium. Velocity and thermal slip boundary conditions are considered. Suitable transformations are used to obtain the nonlinear ordinary differential equations. Series solutions of the resulting systems are constructed. The effects of various pertinent parameters on the axial velocity and temperature distributions are analyzed graphically. The skin friction and the Nusselt number are computed numerically and graphically. [ABSTRACT FROM AUTHOR]

The article discusses a study on a Pakistani family with individuals affected of segregating fingernail dysplasia in an autosomal recessive manner. It mentions affected family members displayed a severe form of onychodystrophy with mild erythema and swelling of the proximal and lateral nail folds. it also mentions differences in phenotype severity among affected individuals suggest the possible role of factors such as heterogeneity in genetic background, modifier genes or environmental factors.

The genus Phytopythium (Peronosporales) has been described, but a complete circumscription has not yet been presented. In the present paper we provide molecular-based evidence that members of Pythium clade K as described by Lévesque & de Cock (2004) belong to Phytopythium. Maximum likelihood and Bayesian phylogenetic analysis of the nuclear ribosomal DNA (LSU and SSU) and mitochondrial DNA cytochrome oxidase subunit 1 (COI) as well as statistical analyses of pairwise distances strongly support the status of Phytopythium as a separate phylogenetic entity. Phytopythium is morphologically intermediate between the genera Phytophthora and Pythium. It is unique in having papillate, internally proliferating sporangia and cylindrical or lobate antheridia. The formal transfer of clade K species to Phytopythium and a comparison with morphologically similar species of the genera Pythium and Phytophthora is presented. A new species is described, Phytopythium mirpurense. [ABSTRACT FROM AUTHOR]

The relationships between salinity and mineral nutrition are extremely complex and may change depending on many factors in soil-plant system. We investigated the contribution of silicon (Si at 50 mg kg−1soil) and potassium (K at 40 and 60 mg K2O kg−1soil) to improve salt tolerance in sunflower grown with 100 mM sodium chloride (NaCl). The experimental design was factorial based on a completely randomized design with five replications. Added NaCl increased sodium ion (Na+) accumulation by 966 percent in shoots and 1200 percent in roots but reduced shoot potassium ion (K+) concentration by 49 percent, root K+51 percent, and shoot K+/Na+ratio 95 percent. However, Si and K application effectively reduced Na+accumulation and increased K+concentration and K+:Na+ratio, with a significant improvement in plant growth and yield. Among all treatments, greater alleviative effects of Si and K were observed for 50 mg Si + 60 mg K2O kg−1soil, which decreased shoot Na+concentration by 67 percent, root Na+18 percent, and shoot Na+/root Na+ratio 60 percent and increased shoot K+by 198 percent, shoot K+/Na+ratio 812 percent, membrane stability index (MSI) 35 percent, relative water content (RWC) 26 percent, and seed weight head−186 percent compared to salt-stressed plants without supplemental Si and K. Most of the plant growth parameters were negatively correlated with Na+accumulation but positively correlated with K+and K+/Na+ratio. This study suggests that Si and K mediated reduction in Na+accumulation, and increase in K+concentration, K+/Na+ratio, RWC, and MSI are the main factors contributing to improved adaptation capability of sunflower to NaCl stress. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to examine the safety and efficacy of laser-assisted lead extraction and the indications, outcomes, and risk factors in a large series of consecutive patients. Background: The need for lead extraction has been increasing in direct relationship to the increased numbers of cardiovascular implantable electronic devices. Methods: Consecutive patients undergoing transvenous laser-assisted lead extraction at 13 centers were included. Results: Between January 2004 and December 2007, 1,449 consecutive patients underwent laser-assisted lead extraction of 2,405 leads (20 to 270 procedures/site). Median implantation duration was 82.1 months (0.4 to 356.8 months). Leads were completely removed 96.5% of the time, with a 97.7% clinical success rate whereby clinical goals associated with the indication for lead removal were achieved. Failure to achieve clinical success was associated with body mass index <25 kg/m2 and low extraction volume centers. Procedural failure was higher in leads implanted for >10 years and when performed in low volume centers. Major adverse events in 20 patients were directly related to the procedure (1.4%) including 4 deaths (0.28%). Major adverse effects were associated with patients with a body mass index <25 kg/m2. Overall all-cause in-hospital mortality was 1.86%; 4.3% when associated with endocarditis, 7.9% when associated with endocarditis and diabetes, and 12.4% when associated with endocarditis and creatinine ≥2.0. Indicators of all-cause in-hospital mortality were pocket infections, device-related endocarditis, diabetes, and creatinine ≥2.0. Conclusions: Lead extraction employing laser sheaths is highly successful with a low procedural complication rate. Total mortality is substantially increased with pocket infections or device-related endocarditis, particularly in the setting of diabetes, renal insufficiency, or body mass index <25 kg/m2. Centers with smaller case volumes tended to have a lower rate of successful extraction. [Copyright &y& Elsevier]

The novel 7-transmembrane receptor MrgX1 is located predominantly in the dorsal root ganglion and has consequently been implicated in the perception of pain. Here we describe the discovery and optimization of a small molecule agonist and initial docking studies of this ligand into the receptor in order to provide a suitable lead and tool compound for the elucidation of the physiological function of the receptor. [ABSTRACT FROM AUTHOR]

Abstract: Solid phase synthesis has been used to carry out intramolecular aromatic homolytic substitution with benzoimidazole precursors. The protocol attaches the radical precursors to the resins via the radical leaving groups (in the aromatic homolytic substitution). When the radical reactions are complete, the leaving group, unaltered starting material and reduced uncylised products remain attached to the resin, which facilitates easy separation of the cyclised products. Novel use of focussed microwave irradiation in solid phase radical reactions drastically shortens the reactions times. Tributylgermanium hydride has been used to replace the toxic and troublesome tributyltin hydride in the radical reactions. [Copyright &y& Elsevier]

Abstract: 2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1-a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1-a]isoquinoline-3-carboxylate were determined by X-ray crystallography. [Copyright &y& Elsevier]

Crystals of the title compound, C7H4BrNO, are twinned by a twofold rotation about [001]. The crystal structure is stabilized by π-stacking of the virtually planar fused ring system along the crystallographic a axis, and through weak intermolecular C—H...O, C—H...N and C—H...Br interactions. [ABSTRACT FROM AUTHOR]