bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications
Authors: Croissant Jonas G. , Fatieiev Yevhen , Almalik Abdulaziz , Khashab Niveen M.
Published: November 2017

Predetermining the physico‐chemical properties, biosafety, and stimuli‐responsiveness of nanomaterials in biological environments is essential for safe and effective biomedical applications. At the forefront of biomedical research, mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are increasingly investigated to predict their biological outcome by materials design. In this review, it is first chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica (periodic mesoporous organosilicas) governs not only the physico‐chemical properties but also the biosafety of the nanoparticles. The impact of the hybridization on the biocompatibility, protein corona, biodistribution, biodegradability, and clearance of the silica‐based particles is described. Then, the influence of the surface engineering, the framework hybridization, as well as the morphology of the particles, on the ability to load and controllably deliver drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To conclude, trends in the biomedical applications of silica and organosilica nanovectors are delineated, such as unconventional bioimaging techniques, large cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial protection, and Alzheimer's disease therapy.
Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials
Authors: Bruggeman Kiara F. , Williams Richard J. , Nisbet David R.
Published: November 2017

Tissue engineering scaffolds are designed to mimic physical, chemical, and biological features of the extracellular matrix, thereby providing a constant support that is crucial to improved regenerative medicine outcomes. Beyond mechanical and structural support, the next generation of these materials must also consider the more dynamic presentation and delivery of drugs or growth factors to guide new and regenerating tissue development. These two aspects are explored expansively separately, but they must interact synergistically to achieve optimal regeneration. This review explores common tissue engineering materials types, electrospun polymers and hydrogels, and strategies used for incorporating drug delivery systems into these scaffolds.
Ligand‐Assisted Pd‐Catalyzed N‐Dealkylative Carbonylation of Tertiary Amines with (Hetero)Aryl Halides to Tertiary Amides
Authors: Mane Rajendra S. , Bhanage Bhalchandra M.
Published: November 2017

This work reports an efficient synthesis of tertiary amides using a ligand‐assisted Pd‐catalyzed carbonylation of (hetero)aryl halides with tertiary amines. A key step in this reaction is C(sp3)−N bond cleavage using CuO as an oxidant. The reaction proceeds with high efficiency employing a bidentate phosphine ligand (dppp), which is a key for the carbonylation of unreactive (hetero)aryl halides and series of tertiary amines at atmospheric pressure of carbon monoxide.
Diverged Plant Terpene Synthases Reroute the Carbocation Cyclization Path towards the Formation of Unprecedented 6/11/5 and 6/6/7/5 Sesterterpene Scaffolds
Authors: Huang Ancheng C. , Hong Young J. , Bond Andrew D. , Tantillo Dean J. , Osbourn Anne
Published: November 2017

Sesterterpenoids are a relatively rare class of plant terpenes. Sesterterpene synthase (STS)‐mediated cyclization of the linear C25 isoprenoid precursor geranylfarnesyl diphosphate (GFPP) defines sesterterpene scaffolds. So far only a very limited number of STSs have been characterized. The discovery of three new plant STSs is reported that produce a suite of sesterterpenes with unprecedented 6/11/5 and 6/6/7/5 fused ring systems when transiently co‐expressed with a GFPP synthase in Nicotiana benthamiana. Structural elucidation, feeding experiments, and quantum chemical calculations suggest that these STSs catalyze an unusual cyclization path involving reprotonation, intramolecular 1,6 proton transfer, and concerted but asynchronous bicyclization events. The cyclization is diverted from those catalyzed by the characterized plant STSs by forming unified 15/5 bicyclic sesterterpene intermediates. Mutagenesis further revealed a conserved amino acid residue implicated in reprotonation.
PET/CT imaging in management of concomitant Hodgkin lymphoma and tuberculosis – a problem solver tool
Authors: Jehanno Nina , Cassou‐Mounat Thibaut , Vincent‐Salomon Anne , Luporsi Marie , Bedoui Manel , Kuhnowski Frédérique
Published: November 2017

Key Clinical Message

Infectious lymph nodes mimicking lymphoma is challenging for accurate staging. Although 18F‐FDG is a nonspecific tracer accumulating not only in tumor cells but also in inflammatory tissues, the metabolic features and uptake kinetics give valuable information: 18F‐FDG PET/CT appears as a useful problem solver tool in ambiguous situation.
Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design
Authors: Axer Alexander , Hermann Sven , Kehr Gerald , Clases David , Karst Uwe , Fischer‐Riepe Lena , Roth Johannes , Fobker Manfred , Schäfers Michael , Gilmour Ryan , Faust Andreas
Published: November 2017

Diagnosis and localization of bacterial infections remains a significant clinical challenge. Harnessing bacteria‐specific metabolic pathways, such as the maltodextrin transport mechanism, may allow specific localization and imaging of small or hidden colonies. This requires that the intrabacterial tracer accumulation provided by the transporter is matched by high serum stability of the tracer molecule. Herein, radiolabeled maltodextrins of varying chain lengths and with free nonreducing/reducing ends are reported and their behavior against starch‐degrading enzymes in the blood, which compromise their serum stability, is evaluated. Successful single‐photon emission computed tomography (SPECT) imaging is shown in a footpad infection model in vivo by using the newly developed model tracer, [99mTc]MB1143, and the signal is compared with that of 18F‐fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) as a nonbacterial specific marker for inflammation. Although the [99mTc]MB1143 imaging signal is highly specific, it is low, most probably due to insufficient serum stability of the tracer. A series of stability tests with different 18F‐labeled maltodextrins finally yielded clear structural guidelines regarding substitution patterns and chain lengths of maltodextrin‐based tracers for nuclear imaging of bacterial infections.
Computational Screening of Doped α‐MnO2 Catalysts for the Oxygen Evolution Reaction
Authors: Tripkovic Vladimir , Hansen Heine Anton , Vegge Tejs
Published: November 2017

Minimizing energy and materials costs for driving the oxygen evolution reaction (OER) is paramount for the commercialization of water electrolysis cells and rechargeable metal–air batteries. Structural stability, catalytic activity, and electronic conductivity of pure and doped α‐MnO2 for the OER are studied using density functional theory calculations. As model surfaces, we investigate the (110) and (100) facets, on which three possible active sites are identified: a coordination unsaturated, a bridge, and a bulk site. For pure and Cr‐, Fe‐, Co‐, Ni‐, Cu‐, Zn‐, Cd‐, Mg‐, Al‐, Ga‐, In‐, Sc‐, Ru‐, Rh‐, Ir‐, Pd‐, Pt‐, Ti‐, Zr‐, Nb‐, and Sn‐doped α‐MnO2, the preferred valence at each site is imposed by adding/subtracting electron donors (hydrogen atoms) and electron acceptors (hydroxy groups). From a subset of stable dopants, Pd‐doped α‐MnO2 is identified as the best catalyst and the only material that can outperform pristine α‐MnO2. Different approaches to increase the bulk electron conductivity of semiconducting α‐MnO2 are discussed.
Contribution of cardiac and extra‐cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure
Authors: Wolsk Emil , Claggett Brian , Køber Lars , Pocock Stuart , Yusuf Salim , Swedberg Karl , McMurray John J.V. , Granger Christopher B. , Pfeffer Marc A. , Solomon Scott D.
Published: November 2017

Aims

Patients with heart failure (HF) often have multiple co‐morbidities that contribute to the risk of adverse cardiovascular (CV) and non‐CV outcomes. We assessed the relative contribution of cardiac and extra‐cardiac disease burden and demographic factors to CV outcomes in HF patients with reduced (HFrEF) or preserved (HFpEF) left ventricular ejection fraction (LVEF).

Methods and results

We utilized data from the CHARM trial, which enrolled HF patients across the ejection fraction spectrum. We decomposed the previously validated MAGGIC risk score into cardiac (LVEF, New York Heart Association class, systolic blood pressure, time since HF diagnosis, HF medication use), extra‐cardiac (body mass index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease, smoker), and demographic (age, gender) categories, and calculated subscores for each patient representing the burden of each component. Cox proportional hazards models were used to estimate the population attributable risk (PAR) associated with each component to the outcomes of death, CV death, HF, myocardial infarction, and stroke relative to patients with the lowest risk score. PARs for each component were depicted across the spectrum of LVEF. in 2675 chronic HF patients from North America [HFrEF (LVEF ≤40%): n = 1589, HFpEF (LVEF >40%): n = 1086] with data available for calculation of the MAGGIC score, the highest risk of death and CV death was attributed to cardiac burden. This was especially evident in HFrEF patients (PAR: 76% cardiac disease vs. 58% extra‐cardiac disease, P < 0.05). Conversely, in HFpEF patients, extra‐cardiac burden accounted for a greater proportion of risk for death than cardiac burden (PAR: 15% cardiac disease vs. 49% extra‐cardiac disease, P < 0.05). For HF hospitalization, the contribution of both cardiac and extra‐cardiac burden was comparable in HFpEF patients (PAR: 42% cardiac disease vs. 53% extra‐cardiac disease, P = NS). In addition, demographic burden was especially high in HFpEF patients, with 62% of deaths attributable to demographic characteristics.

Conclusion

In North American HF patients enrolled in the CHARM trials, the relative contribution of cardiac and extra‐cardiac disease burden to CV outcomes and death differed depending on LVEF. The high risk of events attributable to non‐cardiac disease burden may help explain why cardiac disease‐modifying medication proven to be efficacious in HFrEF patients has not proven beneficial in HFpEF.
Joint dynamic access points grouping and resource allocation for coordinated transmission in user‐centric UDN
Authors: Wang Chuan'an , Hu Bo , Chen Shanzhi , Wang Yingying
Published: November 2017

We consider the resource allocation problem in user‐centric ultradense network, where each user equipment (UE) is served by its own access points group (APG), and the APG will be dynamically adjusted to support UE's movement. In this context, our scheme is to jointly design dynamic APs grouping and the resource allocation for coordinated transmission in user‐centric ultradense network. First, a user‐centric dynamic APs grouping approach is considered, where the APGs are formed based on cooperation benefits that UEs experience to different access points (APs). Accordingly, due to resource allocation constraints unbounded among the overlapped APGs, which result in the resource allocation optimization problem being nonconvex. To address this issue, the resource allocation problem is divided into the subchannel (SC) allocation subproblem and the power allocation subproblem. With the SC allocation results, an iterative power allocation algorithm is carried out over all SCs at each AP to get an optimal power allocation. The performance of the proposed scheme is also demonstrated through simulations.
Interleukin‐17 and Toll‐like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis
Authors: Vrgoc Goran , Vrbanec Jurica , Eftedal Randi K. , Dembic Petra L. , Balen Sanja , Dembic Zlatko , Jotanovic Zdravko
Published: November 2017

Primary osteoarthritis (OA) is the most common type of a joint disease. It has a polygenic risk inheritance pattern and affects older people. The etiology of this disease is not fully understood. The aim of this study was to investigate the associations between polymorphisms in pro‐inflammatory interleukin‐17 (IL17A and IL17F) and anti‐inflammatory Toll‐like Receptor 10 (TLR10) genes with the risk for development of advanced stage hip and knee primary OA in the Croatian population. A total of 500 OA patients and 597 controls were genotyped for IL17A SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957) genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed statistically significant differences in comparisons of controls with hip—but not knee—OA patients. The major allele (T) of rs763780 was associated with the lower risk for developing hip OA (p = 7.9 × 10−4, OR = 0.45, 95%CI = 0.27–0.74), whereas the minor allele (C) was associated with susceptibility to hip OA (p = 7.9 × 10−4, OR = 2.24, 95%CI = 1.35–3.72). The genotype T/T was associated with the protection to hip OA (p = 3.9 × 10−4, OR = 0.41, 95%CI = 0.24–0.70), and, lastly, the genotype T/C was associated with the higher risk to acquiring hip OA (p = 2.6 × 10−4, OR = 2.50, 95%CI = 1.47–4.25). TLR10 SNP rs11096957 was found significantly associated with predisposition to hip OA (p = 0.04, OR = 1.41, 95%CI = 1.02–1.94) but not knee OA. Our findings suggest that hip OA in Croatian population might have a different genetic risk regarding the IL17 and TLR10 gene locus than knee OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1684–1693, 2018.
Validity of Ultrasound Lung Comets for Assessment of the Severity of Interstitial Pneumonia
Authors: Asano Mariko , Watanabe Hiroyuki , Sato Kazuhiro , Okuda Yuji , Sakamoto Sho , Hasegawa Yukiyasu , Sudo Kazuhisa , Takeda Masahide , Sano Masaaki , Kibira Satoshi , Ito Hiroshi
Published: November 2017

Objectives

Ultrasound (US) lung comets are often observed in patients with interstitial lung disease or congestive heart failure, but few studies have explored the clinical importance of US lung comets in patients with the former condition. We explored whether the US lung comet number could be used to assess the severity of interstitial pneumonia.

Methods

Forty stable patients with interstitial pneumonia were examined. Lung comets evident on transthoracic US imaging in 12 selected regions of the posterior chest wall were analyzed. We defined lung comets accompanied by thickened and irregular pleural lines as interstitial US lung comets; these predominated in patients with interstitial pneumonia. The total number of interstitial US lung comets was correlated with the data from chest high‐resolution computed tomography, pulmonary function tests, serologic tests, and the 6‐minute walk test.

Results

The 40 patients included 16 with idiopathic pulmonary fibrosis and 24 with nonspecific interstitial pneumonia. Thirty‐four patients had interstitial US lung comets, which were more common in the lower than the upper lung area. Good correlations were evident between the lung comet number and the extent of the reticular pattern on chest high‐resolution computed tomography (r = 0.710; P < .01), predicted forced vital capacity (r = −0.614; P < .01), and lung diffusion capacity for carbon monoxide (r = −0.577; P < .01). Notably, the lung comet number had a strong negative correlation with the percutaneous oxygen saturation level after the 6‐minute walk test (r = −0.751; P < .01).

Conclusions

The number of interstitial US lung comets evident on transthoracic US imaging may be a valuable marker of disease severity in patients with interstitial pneumonia.
Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype
Authors: Asur Rajalakshmi S. , Kimble Danielle C. , Lach Francis P. , Jung Moonjung , Donovan Frank X. , Kamat Aparna , Noonan Raymond J. , Thomas James W. , Park Morgan , Chines Peter , Vlachos Adrianna , Auerbach Arleen D. , Smogorzewska Agata , Chandrasekharappa Settara C.
Published: November 2017

Background

Fanconi anemia (FA) is a rare disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer. Patients harboring X‐linked FANCB pathogenic variants usually present with severe congenital malformations resembling VACTERL syndrome with hydrocephalus.

Methods

We employed the diepoxybutane (DEB) test for FA diagnosis, arrayCGH for detection of duplication, targeted capture and next‐gen sequencing for defining the duplication breakpoint, PacBio sequencing of full‐length FANCB aberrant transcript, FANCD2 ubiquitination and foci formation assays for the evaluation of FANCB protein function by viral transduction of FANCB‐null cells with lentiviral FANCB WT and mutant expression constructs, and droplet digital PCR for quantitation of the duplication in the genomic DNA and cDNA.

Results

We describe here an FA‐B patient with a mild phenotype. The DEB diagnostic test for FA revealed somatic mosaicism. We identified a 9154 bp intragenic duplication in FANCB, covering the first coding exon 3 and the flanking regions. A four bp homology (GTAG) present at both ends of the breakpoint is consistent with microhomology‐mediated duplication mechanism. The duplicated allele gives rise to an aberrant transcript containing exon 3 duplication, predicted to introduce a stop codon in FANCB protein (p.A319*). Duplication levels in the peripheral blood DNA declined from 93% to 7.9% in the span of eleven years. Moreover, the patient fibroblasts have shown 8% of wild‐type (WT) allele and his carrier mother showed higher than expected levels of WT allele (79% vs. 50%) in peripheral blood, suggesting that the duplication was highly unstable.

Conclusion

Unlike sequence point variants, intragenic duplications are difficult to precisely define, accurately quantify, and may be very unstable, challenging the proper diagnosis. The reversion of genomic duplication to the WT allele results in somatic mosaicism and may explain the relatively milder phenotype displayed by the FA‐B patient described here.
Poly(vinyl alcohol)‐based electrospun nanofibers for the sustained release of celecoxib: Characterization and evaluation of drug release mechanism
Authors: Dinari Mohammad , Bina Fateme , Khayamian Taghi
Published: November 2017

In this research, biodegradable/biocompatible nanofiber electrospun mats of PVA with 3% and 8% w/w of celecoxib (CX) were used for sustained release formulations of CX. The morphology of the nanofibers, distribution of the drug inside the nanofibers and possible reactions between polymers and CX in nanofibers were studied by SEM, XRD and FT‐IR techniques. In vitro CX release from the nanofiber mats were evaluated in solution of HCl (pH = 1.5) and carbonate buffer (pH = 8) through UV‐Vis spectroscopy technique. t50% of CX release for 3% CX‐loaded PVA electrospun mats was 4.49, 8.16 and 13.40 h within environment of HCl, carbonate buffer and carbonate buffer after HCl, respectively. Drug release was dependent on the CX percent and release environment. Korsmeyer‐Peppas release exponent (n) indicates that CX release mechanism was Fickian diffusion for formulations of PVA nanofiber mats. POLYM. COMPOS., 39:E221–E227, 2018. © 2017 Society of Plastics Engineers
Null recurrence and transience of random difference equations in the contractive case
Authors: Alsmeyer Gerold , Buraczewski Dariusz , Iksanov Alexander
Published: November 2017

Given a sequence (Mk, Qk)k ≥ 1 of independent and identically distributed random vectors with nonnegative components, we consider the recursive Markov chain (Xn)n ≥ 0, defined by the random difference equation Xn = MnXn - 1 + Qn for n ≥ 1, where X0 is independent of (Mk, Qk)k ≥ 1. Criteria for the null recurrence/transience are provided in the situation where (Xn)n ≥ 0 is contractive in the sense that M1 ⋯ Mn → 0 almost surely, yet occasional large values of the Qn overcompensate the contractive behavior so that positive recurrence fails to hold. We also investigate the attractor set of (Xn)n ≥ 0 under the sole assumption that this chain is locally contractive and recurrent.
FRAME: femtosecond videography for atomic and molecular dynamics
Authors: Ehn Andreas , Bood Joakim , Li Zheming , Berrocal Edouard , Aldén Marcus , Kristensson Elias
Published: November 2017

Many important scientific questions in physics, chemistry and biology require effective methodologies to spectroscopically probe ultrafast intra- and inter-atomic/molecular dynamics. However, current methods that extend into the femtosecond regime are capable of only point measurements or single-snapshot visualizations and thus lack the capability to perform ultrafast spectroscopic videography of dynamic single events. Here we present a laser-probe-based method that enables two-dimensional videography at ultrafast timescales (femtosecond and shorter) of single, non-repetitive events. The method is based on superimposing a structural code onto the illumination to encrypt a single event, which is then deciphered in a post-processing step. This coding strategy enables laser probing with arbitrary wavelengths/bandwidths to collect signals with indiscriminate spectral information, thus allowing for ultrafast videography with full spectroscopic capability. To demonstrate the high temporal resolution of our method, we present videography of light propagation with record high 200 femtosecond temporal resolution. The method is widely applicable for studying a multitude of dynamical processes in physics, chemistry and biology over a wide range of time scales. Because the minimum frame separation (temporal resolution) is dictated by only the laser pulse duration, attosecond-laser technology may further increase video rates by several orders of magnitude.
Stimulus expectation alters decision criterion but not sensory signal in perceptual decision making
Authors: Bang Ji Won , Rahnev Dobromir
Published: November 2017

Humans are more likely to report perceiving an expected than an unexpected stimulus. Influential theories have proposed that this bias arises from expectation altering the sensory signal. However, the effects of expectation can also be due to decisional criterion shifts independent of any sensory changes. In order to adjudicate between these two possibilities, we compared the behavioral effects of pre-stimulus cues (pre cues; can influence both sensory signal and decision processes) and post-stimulus cues (post cues; can only influence decision processes). Subjects judged the average orientation of a series of Gabor patches. Surprisingly, we found that post cues had a larger effect on response bias (criterion c) than pre cues. Further, pre and post cues did not differ in their effects on stimulus sensitivity (d’) or the pattern of temporal or feature processing. Indeed, reverse correlation analyses showed no difference in the temporal or feature-based use of information between pre and post cues. Overall, post cues produced all of the behavioral modulations observed as a result of pre cues. These findings show that pre and post cues affect the decision through the same mechanisms and suggest that stimulus expectation alters the decision criterion but not the sensory signal itself.
Electrostatic Map Of Proteasome α-Rings Encodes The Design of Allosteric Porphyrin-Based Inhibitors Able To Affect 20S Conformation By Cooperative Binding
Authors: Dato Antonio Di , Cunsolo Alessandra , Persico Marco , Santoro Anna Maria , D’Urso Alessandro , Milardi Danilo , Purrello Roberto , Stefanelli Manuela , Paolesse Roberto , Tundo Grazia R. , Sbardella Diego , Fattorusso Caterina , Coletta Massimo
Published: November 2017

The importance of allosteric proteasome inhibition in the treatment of cancer is becoming increasingly evident. Motivated by this urgent therapeutic need, we have recently identified cationic porphyrins as a highly versatile class of molecules able to regulate proteasome activity by interfering with gating mechanisms. In the present study, the mapping of electrostatic contacts bridging the regulatory particles with the α-rings of the human 20S proteasome led us to the identification of (meso-tetrakis(4-N-methylphenyl pyridyl)-porphyrin (pTMPyPP4) as a novel non-competitive inhibitor of human 20S proteasome. pTMPyPP4 inhibition mechanism implies a positive cooperative binding to proteasome, which disappears when a permanently open proteasome mutant (α-3ΔN) is used, supporting the hypothesis that the events associated with allosteric proteasome inhibition by pTMPyPP4 interfere with 20S gating and affect its “open-closed” equilibrium. Therefore, we propose that the spatial distribution of the negatively charged residues responsible for the interaction with regulatory particles at the α-ring surface of human 20S may be exploited as a blueprint for the design of allosteric proteasome regulators.
Interplay between global and pathway-specific synaptic plasticity in CA1 pyramidal cells
Authors: Berberich Sven , Pohle Jörg , Pollard Marie , Barroso-Flores Janet , Köhr Georg
Published: November 2017

Mechanisms underlying information storage have been depicted for global cell-wide and pathway-specific synaptic plasticity. Yet, little is known how these forms of plasticity interact to enhance synaptic competition and network stability. We examined synaptic interactions between apical and basal dendrites of CA1 pyramidal neurons in mouse hippocampal slices. Bursts (50 Hz) of three action potentials (AP-bursts) paired with preceding presynaptic stimulation in stratum radiatum specifically led to LTP of the paired pathway in adult mice (P75). At adolescence (P28), an increase in burst frequency (>50 Hz) was required to gain timing-dependent LTP. Surprisingly, paired radiatum and unpaired oriens pathway potentiated, unless the pre-post delay was shortened from 10 to 5 ms, which selectively potentiated paired radiatum pathway, since unpaired oriens pathway decreased back to baseline. Conversely, the exact same 5 ms pairing in stratum oriens potentiated both pathways, as did AP-bursts alone, which potentiated synaptic efficacy as well as current-evoked postsynaptic spiking. L-type voltage-gated Ca2+ channels were involved in mediating synaptic potentiation in oriens, whereas NMDA and adenosine receptors counteracted unpaired stratum oriens potentiation following pairing in stratum radiatum. This asymmetric plasticity uncovers important insights into alterations of synaptic efficacy and intrinsic neuronal excitability for pathways that convey hippocampal and extra-hippocampal information.
The Genetic Spectrum of Familial Hypercholesterolemia (FH) in the Iranian Population
Authors: Fairoozy R. H. , Futema M. , Vakili R. , Abbaszadegan M. R. , Hosseini S. , Aminzadeh M. , Zaeri H. , Mobini M. , Humphries S. E. , Sahebkar A.
Published: November 2017

Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and PCSK9 genes are known to cause FH. In this study, we analysed the genetic spectrum of the disease in subjects from the Iranian population with a clinical diagnosis of FH. Samples were collected from 16 children and family members from five different cities of Iran. Probands were screened for mutations in the LDLR, APOB, and PCSK9 genes using next generation sequencing, with results confirmed by Sanger sequencing. The likely pathology of identified variants was examined using in silico tools. Of the probands, 14 had a clinical diagnosis of homozygous FH and two of heterozygous FH. No mutations were found in either APOB or PCSK9, but nine probands were homozygous for seven different LDLR mutations, with p.(Trp577Arg) occurring in three and p.Val806Glyfs*11 occurring in two patients. Two mutations were novel: p.(Leu479Gln) and p.(Glu668*). Seven probands with a clinical diagnosis of FH were mutation negative. This pilot study, integrating clinical and molecular-based techniques, begins to elucidate the FH heterogeneity and the mutation spectrum in the Iranian population. Such information is important for future disease management and cost savings.
Emerging Role for the PERK/eIF2α/ATF4 in Human Cutaneous Leishmaniasis
Authors: Dias-Teixeira Karina Luiza , Calegari-Silva Teresa C. , Medina Jorge M. , Vivarini Áislan C. , Cavalcanti Átila , Teteo Nataly , Santana Alynne Karen M. , Real Fernando , Gomes Ciro M. , Pereira Renata Meirelles Santos , Fasel Nicolas , Silva João S. , Aktas Bertal H. , Lopes Ulisses G.
Published: November 2017

Leishmania parasites utilize adaptive evasion mechanisms in infected macrophages to overcome host defenses and proliferate. We report here that the PERK/eIF2α/ATF4 signaling branch of the integrated endoplasmic reticulum stress response (IERSR) is activated by Leishmania and this pathway is important for Leishmania amazonensis infection. Knocking down PERK or ATF4 expression or inhibiting PERK kinase activity diminished L. amazonensis infection. Knocking down ATF4 decreased NRF2 expression and its nuclear translocation, reduced HO-1 expression and increased nitric oxide production. Meanwhile, the increased expression of ATF4 and HO-1 mRNAs were observed in lesions derived from patients infected with the prevalent related species L.(V.) braziliensis. Our data demonstrates that Leishmania parasites activate the PERK/eIF2α/ATF-4 pathway in cultured macrophages and infected human tissue and that this pathway is important for parasite survival and progression of the infection.
NSD1 inactivation defines an immune cold, DNA hypomethylated subtype in squamous cell carcinoma
Authors: Brennan Kevin , Shin June Ho , Tay Joshua K. , Prunello Marcos , Gentles Andrew J. , Sunwoo John B. , Gevaert Olivier
Published: November 2017

Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions inNSD1. The ‘NSD1 subtypes’ of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germlineNSD1mutations. Further, the NSD1 subtype of HNSC displays an ‘immune cold’ phenotype characterized by low infiltration of tumor-associated leukocytes, particularly macrophages and CD8+T cells, as well as low expression of genes encoding the immunotherapy target PD-1 immune checkpoint receptor and its ligands. Using anin vivomodel, we demonstrate that NSD1 inactivation results in reduced T cell infiltration into the tumor microenvironment, implicating NSD1 as a tumor cell-intrinsic driver of an immune cold phenotype. NSD1 inactivation therefore causes epigenetic deregulation across cancer sites, and has implications for immunotherapy.
Preparation of Permanent Magnetic Resin Crosslinking by Diallyl Itaconate and Its Adsorptive and Anti-fouling Behaviors for Humic Acid Removal
Authors: Li Qimeng , Wu Ji , Hua Ming , Zhang Guang , Li Wentao , Shuang Chendong , Li Aimin
Published: November 2017

In this research, a series of permanent magnetic anion exchange resins (MAERs) were prepared by polymerizing glycidyl methacrylate monomer and crosslinking diallyl itaconate (DAI) and divinylbenzene. The properties and performances of these novel MAERs were systematically characterized and evaluated for humic acid (HA) adsorption by batch experiments. With the increase of DAI content from 0 to 15%, the moisture of MAERs was elevated from 50.23% to 68.53%, along with the adsorption capacity increasing from 2.57 to 3.14 mmol g−1. As the concentrations of co-existing cation (Ca2+ and Mg2+) increased, the adsorption amounts of HA dropped drastically at first and increased a little at high cation concentrations. Although ion exchange was the primary mechanism for HA adsorption, other physical interactions and electrostatic attraction between HA molecules and newly formed oxonium group also played significant roles for HA adsorption. The MAERs could be efficiently regenerated by a mixture of NaCl/NaOH solution (10%/1%), and notably, the MAER-3 with the highest DAI content displayed unapparent loss of adsorption capacity during twenty-one successive adsorption-desorption cycles. These results suggested a novel resin adsorbent for its excellent performances on adsorption, regeneration, and sedimentation in water treatment for natural organic matter removal.
First-principles study of nonmetal doped monolayer MoSe2 for tunable electronic and photocatalytic properties
Authors: Zhao Yafei , Wang Wei , Li Can , He Liang
Published: November 2017

Recently, two dimensional transition metal dichalcogenides become popular research topics because of their unique crystal and electronic structure. In this work, the geometrical structure, electronic, electrical transport, redox potentials and photocatalytic properties of nonmetal (H, B, C, Si, N, P, As, O, S, Te, F, Cl, Br and I) doped monolayer MoSe2 were investigated by first principle calculations. The binding energy indicates that nonmetal doped MoSe2 are energetically favorable compared to Se vacancies, except B- and C-doped. We have found that nonmetal dopants with an even number of valence electrons doped MoSe2 have p-type conductivity. On the contrary, nonmetal dopants with an odd number of valence electrons doped MoSe2 have p-type or n-type conductivity; and they have better photocatalytic performance.
Rational construction of a stable Zn4O-based MOF for highly efficient CO2 capture and conversion
Authors: Zhou Hui-Fang , Liu Bo , Hou Lei , Zhang Wen-Yan , Wang Yao-Yu
Published: November 2017

An exceptionally stable Zn4O-MOF has been rationally synthesized, which exhibits high CO2 capture and efficient catalytic conversion for CO2 cycloaddition with epoxides under mild conditions.
Signatures of a quantum diffusion limited hydrogen atom tunneling reaction
Authors: Balabanoff Morgan E. , Ruzi Mahmut , Anderson David T.
Published: November 2017

We are studying the details of hydrogen atom (H atom) quantum diffusion in parahydrogen quantum solids in an effort to better understand H atom transport and reactivity under these conditions.
Attractive non-DLVO forces induced by adsorption of monovalent organic ions
Authors: Smith Alexander M. , Maroni Plinio , Borkovec Michal
Published: November 2017

Direct force measurements between negatively charged colloidal particles were carried out using an atomic force microscope (AFM) in aqueous solutions containing monovalent organic cations, namely tetraphenylarsonium (Ph4As+), 1-hexyl-3-methylimidazolium (HMIM+), and 1-octyl-3-methylimidazolium (OMIM+).
Do protocells preferentially retain macromolecular solutes upon division/fragmentation? A study based on the extrusion of POPC giant vesicles
Authors: Fanti Alessio , Gammuto Leandro , Mavelli Fabio , Stano Pasquale , Marangoni Roberto
Published: November 2017

A key process of protocell behaviour is their recursive growth and division, while keeping solutes inside.
N-Propyl benzoguanamine sulfonic acid supported on magnetic Fe3O4 nanoparticles: a novel and efficient magnetically heterogeneous catalyst for the synthesis of 1,8-dioxo-decahydroacridine derivatives
Authors: Gholami Dehbalaei Masoumeh , Foroughifar Naser , Pasdar Hoda , Khajeh-Amiri Alireza
Published: November 2017

An MNPs-N-propyl-benzoguanamine-SO3H nanocatalyst as a novel, retrievable, economic and heterogeneous catalyst is prepared for the synthesis of 1,8-dioxo-decahydroacridine derivatives.
A coelenterazine-type bioluminescent probe for nitroreductase imaging
Authors: Yang Xingye , Li Zhenzhen , Jiang Tianyu , Du Lupei , Li Minyong
Published: November 2017

Novel coelenterazine-type bioluminescent probes have been designed and synthesized to detect nitroreductase (NTR) in hypoxic tumors.
Temperature-dependent IR-transition moment orientational analysis applied to thin supported films of poly-ε-caprolactone
Authors: Kossack Wilhelm , Schulz Martha , Thurn-Albrecht Thomas , Reinmuth Jörg , Skokow Viktor , Kremer Friedrich
Published: November 2017

A novel experimental setup based on infrared spectroscopy is described. It enables one to determine the molecular order of amorphous strands and crystalline lamellae in polymer films depending on temperature.
Synthesis of fluorine-modified polysilazanesviaSi–H bond activation and their application as protective hydrophobic coatings
Authors: Furtat P. , Lenz-Leite M. , Ionescu E. , Machado R. A. F. , Motz G.
Published: November 2017

A new method to synthesize fluorine-modified polysilazanes for processing of hydrophobic coatings with remarkable chemical stability for corrosion protection of metals.
Encapsulating nanoscale zero-valent iron with a soluble Mg(OH)2 shell for improved mobility and controlled reactivity release
Authors: Hu Yi-bo , Zhang Miaoyue , Qiu Rongliang , Li Xiao-yan
Published: November 2017

NZVI with novel Mg(OH)2 encapsulation for considerably improved mobility, chemical stability, and controlled reactivity release for environmental remediation.
MoS2–MoP heterostructured nanosheets on polymer-derived carbon as an electrocatalyst for hydrogen evolution reaction
Authors: Wu Zexing , Wang Jie , Xia Kedong , Lei Wen , Liu Xien , Wang Deli
Published: November 2017

MoS2–MoP/C prepared through a facile and scalable strategy exhibited excellent electrocatalytic activity and long-term stability for HER in acid medium. The electronic interactions, relative high specific surface area and synergistic effects of the doped heteroatoms contribute to the superior catalytic performance.
Rational design of asymmetric benzodithiophene based photovoltaic polymers for efficient solar cells
Authors: Zhu Tingting , Liu Deyu , Zhang Kaili , Li Yonghai , Liu Zhe , Gao Xudong , Bao Xichang , Sun Mingliang , Yang Renqiang
Published: November 2017

Asymmetric-modified benzodithiophene moiety is designed for D–A conjugated photovoltaic materials, and PCE exceeding 10% is achieved with ITIC as an acceptor.
Responsive crosslinked polymer nanogels for imaging and therapeutics delivery
Authors: Ekkelenkamp Antonie E. , Elzes M. Rachèl , Engbersen Johan F. J. , Paulusse Jos M. J.
Published: November 2017

Nanogels are water-soluble crosslinked polymer networks with tremendous potential in targeted imaging and controlled drug and gene delivery.
Inversion of charge carrier polarity and boosting the mobility of organic semiconducting polymers based on benzobisthiadiazole derivatives by fluorination
Authors: Wang Yang , Tan Aaron Tze-Rue , Mori Takehiko , Michinobu Tsuyoshi
Published: November 2017

The first fluorinated copolymers based on benzobisthiadiazole (BBT) and its derivatives are newly synthesized, which show an inversion of charge carrier polarity and dramatic improvement of the mobility.
The lung microbiome
Authors: Rogers Geraint B.
Published: November 2017

Historically, our understanding of lung microbiology has relied on insight gained through culture-based diagnostic approaches that employ selective culture conditions to isolate specific pathogens. The relatively recent development of culture-independent microbiota-profiling techniques, particularly 16S rRNA (ribosomal ribonucleic acid) gene amplicon sequencing, has enabled more comprehensive characterisation of the microbial content of respiratory samples. The widespread application of such techniques has led to a fundamental shift in our view of respiratory microbiology. Rather than a sterile lung environment that can become colonised by microbes during infection, it appears that a more nuanced balance exists between what we consider respiratory health and disease, mediated by mechanisms that influence the clearance of microbes from the lungs. Where airway defences are compromised, the ongoing transient exposure of the lower airways to microbes can lead to the establishment of complex microbial communities within the lung. Importantly, the characteristics of these communities, and the manner in which they influence lung pathogenesis, can be very different from those of their constituent members when viewed in isolation. The lung microbiome, a construct that incorporates microbes, their genetic material, and the products of microbial genes, is increasingly central to our understanding of the regulation of respiratory physiology and the processes that underlie lung pathogenesis.
Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases
Authors: O'Neill Ian , Schofield Zoe , Hall Lindsay J.
Published: November 2017

The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout our lifetime and have been shown to modulate specific immune cells and pathways. Notably, reductions in this genus have been associated with several diseases, including inflammatory bowel disease. In this review, we provide an overview of bifidobacteria profiles throughout life and how different strains of bifidobacteria have been implicated in immune modulation in disease states. The focus will be examining preclinical models and outcomes from clinical trials on immune-linked chronic conditions. Finally, we highlight some of the important unresolved questions in relation to Bifidobacterium-mediated immune modulation and implications for future directions, trials, and development of new therapies.
Structured distance to non‐surjectivity of convex processes and its applications to robust controllability under structured perturbations
Authors: Son Nguyen Khoa , Thuan Do Duc
Published: November 2017

In this study, some computational expressions for the distance to non‐surjectivity of convex processes subjected to structured perturbations are established. The results are then applied to calculate the structured controllability radius of differential and difference inclusions. Examples are given to illustrate the obtained results.
Dynamic reserve demand estimation model and cost‐effectivity oriented reserve allocation strategy for multi‐area system integrated with wind power
Authors: Jiang Haiyan , Xu Jian , Sun Yuanzhang , Liao Siyang , Ke Deping , Jiang Yibo , Tang Bowen
Published: November 2017

Optimisation of reserve purchased in advance becomes increasingly essential to hedge against the growing level of power unbalance brought by the integration of large‐scale wind power. Moreover, due to the centralised integration mode of wind farms, cross‐region reserve sharing strategy becomes quite imperative. Therefore, this study presents a dynamic reserve demand estimation (DRDE) model, which synthetically considers N  − 1 contingency along with load and wind forecast error. In the proposed approach, historical data is rearranged by a two‐dimensional binning technique and fitted by the versatile probability distribution model, which assisting the model reacts to different prediction level in each dispatch period dynamically. Furthermore, a cost‐effectivity oriented reserve allocation strategy for the multi‐area system is developed based on the DRDE model. The efficiency of the proposed method is tested in both 6‐bus test system and IEEE 118‐bus test system. The results show that, whether in the scenario of self‐sufficient reserve supplying or cross‐region reserve sharing strategy, the proposed estimation model effectively reduces the expectation of both load shedding and wind curtailment. Moreover, the proposed strategy improves the economy of system operation on the premise of ensuring system reliability.
Resonant frequency identification based on harmonic injection measuring method for traction power supply systems
Authors: Qiujiang Liu , Mingli Wu , Junqi Zhang , Kejian Song , Liran Wu
Published: November 2017

Accidents related with high‐order harmonic resonance seriously threaten the safety and stable operation of traction power supply systems (TPSSs). Generally, the resonant frequency of a TPSS, which is the crucial information for resonance suppression, cannot be accurately obtained through model‐based methods due to the TPSS complexity. This study proposes a direct measuring method that harmonic currents at different frequencies and amplitudes are injected into the TPSS by a harmonic generator (HG). Then, the resonant frequency can be identified by measuring the harmonic response. The HG based on a single‐phase cascaded H‐bridge converter and its control algorithms are developed. Both simulations on a railway system model and experimental results on an equivalent resonant circuit are carried out to validate the feasibility and effectiveness of the proposed method.
Synthesis of the C1–C9, C11–C19 Pyran Core and C19–C24 Fragments­ of Macrolactin 3
Authors: Maheshwar Reddy A. , Sabitha Gowravaram
Published: November 2017

We describe herein an efficient synthesis of the C1–C9, C11–C19 pyran moiety and C18–C24 core fragments of macrolactin 3. The prominent features of this work include construction of the Z-double bond of the 1,3-(Z,E)-diene system utilizing Horner–Wadsworth–Emmons­ reaction under Still–Gennari conditions. A Sharpless asymmetric epoxidation and subsequent epoxide opening under BF3·OEt2 conditions were applied to generate the stereogenic centers at C15 and C16, oxa-Michael addition and Jacobsen resolution facilitate the synthesis of the fragments.
Double-Layer Reconstruction of the Achilles’ Tendon Using a Modified Lindholm's Technique and Vascularized Fascia Lata
Authors: Kelahmetoglu Osman , Gules Mustafa , Elmadag Nuh , Guneren Ethem , Sonmez Ergun Selma
Published: November 2017

Loss of the Achilles’ tendon with overlying soft tissue and skin defects remains a complex reconstructive challenge. Herein we present our experience using a free composite anterolateral thigh (ALT) flap with vascularized fascia lata and a modified Lindholm's technique to repair the Achilles’ tendon. A 37-year-old man suffered from tertiary Achilles’ tendon rupture. For reconstruction, the free composite ALT flap with vascularized fascia lata was used to wrap Achilles’ tendon. A modified Lindholm's technique was used to cover overlying soft tissue defects. The patient was followed up for 12 months. No wound healing problems were reported, and the patient was able to walk and return to his daily ambulating activities without any support after 5 months postoperatively. This technique may be useful to achieve satisfactory outcomes in patients with ruptured Achilles’ tendons following tertiary repair.