bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling
Authors: Gargano Stacey M. , Senarathne Wijendra , Feldman Rebecca , Florento Elena , Stafford Phillip , Swensen Jeffrey , Vranic Semir , Gatalica Zoran
Published: October 2019

Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%‐8%) programmed death ligand 1 (PD‐L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre‐treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti‐androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD‐L1, mitogen‐activated protein kinase, and PIK3CA pathways.
Investigation of a New Type I Baeyer–Villiger Monooxygenase from Amycolatopsis thermoflava Revealed High Thermodynamic but Limited Kinetic Stability
Authors: Mansouri Hamid R. , Mihovilovic Marko D. , Rudroff Florian
Published: October 2019

Baeyer–Villiger monooxygenases (BVMOs) are remarkable biocatalysts, but, due to their low stability, their application in industry is hampered. Thus, there is a high demand to expand on the diversity and increase the stability of this class of enzyme. Starting from a known thermostable BVMO sequence from Thermocrispum municipale (TmCHMO), a novel BVMO from Amycolaptosis thermoflava (BVMOFlava), which was successfully expressed in Escherichia coli BL21(DE3), was identified. The activity and stability of the purified enzyme was investigated and the substrate profile for structurally different cyclohexanones and cyclobutanones was assigned. The enzyme showed a lower activity than that of cyclohexanone monooxygenase (CHMOAcineto) from Acinetobacter sp., as the prototype BVMO, but indicated higher kinetic stability by showing a twofold longer half‐life at 30 °C. The thermodynamic stability, as represented by the melting temperature, resulted in a Tm value of 53.1 °C for BVMOFlava, which was comparable to the Tm of TmCHMO (ΔTm=1 °C) and significantly higher than the Tm value for CHMOAcineto ((ΔTm=14.6 °C)). A strong deviation between the thermodynamic and kinetic stabilities of BVMOFlava was observed; this might have a major impact on future enzyme discovery for BVMOs and their synthetic applications.
It hurts to swallow! Pseudoachalasia resulting from attempted transcatheter occlusion of a giant congenital coronary artery fistula
Authors: Le Jonathan , Deano Roderick C. , Raval Amish N.
Published: October 2019

Congenital coronary artery fistula (CAF) is a rare anomaly that can cause heart failure and myocardial ischemia. In recent decades, transcatheter approaches to occlude CAF have emerged as minimally invasive alternatives to surgical ligation. Reported complications with transcatheter CAF occlusion include device embolization and dissection. We report the first case of attempted transcatheter occlusion of a giant CAF that resulted in severe pseudoachalasia.
Sugar Puckering Drives G‐Quadruplex Refolding: Implications for V‐Shaped Loops
Authors: Haase Linn , Dickerhoff Jonathan , Weisz Klaus
Published: October 2019

A DNA G‐quadruplex adopting a (3+1) hybrid structure was modified in two adjacent syn positions of the antiparallel strand with anti‐favoring 2′‐deoxy‐2′‐fluoro‐riboguanosine (FrG) analogues. The two substitutions promoted a structural rearrangement to a topology with the 5′‐terminal G residue located in the central tetrad and the two modified residues linked by a V‐shaped zero‐nucleotide loop. Strikingly, whereas a sugar pucker in the preferred north domain is found for both modified nucleotides, the FrG analogue preceding the V‐loop is forced to adopt the unfavored syn conformation in the new quadruplex fold. Apparently, a preferred C3′‐endo sugar pucker within the V‐loop architecture outweighs the propensity of the FrG analogue to adopt an anti glycosidic conformation. Refolding into a V‐loop topology is likewise observed for a sequence modified at corresponding positions with two riboguanosine substitutions. In contrast, 2′‐F‐arabinoguanosine analogues with their favored south‐east sugar conformation do not support formation of the V‐loop topology. Examination of known G‐quadruplexes with a V‐shaped loop highlights the critical role of the sugar conformation for this distinct structural motif.
Peralkynylated Tetraazaacene Derivatives
Authors: Reiss Hilmar , Rominger Frank , Freudenberg Jan , Bunz Uwe H. F.
Published: October 2019

The synthesis of a decaethynylated tetraazapentacene is described. It was obtained by a combination of condensation reactions giving the two pyrazine rings and subsequent consecutive Stille‐type couplings. This is the first example of any higher (hetero)acene that is peralkynylated. The presence of the four nitrogen atoms removes the peri interaction of the substituted alkyne groups, giving this rock‐stable and highly twisted heteroacene.
A Highly Stabilized Phosphonium Ylide that Forms Supramolecular Dimers in Solution and the Solid State
Authors: Kim Min Ji , Luo Stella M. , Greenlee Andrew J. , Young Victor G. , Cao Dennis D.
Published: October 2019

This work describes the unexpected formation of an unusual phosphonium ylide when attempting the synthesis of bisphosphonium pyromellitic diimides. Spectroscopic and crystallographic characterization reveals that a combination of π–π and CH⋅⋅⋅O interactions leads to supramolecular homodimerization of the ylide both in solution and in the solid‐state. Only strong acids are able to protonate the ylide, which is otherwise inert to Wittig and alkylation reactivity. Taken together, these observations indicate that this compound is one of the most highly stabilized phosphonium ylides discovered to date.
Saturated N‐Heterocyclic Carbene Based Thiele's Hydrocarbon with a Tetrafluorophenylene Linker
Authors: Kundu Gargi , De Sriman , Tothadi Srinu , Das Abhishek , Koley Debasis , Sen Sakya S.
Published: October 2019

The synthesis of a SIPr [1,3‐bis(2,6‐diisopropylphenyl)‐imidazolin‐2‐ylidene] derived Kekulé diradicaloid with a tetrafluorophenylene spacer (3) has been described. Two synthetic routes have been reported to access 3. The cleavage of C−F bond of C6F6 by SIPr in the presence of BF3 led to double C−F activated compound with two tetrafluoro borate counter anions (2), which upon reduction by lithium metal afforded 3. Alternatively, 3 can be directly accessed in one step by reacting SIPr with C6F6 in presence of Mg metal. Compounds 2 and 3 were well characterized spectroscopically and by single‐crystal X‐ray diffraction studies. Experimental and computational studies support the cumulenic closed‐shell singlet state of 3 with a singlet‐triplet energy gap (ΔES–T) of 23.7 kcal mol−1.
Theoretical Investigation of Cyano‐Chalcogen Dimers and Their Importance in Molecular Recognition
Authors: Previtali Viola , Sánchez‐Sanz Goar , Trujillo Cristina
Published: October 2019

In this manuscript the different noncovalent interactions established between (HYCN)2dimers (Y=S, Se and Te) have been studied at the MP2 and CCSD(T) level of theory. Several homodimers have been taken into account, highlighting the capacity of these compounds to act both as electron donor and acceptor. The main properties studied were geometries, binding energy (Eb), and molecular electrostatic potential (MEP). Given the wide application of chalcogen bonds, and more specifically of cyano‐chalcogen moieties in molecular recognition, natural bond orbital (NBO), “atoms‐in‐molecules” (AIM), and electron density shift (EDS) analysis were also used to analyse the different noncovalent interactions upon complexation. The presence of hydrogen, chalcogen and dipole‐dipole interactions was confirmed and their implications on molecular recognition were analysed.
Deoxyguanosine is a TLR7 agonist
Authors: Davenne Tamara , Bridgeman Anne , Rigby Rachel E. , Rehwinkel Jan
Published: October 2019

Toll‐like receptor 7 (TLR7) is an innate immune sensor for single‐strand RNA (ssRNA). Recent structural analysis revealed that TLR7 has an additional binding site for nucleosides such as guanosine, and is activated when both guanosine and ssRNA bind. The nucleoside binding site also accommodates imidazoquinoline derivatives such as R848, which activate TLR7 in the absence of ssRNA. Here, we report that deoxyguanosine (dG) triggered cytokine production in murine bone marrow derived macrophages and plasmacytoid dendritic cells, as well as in human peripheral blood mononuclear cells, including type I interferons and pro‐inflammatory factors such as TNF and IL‐6. This signalling activity of dG was dependent on TLR7 and its adaptor MyD88 and did not require amplification via the type I interferon receptor. dG‐triggered cytokine production required endosomal maturation but did not depend on the concurrent provision of RNA. We conclude that dG induces an inflammatory response through TLR7 and propose that dG is an RNA‐independent TLR7 agonist.
In situ Electrochemical Synthesis of a Composite Film Containing Nickel Hexacyanoferrate and Bentonite Clay for the Sensitive Determination of Acetaminophen and Dopamine
Authors: Yadav Mamta , Singh Preeti , Ganesan Vellaichamy , Gupta Rupali , Sonkar Piyush Kumar , Yadav Dharmendra Kumar
Published: October 2019

A composite film of nickel hexacyanoferrate (NiHCF) and bentonite (Bt) clay (abbreviated as NiHCF−Bt) is synthesized by an in situ electrochemical method. For this synthesis, nickel ions are immobilized on Bt clay by an ion‐exchange process, equilibrating Bt clay with nickel nitrate. On a glassy carbon electrode (GCE), the nickel ion‐exchanged Bt clay (Ni2+−Bt) is coated to get the modified electrode which is represented as GCE/Ni2+−Bt. The NiHCF−Bt composite film is prepared on the GCE surface using the GCE/Ni2+−Bt and scanning the electrode potentials between −0.10 to 1.00 V continuously in an aqueous solution containing potassium hexacyanoferrate and potassium chloride. This NiHCF−Bt modified GCE (GCE/NiHCF−Bt) exhibits redox peaks due to the oxidation and reduction of the central metal ion, Fe2+. The electro‐generated Fe3+ present in the GCE/NiHCF−Bt, electrocatalytically oxidizes a range of drugs like acetaminophen (AC), dopamine (DA), and tyrosine (TY) at decreased overpotentials with high current. This property is advantageously used for the precise quantification of AC, DA, and TY. Sensitivity, limit of detection, and linear calibration range for the determination of AC are found to be 0.20 μA μM−1 cm−2, 1.5 μM, and 25.0–1000.0 μM, respectively. Further, the amount of AC present in pharmaceutical products is satisfactorily quantified which demonstrated the use of the NiHCF−Bt composite film in electroanalysis.
Activated hepatic stellate cells promote angiogenesis in hepatocellular carcinoma by secreting angiopoietin‐1
Authors: Lin Nan , Meng Lili , Lin Jizong , Chen Shuxian , Zhang Peng , Chen Qilong , Lin Yang
Published: October 2019

Angiogenesis is the central pathological process in hepatocellular carcinoma (HCC), and its progression is affected by tumor cells and the microenvironment. Activated hepatic stellate cells (aHSCs) are the most significant stromal cells involved in HCC. This study was aimed to explore the effects and mechanisms of aHSCs on angiogenesis in HCC. We isolated primary hepatoma cells, aHSCs, and hepatic vascular endothelial cells from human HCC samples. Then, we performed a novel in vitro assay and in vivo experiment in a nude mouse HCC model to investigate the functions of aHSCs on angiogenesis in HCC. Our results demonstrated that aHSCs are the primary sources of angiopoietin‐1 (Ang‐1) in human HCC in vitro, and aHSCs could promote hepatic vascular endothelial cell (HVEC) growth by secreting Ang‐1. Furthermore, aHSCs could induce HVEC microtubule formation, and this ability was reduced when Ang‐1 expression was silenced in aHSCs. In addition, CD34 expression in a nude mouse HCC model was downregulated when Ang‐1 messenger RNA was silenced in aHSCs. Our data also indicated that HSC Ang‐1 expression could be inhibited by overexpressing Raf kinase inhibitor protein. Therefore, we suggest that aHSCs promote angiogenesis through secreting Ang‐1, potentially providing an interesting target for antiangiogenic therapies for HCC.
Long noncoding RNA LINC00319 regulates ROMO1 expression and promotes bladder cancer progression via miR‐4492/ROMO1 axis
Authors: Yang Yu , Zhang Fangyi , Huang Hang , Xie Zhiyue , Huang Weiping , Xie Hui , Wang Feng
Published: October 2019

Growing reports indicate that long noncoding RNA (lncRNA) are involved in the regulation of various biological processes of cancer cells. LINC00319 is an ill investigated lncRNA and has been shown to regulate lung cancer, nasopharyngeal carcinoma and ovarian cancer. Nevertheless, its roles in bladder cancer (BCa) remain unclear. In our research, LINC00319 was shown to be an upregulated lncRNA in BCa tissues. LINC00319 expression is negatively correlated with the patient's prognosis. Silencing of LINC00319 suppressed BCa proliferation and invasiveness. In addition, the data indicated LINC00319 was a sponge for miR‐4492 and miR‐4492 suppressed ROMO1 expression in BCa. Furthermore, our results illustrated miR‐4492/ROMO1 axis regulates proliferation, migration, and invasion and LINC00319 exerts oncogenic roles through modulating miR‐4492/ROMO1 axis. In sum, this study suggested that LINC00319 acts as oncogenic roles in BCa progression.
Complicated trafficking behaviors involved in paradoxical regulation of sortilin in lipid metabolism
Authors: Sun Sha , Yang Jing , Xie Wei , Peng Tianhong , Lv Yuncheng
Published: October 2019

This review aims to summarize and discuss the most recent advances in our understanding of the underlying mechanisms of the paradoxical effects of sortilin on lipid metabolism. The vacuolar protein sorting 10 protein (Vps10p) domain in the sortilin protein is responsible for substrate binding. Its cytoplasmic tail interacts with adaptor molecules, and modifications can determine whether sortilin trafficking occurs via the anterograde or retrograde pathway. The complicated trafficking behaviors likely contribute to the paradoxical roles of sortilin in lipid metabolism. The anterograde pathway of sortilin trafficking in hepatocytes, enterocytes, and peripheral cells likely causes an increase in plasma lipid levels, while the retrograde pathway leads to the opposite effect. Hepatocyte sortilin functions via the anterograde or retrograde pathway in a complicated and paradoxical manner to regulate apoB‐containing lipoprotein metabolism. Clarifying the regulatory mechanisms underlying the trafficking behaviors of sortilin is necessary and may lead to artificial sortilin intervention as a potential therapeutic strategy for lipid disorder diseases. Conclusively, the paradoxical regulation of sortilin in lipid metabolism is likely due to its complicated trafficking behaviors.
Peripheral nerve injury and myelination: Potential therapeutic strategies
Authors: Modrak Max , Talukder M. A. Hassan , Gurgenashvili Khatuna , Noble Mark , Elfar John C.
Published: October 2019

Traumatic peripheral nerve injury represents a major clinical and public health problem that often leads to significant functional impairment and permanent disability. Despite modern diagnostic procedures and advanced microsurgical techniques, functional recovery after peripheral nerve repair is often unsatisfactory. Therefore, there is an unmet need for new therapeutic or adjunctive strategies to promote the functional recovery in nerve injury patients. In contrast to the central nervous system, Schwann cells in the peripheral nervous system play a pivotal role in several aspects of nerve repair such as degeneration, remyelination, and axonal growth. Several non‐surgical approaches, including pharmacological, electrical, cell‐based, and laser therapies, have been employed to promote myelination and enhance functional recovery after peripheral nerve injury. This review will succinctly discuss the potential therapeutic strategies in the context of myelination following peripheral neurotrauma.
Quadriceps Muscle Size Following ACL Injury and Reconstruction: A Systematic Review
Authors: Birchmeier Thomas , Lisee Caroline , Kane Kevin , Brazier Brett , Triplett Ashley , Kuenze Christopher
Published: October 2019

Image‐based assessments of quadriceps muscle size facilitate examination of structural changes after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Understanding the effects of ACLR on muscle size measures may aid in clarifying the contribution of quadriceps atrophy toward quadriceps strength. The purpose of this study was to systematically review the literature examining the effects of ACLR on quadriceps muscle volume and cross‐sectional area (CSA). An online database search was conducted using Web of Science, SportDISCUS, PubMed (Medline), CINHAL (EBSCO), and Cochrane Library limited to articles published after January 1, 1980. Means and standard deviations were extracted for the ACLR limb and the contralateral limb, and sample characteristics from relevant articles. Magnitude of between limb differences were assessed using pooled effect sizes (Hedge's g) and 95% confidence intervals. Eleven articles (five CSA, six muscle volume) were included in this systematic review. Included studies reported negative effective sizes, indicating that the ACLR limb was smaller in CSA or muscle volume compared with the contralateral limb; however, 36% of the included articles reported meaningful difference between the limbs. Quadriceps atrophy may occur following ACL injury and persist after rehabilitation, however, the magnitude of these reductions may not be clinically meaningful and may only partially explain the persistent quadriceps weakness that is ubiquitous among this patient population. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:598–608, 2020
Effects of Sprifermin, IGF1, IGF2, BMP7, or CNP on Bovine Chondrocytes in Monolayer and 3D Culture
Authors: Müller Sylvia , Lindemann Sven , Gigout Anne
Published: October 2019

One possible approach to treat osteoarthritis (OA) is to counteract cartilage degeneration with anabolic compounds that stimulate chondrocyte proliferation and/or extracellular matrix (ECM) production. Several molecules including sprifermin (recombinant human fibroblast growth factor [FGF18]), insulin‐like growth factor‐1 [IGF1] and ‐2 [IGF2], C‐type natriuretic peptide [CNP], and bone metamorphic protein 7 [BMP7] have been shown to have these characteristics both in vitro and in vivo. However, it is not known how these molecules compare each other regarding their effect on phenotype and stimulation of ECM production in primary chondrocytes. The effects of sprifermin, IGF1, IGF2, CNP, and BMP7 were evaluated on bovine articular chondrocytes, first in monolayer to determine their effective concentrations, and then in three‐dimensional (3D) culture at concentrations of 100 ng/ml for sprifermin; 300 ng/ml for IGF1, IGF2, and BMP7; and 10 nM for CNP. In 3D culture, the effects of a permanent exposure or a cyclic exposure consisting of 24 h incubation per week with the compounds were evaluated. All growth factors increased ECM production and cell proliferation to a similar extent but CNP had almost no effect on bovine chondrocytes. Sprifermin was more effective with cyclic exposure, IGF1, and IGF2 with permanent exposure, and BMP7 showed similar results with both exposures. Regarding the cell phenotype, sprifermin appeared to be the only compound favoring the chondrocyte phenotype; it decreased type I collagen expression and had no hypertrophic effect. Together, these results confirmed that sprifermin is a promising disease‐modifying OA drug. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:653–662, 2020
BMSCs‐Derived Exosomes Ameliorate Pain Via Abrogation of Aberrant Nerve Invasion in Subchondral Bone in Lumbar Facet Joint Osteoarthritis
Authors: Li Jinsong , Ding Zhiyu , Li Yuezhan , Wang Weiguo , Wang Jianlong , Yu Haiyang , Liu Ansong , Miao Jinglei , Chen Shijie , Wu Tianding , Cao Yong
Published: October 2019

Lumbar facet joint osteoarthritis (LFJ OA) is regarded as one of the common causes of low back pain (LBP). The pathogenesis and underlying mechanism of this disease are largely unknown, there is still no effective disease‐modifying therapy. This study aims to investigate the efficacy of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the pathogenesis and behavioral signs of LBP in the LFJ OA mouse model. The pathogenetic change in cartilage and aberrant nerve invasion in the subchondral bone of LFJ in a mouse model after treatment with BMSC‐exosomes was evaluated. BMSC‐exosomes could relieve pain via abrogation of aberrant CGRP‐positive nerve and abnormal H‐type vessel formation in the subchondral bone of LFJ. Moreover, BMSC‐exosomes attenuated cartilage degeneration and inhibited tartrate‐resistant acid phosphatase expression and RANKL‐RANK‐TRAF6 signaling activation to facilitate subchondral bone remodeling. These results indicated that BMSC‐exosomes could relive behavioral signs of LBP and pathological processes in LFJ OA. BMSC‐exosomes have a prominent protective effect and might be a potential therapeutic option for the treatment of LFJ OA causing LBP. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:670–679, 2020
Low‐Dielectric Constant and Low‐Temperature Curable Polyimide/POSS Nanocomposites
Authors: Huang Chao , Li Jinhui , Xie Guangxia , Han Fei , Huang Dongxu , Zhang Fan , Zhang Bo , Zhang Guoping , Sun Rong , Wong Ching‐Ping
Published: October 2019

With the rapid development of ultra large scale integrated circuits, low stress, low thermal expansion, low dielectric constant, and low temperature curable (<250 °C) polyimides (PIs) with excellent mechanical, thermal properties are required. Unfortunately, high curing temperatures above 300 °C and limited dielectric property still remain to be solved. Herein, a new type of aminopropyl isobutyl polysilsesquioxane (POSS) with single vertex activity is introduced by in situ polymerization resulting in the PI‐POSS nanocomposites which exhibit a low dielectric constant (κ ≤ 2.6). Furthermore, low‐temperature curing at 200 °C (99.4% imidization) under the catalysis of quinoline is also achieved. The as‐prepared PI‐POSS nanocomposites also show excellent mechanical properties of which the tensile strength can reach up to 148 MPa and the elongation at break achieves 98%. Moreover, the temperature of weight loss 5% is as high as 550 °C and the glass transition temperature can also reach 349 °C. The as‐prepared PI‐POSS nanocomposites prove excellent electrical performance and mechanical properties, showing a huge market prospect of 5G chip packaging and millimeter wave antenna in the future.
Diversity of small molecule HIV‐1 latency reversing agents identified in low‐ and high‐throughput small molecule screens
Authors: Hashemi Pargol , Sadowski Ivan
Published: October 2019

The latency phenomenon produced by human immunodeficiency virus (HIV‐1) prevents viral clearance by current therapies, and consequently development of a cure for HIV‐1 disease represents a formidable challenge. Research over the past decade has resulted in identification of small molecules that are capable of exposing HIV‐1 latent reservoirs, by reactivation of viral transcription, which is intended to render these infected cells sensitive to elimination by immune defense recognition or apoptosis. Molecules with this capability, known as latency‐reversing agents (LRAs) could lead to realization of proposed HIV‐1 cure strategies collectively termed “shock and kill,” which are intended to eliminate the latently infected population by forced reactivation of virus replication in combination with additional interventions that enhance killing by the immune system or virus‐mediated apoptosis. Here, we review efforts to discover novel LRAs via low‐ and high‐throughput small molecule screens, and summarize characteristics and biochemical properties of chemical structures with this activity. We expect this analysis will provide insight toward further research into optimized designs for new classes of more potent LRAs.
Dynamics of a Majorana Trijunction in a Microwave Cavity
Authors: Trif Mircea , Simon Pascal
Published: October 2019

A trijunction made of three topological semiconducting wires, each supporting a Majorana bound state (MBS) at its two extremities, appears as one of the simplest geometries in order to perform braiding of Majorana fermions. Embedding the trijunction into a microwave cavity allows to study the intricate dynamics of the low‐energy MBSs coupled to the cavity electric field under a braiding operation. Extending a previous work [Phys. Rev. Lett. 2019, 122, 236803], the full time evolution of the density matrix of the low‐energy states, including various relaxation channels, is computed both in the adiabatic regime, as well as within the Floquet formalism in the case of periodic driving. It turns out that in the stationary state the observables of the system depend on both the parity of the ground state and on the non‐Abelian Berry phase acquired during braiding. The average photon number and the second‐order photon coherence function g(2)(0) are explicitly evaluated and reveal the accumulated non‐Abelian Berry phase during the braiding process.
Van der Waals Integration of Bismuth Quantum Dots–Decorated Tellurium Nanotubes (Te@Bi) Heterojunctions and Plasma‐Enhanced Optoelectronic Applications
Authors: Zhang Ye , Zhang Feng , Wu Leiming , Zhang Yupeng , Huang Weichun , Tang Yanfeng , Hu Lanping , Huang Pu , Zhang Xiuwen , Zhang Han
Published: October 2019

Van der Waals (vdW)‐integrated heterojunctions have been widely investigated in optoelectronics due to their superior photoelectric conversion capability. In this work, 0D bismuth quantum dots (Bi QDs)‐decorated 1D tellurium nanotubes (Te NTs) vdW heterojunctions (Te@Bi vdWHs) are constructed by a facile bottom‐up assembly process. Transient absorption spectroscopy suggests that Te@Bi vdWH is a promising candidate for new‐generation optoelectronic devices with fast response properties. The subsequent experiments and density functional theory calculations demonstrate the vdW interaction between Te NTs and Bi QDs, as well as the enhanced optoelectronic characteristics owing to the plasma effects at the interface between Te NTs and Bi QDs. Moreover, Te@Bi vdWHs‐based photodetectors show significantly improved photoresponse behavior in the ultraviolet region compared to pristine Te NTs or Bi QDs‐based photodetectors. The proposed integration of vdWHs is expected to pave the way for constructing new nanoscale heterodevices.
Assessment of hematologic and corticosterone response in free‐living eastern box turtles (Terrapene carolina carolina) at capture and after handling
Authors: Boers Kayla L. , Allender Matthew C. , Novak Lauren J. , Palmer Jamie , Adamovicz Laura , Deem Sharon L.
Published: October 2019

Hematology is a common tool for wildlife health assessments. Manual leukocyte counts are required in reptiles, however, disagreement between quantification methods has been observed in some chelonians. This study determined agreement between two methods of leukocyte quantification, eosinophilic leukopet, and blood film white blood cell (WBC) estimates, in free‐living eastern box turtles (Terrapene carolina carolina). Simultaneously, we assessed the impact of handling duration on both leukocyte quantity and corticosterone levels. We collected blood at capture (<2 min from disturbance) and again before release 30–150 min later from 92 box turtles at six sites in Illinois and Tennessee. Constant and proportional error was present in the leukopet results for WBC, lymphocytes, and basophils compared to the estimate method. Both methods were in agreement for heterophils, monocytes, and eosinophils. Agreement between the methods was significantly more likely at WBC counts below 23,241/µl. All hematologic parameters were significantly higher at the final blood draw compared to the initial blood draw using both WBC determination methods, except relative eosinophil and basophil counts. Corticosterone levels varied with time, with maximum concentrations reached at 54 min postcapture, followed by a rapid return to baseline levels. Corticosterone level was not significantly associated with any hematologic parameter or sex. This study provides a framework for understanding the effects of animal handling methodology and diagnostic modality when evaluating hematologic health in box turtles.
Dimensional regularization for holographic RG flows
Authors: Bzowski Adam , Schillo Marjorie
Published: October 2019

Abstract

In this work, we present a holographic renormalization scheme for asymptotically anti-de Sitter spacetimes in which the dual renormalization scheme of the boundary field theory is dimensional regularization. This constitutes a new level of precision in the holographic dictionary and paves the way for the exact matching of scheme dependent quantities, such as holographic beta functions, with field theory computations. Furthermore, the renormalization procedure identifies a local source field which satisfies the equations of motion along renormalization group flows, resolving a long-standing puzzle regarding the Wilsonian coupling in holography. This identification of the source field also provides new insight into field theories deformed by marginal operators, which have been traditionally difficult to analyze due to altered bulk asymptotics. Finally, we demonstrate a new relation equating the analyticity of the holographic beta function to the absence of conformal anomalies, and conjecture that the conformal anomaly should vanish in the UV for all holographic constructions.
Proinsulin peptide promotes autoimmune diabetes in a novel HLA-DR3-DQ2-transgenic murine model of spontaneous disease
Authors: Verhagen Johan , Yusuf Norkhairin , Smith Emma L. , Whettlock Emily M. , Naran Kerina , Arif Sefina , Peakman Mark
Published: October 2019

Aims/hypothesis

The molecular basis for the pathological impact of specific HLA molecules on autoimmune diseases such as type 1 diabetes remains unclear. Recent natural history studies in children have indicated a link between specific HLA genotypes and the first antigenic target against which immune responses develop. We set out to examine this link in vivo by exploring the diabetogenicity of islet antigens on the background of a common diabetes-associated HLA haplotype.

Methods

We generated a novel HLA-transgenic mouse model that expresses high-risk genes for type 1 diabetes (DRB1*03:01-DQA1*05:01-DQB1*02:01) as well as human CD80 under the rat insulin promoter and human CD4, on a C57BL/6 background. Adjuvanted antigen priming was used to reveal the diabetogenicity of candidate antigens and peptides.

Results

HLA-DR3-DQ2+huCD4+IA/IE−/−RIP.B7.1+ mice spontaneously developed autoimmune diabetes (incidence 46% by 35 weeks of age), accompanied by numerous hallmarks of human type 1 diabetes (autoantibodies against GAD65 and proinsulin; pancreatic islet infiltration by CD4+, CD8+ B220+, CD11b+ and CD11c+ immune cells). Disease was markedly accelerated and had deeper penetrance after adjuvanted antigen priming with proinsulin (mean onset 11 weeks and incidence 100% by 20 weeks post challenge). Moreover, the diabetogenic effect of proinsulin located to the 15-residue B29-C11 region.

Conclusions/interpretation

Our study identifies a proinsulin-derived peptide region that is highly diabetogenic on the HLA-DR3-DQ2 background using an in vivo model. This approach and the peptide region identified may have wider implications for future studies of human type 1 diabetes.
Response surface methodology for the optimization of acid dye adsorption onto activated carbon prepared from wild date stones
Authors: Brahmi Lamia , Kaouah Farida , Boumaza Salim , Trari Mohamed
Published: October 2019

In the present study,wild date stones(WDS) were used as a novel and sustainable precursor for high-quality activated carbon preparation to be applied for the removal of Acid Blue 25 dye (AB25) from synthetic water. The carbonization temperature of the raw material was selected at 850 °C on the basis of thermo-gravimetric analysis. The adsorbents were characterized by the BET method, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results indicated that the activated carbon presents a high specific surface area (610.84 m2 g−1) and a pore volume (0.224 cm3 g−1) compared with the natural material. Based on the central composite design, the effect of different parameters such as the biomass dose, initial dye concentration, contact time and temperature was optimized and the optimal removal of AB25 (99.61%) was achieved for AB25 concentration of 100 mg L−1and an adsorbent dose of 0.8 g L−1, at 45 °C after 120 min. The kinetic studies indicated that the pseudo-second-order model was appropriately applied for the adsorption kinetic of AB25 onto wild date stones activated carbon. The intraparticle diffusion model is not the only controlling step, and other mechanisms may be involved in the adsorption process. The Langmuir isotherm provided the best fit with a high correlation coefficient (R2) of 0.993 and a maximum monolayer adsorption capacity of 181.59 mg g−1.
Comparison of the experimental results with the Langmuir and Freundlich models for copper removal on limestone adsorbent
Authors: Khayyun Thair Sharif , Mseer Ayad Hameed
Published: October 2019

The purpose of this study was to investigate the possibility of the limestone as an adsorbed media and low-cost adsorbent. Batch adsorption studies were conducted to examine the effects of the parameters such as initial metal ion concentration C0, particle size of limestone DL, adsorbent dosage and equilibrium concentration of heavy metal Ce on the removal of the heavy metal (Cu) from synthetic water solution by limestone. The removal efficiency is increased with the increase in the volume of limestone (influenced by the media specific area). It has been noted that the limestone with diameter of 3.75 is the most effective size for removal of copper from synthetic solution. The adsorption data were analyzed by the Langmuir and Freundlich isotherm model. The average values of the empirical constant and adsorption constant (saturation coefficient) for the Langmuir equation were a = 0.022 mg/g and b = 1.46 l/mg, respectively. The average values of the Freundlich adsorption constant and empirical coefficient were Kf = 0.010 mg/g and n = 1.58 l/mg, respectively. It was observed that the Freundlich isotherm model described the adsorption process with high coefficient of determination R2, better than the Langmuir isotherm model and for low initial concentration of heavy metal. Also, when the values of amount of heavy metal removal from solution are predicted by the Freundlich isotherm model, it showed best fits the batch study. It is clear from the results that heavy metal (Cu) removal with the limestone adsorbent appears to be technically feasible and with high efficiency.
The Proof Is in the Process: Self-Reporting Under International Human Rights Treaties
Authors: Creamer Cosette D. , Simmons Beth A.
Published: October 2019

Recent research has shown that state reporting to human rights monitoring bodies is associated with improvements in rights practices, calling into question earlier claims that self-reporting is inconsequential. Yet little work has been done to explore the theoretical mechanisms that plausibly account for this association. This Article systematically documents—across treaties, countries, and years—four mechanisms through which reporting can contribute to human rights improvements: elite socialization, learning and capacity building, domestic mobilization, and law development. These mechanisms have implications for the future of human rights treaty monitoring.
Vestibular Exercises as a Fall Prevention Strategy in Patients with Cognitive Impairment
Authors: Varriano Brenda , Sulway Shaleen , Wetmore Curtis , Dillon Wanda , Misquitta Karen , Multani Namita , Anor Cassandra , Martinez Maria , Cacchione Elena , Rutka John , Tartaglia Maria Carmela
Published: October 2019

Vestibular impairment (VI) and cognitive impairment (CI) are risk factors for senior falls. We tested the feasibility of a self-directed 12-week vestibular rehabilitation (VR) program in Memory Clinic patients (65 years+) with a fall, CI and VI. We assessed recruitment, exercise adherence and ability to complete questionnaires/assessments. Twelve patients with CI and falls were screened and 8/12 (75% – prevalence) had VI. All patients completed the screening tests/questionnaires (100% – completeness); 7/8 patients were recruited (87.5% – recruitment); 1/7 (85.7% – attrition) patient attended follow-up. VI is prevalent in patients with CI experiencing falls but traditional VR is not feasible, so a novel delivery of VR must be explored.
Navigating Inland: Bronze Age Watercraft and the Lakes of Southern Sweden
Authors: Nimura Courtney , Skoglund Peter , Bradley Richard
Published: October 2019

The rock art of southern Scandinavia is characterized by depictions of watercraft. The majority are close to the coast, and they have been the primary focus of research. Less attention has been paid to similar representations associated with two large inland lakes in southern Sweden. In this article we present the results of fieldwork around Lake Vänern and Lake Vättern and consider the relationship of this rock art to the better-known images on the coast. We explore the practicalities of navigating between the sea and the interior and suggest that there was an important contrast between an early eastern sphere extending to Lake Vättern from the Baltic and a later western sphere connecting Lake Vänern with the Atlantic.
Persistent Patterns in the U.S. Alcohol Market: Looking at the Link between Demographics and Drinking
Authors: Hart Jarrett , Alston Julian M.
Published: October 2019

Global consumption patterns for alcoholic beverages are evolving, with some convergence in per capita consumption among nations, as traditionally beer-drinking nations increase their consumption of wine and, conversely, wine-consuming nations shift towards beer. In a forthcoming article (Hart and Alston, 2019), we explore regional patterns of alcoholic beverage consumption within the United States. One purpose is to see if similar patterns of spatial convergence in consumption patterns can be observed within countries as have been documented in international comparisons. A more fundamental purpose is to explore the converse question and seek to better understand the persistent differences in alcoholic beverage consumption among groups. These issues are addressed using annual U.S. national and state-level data over four decades and, for the more recent period, supermarket scanner data at finer scales of geopolitical aggregation. This proceedings article focuses on the analysis using supermarket scanner data. We find that socioeconomic and demographic variables appear to play significant roles in accounting for the spatial differences in consumption patterns. (JEL Classifications: D12, L66)
Power, competition, and the nature of history
Authors: Vermeij Geerat J.
Published: October 2019

Historians have debated whether pathways and events from the past to the present are influenced largely by contingency, the dependence of outcomes on particular prior conditions, or whether there is long-term emergent directional change. Previous arguments for predictability in evolutionary history relied on the high frequency of convergence, but the repeated evolution of widely favored adaptations need not imply long-term directionality. Using evidence from the fossil record and arguments concerning the metabolic evolution of organisms, I show here that power (total energy taken up and expended per unit time) has increased stepwise over time at ecosystem-level and global scales thanks to the ratchet-like, cumulative effects of competition and cooperation and to the disproportionate influence of powerful top competitors and opportunistic species on emergent ecosystem properties and processes. The history of life therefore exhibits emergent directionality at large ecosystem-wide scales toward greater power.
Height inequality and socioeconomic implications in Korea: analysis of individuals born between 1890 and 1919
Authors: Choi Seong-jin
Published: October 2019

This study examined height inequality as an indicator of income inequality during the colonial period (1910–1945) in Korea. Data were taken from a sample of 1796 male prisoners from a wide range of geographical locations and with varied socioeconomic backgrounds. Height inequality was measured using the coefficient of variation of height (CV) for each birth decade. The results indicated that height inequality, as measured by the CV, increased slightly from 3.32 to 3.35 for the birth decades 1890–99 and 1900–09, then jumped to 3.50 for the birth decade 1910–19. Considering the Kuznets curve, the presented results have socioeconomic implications for Japan’s impact in Korea, at least during the early colonial period.
Towards meaningful mobility: a research agenda for movement within and between places in later life
Authors: Meijering Louise
Published: October 2019

Mobility or physical movement contributes to health and wellbeing in later life. Most studies have focused on the contribution of outdoor mobility to active ageing, but physical and cognitive impairments restrict the mobility of many older adults. This article aims to explore the gaps in the current literature on mobility in later life, and identify required innovations in the field through laying out key areas for future research. It discusses two, largely separate, areas of research, namely on mobility patterns and mobility experiences. The first focuses on quantitative and spatial research on outdoor mobility patterns in terms of routes, timing and transport modes. The second mainly concerns qualitative research on how older adults perceive mobility in their everyday lives. This article identifies three areas for future research on mobility in later life: (a) beyond outdoor movement; (b) diversity in mobility; and (c) the role of time in mobility. To conclude, addressing these areas jointly will contribute to further unpacking the concept of mobility as meaningful practice and to integrating quantitative and qualitative methods when studying mobility in later life. This will result in policy inputs on the mobility and wellbeing of our ageing population.
Quintuple-mode wideband bandpass filters with improved out-of-band rejection
Authors: Hameed Musab , Xiao Gaobiao , Qiu Lina , Hameed Tayyab
Published: October 2019

This paper presents design of quintuple-mode wideband bandpass filters, implemented with off-centered perturbed metallic cylinders in a rectangular waveguide cavity. Three perturbation cylinders are placed at the bottom of the rectangular waveguide cavity, along with a pair of perpendicularly fed coaxial lines; excite five quasi-transverse magnetic modes to realize the desired passband. The height of the waveguide cavity and the shape of the perturbation cylinders are exploited to shift the resonant modes far away from the passband and achieve a good out-of-band rejection and sharp skirt selectivity. The filter operates at the center frequency of 2.68 GHz with a wide fractional bandwidth of 43%. The proposed filter is fabricated with aluminum. The measured and simulated results are in good agreement with each other.
Variation of Iron Species in Plagioclase Crystals by X‐ray Absorption Fine Structure Analysis
Authors: Nakada Ryoichi , Sato Masahiko , Ushioda Masashi , Tamura Yujiro , Yamamoto Shinji
Published: October 2019

Speciation analysis of Fe in single plagioclase crystals separated from two different gabbros was performed to understand the crystallization mechanisms of magnetite exsolution. Iron species in single crystals were measured using Fe K‐ and LIII‐edge X‐ray absorption fine structure (XAFS) analysis. The K‐edge pre‐edge analysis showed variation in the averaged valence state of Fe in plagioclase crystals even if they had been separated from the same gabbro that was further confirmed by the LIII‐edge analysis. The K‐edge pre‐dedge analysis also suggests the various degrees of contribution from tetrahedral Fe. The mixing of tetrahedral and octahedral Fe leads to an underestimation of the averaged valence state of Fe for the K‐edge pre‐edge analysis; thus, we adopted the LIII‐edge result for the valence state of Fe in plagioclase crystals. Iron K‐edge extended XAFS (EXAFS) analysis of two plagioclase crystals separated from the same gabbro clearly showed different coordination environments. A weakening of EXAFS oscillation was recognized in one sample, because two Fe–O bonds (Fe3+–O1 and Fe2+–O2) cancelled out the oscillations of each other. The EXAFS spectrum of the other plagioclase crystal suggested a homogeneous distribution of Fe. The content of exsolved magnetite in these crystals is nearly identical, indicating that the exsolution of magnetite in plagioclase crystal had been completed before the temperature decrease that stopped the ordering of Fe ions in tetrahedral sites.
Subseafloor Fluid and Chemical Fluxes Along a Buried‐Basement Ridge on the Eastern Flank of the Juan de Fuca Ridge
Authors: Hulme Samuel M. , Wheat C. Geoffrey
Published: October 2019

Hydrothermal circulation of low‐temperature fluids within oceanic crust affects global biogeochemical cycles. We present data from a warm temperature (64 °C) hydrothermal system on the eastern flank of the Juan de Fuca Ridge to assess whether chemical fluxes to the ocean from these systems arise from the basaltic crust or the overlying sediment pore waters. Extensive sampling of this system included fluid chemical data from deep sea drilling, gravity coring, and submersible operations from five sites on a buried ridge that is parallel to the spreading center to the west. These data were subjected to a transport (advection‐diffusion) model to constrain chemical and fluid fluxes along this five‐site transect. Solutes (K, Cl, sulfate, Ba, Sr, Cs, Mo, and Y) that are nonreactive within the basaltic crust constrain the volumetric fluid flux per unit width within the basaltic crust from 0.05 to 0.2 m3 ·year−1 · cm−1, consistent with a recent tracer study. Using this average fluid flux, reactive fluxes were determined for twenty‐four solutes and partitioned among seawater, sediment and basaltic sources and sinks. Only Ca, Ce, and Gd were released from basaltic basement to the ocean, whereas other solutes (sulfate, Mg, K, Li, Rb, Cd, U, Y, Yb, Gd, and La) were consumed in the basaltic crust, and still others (Cl, Ba, Sr, Cs, Mo, Mn, Fe, Co, NH3, and Zn) had a sediment origin with a net flux to the ocean. Diffusive exchange with the overlying sediment had a greater impact than seawater‐basalt reactions for some solutes.