bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Antibacterial Development Risk for GSK1322322 by Exploring Potential Human Dose Regimens in Nonclinical Efficacy Studies Using Immunocompetent Rats
Authors: Hoover Jennifer L. , Singley Christine M. , Elefante Philippa , DeMarsh Peter , Zalacain Magdalena , Rittenhouse Stephen
Published: August 2017

Directly testing proposed clinical dosing regimens in nonclinical studies can reduce the risk during the development of novel antibacterial agents. Optimal dosing regimens can be identified in animal models by testing recreated human pharmacokinetic profiles. An example of this approach using continuous intravenous infusions of GSK1322322 in immunocompetent rats to evaluate recreated human exposures from phase I trials in pneumonia models with
Streptococcus pneumoniae
and
Haemophilus influenzae
and an abscess model with
Staphylococcus aureus
is presented. GSK1322322 was administered via continuous intravenous infusion to recreate 1,000- or 1,500-mg oral doses every 12 h in humans. Significant reductions (
P
≤ 0.05 for all comparisons) in bacterial numbers compared with those for the baseline controls were observed for
S. pneumoniae
and
H. influenzae
(mean log
10
reductions, 1.6 to ≥2.7 and 1.8 to 3.3 CFU/lungs, respectively) with the recreated 1,000-mg oral dose. This profile was also efficacious against
S. aureus
(mean log
10
reduction, 1.9 to 2.4 CFU/abscess). There was a nonsignificant trend for improved efficacy against
S. aureus
with the 1,500-mg oral dose (mean log
10
reduction, 2.4 to 3.1 CFU/abscess). These results demonstrate that the human oral 1,000- or 1,500-mg exposure profiles of GSK1322322 recreated in rats were effective against representative community-associated pathogens and supported selection of the 1,500-mg oral dose given every 12 h for a phase II clinical skin infection study. Furthermore, this work exemplifies how the testing of recreated human pharmacokinetic profiles can be incorporated into the development process and serve as an aid for selecting optimal dosing regimens prior to conducting large-scale clinical studies.
The
rph-1
-Encoded Truncated RNase PH Protein Inhibits RNase P Maturation of Pre-tRNAs with Short Leader Sequences in the Absence of RppH
Authors: Bowden Katherine E. , Wiese Nicholas S. , Perwez Tariq , Mohanty Bijoy K. , Kushner Sidney R.
Published: August 2017

RNase PH, encoded by the
rph
gene, is a 3′→5′ exoribonuclease that in
E. coli
participates primarily in the 3′ maturation of pre-tRNAs and the degradation of rRNA in stationary-phase cells. Interestingly, the routinely used laboratory strains of MG1655 and W3110 have naturally acquired the
rph-1
allele, encoding a truncated catalytically inactive RNase PH protein which is widely assumed to be benign. Contrary to this assumption, we show that the
rph-1
-encoded Rph-1 protein inhibits RNase P-mediated 5′-end maturation of primary pre-tRNAs with leaders of <5 nucleotides in the absence of RppH, an RNA pyrophosphohydrolase. In contrast, RppH is not required for 5′-end maturation of endonucleolytically generated pre-tRNAs in the
rph-1
strain and for any tRNAs in Δ
rph
mutant or
rph

+

strains. We propose that the Rph-1 protein bound to the 3′ end of the substrate creates a steric hindrance that in the presence of a triphosphate at the 5′ end reduces the ability of RNase P to bind to the pre-tRNA.

IMPORTANCE
In this paper, we demonstrate that the
rph-1
mutation found in commonly used
E. coli
strains leads to the synthesis of a truncated functionally inactive RNase PH protein that interferes with the 5′-end maturation of specific tRNAs with short 5′ leaders by RNase P in the absence of RppH, an RNA pyrophosphohydrolase that converts primary 5′ triphosphates into 5′ monophosphates. The data presented indicate that the presence of the triphosphate interferes with RNase P binding to the pre-tRNA.
Use of multielement stable isotope ratios to investigate ontogenetic movements of Micropogonias furnieri in a tropical Brazilian estuary
Authors: Pizzochero Ana Carolina , Michel Loïc N. , Chenery Simon R. , McCarthy Ian D. , Vianna Marcelo , Malm Olaf , Lepoint Gilles , Das Krishna , Dorneles Paulo R.
Published: August 2017

The whitemouth croaker, Micropogonias furnieri, is a long-lived fish of high commercial importance in the western Atlantic Ocean. Here, we used stable isotope ratios of carbon, sulfur, and nitrogen and isotopic niche metrics (SIBER) to study feeding habits and track habitat use by whitemouth croakers in Guanabara Bay, an estuary in Rio de Janeiro state, Brazil. Our results highlighted size-related habitat segregation, with small juvenile fishes (<30 cm) residing mostly inside estuaries and large adult fishes (>60 cm) feeding mainly in Continental Shelf waters. Medium adult fishes (30–60 cm) appear to feed in multiple coastal and Continental Shelf habitats. Moreover, their feeding ecology showed strong temporal differences, linked with seasonal and, to a lesser extent, interannual variation in oceanographic features of the ecosystem in which they live. Overall, these differences in ecological features suggest that (1) adult and juvenile whitemouth croakers should be treated as different components of the food web and (2) the conservation of these habitats should be prioritized to better manage and sustain the coastal fisheries in Guanabara Bay.
Accounting for uncertainty due to data processing in virtual population analysis using Bayesian multiple imputation
Authors: Carruthers Thomas , Kell Laurence , Palma Carlos
Published: August 2017

Virtual population analysis (VPA) is used in many stock assessment settings and requires a total catch-at-age data set where an age is assigned to each fish that has been caught. These data sets are typically constructed using ad hoc methods that rely on numerous assumptions. Although approaches are available to account for observation error in these data, no statistically rigorous methods have been developed to account for uncertainty from data processing. To address this, we investigated a Bayesian multiple imputation approach to filling missing size data. Using Atlantic yellowfin tuna (Thunnus albacares) and bigeye tuna (Thunnus obesus) as case studies, we evaluated the hypothesis that data processing is as important in determining management reference points in stock assessments as conventional sources of uncertainty. Size imputation models accounting for location, season, and year provided good predictive capacity. Uncertainty from data processing could be large; however, the circumstances for this were unpredictable and varied depending on the stock. These results indicate that VPA assessments should attempt to account for uncertainty in data processing to avoid potentially large compression of uncertainty in assessment results.
Heat transfer and flow of nanofluids: Effect of shear thinning viscosity
Authors: Wu Wei-Tao , Li Yubai , Zhou Zhi-Fu
Published: August 2017

In this paper, we study the heat transfer and flow characteristics of a pressure-driven flow of nanofluids between two plates. For modelling the motion of nanoparticles, a concentration convection–diffusion equation is applied, where the effect of the Brownian motion and thermophoretic diffusion are included. We consider that the shear viscosity and the thermal conductivity of the nanofluids depend on the concentration of the nanoparticles. Furthermore, the viscosity is also a function of shear rate, which has been widely observed by many experiments. The flow is assumed to be fully developed and steady state. The effect of the dimensionless parameters related to shear thinning viscosity, thermal diffusivity, particle transport flux, etc., are studied numerically.
Raising the SUSY-breaking scale in a Goldstone–Higgs model
Authors: Alanne Tommi , Rzehak Heidi , Sannino Francesco , Thomsen Anders Eller
Published: August 2017

We show that by combining the elementary Goldstone–Higgs scenario and supersymmetry it is possible to raise the scale of supersymmetry breaking to several TeVs by relating it to the spontaneous-symmetry-breaking one. This is achieved by first enhancing the global symmetries of the super-Higgs sector to SU(4) and then embedding the electroweak sector and the Standard Model (SM) fermions. We determine the conditions under which the model achieves a vacuum such that the resulting Higgs is a pseudo-Goldstone boson (pGB). The main results are: the supersymmetry-breaking scale is identified with the spontaneous-symmetry-breaking scale of SU(4) which is several TeVs above the radiatively induced electroweak scale; intriguingly the global symmetry of the Higgs sector predicts the existence of two super-Higgs multiplets with one mass eigenstate playing the role of the pseudo-Goldstone Higgs; the symmetry-breaking dynamics fixes [Formula: see text] and requires a supplementary singlet chiral superfield. We finally discuss the spectrum of the model that now features the superpartners of the SM fermions and gauge bosons in the multi-TeV range.
A possible new cosmological redshift effect due to Λ on traveling gravitational waves in Friedmann universes
Authors: Viaggiu Stefano
Published: August 2017

In this paper, we continue the investigation concerning the propagation of gravitational waves in a cosmological background using Laplace transform.aWe analyze the possible physical consequences of the result present in Ref. 19 where it is argued that a nonvanishing positive abscissa of convergence caused by the de Sitter expansion factor [Formula: see text] implies a shift in the frequencies domain of a traveling gravitational wave as measured by a comoving observer. In particular, we show that in a generic asymptotically de Sitter cosmological universe, this redshift effect does also arise. Conversely, in a universe expanding with, for example, a power law expansion, this phenomenon does not happen. This physically possible new redshift effect, although negligible for the actual very low value of [Formula: see text], can have interesting physical consequences concerning for example its relation with Bose–Einstein condensation or more speculatively with the nature of the cosmological constant in terms of gravitons, as recently suggested in Ref. 21 near a Bose–Einstein condensation phase.
Early Mesozoic sinistral transpression along the Pai-Khoi–Novaya Zemlya fold–thrust belt, Russia
Authors: Curtis Michael L. , Lopez-Mir Berta , Scott Robert A. , Howard James P.
Published: August 2017

The NW–SE-trending Pai-Khoi fold–thrust belt links the Permian Uralian Orogen in the Polar Urals with the early Mesozoic fold belt on Novaya Zemlya. An interpretation of structural lineaments present in southern Novaya Zemlya suggests that the NW–SE-trending fold belt in southernmost Novaya Zemlya may have formed contemporaneously with parallel sinistral strike-slip faults. Analysis of regional-scale geological maps of the adjacent Pai-Khoi fold–thrust belt reveals large-scale structural relationships indicative of sinistral shear along the fold–thrust belt, including the presence of left-stepping en echelon folds within the Kara Shale Allochthon. This interpretation is corroborated by a field study of the allochthon-bounding Main Pai-Khoi Thrust, which reveals a consistently oblique tectonic stretching lineation, pitching 56° towards the east, suggesting tectonic displacement towards the west. It is therefore proposed that the Pai-Khoi fold–thrust belt is best described as a zone of sinistral inclined transpression. The interpretation of the Pai-Khoi fold–thrust belt as a zone of sinistral transpression has important implications for the interpretation of this tectonic boundary. This is reflected in a new structural cross-section through southernmost Novaya Zemlya, which is characterized by thick-skinned tectonics and steep strike-slip faults. These faults may link at depth with the Baidaratsky Fault.
miRNA Expression Profile and Effect of Wenxin Granule in Rats with Ligation-Induced Myocardial Infarction
Authors: Wu Aiming , Lou Lixia , Zhai Jianying , Zhang Dongmei , Chai Limin , Nie Bo , Zhu Haiyan , Gao Yonghong , Shang Hongcai , Zhao Mingjing
Published: August 2017

Wenxin Granule (WXKL) is a traditional Chinese medicine used for treatment of myocardial infarction (MI) and arrhythmias. However, the genomic pathological mechanisms of MI and mechanisms of WXKL are largely unknown. This study aims to investigate a comprehensive miRNA expression profile, and the predicted correlation pathways to be targeted by differentially expressed miRNAs in MI, and mechanisms of WXKL from a gene level. MI rat model was established by a coronary artery ligation surgery. miRNA expression microarrays were performed and the data were deposited in Gene Expression Omnibus (GEO number GSE95855). And, pathway analysis was performed by using the DIANA-miRPath v3.0 online tool. The expressions of miR-1, miR-133, Cx43, and Cx45 were detected by quantitative real-time PCR. It was found that 35 differentially expressed miRNAs and 23 predicted pathways, including miR-1, miR-133, and gap junction pathway, are involved in the pathogenesis of MI. And, WXKL increased the expressions of miR-1 and miR-133, while also increased the mRNA levels of Cx43 and Cx45, and, especially, recovered the Cx43/Cx45 ratio near to normal level. The results suggest that regulatory effects on miR-1, miR-133, Cx43, and Cx45 might be a possible mechanism of WXKL in the treatment of MI at the gene level.
Processes Governing Alkaline Groundwater Chemistry within a Fractured Rock (Ophiolitic Mélange) Aquifer Underlying a Seasonally Inhabited Headwater Area in the Aladağlar Range (Adana, Turkey)
Authors: Güler Cüneyt , Thyne Geoffrey D. , Tağa Hidayet , Yıldırım Ümit
Published: August 2017

The aim of this study was to investigate natural and anthropogenic processes governing the chemical composition of alkaline groundwater within a fractured rock (ophiolitic mélange) aquifer underlying a seasonally inhabited headwater area in the Aladağlar Range (Adana, Turkey). In this aquifer, spatiotemporal patterns of groundwater flow and chemistry were investigated during dry (October 2011) and wet (May 2012) seasons utilizing 25 shallow hand-dug wells. In addition, representative samples of snow, rock, and soil were collected and analyzed to constrain the PHREEQC inverse geochemical models used for simulating water-rock interaction (WRI) processes. Hydrochemistry of the aquifer shows a strong interseasonal variability where Mg–HCO3 and Mg–Ca–HCO3 water types are prevalent, reflecting the influence of ophiolitic and carbonate rocks on local groundwater chemistry. R-mode factor analysis of hydrochemical data hints at geochemical processes taking place in the groundwater system, that is, WRI involving Ca- and Si-bearing phases; WRI involving amorphous oxyhydroxides and clay minerals; WRI involving Mg-bearing phases; and atmospheric/anthropogenic inputs. Results from the PHREEQC modeling suggested that hydrogeochemical evolution is governed by weathering of primary minerals (calcite, chrysotile, forsterite, and chromite), precipitation of secondary minerals (dolomite, quartz, clinochlore, and Fe/Cr oxides), atmospheric/anthropogenic inputs (halite), and seasonal dilution from recharge.
Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment
Authors: Paragh Lilla , Törőcsik Daniel
Published: August 2017

The role of factor XIII subunit A (FXIII-A) is not restricted to hemostasis. FXIII-A is also present intracellularly in several human cells and serves as a diagnostic marker in a wide range of dermatological diseases from inflammatory conditions to malignancies. In this review, we provide a guide on the still controversial interpretation of dermal cell types expressing FXIII-A and assess the previously described mechanisms behind their accumulation under physiological and pathological conditions of the human skin. We summarize the intracellular functions of FXIII-A as well as its possible sources in the extracellular space of the dermis with a focus on its relevance to skin homeostasis and disease pathogenesis. Finally, the potential role of FXIII-A in wound healing, as a field with long-term therapeutic implications, is also discussed.
Gutman Index and Detour Gutman Index of Pseudo-Regular Graphs
Authors: Kavithaa S. , Kaladevi V.
Published: August 2017

The Gutman index of a connected graph G is defined as Gut(G)=∑u≠vd(u)d(v)d(u,v), where d(u)  and  d(v) are the degree of the vertices u  and  v and d(u,v) is the distance between vertices u  and  v. The Detour Gutman index of a connected graph G is defined as   GutG=∑u≠vd(u)d(v)D(u,v), where D(u,v) is the longest distance between vertices u  and  v. In this paper, the Gutman index and the Detour Gutman index of pseudo-regular graphs are determined.
Distribution and Thermal Maturity of Devonian Carbonate Reservoir Solid Bitumen in Desheng Area of Guizhong Depression, South China
Authors: Hou Yuguang , Liang Yaqi , He Sheng , Liu Yukun , Fan Zhiwei , Song Yingrui
Published: August 2017

The distribution of solid bitumen in the Devonian carbonate reservoir from well Desheng 1, Guizhong Depression, was investigated by optical microscope and hydrocarbon inclusions analysis. Vb and chemical structure indexes measured by bitumen reflectance, laser Raman microprobe (LRM), and Fourier transform infrared spectroscopy (FTIR) were carried out to determine the thermal maturity of solid bitumen. Based on the solid bitumen thermal maturity, the burial and thermal maturity history of Devonian carbonate reservoir were reconstructed by basin modeling. The results indicate that the fractures and fracture-related dissolution pores are the main storage space for the solid bitumen. The equivalent vitrinite reflectance of solid bitumen ranges from 3.42% to 4.43% converted by Vb (%) and LRM. The infrared spectroscopy analysis suggests that there are no aliphatic chains detected in the solid bitumen which is rich in aromatics C=C chains (1431–1440 cm−1). The results of Vb (%), LRM, and FTIR analysis demonstrate that the solid bitumen has experienced high temperature and evolved to the residual carbonaceous stage. The thermal evolution of Devonian reservoirs had experienced four stages. The Devonian reservoirs reached the highest reservoir temperature 210–260°C during the second rapid burial-warming stage, which is the main period for the solid bitumen formation.
Prevalence of Anemia, Overweight/Obesity, and Undiagnosed Hypertension and Diabetes among Residents of Selected Communities in Ghana
Authors: Anderson Alex Kojo
Published: August 2017

The increasing numbers of lifestyle related chronic diseases in developing countries call for awareness, early detection, and effective management. The objective of this paper is to report the prevalence of undiagnosed hypertension, diabetes, overweight/obesity, and anemia among residents of selected communities in Ghana. The data comes from a community screening conducted in Ghana as part of the University of Georgia Summer Service Learning Program. Descriptive statistics were used to summarize the data while chi-square and independentt-test compared groups. A total of 976 participants (37.9% males and 62.1% females), 18 years and older, were screened. Mean age was46.25±17.14years, BMI was25.44±5.26 kgm−2, and hemoglobin was12.04±2.22 g/dL. 3.1% and 12.6% reported existing diagnosis for diabetes and hypertension, respectively. Almost half (47.8%) were overweight/obese; 27.0% were hypertensive while 34.0% had diabetes. Also, 28.8% males compared to 37.8% females had diabetes (P=0.015), while 28.2% males compared to 26.2% females were hypertensive (P=0.635). There were differences in BMI (P<0.0001), anemia (P=0.007), and undiagnosed diabetes (P<0.0001) and hypertension (P<0.0001) by community (Takoradi versus Cape Coast) where the screening took place. Findings from the screening exercise call for improved public health education with a focus on lifestyle habits and health seeking behaviors among Ghanaians.
SDRE Control Applied to the Wheel Speed of a Compressed Air Engine with Crank-Connecting-Rod Mechanism
Authors: Alves Alexandre de Castro , Tusset Angelo Marcelo , Balthazar Jose Manoel , Lima Jeferson Jose de , Janzen Frederic Conrad , Rocha Rodrigo Tumolin , Nabarrete Airton
Published: August 2017

Renewable energy sources for vehicles have been the motivation of many researches around the world. The reduction of fossil fuels deposits and increase of the pollution in cities bring the need of more efficient and cleaner energy sources. In this way, this work will present the application of a compressed air engine applied to a bicycle. The engine is composed of two pneumatic cylinders connected to the bicycle wheel through a crank-connecting-rod mechanism. In order to control the velocity of the bicycle, a strategy of control composed of two controls was implemented: a feedback and a feedforward control. For feedback control, the State-Dependent Riccati Equation (SDRE) control and also a proportional-derivative (PD) control are considered, considering three cases for velocity bicycle variation: 10 km/h, 20 km/h, and 30 km/h. The equations of motion of the system were obtained through the Lagrangian energy method. Numerical simulations were performed in order to analyze the dynamics of the system and the efficiency of the controllers.
Identification of Multiple Dehalogenase Genes Involved in Tetrachloroethene-to-Ethene Dechlorination in aDehalococcoides-Dominated Enrichment Culture
Authors: Ismaeil Mohamed , Yoshida Naoko , Katayama Arata
Published: August 2017

Chloroethenes (CEs) are widespread groundwater toxicants that are reductively dechlorinated to nontoxic ethene (ETH) by members ofDehalococcoides. This study established aDehalococcoides-dominated enrichment culture (designated “YN3”) that dechlorinates tetrachloroethene (PCE) to ETH with high dechlorination activity, that is, complete dechlorination of 800 μM PCE to ETH within 14 days in the presence ofDehalococcoidesspecies at5.7±1.9×107 copies of 16S rRNA gene/mL. The metagenome of YN3 harbored 18rdhAgenes (designatedYN3rdhA1–18) encoding the catalytic subunit of reductive dehalogenase (RdhA), four of which were suggested to be involved in PCE-to-ETH dechlorination based on significant increases in their transcription in response to CE addition. The predicted proteins for two of these four genes, YN3RdhA8 and YN3RdhA16,showed 94% and 97% of amino acid similarity with PceA and VcrA, which are well known to dechlorinate PCE to trichloroethene (TCE) and TCE to ETH, respectively. The other twordhAs,YN3rdhA6andYN3rdhA12,which were never proved asrdhAfor CEs, showed particularly high transcription upon addition of vinyl chloride (VC), with75±38and16±8.6mRNA copies per gene, respectively, suggesting their possible functions as novel VC-reductive dehalogenases. Moreover, metagenome data indicated the presence of three coexisting bacterial species, including novel species of the genusBacteroides, which might promote CE dechlorination byDehalococcoides.
Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer
Authors: Gulbahce Natali , Magbanua Mark Jesus M. , Chin Robert , Agarwal Misha R. , Luo Xuhao , Liu Jia , Hayden Daniel M. , Mao Qing , Ciotlos Serban , Li Zhenyu , Chen Yanxiang , Chen Xingpeng , Li Yuxiang , Zhang Rebecca Yu , Lee Katharine , Tearle Rick , Park Emily , Drmanac Snezana , Rugo Hope S. , Park John W. , Drmanac Radoje , Peters Brock A.
Published: August 2017

Much effort has been dedicated to developing circulating tumor cells (CTC) as a noninvasive cancer biopsy, but with limited success as yet. In this study, we combine a method for isolation of highly pure CTCs using immunomagnetic enrichment/fluorescence-activated cell sorting with advanced whole genome sequencing (WGS), based on long fragment read technology, to illustrate the utility of an accurate, comprehensive, phased, and quantitative genomic analysis platform for CTCs. Whole genomes of 34 CTCs from a patient with metastatic breast cancer were analyzed as 3,072 barcoded subgenomic compartments of long DNA. WGS resulted in a read coverage of 23× per cell and an ensemble call rate of >95%. These barcoded reads enabled accurate detection of somatic mutations present in as few as 12% of CTCs. We found in CTCs a total of 2,766 somatic single-nucleotide variants and 543 indels and multi-base substitutions, 23 of which altered amino acid sequences. Another 16,961 somatic single nucleotide variant and 8,408 indels and multi-base substitutions, 77 of which were nonsynonymous, were detected with varying degrees of prevalence across the 34 CTCs. On the basis of our whole genome data of mutations found in all CTCs, we identified driver mutations and the tissue of origin of these cells, suggesting personalized combination therapies beyond the scope of most gene panels. Taken together, our results show how advanced WGS of CTCs can lead to high-resolution analyses of cancers that can reliably guide personalized therapy. Cancer Res; 77(16); 4530–41. ©2017 AACR.
S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma
Authors: Chow Kin-Hoe , Park Hee Jung , George Joshy , Yamamoto Keiko , Gallup Andrew D. , Graber Joel H. , Chen Yuanxin , Jiang Wen , Steindler Dennis A. , Neilson Eric G. , Kim Betty Y.S. , Yun Kyuson
Published: August 2017

Glioma stem cells (GSC) and epithelial–mesenchymal transition (EMT) are strongly associated with therapy resistance and tumor recurrence, but the underlying mechanisms are incompletely understood. Here, we show that S100A4 is a novel biomarker of GSCs. S100A4+ cells in gliomas are enriched with cancer cells that have tumor-initiating and sphere-forming abilities, with the majority located in perivascular niches where GSCs are found. Selective ablation of S100A4-expressing cells was sufficient to block tumor growth in vitro and in vivo. We also identified S100A4 as a critical regulator of GSC self-renewal in mouse and patient-derived glioma tumorspheres. In contrast with previous reports of S100A4 as a reporter of EMT, we discovered that S100A4 is an upstream regulator of the master EMT regulators SNAIL2 and ZEB along with other mesenchymal transition regulators in glioblastoma. Overall, our results establish S100A4 as a central node in a molecular network that controls stemness and EMT in glioblastoma, suggesting S100A4 as a candidate therapeutic target. Cancer Res; 77(19); 5360–73. ©2017 AACR.
Ponatinib-Induced Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant
Authors: Petrungaro Annamaria , Gentile Massimo , Mazzone Carla , Greco Rosa , Uccello Giuseppina , Recchia Anna Grazia , De Stefano Laura , Bossio Sabrina , Palummo Angela , Morelli Rosellina , Musolino Caterina , Morabito Fortunato , Vigna Ernesto
Published: August 2017

We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease in minimal residual disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib treatment was well tolerated and considered safe with easily manageable side effects.
Cerebral Small Vessel Disease Is Associated with Dysregulation in the Ubiquitin Proteasome System and Other Major Cellular Pathways in Specific Brain Regions
Authors: Ritz Marie-Françoise , Grond-Ginsbach Caspar , Fluri Felix , Kloss Manja , Tolnay Markus , Peters Nils , Engelter Stefan , Lyrer Philippe
Published: August 2017

Background/Aims: Cerebral small vessel disease (SVD) is characterized by periventricular white matter (WM) changes and can lead to vascular dementia, the second most common form of age-dependent dementia. The pathogenesis of the disease remains poorly understood, and studies of its molecular basis are limited. By profiling gene expression of dissected postmortem brain tissue in SVD patients and comparisons with tissue of nonneurological controls, we aimed to identify genes and processes that are involved in the pathogenesis of SVD to gain new pathogenetic insights. Methods: We performed genome-wide expression analyses in postmortem brain tissue samples dissected from frontal, temporal, and occipital lobes as well as basal nuclei comprising thalamus, basal ganglia, and hippocampus from 5 SVD cases and 5 nonaffected control cases. Cellular pathways associated with differently expressed genes were identified in each brain region individually. Results: This analysis disclosed regional differences, with frontal lobe and thalamus showing the highest numbers of genes with significantly altered expression. Biological functions and pathways associated with changed gene expression depicted brain area-specific defective pathways. Vessel-associated functions, such as increased extracellular matrix-receptor interactions and cell adhesion molecules, were enhanced in all regions. Inflammation and apoptosis were induced particularly in basal nuclei and temporal and occipital regions. Interestingly, genes associated with the ubiquitin-dependent proteolysis (ubiquitin proteasome system) pathway were downregulated in the frontal lobe and in the thalamus, leading to the formation of protein aggregates. Conclusion: This analysis deciphers brain region-specific molecular processes to increase the present knowledge of SVD pathology and determine new potential therapeutic targets.
Tooth Wear Inclination in Great Ape Molars
Authors: Knight-Sadler Jordan , Fiorenza Luca
Published: August 2017

Primate dietary diversity is reflected in their dental morphology, with differences in size and shape of teeth. In particular, the tooth wear angle can provide insight into a species' ability to break down certain foods. To examine dietary and masticatory information, digitized polygon models of dental casts provide a basis for quantitative analysis of wear associated with tooth attrition. In this study, we analyze and compare the wear patterns of Pongo pygmaeus, Gorilla gorilla gorilla and Pan troglodytes schweinfurthii lower molars, focusing on the degree of inclination of specific wear facets. The variation in wear angles appears to be indicative of jaw movements and the specific stresses imposed on food during mastication, reflecting thus the ecology of these species. Orangutans exhibit flatter wear angles, more typical of a diet consisting of hard and brittle foods, while gorillas show a wear pattern with a high degree of inclination, reflecting thus their more leafy diet. Chimpanzees, on the other hand, show intermediate inclinations, a pattern that could be related to their highly variable diet. This method is demonstrated to be a powerful tool for better understanding the relationship between food, mastication and tooth wear processes in living primates, and can be potentially used to reconstruct the diet of fossil species.
The Impact of the Hepatitis B Core Antibody Status on Recurrence in Patients with Non-B Non-C Hepatocellular Carcinoma after Curative Surgery
Authors: Okamura Yukiyasu , Sugiura Teiichi , Ito Takaaki , Yamamoto Yusuke , Ashida Ryo , Uesaka Katsuhiko
Published: August 2017

Background: The serum antibody to hepatitis B core antigen (HBcAb) is considered a risk factor of liver carcinogenesis. This study aimed to reveal whether HBcAb status is a prognostic factor after hepatectomy is performed for treating hepatocellular carcinoma (HCC). Methods: This retrospective study enrolled 272 patients who underwent hepatectomy as the initial treatment for HCC and who were followed up over 5 years after surgery. The types of HCC were classified into the following 3 types according to the hepatitis virus infection status and the patients without hepatitis virus infection non-B non-C HCC (NBNC-HCC) were further classified into 2 groups. Results: There is no novel finding as a result of the comparison made among hepatitis virus status. Of 90 patients (33.1%) with NBNC-HCC, 10 patients were excluded because the preoperative HBcAb status was not measured. There were 51 patients (63.8%) who were HBcAb-positive and 29 patients (36.2%) who were HBcAb-negative. In multivariate analysis, the presence of HBcAb-negative (hazard ratio 2.10, 95% CI 1.09-4.03, p = 0.026) remained as significant independent risk factors for recurrence in NBNC-HCC. Conclusions: This study shows that the HBcAb-positive is rather a favorable predictor for recurrence after curative resection in NBNC-HCC.
Physical Inactivity Predicts Slow Gait Speed in an Elderly Multi-Ethnic Cohort Study: The Northern Manhattan Study
Authors: Willey Joshua Z. , Moon Yeseon P. , Kulick Erin R. , Cheung Ying Kuen , Wright Clinton B. , Sacco Ralph L. , Elkind Mitchell S.V.
Published: August 2017

Introduction: Gait speed is associated with multiple adverse outcomes of aging. We hypothesized that physical inactivity would be prospectively inversely associated with gait speed independently of white matter hyperintensity volume and silent brain infarcts on MRI. Methods: Participants in the Northern Manhattan Study MRI sub-study had physical activity assessed when they were enrolled into the study. A mean of 5 years after the MRI, participants had gait speed measured via a timed 5-meter walk test. Physical inactivity was defined as reporting no leisure-time physical activity. Multi-variable logistic and quantile regression was performed to examine the associations between physical inactivity and future gait speed adjusted for confounders. Results: Among 711 participants with MRI and gait speed measures (62% women, 71% Hispanic, mean age 74.1 ± 8.4), the mean gait speed was 1.02 ± 0.26 m/s. Physical inactivity was associated with a greater odds of gait speed in the lowest quartile (<0.85 m/s, adjusted OR 1.90, 95% CI 1.17-3.08), and in quantile regression with 0.06 m/s slower gait speed at the lowest 20 percentile (p = 0.005). Conclusions: Physical inactivity is associated with slower gait speed independently of osteoarthritis, grip strength, and subclinical ischemic brain injury. Modifying sedentary behavior poses a target for interventions aimed at reducing decline in mobility.
Por uma interpretação humanista da relação entre lugar e mobilidade
Authors: Brum Jean Lucas da Silva
Published: August 2017

Este ensaio apresenta uma reflexão crítica sobre a construção de sentidos de lugar pela prática da mobilidade, à luz de um olhar humanista-cultural. Limitamo-nos a construir um debate essencialmente teórico, baseando nas principais referências sobre lugar no entendimento humanista em geografia. Diferentemente do que apontam muitos geógrafos, acreditamos que a perspectiva humanista não exclui o papel da mobilidade na produção dos lugares. Muito embora o termo lugar seja um dos principais conceitos em geografia, o debate sobre sua definição ainda é escasso, sobretudo no que tange à relação entre lugar e mobilidade. Com este trabalho, pretendemos enriquecer a discussão em torno do conceito de lugar e sua importância na interpretação geográfica.
Unidades de paisagem na bacia hidrográfica do Ribeirão Preto, Serra do Gandarela-MG
Authors: Marent Breno Ribeiro , Portilho Sidney
Published: August 2017

Este trabalho estuda a relação entre geologia, relevo, solo, vegetação e uso da terra na bacia hidrográfica do Ribeirão Preto. Para tanto, recorreu-se à abordagem geossistêmica, na qual o relevo foi o parâmetro usado para delimitar as unidades de paisagem. Esses atributos foram relacionados a partir de mapas temáticos, quadro síntese e perfil transversal. O relevo foi um parâmetro adequado para delimitar as unidades de paisagem, apresentando correlação entre os elementos analisados. O relevo movimentado está relacionado à geologia. Esses elementos condicionam a formação dos solos, predominando neossolos e cambissolos. A vegetação está relacionada à interação entre geologia, relevo e solos. As características da área a tornam extremamente frágil diante das intervenções antrópicas. Considerados importantes para a conservação, seus atributos indicam-na como propícia ao estabelecimento de unidade de conservação, permitindo a manutenção desses ambientes.
O campo na dialética da geografia
Authors: Tricart Jean
Published: August 2017

A análise de fenômenos particulares, tal como é encarada pelas diversas disciplinas, não deve conduzir ao isolamento desses fenômenos. Uma atitude dialética deve permitir a recolocação dos resultados analíticos obtidos em seu contexto de interferências. Em síntese, nossa abordagem é decididamente sistêmica, já que a nosso ver a teoria dos sistemas é o melhor instrumento lógico de que dispomos atualmente. Ela engloba e supera a “dialética da natureza” esboçada há um século por Engels.
A técnica logística no toyotismo: uma aproximação geográfica do just-in-time
Authors: Carvalho André Simplício
Published: August 2017

Entre outros sistemas de ordenamento logístico, o just-in-time é muito citado por geógrafos dedicados a estudos sobre economia e transporte – especialmente no contexto do toyotismo –, mas pouco esclarecido. Assim, propõe-se neste artigo esclarecer o que é exatamente o just-in-time, contextualizando-o no âmago das mudanças do processo produtivo que consolidou a globalização a partir da década de 1970, ensejando sua aproximação geográfica. Essa aproximação permite interpretar o just-in-time como uma técnica de ordenamento de fluxos que se revela no espaço como uma rede, ordenada por uma lógica produtiva de desperdício zero.
O caçador de pedreiros-livres: José Anastácio Lopes Cardoso e sua ação contra a maçonaria luso-brasílica (1799-1804)
Authors: Magalhães Pablo Antonio Iglesias
Published: August 2017

Este artigo fundamenta-se nas ideias e observações contidas num relatório feito pelo corregedor José Anastácio Lopes Cardoso, ao então intendente da polícia em Lisboa e seu chefe imediato Diogo Inácio de Pina Manique. A leitura do documento revela a influência das ideias conspiratórias do jesuíta Augustin Barruel nas proposições e nas ações policiais executadas pelo corregedor contra as associações maçônicas e os pedreiros-livres de Portugal e do Brasil.
O terreiro do Gantois: redes sociais e etnografia histórica no século XIX
Authors: Castillo Lisa Earl
Published: August 2017

O Ilê Iyá Omi Axé Iyamassé, localizado na cidade de Salvador e mais conhecido como o Terreiro do Gantois, é um dos mais antigos candomblés da Bahia, comentado nos estudos afro-brasileiros desde os tempos de Nina Rodrigues e reconhecido como patrimônio histórico do Brasil desde 2002. Contudo, pouco se sabe sobre seus primeiros tempos, além de tradições orais sobre o envolvimento da fundadora no legendário Candomblé da Barroquinha. Este texto cruza dados das tradições orais com pesquisa documental e etnográfica, reconstruindo assim as histórias de vida da fundadora, Maria Júlia da Conceição, e de seu marido, Francisco Nazareth d’Etra, desde o cativeiro até a liberdade. A fundadora era de nação nagô, mas seu marido era jeje e as evidências sobre os primeiros tempos da comunidade religiosa apontam para a importância de influências jejes. O texto ainda traz novas reflexões sobre a antiga relação entre o Gantois e o Ilê Axé Iyá Nassô Oká (Casa Branca), sugerindo uma nova cronologia para a cisão entre as duas comunidades.
O “Corisco Preto”: cangaço, raça e banditismo no Nordeste brasileiro
Authors: Domingues Petrônio
Published: August 2017

A finalidade deste artigo é reconstituir os fatos que levaram à prisão de Manoel Luiz de Jesus – um bandido negro que se identificava como Corisco Preto, do bando de Lampião –, no sertão nordestino, em 1931, para daí discutir os relatórios e pareceres produzidos sobre ele pelo sistema penitenciário de Sergipe, especialmente pelo Gabinete de Biologia Criminal, responsável por periciar o grau de degenerescência do delinquente. Para além de desvelar aspectos da trajetória de Manoel Luiz, a proposta é surpreender, a partir desse personagem, as conexões sinuosas entre cangaço, raça e banditismo à luz da medicina legal.
A função da historiografia na obra de Droysen
Authors: Lobo Ana Lucia Mandacaru
Published: August 2017

Resenha de: ASSIS, Arthur Alfaix. What is history for? Johann Gustav Droysen and the functions of historiography. Oxford: Berghahn Books, 2014.
Investigating the Genetic Causes of Sudden Unexpected Death in Children Through Targeted Next-Generation Sequencing Analysis
Authors: Dewar Laura J. , Alcaide Miguel , Fornika Daniel , D’Amato Luisa , Shafaatalab Sanam , Stevens Charles M. , Balachandra Thambirajah , Phillips Susan M. , Sanatani Shubhayan , Morin Ryan D. , Tibbits Glen F.
Published: August 2017

Background—

Inherited arrhythmia syndromes are responsible for a significant portion of autopsy-negative sudden unexpected death (SUD) cases, but molecular autopsy used to identify potentially causal variants is not routinely included in SUD investigations. We collaborated with a medical examiner's office to assist in finding a diagnosis for their autopsy-negative child SUD cases.

Methods and Results—

191 child SUD cases (<5 years of age) were selected for analyses. Our next generation sequencing panel incorporated 38 inherited arrhythmia syndrome candidate genes and another 33 genes not previously investigated for variants that may underlie SUDY pathophysiology. Overall, we identified 11 potentially causal disease-associated variants in 12 cases, for an overall yield of 6.3%. We also identified 31 variants of uncertain significance in 36 cases and 16 novel variants predicted to be pathogenic in silico in 15 cases. The disease-associated variants were reported to the medical examiner to notify surviving relatives and recommend clinical assessment.

Conclusions—

We have identified variants that may assist in the diagnosis of at least 6.3% of autopsy-negative child SUD cases and reduce risk of future SUD in surviving relatives. We recommend a cautious approach to variant interpretation. We also suggest inclusion of cardiomyopathy genes as well as other candidate SUD genes in molecular autopsy analyses.
Interstitial Occupancies: From Industrialization to Informal Urbanism in Monterrey, Mexico
Authors: Marinic Gregory , Qureshi Ziad
Published: August 2017

As the third largest city in Mexico, Monterrey is a manufacturing hub that offers a provocative counterpoint to industrial cities in developed countries. Suburban sprawl, political instability, violence, social injustice, and de-industrialization illustrate increasing fragmentation—or terrain vague—where the conventional urban fabric unravels and less formal occupancies unfold. Defined by Catalan architect and theorist Ignasi Solà-Morales, terrain vague is expressed through obsolescence and various organic practices that react to depopulation and under-productivity. Investigating production and city-building, this article positions post-industrial Monterrey as a place of difference reflecting hybridized Latin American and American normative conditions. It surveys processes of industrialization and changing technology to situate iconic European and American architectural and urban precedents as forerunners of similar conditions in Monterrey.
Stinging Auloi
Authors: Moore Timothy J.
Published: August 2017

When Dikaiopolis calls theauletaiaccompanying the Theban who comes to trade with him wasps (Ach. 864), he responds in part to a buzz-like sound produced by theirauloi. Contributing to the instruments’ buzzing may have been dissonance caused by so many pipes played at once, the pipes’ material (bone), and a playing technique that placed emphasis on the lowest notes. The instruments’ music is out of place because the scene is in iambic trimeters, which were almost always performed without accompaniment. Dikaiopolis also calls theauletaiwasps because their arrival reminds him of the Spartan army, which regularly marched, fought, and performed rituals to the accompaniment of multipleauloi.
The Monody of the Hoopoe in Aristophanes’
Authors: Pöhlmann Egert
Published: August 2017

Animal choruses are familiar in ancient Greek comedy. Besides Aristophanes, there are 13 examples of them. Vase paintings provide evidence from the beginnings of Old Comedy. They had to sing the traditional melic parts of the agon and the parabasis. Aristophanes used the comic animal chorus in Knights (424 bc), Wasps (422), Birds (414), Frogs (405) and Storks (395-387). Moreover, with the song of the Hoopoe in the Birds 227-62, Aristophanes presents an animal as soloist which sings an extended monody, a perfect example of the astropha, the structure of which is defined by content, changes of metre and probably of music, but not by alternating strophes and antistrophes. It can be demonstrated that the Hoopoe’s monody follows the model of the late astrophic monodies of Euripides and mirrors the astrophic structures of the New Dithyramb, later parodied by Aristophanes (Birds 1373-1409) in the person of the dithyrambic poet Cinesias.
Aristolochia longeracemosa, a new synonym of A. chlamydophylla (Aristolochiaceae)
Authors: DO TRUONG VAN , GAO XIN-FEN
Published: August 2017

Aristolochia Linnaeus (1753: 960) (Aristolochiaceae) comprises about 500 species. The genus has worldwide distribution (Wanke et al. 2006). Recent findings of Aristolochia (Phuphathanaphong 2006, Xu et al. 2011, Huong et al. 2014, Do et al. 2015, Wu et al. 2015), together with the previous treatments for the Flora of Thailand (Phuphathanaphong 1987), the Flora of Vietnam (Pham 2000) and the Flora of China (Huang et al. 2003) confirmed the Thai & Indo-Chinese floristic region as a center of diversity for Aristolochia, with currently about 90 species. A high degree of endemism is found for specific countries (Huang et al. 2003, Phuphathanaphong 2006). However, the delimitation and taxonomic status of some species are still unclear due to limited access to specimen databases, especially for the type specimens in those countries. Notably, recent studies have significantly revised the taxonomic status of several previously described Aristolochia species when herbarium materials from multiple countries in the region were consulted (Do et al. 2014, Do 2016, Zu et al. 2016). On the basis of the examination of the protologue, the type specimens, and recent collections from the herbaria BKF, C, GXMI, HITBC, IBSC, KUN, PE and PEM, we conclude that Aristolochia longeracemosa B. Hansen & Leena Phuphathanaphong (1999: 557), described from collections made in northern Thailand, is conspecific with A. chlamydophylla C.Y. Wu ex S. M. Hwang (1981: 223) from southern China. Hence, we here propose the former as a new synonym of the latter. A detailed comparison of the morphological characters and habitat of these two species is provided.
Nomenclatural notes on Macaronesian Micromeria (Lamiaceae)
Authors: PUPPO PAMELA , MEIMBERG HARALD , PÉREZ DE PAZ PEDRO LUIS , BRÄUCHLER CHRISTIAN
Published: August 2017

Recently, the authors presented a proposal to conserve the names Micromeria varia Bentham (1834: 374) with a conserved type and M. hyssopifolia Webb & Berthelot (1844: 72) against Thymus ericifolius Roth (1800: 50) (Puppo et al. 2014a) to avoid disruption of current usage of these two well established names. This proposal, however, was not recommended by the Nomenclature Committee (Applequist 2016) and subsequently turned down by the General Committee (Wilson 2017). While regretting this decision, we are prepared to accept the taxonomic and nomenclatural implications.