bluuebunny/crossref_metadata_2025 huggingface dataset:
The Psychosocial Effects of Drone Violence: Social Isolation, Self‐Objectification, and Depoliticization
Authors: Edney‐Browne Alex
Published: October 2019

The U.S.‐led drone program has severe and wide‐ranging psychosocial and political effects on people in targeted areas. This article draws upon the author's interviews with people living under drones in Afghanistan to argue that drone surveillance and bombardment causes social isolation and self‐objectification. Interviewees reported that social gatherings, and any activities that involve nighttime travel, are shortened or avoided out of fear that drone surveillance will spot so‐called “nefarious activity” and bombardment will follow. Drawing upon feminist and postcolonial scholarship, the article contends that drone surveillance constitutes a form of psychological colonization. Civilians are frequently made to think of how they look to drone operators and change their behaviors accordingly—therein “self‐objectifying.” Narratives of “precision” warfare allow citizens of Western liberal democracies leading/supporting the drone program to avoid psychologically confronting these effects, while people living under drones face relentless psychological insecurities.
Alternative Land‐Price Indexes for Commercial Properties in Tokyo
Authors: Diewert Erwin , Shimizu Chihiro
Published: October 2019

The System of National Accounts (SNA) requires separate estimates for the land and structure components of a commercial property. Using transactions data for the sales of office buildings in Tokyo, a hedonic regression model (the “builder’s model”) was estimated and this model generated an overall property price index as well as subindexes for the land and structure components of the office buildings. The builder’s model was also estimated using appraisal data on office building real estate investment trusts (REITs) for Tokyo. These hedonic regression models also generated estimates for net depreciation rates, which can be compared. Finally, the Japanese government constructs annual official land prices for commercial properties based on appraised values. The paper compares these official land prices with the land prices generated by the hedonic regression models based on transactions data and on REIT data. The results reveal that commercial property indexes based on appraisal and assessment prices lag behind the indexes based on transaction prices.
The labor market effects of the China Syndrome: Evidence from South Korean manufacturing
Authors: Choi Jaerim , Xu Mingzhi
Published: October 2019

We evaluate the direct impact of China trade shock on the Korean labour market following the approach of Acemoglu, Autor, Dorn, Hanson, and Price (Journal of Labor Economics, 2016, 34, S1). Using firm‐ and industry‐level data for the period 1993–2013, our direct estimates imply that the net employment effect of the China shock in the manufacturing sector is the creation of 0.52 million jobs. The positive impact is mostly driven by China's rising demand for intermediate inputs and capital goods from Korea to support its export expansion to the global economy. The import‐competition channel plays a negligible role in manufacturing employment because it creates temporary jobs that merely compensate for the loss in permanent jobs. By contrast, over the same period, the average wage declined by 2.4%, and income inequality, measured as the gap between the high‐ and low‐income quantile, grew substantially in manufacturing. In addition, we find that the direct effect of China shock lowers labour market concentration by shifting workers from big firms to small‐ and medium‐sized firms.
Time-Dependent Reliability Model of Structures Under Different Stochastic Loads
Authors: Qian Hua-Ming , Huang Tudi , Huang Hong-Zhong
Published: October 2019

This paper proposes the time-dependent reliability model of structures under different stochastic loads based on the stress–strength interference (SSI) model and probabilistic statistical theory. First, the different stochastic loads mean that the loads are discrete, and that one applied load is from random variable and the other applied load may be from another random variable, and the cumulative effect and correlation are considered when they are applied for multiple times. Second, two different time-dependent reliability models, with and without considering strength degradation, are established in this paper. Meanwhile, the relationship between the discrete load frequency and time is described using Poisson process, and the time-dependent reliability model under continuous time is also provided. Finally, the proposed time-dependent reliability model of structures is validated with the Monte Carlo simulation (MCS), and the effectiveness of the proposed method is testified.
Quantifying vocal effort from the shape of the one-third octave long-term-average spectrum of speech
Authors: Liénard Jean-Sylvain
Published: October 2019

Vocal effort is a major source of variability in speech processing. The present study examines its spectral effects from calibrated data recorded in 1977. The 97 talkers were instructed to vary their vocal effort in five degrees. Each sequence was represented by its sound level and its 1/3 octave long-term-average spectrum. After normalization to a common arbitrary level, comparing each spectrum to the others demonstrated that the original sound level could be recovered within a 5 dB error margin. A principal component analysis brought out several spectral features involved in the quantitative relationship between spectral shape and sound level.
Synergistic Meropenem-Tobramycin Combination Dosage Regimens against Clinical Hypermutable Pseudomonas aeruginosa at Simulated Epithelial Lining Fluid Concentrations in a Dynamic Biofilm Model
Authors: Bilal Hajira , Bergen Phillip J. , Kim Tae Hwan , Chung Seung Eun , Peleg Anton Y. , Oliver Antonio , Nation Roger L. , Landersdorfer Cornelia B.
Published: October 2019

Exacerbations of chronic
Pseudomonas aeruginosa
infections are a major treatment challenge in cystic fibrosis due to biofilm formation and hypermutation. We aimed to evaluate different dosage regimens of meropenem and tobramycin as monotherapies and in combination against hypermutable carbapenem-resistant
P. aeruginosa
. A hypermutable
P. aeruginosa
isolate (meropenem and tobramycin MICs, 8 mg/liter) was investigated in the dynamic CDC biofilm reactor over 120 h.
A Systematic Review and Meta-analysis of the Prevalence of Community-Onset Bloodstream Infections among Hospitalized Patients in Africa and Asia
Authors: Marchello Christian S. , Dale Ariella P. , Pisharody Sruti , Rubach Matthew P. , Crump John A.
Published: October 2019

Community-onset bloodstream infections (CO-BSI) are major causes of severe febrile illness and death worldwide. In light of new data and the growing problem of antimicrobial resistance (AMR) among pathogens causing BSI, we undertook a systematic review of hospital-based studies of CO-BSI among patients hospitalized with fever.
Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
Authors: Job E. R. , Ysenbaert T. , Smet A. , Van Hecke A. , Meuris L. , Kleanthous H. , Saelens X. , Vogel T. U.
Published: October 2019

There is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by antibodies directed to NA remain largely unexplored. Herein, we show that antibody Fc interaction with Fcγ receptors (FcγRs) expressed on effector cells contributes to viral control in a murine model of influenza. Importantly, a chimeric mouse-human IgG1 with no direct antiviral activity was demonstrated to solely rely on FcγRs to protect mice from disease. Therefore, antibodies without NA enzymatic inhibitory activity may also play a role in controlling influenza viruses and should be of consideration when designing NA-based vaccines and assessing immunogenicity.
A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins
Authors: D’Gama Jonathan D. , Ma Zhe , Zhang Hailong , Liu Xu , Fan Hongjie , Morris Ellen Ruth A. , Cohen Noah D. , Cywes-Bentley Colette , Pier Gerald B. , Waldor Matthew K.
Published: October 2019

M proteins are surface-anchored virulence factors in group A streptococci, human pathogens. Here, we identified an M-like protein, SzM, and its positive regulator, SezV, in
Streptococcus equi
subspecies
zooepidemicus
(SEZ), an important group of pathogens for domesticated animals, including horses and pigs. SzM and SezV homologues were found in the genomes of all SEZ and
S. equi
subspecies
equi
and M18 group A streptococcal strains analyzed but not in other streptococci. Mutant SEZ strains lacking either
sezV
or
szM
were highly attenuated in a mouse model of infection. Collectively, our findings suggest that SezV-related regulators and the linked SzM family of M-like proteins define a new subset of virulent streptococci.
Molecular Mechanism of SR Protein Kinase 1 Inhibition by the Herpes Virus Protein ICP27
Authors: Tunnicliffe Richard B. , Hu William K. , Wu Michele Y. , Levy Colin , Mould A. Paul , McKenzie Edward A. , Sandri-Goldin Rozanne M. , Golovanov Alexander P.
Published: October 2019

Serine arginine (SR) proteins are a family of mRNA regulatory proteins that can modulate spliceosome association with different splice sites and therefore regulate alternative splicing. Phosphorylation within SR proteins is necessary for splice-site recognition, and this is catalyzed by SR protein kinase 1 (SRPK1). The herpes simplex virus (HSV-1) protein ICP27 has been shown previously to interact with and downregulate SRPK1 activity
in vivo
; however, the molecular mechanism for this interaction and inhibition was unknown. Here, we demonstrate that the isolated peptide fragment of ICP27 containing RGG box binds to SRPK1 with high affinity, and competes with a native cellular substrate. Elucidation of the SRPK1-RGG box crystal structure further showed that a short palindromic RGRRRGR sequence binds in the substrate docking groove of SRPK1, mimicking the binding of SR repeats of substrates. These data reveal how the viral protein ICP27 inactivates SRPK1, promoting hypophosphorylation of proteins regulating splicing.
ACE gene missense mutation in a case with early-onset, rapid progressing dementia
Authors: Ni Jing , Xiao Shifu , Li Xia , Sun Lin
Published: October 2019

The population of early-onset Alzheimer’s disease (EOAD) accounts for 1%–2% of the total population of Alzheimer’s disease, and genetic mutations are more common in EOAD. The first symptom of the patient in the present case report was the decline in memories of recent events, and the disease progressed rapidly in the following 2 years. Genetic testing has revealed the presence of genetic mutations (c.A479G, p.N160S) of ACE, which causes the 160th codon of the ACE protein to change from aspartic acid to serine, and at the same time genotype of apolipoprotein E (APOE) is ɛ3/ɛ4. We think that this patient carries the mutation type of the sensitive gene ACE and the risk gene APOE of Alzheimer’s disease, and this is the reason why the disease progressed rapidly. Moreover, we discussed ACE genetic mutation’s meaning in EOAD progression.
An accelerating cosmological model from a parametrization of Hubble parameter
Authors: Pacif S. K. J. , Khan Md Salahuddin , Paikroy L. K. , Singh Shalini
Published: October 2019

In view of late-time cosmic acceleration, a dark energy cosmological model is revisited wherein Einstein’s cosmological constant is considered as a candidate of dark energy. Exact solution of Einstein field equations (EFEs) is derived in a homogeneous isotropic background in classical general relativity. The solution procedure is adopted in a model-independent way (or the cosmological parametrization). A simple parametrization of the Hubble parameter (H) as a function of cosmic time t is considered which yields an exponential type of evolution of the scale factor (a) and also shows a negative value of deceleration parameter at the present time with a signature flip from early deceleration to late acceleration. Cosmological dynamics of the model obtained have been discussed illustratively for different phases of the evolution of the universe. The evolution of different cosmological parameters is shown graphically for flat and closed cases of Friedmann–Lemaitre–Robertson–Walker (FLRW) spacetime for the presented model (open case is incompatible to the present scenario). We have also constrained our model parameters with the updated (36 points) observational Hubble dataset.
𝒫𝒯-symmetric quantum field theory on the noncommutative spacetime
Authors: Novikov Oleg O.
Published: October 2019

We consider the [Formula: see text]-symmetric quantum field theory on the noncommutative spacetime with angular twist and construct its pseudo-Hermitian interpretation. We explore the differences between internal and spatial parities in the context of the angular twist and for the latter we find new [Formula: see text]-symmetric interactions that are nontrivial only for the noncommutative spacetime. We reproduce the same formula for the leading order T-matrix of the equivalent Hermitian model as the one obtained earlier for the quantum field theory on the commutative spacetime. This formula implies that the leading order scattering amplitude preserves the symmetries of the noncommutative geometry if they are not broken in the non-Hermitian formulation.
Difference of Cyclooxygenase-2 (COX2) Expression in Endometrium Between Patients with Polycystic Ovary Syndrome (PCOS) and Fertile Women
Authors: Budihastuti Uki Retno , Melinawati Eriana , Sulistyowati Sri , Laqief Abdurrahman , Dekawan M. Firdinan
Published: October 2019

Objective: The study was conducted to determine whether there were differences in COX-2 expression in endometrial women with PCOS compared to fertile women.

Methods: This study is a case-control study investigating the relationship between exposure (research factors) and disease, by comparing case group and control group based on their exposure status. The samples of this study were infertile polycystic ovary syndrome patients who were treated at the Sekar Fertility Clinic in Dr. Moewardi Hospital Surakarta, and fertile women seeking treatment at Dr. Moewardi Hospital Surakarta. The number of samples were 60 subjects consisting of 30 PCOS patients and 30 fertile women. The expression of COX-2 in endometrial biopsy LH + 5 until LH + 10 which meet the inclusion with Rotterdam criteria and exclusion criteria was checked by immunohistochemistry. The data was analyzed using the Mann-Whitney test.

Results: The mean COX-2 expression in PCOS (10.83 ± 5.35) in fertile women (37.00 ± 7.76), p = 0.005. Regression test of COX-2 by adjusting external variables (occupation, age, education, menstrual disorders, familial history, menstrual cycle, menarche, obesity, contraception history) shows also higher expression in PCOS patient with OR = -7.063; CI = 0.462–108.066; p = 0.160.

Conclusion: COX-2 expression in endometrium of women with PCOS is lower than it is in fertile women.
Non-smooth Newton Methods for Deformable Multi-body Dynamics
Authors: Macklin Miles , Erleben Kenny , Müller Matthias , Chentanez Nuttapong , Jeschke Stefan , Makoviychuk Viktor
Published: October 2019

We present a framework for the simulation of rigid and deformable bodies in the presence of contact and friction. Our method is based on a non-smooth Newton iteration that solves the underlying nonlinear complementarity problems (NCPs) directly. This approach allows us to support nonlinear dynamics models, including hyperelastic deformable bodies and articulated rigid mechanisms, coupled through a smooth isotropic friction model. The fixed-point nature of our method means it requires only the solution of a symmetric linear system as a building block. We propose a new complementarity preconditioner for NCP functions that improves convergence, and we develop an efficient GPU-based solver based on the conjugate residual (CR) method that is suitable for interactive simulations. We show how to improve robustness using a new geometric stiffness approximation and evaluate our method’s performance on a number of robotics simulation scenarios, including dexterous manipulation and training using reinforcement learning.
Fantastic Linguistics
Authors: Thomason Sarah , Poser William
Published: October 2019

Many nonlinguists believe that their ability to speak at least one language provides special insight into the essence of languages and their histories. One result of this belief is a plethora of theories about language from a surprising variety of perspectives: where particular languages (or all languages) originated, which languages are related by a shared history, how undeciphered writings or pseudowritings are to be read, how language figures in paranormal claims as “evidence” for reincarnation and channeled entities, and much, much more. This review surveys some of the major areas in which fringe and crackpot claims about language thrive. Only a few topics and examples can be covered in the limited space of a single article, but these should be enough, we hope, to suggest the range of wonderfully wacky pseudolinguistic notions out there.
JTZ-951, an HIF prolyl hydroxylase inhibitor, suppresses renal interstitial fibroblast transformation and expression of fibrosis-related factors
Authors: Wakashima Takeshi , Tanaka Tetsuhiro , Fukui Kenji , Komoda Yasumasa , Shinozaki Yuichi , Kobayashi Hatsue , Matsuo Akira , Nangaku Masaomi
Published: October 2019

Some preceding studies have provided evidence that hypoxia-inducible factor (HIF)-prolyl hydroxylase (PH) inhibitors have therapeutic potential against tubular interstitial fibrosis (TIF). Recently, transformation of renal interstitial fibroblasts (RIFs) into α-smooth muscle actin-positive myofibroblasts with loss of their hypoxia-inducible erythropoietin (EPO) expression has been hypothesized as the central mechanism responsible for TIF with renal anemia (the RIF hypothesis). These reports have suggested that HIF-PH inhibitors may suppress TIF via suppressing transformation of RIFs. However, the direct effect of HIF-PH inhibitors on transformation of RIFs has not been demonstrated because there has been no appropriate assay system. Here, we established a novel in vitro model of the transformation of RIFs. This model expresses key phenotypic changes such as transformation of RIFs accompanied by loss of their hypoxia-inducible EPO expression, as proposed by the RIF hypothesis. Using this model, we demonstrated that JTZ-951, a newly developed HIF-PH inhibitor, stabilized HIF protein in RIFs, suppressed transformation of RIFs, and maintained their hypoxia-inducible EPO expression. JTZ-951 also suppressed the expression of FGF2, FGF7, and FGF18, which are upregulated during transformation of RIFs. Furthermore, expression of Fgf2, Fgf7, and Fgf18 was correlated with TIF in an animal model of TIF. We also demonstrated that not only FGF2, which is a well-known growth-promoting factor, but also FGF18 promoted proliferation of RIFs. These data suggest that JTZ-951 has therapeutic potential against TIF with renal anemia. Furthermore, FGF2, FGF7, and FGF18, which faithfully reflect the anti-TIF effects of JTZ-951, have potential as TIF biomarkers.
Kinematic Parameters for Tracking Patient Progress during Upper Limb Robot-Assisted Rehabilitation: An Observational Study on Subacute Stroke Subjects
Authors: Goffredo Michela , Mazzoleni Stefano , Gison Annalisa , Infarinato Francesco , Pournajaf Sanaz , Galafate Daniele , Agosti Maurizio , Posteraro Federico , Franceschini Marco
Published: October 2019

Background. Upper limb robot-assisted therapy (RT) provides intensive, repetitive, and task-specific treatment, and its efficacy for stroke survivors is well established in literature. Biomechanical data from robotic devices has been widely employed for patient’s assessment, but rarely it has been analysed for tracking patient progress during RT. The goal of this retrospective study is to analyse built-in kinematic data registered by a planar end-effector robot for assessing the time course of motor recovery and patient’s workspace exploration skills. A comparison of subjects having mild and severe motor impairment has been also conducted. For that purpose, kinematic data recorded by a planar end-effector robot have been processed for investigating how motor performance in executing point-to-point trajectories with different directions changes during RT.Methods. Observational retrospective study of 68 subacute stroke patients who conducted 20 daily sessions of upper limb RT with the InMotion 2.0 (Bionik Laboratories, USA): planar point-to-point reaching tasks with an “assist as needed” strategy. The following kinematic parameters (KPs) were computed for each subject and for each point-to-point trajectory executed during RT: movement accuracy, movement speed, number of peak speed, and task completion time. The Wilcoxon signed-rank tests were used with clinical outcomes. the Friedman test and post hoc Conover’s test (Bonferroni’s correction) were applied to KPs. A secondary data analysis has been conducted by comparing patients having different severities of motor impairment. The level of significance was set atpvalue < 0.05.Results. At the RT onset, the movements were less accurate and smoothed, and showed higher times of execution than those executed at the end of treatment. The analysis of the time course of KPs highlighted that RT seems to improve the motor function mainly in the first sessions of treatment: most KPs show significant intersession differences during the first 5/10 sessions. Afterwards, no further significant variations occurred. The ability to perform movements away from the body and from the hemiparetic side remains more challenging. The results obtained from the data stratification show significant differences between subjects with mild and severe motor impairment.Conclusion. Significant improvements in motor performance were registered during the time course of upper limb RT in subacute stroke patients. The outcomes depend on movement direction and motor impairment and pave the way to optimize healthcare resources and to design patient-tailored rehabilitative protocols.
Generalized Halanay Inequalities with Applications to Generalized Exponential Stability and Boundedness of Time‐Delay Systems
Authors: Ruan Dehao , Liu Yue
Published: October 2019

In this paper, a class of generalized Halanay inequalities is investigated. Under some assumptions, the generalized exponential stability and boundedness are discussed by means of integral inequalities. We do not require the boundedness of the time‐varying delays and coefficients. In addition, our results improve some previous works. At last, three examples and simulations are given to illustrate the effectiveness of the main results.
Submacular Injection of Ranibizumab as a New Surgical Treatment for Refractory Diabetic Macular Edema
Authors: El-Baha Samir M. , Abdel Hadi Ahmed M. , Abouhussein Mahmoud A.
Published: October 2019

Purpose. In this study, we describe a new surgical technique for the treatment of refractory DME. The technique consists of vitrectomy with ILM peeling with a subretinal injection of ranibizumab. Methods. This is a prospective interventional noncomparative study including patients with refractory DME. Included patients were subjected to the new surgical technique of pars plana vitrectomy with subretinal injection of ranibizumab. Results. The study included 19 eyes with refractory macular edema, in which this novel technique was attempted. There were 10 males and 9 females. The age of the patients ranged from 17 to 67 years with a mean of 55.58 ± 13.242 years. The duration of diabetes before enrollment in the study ranged from 7 to 25 years with a mean of 16.3 years. Preoperatively, the mean CMT of the eyes ranged from 352 to 883 microns with mean ± SD of 498.58 ± 152.16 microns. Postoperatively, this improved significantly to 373.5 ± 100.3, 355.9 ± 89.8, and 365.74 ± 120.12 microns at 1, 3, and 6 months, respectively (p≤0.001 for all). Conclusion. This novel surgical procedure of vitrectomy with ILM peeling with a subretinal injection of ranibizumab is effective in cases of refractory DME. The study has been registered in Contact ClinicalTrials.gov PRS Identifier: NCT03975088.
Relationships between Ghrelin and Obestatin with MDA, Proinflammatory Cytokines, GSH/GSSG Ratio, Catalase Activity, and Semen Parameters in Infertile Patients with Leukocytospermia and Varicocele
Authors: Micheli Lucia , Collodel Giulia , Cerretani Daniela , Menchiari Andrea , Noto Daria , Signorini Cinzia , Moretti Elena
Published: October 2019

Ghrelin and obestatin are involved in many biological functions including reproduction. Growing evidences suggest that both peptides could exert protective and antioxidant activities. In this study, the relationships between ghrelin/obestatin, interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), expressed as the GSH/GSSG ratio, catalase (CAT), and semen parameters in infertile patients with varicocele or leukocytospermia and controls were investigated. Fifty-six infertile patients (32 with leukocytospermia and 24 with varicocele) and 14 controls participated in this study. Semen analysis was performed following the WHO guidelines. Apoptotic and necrotic sperm were scored by annexin V/propidium iodide assay. Seminal plasma samples were used for the following determinations: ghrelin, obestatin, IL-6, and TNF-αwere measured by an immunological method, GSH/GSSG by an enzymatic method, and CAT by spectrophotometric determination. With respect to controls, both the leukocytospermia and varicocele groups showed altered sperm parameters, significantly increased sperm apoptosis (P=0.009andP=0.011, respectively), IL-6 (P=0.0001andP=0.004, respectively), and TNF-αlevels (P=0.0001andP=0.002, respectively); both groups had significantly decreased levels of ghrelinP=0.0001, obestatin (P=0.0001andP=0.006, respectively), and GSH/GSSG ratio (P=0.003andP=0.0001, respectively). The MDA concentration was significantly increased in the leukocytospermia groupvs.controlsP=0.0001, in the varicocele groupvs.controlsP=0.011, and in the leukocytospermia groupvs.the varicocele groupP=0.008. CAT activity was augmented in both the leukocytospermia and varicocele groupsP=0.0001vs.controls. The results indicate that both ghrelin and obestatin may play a protective role in human semen and this effect is probably due to their antioxidant properties.
Effect of Sulfated Polysaccharide from Undaria pinnatifida (SPUP) on Proliferation, Migration, and Apoptosis of Human Prostatic Cancer
Authors: Xu Xiaolin , Zhu Xin , Lu Wenglong , He Yandong , Wang Yihan , Liu Feng
Published: October 2019

Objective. To observe the effect of sulfated polysaccharide from Undaria pinnatifida (SPUP) on proliferation, migration, and apoptosis of human prostatic cancer. Methods. DU145 human prostate cancer cells were cultured in vitro, and the proliferation activity both in the control group and the SPUP treatment groups (25, 50, 100, 200 μg/ml) was measured by CCK-8 assay. The wound healing assay was conducted to detect the cell migration. Cell apoptosis was measured by flow cytometry. The protein and mRNA expressions of matrix metalloproteinase-9 (MMP-9) and apoptosis-related factor Bax were detected by qRT-PCR and Western blot. The expressions of cleaved caspase-3 and cleaved caspase-9 were also determined by Western blot. Results. (1) CCK-8 results showed that the proliferative activity of DU145 cells was significantly decreased with the increase of SPUP treatment concentration (P<0.05) in a dose-dependent manner and that the inhibitory effect of SPUP was most significant at 72 h (P<0.05) as compared with the control group; (2) the migration rate of SPUP-treated cells was significantly decreased (P<0.05) as compared with the control group. And the results of qRT-PCR and Western blot assays showed that SPUP inhibited the expression of MMP-9 in DU145 cells; (3) compared with the control group, the SPUP-treated groups had increased apoptosis of the cells. The expressions of apoptosis-related factors cleaved caspase-3, cleaved caspase-9, and Bax were upregulated (P<0.05), and the mRNA expression of Bax was increased (P<0.05). Conclusion. SPUP showed an antitumor activity in prostatic cancer, and the underlying mechanism may be pertaining to inhibition of migration, proliferation, and induction of apoptosis of cancer cells.
Simultaneous Determination of Three Bioactive Constituents from Bletilla striata by UPLC-MS/MS and Application of the Technique to Pharmacokinetic Analyses
Authors: Chen Hao , Zheng Lin , Mei Chao-Ye , Gong Zi-Peng , Li Yong-Jun , Chen Si-Ying , Lan Yan-Yu , Wang Yong-Lin , Wang Ai-Min , Li Yue-Ting , Huang Yong
Published: October 2019

Bletilla striata has been widely used as a valuable hemostatic agent for thousands of years due to the high levels of bioactive constituents it contains. Here, we used a sensitive ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method for the simultaneous determination of three major active ingredients of the B. striata extract, namely, α-isobutylmalic acid, gymnoside I, and militarine in rat plasma. The three major active ingredients were determined using the multiple reaction monitoring (MRM) mode at m/z 189 ⟶ 129 for α-isobutylmalic acid, m/z 457.2 ⟶ 285.1 for gymnoside I, m/z 725.3 ⟶ 457.2 for militarine, and m/z 417.0 ⟶ 267.0 for the IS puerarin. All calibration curves showed good linearity (R2 ≥ 0.999) over the concentration range with the lower limit of quantification between 0.015 and 0.029 μg/mL. The relative standard deviations of intraday and interday measurements were less than 15%, and the method was accurate within 93.3–100.4%. The extraction recovery was 92.65–100.98%, and no matrix effect was observed. The results indicated that after oral administration of B. striata in rats, the Tmax of α-isobutylmalic acid was significantly longer than that of gymnoside I and militarine and the mean residence time and area under the curve of α-isobutylmalic acid and gymnoside I in rats were significantly higher than those of militarine. Moreover, the blood concentration-time curve of α-isobutylmalic acid showed double peaks, suggesting that α-isobutylmalic acid could exhibit the phenomenon of enterohepatic circulation or metabolic conversion. We also explored some of the pharmacokinetic characteristics of three ingredients from B. striata extract in vivo, and the data obtained may provide a basis for the further investigation of B. striata.
Phase I Clinical Trial of Selinexor in Combination with Daunorubicin and Cytarabine in Previously Untreated Poor-Risk Acute Myeloid Leukemia
Authors: Sweet Kendra , Komrokji Rami , Padron Eric , Cubitt Christopher L. , Turner Joel G. , Zhou Junmin , List Alan F. , Sallman David A. , Dawson Jana L. , Sullivan Daniel M. , Chavez Julio , Shah Bijal D. , Lancet Jeffrey E.
Published: October 2019

Purpose:

Induction chemotherapy results in complete remission (CR) rates of 20% to 50% among patients with poor-risk AML. Selinexor is an oral selective inhibitor of nuclear export with promising single-agent activity. By inhibiting the primary export protein, XPO1, selinexor localizes and activates tumor suppressor proteins in the nucleus and inhibits DNA damage repair, rationalizing combination with DNA-damaging agents.

Patients and Methods:

This was a single-arm phase I clinical trial of selinexor combined with cytarabine and daunorubicin (7+3). Dose escalation was selinexor alone (3+3) with an expansion at the MTD. Cohorts 1 and 2 received 60 and 80 mg orally, respectively, twice weekly during induction. Consolidation cycles (≤ 2) with selinexor at induction dose plus 5+2 were allowed for patients who achieved CR. MTD and recommended phase II dose of selinexor were the primary endpoints.

Results:

Twenty-one patients with poor-risk AML were enrolled. All 21 patients were included in the safety evaluations and survival analyses (4 in each of 2 cohorts; 13 in the expansion); 8 (53%) of the 19 patients evaluable for response achieved CR/CRi. MTD was not reached. Selinexor 80 mg (orally, twice weekly) was used in the expansion phase. The most common grade 3/4 nonhematologic treatment-emergent adverse events were febrile neutropenia (67%), diarrhea (29%), hyponatremia (29%), and sepsis (14%). At median follow-up (28.9 months), 38% of patients were alive. Median overall survival was 10.3 months.

Conclusions:

Selinexor plus 7+3 is a safe regimen for patients with newly diagnosed poor-risk AML and warrants further investigation in a larger clinical trial.
Autoimmune Pancreatitis in an Adolescent: A Diagnostic Challenge
Authors: Ramos Rita , Carneiro Inês , Palma Rui , Calhau Paulo
Published: October 2019

Autoimmune pancreatitis (AIP) is a distinct subtype of pancreatitis, rare in the pediatric population. Its pathophysiology is poorly understood. A pancreatic focal mass is frequently the clinical presentation, which imposes the differential diagnosis with a pancreatic tumor. This distinction is essential because the treatment of pancreatic tumors is surgical in contrast to the treatment of AIP, which is pharmacological. We describe a case of a 16-year-old girl with AIP who presented with obstructive jaundice, weight loss, fatigue, and a pancreatic mass. This case emphasizes the importance of considering this diagnosis to correctly treat and prevent an abusive pancreatic resection.
Activation of a Classic Hunger Circuit Slows Luteinizing Hormone Pulsatility
Authors: Coutinho Eulalia A. , Prescott Melanie , Hessler Sabine , Marshall Christopher J. , Herbison Allan E. , Campbell Rebecca E.
Published: October 2019

Introduction: The central regulation of fertility is carefully coordinated with energy homeostasis, and infertility is frequently the outcome of energy imbalance. Neurons in the hypothalamus expressing neuropeptide Y and agouti-related peptide (NPY/AgRP neurons) are strongly implicated in linking metabolic cues with fertility regulation. Objective: We aimed here to determine the impact of selectively activating NPY/AgRP neurons, critical regulators of metabolism, on the activity of luteinizing hormone (LH) pulse generation. Methods: We employed a suite of in vivo optogenetic and chemogenetic approaches with serial measurements of LH to determine the impact of selectively activating NPY/AgRP neurons on dynamic LH secretion. In addition, electrophysiological studies in ex vivo brain slices were employed to ascertain the functional impact of activating NPY/AgRP neurons on gonadotropin-releasing hormone (GnRH) neurons. Results: Selective activation of NPY/AgRP neurons significantly decreased post-castration LH secretion. This was observed in males and females, as well as in prenatally androgenized females that recapitulate the persistently elevated LH pulse frequency characteristic of polycystic ovary syndrome (PCOS). Reduced LH pulse frequency was also observed when optogenetic stimulation was restricted to NPY/AgRP fiber projections surrounding GnRH neuron cell bodies in the rostral preoptic area. However, electrophysiological studies in ex vivo brain slices indicated these effects were likely to be indirect. Conclusions: These data demonstrate the ability of NPY/AgRP neuronal signaling to modulate and, specifically, reduce GnRH/LH pulse generation. The findings suggest a mechanism by which increased activity of this hunger circuit, in response to negative energy balance, mediates impaired fertility in otherwise reproductively fit states, and highlight a potential mechanism to slow LH pulsatility in female infertility disorders, such as PCOS, that are associated with hyperactive LH secretion.
Pesquisa em educação: diversidade e desafios
Authors:   Universidade de São Paulo. Faculdade de Educação, Ricardo Elio Carlos , Pataca Ermelinda Moutinho  Pataca ,   Universidade de São Paulo. Faculdade de Educação, Ginzel Flávia ,   Universidade de São Paulo. Faculdade de Educação, Onisaki Hadassa Harumi Castelo Onisaki ,   Universidade de São Paulo. Faculdade de Educação, Tomizaki Kimi ,   Universidade de São Paulo. Faculdade de Educação, Pino Larissa Jordão ,   Universidade de São Paulo. Faculdade de Educação, Silva Livia Viana Ribeiro da ,   Universidade de São Paulo. Faculdade de Educação, Setton Maria da Graça Jacintho ,   Universidade de São Paulo. Faculdade de Educação, Biccas Maurilane de Souza ,   Universidade de São Paulo. Faculdade de Educação, Cacete Nuria Hanglei ,   Universidade de São Paulo. Faculdade de Educação, Martins Tatiana Carence ,   Universidade de São Paulo. Faculdade de Educação, Araújo Valéria Amorim Arantes de ,   Universidade de São Paulo. Faculdade de Educação
Published: October 2019

Esta publicação foi inspirada a partir dos debates e discussões ocorridos no âmbito das reuniões do Programa de Pós-graduação em Educação da Faculdade de Educação da USP (PPGE/FEUSP) e foi concebida tendo como objetivo central divulgar, por meio de acesso livre, a produção dos discentes do PPGE/FEUSP, mostrando as tendências temáticas, teóricas e metodológicas dos estudos educacionais desenvolvidos no âmbito da Universidade de São Paulo. Além disso, a obra conta com a preciosa colaboração da professora Maria Isabel de Almeida, cujo texto “Qual o papel da PósGraduação em Educação no Brasil atual? Reflexões sobre o nosso percurso” introduz o debate que se alongará pelos demais textos que, os organizadores esperam, constitua uma contribuição importante para o campo de estudos da Educação.
El papel del movimiento Jaranero en la salvaguarda del fandango Jarocho (México)
Authors: Sonderegger Melba , Lessa Giane Da Silva Mariano
Published: October 2019

El fandango jarocho es un evento festivo comunitario con música y baile, producto del mestizaje, cuya tradición hunde sus raíces desde la época colonial. Durante la primera mitad del siglo XX, el fandango jarocho atravesó un punto crítico para la continuación de su práctica, por lo que, a partir de la década de los 80, surge un colectivo interesado en su investigación, revitalización y difusión, denominado Movimiento jaranero. En estas páginas se explicita el proceso de salvaguarda del fandango jarocho iniciado por el Movimiento jaranero, entendido como una articulación socio-estatal, que buscó garantizar una generación de relevo y la pervivencia del fandango. Como resultado de la tensión entre pasado y presente, actualmente el fandango y el sonjarocho – el género musical que le hace parte – se manifiestan en diversas esferas y con variacionesque alcanzan incluso la fusión con otros géneros musicales.
A Tríplice Fronteira como região
Authors: Gimenez Heloisa Marques , Lisboa Marcelino Teixeira , Silva Micael Alvino , Diallo Mamadou Alpha
Published: October 2019

este artigo propõe a compreensão da Tríplice Fronteira Argentina-Brasil-Paraguai (TF) como região internacional, em duas dimensões: local e global. A primeira diz respeito à articulação do território fronteiriço compartilhado pelos três Estados por meio de infraestrutura e fluxos de pessoas e mercadorias, criando uma dinâmica local de característica internacional. A segunda refere-se à contemporânea menção da TF como região relacionada aos novos temas da agenda internacional, devido aos desdobramentos dos fluxos de pessoas e mercadorias. O artigo vale-se de uma reflexão conceitual, de dados históricos e de uma contextualização do caráter dos fluxos verificados em consonância com a agenda internacional.
Evolução estrutural dos Granitoides Arroio Divisa durante o movimento transcorrente da Zona de Cisalhamento Quitéria-Serra do Erval, Rio Grande do Sul
Authors: Schnorr Evelin Roberta , Bitencourt Maria De Fátima
Published: October 2019

Os Granitoides Arroio Divisa (GAD) compreendem uma associação de rochas predominantemente granodioríticas, com termos dioríticos e tonalíticos em menor expressão. Apresentam textura heterogranular média a grossa e são sempre foliadas. Suas estruturas sugerem posicionamento em zona de cisalhamento dúctil correlacionada ao Cinturão de Cisalhamento Sul-brasileiro (CCSb), de idade neoproterozoica. Essas rochas registram cristalização com concomitante história deformacional sob condições de temperatura decrescente, evidenciada pela sobreposição concordante de estruturas magmáticas por estruturas de deformação de estado sólido em temperatura decrescente. A distribuição da deformação se dá de forma heterogênea ao longo da intrusão, gerando-se zonas de baixa e alta deformação inicialmente magmáticas e progredindo para o estado sólido. Nas porções internas do corpo intrusivo predominam estruturas de fluxo em que o alinhamento preferencial de forma é dominante, e a deformação interna dos marcadores é pouco desenvolvida. Em direção à borda norte da intrusão, a morfologia dessas estruturas progride por aumento na intensidade da deformação, com a geração de uma foliação fortemente milonítica paralela à trama magmática. Feições microestruturais de alta temperatura incluem o desenvolvimento de subgrãos em padrão tabuleiro de xadrez no quartzo, “e a geração de subgrãos grandes em cristais de K-feldspato e plagioclásio, que são compatíveis com temperaturas da fácies anfibolito superior e com a temperatura solidus de composições granítcas. As feições microestruturais de baixa temperatura consistem na recristalização dos cristais de quartzo por bulging, na neoformação de grãos finos ao redor dos cristais de feldspatos e no desenvolvimento de pertitas em chamas no K-feldspato, compatíveis com temperaturas da fácies xisto verde, bem abaixo da solidus. Portanto, as microestruturas de alta temperatura estariam associadas aos estágios iniciais de resfriamento
A20 in Myeloid Cells Protects Against Hypertension by Inhibiting Dendritic Cell-Mediated T-Cell Activation
Authors: Lu Xiaohan , Rudemiller Nathan P. , Wen Yi , Ren Jiafa , Hammer Gianna E. , Griffiths Robert , Privratsky Jamie R. , Yang Bo , Sparks Matthew A. , Crowley Steven D.
Published: October 2019

Rationale:

The ubiquitin-editing protein A20 in dendritic cells (DCs) suppresses NF-κB (nuclear factor-κB) signaling and constrains DC-mediated T-cell stimulation, but the role of A20 in modulating the hypertensive response requires elucidation.

Objective:

Here, we tested the hypothesis that A20 in CD11c-expressing myeloid cells mitigates Ang II (angiotensin II)–induced hypertension by limiting renal T-cell activation.

Methods and Results:

Mice with heterozygous deletion of A20 in CD11c-expressing myeloid cells (DC ACT[
Cd11c-Cre
+
A20

flox/wt

]) have spontaneous DC activation but have normal baseline blood pressures. In response to low-dose chronic Ang II infusion, DC ACT mice compared with WT (wild type) controls had an exaggerated hypertensive response and augmented proportions of CD62L
lo
CD44
hi
effector memory T lymphocytes in the kidney lymph node. After 10 days of Ang II, DC ACT kidneys had increased numbers of memory effector CD8
+
, but not CD4
+
T cells, compared with WTs. Moreover, the expressions of TNF-α (tumor necrosis factor-α) and IFN-γ (interferon-γ) were upregulated in the DC ACT renal CD8
+
T cells but not CD4
+
T cells. Saline challenge testing revealed enhanced renal fluid retention in the DC ACT mice. DC ACT kidneys showed augmented protein expression of γ-epithelial sodium channel and NHE3 (sodium-hydrogen antiporter 3). DC ACT mice also had greater reductions in renal blood flow following acute injections with Ang II and enhanced oxidant stress in the vasculature as evidenced by higher circulating levels of malondialdehyde compared with WT controls. To directly test whether enhanced T-cell activation in the DC ACT cohort was responsible for their exaggerated hypertensive response, we chronically infused Ang II into lymphocyte-deficient DC ACT Rag1 (recombination activating protein 1)-deficient (
Rag1
−/−
) mice and WT (
Cd11c
-
Cre
−
A20

flox/wt

) Rag1
−/−
controls. The difference in blood pressure elevation accruing from DC activation was abrogated on the Rag1
−/−
strain.

Conclusions:

Following stimulation of the renin-angiotensin system, A20 suppresses DC activation and thereby mitigates T-cell–dependent blood pressure elevation.
Technology-Enabled Clinical Trials
Authors: Marquis-Gravel Guillaume , Roe Matthew T. , Turakhia Mintu P. , Boden William , Temple Robert , Sharma Abhinav , Hirshberg Boaz , Slater Paul , Craft Noah , Stockbridge Norman , McDowell Bryan , Waldstreicher Joanne , Bourla Ariel , Bansilal Sameer , Wong Jennifer L. , Meunier Claire , Kassahun Helina , Coran Philip , Bataille Lauren , Patrick-Lake Bray , Hirsch Brad , Reites John , Mehta Rajesh , Muse Evan D. , Chandross Karen J. , Silverstein Jonathan C. , Silcox Christina , Overhage J. Marc , Califf Robert M. , Peterson Eric D.
Published: October 2019

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.
Mild Coarctation of Aorta is an Independent Risk Factor for Exercise-Induced Hypertension
Authors: Egbe Alexander C. , Allison Thomas G. , Ammash Naser M.
Published: October 2019

Exercise-induced hypertension is a predictor of cardiovascular events in patients with coarctation of aorta (COA). However, it is unclear whether mild COA diagnosis is an independent risk factor of exercise-induced hypertension. We hypothesized that for every unit increase in exercise, patients with COA (without hemodynamically significant coarctation) will have a higher rise in systolic blood pressure (SBP) compared with matched controls. One hundred forty-nine patients with COA (aortic coarctation peak velocity <2 m/s) who underwent exercise testing were matched 1:1 to controls using propensity score method based on age, sex, body mass index, hypertension diagnosis, and SBP at rest. We compared exercise-induced change in SBP between patients with COA and controls and also assessed the correlation between Doppler-derived aortic vascular function indices (effective arterial elastance index and total arterial compliance index) and exercise-induced changes in SBP. Compared with controls, patients with COA had a greater change in SBP per unit metabolic equivalent (β=2.86; 95% CI, 1.96–4.77 versus 1.07, 95% CI, −0.15 to 1.75;
P
=0.018) and per unit oxygen pulse (β=4.57; 95% CI, 2.97–7.12 versus 1.45, 95% CI, −0.79 to 2.09,
P
<0.001). There was a correlation between SBP
peak
−SBP
rest
and elastance index (
r
=0.38,
P
=0.032) and between SBP
peak
−SBP
rest
and total arterial compliance index (
r
=−0.51,
P
=0.001), suggesting an association between vascular dysfunction and exercise-induced BP changes. Patients with COA, without significant obstruction, had higher exercise-induced changes in SBP after adjustment for other risk factors for hypertension. Considering the already known prognostic importance of exercise-induced hypertension, the current study highlights the potential role of exercise testing for risk stratification of patients with mild COA.