bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Time Swing-up and Stabilization Control of a Cart-Pendulum System with Constrained Cart Movement
Authors: Singla Ashish , Singh Gurminder
Published: September 2017

The cart-pendulum system is a typical benchmark problem in the control field. It is a fully underactuated system having one control input for two degrees-of-freedom (DOFs) system. It has highly nonlinear structure, which can be used to validate different nonlinear and linear controllers and has wide range of real-time (realistic) applications like rockets propeller, tank missile launcher, self-balancing robot, stabilization of ships, design of earthquake resistant buildings, etc. In this work, modeling, simulation and real-time control of a cart-pendulum system is performed. The mathematical model of the system is developed using Euler-Lagrange approach. In order to achieve a more realistic model, the actuator dynamics is considered in the mathematical model. The main aim of this work is to investigate the performance of two different control strategies- first to swing-up the pendulum to near unstable equilibrium region and second to stabilize the pendulum at unstable equilibrium point. The swing-up problem is addressed by using energy controller in which cart is accelerated by providing a force to the cart with a AC servo motor with the help of timing pulley arrangement. The initial velocity of the cart is taken into account to confirm swing-up in the restricted track length. The cart displacement in the restricted track length is verified by simulation and experimental test-run. The regulation problem of stabilization of pendulum is addressed by developing the controller using Pole Placement Controller (PPC) and LQR Controller (LQRC). Both the control strategies are performed analytically and experimentally using the Googoltech Linear Inverted Pendulum (GLIP) setup. The analytical results, simulated in MATLAB and SIMULINK environment, are found in close agreement with the experimental results. In order to demonstrate the effect of both the stabilizing controllers on the performance of the system, comparison of the experimental results is reported in this work. It is demonstrated experimentally that LQR controller outperforms the Pole Placement controller, in terms of reduction in the oscillations of the inverted pendulum (56 %), as well as the magnitude of maximum control input (66.7 %). Further, robustness of the closed-loop system is investigated by providing external disturbances.
Towards the Moho depth and Moho density contrast along with their uncertainties from seismic and satellite gravity observations
Authors: Abrehdary M. , Sjöberg L.E. , Bagherbandi M. , Sampietro D.
Published: September 2017

We present a combined method for estimating a new global Moho model named KTH15C, containing Moho depth and Moho density contrast (or shortly Moho parameters), from a combination of global models of gravity (GOCO05S), topography (DTM2006) and seismic information (CRUST1.0 and MDN07) to a resolution of 1° × 1° based on a solution of Vening Meinesz-Moritz’ inverse problem of isostasy. This paper also aims modelling of the observation standard errors propagated from the Vening Meinesz-Moritz and CRUST1.0 models in estimating the uncertainty of the final Moho model. The numerical results yield Moho depths ranging from 6.5 to 70.3 km, and the estimated Moho density contrasts ranging from 21 to 650 kg/m3, respectively. Moreover, test computations display that in most areas estimated uncertainties in the parameters are less than 3 km and 50 kg/m3, respectively, but they reach to more significant values under Gulf of Mexico, Chile, Eastern Mediterranean, Timor sea and parts of polar regions. Comparing the Moho depths estimated by KTH15C and those derived by KTH11C, GEMMA2012C, CRUST1.0, KTH14C, CRUST14 and GEMMA1.0 models shows that KTH15C agree fairly well with CRUST1.0 but rather poor with other models. The Moho density contrasts estimated by KTH15C and those of the KTH11C, KTH14C and VMM model agree to 112, 31 and 61 kg/m3 in RMS. The regional numerical studies show that the RMS differences between KTH15C and Moho depths from seismic information yields fits of 2 to 4 km in South and North America, Africa, Europe, Asia, Australia and Antarctica, respectively.
Understanding fetal factors that contribute to preterm birth: Sjögren-Larsson syndrome as a model
Authors: Staps Pippa , Hogeveen Marije , Fuijkschot Joris , van Drongelen Joris , Willemsen Michèl A.A.P.
Published: September 2017

Aim:

Preterm birth is the world’s leading cause of neonatal death. Unfortunately, the pathophysiology of preterm birth remains poorly understood. Sjögren-Larsson syndrome is a rare, neurometabolic disorder caused by a fatty aldehyde dehydrogenase deficiency. A majority of patients with Sjögren-Larsson syndrome is born preterm.

Methods:

Data of all known Dutch patients with Sjögren-Larsson syndrome and all cases reported in literature were analyzed to learn from preterm birth in context of this rare disease.

Results:

Exact gestational age was known in 33 Dutch patients; 24 (73%) of them were born preterm, with a median gestational age of 36 weeks. The literature search confirmed our findings: 13 (59%) of 22 cases was born preterm.

Conclusions:

Preterm birth is a hallmark of Sjögren-Larsson syndrome, presumably caused by the abnormal lipid metabolism of the fetus. At least five additional rare genetic disorders (namely Ehlers-Danlos syndrome, ichthyosis prematurity syndrome, congenital analbuminemia, osteogenesis imperfecta type II and restrictive dermopathy) were found in literature that lead to preterm birth of the affected fetus. These disorders are in fact “experiments of nature” and as such they shed new lights on the mechanisms causing preterm birth.
Placental examination in nonmacerated stillbirth versus neonatal mortality
Authors: Stanek Jerzy
Published: September 2017

Aim:

To retrospectively statistically compare clinical and placental phenotypes of nonmacerated fetuses and live-born perinatal deaths in 3rdtrimester pregnancies.

Methods:

Twenty-five clinical and 47 placental phenotypes were statistically compared among 93 cases of nonmacerated (intrapartum, or recent antepartum death) 3rdtrimester fetal deaths (Group 1), 118 3rdtrimester neonatal deaths (Group 2) and 4285 cases without perinatal mortality (Group 3).

Results:

Sixteen clinical and placental phenotypes were statistically significantly different between Group 3 and the two groups of perinatal deaths, which included eight placental phenotypes of fetal vascular malperfusion and eight other placental phenotypes of various etiology (amnion nodosum, 2-vessel umbilical cord, villous edema, increased extracellular matrix of chorionic villi, erythroblasts in fetal blood and trophoblastic lesions of shallow placentation). Statistically significant differences between Groups 1 and 2 were scant (oligohydramnios, fetal malformations, cesarean sections, hypercoiled umbilical cord and amnion nodosum being more common in the latter, and retroplacental hematoma more common in the former).

Conclusion:

Placental examination in neonatal mortality shows thrombotic pathology related to umbilical cord compromise and features of shallow placental implantation that are similar to those in nonmacerated stillbirth; however, the features of placental abruption were more common in recent antepartum death, as were the features related to neonatal congenital malformations in neonatal deaths.
Anomalous extinction in index-matched terahertz nanogaps
Authors: Jeong Jeeyoon , Kim Dasom , Park Hyeong-Ryeol , Kang Taehee , Lee Dukhyung , Kim Sunghwan , Bahk Young-Mi , Kim Dai-Sik
Published: September 2017

Slot-type nanogaps have been widely utilized in transmission geometry because of their advantages of exclusive light funneling and exact quantification of near-field enhancement at the gap. For further application of the nanogaps in electromagnetic interactions with various target materials, complementary studies on both transmission and reflection properties of the nanogaps are necessary. Here, we observe an anomalous extinction of terahertz waves interacting with rectangular ring-shaped sub-30 nm wide gaps. Substrate works as an index matching layer for the nanogaps, leading to a stronger field enhancement and increased nonlinearity at the gap under substrate-side illumination. This effect is expressed in reflection as a larger dip at the resonance, caused by destructive interference of the diffracted field from the gap with the reflected beam from the metal. The resulting extinction at the resonance is larger than 60% of the incident power, even without any absorbing material in the whole nanogap structure. The extinction even decreases in the presence of an absorbing medium on top of the nanogaps, suggesting that transmission and reflection from nanogaps might not necessarily represent the absorption of the whole structure.
Buying Friends? The Importance of Economic Flows in Assembling the Iraq War Coalition
Authors: Riegler Robert , Lis Piotr , Hisarciklilar Mehtap
Published: September 2017

Economic ties between countries are likely to influence the alignment of their international policies. This paper investigates whether countries’ historical economic ties with the United States and their expectation of changes in future economic flows had a role in their decision to join the US-led coalition in Iraq from 2003 onwards. We use data on 115 countries over the period 2003–2009 to estimate panel random effects probit models of war coalition participation. We measure the intensity of economic ties with three variables: bilateral trade flows between the partner country and the US as well as FDI and aid flows from the US to the partner country. Our results suggest that both good trade relations prior to the conflict and the prospects of their further improvements increase the willingness of countries to join the coalition. In spite of the anecdotal evidence, we find no empirical evidence that the dependence on American FDI or aid affected countries’ decision on Iraq war participation.
Influence of a locally variable mold temperature on injection molded thin-wall components
Authors: Fischer Christopher , Jungmeier Ariane , Peters Guido , Drummer Dietmar
Published: September 2017

Regarding injection-molding of semi-crystalline thermoplastics, controlling mold temperature and, therefore, the polymer melt’s cooling conditions can significantly affect component properties. In this research, an innovative dynamically tempered mold technology with different temperature zones is investigated, which will allow the production of thin-wall components with locally different component properties. First results show that due to influencing inner component properties, significant differences in optical and mechanical component properties can be achieved.
Molecular, vibrational and electronic structure of 4-bromo-2-halogenobenzaldehydes: Halogen and solvent effects
Authors: Fernández David , Parlak Cemal , Bilge Metin , Kaya Mehmet Fatih , Tursun Mahir , Keşan Gürkan , Rhyman Lydia , Ramasami Ponnadurai , Şenyel Mustafa
Published: September 2017

The halogen and solvent effects on the structure of 4-bromo-2-halogenobenzaldehydes [C
Effect of pKa on the extraction behavior of Am(III) in organo phosphorus acid and diglycolamide solvent system
Authors: Rama Swami K. , Kumaresan R. , Nayak P. K. , Venkatesan K. A. , Antony M. P.
Published: September 2017

A combination of neutral and acidic extractant has been proposed for the single-cycle separation of trivalent actinides from high-level liquid waste (HLLW). The nature of acidic extractant in the combined solvent formulation plays a profound role in deciding the extraction and stripping of trivalent actinides. Therefore, the extraction behavior of Am(III) in a solution of tetra-bis(2-ethylhexyl)-diglycolamide (TEHDGA) and acidic extractant (HA) was studied from nitric acid medium. The acidic extractants chosen were bis(2-ethylhexyl)phosphoric acid (HDEHP), bis(2-ethylhexyl)phosphonic acid (PC88A) and bis(2,4,4-trimethylpentyl)phosphinic acid (CYANEX-272) whose pKa values were 3.24, 4.51 and 6.37, respectively. The distribution ratio of Am(III) was measured as a function of various parameters such as concentration of nitric acid, TEHDGA, HA etc. The data were compared with those obtained in individual solvent systems namely 0.1 M TEHDGA/n-DD and HA/n-DD. Slope analysis of the extraction data indicated the synergic participation of both TEHDGA and HDEHP in the extraction of Am(III) at all acidities. However, antagonistic effect was observed at lower acidity when TEHDGA was mixed to PC88A or CYANEX-272 present in n-DD. Accordingly, a suitable mechanism has been proposed for the extraction of Am(III) at all acidities using these combined solvent formulation. Studies with fast reactor simulated high level liquid waste indicated that extraction of Am(III) was accompanied by co-extraction of lanthanides and unwanted metal ions such as Zr(IV), Mo(VI), Y(III) and Pd(II). However, addition of trans-1,2-diaminocyclohexane-N,N,N,N′-tetraaceticacid (CyDTA) reduced the extraction of unwanted metal ions. Batch extraction and stripping studies indicated the possibility of using 0.1 M TEHDGA+0.25 M HDEHP in n-dodecane for the single cycle separation of Am(III) from FR-SHLLW.
Survival and stability of patients with urothelial cancer and spinal bone metastases after palliative radiotherapy
Authors: Foerster Robert , Hees Katharina , Bruckner Thomas , Bostel Tilman , Schlampp Ingmar , Sprave Tanja , Nicolay Nils H. , Debus Juergen , Rief Harald
Published: September 2017

Background

The aim of the study was to analyze survival and stability of patients with urothelial cell cancer and spinal bone metastases (SBM) after radiotherapy (RT). Furthermore, to assess the effects of RT on bone mineral density (BMD) as a local response in SBM after RT.

Patients and methods

Survival of 38 patients with 132 SBM from urothelial cancer, treated from January 2000 to January 2012, was calculated. Stability of irradiated thoracic and lumbar SBM was retrospectively evaluated in computed tomography (CT) scans using the validated Taneichi et al. score. Difference in BMD, measured in Hounsfield units (HU), of the SBM before and at 3 and 6 months after RT was analyzed.

Results

All patients died during follow-up. Overall survival (OS) after 6 months, 1 year and 2 years was 90%, 80% and 40%, respectively. Bone survival (BS) was 85%, 64% and 23% after 6 months, 1 year and 2 years, respectively. Survival from start of RT (RTS) was 42% after 6 months, 18% after 1 year and 5% after 2 years. Only 11% received bisphosphonates. Stability did not improve at 3 or 6 months after RT. BMD increased by 25.0 HU ± 49.7 SD after 3 months (p = 0.001) and by 24.2 HU ± 52.2 SD after 6 months (p = 0.037). Pain relief (> 2 points on the visual analogue scale) was achieved in only 27% of patients.

Conclusions

Benefit from palliative RT of painful or unstable SBM is limited in these patients and they should be carefully selected for RT. Shorter fractionation schedules may be preferred and outcome may improve with concomitant bisphosphonates.
Outcomes of the surgical treatment for adenocarcinoma of the cardia – single institution experience
Authors: Potrc Stojan , Ivanecz Arpad , Krebs Bojan , Marolt Urska , Iljevec Bojan , Jagric Tomaz
Published: September 2017

Background

Adenocarcinomas at the cardia are biologically aggressive tumors with poor long-term survival following curative resection. For resectable adenocarcinoma of the cardia, mostly esophagus extended total gastrectomy or esophagus extended proximal gastric resection is performed; however, the surgical approach, transhiatal or transthoracic, is still under discussion. Postoperative morbidity, mortality and long-term survival were analyzed to evaluate the potential differences in clinically relevant outcomes.

Patients and methods

Of altogether 844 gastrectomies performed between January 2000 and December 2016, 166 were done for the adenocarcinoma of the gastric cardia, which we analyzed with using the Cox proportional hazards model.

Results

136 were esophagus extended total gastrectomy and 125 esophagus extended proximal gastric resection. A D2 lymphadenectomy was performed in 88.2%, splenectomy in 47.2%, and multivisceral resections in 12.4% of patients. R0 resection rate was 95.7%. The mean proximal resection margin on the esophagus was 42.45 mm. It was less than 21 mm in 9 patients. Overall morbidity regarding Clavien-Dindo classification (> 1) was altogether 28.6%. 15.5% were noted as surgical and 21.1% as medical complications. The 30-day mortality was 2.2%. The 5-year survival for R0 resections was 33.4%. Multivisceral resection, depth of tumor infiltration, nodal stage, and curability of the resection were identified as independent prognostic factors.

Conclusions

Transhiatal approach for resection of adenocarcinoma of the cardia is a safe procedure for patients with Siewert II and III regarding the postoperative morbidity and mortality; moreover, long-term survival is comparable to transthoracic approach. The complications associated with thoracoabdominal approach can therefore be avoided with no impact on the rate of local recurrence.
Air pollution, aeroallergens and suicidality: a review of the effects of air pollution and aeroallergens on suicidal behavior and an exploration of possible mechanisms
Authors: Ragguett Renee-Marie , Cha Danielle S. , Subramaniapillai Mehala , Carmona Nicole E. , Lee Yena , Yuan Duanduan , Rong Carola , McIntyre Roger S.
Published: September 2017

Objective:

Risk factors for suicide can be broadly categorized as sociodemographic, clinical and treatment. There is interest in environmental risk and protection factors for suicide. Emerging evidence suggests a link between environmental factors in the form of air pollution and aeroallergens in relation to suicidality.

Methods:

Herein, we conducted a systematic review of 15 articles which have met inclusion criteria on the aforementioned effects.

Results:

The majority of the reviewed articles reported an increased suicide risk alongside increased air pollutants or aeroallergens (i.e. pollen) increase; however, not all environmental factors were explored equally. In specific, studies that were delimited to evaluating particulate matter (PM) reported a consistent association with suicidality. We also provide a brief description of putative mechanisms (e.g. inflammation and neurotransmitter dysregulation) that may mediate the association between air pollution, aeroallergens and suicidality.

Conclusion:

Available evidence suggests that exposure to harmful air quality may be associated with suicidality. There are significant public health implications which are amplified in regions and countries with greater levels of air pollution and aeroallergens. In addition, those with atopic sensitivity may represent a specific subgroup that is at risk.
Mere Preparation
Authors: Mungan Murat C.
Published: September 2017

Acts that are merely in preparation for the commission of a crime are not punished in many jurisdictions. This article provides a wrongful-imprisonment-cost-minimization based justification for this practice. It highlights that conceiving of sufficient proximity based on the trade-off between error-costs and deterrence-benefits may be a more useful alternative to conceptions that rely on physical or temporal proximity to define merely preparatory acts.
D. Timothy Goering: System der Käseplatte. Aufstieg und Fall der Dialektischen Theologie
Authors: Goering D. Timothy
Published: September 2017

The group of Dialectical Theology (also known as Neo-Orthodoxy) included some of the most well-known theologians of the 20th century – Karl Barth, Rudolf Bultmann, Friedrich Gogarten, Eduard Thurneysen, Georg Merz und Emil Brunner. In the summer of 1922 they founded the journal Zwischen den Zeiten, which launched Dialectical Theology as the most influential avant-garde movement in Protestantism during the Weimar Republic. Due to internal strife and theological disagreements, the group began to lose strength in the early 1930s and eventually split up and ceased publishing Zwischen den Zeiten in 1933. The individual members later became fierce critics of each other’s theological works. Gogarten and Barth became arch enemies during the so-called “church struggle” (Kirchenkampf), and Bultmann and Barth became each other’s nemesis in the Federal Republic of Germany.

In this article I examine the rise and fall of this movement. I argue that the concept “generation” was central to the early self-understanding and selfjustification of the group. It allowed the group to forge an alliance and oppose an antagonistic group of influential theologians. The claim to speak up for a young generation of theologians and pastors – in opposition to an older, liberal generation – became the rallying cry for Dialectical Theology. Further, I argue that conferences, not only the theological writings, played a central, constitutive role in establishing the group as a theological movement. It was at conferences that the members of Dialectical Theology could challenge the older generation and assert their own theological stance. Instead of merely concentrating on the published theological writings of each of the members, I thus argue that one must additionally focus on the applied concepts and the role of conferences to understand the history of Dialectical Theology. It is only when we include these additional contexts that we understand how Dialectical Theology was able to be launched and sustained as a theological movement despite the irreconcilable differences amongst the members.
Equity of Physical Characteristics Between Adolescent Males and Females Participating in Single- or Mixed-Sex Sport
Authors: Krause Lyndon M. , Naughton Geraldine A. , Benson Amanda C. , Tibbert Stephanie
Published: September 2017

Krause, LM, Naughton, GA, Benson, AC, and Tibbert, S. Equity of physical characteristics between adolescent males and females participating in single- or mixed-sex sport. J Strength Cond Res 32(5): 1415–1421, 2018—Policies on single- or mixed-sex junior sports participation continue to be challenged publically and legally. Often challenges relate to perceptions of size and performance variability between adolescent males and females, yet the evidence base behind these challenges lacks recent review and rigor. Physical performance was compared between males and females from 2 groups of younger (<13 years, n = 109, 67% females, 33% males) and older (≥13 years, n = 108, 43% females, 57% males) adolescents. Using a cross-sectional design, adolescents were tested for speed, strength, power, and endurance. No sex differences were found for most of the physical test results in the <13 years age group, although males showed greater endurance (p = 0.020) and upper-body strength (p = 0.010) than females. However, among adolescents aged ≥13 years, males scored better than females in all physical tests, without exception (p > 0.05). Further explorations comparing how many females in the same age grouping shared test results equal to or greater than the top third of males were fewer in the older than younger age group. Equality of participation in mixed-sex sport becomes more difficult to guarantee for older adolescents when results from generic sport-related physical test performances are considered.
Acute Effects of Ammonia Inhalants on Strength and Power Performance in Trained Men
Authors: Bartolomei Sandro , Nigro Federico , Gubellini Luca , Semprini Gabriele , Ciacci Simone , Hoffman Jay R. , Merni Franco
Published: September 2017

Bartolomei, S, Nigro, F, Luca, G, Gabriele, S, Ciacci, S, Hoffman, JR, and Merni, F. Acute effects of ammonia inhalants on strength and power performance in trained men. J Strength Cond Res 32(1): 244–247, 2018—The aim of the present study was to investigate the influence of ammonia inhalants on lower body power and maximal isometric strength in trained men. Twenty experienced resistance trained men (age = 26.7 ± 3.7 years; body weight = 80.59 ± 9.0 kg; body height = 179.5 ± 5.7 cm) were tested for counter movement jump power (CMJP), maximal force, and peak rate of force development (pRFD20) expressed during an isometric midthigh pull (IMTP). Assessments were performed using either an ammonia inhalant (AI), a placebo (PL), or no inhalants (N). One-way analysis of variance (ANOVA) with repeated measures was used to compare strength and power performance between the different trials. A significant (p < 0.01) increase in pRFD20 was detected following the use of AI. No significant effects of trial were noted for CMJP and IMTP maximal force (p = 0.251 and p = 0.075, respectively). Results of the present study showed a potential ergogenic effect of AI on rate of force development (i.e., explosive force output), with a trend toward an improvement in maximal force production. The mechanism of action may be related to the stimulatory action of AI often reported by athletes as a “psyching-up” effect. The positive effect of AI on the rate of force development may represent an advantage in sports requiring high rates of force production.
Influence of the Heat Treatment Processes on the Properties of High Entropy Alloys Based on Al-Cr-Fe-Mn-Ni System
Authors: Mitrica Dumitru , Soare Vasile , Constantin Ionut , Burada Marian , Olaru Mihai T. , Badilita Viorel , Soare Victoria , Stoiciu Florentin , Popescu Gabriela , Carcea Ioan
Published: September 2017

In the present paper, high entropy alloys based on an aluminum-chromium-iron-manganese-nickel (Al-Cr-Fe-Mn-Ni) system were prepared by induction melting and annealed in an inert atmosphere. The resulting samples were analyzed by optical microscopy, scanning electron microscopy, and X-ray diffraction to determine the structural characteristics before and after the heat treatment process. Significant phase transformations and changes in the phase distribution were noticed after the heat treatment process. The results were discussed against the thermodynamic criteria calculations for most promising compositions. Hardness tests were provided for the selected samples to indicate the changes in the mechanical properties between various compositions and between as-cast and annealed samples. Results indicated that the heat treatment process determined a significant hardness increase in one of the studied high entropy alloys.
Oscillatory Reinstatement Enhances Declarative Memory
Authors: Javadi Amir-Homayoun , Glen James C. , Halkiopoulos Sara , Schulz Mei , Spiers Hugo J.
Published: September 2017

Declarative memory recall is thought to involve the reinstatement of neural activity patterns that occurred previously during encoding. Consistent with this view, greater similarity between patterns of activity recorded during encoding and retrieval has been found to predict better memory performance in a number of studies. Recent models have argued that neural oscillations may be crucial to reinstatement for successful memory retrieval. However, to date, no causal evidence has been provided to support this theory, nor has the impact of oscillatory electrical brain stimulation during encoding and retrieval been assessed. To explore this we used transcranial alternating current stimulation over the left dorsolateral prefrontal cortex of human participants [n= 70, 45 females; age mean (SD) = 22.12 (2.16)] during a declarative memory task. Participants received either the same frequency during encoding and retrieval (60–60 or 90–90 Hz) or different frequencies (60–90 or 90–60 Hz). When frequencies matched there was a significant memory improvement (at both 60 and 90 Hz) relative to sham stimulation. No improvement occurred when frequencies mismatched. Our results provide support for the role of oscillatory reinstatement in memory retrieval.

SIGNIFICANCE STATEMENTRecent neurobiological models of memory have argued that large-scale neural oscillations are reinstated to support successful memory retrieval. Here we used transcranial alternating current stimulation (tACS) to test these models. tACS has recently been shown to induce neural oscillations at the frequency stimulated. We stimulated over the left dorsolateral prefrontal cortex during a declarative memory task involving learning a set of words. We found that tACS applied at the same frequency during encoding and retrieval enhances memory. We also find no difference between the two applied frequencies. Thus our results are consistent with the proposal that reinstatement of neural oscillations during retrieval supports successful memory retrieval.
Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia
Authors: Seo Jinsoo , Kritskiy Oleg , Watson L. Ashley , Barker Scarlett J. , Dey Dilip , Raja Waseem K. , Lin Yuan-Ta , Ko Tak , Cho Sukhee , Penney Jay , Silva M. Catarina , Sheridan Steven D. , Lucente Diane , Gusella James F. , Dickerson Bradford C. , Haggarty Stephen J. , Tsai Li-Huei
Published: September 2017

Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease. Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double-transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KImice. We observed significant reduction of phosphorylated tau and its seeding activity in the brain of double transgenic mice compared with the P301S mice. Furthermore, synaptic loss and impaired LTP at hippocampal CA3 region ofP301Smice were attenuated by blocking p25 generation. To further validate the role of p25/Cdk5 in tauopathy, we used frontotemporal dementia patient-derived induced pluripotent stem cells (iPSCs) carrying the Tau P301L mutation and generated P301L:Δp35KI isogenic iPSC lines using CRISPR/Cas9 genome editing. We created cerebral organoids from the isogenic iPSCs and found that blockade of p25 generation reduced levels of phosphorylated tau and increased expression of synaptophysin. Together, these data demonstrate a crucial role for p25/Cdk5 in mediating tau-associated pathology and suggest that inhibition of this kinase can remedy neurodegenerative processes in the presence of pathogenic tau mutation.

SIGNIFICANCE STATEMENTAccumulation of p25 results in aberrant Cdk5 activation and induction of numerous pathological phenotypes, such as neuroinflammation, synaptic loss, Aβ accumulation, and tau hyperphosphorylation. However, it was not clear whether p25/Cdk5 activity is necessary for the progression of these pathological changes. We recently developed the Δp35KItransgenic mouse that is deficient in p25 generation and Cdk5 hyperactivation. In this study, we used this mouse model to elucidate the role of p25/Cdk5 in FTD mutant tau-mediated pathology. We also used a frontotemporal dementia patient-derived induced pluripotent stem cell carrying the Tau P301L mutation and generated isogenic lines in which p35 is replaced with noncleavable mutant Δp35. Our data suggest that p25/Cdk5 plays an important role in tauopathy in both mouse and human model systems.
Visual Motion Discrimination by Propagating Patterns in Primate Cerebral Cortex
Authors: Townsend Rory G. , Solomon Selina S. , Martin Paul R. , Solomon Samuel G. , Gong Pulin
Published: September 2017

Visual stimuli can evoke waves of neural activity that propagate across the surface of visual cortical areas. The relevance of these waves for visual processing is unknown. Here, we measured the phase and amplitude of local field potentials (LFPs) in electrode array recordings from the motion-processing medial temporal (MT) area of anesthetized male marmosets. Animals viewed grating or dot-field stimuli drifting in different directions. We found that, on individual trials, the direction of LFP wave propagation is sensitive to the direction of stimulus motion. Propagating LFP patterns are also detectable in trial-averaged activity, but the trial-averaged patterns exhibit different dynamics and behaviors from those in single trials and are similar across motion directions. We show that this difference arises because stimulus-sensitive propagating patterns are present in the phase of single-trial oscillations, whereas the trial-averaged signal is dominated by additive amplitude effects. Our results demonstrate that propagating LFP patterns can represent sensory inputs at timescales relevant to visually guided behaviors and raise the possibility that propagating activity patterns serve neural information processing in area MT and other cortical areas.

SIGNIFICANCE STATEMENTPropagating wave patterns are widely observed in the cortex, but their functional relevance remains unknown. We show here that visual stimuli generate propagating wave patterns in local field potentials (LFPs) in a movement-sensitive area of the primate cortex and that the propagation direction of these patterns is sensitive to stimulus motion direction. We also show that averaging LFP signals across multiple stimulus presentations (trial averaging) yields propagating patterns that capture different dynamic properties of the LFP response and show negligible direction sensitivity. Our results demonstrate that sensory stimuli can modulate propagating wave patterns reliably in the cortex. The relevant dynamics are normally masked by trial averaging, which is a conventional step in LFP signal processing.
Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing’s disease
Authors: Bansal Prachi , Lila Anurag , Goroshi Manjunath , Jadhav Swati , Lomte Nilesh , Thakkar Kunal , Goel Atul , Shah Abhidha , Sankhe Shilpa , Goel Naina , Jaguste Neelam , Bandgar Tushar , Shah Nalini
Published: September 2017

Purpose

Transsphenoidal surgery (TSS) is the primary treatment modality for Cushing’s disease (CD). However, the predictors of post-operative remission and recurrence remain debatable. Thus, we studied the post-operative remission and long-term recurrence rates, as well as their respective predictive factors.

Methods

A retrospective analysis of case records of 230 CD patients who underwent primary microscopic TSS at our tertiary care referral centre between 1987 and 2015 was undertaken. Demographic features, pre- and post-operative hormonal values, MRI findings, histopathological features and follow-up data were recorded. Remission and recurrence rates as well as their respective predictive factors were studied.

Results

Overall, the post-operative remission rate was 65.6% (early remission 46%; delayed remission 19.6%), while the recurrence rate was 41% at mean follow-up of 74 ± 61.1 months (12–270 months). Significantly higher early remission rates were observed in patients with microadenoma vs macroadenoma (51.7% vs 30.6%, P = 0.005) and those with unequivocal vs equivocal MRI for microadenoma (55.8% vs 38.5%, P = 0.007). Patients with invasive macroadenoma had poorer (4.5% vs 45%, P = 0.001) remission rates. Recurrence rates were higher in patients with delayed remission than those with early remission (61.5% vs 30.8%, P = 0.001). Duration of post-operative hypocortisolemia ≥13 months predicted sustained remission with 100% specificity and 46.4% sensitivity. Recurrence could be detected significantly earlier (27.7 vs 69.2 months, P < 0.001) in patients with available serial follow-up biochemistry as compared to those with infrequent follow-up after remission.

Conclusion

In our study, remission and recurrence rates were similar to that of reported literature, but proportion of delayed remission was relatively higher. Negative/equivocal MRI findings and presence of macroadenoma, especially those with cavernous sinus invasion were predictors of poor remission rates. In addition to early remission, longer duration of post-operative hypocortisolism is an important predictor of sustained remission. Regular biochemical surveillance may help in identifying recurrence early.
miR-212 mediates counter-regulation on CRH expression and HPA axis activity in male mice
Authors: Tang Yuxiao , Cai Xingjian , Zhang Hongwei , Shen Hui , Wang Wanyin , Shen Zhilei , Gu Wei , Ling Changquan , Li Min
Published: September 2017

The mechanisms of hypothalamic–pituitary–adrenal (HPA) axis regulation have been studied persistently but still are not elucidated. Considering the emerging roles of microRNA in stress response, we conducted a microRNA microarray in mice hypothalamus to identify the potential role of microRNAs in regulating the HPA axis. In total, 41 microRNAs changed during heat stress in which we found that miR-212 contains a binding sequence with corticotropin-releasing hormone (Crh) 3′UTR according to a sequence analysis. We observed that miR-212 expression in the hypothalamus was escalated by repeated heat and restraint stress. By overexpression or inhibition of miR-212 and the dual-luciferase reporter assay, we proved that miR-212 could bind withCrh3′UTR to regulate its expression in mice hypothalamus primary cells and in the hippocampus neuron cell line HT-22. In addition, we injected miR-212 agomir or antagomir in mice hypothalamus to overexpress or inhibit miR-212, which leads to alterations of CRH expression and HPA axis activityin vivo. Furthermore, miR-212 and CRH were both transcribed by the cAMP response element-binding protein (CREB). Overexpression and inhibition of miR-212 affect CREB-dependent CRH expression. Taken together, our results suggest an inhibitory role of miR-212 on the HPA axis, which acts in a counter-regulatory manner.
Antioxidative potential of two chemically characterized Ocimum (Tulsi) species extracts
Authors: Agarwal Karishma , Singh Dhananjay Kumar , Jyotshna Jyotshna , Ahmad Ateeque , Shanker Karuna , Tandon Sudeep , Luqman Suaib
Published: September 2017

Background: Ocimum sanctum and Ocimum kilimandscharicum are cultivated in Indian subcontinent both for the religious and medicinal properties. Traditionally, the leaves have been reported for their enormous therapeutic potentials but the roots which are otherwise considered as a waste part have not been explored for their pharmacological activity.
Methods: Total phenolic content, free radical scavenging and ferric reducing antioxidant potential of various extracts from Ocimum sanctum and Ocimum kilimandscharicum were assessed and compared. In vitro antioxidant activity was estimated spectrophotometrically and the most potent ethyl acetate extract was chemically characterized by developing the chemical fingerprint and quantifying the probable constituents with the help of HPLC/LC-MS techniques.
Results: The ethyl acetate extract of both the species exhibited significant free radical scavenging potential and also reduced the ferric ions. It was observed that ethyl acetate extract have superior ferric reducing potential than other tested extracts, which were evidenced by high ferrous sulphate equivalent value of 77.05 ± 1.54 and 80.98 ± 0.80 at 100 µg/ml for O. sanctum and O. kilimandscharium respectively. The ferric reducing capacity of ethyl acetate extract for both the species was also evidenced by an elevated optical density of 1.64 ± 0.12 and 2.14 ± 0.08. Ocimum sanctum exhibited better antioxidant capacity (11.31 ± 0.20 AScE) as compared to Ocimum kilimandscharium (9.08 ± 0.27 AScE). The total phenolic and flavonoid content were estimated by spectrophotometric method and tentatively characterized by HPLC/LC-MS profiling which revealed the presence of rosmarinic acid, caffeic acid along with its derivatives such as caffeoyl-dihydroxyphenyllactoyl-tartaric acid.
Conclusion: The ethyl acetate extract of both the species being rich in phenolic and flavonoid contents exhibited potent antioxidant activity. The presence of flavonoid in ethyl acetate extracts further co-relates the antioxidative properties of roots extracts.  To the best of our knowledge and understanding this is the first report of comparative chemical profiling by RP-HPLC/LC-MS and antioxidant potential of roots of two Ocimum species.
Peer Review Details

Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy
Plagiarism software screening?: Yes
Date of Original Submission: 27 July 2017
Date accepted: 23 August 2017
Peer reviewers approved by: Dr. Lili Hami
Editor who approved publication: Dr. Phuc Van Pham
Stability-indicating HPLC method for simultaneous determination of degradation products and process-related impurities of avanafil in avanafil tablets
Authors: Kumar Nitin , Sangeetha D. , Kalyanraman L. , Sainath K.
Published: September 2017

The objective of the current research is to understand the degradation behavior of avanafil under different stress conditions and to develop a stability-indicating high-performance liquid chromatography (HPLC) method for simultaneous determination of degradants observed during degradation. Avanafil tablets were exposed to acid, base, water, oxidative, thermal, and photolytic degradation conditions. In acid, oxidative, thermal, and humidity degradation, significant degradation was observed. All the degradants observed during degradation were separated from known impurities of avanafil by using reverse-phase (RP)-HPLC. Mobile phase A, 0.1% trifluoro acetic acid and triethylamine in water, and mobile phase B, water and acetonitrile in the ratio of 20:80 (v/v), were used at a flow rate of 1.2 mL/min in gradient elution mode. Separation was achieved by using Inertsil ODS 3 column (3 μm, 4.6 mm × 250 mm) at 45 °C. Peak responses were recorded at 245 nm. Method capability for detecting and quantifying the degradants, which can form during stability, was proved by demonstrating the peak purity of avanafil peak in all the stressed samples. Mass balance was established by performing the assay of stressed sample against reference standard. Mass balance was found >97% for all the stress conditions. The developed analytical method was validated as per International Conference on Harmonization (ICH) guidelines. The method was found specific, linear, accurate, precise, rugged, and robust.
Undergraduate medical students’ attitudes towards patient-centredness: a longitudinal study
Authors: Archer Elize , van Heerden Ben Barend
Published: September 2017

This article was migrated. The article was not marked as recommended. ObjectiveDue to various reasons patient-centredness has become an attribute most medical institutions aim to develop in their graduates. Research however indicates that there is a decline in undergraduate medical students' attitudes towards patient-centredness as they progress through their training. Most of the studies available are cross sectional studies, therefore a longitudinal study to look at how the attitudes of a specific group of undergraduate medical students change over time can be very useful.Methods A longitudinal study involving undergraduate medical students was employed. These students completed the Patient Practitioner Orientation Scale (PPOS) over the last four years of their training and the mean scores of the PPOS was compared. The PPOS measures two constructs related to patient-centrendness namely "caring" and "sharing".Results and discussionPPOS results indicated that students already exhibited fairly low attitudes towards patient-centredness at the beginning of their clinical rotations in their third year, with no significant decline over the next three years. Reasons why the PPOS scores in this study are generally lower than in other similar populations is not clear, but possibilities that are mentioned are that it might be low from the first year already as well as the lack of a comprehensive communication skills training curriculum.ConclusionOur study showed that students' relatively low attitudes towards patient-centredness did not change significantly during their last four years of training. Implications for this finding is that selection criteria of students could perhaps be reconsidered and deliberate teaching and learning interventions to promote positive attitudes towards patient-centredness should be included as part of a comprehensive communication skills curriculum until students graduate.
Dos livros didáticos aos protótipos de ensino: em direção a um web-currículo
Authors: Marsaro-Pavan Fabiana
Published: September 2017

Embora o desenvolvimento e a popularização das Tecnologias Digitais da Comunicação e da Informação (TIDC) as estejam aproximado cada vez mais da sala de aula, não podemos negar que elas ainda estão longe de integrar efetivamente o cotidiano escolar. Mesmo que nossa realidade seja cada vez mais on-line, digital, multissemiótica e plural, o que tem nos levado a questionar até mesmo o papel (e o futuro) da escola, os materiais mais tradicionais como livros didáticos, apostilados e sequências didática continuam a circular, ainda que por vezes disputem espaço com computadores, tablets, Objetos Digitais de Aprendizagem (ODA) e Objetos Educacionais Digitais (OED), geralmente em iniciativas bastante difusas, irregulares e desencontradas. Levando em conta que, em um contexto de novos multiletramentos (ROJO, no prelo), torna-se cada vez mais necessário estudar dispositivos didáticos que sejam capazes de atender mais satisfatoriamente às demandas atuais, no espaço disponível neste artigo buscaremos estabelecer um breve panorama do status atual dos materiais didáticos que têm circulado na escola brasileira, procurando identificar as características e fragilidades que fazem com que eles nos pareçam cada vez menos adequados para concretizar o que Almeida (2014) convencionou chamar de web-currículos.
Editorial English
Authors: Santos Gildenir Carolino
Published: September 2017

With great satisfaction, we are opening 2010 year with this special issue, "Psychoanalysis and Philosophy: possible dialog?” with 15 studies: five articles, nine dossier texts and one experience report. Here we are addressing the representativity of two areas of the knowledge field: psychoanalysis and philosophy. In the dialogues outlined in this special issue, several authors have brought their contributions from different places and countries: Uruguay, Brazil and England. With this, we could devise an opening cover for the journal representing psychoanalysts and philosophers of the involved areas, discussed in several papers in this number: Jacques Lacan, Sigmund Freud, Michel Foucault, Gilles Deleuze and Friedrich Niestche, as a link among these authors in this puzzle.
Analisis Pesan Dakwah dalam Novellet â€œKetika Mas Gagah Pergiâ€™ Karya Helvy Tiana Rosa
Authors: Fitriyah Diah Hikmah , Lubis Zulkifli , Mardhiah Izzatul
Published: September 2017

The development of the present age experiencing such a big challenge that is crisis morality (moral decadence) as well as social damage. Resulting in a shift in values both religious and social values. This is due to the mass media. Therefore, This research was conducted to examine the contents of messages submitted media to the public, so that people are not trapped by the contents of rhetoric contained in the mass media. This research uses discourse analysis of Teun A. Van Dijk type to know the discourse of moral messages contained in the novel "Ketika Mas Gagah Pergi" and want to know the forms of moral messages contained in the novel.

 Keywords: Discourse Analysis, Moral Message, Ketika Mas Gagah Pergi

Abstrak

Perkembangan zaman saat ini mengalami tantangan yang begitu besar yakni krisisnya moralitas (dekadensi moral) serta kerusakan sosial. Sehingga terjadinya pergeseran nilai-nilai baik nilai-nilai agama maupun sosial. Hal ini disebabkan merebaknya media massa. Oleh karena itu, Penelitian ini dilakukan untuk mengkaji isi pesan yang disampaikan media kepada masyarakat, agar masyarakat tidak terjebak oleh isi retorika yang terdapat dalam media massa tersebut. Penelitian ini menggunakan analisis wacana model Teun A. Van Dijk untuk mengetahui wacana pesan akhlak yang terdapat dalam novellet â€œKetika Mas Gagah Pergiâ€ serta ingin mengetahui bentuk-bentuk pesan akhlak yang terdapat dalam novellet tersebut.

 Kata Kunci: Analisis Wacana, Pesan Akhlak, Ketika Mas Gagah Pergi.