bluuebunny/crossref_metadata_2025 huggingface dataset:
C/EBPα overrides epigenetic reprogramming by oncogenic transcription factors in acute myeloid leukemia
Authors: Loke Justin , Chin Paulynn Suyin , Keane Peter , Pickin Anna , Assi Salam A. , Ptasinska Anetta , Imperato Maria Rosaria , Cockerill Peter N. , Bonifer Constanze
Published: February 2018

Key Points

C/EBPα directly represses the leukemia maintenance program; however, the pattern of repressed genes is specific for each type of AML. Overexpression of C/EBPα does not globally displace these proteins from their binding sites, but overrides their repressive activity.
Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC
Authors: Groveman Bradley R. , Orrù Christina D. , Hughson Andrew G. , Raymond Lynne D. , Zanusso Gianluigi , Ghetti Bernardino , Campbell Katrina J. , Safar Jiri , Galasko Douglas , Caughey Byron
Published: February 2018

The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of α-synuclein (αSynD) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent αSynDseed amplification tests have provided the first prototypes for ultrasensitive and specific detection of αSynDin patients’ cerebrospinal fluid. These prototypic assays require 5–13 days to perform. Here, we describe an improved α-synuclein real time quaking-induced conversion (αSyn RT-QuIC) assay that has similar sensitivity and specificity to the prior assays, but can be performed in 1–2 days with quantitation. Blinded analysis of cerebrospinal fluid from 29 synucleinopathy cases [12 Parkinson’s and 17 dementia with Lewy bodies] and 31 non-synucleinopathy controls, including 16 Alzheimer’s cases, yielded 93% diagnostic sensitivity and 100% specificity for this test so far. End-point dilution analyses allowed quantitation of relative amounts of αSynDseeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 μL. These results confirm that αSynDseeding activity is present in cerebrospinal fluid. We also demonstrate that it can be rapidly detected, and quantitated, even in early symptomatic stages of synucleinopathy.
Adult Acute Lymphoblastic Leukemia: Limitations of Intensification of Therapy in a Developing Country
Authors: Jain Punit , Korula Anu , Deshpande Prashant , PN Nisham , Abu Alex Ansu , Abraham Aby , Srivastava Alok , Janet Nancy Beryl , Lakshmi Kavitha M. , Balasubramanian Poonkuzhali , George Biju , Mathews Vikram
Published: February 2018

Purpose

Limited data exist on intensifying chemotherapy regimens in the treatment of adult acute lymphoblastic leukemia (ALL) outside the setting of a clinical trial.

Materials and Methods

Retrospectively, data from 507 consecutive adults (age ≥ 15 years) with a diagnosis of ALL treated at our center were analyzed. Standard-risk (SR) patients were offered treatment with a modified German Multicenter ALL (GMALL) regimen, whereas high-risk (HR) patients were offered intensification of therapy with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD). Because of resource constraints, a proportion of HR patients opted to receive the same treatment regimen as used for SR patients.

Results

There were 344 SR patients (67.8%) and 163 HR patients (32.2%) at diagnosis. Among the HR patients, 53 (32.5%) opted to receive intensification with the HCVAD regimen. The SR cohort showed a superior 5-year event-free survival rate compared with the HR cohort (47.3% v 23.6%, respectively; P < .001). Within the HR subgroup, there was no statistically significant difference in overall survival or event-free survival between patients who received the modified GMALL regimen (n = 59) and patients who received HCVAD (n = 53).

Conclusion

Intensified therapy in the HR subset was associated with a significant increase in early treatment-related mortality and cost of treatment. A modified GMALL regimen was found to be cost-effective with clinical outcomes comparable to those achieved with more intensive regimens.
Outcomes in Treatment-Naïve Patients With Metastatic Extremity Osteosarcoma Treated With OGS-12, a Novel Non–High-Dose Methotrexate–Based, Dose-Dense Combination Chemotherapy, in a Tertiary Care Cancer Center
Authors: Bajpai Jyoti , Chandrasekharan Arun , Simha Vijai , Talreja Vikas , Karpe Ashay , Pandey Nikihil , Singh Ashish , Rekhi Bharat , Vora Tushar , Ghosh Jaya , Banavali Shripad , Gupta Sudeep
Published: February 2018

Purpose

Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)–based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX–based regimen is worth exploring, especially in India and low- and middle-income countries.

Materials and Methods

All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic response, event-free survival (EFS), overall survival (OS), and toxicity data were prospectively collected.

Results

Three hundred seventeen patients were enrolled onto the OGS-12 protocol from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17 years. The majority of patients were nutritionally challenged with high-risk features. At presentation, 83% of patients (66 patients) had lung metastases. After neoadjuvant chemotherapy, 57% of patients were histologically good responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the intent-to-treat population and 27% and 29%, respectively, in the per-protocol analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%), thrombocytopenia (36%), and anemia (54%). Histologic response was an independent predictor for EFS and OS in patients who underwent surgery. Surgical intervention was found to be significant for survival in univariable analysis.

Conclusion

The novel, low-cost, non-HDMTX–based, dose-dense OGS-12 regimen has shown comparable outcomes to international standards in metastatic osteosarcomas and is worthy of wider clinical application. An aggressive multimodality approach may result in long-term survival in a select group of patients and, hence, is worth considering.
Integrated Biomedical System
Authors: Ricke Darrell O. , Harper James , Shcherbina Anna , Chiu Nelson , Boettcher Tara
Published: February 2018

Background: Capabilities for generating and storing large amounts of data relevant to individual health and performance are rapidly evolving and have the potential to accelerate progress toward quantitative and individualized understanding of many important issues in health and medicine. Recent advances in clinical and laboratory technologies provide increasingly complete and dynamic characterization of individual genomes, gene expression levels for genes, relative abundance of thousands of proteins, population levels for thousands of microbial species, quantitative imaging data, and more – all on the same individual.  Personal and wearable electronic devices are increasingly enabling these same individuals to routinely and continuously capture vast amounts of quantitative data including activity, sleep, nutrition, environmental exposures, physiological signals, speech, and neurocognitive performance metrics at unprecedented temporal resolution and scales. While some of the companies offering these measurement technologies have begun to offer systems for integrating and displaying correlated individual data, these are either closed/proprietary platforms that provide limited access to sensor data or have limited scope that focus primarily on one data domain (e.g. steps/calories/activity, genetic data, etc.).

Methods: The Integrated Biomedical System is developed as a Ruby on Rails application with a relational database.

Results: Data from multiple wearable monitors for activity, sleep, and physiological measurements, phone GPS tracking, individual genomics, air quality monitoring, etc. have been integrated into the Integrated Biomedical System.

Conclusions: The Integrated Biomedical System is being developed to demonstrate an adaptable open-source tool for reducing the burden associated with integrating heterogeneous genome, interactome, and exposome data from a constantly evolving landscape of biomedical data generating technologies.  The Integrated Biomedical System provides a scalable and modular framework that can be extended to include support for numerous types of analyses and applications at scales ranging from personal users, communities and groups, to potentially large populations.
Using theories of change to design monitoring and evaluation of community engagement in research: experiences from a research institute in Malawi
Authors: Gooding Kate , Makwinja Regina , Nyirenda Deborah , Vincent Robin , Sambakunsi Rodrick
Published: February 2018

Background: Evaluation of community and public engagement in research is important to deepen understanding of how engagement works and to enhance its effectiveness. Theories of change have been recommended for evaluating community engagement, for their ability to make explicit intended outcomes and understandings of how engagement activities contribute to these outcomes. However, there are few documented examples of using theories of change for evaluation of engagement. This article reports experience of using theories of change to develop a framework for evaluating community engagement in research at a clinical research organisation in Malawi. We describe the steps used to develop theories of change, and the way theories of change were used to design data collection plans. Based on our experience, we reflect on the advantages and challenges of the theory of change approach.

Methods: The theories of change and evaluation framework were developed through a series of workshops and meetings between engagement practitioners, monitoring and evaluation staff, and researchers. We first identified goals for engagement, then used ‘so that’ chains to clarify pathways and intermediate outcomes between engagement activities and goals. Further meetings were held to refine initial theories of change, identify priority information needs, and define feasible evaluation methods.

Results: The theory of change approach had several benefits. In particular, it helped to construct an evaluation framework focused on relevant outcomes and not just activities. The process of reflecting on intended goals and pathways also helped staff to review the design of engagement activities. Challenges included practical considerations around time to consider evaluation plans among practitioners (a challenge for evaluation more generally regardless of method), and more fundamental difficulties related to identifying feasible and agreed outcomes.

Conclusions: These experiences from Malawi provide lessons for other research organisations considering use of theories of change to support evaluation of community engagement.
RESEARCH OF CHLOROGENIC ACID CONTENT IN CERTAIN NUMBER OF VEGETABLES AND FRUITS
Authors: Арзуманян Лилия , Arzuamanyan Lilia
Published: February 2018

This article is devoted to the research of chlorogenic acid, one of antioxidants and the substance which counteracts the effect of free radicals which cause cell disorder and variety of diseases. This article presents the results of research concerning chlorogenic acid content in vegetables and fruits as well as identification of the most wholesome vegetables and fruits from the point of this chlorogenic acid content
The body as site of interweaving performance cultures: Between being a body and having a body
Authors: Fischer-Lichte Erika
Published: February 2018

This article deals with problems arising from the globalization of ‘embodied knowledge’ in the performing arts. Proceeding from the theories of Marcel Mauss and Hellmuth Plessner, the article introduces the concepts of the body-object and the body-subject, and discusses whether embodied knowledge only refers to certain specific body techniques, which will only impact upon the body as the object, or whether it also impacts upon the body as the site of the subject. Whether or not embodied knowledge practised by an actor/performer is part of a much broader field of knowledge, such as aesthetics, philosophy or religion, is also an important question that contributes to the fundamental argument of the article. To shed light on this issue, the article examines two treatises on acting from two different cultures, Bharata Muni’s the Natyasastra (second century bce and second century ce) and Johann Jakob Engel’s Practical Illustrations of Rhetorical Gestures and Action (1785–86), in order to evaluate their proposal on how to represent emotions in performance and what kinds of responses this may elicit from spectators. Similarly, I will examine two modes of interweaving performance practice: first, the actors who were trained in one particular style or tradition but acquired the bodily techniques of another cultural style later in their performance career; and second, the co-performing actors who were trained in and belonged to different performance traditions yet worked together onstage.
Fatwa on satellite TV and the development of Islamic religious discourse
Authors: Miladi Noureddine , Karim Saleh , Athambawa Mahroof
Published: February 2018

Satellite TV and the Internet revolutions have reinvigorated religious discourse in public spaces. Across the world, religious TV channels and Internet religious websites have taken up the roles of traditional religious spaces such as churches, mosques, synagogues, gurdwaras and temples. Islamic religious content through fatwa (religious verdict) programmes and other online and satellite TV genre has attracted considerable attention over the last fifteen years. Such programmes have become influential platforms in constructing people’s opinions. On Islamic-oriented satellite TV channels, fatwa provision has nowadays become a sophisticated phenomenon exceeding the traditional scope of religious teaching. To understand fatwa and its possible impact, it is necessary to gauge the plethora of platforms available for audiences and users as sources of understanding their religious needs starting with satellite TV programmes to the unlimited online platforms for the diffusion of their religious decree. This research attempts to understand the extent to which fatwa programmes on satellite TV and radio are significant in shaping people’s opinion. Through the implementation of an extensive survey questionnaire on a sample of the Qatari society in addition to interviews with experts and religious scholars, findings show that fatwa on satellite programme can be very important in helping viewers better understand their religion. The results also indicated that respondents included in the survey showed apathy when it comes to the implementation of rulings coming from muftis on TV. In short, respondents may watch fatwa or religious programmes on satellite TV or they may listen to them on the Qur’an radio in Qatar but they do not necessarily consider them as totally authentic. Authentic scholarly views on matters of religious seem to be more credible when they originate from a reputable Imam whom they see face to face. Moreover, results show that satellite TV has facilitated the emergence of the pan-Arab mufti or global Faqeeh. It has also facilitated the emergence of independent muftis and freed fatwa from the official religious authorities in various countries.
Korosi Retak Tegang pada Pipa Superheater Ketel Uap yang Baru Dibangun [Stress Corrosion Cracking of Cage Superheater Tubes of a Newly Built Boiler]
Authors: Adnyana D.N.
Published: February 2018

A number of cage superheater tubes of a newly built steam boiler have been leaking during boiler’s first start-up commissioning. Leaking occurred when the boiler had just reached a pressure of 23.7 barg and temperature 4050 C from the intended operating pressure of 53 barg and temperature of 4850C. Type of failure and factors that may have caused the leakage of the cage superheater tube are discussed in this paper. The metallurgical assessment was conducted by preparing a number of specimens from the as received leaked cage superheater tube. Various laboratory examinations were performed including macroscopic examination, chemical composition analysis, metallographic examination, hardness test and SEM (scanning electron microscopy) examination equipped with EDS (energy dispersive spectroscopy) analysis. Results of the metallurgical assessment obtained show that the leaked cage superheater tubes have been experiencing stress-corrosion cracking (SCC) caused by the combined effect of corrosion and tensile stress. The corrosion agent that may have been responsible for the occurrence of SCC in the tube was mostly due to caustic sodium (Na) and other elements in a lesser extent such as Ca, Cl, S and P.AbstrakSejumlah pipa penukar panas lanjut pada sebuah ketel uap yang baru dibangun diketemukan bocor selama operasi komisioning yang pertama. Kebocoran terjadi ketika ketel uap baru saja mencapai tekanan 23,7 barg dan temperatur 405 °C dari tekanan dan temperatur operasi yang direncanakan yaitu 53 barg dan 485 °C. Dalam makalah ini dibahas jenis kerusakan dan faktor-faktor yang kemungkinan telah menyebabkan terjadinya kebocoran pada pipa penukar panas lanjut tersebut. Penelitian/pengujian metalurgi telah dilakukan dengan mempersiapkan sejumlah benda uji yang diperoleh dari salah satu potongan pipa yang bocor tersebut. Berbagai pengujian laboratorium telah dilakukan meliputi: uji makro, analisa komposisi kimia, uji metalografi, uji kekerasan dan uji SEM (scanning electron microscopy) yang dilengkapi dengan analisis EDS (energy dispersive spectroscopy). Hasil penelitian/pengujian metalurgi yang diperoleh menunjukkan bahwa pipa penukar panas lanjut yang bocor tersebut telah mengalami retak korosi tegangan yang disebabkan oleh efek kombinasi antara korosi dan tegangan tarik. Unsur korosif yang kemungkinan dapat menimbulkan terjadinya retak korosi tegangan pada pipa penukar panas lanjut adalah kaustik sodium (Na) dan elemen-elemen lainnya pada tingkatan yang relatif rendah seperti Ca, Cl, S dan P.
On the non-existence of the Mackey topology for locally quasi-convex groups
Authors: Außenhofer Lydia
Published: February 2018

We give a self-contained proof that the Graev free abelian group over a convergent sequence has no Mackey topology. This means the supremum of all locally quasi-convex compatible topologies of this group is no longer compatible.
Variational Approaches to P(X)-Laplacian-Like Problems with Neumann Condition Originated from a Capillary Phenomena
Authors: Heidarkhani Shapour , Afrouzi Ghasem A. , Moradi Shahin
Published: February 2018

This article presents several sufficient conditions for the existence of at least one weak solution and infinitely many weak solutions for the following Neumann problem, originated from a capillary phenomena,

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. Our technical approach is based on variational methods and we use a more precise version of Ricceri’s Variational Principle due to Bonanno and Molica Bisci. Some recent results are extended and improved. Some examples are presented to illustrate the application of our main results.
Numerical Investigation of the Wave-Front Tracking Algorithm for the Full Ultra-Relativistic Euler Equations
Authors: Abdelrahman Mahmoud A.E.
Published: February 2018

We introduce a generalized version of the front tracking algorithm for the full ultra-relativistic Euler system. The construction and analysis of this algorithm are somewhat simpler than other algorithms. Moreover, this scheme leads to a more robust and efficient result. The scheme also satisfies positivity. This scheme is compared with other two schemes by two numerical test cases. Furthermore we give another application of this scheme, namely we check the explicit formula of interaction of two generalized shocks, by further numerical test case.
On dynamical reconstruction of an input in a linear system under measuring a part of coordinates
Authors: Maksimov Vyacheslav I.
Published: February 2018

The problem of reconstructing an unknown input under measuring a part of phase coordinates of a system of ordinary differential equations is considered.
We propose a solving algorithm that is stable to perturbations and is based on the combination of ideas from the theory of dynamical inversion and the theory of guaranteed control.
The algorithm consists of two blocks: the block of dynamical reconstruction of unmeasured coordinates and the block of dynamical reconstruction of an input.
Accelerated mechanical fatigue interconnect testing method for electrical wire bonds
Authors: Czerny Bernhard , Khatibi Golta
Published: February 2018

Every new development in device performance and packaging design, can drastically affect the reliability of devices due to implementation of new materials and design changes. High performance and high reliability demands in power electronics over several decades and a short time to market development, raise the need for very fast reliability testing methods. In this study a mechanical fatigue testing method is presented for evaluating the interfacial fatigue resistance of heavy Al wire bonded interconnects in high power modules. By separating the concurrent thermal, mechanical and environmental failure mechanisms a selective investigation of the desired failure mode is possible. The setup is designed to reproduce the thermo-mechanical shear stresses by mechanical means, while provoking the same lift-off failure mode as in power cycling tests. With a frequency variable test setup of a few Hz up to several kHz, measurements from 103 up to 108 loading cycles and determining the influence of the testing frequency on the fatigue life are possible. A semi-automated bond wire fatigue tester operating at 60 kHz is presented which is suitable for rapid screening and qualification of a variety of wire bonds at the stages of development and during the production.
Correlations, Nonlocality and Usefulness of an Efficient Class of Two-Qubit Mixed Entangled States
Authors: Singh Parvinder , Kumar Atul
Published: February 2018

We establish an analytical relation between the Bell-Clauser-Horne-Shimony-Holt (Bell-CHSH) inequality and weak measurement strengths under noisy conditions. We show that the analytical results obtained in this article are of utmost importance for proposing a new class of two-qubit mixed states for quantum information processing. Our analysis further shows that the states proposed here are better resources for quantum information in comparison to other two-qubit mixed entangled states.
Photocatalytic Iron Oxide Micro-Swimmers for Environmental Remediation
Authors: Richard Cynthia , Simmchen Juliane , Eychmüller Alexander
Published: February 2018

Harvesting energy from photochemical reactions has long been studied as an efficient means of renewable energy, a topic that is increasingly gaining importance also for motion at the microscale. Iron oxide has been a material of interest in recent studies. Thus, in this work different synthesis methods and encapsulation techniques were used to try and optimize the photo-catalytic properties of iron oxide colloids. Photodegradation experiments were carried out following the encapsulation of the nanoparticles and the Fenton effect was also verified. The end goal would be to use the photochemical degradation of peroxide to propel an array of swimmers in a controlled manner while utilizing the Fenton effect for the degradation of dyes or waste in wastewater remediation.
Evaluation of Segregation in Asphalt Pavement Surface Using Concave Multifractal Distribution
Authors: Ran Mao-ping , Xiao Shenqing , Zhou Xing-lin , Xiao Wang-xin
Published: February 2018

Surface segregation of asphalt mixtures is a common problem encountered when determining segregation level, which is a criterion of pavement quality evaluation. A method to evaluate segregation levels of asphalt pavement surface was presented based on the concave multifractal characteristic in a binary image of a pavement surface, which was obtained by digital image processing technology and mathematical morphology. The practical value of the proposed method was verified in a newly built asphalt pavement, and the segregation level was divided into five sections based on the recommended texture ratio in practical engineering. Results show that the multifractal spectrum width (Δα) quantifies the uniformity of the concave distribution. The pixel percentage of the concave (P) characterizes the ratio of the occupied area. The product of Δα and P (PWP) was quantified as the surface segregation level, which has good linear relevance with texture depth evaluation results. The proposed evaluation technique (PWP) can be used as an alternative to the sand patch method.
“Just Like Someone Without Mental Illness, Only More So”: Normalizing Beliefs and their Buffering Effects on Psychiatric Symptoms
Authors: Buck Benjamin , Hester Neil
Published: February 2018

Self-stigma leads sufferers of psychiatric conditions to experience reduced self-efficacy and self-esteem as well as avoid treatment, employment, and social opportunities. There is a dearth of research on the mechanisms underlying individuals' ability to resist stigmatizing beliefs; furthermore, research has revealed limitations in current popular approaches to de-stigmatization, such as emphasizing the biological and genetic characteristics of symptoms. We propose normalization—the understanding of psychiatric phenomena as varying degrees of normative, understandable, and common experiences—as a cross-diagnostic protective factor against self-stigma. We recruited a sample of 137 online study participants to pilot an assessment of normalization, predicting that normalizing beliefs about psychiatric symptoms would positively influence quality of life, especially for those who report personal experience of symptoms. We found evidence for this prediction: belief that psychiatric symptoms were relatively common, buffered the negative effect of people's own psychiatric symptoms on quality of life. Cross-diagnostic symptom normalization may function as a protective factor against the negative effects of psychiatric symptoms and associated stigma.
Combinatorial Effects of Alpha- and Gamma-Protocadherins on Neuronal Survival and Dendritic Self-Avoidance
Authors: Ing-Esteves Samantha , Kostadinov Dimitar , Marocha Julie , Sing Anson D. , Joseph Kezia S. , Laboulaye Mallory A. , Sanes Joshua R. , Lefebvre Julie L.
Published: February 2018

The clustered protocadherins (Pcdhs) comprise 58 cadherin-related proteins encoded by three tandemly arrayed gene clusters,Pcdh-α,Pcdh-β, andPcdh-γ (Pcdha,Pcdhb, andPcdhg, respectively). Pcdh isoforms from different clusters are combinatorially expressed in neurons. They form multimers that interact homophilically and mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, axonal tiling, and dendritic self-avoidance. Most studies have analyzed clusters individually. Here, we assessed functional interactions betweenPcdhaandPcdhgclusters. To circumvent neonatal lethality associated with deletion ofPcdhgs, we used Crispr-Cas9 genome editing in mice to combine a constitutivePcdhamutant allele with a conditionalPcdhgallele. We analyzed roles of Pcdhas and Pcdhgs in the retina and cerebellum from mice (both sexes) lacking one or both clusters. In retina, Pcdhgs are essential for survival of inner retinal neurons and dendritic self-avoidance of starburst amacrine cells, whereas Pcdhas are dispensable for both processes. Deletion of bothPcdhaandPcdhgclusters led to far more dramatic defects in survival and self-avoidance thanPcdhgdeletion alone. Comparisons of an allelic series of mutants support the conclusion that Pcdhas and Pcdhgs function together in a dose-dependent and cell-type-specific manner to provide a critical threshold of Pcdh activity. In the cerebellum, Pcdhas and Pcdhgs also cooperate to mediate self-avoidance of Purkinje cell dendrites, with modest but significant defects in either single mutant and dramatic defects in the double mutant. Together, our results demonstrate complex patterns of redundancy between Pcdh clusters and the importance of Pcdh cluster diversity in postnatal CNS development.

SIGNIFICANCE STATEMENTThe formation of neural circuits requires diversification and combinatorial actions of cell surface proteins. Prominent among them are the clustered protocadherins (Pcdhs), a family of ∼60 neuronal recognition molecules. Pcdhs are encoded by three closely linked gene clusters calledPcdh-α,Pcdh-β, andPcdh-γ. The Pcdhs mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, and spatial patterning of axons and dendrites. Most studies to date have been limited to single clusters. Here, we used genome editing to assess interactions betweenPcdh-α andPcdh-γ gene clusters. We examined two regions of the CNS, the retina and cerebellum and show that the 14 α-Pcdhs and 22 γ-Pcdhs act synergistically to mediate neuronal survival and dendrite patterning.
Somatic Hybridization
Authors: Holmes Matthew
Published: February 2018

Somatic hybridization is the particle collider of the biological world: where plant cells stripped of their cell wall are fused to create interspecific crosses containing a huge range of genetic information. This paper charts the origins of somatic hybridization and its rise and fall as a plant breeding technique. During the 1960s and 1970s, the creation of somatic hybrids through cell fusion promised a new era of crop improvement. Yet the promises of somatic hybridization were instead fulfilled by advances in recombinant DNA technology. Rather than cast somatic hybridization as a failed research program, this paper argues that a number of factors significantly slowed, but did not halt, developments in somatic hybridization research from the 1960s; the technique should therefore be considered a dormant biotechnology. Reconstructing the history of somatic hybridization reveals a new history of modern biotechnology beyond genetic modification, dominated by plant physiologists.
The Historyless Heathen and the Stagnating Pagan: History as Non-Native Category?
Authors: Lum Kathryn Gin
Published: February 2018

This article asks whether and how J. Z. Smith's contention that religion is a “non-native category” might be applied to the discipline of history. It looks at how nineteenth-century Americans constructed their own understandings of “proper history”—authenticatable, didactic, and progressive—against the supposed historylessness of “heathen” Hawaiians and stagnation of “pagan” Chinese. “True” history, for these nineteenth-century historians, changed in the past and pointed to change in the future. The article asks historians to think about how they might be replicating some of the same assumptions about forward-moving history by focusing on change over time as a core component of historical narration. It urges historians to instead also incorporate the native historical imaginations of our subjects into our own methods, paying attention to when those imaginations are cyclical and reiterative as well as directional, and letting our subjects' assumptions about time and history, often shaped by religious perspectives, orient our own decisions about how to structure the stories we tell.
Modjeska, Paderewski, and the California Landscape
Authors: Marcus Kenneth H.
Published: February 2018

Two Polish artists—the renowned actress Helena Modjeska and the famous composer and pianist Ignacy Jan Paderewski—were drawn to California in the 1870s and 1910s respectively. Their bond with the California landscape in Modjeska’s ranch, El Refugio, near Santa Ana, and Paderewski’s Rancho San Ignacio, near Paso Robles, offered them retreats from their performance tours, restored their health, and gave them a sense of belonging. In turn, both transformed the landscape of the imaginary as they developed productive agriculture.
Limitations of insulin resistance assessment in polycystic ovary syndrome
Authors: Lewandowski Krzysztof C , Płusajska Justyna , Horzelski Wojciech , Bieniek Ewa , Lewiński Andrzej
Published: February 2018

Background

Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable.

Subjects and methods

In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices).

Results

There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P < 0.001 for all), contrasting with a significant (P < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations.

Conclusions

Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution.
Sulforaphane metabolites cause apoptosis via microtubule disruption in cancer
Authors: Zhou Yan , Yang Gaoxiang , Tian Hua , Hu Yabin , Wu Sai , Geng Yang , Lin Kai , Wu Wei
Published: February 2018

Sulforaphane (SFN) inhibited growth in many cancers, but its half-life is 2 h in circulation. However, its metabolites, sulforaphane-cysteine (SFN-Cys) and sulforaphane-N-acetyl-cysteine (SFN-NAC) had longer half-lives and decreased the cell viability in both dose- and time-dependent manners in human prostate cancer. Flow cytometry assay revealed that these two SFN metabolites induced apoptosis with the features such as vacuolization, disappeared nuclear envelope, nuclear agglutination and fragmentation via transmission electron microscopy observation. Western blot showed that the sustained phosphorylation of ERK1/2 mediated by SFN metabolites caused activation and upregulation of cleaved Caspase 3 and downregulation of α-tubulin. High expression of α-tubulin was demonstrated to be positively correlated with cancer pathological grading. Both co-immunoprecipitation and immunofluorescence staining implicated the interaction between SFN metabolite-induced phosphorylated ERK1/2 and α-tubulin, and Caspase 3 cleavage assay showed that α-tubulin might be the substrate for cleaved Caspase 3. More, the SFN metabolite-mediated reduction of α-tubulin increased the depolymerization and instability of microtubules by microtubule polymerization assay. Reversely, microtubule-associated protein Stathmin-1 phosphorylation was increased via phosphorylated ERK1/2 and total Stathmin-1 was reduced, which might promote over-stability of microtubules. Immunofluorescence staining also showed that SFN metabolites induced the ‘nest-like’ structures of microtubule distribution resulting from the disrupted and aggregated microtubules, and abnormal nuclear division, suggesting that the disturbance of spindle formation and mitosis turned up. Thus, SFN-Cys and SFN-NAC triggered the dynamic imbalance of microtubules, microtubule disruption leading to cell apoptosis. These findings provided a novel insight into the chemotherapy of human prostate cancer.
Molecular regulation of follicle-stimulating hormone synthesis, secretion and action
Authors: Das Nandana , Kumar T Rajendra
Published: February 2018

Follicle-stimulating hormone (FSH) plays fundamental roles in male and female fertility. FSH is a heterodimeric glycoprotein expressed by gonadotrophs in the anterior pituitary. The hormone-specific FSHβ-subunit is non-covalently associated with the common α-subunit that is also present in the luteinizing hormone (LH), another gonadotrophic hormone secreted by gonadotrophs and thyroid-stimulating hormone (TSH) secreted by thyrotrophs. Several decades of research led to the purification, structural characterization and physiological regulation of FSH in a variety of species including humans. With the advent of molecular tools, availability of immortalized gonadotroph cell lines and genetically modified mouse models, our knowledge on molecular mechanisms of FSH regulation has tremendously expanded. Several key players that regulate FSH synthesis, sorting, secretion and action in gonads and extragonadal tissues have been identified in a physiological setting. Novel post-transcriptional and post-translational regulatory mechanisms have also been identified that provide additional layers of regulation mediating FSH homeostasis. Recombinant human FSH analogs hold promise for a variety of clinical applications, whereas blocking antibodies against FSH may prove efficacious for preventing age-dependent bone loss and adiposity. It is anticipated that several exciting new discoveries uncovering all aspects of FSH biology will soon be forthcoming.
Influence of antifertility agents Dutasteride and Nifedipine on CatSper gene level in epididymis during sperm maturation in BALB/c mice
Authors: Srivastav Archana , Changkija Bendangla , Sharan Kunal , Nagar Geet Kumar , Bansode Falgun W
Published: February 2018

Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca2+through CatSper (sperm-specific cation channel). The CatSper channel complex contains four pore-forming α subunits (CatSper1–4) and five accessory subunits called β, δ, ε, γ and ζ. Genetic deletion of any of the fourCatSpergenes in mice results in loss of hyperactivated motility and male infertility. Despite their vital role in male fertility, almost very little is known about influence of antifertility agents onCatSpergene expression in epididymis and epididymal spermatozoa. Therefore, we performed quantitative real-time qPCR analysis forCatSperexpression in the epididymis and epididymal sperm of BALB/c mice after treatment with Dutasteride (DS), a dual 5-α reductase inhibitor and Nifedipine (NF) a calcium channel blocker as positive control. We observed that treatment with antifertility agents Dutasteride and Nifedipine induced significant decreases in the caput and cauda epididymal sperm counts, motility and fertility which could partly be attributed to alteration in the normal morphology of the sperm associated with downregulation/upregulation ofCatSpermRNAs in epididymis and epididymal spermatozoa of male BALB/c mice. These can be explained on the basis of interference with mechanisms affecting calcium ion signaling resulting in changes in intracellular calcium required for sperm activity, finally affecting sperm maturation and fertility of male BALB/c mice. These studies provide some novel avenues for developing new male contraceptives in future.
N-terminal Sumoylation of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization to Non-centromeric Chromatin
Authors: Ohkuni Kentaro , Levy-Myers Reuben , Warren Jack , Au Wei-Chun , Takahashi Yoshimitsu , Baker Richard E , Basrai Munira A
Published: February 2018

Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we have identified lysine 65 (K65) in Cse4 as a site that regulates sumoylation and ubiquitin-mediated proteolysis of Cse4 by Slx5. Strains expressing cse4 K65R exhibit reduced levels of sumoylated and ubiquitinated Cse4 in vivo. Furthermore, co-immunoprecipitation experiments reveal reduced interaction of cse4 K65R with Slx5, leading to increased stability and mislocalization of cse4 K65R under normal physiological conditions. Based on the increased stability of cse4 K65R in psh1∆ strains but not in slx5∆ strains, we conclude that Slx5 targets sumoylated Cse4 K65 for ubiquitination-mediated proteolysis independent of Psh1. In summary, we have identified and characterized the physiological role of Cse4 K65 in sumoylation, ubiquitin-mediated proteolysis, and localization of Cse4 for genome stability.
Amerikalı Bir Asker Ve Gazetecinin Gözünden Çanakkale Savaşları
Authors: Karacakaya Furkan
Published: February 2018

Türk tarihinin en önemli zaferlerinden
biri olan Çanakkale Savaşları bütün dünyanın ilgisini çekmiştir. Cephede neler
olduğunu yerinde görüp öğrenebilmek için bir çok gazeteci Osmanlı Devleti‘nin
izniyle savaş bölgesine gitmiştir. Bunlardan birisi de Amerikalı Granville
Fortescue‘dur. Askerlikten ayrılarak gazetecilik yapmaya başlayan Fortescue,
savaş bölgesine giderek savaşı yerinde izlemiş, birçok not tutmuş ve
gözlemlerde bulunmuştur. Tuttuğu bu notları ve gözlemlerini daha savaş bitmeden
İngiltere‘de kitap haline getirmiştir.
Suriyeli Mültecilerin Etkileri Kapsamında Ürdün’de Su Sorunu
Authors: AYDIN Ayşegül
Published: February 2018

Bu
çalışmada Ürdün’deki su sıkıntısı ve özellikle mültecilerin bu duruma etkisi
değerlendirilmiştir. Ürdün’deki su kaynaklarının yetersizliği ele alınmış ve
suyun korunmasının önemi vurgulanmıştır. Sürdürülebilir etkin bir su yönetiminin, mülteci sayısı
ve olası göç akışını göz ardı etmeden mümkün olacağı sonucuna ulaşılmıştır.
Yapılan değerlendirmeler, yaşanan su sıkıntısının bölgedeki topluluklar ve
devletlerarasındaki çatışmalara neden olabileceği ve Ortadoğu'da işbirliği
sağlanmadan su sıkıntısı ve kuraklıkla mücadele sürecinin tamamlanamayacağını
göstermiştir. Nüfus artışı
ve iklim değişikliği, özellikle bu bölgede, yağışın daha belirsiz ve
değişkenliğine neden olduğundan, su kıtlığı önümüzdeki yirmi yıl içinde daha da
büyük bir sorun haline geleceği öngörülmektedir. Su miktarı ve kalitesi de
sağlık ve çevre üzerinde önemli etkilere sahiptir.  Bu etkilerin alternatif su yönetimi ve
verimlilik stratejilerine karşı değerlendirilmesi ve politika maliyetleri ve
ekonomik kalkınma konularının ışığında, kıt kaynak kullanımı optimize
edilebilir. Ürdün uzun
süredir iklim değişikliği, nüfus artışı, çatışmalar ve mülteci krizleri
nedeniyle artan su kıtlığı ile karşı karşıyadır. The desert kingdom has one of the lowest levels of water
availability in the world and hosts the second largest number of Syrian
refugees per person, following Lebanon.Dünyadaki en düşük su miktarına
sahip olması ile birlikte kişi başına düşen en çok sayıda Suriyeli mülteciye ev
sahipliği yapıyor olması Ürdün’ün su kaynakları için büyük bir sorun
yaratmaktadır.
Dede Korkut Kitabı’nın Kronotop Bağlamında İncelenmesi
Authors: Kuzay Demir Gonca
Published: February 2018

Türk halk edebiyatının en önemli
eserlerinden biri olarak kabul edilen Dede Korkut Kitabı, günümüze biri
Vatikan’da diğeri ise Dresden’de bulunan yazılı iki nüsha ve sözlü kültürde
sayısız versiyonları ile ulaşmıştır. Değerine nazaran geç bir tarihte bilim
dünyasına tanıtılan Dede Korkut Kitabı, özellikle son yıllarda oldukça fazla
araştırmaya konu olmuştur. Dede Korkut Kitabı, Oğuz boyunun dünya görüşünü ve
yaşam tarzını anlatan bir eser olmakla birlikte, tüm Türk boyları tarafından
sahiplenilmektedir. Bu durum eserin sözlü anlatı geleneğinin bir parçası
olmasından kaynaklandığı gibi, daha çok eserde kullanılan zaman ve mekân
birlikteliğinin geçmiş ile gelecek arasında bir bağ kurarak, eserin yerelden
evrensele ulaşan değerlere sahip olmasından kaynaklanmaktadır. Bu nedenle Dede
Korkut Kitabı’ndaki zaman ve mekân ilişkisi son derece önemlidir. Bu makalede;
Dede Korkut Kitabı’ndaki zaman ve mekân ilişkisi üzerinde durulmuştur.
İncelemede zaman ve mekân ilişkisini bir kuramsal çerçevede ele alan, M. M.
Bakhtin’in kronotop kuramı kullanılmıştır. Bu nedenle öncelikle Bahktin’in
edebiyat teorisine kazandırdığı “kronotop” terimi ve kuramın temel özellikleri
açıklanmış, daha sonra Dede Korkut Kitabı’nda yer alan kronotoplar belirlenip,
kronotopların anlatmalardaki işlevleri üzerinde durulmuştur. Böylelikle
kronotoplar bağlamında, Dede Korkut anlatmalarını geçmişten geleceğe taşıyan
özellikler tespit edilmiştir.
Milli Mücadele Döneminde Elbistan
Authors: KILIÇ Fahri
Published: February 2018

İngilizlerin Maraş’ta
yaklaşık sekiz ay boyunca sürdürdükleri işgalin sona ermesinin ardından şehri 1
Kasım 1919’da Fransızlar işgal etmiştir. Bu haksız işgallerin ardından Temsil
Heyeti Başkanı Mustafa Kemal Paşa, Maraş’ta milli direnişi başlatmak için bir
milli teşkilat kurulmasına karar vermiştir. Bu amaçla da bölgenin kurtuluşu
için hali hazırda işgal altında bulunmayan ve coğrafi bakımdan doğal bir
güvenliğe sahip olan Elbistan merkez olarak seçilmiştir. Bu gelişmelerden sonra
emekli eski Şam Sulh hâkimi Ali Rıza Bey’in başkanlığında Elbistan’da bir
Müdafaa-i Hukuk Cemiyeti kurulmuştur. Cemiyet, yaptığı çalışmalarla kısa sürede
Mustafa Kemal Paşa’nın Güney Cephesine yönelik uygulamalarının en önemli unsuru
haline gelmiştir. Maraş’a Elbistan üzerinden sürekli askeri yardımlarda
bulunmuş, Maraş’ın kuzeyinde bir savunma hattı oluşturulmuştur. Bu çalışma, Milli Mücadele’nin en parlak
destanlarından birini oluşturan Maraş Müdafaasına Elbistan aracılığıyla yapılan
katkıları kapsamıştır. Bulgular ışığında güney cephesinde Elbistan’ın stratejik
ve lojistik önemi ortaya konulmuştur. Araştırma verileri döneme ilişkin arşiv
kaynakları, süreli yayınlar ve anılardan oluşturulmuştur.