bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTOR signaling in stem and progenitor cells
Authors: Meng Delong , Frank Anderson R. , Jewell Jenna L. 
Published: January 2018

ABSTRACT
The mammalian target of rapamycin (mTOR) senses nutrients and growth factors to coordinate cell growth, metabolism and autophagy. Extensive research has mapped the signaling pathways regulated by mTOR that are involved in human diseases, such as cancer, and in diabetes and ageing. Recently, however, new studies have demonstrated important roles for mTOR in promoting the differentiation of adult stem cells, driving the growth and proliferation of stem and progenitor cells, and dictating the differentiation program of multipotent stem cell populations. Here, we review these advances, providing an overview of mTOR signaling and its role in murine and human stem and progenitor cells.
Revealing age-related changes of adult hippocampal neurogenesis using mathematical models
Authors: Ziebell Frederik , Dehler Sascha , Martin-Villalba Ana , Marciniak-Czochra Anna 
Published: January 2018

ABSTRACT
New neurons are continuously generated in the dentate gyrus of the adult hippocampus. This continuous supply of newborn neurons is important to modulate cognitive functions. Yet the number of newborn neurons declines with age. Increasing Wnt activity upon loss of dickkopf 1 can counteract both the decline of newborn neurons and the age-related cognitive decline. However, the precise cellular changes underlying the age-related decline or its rescue are fundamentally not understood. The present study combines a mathematical model and experimental data to address features controlling neural stem cell (NSC) dynamics. We show that available experimental data fit a model in which quiescent NSCs may either become activated to divide or may undergo depletion events, such as astrocytic transformation and apoptosis. Additionally, we demonstrate that old NSCs remain quiescent longer and have a higher probability of becoming re-activated than depleted. Finally, our model explains that high NSC-Wnt activity leads to longer time in quiescence while enhancing the probability of activation. Altogether, our study shows that modulation of the quiescent state is crucial to regulate the pool of stem cells throughout the life of an animal.
Cytoplasmic polyadenylation-mediated translational control of maternal mRNAs directs maternal-to-zygotic transition
Authors: Winata Cecilia Lanny , Łapiński Maciej , Pryszcz Leszek , Vaz Candida , bin Ismail Muhammad Hisyam , Nama Srikanth , Hajan Hajira Shreen , Lee Serene Gek Ping , Korzh Vladimir , Sampath Prabha , Tanavde Vivek , Mathavan Sinnakaruppan 
Published: January 2018

ABSTRACT
In the earliest stages of animal development following fertilization, maternally deposited mRNAs direct biological processes to the point of zygotic genome activation (ZGA). These maternal mRNAs undergo cytoplasmic polyadenylation (CPA), suggesting translational control of their activation. To elucidate the biological role of CPA during embryogenesis, we performed genome-wide polysome profiling at several stages of zebrafish development. Our analysis revealed a correlation between CPA and polysome-association dynamics, demonstrating a coupling of translation to the CPA of maternal mRNAs. Pan-embryonic CPA inhibition disrupted the maternal-to-zygotic transition (MZT), causing a failure of developmental progression beyond the mid-blastula transition and changes in global gene expression that indicated a failure of ZGA and maternal mRNA clearance. Among the genes that were differentially expressed were those encoding chromatin modifiers and key transcription factors involved in ZGA, including nanog, pou5f3 and sox19b, which have distinct CPA dynamics. Our results establish the necessity of CPA for ensuring progression of the MZT. The RNA-seq data generated in this study represent a valuable zebrafish resource for the discovery of novel elements of the early embryonic transcriptome.
Glucose deprivation induces primary cilium formation through mTORC1 inactivation
Authors: Takahashi Kengo , Nagai Tomoaki , Chiba Shuhei , Nakayama Keiko , Mizuno Kensaku 
Published: January 2018

ABSTRACT
Primary cilia are antenna-like sensory organelles extending from the surface of many cell types that play critical roles in tissue development and homeostasis. Here, we examined the effect of nutrient status on primary cilium formation. Glucose deprivation significantly increased the number of ciliated cells under both serum-fed and -starved conditions. Glucose deprivation-induced ciliogenesis was suppressed by overexpression of Rheb, an activator of the mammalian target of rapamycin complex-1 (mTORC1). Inactivating mTORC1 by rapamycin treatment or Raptor knockdown significantly promoted ciliogenesis. These results indicate that glucose deprivation promotes primary cilium formation through mTORC1 inactivation. Rapamycin treatment did not promote autophagy or degradation of OFD1, a negative regulator of ciliogenesis. In contrast, rapamycin treatment increased the level of the p27KIP1 (also known as CDKN1B) cyclin-dependent kinase inhibitor, and rapamycin-induced ciliogenesis was abrogated in p27KIP1-depleted cells. These results indicate that mTORC1 inactivation induces ciliogenesis through p27KIP1 upregulation, but not through autophagy. By contrast, glucose deprivation or rapamycin treatment shortened the cilium length. Thus, glucose deprivation and subsequent inactivation of mTORC1 play dual roles in ciliogenesis: triggering primary cilium formation and shortening cilium length.
This article has an associated First Person interview with the first author of the paper.
Meeting report – shining light on septins
Authors: Caudron Fabrice , Yadav Smita 
Published: January 2018

ABSTRACT
Septins are enigmatic proteins; they bind GTP and assemble together like molecular Lego blocks to form intracellular structures of varied shapes such as filaments, rings and gauzes. To shine light on the biological mysteries of septin proteins, leading experts in the field came together for the European Molecular Biology Organization (EMBO) workshop held from 8–11 October 2017 in Berlin. Organized by Helge Ewers (Freie Universität, Berlin, Germany) and Serge Mostowy (Imperial College, London, UK), the workshop convened at the Harnack-Haus, a historic hub of scientific discourse run by the Max Planck Society.
Filamentous Viruses as Building Blocks for Hierarchical Self-Assembly toward Functional Soft Materials
Authors: Sawada Toshiki , Serizawa Takeshi 
Published: January 2018

Abstract
This review describes the utilization of M13 phage, one of the filamentous viruses, for the development of novel functional soft materials. Traditionally, M13 phage has been widely used as a scaffold to display peptides or proteins on the surface of M13 phage through genetic engineering. This technology is well known as “phage display”, and generally used nowadays for the construction of peptide or protein libraries on M13 phage surfaces to identify peptides or proteins with desired functions. Recently, construction of hierarchical assembled structures composed of M13 phage as a building block has generated great interest as a means of using the excellent properties of M13 phage for the development of novel classes of soft materials. In this case, liquid crystalline formation of M13 phage is effectively used to fabricate structurally regulated assemblies. Further combination of the phage display technique and liquid crystalline formation widely expands the applicability of M13 phage to various fields such as devices, sensors, and biomedicines. Such approaches to M13 phage should contribute to novel attractive opportunities for next-generation soft materials for science and technology.
Investigation of the use of external aluminium targets for portal imaging in a medical accelerator using Geant4 Monte Carlo simulation
Authors: Kim Hyungdong , Kim Byungyong , Baek Jonggeun , Oh Youngkee , Yun Sangmo , Jang Hyunsoo 
Published: January 2018

Objective:
To install a low-Z target on the wedge tray mount of a medical linear accelerator to create a new image beam and to confirm image contrast enhancement.

Methods:
Experimental low-energy photon beams were produced with the linac running in the 6 MeV electron mode and with a low-Z target installed on the wedge tray mount [denoted 6 MeV (low-Z target)]. Geant4 Monte Carlo simulation was performed to analyse the energy spectrum and image contrast of a 6 MeV (low-Z target) beam. This study modelled the 6 MeV (low-Z target) beam and the 6 MV (megavoltage) radiotherapy photon beam and verified model validity by measurement. In addition, a contrast phantom was modelled to quantitatively compare the image contrasts of the 6 MeV (low-Z target) beam and the 6 MV radiotherapy photon beam. A low-Z target was fabricated to generate low-energy photons (25–150 keV) from incident electrons, and a portal image of the Alderson RANDO phantom was acquired using a clinical linear accelerator for qualitative analysis.

Results:
The measured and calculated percentage depth dose of the 6 MV photon and 6 MeV (Al) beams were consistent within 1.5 and 1.6%, respectively, and calculated lateral profiles of the 6 MV photon beam and the 6 MeV (Al) beam were consistent with the measured results within 1.5 and 1.9%, respectively. Although low-energy photons (25–150 keV) of the 6 MV photon beam were only 0.3%, the Be, C, and Al low-Z targets, but not the Ti target, generated 34.4 to 38.5% low-energy photons. In 5 to 20 cm water phantoms, contrast of the 6 MeV (Al) beam was approximately 1.16 times greater than that of the 6 MV beam. The contrasts of 6 MeV (Al) and 6 MV photon beams in the 20 cm water phantom were ~34% lower than those in the 5 cm water phantom. 6 MeV (Al)/CR (computed radiography) images of the human body phantom were more vivid and detailed than 6 MV/EPID (electronic portal imaging device) and 6 MeV (Al)/EPID images.

Conclusion:
The experimental beam with a low-Z target, which was simply installed on the wedge tray mount of the radiotherapy linear accelerator, generated significantly more low-energy photons than the 6 MV radiotherapy photon beam, and provided better quality portal images.

Advances in knowledge:
This study shows that, unlike the existing low-Z beam studies, a low-Z target can be installed outside the head of a linear accelerator to improve portal image quality.
Οι έμφυλες κατασκευές των παιδιών νηπιαγωγείου για τα επαγγέλματα
Authors: Παπαναστασίου Έμη 
Published: January 2018

Το περιβάλλον των παιδιών τους προσφέρει πολλές πληροφορίες και γνώσεις σε σχέση με τα φύλα και τα επαγγέλματα, οι οποίες εκφράζονται με διάφορους τρόπους. Η έρευνα που παρουσιάζεται στο παρόν άρθρο περιγράφει τις αντιλήψεις/κατασκευές παιδιών νηπιαγωγείου σε σχέση με το επάγγελμα που θα ήθελαν να ακολουθήσουν αλλά και με τα επαγγέλματα που «αρμόζουν» στο κάθε φύλο. Η έρευνα πραγματοποιήθηκε με τη μέθοδο των ημι-δομημένων συνεντεύξεων που αναλύθηκαν υπό το θεωρητικό πρίσμα της φεμινιστικής κοινωνικής κατασκευής. Τα ευρήματα δείχνουν ότι τα παιδιά βασίζονται κυρίως σε δυιστικές στερεοτυπικές αντιλήψεις για τα φύλα και την επιλογή επαγγέλματος.
Does evidence support the high expectations placed in precision medicine? A bibliographic review
Authors: Cortés Jordi , González José Antonio , Medina María Nuncia , Vogler Markus , Vilaró Marta , Elmore Matt , Senn Stephen John , Campbell Michael , Cobo Erik 
Published: January 2018

Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, the conventional design of randomized trials assumes that each individual benefits by the same amount. Methods: We reviewed parallel trials with quantitative outcomes published in 2004, 2007, 2010 and 2013. We collected baseline and final standard deviations of the main outcome. We assessed homoscedasticity by comparing the outcome variability between treated and control arms. Results: The review provided 208 articles with enough information to conduct the analysis. At the end of the study, 113 (54%, 95% CI 47 to 61%) papers find less variability in the treated arm. The adjusted point estimate of the mean ratio (treated to control group) of the outcome variances is 0.89 (95% CI 0.81 to 0.97). Conclusions: Some variance inflation was observed in just 1 out of 6 interventions, suggesting the need for further eligibility criteria to tailor precision medicine. Surprisingly, the variance was more often smaller in the intervention group, suggesting, if anything, a reduced role for precision medicine. Homoscedasticity is a useful tool for assessing whether or not the premise of constant effect is reasonable.
Characterizing Polytopes in the 0/1-Cube with Bounded Chvátal-Gomory Rank
Authors: Benchetrit Yohann , Fiorini Samuel , Huynh Tony , Weltge Stefan 
Published: January 2018

Let S ⊆ {0, 1}n and R be any polytope contained in [0, 1]n with R ∩ {0, 1}n = S. We prove that R has bounded Chvátal-Gomory rank (CG-rank) provided that S has bounded notch and bounded gap, where the notch is the minimum integer p such that all p-dimensional faces of the 0/1-cube have a nonempty intersection with S, and the gap is a measure of the size of the facet coefficients of conv(S). Let [Formula: see text] denote the subgraph of the n-cube induced by the vertices not in S. We prove that if [Formula: see text] does not contain a subdivision of a large complete graph, then the notch and the gap are bounded. By our main result, this implies that the CG-rank of R is bounded as a function of the treewidth of [Formula: see text]. We also prove that if S has notch 3, then the CG-rank of R is always bounded. Both results generalize a recent theorem of Cornuéjols and Lee [Cornuéjols G, Lee D (2016) On some polytopes contained in the 0,1 hypercube that have a small Chvátal rank. Louveaux Q, Skutella M, eds. Proc. 18th Internat. Conf. Integer Programming Combinatorial Optim., IPCO ’16 (Springer International, Cham, Switzerland), 300–311], who proved that the CG-rank is bounded by a constant if the treewidth of [Formula: see text] is at most 2.
Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine
Authors: Wu Alan H B , Christenson Robert H , Greene Dina N , Jaffe Allan S , Kavsak Peter A , Ordonez-Llanos Jordi , Apple Fred S 
Published: January 2018

Abstract
This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB,8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: (a) quality control (QC) utilization, (b) validation of the lower reportable analytical limits, (c) units to be used in reporting measurable concentrations for patients and QC materials, (d) 99th percentile sex-specific upper reference limits to define the reference interval; (e) criteria required to define hs-cTn assays, (f) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, (g) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, (h) harmonizing and standardizing assay results and the role of commutable materials, (i) time to reporting of results from sample receipt and sample collection, and (j) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.
KESANTUNAN SEMU PADA TINDAK TUTUR EKSPRESIF MARAH DALAM BAHASA INDONESIA
Authors: Ekawati Mursia 
Published: January 2018

Verbal anger is an expressive speech act. The language function that supported by expressive speech act is interactional, which is used to reveal social relationship and private attitude. The aims of this research is to get patterns of verbal anger in terms of expressive speech act in Bahasa. This research uses socio-pragmatic method to analyze through speech components, involving sociolinguistics and implicature. Data analysis is done by explaining the marker shapes as the indicator of anger and to whom (P1, P2 or P3) the anger is for. The result shows that speech act of anger are done through indirect sentences (interogative and affirmative sentences), implicit meanings and focus on the third party (P3). Anger to third party is realised as a pseudo politeness. The function of pseudo politeness is also for maintaining the social relationship between friends, families, and communities. This speech act of anger can be done through indirect sentences with the explicit meaning and focus on second party (P2). It is also done through direct sentences and explicit meanings with or without response from P2.
KONTRIBUSI AUDIT INTERNAL TERHADAP MANAGEMEN RISIKO
Authors: Hadinata Sofyan 
Published: January 2018

AbstractRisks always exist in a business activity of an organization. Risks are closely related to the differences between the results and the expectations. Risk management focuses on the anticipatory actions by recognizing potential risks and influences. Risk management is part of the entity’s internal control in which the main responsibility is in the hand of the company manager or the entity. Internal auditor as the employee or the internal party has the duty to implement the risk management. Internal auditor conducts an audit process towards internal control and gives assurance in the process of risk management. The internal auditor who takes part in consultation role can assist the organization in identifying, evaluating, and implementing relevant risk management and risk control methodologies. Risk management procedures are identifying risks, constructing plans, and determining solutions. Some of the solutions are avoiding, minimizing, removing, or accepting the risks. Keywords: risk, anticipatory, internal controlAbstrakRisiko melekat pada suatu aktivitas bisnis organisasi. Risiko terkait erat antara ketidaksesuaian hasil dengan yang diharapkan. Managemen risiko merupakan suatu tindakan untuk mengurangi ketidakpastian yang berfokus pada tindakan antisipasi/pencegahan, dengan cara mengidentifikasi risiko yang mungkin terjadi sekaligus dampak yang mungkin ditimbulkan. Managemen risiko merupakan bagian dari pengendalian internal entitas yang tanggung jawab utamanya di tangan manager perusahaan atau entitas. Auditor internal selaku pegawai atau pihak internal perusahaan juga memiliki tugas atau kewajiban atas pelaksanaan managemen risiko. Audit internal melakukan proses audit terhadap pengendalian internal dan memberikan keyakinan terhadap proses managemen risiko. Auditor internal memiliki peran konsultasi yang dapat membantu organisasi dalam mengidentifikasi, mengevaluasi, dan menerapkan metodologi managemen risiko dan pengendalian yang relevan. Langkah-langkah yang harus dilakukan dalam managemen risiko adalah identifikasi risiko, membuat perencanaan, dan menentukan cara penanganannya. Penangannya risiko dapat dilakukan dengan cara yaitu menghindari, mengurangi, memindahkan, atau menerima risiko tersebut.Kata kunci: risiko, antisipasi/pencegahan, pengendalian internal
Implementasi Metode Simplek untuk Mengetahui Optimasi Produksi Gerabah (Studi Kasus: Sentra Kerajinan Kasongan Bantul Daerah Istimewa Yogyakarta)
Authors: Hiswati Marselina Endah , Wicaksono Lutfi Nur 
Published: January 2018

Abstrak Produksi di sebuah perusahaan berjalan setiap hari untuk bertahannya proses kegiatan dan keberlangsungan kehidupan bagi perusahaan tersebut. Perusahan dalam hal ini bagi pengusaha gerabah di daerah Kasongan, dikatakan berjalan dengan baik jika semua unit di setiap bagian perusahaan pun berjalan dengan lancar dan baik pula. Proses produksi yang terjadi juga membutuhkan beberapa komponen yang mendukung proses produksi itu berjalan dengan baik sehingga tujuan perusahaan tercapai. Selain keputusan dari seorang pimpinan perusahaan dalam penentuan jumlah serta kebutuhan produksi, juga dibutuhkn sumber daya - sumber daya lain, misalnya waktu, tenaga kerja, energi, bahan baku, atau uang; atau dapat berupa bentuk batasan pedoman. Secara umum, tujuan perusahaan yang paling sering terjadi adalah sedapat mungkin memaksimumkan laba.Tujuan lain dari unit organisasi yang merupakan bagian dari suatu organisasi biasanya berupa meminimumkan biaya. Ketersediaan sumber daya yang ada inipun sangatlah besar pengaruhnya bagi optimalisasi produksi di perusahaan tercapai. Komponen atau variabel pendukung produksi tidak mungkin hanya terbatas dua variabel saja. Maka hal inilah dibutuhkan sebuah metode yang dapat menangani permasalahan produksi yang lebih komplek yaitu metode Simplek. Penyelesaian digunakan sebuah software aplikasi POM-QM for Windows.Hasil penelitian nantinya bermanfaat bagi perusahaan dalam memaksimalkan keuntungan tapi juga dapat untuk mengetahui bagaimana menentukan formulasi sehingga menghasilkan sebuah solusi optimal di sebuah perusahaan sesuai tujuan perusahaan. Kata kunci : optimasi, metode simplek, POM-QM for Windows.