bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phenomenon of Synonymy: A Comparison of the French and Macedonian Legal Terminologies
Authors: Jakimovska Svetlana
Published: February 2015

The Phenomenon of Synonymy: A Comparison of the French and Macedonian Legal TerminologiesSynonymy is a language phenomenon that is viewed in a different way by the lexicologists and the terminologists. For the lexicologists synonymy contributes to the diversity of the language, whereas for the terminologists it leads to the imprecision of the specialized communication. The aim of this paper is to compare the manifestations of this phenomenon in both French and Macedonian language of law, specialized language that insists a lot on the precise formulation.The comparative analysis takes into consideration two big synonym groups: semantic and stylistic synonyms. The analysis of the synonyms belonging to the first group shows the role of the context when choosing an adequate synonym. On the other hand, the analysis of the stylistic synonyms, concentrates more on the expressive values of different terms. It also shows the presence of different types of synonyms in different languages i.e. presence of geographic synonyms in French, or presence of different types of historic synonyms in the two languages.Pointing out the different meaning nuances and the proper ways of use of the terms can be of crucial importance for the translator, especially for the legal texts translator.Key words: terminology, law, synonyms, French language, Macedonian language.
La poésie dans l’apprentissage du roumain langue étrangère
Authors: Jieanu Ioana
Published: February 2015

La poésie dans l’apprentissage du roumain langue étrangère
Il Novecentismo: »Un’impresa contro il diavolo«. Note sul progetto culturale ed estetico bontempelliano
Authors: Farinelli Patrizia
Published: February 2015

Nel presente contributo, sulla scorta degli interventi teorici e polemici raccolti ne L’avventura novecentista (1938) si ripercorrono le posizioni di Bontempelli legate al progetto di rinnovamento culturale (il Novecentismo) di cui questo intellettuale fu promotore negli anni Venti. Vi si segnalano le battaglie difese e la lungimiranza delle vedute, ma anche i nodi problematici o piuttosto le sfide che quel progetto lanciava. E qui rientrano l’utopica battaglia contro il relativismo, la difesa dell’autonomia dell’arte assieme alla contemporanea richiesta di una sua apertura alle esigenze del proprio tempo, la ricerca di conciliare un fare estetico orientato alla rottura di norme e attese con un concetto di arte e letteratura popolari.
What is Narrative Research?
Authors: Squire Corinne , Davis Mark , Esin Cigdem , Andrews Molly , Harrison Barbara , Hydén Lars-Christer , Hydén Margareta
Published: February 2015

Narrative research has become a catchword in the social sciences today, promising new fields of inquiry and creative solutions to persistent problems.

This book brings together ideas about narrative from a variety of contexts across the social sciences and synthesizes understandings of the field. Rather than focusing on theory, it examines how narrative research is conducted and applied. It operates as a practical introductory guide, basic enough for first-time researchers, but also as a window onto the more complex questions and difficulties that all researchers in this area face.

The authors guide readers through current debates about how to obtain and analyse narrative data, about the nature of narrative, the place of the researcher, the limits of researcher interpretations, and the significance of narrative work in applied and in broader political contexts.
Ethical and clinical dilemmas in patients with head and neck tumors visiting a field hospital in the Philippines
Authors: Marom, MD Tal , Segal, MD David , Erlich, MD Tomer , Tsumi, MD Erez , Merin, MD, MHA Ofer , Lin, MD Guy
Published: February 2015

Objective: To describe clinical and ethical dilemmas in patients presenting with head and neck (HN) tumors to a field hospital in the “subacute” period following a typhoon.Methods: We retrospectively reviewed charts of HN patients presenting to an integrated Israeli-Filipino medical facility, which was operated more than 11 days.Results: Of the 1,844 adult patients examined, 85 (5 percent) presented with HN tumors. Of those, 70 (82 percent) were females, with a mean age of 43 ± 15 years. Thyroid neoplasms were the most common tumors (68, 80 percent). Despite limited resources, we contributed to the workup and treatment of several patients. To better illustrate our dilemmas, we present four key patients, in whom we favored diagnostic/therapeutic interventions in two, and opted to defer any intervention in two.Conclusions: In a relief mission, despite the lack of clinical and pathological staging and questionable continuity of care, surgical interventions can be considered for therapeutic, palliative, and diagnostic purposes.
Book review
Authors: Nurok, MBChB, PhD Michael
Published: February 2015

Toxic Trauma: A Basic Clinical Guide, by David J. Baker. Springer, 2014.
Emergency evacuation orders: Considerations and lessons from Hurricane Sandy
Authors: O’Neil, PhD, Capt. USN (ret) Patrick D.
Published: February 2015

This article analyzes the problems surrounding the execution of emergency evacuation orders by evaluating Hurricane Sandy and the emergency actions taken by the State of New Jersey and the City of Atlantic City New Jersey. The analysis provides an overview of the legal authority granting emergency powers to governors and mayors to issue evacuation proclamations in addition to an evaluation of the New Jersey’s emergency evacuation mandate and subsequent compliance. The article concludes with provision of planning and preparedness recommendations for public managers facing similar hazards, including a recommendation for provision of emergency shelter contingencies within the threat zone in anticipation of citizen noncompliance evacuation orders.
Information and communication technology: Connecting the public and first responders during disasters
Authors: Buzzelli, MS, CHES Michelle M. , Morgan, BA Paula , Muschek, BA Alexander G. , Macgregor-Skinner, BVSc, MSc, MPH, MRCVS Gavin
Published: February 2015

Lack of success in disaster recovery occurs for many reasons, with one predominant catalyst for catastrophic failure being flawed and inefficient communication systems. Increased occurrences of devastating environmental hazards and human-caused disasters will continue to promulgate throughout the United States and around the globe as a result of the continuous intensive urbanization forcing human population into more concentrated and interconnected societies. With the rapid evolutions in technology and the advent of Information and communication technology (ICT) interfaces such as Facebook, Twitter, Flickr, Myspace, and Smartphone technology, communication is no longer a unidirectional source of information traveling from the newsroom to the public. In the event of a disaster, time critical information can be exchanged to and from any person or organization simultaneously with the capability to receive feedback. A literature review of current information regarding the use of ICT as information infrastructures in disaster management during human-caused and natural disasters will be conducted. This article asserts that the integrated use of ICTs as multidirectional information sharing tools throughout the disaster cycle will increase a community's resiliency and supplement the capabilities of first responders and emergency management officials by providing real-time updates and information needed to assist and recover from a disaster.
Volunteers and professional rescue workers: Traumatization and adaptation after an avalanche disaster
Authors: Haraldsdóttir, Cand Psych Helga Arnfridur , Gudmundsdóttir, PhD Drifa , Romano, MSc Eugenia , Þórðardóttir, BA Edda Björk , Guðmundsdóttir, MSc Berglind , Elklit, MSc Ask
Published: February 2015

Objective: To compare the degree of traumatization and adaptation in professional and volunteer rescue workers after two snow avalanches. Method: Questionnaires including demographic questions, the Social Readjustment Rating Scale, the Rescue Workers Questionnaire, the General Health Questionnaire, the Impact of Event Scale, and the Coping Styles Questionnaire were answered by rescue workers (n = 168).Results: In several areas, professional rescuers had stronger fears than volunteers, all the same, volunteers were significantly more anxious and met criteria for PTSD caseness more often than professionals.Conclusion: The findings suggest that voluntary rescue workers suffer from post-traumatic stress disorder symptoms more often than professionals following demanding rescue missions.
Category change and risk perception: Hurricane Irene and coastal North Carolina
Authors: Pace, MA William , Montz, PhD Burrell
Published: February 2015

Objective: This research explores variations in risk perception with location and changes in the intensity of a hurricane (Hurricane Irene in 2011). Design: Surveys were mailed to a random sample of 601 year-round residents of two counties in coastal North Carolina. Within each county, areas were chosen based on their risk with respect to wind or storm surge; an equal number of surveys were sent to each area. A 31 percent return rate was achieved.Setting: Dare County on the Outer Banks of North Carolina and Beaufort County on the Inner Banks were chosen as study areas because of the nature and extent of damage incurred from Hurricane Irene.Main Outcome Measure: Because Hurricane Irene was downgraded before it made landfall in North Carolina, it was anticipated that residents would perceive themselves to be at less risk to hurricane-related hazards with differences related to location on the Atlantic Ocean or on the Sound.Results: Little difference was found between the Inner and Outer Banks locations such that all reported the change in intensity influenced their perceptions by reducing the sense of risk. This varied somewhat, but not significantly, by hazard area.Conclusions: The downgrading of Hurricane Irene created a false sense of security. Residents of the study area believed themselves to be at low risk and were unlikely to evacuate, despite warnings. The long duration of the event, however, led to significant damages, surprising many, and suggesting the need to emphasize impacts in messaging, no matter the storm intensity.
On the use of radon for quantifying the effects of atmospheric stability on urban emissions
Authors: Chambers S. D. , Williams A. G. , Crawford J. , Griffiths A. D.
Published: February 2015

Abstract. Radon is increasingly being used as a tool for quantifying stability influences on urban pollutant concentrations. Bulk radon gradients are ideal for this purpose, since the vertical differencing substantially removes contributions from processes on timescales greater than diurnal and (assuming a constant radon source) gradients are directly related to the intensity of nocturnal mixing. More commonly, however, radon measurements are available only at a single height. In this study we argue that single-height radon observations should not be used quantitatively as an indicator of atmospheric stability without prior conditioning of the time series to remove contributions from larger-scale "non-local" processes. We outline a simple technique to obtain an approximation of the diurnal radon gradient signal from a single-height measurement time series, and use it to derive a four category classification scheme for atmospheric stability on a "whole night" basis. A selection of climatological and pollution observations in the Sydney region are then subdivided according to the radon-based scheme on an annual and seasonal basis. We compare the radon-based scheme against a commonly used Pasquill–Gifford (P–G) type stability classification and reveal that the most stable category in the P–G scheme is less selective of the strongly stable nights than the radon-based scheme; this lead to significant underestimation of pollutant concentrations on the most stable nights by the P–G scheme. Lastly, we applied the radon-based classification scheme to mixing height estimates calculated from the diurnal radon accumulation time series, which provided insight to the range of nocturnal mixing depths expected at the site for each of the stability classes.
Globalization of medical education: Educational Commission for Foreign Medical Graduates (ECFMG) concerns and initiatives
Authors: Cassimatis Emmanuel G.
Published: February 2015

The Educational Commission for Foreign Medical Graduates (ECFMG) certifies international medical graduates (IMGs) for entry into United States graduate medical education. It also promotes medical education through programmatic and research activities. Physician migration is changing and the ECFMG responds to the needs of IMGs coming to the United States to study and to those searching for training opportunities in other countries. It seeks to provide information about national and international medical schools' accreditation status and other similar data. For ECFMG purposes, accreditation of an international medical school by an agency recognized by the Federation for Medical Education (WFME) will meet its new requirement for certification, effective in 2023.
Two vascular variations in one patient of the hepatogastric trunk and retro-aortic left renal vein
Authors: Ibrahim Guler , Yılmaz Mehmet Tugrul , Keskin Suat , Arıbas Alpay , Akın Dondu , Akcan Mustafa , Salbacak Ahmet
Published: February 2015

This study reports the case of a 61-year-old man with right upper quadrant pain who underwent abdominal computed tomography examination. A solid lesion originating from the biliary tract was detected on the images. While evaluating the vascular structures, the splenic artery was seen to directly originate from the abdominal aorta. Retro-aortic left renal vein was also seen on computerised tomography. Splenic artery originating from the abdominal aorta is a rare variation. The retro-aortic left renal vein is a malformation characterized by the presence of a vessel that drains the left renal blood up to the inferior vena cava crossing behind the aortic artery. Such anatomical variations are important for surgeons to be aware of.
TVET Education Reform in the MENA region following the Arab Spring
Authors: Gamar Samah
Published: February 2015

The Arab Spring of 2011 deconstructed enduring post-colonial dictatorships that perpetuated propaganda politics and penalized democratic expression. Within four months of the start of the revolutions, intellectuals began actively discussing how the uprisings of Tunisia, Egypt, Yemen, Libya, and Syria, along with resistance movements in neighbouring countries, offered “a particular opportunity to switch pedagogic and scholarly modes and strategies” in the region (Jadaliyyah, 2011). Indeed, it is an opportune time to discuss fundamental education reforms – amendments that remedy specific ideological paradoxes and
incongruences that have obstructed education for a democratic society and thwarted civil empowerment in the Middle East and North African (MENA) region. This study provides an overview of the major factors that plague MENA education systems which include increasing educational disparity, a decrease in the quality of education despite high per capita education expenditures, and a mismatch between labour market needs and the outputs of education systems. It specifically highlights the post- revolution evolution technical and vocational education and training systems must undergo to effectively address one of the
highest youth unemployment rates in the world – a significant contributor to ongoing unrest among the 85 million youth in the region. Specific recommendations for ways in which TVET reforms can positively impact this demographic through measures that address education quality and relevance are presented.
Human Personhood in Contemporary Islamic Bioethical Discourse
Authors: Ghaly Mohammed
Published: February 2015

The breathtaking panoply of twentieth-century biomedical advancements made it possible to follow, and even sometimes manipulate, what is going on inside the mother's uteruses during the gestational period. These radical scientific developments have had considerable impact on grasping some of the very basic concepts in our lives such as health and sickness, life and death and even the very notion of human personhood.

During the period 15-17 January 1985, about eighty Muslim religious scholars and biomedical scientists participated in a seminar organized by the Islamic Organization for Medical Sciences (IOMS) in order to examine the impact of these scientific developments on understanding (the beginning of) human personhood from an Islamic perspective. This presentation will delineate the main points of the beginning of life debate in the IOMS seminar and highlight the roles of biomedical and religious arguments in this debate.
Law And Ethics In Islamic Bioethics
Authors: Sachedina Abdulaziz
Published: February 2015

While the scope of Islamic Jurisprudence (fiqh) covers, broadly speaking, two areas of human-God (‘ibadat) and human-human (mu’amalat) relations, ethics undergirds the entire value system of the religious law in Islam. Throughout its history Islamic jurisprudence has been guided by the normative system derived from religious texts that has enabled jurists at different times to provide fresh rulings by engaging in ethical analysis as well as textual hermeneutics of the foundational sources of these norms and apply them to the changed circumstances of everyday life of Muslim societies. The growing fatawa literature bears testimony to the ever expanding horizons of human need to be guided by the spiritual and moral values embedded in Islamic religious texts. In more recent years with the emphasis on secular ethics that denies any role to religious ethics to guide moral life of the people, Muslim legal scholars have begun to reexamine the fundamental aspects of Islamic ethics, and the ways in which Muslim jurists in the past have incorporated essentially religious-ethical dimension of Islamic thought in their legal methodology.

However, with a circumscribed role for human reason, traditional religious ethical discourse among Muslim scholars tends to be inadequate in terms of providing justificatory reasoning that undergirds secular ethics. Whether the jurists promote reason-based or revelation-based inquiry, they have, explicitly or implicitly, engaged in adapting ethical values in providing extraordinary solutions in medical practice and research. This paper undertakes to investigate critical relationship between law and ethics in Islamic religious thought as an important methodology in Islamic bioethics. In a number of new proposals for extensive legal methodology, the ethical dimension of Islamic thought is either conspicuously missing or poorly articulated. The study of Muslim rationalist or traditionalist theology is necessary for the emergence of extensive legal methodology. Modern issues related to neuroscience or human personhood can be resolved only when human rational capacity to make ethical decisions is acknowledged as part of the divine endowment for human perfection.
Preserving the Tree of Life: Wisdom Tradition and Jewish Sustainability Ethics
Authors: Troster Rabbi Lawrence
Published: February 2015

It has been widely recognized that one of the root causes of the modern environmental crisis
has been the rise of consumerism as both a kind of religion and a major human activity that is
unsustainable. Many studies have also shown that an excess of consumerism is not a source
of human happiness. While many religious environmental writers have dealt with responding
to this issue, one traditional source has been relatively rare: the Wisdom tradition in the
Hebrew Bible. The Wisdom tradition is found mostly in the books of Proverbs, Ecclesiastes
and Job but also appears in several of the Psalms. Wisdom literature is also found in such
apocryphal books such as Ben Sira and the Wisdom of Solomon. It also is found in the Dead
Sea Scrolls, the New Testament and rabbinic literature. Wisdom literature is also found in
many other ancient Near Eastern cultures in Egypt and Mesopotamia. The Wisdom tradition
sees Creation as a primary source for human happiness through the emulation of the order of
Creation and the values learned. The Wisdom tradition is thus a good source for developing a
Jewish ethic of sustainability. This article will outline the Wisdom tradition’s main ideas as
they relate to sustainability and will show how they can be applied today as a counter
tradition to the religion of consumerism.
Opening Statement
Authors: bin Hamad Al-Attiyah Abdullah
Published: February 2015

The World Health Organisation estimates that climate change since the 1970s is already responsible for 140,000 deaths annually. The uncertainties of climate change raise the possibility that it will bring disaster on a global scale, but also that its impact might be delayed, provided that we take decisive action now. Most of the negative consequences will be felt in the earth's mid-latitudes, already the poorest parts of the world, where secondary effects such as economic disruption, disease, famine and war will be experienced most acutely.

Climate change is caused by humans and all indicators tend to show that it is going to get worse, hence the need for decisive, timely and sustained global political action. These are the expectations with which we host the Doha Climate Change Conference 2012 as part of the 18th session of the Conference of the Parties to the UNFCCC (United Nations Framework Convention on Climate Change).

We hope that through this journal our different religious traditions can guide us, at this crucial time in human history, in developing a common discourse inspired by their ancient wisdom. May it teach us how to relate to the environment and to our fellow humans who, in other countries and in future times, will be affected by the economic decisions we make in our own countries at this present time. Our hope is that our religious traditions can remind us to look beyond selfishness, greed and apathy in making economic decisions informed by ethical principles. May we learn how to walk the earth with humility, like the founders of the various religions did, and to leave the earth in a better condition than that in which we inherited it from our forefathers.
RhoGAPs und Rho-GTPasen in Thrombozyten
Authors: Elvers Margitta
Published: February 2015

Die Reorganisation des Zytoskeletts in Thrombozyten ist essenziell für die Thrombozytenadhäsion und Thrombusbildung in Hämostase und Thrombose. Die Rho-GTPasen RhoA, Rac1 und Cdc42 spielen eine entscheidende Rolle bei der Reorganisation des Zytoskeletts, indem sie die Bildung von Filopodien und Lamellipodien induzieren und somit für die Oberflächenvergrößerung der Thrombozyten wäh-rend der Aktivierung verantwortlich sind. Rho-GTPasen beeinflussen zudem die Prozesse der Thrombozytenaktivität und Aggregatbildung durch Modulation der Sekretion, Integrinaktivierung und arteriellen Thrombusbildung. Die Aktivität der Rho-GTPasen wird von verschiedenen Proteinen kontrolliert, z. B. den GTPase aktivierenden Proteinen (GTPase activating proteins, GAPs). GAPs lösen die Inaktivierung des Guaninnukleotidbindenden Proteins durch Stimulierung der GTPase-Aktivität aus. Die Rolle und Bedeutung von GAPs in Thrombozyten ist nur wenig verstanden und viele der bekannten Rho-GAPs sind bisher nicht in Thrombozyten identifiziert oder hinsichtlich ihrer Funktion charakterisiert worden. Die kürzlich entdeckten RhoGAPs Oligophrenin1 (OPHN1) und Nadrin regulieren die Aktivität von RhoA, Rac1 und Cdc42 und nachfolgend die Reorganisation des Zytoskeletts und die Aktivierung von Thrombozyten sowie die Thrombusbildung. In den letzten Jahren trug die Analyse gene-tisch-modifizierter Mäuse dazu bei, grundlegende Erkenntnisse zur Bedeutung von RhoGTPasen und ihren Regulatoren für die Reorganisation des Zytoskeletts und andere Rhovermittelte zelluläre Prozesse in Thrombozyten zu gewinnen.
Abocats a viure a la llera del riu: el problema de l’infrahabitatge a Sabadell, 1939-1970. De l’habitatge protegit al negoci immobiliari
Authors: Masjuan Eduard
Published: February 2015

En aquesta recerca es pretén mostrar com el dèficit crònic d’habitatge en una ciutat industrial com Sabadell de 1939 a 1970 tingué en les riuades de 1962 el motiu per consolidar les patologies del creixement desregulat dels anys anteriors, i aprofundir així en un model urbà invertebrat que donarà lloc a una difusió suburbial dins la perifèria de Barcelona. Es mostra com els poders econòmics de l’època franquista supeditaren tot intent d’urbanisme al servei de les persones a l’especulació del sòl. L’actual ciutat de Sabadell de després del boom immobiliari recent seria l’hereva d’un passat que transità de l’activitat industrial cap al negoci immobiliari.Les riuades de 1962, juntament amb el creixement ràpid i incontrolat de la població, són aprofitades pel paternalisme franquista local i foren la gran excusa per a la consecució hegemònica del règim de propietat, que va fer quedar en segon terme el de lloguer, una condició prèvia per a la hiperespecialització de la ciutat en el negoci de l’especulació immobiliària. És a partir del que anomena José Manuel Naredo (2010) años del desarrollismo, 1963-1973, que l’embranzida immobiliària representa un augment del 40% de construcció d’habitatges a Espanya, amb el consegüent urbanisme salvatge, resultat d’aquest procés d’urbanització sense precedents.L’objectiu central d’aquest text és establir com, partint de l’excusa d’escassetat inicial d’habitatges —palesa en un primer moment en el barraquisme i el fenomen legal dels rellogats i en un moment de clara hegemonia del règim de lloguer—, el 1962 aquesta situació es comença a invertir per complet, per raons polítiques d’una banda, per aconseguir la pau social, i per una altra, econòmiques, per afavorir l’especulació immobiliària. Tot plegat fou possible a partir de neutralitzar els intents de planificació urbana sorgida a l’empara de la legalitat vigent, sobretot a partir de la Llei del sòl de 1956.
Independent theta phase coding accounts for CA1 population sequences and enables flexible remapping
Authors: Chadwick Angus , van Rossum Mark CW , Nolan Matthew F
Published: February 2015

Hippocampal place cells encode an animal's past, current, and future location through sequences of action potentials generated within each cycle of the network theta rhythm. These sequential representations have been suggested to result from temporally coordinated synaptic interactions within and between cell assemblies. Instead, we find through simulations and analysis of experimental data that rate and phase coding in independent neurons is sufficient to explain the organization of CA1 population activity during theta states. We show that CA1 population activity can be described as an evolving traveling wave that exhibits phase coding, rate coding, spike sequences and that generates an emergent population theta rhythm. We identify measures of global remapping and intracellular theta dynamics as critical for distinguishing mechanisms for pacemaking and coordination of sequential population activity. Our analysis suggests that, unlike synaptically coupled assemblies, independent neurons flexibly generate sequential population activity within the duration of a single theta cycle.
Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron
Authors: Lindström Nils O , Lawrence Melanie L , Burn Sally F , Johansson Jeanette A , Bakker Elvira RM , Ridgway Rachel A , Chang C-Hong , Karolak Michele J , Oxburgh Leif , Headon Denis J , Sansom Owen J , Smits Ron , Davies Jamie A , Hohenstein Peter
Published: February 2015

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.
Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point
Authors: Baeyens Nicolas , Nicoli Stefania , Coon Brian G , Ross Tyler D , Van den Dries Koen , Han Jinah , Lauridsen Holly M , Mejean Cecile O , Eichmann Anne , Thomas Jean-Leon , Humphrey Jay D , Schwartz Martin A
Published: February 2015

Vascular remodeling under conditions of growth or exercise, or during recovery from arterial restriction or blockage is essential for health, but mechanisms are poorly understood. It has been proposed that endothelial cells have a preferred level of fluid shear stress, or ‘set point’, that determines remodeling. We show that human umbilical vein endothelial cells respond optimally within a range of fluid shear stress that approximate physiological shear. Lymphatic endothelial cells, which experience much lower flow in vivo, show similar effects but at lower value of shear stress. VEGFR3 levels, a component of a junctional mechanosensory complex, mediate these differences. Experiments in mice and zebrafish demonstrate that changing levels of VEGFR3/Flt4 modulates aortic lumen diameter consistent with flow-dependent remodeling. These data provide direct evidence for a fluid shear stress set point, identify a mechanism for varying the set point, and demonstrate its relevance to vessel remodeling in vivo.
Synthetic enzyme-substrate tethering obviates the Tolloid-ECM interaction during Drosophila BMP gradient formation
Authors: Winstanley Jennifer , Sawala Annick , Baldock Clair , Ashe Hilary L
Published: February 2015

Members of the Tolloid family of metalloproteinases liberate BMPs from inhibitory complexes to regulate BMP gradient formation during embryonic dorsal-ventral axis patterning. Here, we determine mechanistically how Tolloid activity is regulated by its non-catalytic CUB domains in the Drosophila embryo. We show that Tolloid, via its N-terminal CUB domains, interacts with Collagen IV, which enhances Tolloid activity towards its substrate Sog, and facilitates Tsg-dependent stimulation of cleavage. In contrast, the two most C-terminal Tld CUB domains mediate Sog interaction to facilitate its processing as, based on our structural data, Tolloid curvature positions bound Sog in proximity to the protease domain. Having ascribed functions to the Tolloid non-catalytic domains, we recapitulate embryonic BMP gradient formation in their absence, by artificially tethering the Tld protease domain to Sog. Our studies highlight how the bipartite function of Tolloid CUB domains, in substrate and ECM interactions, fine-tune protease activity to a particular developmental context.
Kin cell lysis is a danger signal that activates antibacterial pathways of Pseudomonas aeruginosa
Authors: LeRoux Michele , Kirkpatrick Robin L , Montauti Elena I , Tran Bao Q , Peterson S Brook , Harding Brittany N , Whitney John C , Russell Alistair B , Traxler Beth , Goo Young Ah , Goodlett David R , Wiggins Paul A , Mougous Joseph D
Published: February 2015

The perception and response to cellular death is an important aspect of multicellular eukaryotic life. For example, damage-associated molecular patterns activate an inflammatory cascade that leads to removal of cellular debris and promotion of healing. We demonstrate that lysis of Pseudomonas aeruginosa cells triggers a program in the remaining population that confers fitness in interspecies co-culture. We find that this program, termed P. aeruginosa response to antagonism (PARA), involves rapid deployment of antibacterial factors and is mediated by the Gac/Rsm global regulatory pathway. Type VI secretion, and, unexpectedly, conjugative type IV secretion within competing bacteria, induce P. aeruginosa lysis and activate PARA, thus providing a mechanism for the enhanced capacity of P. aeruginosa to target bacteria that elaborate these factors. Our finding that bacteria sense damaged kin and respond via a widely distributed pathway to mount a complex response raises the possibility that danger sensing is an evolutionarily conserved process.
Significance of Management System for Effective Organizational Management
Authors: Kazmi Syeda Asiya Zenab , Naarananoja Marja
Published: February 2015

Management system is defined as a strategic process of an organization based on a comprehensive framework of instructions and well-designed set of guiding rules, for undergoing organizational operations for achieving organization targets. The set of directions included in the paper, refers to the key areas involved in effectively accomplishing organizational operational tasks. The conclusion of the paper highlights the key areas of management systems, management processes and the allied components of the PDCA model.
Role of Asphericity in Choice of IOLs for Cataract Surgery
Authors: Khanna Aman , Dhiman Rebika , Khanna Rajinder , Rathore Yajuvendra Singh , Arun Spriha
Published: February 2015

Advances in surgical techniques, as well as the invention of new intraocular lens (IOL) materials and designs, have increased expectations from cataract surgery to beyond simply providing good visual acuity. The cornea itself induces some degree of positive spherical aberration which is compensated by the negative spherical aberration of the clear crystalline lens. However, this compensation gradually decreases as the crystalline lens ages and particularly after cataract extraction and intraocular lens implantation. Conventional spherical IOLs add positive spherical aberration to the pre-existing aberrations caused by the cornea, increasing the total spherical aberration of the eye. One key factor contributing to postoperative spherical aberration is IOL design which has undergone dramatic changes to compensate for the positive corneal spherical aberration, with the emergence of aspheric IOL’s it has become a challenging task for ophthalmologists to choose the appropriate IOL from a wide variety available. This review article will provide information regarding asphericity and different aspheric IOL’s available and application of different strategies while choosing specific IOL.
Current Concepts in Operative Room Sterilisation
Authors: Gupta Chanchal , Vanathi M. , Tandon Radhika
Published: February 2015

Endophthalmitis is the most dreaded complication of any intraocular surgery. The source of these infections can be endogenous or exogenous. By sterile environment in operation theatres major part of such exogenous infections can be controlled. OT should be divided into four zones named protective, clean, aseptic and disposal zones. Proper ventilation, air circulation, temperature, maintenance of sterile environment in operation theatres plays key role in prevention of such infections. Steps for maintaining sterile environment include cleaning and disinfection of operation theatres by various means like chemical disinfection or disinfection with ultraviolet radiation. Along with this surgical instruments also can be a source of exogenous infections. So cleaning, lubrication, packing and sterilisation of instruments are essential for prevention of surgical site infections.
How to Measure Alterations in Alveolar Barrier Function as a Marker of Lung Injury
Authors: Herrero Raquel , Matute‐Bello Gustavo
Published: February 2015

The alveolar capillary membrane maintains the proper water and solute content of the epithelial lining fluid at the alveolar air‐liquid interface, which is critical for adequate gas exchange in the lung. This is possible due to the alveolar fluid clearance (AFC) capacity of this membrane that assists in the removal of salt and water from the alveolar air spaces. The alveolar capillary membrane also provides a barrier that restricts the passage of proteins and water from the interstitial and vascular compartments into the alveolar air spaces. This restricted passage is due to the presence of tight junctions between adjacent alveolar epithelial cells. Severe injury to the alveolar epithelial/endothelial membrane results in increased protein permeability and impairment of AFC, which leads to the formation of protein‐rich edema with the consequent deterioration of gas exchange. Many animal models of lung injury, focused on damage of the alveolar‐capillary membrane, assess the AFC capacity and the barrier function. We describe a simple method to assess the AFC rate in normal and pathological conditions in mice. We also describe two complementary methods to assess the alveolar‐capillary barrier function, which require measuring the concentration of endogenous plasma proteins in bronchoalveolar lavage fluid and detection of tight‐junction proteins in lung tissue by immunofluorescence. © 2015 by John Wiley & Sons, Inc.
Analysis of Protein Ligand‐Receptor Binding by Photoaffinity Cross‐Linking
Authors: Wu Ling , Xu Bin
Published: February 2015

Photoaffinity cross‐linking is a rapidly developing technology for studying biomolecular interactions, including protein ligand‐receptor binding. This technology provides detailed binding information including receptor contact sites, active conformation of receptor‐ligand complexes, global binding surfaces, and binding modes. Advancements in genetic technology have enabled non‐natural photoactive amino acid derivatives to be incorporated into designer or target proteins, providing a host of new opportunities for manufacturing protein photo‐probes while bypassing the traditional peptide or small protein limits of classical chemical synthesis. This unit provides several protocols for performing basic photoaffinity cross‐linking and related analyses for applications in ligand‐receptor binding and protein‐protein interactions. © 2015 by John Wiley & Sons, Inc.
Isolation and Manipulation of Mouse Trophoblast Stem Cells
Authors: Hayakawa Koji , Himeno Emi , Tanaka Satoshi , Kunath Tilo
Published: February 2015

The isolation of stable trophoblast stem (TS) cell lines from early mouse embryos has provided a useful cell culture model to study trophoblast development. TS cells are derived from pre‐implantation blastocysts or from the extraembryonic ectoderm of early post‐implantation embryos. The derivation and maintenance of mouse TS cells is dependent upon continuous fibroblast growth factor (FGF) signaling. Gene expression analysis, differentiation in culture, and chimera formation show that TS cells accurately model the mouse trophoblast lineage. This unit describes how to derive, maintain, and manipulate TS cells, including DNA transfection and chimera formation. © 2015 by John Wiley & Sons, Inc.
Genome‐Wide Fitness and Genetic Interactions Determined by Tn‐seq, a High‐Throughput Massively Parallel Sequencing Method for Microorganisms
Authors: van Opijnen Tim , Lazinski David W. , Camilli Andrew
Published: February 2015

The lagging annotation of bacterial genomes and the inherent genetic complexity of many phenotypes is hindering the discovery of new drug targets and the development of new antimicrobial agents and vaccines. This unit presents Tn‐seq, a method that has made it possible to quantitatively determine fitness for most genes in a microorganism and to screen for quantitative genetic interactions on a genome‐wide scale and in a high‐throughput fashion. Tn‐seq can thus direct studies on the annotation of genes and untangle complex phenotypes. The method is based on the construction of a saturated transposon insertion library. After library selection, changes in the frequency of each insertion mutant are determined by sequencing flanking regions en masse. These changes are used to calculate each mutant's fitness. The method was originally developed for the Gram‐positive bacterium Streptococcus pneumoniae, a causative agent of pneumonia and meningitis, but has now been applied to several different microbial species.
Aminoglycoside‐Enabled Elucidation of Bacterial Persister Metabolism
Authors: Orman Mehmet A. , Mok Wendy W. K. , Brynildsen Mark P.
Published: February 2015

Bacterial persisters are cells with an impressive, yet transient, tolerance toward extraordinary concentrations of antibiotics. Persisters are believed to impose a significant burden on the healthcare system because of their role in the proclivity of infections to relapse. During antibiotic challenge, these rare, phenotypic variants enter a dormant state where antibiotic primary targets are rendered inactive, allowing them to survive. Once the antibiotic is removed, persisters reawaken and resume growth, leading to repopulation of the environment. Metabolism plays a pivotal role in coordinating the entry, maintenance, and exit from the persister state. However, the low abundance, transient nature, and similarity of persisters to other cell types have prevented their isolation, which is needed for direct metabolic measurements. In this unit, we describe a technique known as the aminoglycoside (AG) potentiation assay, which can be used to rapidly and specifically measure the breadth of persister metabolism in heterogeneous populations.
Versatile Syntheses of Hemi‐Cryptophanes and a Metallo‐Cryptophane from a Hexa‐Functionalized C3v‐Symmetrical Tribenzotriquinacene (TBTQ) Derivative
Authors: Wei Jun , Li Zhi‐Min , Jin Xiao‐Jie , Yao Xiao‐Jun , Cao Xiao‐Ping , Chow Hak‐Fun , Kuck Dietmar
Published: February 2015

A number of three‐fold C3v‐symmetrical tribenzotriquinacene (TBTQ) cavitands were synthesized by a “metamorphosis‐to‐half” strategy, employing six‐fold etherification reactions between the hexakis(chloromethyl)‐TBTQ intermediate 2 a and various 5‐functionalized resorcinols. X‐ray structure analyses of single crystals of the cavitands revealed limited rotational flexibility of the resorcinol bridging units, which enables an apical, nearly co‐axial orientation of the three functional groups and, as a consequence, the construction of nanoscale cage‐like molecules via covalent or coordination bonding. On this basis, two TBTQ‐based hemicryptophanes were prepared from the TBTQ cavitands via covalent bond formation in good yields. A dumbbell‐shaped TBTQ‐based metallo‐cryptophane was also synthesized in 34 % yield by a solvothermal reaction between cadmium nitrate and two equivalents of the TBTQ‐cavitand triacid, as confirmed by single‐crystal X‐ray diffraction and MALDI‐ToF mass spectrometry.
Validation of a hydrophilic interaction ultra‐performance liquid chromatography–tandem mass spectrometry method for the determination of gemcitabine in human plasma with tetrahydrouridine
Authors: Mano Yuji , Sakamaki Kenji , Ueno Takuya , Kita Kenji , Ishii Takuho , Hotta Koichiro , Kusano Kazutomi
Published: February 2015

A simple and reproducible bioanalytical method for the determination of gemcitabine in human plasma treated with tetrahydrouridine (THU) was developed and validated using a hydrophilic interaction ultra‐performance liquid chromatography with tandem mass spectrometry (UPLC‐MS/MS). To prevent deamination of gemcitabine, blood was treated with THU, and the plasma samples obtained after centrifugation were used in this study. Gemcitabine and gemcitabine‐13C, 15N2 used as an internal standard, were extracted from human plasma treated with THU using a 96‐well Hybrid SPE‐Precipitation plate. Extracts were chromatographed on a hydrophilic interaction chromatography column with isocratic elution. Detection was performed using Quattro Premier with positive electrospray ionization multiple reaction monitoring mode. The standard curve ranged from 10 to 10,000 ng/mL without carryover. No significant interferences were detected in blank plasma and no interferences by 2′‐2′‐difluoro‐2′‐deoxyuridine, a metabolite of gemcitabine. Accuracy and precision in the intra‐batch reproducibility study using quality control samples with three THU levels did not exceed ±5.4 and 7.3%, respectively, and the inter‐batch reproducibility results also met the criteria. Stability of gemcitabine was ensured in whole blood and plasma as well as stability of THU in solutions. The UPLC‐MS/MS method developed was successfully validated and can be applied for gemcitabine bioanalysis in clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.
Assessment of the hemolysis and endothelial cell cytotoxicity induced by residual linear alkylbenzene sulfonates on pharmaceutical rubber stoppers based on HPLC‐ESI‐MS
Authors: Li Xianghui , Qiu Lu , Li Yueyue , Chen Xiaofei , Zhu Zhenyu , Chai Yifeng
Published: February 2015

This study was designed to develop a high‐performance liquid chromatographic–electrospray ionization–mass spectrometry (HPLC‐ESI‐MS) method for quantitative determination of residual surfactant linear alkylbenzene sulfonate (LAS) compounds on pharmaceutical rubber stoppers. An HPLC‐ESI‐MS method was developed for separation and determination of five LAS homologs (C10–C14) under gradient conditions using methanol and ammonium acetate as mobile phases. Hemolysis activity of residual LAS compounds was analyzed by spectrophotometry. Expression of interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α in human umbilical vein endothelial cells (HUVECs) after LAS compound treatment was examined by enzyme‐linked sorbent assay. LAS compounds were well separated and determined by the established gradient conditions. The linear range was 0.05–8 µg/mL with correlation coefficients ≥0.997. Recoveries were from 73 to 134% and the relative standard deviation was <13.7%. There was a correlation between hemolysis rate and LAS compounds concentration when it was ≥0.8 µg/cm2. LAS compounds decreased the viability of HUVECs and promoted the production of IL‐6 and TNF‐α. The developed analytical method was successful for quantitative determination of residual LAS compounds on pharmaceutical rubber stoppers and it is important to monitor and control the amount of LAS compounds on rubber stoppers. Copyright © 2015 John Wiley & Sons, Ltd.
Validation of an ultra‐performance liquid chromatography–tandem mass spectrometry method for the determination of flecainide in human plasma and its clinical application
Authors: Mano Yuji , Asakawa Yoshiki , Kita Kenji , Ishii Takuho , Hotta Koichiro , Kusano Kazutomi
Published: February 2015

A simple and reproducible bioanalytical method for the determination of flecainide in human plasma was developed and validated using an ultra‐performance liquid chromatography with tandem mass spectrometry (UPLC‐MS/MS) to obtain higher sensitivity than the current available methods. After simple protein precipitation, flecainide and a stable isotope‐labeled internal standard (IS) were chromatographed on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with isocratic elution of mobile phase consisting of 45% methanol containing 0.1% formic acid at a flow rate 0.25 mL/min. Detection was performed in positive electrospray ionization by monitoring the selected ion transitions at m/z 415.4/301.1 for flecainide and m/z 419.4/305.1 for the IS. The method was validated according to current bioanalytical method validation guidelines. The calibration standard curve was linear from 2.5 to 1000 ng/mL using 0.1 mL of plasma. No significant interferences were detected in blank human plasma. Accuracy and precision in the intra‐ and inter‐batch reproducibility study were within acceptance criteria. Neither hemolysis effects nor matrix effects were observed. The UPLC‐MS/MS method developed was successfully applied to determine plasma flecainide concentrations to support clinical studies and incurred sample reanalysis also ensured the reproducibility of the method. Copyright © 2015 John Wiley & Sons, Ltd.