bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Impact of Prosthetic Joint Infection - an Evaluation Within the Portuguese National Health System
Authors: Sousa Arnaldo , Carvalho André , Pereira Cláudia , Reis Ernestina , Santos Ana Cláudia , Abreu Miguel , Soares Daniel , Fragoso Ricardo , Ferreira Susana , Reis Marcio , Sousa Ricardo
Published: October 2018

Abstract. Introduction: Prosthetic infection is a devastating complication of arthroplasty and carries significant economic burden. The objective of this study was to analyze the economic impact of prosthetic hip and knee infection in Portuguese National Health System.Material and Methods: Case-control study carried out from January 2014 to December 2015. The mean costs of primary arthroplasties and prosthetic revision surgeries for non-infectious reasons were compared with the costs of prosthetic infections treated with debridement and preservation of the prosthesis or with two-stage exchange arthroplasty.The reimbursement for these cases was also evaluated and compared with its real costs.Results:A total of 715 primary arthroplasties, 35 aseptic revisions, 16 surgical debridements and 15 revisions for infectious reasons were evaluated. The cost of primary arthroplasties was 3,230€ in the hips and 3,618€ in the knees. The cost of aseptic revision was 6,089€ in the hips and 7,985€ in the knees. In the cases treated with debridement and implant retention the cost was 5,528€ in the hips and 4,009€ in the knees. In cases of infections treated with a two-stage revision the cost was 11,415€ and 13,793€ for hips and knees, respectively.Conclusion: As far as we know this is the first study that analyzes the economic impact of prosthetic infection in the Portuguese context. Although direct compensation for treating infected cases is much lower than calculated costs, infected cases push the overall hospital case-mix-index upwards thus increasing financial compensation for the entire cohort of treated patients. This knowledge will allow for more informed decisions about health policies in the future.
ПРОМОВИСАЊЕ ПОКЛОН БИБЛИОТЕКА С КОРИСНИЦИМА, ЗА КОРИСНИКЕ
Authors: Илић Минић Јелица , Брборић Владимир
Published: October 2018

Спомен библиотека „Слободан Ђукић“ једна је од поклонцелина које библиотека Учитељског факултета Универзитета у Београдучува у свом фонду. Основана је 1969. године када је породица, наконсмрти Слободана Ђукића, поклонила део његове личне библиотекеУчитељској школи, наследници Мушке учитељске школе коју је овајистакнути педагог завршио. Књиге су првобитно биле укључене у општифонд, а од 2018. године издвојене су као библиотека целина СлободанаЂукића. Како се наредне, 2019. године, навршава 50 година од смртидародавца, а и од формирања спомен библиотеке, у току је изложба којаје драгоцено сведочанство о њеном власнику који је дао значајандопринос српској просвети половином прошлог века.Како би се корисници што боље упознали с фондом, односно, самомспомен библиотеком, укључени су и поједини студенти у организовањеизложбе. Осим што су учествовали у одабиру грађе и визуелнимрешењима за изложбену поставку, заједно са библиотекаримаинформишу своје колеге и остале посетиоце изложбе о животу и радудародавца, његовом научном доприносу и публикацијама које је даривао,а које су и даље значајне за наставни процес.Планирано је да буду представљене и остале поклон библиотеке, каопредстојећe самосталне изложбе започетог циклуса о дародавцимаБиблиотеке Учитељског факултета.
ЗНАЧАЈ ДИГИТАЛИЗАЦИЈЕ БИБЛИОТЕЧКЕ ГРАЂЕ ЗА КОРИСНИКЕ-ИСТРАЖИВАЧЕ: ПРИМЈЕР ГРАДА БРОДА
Authors: Благојевић Берислав
Published: October 2018

Дигиталне (виртуелне) библиотеке су реалност 21. вијека какоу институционалном смислу, тако и у контексту стварања дигиталнихбиблиотечких цјелина. Дигитализација библиотечке грађе представљанови искорак у њеној трајнијој заштити, те у доступности и пружањууслуга корисницима. У овом раду ће бити анализиран значајдигитализације уопште, односно, главни аспекти и тенденције удигитализацији библиотечке грађе (књижне и некњижне). Нарочитапажња ће бити посвећена Open Access платформама и пројектима којикорисницима-истраживачима омогућују приступ разноврсној грађи. Наконкретном примјеру града Брода показаћемо како различити профилиистраживача и научних радника могу да имају корист од дигитализованеграђе: географи, историчари, демографи, етнографи, просторни планери,биолози, и други.
ЗНАЧАЈ ДИГИТАЛИЗАЦИЈЕ ЗАВИЧАЈНЕ ЗБИРКЕ ЗА ЛОКАЛНУ ЗАЈЕДНИЦУ
Authors: Вуковић Оријана
Published: October 2018

Развојем информационих технологија и брзимосавремењавањем библиотечких дјелатности, увођењем низа новихбиблиотечких услуга настаје и потреба усавршавања и проширивањадјелатности које су повезане са традиционалним вођењем завичајнезбирке у народним библиотекама.Дигитализација завичајних збирки, њихово прилагођавање савременимтехнологијама намеће се као приоритетан задатак „завичајнихбиблиотекара“. Суочавамо се са потребом дигитализације књига,часописа, новина, фотографија, постера, дигиталних и видео снимака,али и са специфичним начином обраде и описивања дате грађе како бибила претражива, видљива и доступна корисницима због којих народнебиблиотеке и постоје.Наравно, у први план избија потреба стручног усавршавањабиблиотекара који истражују завичајне теме, потреба за сталнимкоришћењем Интернета, разних портала, друштвених мрежа.Библиотекари би требало своју дјелатност на другачији начин да усмјерека корисницима, да их информишу, обуче и учине им доступним свеновине које би дигитализација завичајних збирки омогућила.
УМПЕ-ЛУМПЕ У БИБЛИОТЕКАМА?
Authors: Костић Надица , Митић Бојана
Published: October 2018

Предуслов постојања и опстанка библиотека несумњиво јесукорисници, међутим, пред налетом нових технологија и медија, долазидо преображаја класичних библиотека. Библиотеке се све вишеосавремењују а услуге које пружају својим корисницима се усложњавају,што и од самих библиотекара изискује све веће знање и ангажовање,креативност и иновативност, као одговор на изазов како, у добапрезасићености мноштвом понуда, сачувати или боље рећи однеговати изадржати корисника. У настојању да се отргне од традиционалног моделабиблиотеке и потврди као образовни, научни, културни и информационицентар локалне заједнице, Народна библиотека Пирот последњих годинабележи продор у нове облике комуникације са различитом читалачкомпубликом. Поред тога што није прекинут континуитет у неговању оногшто је раније достигнуто као квалитет, у концептима је доста тога новог ииновативног, попут тинејџерског и кутка за библиотерапију, читаоницеза лица са потешкоћама у читању, манифестација Читалачка значка иФестивал стрипа. Акценат Народне библиотеке Пирот у наредномпериоду биће стављен на формирање читалачких клубова за тинејџере.
БИБЛИОТЕКА И МЛАДИ
Authors: Бојић Милијана , Каралић Весељка
Published: October 2018

Библиотека, једна од најважнијих културних институција усваком друштву, данас се налази пред тешким задатком и питањем, какопривући тинејџере да буду корисници библиотечких услуга. Данас, кадаје доступност информација толико олакшана, да се за пар секунди, наИнтернету, пронађу жељене информације, чини нам се да се улогабиблиотеке, код младих, нашла у запећку. Млади, као специфичан диопопулације сваког друштва, имају посебне потребе и захтјеве. Због тога,библиотека не смије да се задржи у прошлости, већ мора да прати све оношто ће утицати на то да библиотека остане први избор, приликомпроналажења нових знања.У овом раду осврнућемо се на активности Народне и универзитетскебиблиотеке Републике Српске, која у посљедње вријеме поклања све већупажњу у раду са младим корисницима. Приказаћемо начине на које себиблиотека прилагођава данашњем времену, осмишљавајући нове услугеза ту специфичну групу корисника. Бавићемо се тиме какав је њиховоднос према књизи, читању и библиотеци. Поред тога приказаћемо икоји су досадашњи резултати рада са њима и који су планови Народне иуниверзитетске библиотеке Републике Српске у раду са младимкорисницима.
ИНФОРМАЦИОНА УЛОГА БИБЛИОТЕЧКИХ КАТАЛОГА У ФАКУЛТЕТСКИМ БИБЛИОТЕКАМА
Authors: Дуновић Татјана
Published: October 2018

Настали из потребе да одговоре на питања корисника да либиблиотека има одређену публикацију, која све дјела и која издања ипреводе одређеног аутора посједује до база података у којима суорганизовани и идентификовани сви могући дигитални документи,каталози представљају најзначајније организоване скупове информацијао фондовима које једна библиотека ствара и нуди својим корисницима.Овај рад се бави улогом библиотечких каталога као информационихинструмената у мрежи факултетских библиотека Универзитета у БањојЛуци. Подаци које имамо говоре нам да је стање у библиотекаманауједначено. У неким библиотекама су заступљени лисни, затимелектронски каталози које је могуће само интерно претраживати и накрају узајамни електронски каталози као дио јединственог библиотечко-информациног система COBIB.RS.Библиотекари факултетских библиотека морају пратити корак идинамику промјена, како у развоју науке и технологије, образовања идемократизације друштвених процеса, тако и у преобликовању својихзадатака што захтијева промјену у начину рада и пословања. У средиштузанимања факултетске библиотеке и даље остаје корисник, за којег вишеније довољно само прикупити грађу, већ му треба осигурати и приступразличитим врстама информација. На тај начин ће корисник добититачну, брзу и квалитетну информацију коју ће моћи искористити унаучном истраживању.
From solution to surface to filament: actin flux into branched networks
Authors: Mullins Dyche , Bieling Peter , Fletcher Daniel A
Published: October 2018

The actin cytoskeleton comprises a set of filament networks that perform essential functions in eukaryotic cells. The idea that actin filaments incorporate monomers directly from solution forms both the “textbook picture” of filament elongation and a conventional starting point for quantitative modeling of cellular actin dynamics. Recent work, however, reveals that filaments created by two major regulators, the formins and the Arp2/3 complex, incorporate monomers delivered by nearby proteins. Specifically, actin enters Arp2/3-generated networks via binding sites on nucleation promoting factors clustered on membrane surfaces. Here, we describe three functions of this surface-associated actin monomer pool: (1) regulating network density via product inhibition of the Arp2/3 complex; (2) accelerating filament elongation as a distributive polymerase; and (3) converting profilin-actin into a substrate for the Arp2/3 complex. These linked functions control the architecture of branched networks and explain how capping protein enhances their growth.
FORESEE: a tool for the systematic comparison of translational drug response modeling pipelines
Authors: Turnhoff Lisa-Katrin , Hadizadeh Esfahani Ali , Montazeri Maryam , Kusch Nina , Schuppert Andreas
Published: October 2018

Translational models that utilize omics data generated in in vitro studies to predict the drug efficacy of anti-cancer compounds in patients are highly distinct, which complicates the benchmarking process for new computational approaches. In reaction to this, we introduce the uniFied translatiOnal dRug rESponsE prEdiction platform FORESEE, an open-source R-package. FORESEE not only provides a uniform data format for public cell line and patient data sets, but also establishes a standardized environment for drug response prediction pipelines, incorporating various state-of-the-art preprocessing methods, model training algorithms and validation techniques. The modular implementation of individual elements of the pipeline facilitates a straightforward development of combinatorial models, which can be used to re-evaluate and improve already existing pipelines as well as to develop new ones.

Availability and Implementation: FORESEE is licensed under GNU General Public License v3.0 and available at https://github.com/JRC-COMBINE/FORESEE .

Supplementary Information: Supplementary Files 1 and 2 provide detailed descriptions of the pipeline and the data preparation process, while Supplementary File 3 presents basic use cases of the package.

Contact: schuppert@combine.rwth-aachen.de
Conceptual and empirical advances in Neotropical biodiversity research
Authors: Antonelli Alexandre , Ariza María , Albert James , Andermann Tobias , Azevedo Josué , Bacon Christine , Faurby Søren , Guedes Thais , Hoorn Carina , Lohmann Lúcia G. , Matos-Maraví Pável , Ritter Camila D. , Sanmartín Isabel , Silvestro Daniele , Tejedor Marcelo , ter Steege Hans , Tuomisto Hanna , Werneck Fernanda P. , Zizka Alexander , Edwards Scott V.
Published: October 2018

The unparalleled biodiversity found in the American tropics (the Neotropics) has attracted the attention of naturalists for centuries. Despite major advances in recent years in our understanding of the origin and diversification of many Neotropical taxa and biotic regions, many questions remain to be answered. Additional biological and geological data are still needed, as well as methodological advances that are capable of bridging these research fields. In this review, aimed primarily at advanced students and early-career scientists, we introduce the concept of “trans-disciplinary biogeography,” which refers to the integration of data from multiple areas of research in biology (e.g., community ecology, phylogeography, systematics, historical biogeography) and Earth and the physical sciences (e.g., geology, climatology, palaeontology), as a means to reconstruct the giant puzzle of Neotropical biodiversity and evolution in space and time. We caution against extrapolating results derived from the study of one or a few taxa to convey general scenarios of Neotropical evolution and landscape formation. We urge more coordination and integration of data and ideas among disciplines, transcending their traditional boundaries, as a basis for advancing tomorrow’s ground-breaking research. Our review highlights the great opportunities for studying the Neotropical biota to understand the evolution of life.
A new species of the odorous frog genusOdorrana(Amphibia, Anura, Ranidae) from southwestern China
Authors: Li Shize , Xu Ning , Lv Jingcai , Jiang Jianping , Wei Gang , Wang Bin
Published: October 2018

The genusOdorranais widely distributed in the mountains of East and Southeastern Asia. An increasing number of new species in the genus have been recognized especially in the last decade. Phylogenetic studies of theO. schmackerispecies complex with wide distributional range also revealed several cryptic species. Here, we describe a new species in the species complex from Guizhou Province of China. Phylogenetic analyses based on mitochondrial DNA indicated the new species as a monophyly clustered into theOdorranaclade and sister toO. schmackeri, and nuclear DNA also indicated it as an independent lineage separated from its related species. Morphologically, the new species can be distinguished from its congeners based on a combination of the following characters: (1) having smaller body size in males (snout-vent length (SVL) <43.3 mm); (2) head longer than wide; (3) dorsolateral folds absent; (4) tympanum of males large and distinct, tympanum diameter twice as long as width of distal phalanx of finger III; (5) two metacarpal tubercles; (6) relative finger lengths: II < I < IV < III; (7) tibiotarsal articulation reaching to the level between eye to nostril when leg stretched forward; (8) disks on digits with circum-marginal grooves; (9) toes fully webbed to disks; (10) the first subarticular tubercle on fingers weak; (11) having white pectoral spinules, paired subgular vocal sacs located at corners of throat, light yellow nuptial pad on the first finger in males.
A new limestone-dwelling species ofMicryletta(Amphibia: Anura: Microhylidae) from northern Vietnam
Authors: Poyarkov Nikolay A. , Nguyen Tan Van , Duong Tang Van , Gorin Vladislav A. , Yang Jian-Huan
Published: October 2018

We report on a new species of the genusMicrylettafrom limestone karst areas in northern Vietnam, which is described on the basis of molecular and morphological evidence.Micryletta nigromaculatasp. nov. is restricted to narrow areas of subtropical forests covering karst massifs in Cat Ba National Park (Hai Phong Province) and Cuc Phuong National Park (Ninh Binh Province) at elevations of 90–150 m a.s.l. In the phylogenetic analyses, the new species is unambiguously positioned as a sister lineage to all remaining species ofMicryletta. We also discuss genealogical relationships and taxonomic problems within the genusMicryletta, provide molecular evidence for the validity ofM. erythropodaand discuss the taxonomic status ofM. steinegeri. We suggest the new species should be considered as Endangered (B1ab(iii), EN) following the IUCN’s Red List categories. A discussion on herpetofaunal diversity and conservation in threatened limestone karst massifs in Southeast Asia is provided.
Circuit complexity for coherent states
Authors: Guo Minyong , Hernandez Juan , Myers Robert C. , Ruan Shan-Ming
Published: October 2018

Abstract

We examine the circuit complexity of coherent states in a free scalar field theory, applying Nielsen’s geometric approach as in [1]. The complexity of the coherent states have the same UV divergences as the vacuum state complexity and so we consider the finite increase of the complexity of these states over the vacuum state. One observation is that generally, the optimal circuits introduce entanglement between the normal modes at intermediate stages even though our reference state and target states are not entangled in this basis. We also compare our results from Nielsen’s approach with those found using the Fubini-Study method of [2]. For general coherent states, we find that the complexities, as well as the optimal circuits, derived from these two approaches, are different.
Topological fermion condensates from anomalies
Authors: Catterall Simon , Laiho Jack , Unmuth-Yockey Judah
Published: October 2018

Abstract

We show that a class of fermion theory formulated on a compact, curved manifold will generate a condensate whose magnitude is determined only by the volume and Euler characteristic of the space. The construction requires that the fermions be treated as Kähler-Dirac fields and the condensate arises from an anomaly associated with a U(1) global symmetry which is subsequently broken to a discrete subgroup. Remarkably the anomaly survives under discretization of the space which allows us to compute the condensate on an arbitrary triangulation. The results, being topological in character, should hold in a wide range of gravitationally coupled fermion theories both classical and quantum.
GPU-accelerated steady-state computation of large probabilistic Boolean networks
Authors: Mizera Andrzej , Pang Jun , Yuan Qixia
Published: October 2018

Computation of steady-state probabilities is an important aspect of analysing biological systems modelled as probabilistic Boolean networks (PBNs). For small PBNs, efficient numerical methods to compute steady-state probabilities of PBNs exist, based on the Markov chain state-transition matrix. However, for large PBNs, numerical methods suffer from the state-space explosion problem since the state-space size is exponential in the number of nodes in a PBN. In fact, the use of statistical methods and Monte Carlo methods remain the only feasible approach to address the problem for large PBNs. Such methods usually rely on long simulations of a PBN. Since slow simulation can impede the analysis, the efficiency of the simulation procedure becomes critical. Intuitively, parallelising the simulation process is the ideal way to accelerate the computation. Recent developments of general purpose graphics processing units (GPUs) provide possibilities to massively parallelise the simulation process. In this work, we propose a
trajectory-level parallelisation framework
to accelerate the computation of steady-state probabilities in large PBNs with the use of GPUs. To maximise the computation efficiency on a GPU, we develop a dynamical data arrangement mechanism for handling different size PBNs with a GPU. Specially, we propose a
reorder-and-split
method to handle both large and dense PBNs. Besides, we develop a specific way of storing predictor functions of a PBN and the state of the PBN in the GPU memory. Moreover, we introduce a strongly connected component (SCC)-based network reduction technique to further accelerate the computation speed. Experimental results show that our GPU-based parallelisation gains approximately a 600-fold speedup for a real-life PBN compared to the state-of-the-art sequential method.
Results of Duodenopancreatic Reoperations in Multiple Endocrine Neoplasia Type 1
Authors: Albers Max B. , Manoharan Jerena , Bollmann Carmen , Chlosta Maximilian P. , Holzer Katharina , Bartsch Detlef K.
Published: October 2018

Background

To evaluate the outcome of duodenopancreatic reoperations in patients with multiple endocrine neoplasia type 1 (MEN1).

Methods

MEN1 patients who underwent reoperations for duodenopancreatic neuroendocrine neoplasms (dpNENs) were retrieved from a prospective database and retrospectively analyzed.

Results

Twelve of 101 MEN1 patients underwent up to three reoperations, resulting in a total of 18 reoperations for dpNEN recurrence. Patients initially underwent either formal pancreatic resections (n = 7), enucleations (n = 3), or duodenotomy with lymphadenectomy for either NF‐pNEN (seven patients), Zollinger–Ellison syndrome (ZES, three patients), organic hyperinsulinism (one patient) or VIPoma (one patient). Six patients had malignant dpNENs with lymph node (n = 5) and/or liver metastases (n = 2). The indication of reoperations was NF‐pNEN (five patients), ZES (five patients), organic hyperinsulinism (one patient), and recurrent VIPoma (one patient). Median time to first reoperation was 67.5 (range 6–251) months. Five patients required a second duodenopancreatic reoperation for 60–384 months after initial surgery, and one patient underwent a third reoperation after 249 months. The rate of complications (Clavien–Dindo ≥3) was 28%. Four patients required completion pancreatectomy. Six patients developed pancreoprivic diabetes. After a median follow‐up of 18 (6–34) years after initial surgery, ten of 12 patients are alive, one died of metastatic pancreatic VIPoma, and one died of metastatic thymic NEN.

Conclusion

Reoperations are frequently necessary for dpNEN in MEN1 patients, but are not associated with an increased perioperative morbidity in specialized centers. Organ‐sparing resections should be preferred as initial duodenopancreatic procedures to maintain pancreatic function and avoid completion pancreatectomy.
Complete stickiness of nonlocal minimal surfaces for small values of the fractional parameter
Authors: Valdinoci Enrico , Bucur Claudia , Lombardini Luca
Published: October 2018

In this paper, we consider the asymptotic behavior of the fractional mean curvature when

s\rightarrow 0^{ + }

. Moreover, we deal with the behavior of
s
-minimal surfaces when the fractional parameter

s \in (0,1)

is small, in a bounded and connected open set with

C^{2}

boundary

\mathrm{\Omega } \subset \mathbb{R}^{n}

. We classify the behavior of
s
-minimal surfaces with respect to the fixed exterior data (i.e. the
s
-minimal set fixed outside of Ω). So, for
s
small and depending on the data at infinity, the
s
-minimal set can be either empty in Ω, fill all Ω, or possibly develop a wildly oscillating boundary.

Also, we prove the continuity of the fractional mean curvature in all variables, for

s \in [0,1]

. Using this, we see that as the parameter
s
varies, the fractional mean curvature may change sign.
Critically Civic Teacher Perception, Posture and Pedagogy: Negating Civic Archetypes
Authors: Magill Kevin Russel
Published: October 2018

Critical pedagogy is an optimistic approach for achieving transformative agency, which remains an elusive and vital aspect of civic education. Therefore, the purpose of this study was to examine the pedagogical approach of three critically identifying teachers. Specifically, this study was interested in understanding participant teacher critically civic ontological postures. The posture implies an understanding of the power inherent to civic relation and pedagogy. Participant teachers uniquely demonstrated postures that allowed them to address conceptual, personal, and material aspects of civics education. Participants achieved this first by making clear temporal connections between citizenship and disciplines; second, by incorporating student experiences; and lastly by utilizing a range of instructional approaches to negate traditional civic archetypes. Findings suggest that critical civic ontological postures are dynamic, contextual, and disciplinarily situated. Authentically critically civic ontological postures include developing intellectual solidarity with students and those in educational communities.
The Role of the Family in Preventing the Transformation of Western Youngsters
into Jihadi Fighters
Authors: Barna Cristian
Published: October 2018

The mother–child relationship is essential in the development of a healthy child, who can
grow up trusting his/her own perceptions and understanding of the social environment.
Teenagers naturally experience a period of transition in search of their own identity as
individuals, thus being really exposed and vulnerable to being recruited by jihadists. In
this particular stage of development, the teenager tries to free himself/herself from the
tutorship of the family and looks to experience something new outside the family frame. One
of the defining characteristics of this stage is a tendency to take things to an extreme and
to see things in black and white, while emotions are experienced as very intense,
overwhelming and sometimes difficult to control. Teenagers are easy to impress, convince and
manipulate, especially by their social milieu outside the family of origin. In the cases
when the relationship with the family of origin becomes tensed – whether the child has been
neglected or spoiled during childhood, or when there are tensions between parents or the
family is conflicting – the teenager looks for validation outside the family environment.
Any opportunity to do something out of the ordinary and apparently easy to accomplish might
seem attractive for this category of individuals, especially for those that do not enjoy
family support. The illusion of becoming famous or the attraction of glamour might seem
desirable at this age. This is one of the main reasons why Jihad has had
such a significant impact on Western converts to Islam. Therefore, the aim of this study is
to provide an analysis of the case of Boicea Luigi Constantin (Umar al Rumaani), a Romanian
that adhered to the extremist ideology of the Islamic State, who does not come from a Muslim
family, yet underwent a fast self-radicalization process. In order to better understand
Boicea’s case, we will try to present the result of the investigation conducted on the
family environment, his interests manifested at an early age, and the tragic events that
contributed to his radicalization; in other words, we will try to present the general
context in which self-radicalization occurred.
A Theory of Statistical Inference for Matching Methods in Causal Research
Authors: Iacus Stefano M. , King Gary , Porro Giuseppe
Published: October 2018

Researchers who generate data often optimize efficiency and robustness by choosing stratified over simple random sampling designs. Yet, all theories of inference proposed to justify matching methods are based on simple random sampling. This is all the more troubling because, although these theories require exact matching, most matching applications resort to some form of ex post stratification (on a propensity score, distance metric, or the covariates) to find approximate matches, thus nullifying the statistical properties these theories are designed to ensure. Fortunately, the type of sampling used in a theory of inference is an axiom, rather than an assumption vulnerable to being proven wrong, and so we can replace simple with stratified sampling, so long as we can show, as we do here, that the implications of the theory are coherent and remain true. Properties of estimators based on this theory are much easier to understand and can be satisfied without the unattractive properties of existing theories, such as assumptions hidden in data analyses rather than stated up front, asymptotics, unfamiliar estimators, and complex variance calculations. Our theory of inference makes it possible for researchers to treat matching as a simple form of preprocessing to reduce model dependence, after which all the familiar inferential techniques and uncertainty calculations can be applied. This theory also allows binary, multicategory, and continuous treatment variables from the outset and straightforward extensions for imperfect treatment assignment and different versions of treatments.
Crystal structure of vardenafil hydrochloride trihydrate, C23H33N6O4SCl (H2O)3
Authors: Wheatley Austin M. , Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: October 2018

The crystal structure of vardenafil hydrochloride trihydrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Vardenafil hydrochloride trihydrate crystallizes in space group C2/c (#15) with a = 34.78347(16), b = 11.56752(4), c = 14.69308(5) Å, β = 93.3410(4), V = 5901.839(30) Å3, and Z = 8. The fused ring system and the phenyl ring are nearly co-planar; the interplanar angle between them is 6.0°. Two intramolecular hydrogen bonds help determine this conformation. These planes stack along the c-axis. The side chains of these ring systems have a large Uiso and are neighbors in the stacks. Along the a-axis, these stacks are separated by hydrophilic layers of chloride, water molecules, and the positively charged nitrogen atoms of the vardenafil cation. Hydrogen bonds are prominent in the crystal structure. The protonated nitrogen atom forms a strong hydrogen bond to the chloride anion. The water molecules form a hexagon, making hydrogen bonds with themselves, as well as the C1 and a ring nitrogen atom. These discrete hydrogen bonds form a cluster, and there is no extended hydrogen bond network. There are many C–H⋯Cl, C–H⋯O, and C–H⋯N hydrogen bonds, which (although individually weak) contribute significantly to the crystal energy. The powder pattern is included in the Powder Diffraction File™ as entry 00-066-1620.
Three embassies, one courtyard: formal play in the work of Guillermo Jullian de la Fuente
Authors: Fracalossi Igor
Published: October 2018

[…] only those who play are serious types […] the mountain climbers, the rugby players and the card players, and the gamblers, are all frauds, for they do not play […] (L-C) […] to my friend Jullian, questing to redefine his rules […] who has now begun to play […].

—Bob Slutzky, 1978

This article approaches three architectural facts, three works of architecture: three embassies designed by the same architect. They are the centre and horizon of the article and its goal is to make explicit the architectural processes, strategies, and decisions of conceiving and designing them. Therefore, this article gives words to things above all, while citing one or two insightful ideas from other authors. Its immanent verbs are to show and to reveal. Through dense descriptions and critical redrawings, this article seeks to prove that the creative design process of Guillermo Jullian de la Fuente is a continuous one, which can be seen through a deep examination of his buildings’ courtyards, the apparently empty residual useless spaces. The idea of courtyard is what gives purpose to Jullian's whole design process. Jullian's game is to decide their formal characteristics through a series of abstract matrices of lines and patches. In his design process, every step and every work is a possibility for evolution, variation, or disruption. There are no intellectual causes behind these foral studies but a set of creative decisions. This article also tries to show when and where those decisions occur. It seeks to contribute to the practice of design research.
Christopher N. K. Mooers (1935–2018)
Authors: Mellor George , Bowman Malcolm , Collins Curtis
Published: October 2018

This passionate physical oceanographer, a leader and catalyst in coastal studies, explored many facets of nearshore circulation and advanced the modeling and forecasting of coastal dynamics.
Sex-specific correlation of IGFBP-2 and IGFBP-3 with vitamin D status in adults with obesity: a cross-sectional serum proteomics study
Authors: Al-Daghri Nasser M. , Manousopoulou Antigoni , Alokail Majed S. , Yakout Sobhy , Alenad Amal , Garay-Baquero Diana J. , Fotopoulos Miltiadis , Teng Jie , Al-Attas Omar , Al-Saleh Yousef , Sabico Shaun , Chrousos George P. , Garbis Spiros D.
Published: October 2018

Objective

Subjects with low vitamin D levels are at risk of cardiometabolic disease. The aim of this study was to identify novel serological markers linking vitamin D status with cardiometabolic profile in non-diabetic adults with obesity.

Methods

For the discovery phase, we used quantitative serum proteomics in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25–35 kg/m2] and low [25(OH)D < 50 nmol/L] vs. high vitamin D status [25(OH)D > 50 nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort with similar characteristics (n = 179).

Results

We identified 423 and 549 differentially expressed proteins in the high vs. low vitamin D groups of the male and female cohorts, respectively. The small molecule biochemistry protein networks and the glycolysis|gluconeogenesis pathway were significantly enriched in the DEPs of both sexes. As surrogate markers to these processes, the insulin-like growth factor binding protein -2  (IGFBP-2) was upregulated in males, whereas   IGFBP-3 was upregulated in females from the high Vitamin D status. This sex-specific trend  was confirmed using Luminex ELISA to an independent but clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p = 0.03).

Conclusions

The high Vitamin D status correlated with the serological upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may constitute surrogate markers of risk reduction of cardiometabolic disease.
MicroRNA-transcription factor network analysis reveals miRNAs cooperatively suppress RORA in oral squamous cell carcinoma
Authors: Zheng Xueqing , Wu Kejing , Liao Shengjie , Pan Yuemei , Sun Yanan , Chen Xinming , Zhang Yi , Xia Shu , Hu Yaying , Zhang Jiali
Published: October 2018

Abstract

Oral squamous cell carcinoma (OSCC) represents over 90% of oral cancer incidence, while its mechanisms of tumorigenesis remain poorly characterized. In this study, we applied RNA-seq and microRNA-seq methodologies in four pairs of cancer and adjacent normal tissues to profile the contribution of miRNAs to tumorigenesis-altered functional pathways by constructing a comprehensive miRNA-mediated mRNA regulatory network. There were 213 differentially expressed (DE) miRNAs and 2172 DE mRNAs with the involvement of negative miRNA-mRNA interactions identified by at least two pairs of cancerous tissues. GO analysis revealed that the upregulated microRNAs significantly contributed to a global down-regulation of a number of transcription factors (TFs) in OSCC. Among the negative regulatory networks between the selected miRNAs (133) and TFs (167), circadian rhythm genes (RORA, RORB, RORC, and CLOCK) simultaneously regulated by multiple microRNAs were of particular interest. For instance, RORA transcript was predicted to be targeted by 25 co-upregulated miRNAs, of which, miR-503-5p, miR-450b-5p, miR-27a-3p, miR-181a-5p and miR-183-5p were further validated to directly target RORA, resulting in a stronger effect on RORA suppression together. In addition, we showed that the mRNA and protein expression levels of RORα were significantly decreased in most OSCC samples, associated with advanced clinical stage and poor prognosis. RORα significantly suppressed the proliferation of OSCC cells in vitro and in vivo. Attenuated RORα decreased p53 protein expression and suppressed p53 phosphorylation activity. Altogether, our results strongly suggest the importance of the role of miRNAs in regulating the activity of circadian rhythm-related TFs network during OSCC tumorigenesis, and provide further clues to understand the clinical link between circadian rhythm and cancer therapy.
Altered cerebral benzodiazepine receptor binding in post-traumatic stress disorder
Authors: Reuveni Inbal , Nugent Allison C. , Gill Jessica , Vythilingam Meena , Carlson Paul J. , Lerner Alicja , Neumeister Alexander , Charney Dennis S. , Drevets Wayne C. , Bonne Omer
Published: October 2018

Agonists of the γ-aminobutyric acid (GABA) type A benzodiazepine (BZD) receptor exert anxiolytic effects in anxiety disorders, raising the possibility that altered GABA-ergic function may play a role in the pathophysiology of anxiety disorders, such as post-traumatic stress disorder (PTSD). However, few neuroimaging studies have assessed the function or binding potential of the central GABAA BZD receptor system in PTSD. Therefore, our aim was to compare the BZD receptor binding potential between PTSD patients and healthy controls. Twelve medication-free participants with a current diagnosis of PTSD and 15 matched healthy controls underwent positron emission tomography (PET) imaging using [11C] flumazenil. Structural magnetic resonance imaging (MRI) scans were obtained and co-registered to the PET images to permit co-location of neuroanatomical structures in the lower resolution PET image data. Compared to healthy controls, PTSD patients exhibited increased BZD binding in the caudal anterior cingulate cortex and precuneus (p’s < 0.05). Severity of PTSD symptoms positively correlated with BZD binding in the left mid- and anterior insular cortices. This study extends previous findings by suggesting that central BZD receptor system involvement in PTSD includes portions of the default mode and salience networks, along with insular regions that support interoception and autonomic arousal.
Procaspase-3-activating compound 1 stabilizes hypoxia-inducible factor 1α and induces DNA damage by sequestering ferrous iron
Authors: Li Feifei , Wei Aili , Bu Lijuan , Long Long , Chen Wei , Wang Chen , Zhao Changqi , Wang Lili
Published: October 2018

Procaspase-3-activating compound 1 (PAC-1) induces procaspase-3 activation via zinc chelation. However, whether PAC-1 employs other mechanisms remains unknown. Here we systematically screened for potent PAC-1 targets using 29 enhanced green fluorescent protein-labeled reporter cell lines and identified hypoxia-inducible factor 1α (HIF1α) and RAD51 pathways as PAC-1 targets. These results were verified in HepG2 cells and two other cancer cell lines. Mechanistically, PAC-1 specifically blocked HIF1α hydroxylation and upregulated HIF1α target genes. In addition, DNA damage, G1/S cell cycle arrest, and the inhibition of DNA synthesis were induced following PAC-1 administration. Interestingly, by using ferrozine-iron sequestration and iron titration assays, we uncovered the iron sequestering capacity of PAC-1. Additionally, the expression levels of iron shortage-related genes were also increased in PAC-1-treated cells, and iron (II) supplementation reversed all of the observed cellular responses. Thus, our results indicate that PAC-1 induces HIF1α stabilization and DNA damage by sequestering ferrous iron.
Maintenance of human haematopoietic stem and progenitor cells in vitro using a chemical cocktail
Authors: Jiang Mengmeng , Chen Haide , Lai Shujing , Wang Renying , Qiu Yunfei , Ye Fang , Fei Lijiang , Sun Huiyu , Xu Yang , Jiang Xinyi , Zhou Ziming , Zhang Tingyue , Li Yanwei , Xie Jin , Fang Qun , Gale Robert Peter , Han Xiaoping , Huang He , Guo Guoji
Published: October 2018

Identification of effective culture conditions to maintain and possibly expand human HSPCs in vitro is an important goal. Recent advances highlight the efficacy of chemicals in maintaining and converting cell fates. We screened 186 chemicals and found that a combination of CHIR-99021, Forskolin and OAC1 (CFO) maintained human CD34-positive cells in vitro. Efficiency of the culture system was characterized using flow cytometry for CD34-positive cells, a colony-forming assay and xeno-transplants. We found that human CD34-positive cells treated with this combination had enhanced expression of human HSPC markers and increased haematopoietic re-populating ability in immune-deficient mice. Single-cell RNA-seq analyses showed that the in vitro cultured human CD34-positive cells were heterogeneous. We found that CFO supports maintenance of human CD34-positive cells by activating HOXA9, GATA2 and AKT-cAMP signaling pathway. These data have implications in therapies requiring maintenance and/or expansion of human HSPCs.
Electrically reconfigurable terahertz signal processing devices using liquid metal components
Authors: Reichel Kimberly S. , Lozada-Smith Nicolas , Joshipura Ishan D. , Ma Jianjun , Shrestha Rabi , Mendis Rajind , Dickey Michael D. , Mittleman Daniel M.
Published: October 2018

Many applications of terahertz (THz) technology require the ability to actively manipulate a free space THz beam. Yet, although there have been many reports on the development of devices for THz signal processing, few of these include the possibility of electrical control of the functionality, and novel ideas are needed for active and reconfigurable THz devices. Here, we introduce a new approach, based on the integration of electrically actuated liquid metal components in THz waveguides. This versatile platform offers many possibilities for control of THz spectral content, wave fron"ts, polarization, and power flow. We demonstrate two illustrative examples: the first active power-splitting switch, and the first channel add–drop filter. We show that both of these devices can be used to electrically switch THz communication signals while preserving the information in a high bit-rate-modulated data stream.
Low threshold and efficient multiple exciton generation in halide perovskite nanocrystals
Authors: Li Mingjie , Begum Raihana , Fu Jianhui , Xu Qiang , Koh Teck Ming , Veldhuis Sjoerd A. , Grätzel Michael , Mathews Nripan , Mhaisalkar Subodh , Sum Tze Chien
Published: October 2018

Multiple exciton generation (MEG) or carrier multiplication, a process that spawns two or more electron–hole pairs from an absorbed high-energy photon (larger than two times bandgap energy Eg), is a promising way to augment the photocurrent and overcome the Shockley–Queisser limit. Conventional semiconductor nanocrystals, the forerunners, face severe challenges from fast hot-carrier cooling. Perovskite nanocrystals possess an intrinsic phonon bottleneck that prolongs slow hot-carrier cooling, transcending these limitations. Herein, we demonstrate enhanced MEG with 2.25Eg threshold and 75% slope efficiency in intermediate-confined colloidal formamidinium lead iodide nanocrystals, surpassing those in strongly confined lead sulfide or lead selenide incumbents. Efficient MEG occurs via inverse Auger process within 90 fs, afforded by the slow cooling of energetic hot carriers. These nanocrystals circumvent the conundrum over enhanced Coulombic coupling and reduced density of states in strongly confined nanocrystals. These insights may lead to the realization of next generation of solar cells and efficient optoelectronic devices.
Efficient carrier multiplication in CsPbI3 perovskite nanocrystals
Authors: de Weerd Chris , Gomez Leyre , Capretti Antonio , Lebrun Delphine M. , Matsubara Eiichi , Lin Junhao , Ashida Masaaki , Spoor Frank C. M. , Siebbeles Laurens D. A. , Houtepen Arjan J. , Suenaga Kazutomo , Fujiwara Yasufumi , Gregorkiewicz Tom
Published: October 2018

The all-inorganic perovskite nanocrystals are currently in the research spotlight owing to their physical stability and superior optical properties—these features make them interesting for optoelectronic and photovoltaic applications. Here, we report on the observation of highly efficient carrier multiplication in colloidal CsPbI3 nanocrystals prepared by a hot-injection method. The carrier multiplication process counteracts thermalization of hot carriers and as such provides the potential to increase the conversion efficiency of solar cells. We demonstrate that carrier multiplication commences at the threshold excitation energy near the energy conservation limit of twice the band gap, and has step-like characteristics with an extremely high quantum yield of up to 98%. Using ultrahigh temporal resolution, we show that carrier multiplication induces a longer build-up of the free carrier concentration, thus providing important insights into the physical mechanism responsible for this phenomenon. The evidence is obtained using three independent experimental approaches, and is conclusive.
Structural insights on TRPV5 gating by endogenous modulators
Authors: Hughes Taylor E. T. , Pumroy Ruth A. , Yazici Aysenur Torun , Kasimova Marina A. , Fluck Edwin C. , Huynh Kevin W. , Samanta Amrita , Molugu Sudheer K. , Zhou Z. Hong , Carnevale Vincenzo , Rohacs Tibor , Moiseenkova-Bell Vera Y.
Published: October 2018

TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.