bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR04: Intravital imaging of cytolytic activity reveals how poor tumor vascularization and hypoxia limit tumor rejection
Authors: Shakhar Guy , Manaster Yoav , Feferman Tali 
Published: December 2015

Abstract
Background: Immunotherapies that harness cytotoxic T lymphocytes (CTLs) to eradicate solid tumors, melanoma in particular, have re-emerged as potent clinical options in recent years. Improving the dispersion and cytotoxicity of intratumoral CTLs may further benefit patients. One of the obstacles to successful treatment is thought to be poor vascularization of tumors, which leads to sub-optimal tumor infiltration. In contrast, the effects of disrupted vascularization and the hypoxia it introduces on CTL migration and function within tumors have not been investigated.
Methods: To study whether tumor vascularity can shape anti-tumor CTL responses, we combined immunohistochemistry of human melanoma samples with dynamic two-photon imaging within B16 melanoma tumors expressing ovalbumin (OVA) in live mice.
Results: In patients, CD8 T cells were twofold denser around peripheral vessels than around deep vessels, and fourfold denser than in avascular areas. This pattern was clearest in poorly-infiltrated tumors. Correspondingly, in mice, adoptively transferred OT-I CTLs, specific for OVA, preferentially infiltrated B16-OVA tumors through peripheral ICAM1+ vessels. CTLs remained initially at their entry areas, crawling vigorously only within 50µm of flowing blood vessels. These dense CTLs swarms efficiently cleared perivascular areas of tumor cells but left avascular areas intact. In contrast, Foxp3+ regulatory T cells could venture farther away from blood vessels. Target killing was antigen-specific, contact-dependent and perforin-mediated, and required multiple CTLs to engage one target cell to be effective. Several findings converge to suggest that perivascular CTL confinement is oxygen-dependent: occlusion of intratumoral blood vessels resulted in instantaneous and reversible arrest of CTLs. Immunohistology indicated that CTLs avoided hypoxic tumor areas. Hypoxia and mitochondrial uncoupling interfered with CTL migration in vitro and, finally, highly vascular tumors grown in a matrix containing the pro-angiogenic factor bFGF were more easily rejected after CTL injection, displayed delayed growth in untreated mice but were not affected in immunodeficient mice. Although such normalized tumors attracted normal numbers of CTLs, these cells migrated more freely within the tumors.
Conclusions: We propose that CTLs depend on oxygen for intratumoral locomotion and cytolysis. Incomplete vascularization promotes patchy infiltration and tumor escape; tumor immunotherapy may thus benefit from an extensive and functional vasculature.
Citation Format: Guy Shakhar, Yoav Manaster, Tali Feferman. Intravital imaging of cytolytic activity reveals how poor tumor vascularization and hypoxia limit tumor rejection. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr PR04.
Can Nonnative Speakers Reduce English Vowels in a Native-Like Fashion? Evidence from L1-Spanish L2-English Bilinguals
Authors: Rallo Fabra Lucrecia 
Published: December 2015

AbstractThis paper investigates the production of English unstressed vowels by two groups of early (ESp) and late Spanish (LSp) bilinguals and a control group of native English (NE) monolinguals. Three acoustic measurements were obtained: duration and intensity ratios of unstressed to stressed vowels, normalized vowel formants and euclidean distances. Both groups of bilinguals showed significantly fewer differences in duration between stressed and unstressed vowels than the NE monolinguals. Intensity differences depended on whether the stress pattern of the target English words matched the stress pattern of their Spanish cognates. As for vowel quality, the early bilinguals reduced the unstressed vowels, which clustered around the midcenter area of the vowel space, in the same fashion as the NE monolinguals, suggesting that vowel reduction might be operating at the phonological level. However, the late bilinguals showed a context-dependent, phonetic-level pattern with vowels that were more peripheral in the vowel space.
Imagens que faltam, imagens que restam: a tortura em Cabra Marcado para Morrer.
Authors: Machado Patrícia Furtado Mendes 
Published: December 2015

<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p class="Padro">Diante da falta de imagens das torturas praticadas durante a ditadura militar brasileira, quais as estratégias usadas por <em>Cabra Marcado para Morrer</em><em> </em>(1984), de Eduardo Coutinho, para transformar em experiência sensível essa ausência? Exibido em 1984, no início do processo de redemocratização, o filme elabora memórias sufocadas pela repressão. Nesse artigo, propomos uma análise minuciosa das imagens e falas que remetem à tortura. Para dar um sentido renovado aos testemunhos e aos registros que restam da época, retomados no filme, fomos em busca de documentos da polícia política que se referem aos personagens que o regime procurou tornar invisíveis.</p><p class="Padro"> </p><br /><p class="Padro"> </p></div></div></div>
Fuel poverty-induced ‘prebound effect’ in achieving the anticipated carbon savings from social housing retrofit
Authors: Teli D , Dimitriou T , James PAB , Bahaj AS , Ellison L , Waggott A 
Published: December 2015

Social housing retrofit is often seen as a way to contribute to carbon reductions as it typically encompasses large-scale interventions managed by one landlord. This work investigates the carbon savings potential of a deep retrofit in a local authority owned 107-flat tower block, taking into account the tenants' pre-retrofit heating strategies. Prior to the retrofit, temperature and relative humidity monitoring were undertaken in 18 flats for 35 days. The measurements were then used to develop occupant heating profiles in the 18 homes. Dynamic thermal simulation of the flats pre- and post-retrofit using the identified user heating profiles highlights that for these fuel poverty-constrained flats, the estimated carbon savings of retrofit will be typically half those predicted using standard rules for temperatures in living spaces. Practical application: The findings presented in this paper demonstrate the impact of fuel poverty on the expected benefits from social housing retrofit schemes, providing information relevant to multiple stakeholders: (1) building industry: The study highlights the need to use empirical data in building energy modelling, as typical conditions could be far from representative in social homes (2) Policy makers and social landlords: Targets for CO2 reduction may not be achieved through retrofitting, but the social impact could be much greater and more critical than assumed. The findings under this work help to direct incentives for retrofit schemes towards the social and health benefits achieved.
Local and global: Seafaring communities in the North Sea area, c. 1600–2000
Authors: Davids Karel 
Published: December 2015

A seafaring community is a village, a small town or a neighbourhood where a substantial part of the population earns its livelihood wholly or partly by work at sea or is directly dependent on seafaring. A seafaring community can arise because an established population at a particular locality increasingly takes up seafaring, or it can be created by the settlement of a sizeable number of seafaring immigrants. The former type of community might be called ‘endogenous’, the latter one ‘exogenous’. This essay analyses in what respect seafaring communities of these two types (or mixtures between them) in the North Sea area changed over time and in what ways these changes were connected to larger, transnational processes or to local conditions. It examines three periods of great transformation: the seventeenth and early eighteenth centuries; the period between about 1850 and the First World War; and the last decades of the twentieth century. The story of endogenous seafaring communities in the North Sea area differed from the story of exogenous communities in many ways. While seafaring communities in villages and small towns vanished in one region and emerged in another, social differentiation within communities increased as well, with shipmasters organising separately from common seamen; eventually, this type of seafaring community disappeared in the late twentieth century. Seafaring communities in big port cities, by contrast, thanks to immigration, continued to exist, although this category, too, has seen shifts in geography in the last 150 years, notably from Amsterdam and London to Rotterdam and Hamburg; moreover, the origin of immigrant seamen vastly changed. This article offers several explanations for these changes and variations.
Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus
Authors: Yang J , Li Q , Yang X , Li M 
Published: December 2015

Objective Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Methods Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. Results The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. Conclusion These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity.
Prevalence of premature ovarian failure in patients with systemic lupus erythematosus
Authors: Mayorga J , Alpízar-Rodríguez D , Prieto-Padilla J , Romero-Díaz J , Cravioto M C 
Published: December 2015

Objective To estimate the prevalence of premature ovarian failure (POF) and its associated factors in patients with systemic lupus erythematosus (SLE). Methods Cross-sectional study including consecutive SLE women <60 years of age attending a rheumatology clinic. A face-to-face interview was undertaken to obtain demographic, gynaecological and lupus characteristics. Additional rheumatologic and endocrine data were retrieved from patients’ medical records. POF prevalence was estimated in the study sample and in a subgroup of patients aged <40 years at interview. Associations between POF and selected variables were assessed by logistic regression analyses. Results A total of 961 patients were analysed. Prevalence of POF, secondary amenorrhea of known cause, menopause and hysterectomy were 5.4%, 0.8%, 7.8% and 4.4%, respectively. In 674 (70%) patients who had not been exposed to cyclophosphamide (CYC) the prevalence of POF was 0.6%. Disease activity over time (OR 1.4 (CI 95% 1.0–1.8, p < 0.05)) and CYC treatment (OR 5.9 (CI 95% 1.8–18.8, p < 0.01)) were associated with higher prevalence. Association between POF and endocrine autoimmune diseases was not found. Conclusions In the absence of CYC treatment, the prevalence of POF in lupus patients is consistent with that reported in the general population. The existence of autoimmune processes at the ovary seems unlikely in most lupus patients.
Multiplanar CT Analysis of Fifth Metatarsal Morphology
Authors: DeSandis Bridget , Murphy Conor , Rosenbaum Andrew , Levitsky Matthew , O’Malley Quinn , Konin Gabrielle , Drakos Mark 
Published: December 2015

Background: Percutaneous internal fixation is currently the method of choice treating proximal zone II fifth metatarsal fractures. Complications have been reported due to poor screw placement and inadequate screw sizing. The purpose of this study was to define the morphology of the fifth metatarsal to help guide surgeons in selecting the appropriate screw size preoperatively. Methods: Multiplanar analysis of fifth metatarsal morphology was completed using computed tomographic (CT) scans from 241 patients. Specific parameters were analyzed and defined in anteroposterior (AP), lateral, and oblique views including metatarsal length, distance from the base to apex of curvature, apex medullary canal width, apex height, and fifth metatarsal angle. Results: The average metatarsal length in the AP view was 71.4 ± 6.1 mm and in the lateral view 70.4 ± 6.0 mm, with 95% of patients having lengths between 59.3 and 83.5 mm and 58.4 and 82.4 mm, respectively. The average canal width at the apex of curvature was 4.1 ± 0.9 mm in the AP view and 5.3 ± 1.1 mm in the lateral view, with 95% of patients having widths between 2.2 and 5.9 mm and 3.2 and 7.5 mm, respectively. Average distance from apex to base was 42.6 ± 5.8 mm in the AP and 40.4 ± 6.4 mm in the lateral views. Every measurement taken in all 3 views had a significant correlation with height. Conclusions: When determining screw length, we believe lateral radiographs should be used since the distance from the base of the metatarsal to the apex was smaller in the lateral view. On average, the screw should be 40 mm or less to reduce risk of distraction. For screw diameter, the AP view should be used because canal shape is elliptical, and width was found to be significantly smaller in the AP view. Most canals can accommodate a 4.0- or 4.5-mm-diameter screw, and one should use the largest diameter screw possible. Larger individuals were likely to have more bowing in their metatarsal shaft, which may lead to a higher tendency to distract. Level of Evidence: Level III, comparative series.
Age-related upper limits of normal for maximum upright exercise pulmonary haemodynamics
Authors: Oliveira Rudolf K.F. , Agarwal Manyoo , Tracy Julie A. , Karin Abbey L. , Opotowsky Alexander R. , Waxman Aaron B. , Systrom David M. 
Published: December 2015

The exercise definition of pulmonary hypertension was eliminated from the pulmonary hypertension guidelines in part due to uncertainty of the upper limits of normal (ULNs) for exercise haemodynamics in subjects >50 years old.The present study, therefore, evaluated the pulmonary haemodynamic responses to maximum upright incremental cycling exercise in consecutive subjects who underwent an invasive cardiopulmonary exercise testing for unexplained exertional intolerance, deemed normal based on preserved exercise capacity and normal resting supine haemodynamics. Subjects aged >50 years old (n=41) were compared with subjects ≤50 years old (n=25). ULNs were calculated as mean+2sd.Peak exercise mean pulmonary arterial pressure was not different for subjects >50 and ≤50 years old (23±5versus22±4 mmHg, p=0.22), with ULN of 33 and 30 mmHg, respectively. Peak cardiac output was lower in older subjects (median (interquartile range): 12.1 (9.4–14.2)versus16.2 (13.8–19.2) L·min−1, p<0.001). Peak pulmonary vascular resistance was higher in older subjects compared with younger subjects (mean±sd: 1.20±0.45versus0.82±0.26 Wood units, p<0.001), with ULN of 2.10 and 1.34 Wood units, respectively.We observed that subjects >50 and ≤50 years old have different pulmonary vascular responses to exercise. Older subjects have higher pulmonary vascular resistance at peak exercise, resulting in different exercise haemodynamics ULNs compared with the younger population.
Asthma phenotypes and IgE responses
Authors: Froidure Antoine , Mouthuy Jonathan , Durham Stephen R. , Chanez Pascal , Sibille Yves , Pilette Charles 
Published: December 2015

The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma.In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcεRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcεRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma.
Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy
Authors: Xu Chong-Chong , Denton Kyle R. , Wang Zhi-Bo , Zhang Xiaoqing , Li Xue-Jun 
Published: December 2015

ABSTRACT
Spinal muscular atrophy (SMA), characterized by specific degeneration of spinal motor neurons, is caused by mutations in the survival of motor neuron 1, telomeric (SMN1) gene and subsequent decreased levels of functional SMN. How the deficiency of SMN, a ubiquitously expressed protein, leads to spinal motor neuron-specific degeneration in individuals affected by SMA remains unknown. In this study, we examined the role of SMN in mitochondrial axonal transport and morphology in human motor neurons by generating SMA type 1 patient-specific induced pluripotent stem cells (iPSCs) and differentiating these cells into spinal motor neurons. The initial specification of spinal motor neurons was not affected, but these SMA spinal motor neurons specifically degenerated following long-term culture. Moreover, at an early stage in SMA spinal motor neurons, but not in SMA forebrain neurons, the number of mitochondria, mitochondrial area and mitochondrial transport were significantly reduced in axons. Knocking down of SMN expression led to similar mitochondrial defects in spinal motor neurons derived from human embryonic stem cells, confirming that SMN deficiency results in impaired mitochondrial dynamics. Finally, the application of N-acetylcysteine (NAC) mitigated the impairment in mitochondrial transport and morphology and rescued motor neuron degeneration in SMA long-term cultures. Furthermore, NAC ameliorated the reduction in mitochondrial membrane potential in SMA spinal motor neurons, suggesting that NAC might rescue apoptosis and motor neuron degeneration by improving mitochondrial health. Overall, our data demonstrate that SMN deficiency results in abnormal mitochondrial transport and morphology and a subsequent reduction in mitochondrial health, which are implicated in the specific degeneration of spinal motor neurons in SMA.
The role of palmitoylation and transmembrane domain in sorting of transmembrane adaptor proteins
Authors: Chum Tomáš , Glatzová Daniela , Kvíčalová Zuzana , Malínský Jan , Brdička Tomáš , Cebecauer Marek 
Published: December 2015

ABSTRACT
Plasma membrane proteins synthesised at the endoplasmic reticulum are delivered to the cell surface via sorting pathways. Hydrophobic mismatch theory based on the length of the transmembrane domain (TMD) dominates discussion about determinants required for protein sorting to the plasma membrane. Transmembrane adaptor proteins (TRAP) are involved in signalling events which take place at the plasma membrane. Members of this protein family have TMDs of varying length. We were interested in whether palmitoylation or other motifs contribute to the effective sorting of TRAP proteins. We found that palmitoylation is essential for some, but not all, TRAP proteins independent of their TMD length. We also provide evidence that palmitoylation and proximal sequences can modulate sorting of artificial proteins with TMDs of suboptimal length. Our observations point to a unique character of each TMD defined by its primary amino acid sequence and its impact on membrane protein localisation. We conclude that, in addition to the TMD length, secondary sorting determinants such as palmitoylation or flanking sequences have evolved for the localisation of membrane proteins.
p120-catenin controls contractility along the vertical axis of epithelial lateral membranes
Authors: Yu Huapeng H. , Dohn Michael R. , Markham Nicholas O. , Coffey Robert J. , Reynolds Albert B. 
Published: December 2015

ABSTRACT
In vertebrate epithelia, p120-catenin (hereafter referred to as p120; also known as CTNND1) mediates E-cadherin stability and suppression of RhoA. Genetic ablation of p120 in various epithelial tissues typically causes striking alterations in tissue function and morphology. Although these effects could very well involve p120's activity towards Rho, ascertaining the impact of this relationship has been complicated by the fact that p120 is also required for cell–cell adhesion. Here, we have molecularly uncoupled p120's cadherin-stabilizing and RhoA-suppressing activites. Unexpectedly, removing p120's Rho-suppressing activity dramatically disrupted the integrity of the apical surface, irrespective of E-cadherin stability. The physical defect was tracked to excessive actomyosin contractility along the vertical axis of lateral membranes. Thus, we suggest that p120's distinct activities towards E-cadherin and Rho are molecularly and functionally coupled and this, in turn, enables the maintenance of cell shape in the larger context of an epithelial monolayer. Importantly, local suppression of contractility by cadherin-bound p120 appears to go beyond regulating cell shape, as loss of this activity also leads to major defects in epithelial lumenogenesis.
Lomonosov and Computer Technology in Teaching Descriptive Geometry
Authors: Короткий  , Korotkiy Viktor , Хмарова  , Khmarova Lyudmila 
Published: December 2015

The famous phrase of M.V. Lomonosov: &#34;Mathematics
should be studied for it puts mind in order&#34;. It is quite possible to
rephrase it for descriptive geometry, because geometry is math too.
The invention of microprocessor technology, the advent of the
personal computer, the discovery of the GMR effect (1988), which
dramatically increased the speed and memory capacity of the PC,
are called the fourth information revolution in the history of mankind.
The whole world took note of this and began to apply, only
in Russia some extreme reformers of geometry assumed that if
computer graphics arose, it might well replace geometry.
Computer graphics, of course, can be applied to solve various
geometric problems. But what is important for a University that
aims to teach? The process of learning or the mere result on display
obtained just by pressing the buttons? More important is how this
result is obtained and with what algorithm. Therefore, the feasibility
of the use of graphic programs in solving typical tasks of descriptive
geometry is very much an open question.
A student solving the task via computer is concerned not with
the search of geometric algorithm, but with the search of a suitable
option that could give an answer. But not all geometrical problems
are amenable to the available buttons.
Submerged into virtual world, a student begins to think in terms
of this world and cease to be aware and to pay attention to fundamental,
basic geometric regularities taught in descriptive geometry
course.
Comparing geometric and computational algorithms is incorrect
because there is no knowledge of the “hidden files” of graphic
editor. We can assume that the iterative scheme is implemented.
Frontal iterative computer graphics schemes are good for getting
answers, but unsuitable for the study of constructive geometry
methods.