bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of rare factor deficiencies in 2016
Authors: Peyvandi Flora , Menegatti Marzia 
Published: December 2016

Abstract
Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K–dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population. Patients affected with RBDs may present a wide range of clinical symptoms, varying from mucocutaneous bleeding, common to all types of RBDs to the most life-threatening symptoms such as central nervous system and gastrointestinal bleeding. Treatment of these disorders is mainly based on the replacement of the deficient factor, using specific plasma-derived or recombinant products. In countries where these facilities are not available, bleedings could be managed using cryoprecipitate, fresh frozen plasma (FFP), or virus-inactivated plasma. Minor bleedings could be managed using antifibrinolytic agents. Recently, 2 novel drugs, recombinant FXIIIA and a plasma-derived FX, have been added to the list of available specific hemostatic factors; only prothrombin and FV deficiencies still remain without a specific product. Novel no-replacement therapies, such as monoclonal antibody anti–tissue factor pathway inhibitor, RNA interference, and a bispecific antibody that is an FVIIIa mimetic, enhancing thrombin generation through different mechanisms, were developed for patients with hemophilia and may in the future be a good therapeutic option also in RBDs.
Diagnosing von Willebrand disease: genetic analysis
Authors: Goodeve Anne 
Published: December 2016

Abstract
Investigation of a patient with possible von Willebrand disease (VWD) includes a range of phenotypic analyses. Often, this is sufficient to discern disease type, and this will suggest relevant treatment. However, for some patients, phenotypic analysis does not sufficiently explain the patient’s disorder, and for this group, genetic analysis can aid diagnosis of disease type. Polymerase chain reaction and Sanger sequencing have been mainstays of genetic analysis for several years. More recently, next-generation sequencing has become available, with the advantage that several genes can be simultaneously analyzed where necessary, eg, for discrimination of possible type 2N VWD or mild hemophilia A. Additionally, several techniques can now identify deletions/duplications of an exon or more that result in VWD including multiplex ligation-dependent probe amplification and microarray analysis. Algorithms based on next-generation sequencing data can also identify missing or duplicated regions. These newer techniques enable causative von Willebrand factor defects to be identified in more patients than previously, aiding in a specific VWD diagnosis. Genetic analysis can also be helpful in the discrimination between type 2B and platelet-type VWD and in prenatal diagnosis for families with type 3.
CD4 downregulation by the HIV-1 protein Nef reveals distinct roles for the γ1 and γ2 subunits of the AP-1 complex in protein trafficking
Authors: Tavares Lucas A. , da Silva Eulália M. L. , da Silva-Januário Mara E. , Januário Yunan C. , de Cavalho Julianne V. , Czernisz Érika S. , Mardones Gonzalo A. , daSilva Luis L. P. 
Published: December 2016

ABSTRACT
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and its subsequent targeting to lysosomes. Herein, we report that this lysosomal targeting requires a variant of AP-1 containing isoform 2 of γ-adaptin (AP1G2, hereafter γ2). Depletion of the γ2 or μ1A (AP1M1) subunits of AP-1, but not of γ1 (AP1G1), precludes Nef-mediated lysosomal degradation of CD4. In γ2-depleted cells, CD4 internalized by Nef accumulates in early endosomes and this alleviates CD4 removal from the cell surface. Depletion of γ2 also hinders EGFR–EGF-complex targeting to lysosomes, an effect that is not observed upon γ1 depletion. Taken together, our data provide evidence that the presence of γ1 or γ2 subunits delineates two distinct variants of AP-1 complexes, with different functions in protein sorting.
Integration of transmembrane domains is regulated by their downstream sequences
Authors: Junne Tina , Spiess Martin 
Published: December 2016

ABSTRACT
The Sec61 translocon catalyzes translocation of proteins into the endoplasmic reticulum and the lateral integration of transmembrane segments into the lipid bilayer. Integration is mediated by the hydrophobicity of a polypeptide segment consistent with thermodynamic equilibration between the translocon and the lipid membrane. Integration efficiency of a generic series of increasingly hydrophobic sequences (H-segments) was found to diverge significantly in different reporter constructs as a function of the ∼100 residues that are C-terminal to the H-segments. The hydrophobicity threshold of integration was considerably lowered through insertion of generic ∼20-residue peptides either made of flexible glycine–serine repeats, containing multiple negative charges, or consisting of an oligoproline stretch. A highly flexible, 100-residue glycine–serine stretch maximally enhanced this effect. The apparent free energy of integration was found to be changed by more than 3 kcal/mol with the downstream sequences tested. The C-terminal sequences could also be shown to affect integration of natural mildly hydrophobic sequences. The results suggest that the conformation of the nascent polypeptide in the protected cavity between the ribosome and translocon considerably influences the release of the H-segment into the bilayer.
Mortalin-mediated and ERK-controlled targeting of HIF-1α to mitochondria confers resistance to apoptosis under hypoxia
Authors: Mylonis Ilias , Kourti Maria , Samiotaki Martina , Panayotou George , Simos George 
Published: December 2016

Abstract
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK1 and/or ERK2 (MAPK3 and MAPK1, respectively; hereafter ERK) stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1 (XPO1)-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a so-far-unknown interaction partner identified as mortalin (also known as GRP75 and HSPA9), which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α that lacks modification by ERK, and the HIF-1α–mortalin complex is localized outside the nucleus. Under hypoxia, mortalin mediates targeting of unmodified HIF-1α to the outer mitochondrial membrane, as well as association with VDAC1 and hexokinase II, which promotes production of a C-terminally truncated active form of VDAC1, denoted VDAC1-ΔC, and protection from apoptosis when ERK is inactivated. Under normoxia, transcriptionally inactive forms of unmodified HIF-1α or its C-terminal domain alone are also targeted to mitochondria, stimulate production of VDAC1-ΔC and increase resistance to etoposide- or doxorubicin-induced apoptosis. These findings reveal an ERK-controlled, unconventional and anti-apoptotic function of HIF-1α that might serve as an early protective mechanism upon oxygen limitation and promote cancer cell resistance to chemotherapy.
Heterochromatin aggregation during DNA elimination in Tetrahymena is facilitated by a prion-like protein
Authors: Kataoka Kensuke , Mochizuki Kazufumi 
Published: December 2016

ABSTRACT
Regulated aggregations of prion and prion-like proteins play physiological roles in various biological processes. However, their structural roles in the nucleus are poorly understood. Here, we show that the prion-like protein Jub6p is involved in the regulation of chromatin structure in the ciliated protozoan Tetrahymena thermophila. Jub6p forms sodium dodecyl sulfate (SDS)-resistant aggregates when it is ectopically expressed in vegetative cells and binds to RNA in vitro. Jub6p is a heterochromatin component and is important for the formation of heterochromatin bodies during the process of programmed DNA elimination. We suggest that RNA–protein aggregates formed by Jub6p are an essential architectural component for the assembly of heterochromatin bodies.
Beneficial effects of rapamycin in a Drosophila model for hereditary spastic paraplegia
Authors: Xu Shiyu , Stern Michael , McNew James A. 
Published: December 2016

ABSTRACT
The locomotor deficits in the group of diseases referred to as hereditary spastic paraplegia (HSP) reflect degeneration of upper motor neurons, but the mechanisms underlying this neurodegeneration are unknown. We established a Drosophila model for HSP, atlastin (atl), which encodes an ER fusion protein. Here, we show that neuronal atl loss causes degeneration of specific thoracic muscles that is preceded by other pathologies, including accumulation of aggregates containing polyubiquitin, increased generation of reactive oxygen species and activation of the JNK–Foxo stress response pathway. We show that inhibiting the Tor kinase, either genetically or by administering rapamycin, at least partially reversed many of these pathologies. atl loss from muscle also triggered muscle degeneration and rapamycin-sensitive locomotor deficits, as well as polyubiquitin aggregate accumulation. These results indicate that atl loss triggers muscle degeneration both cell autonomously and nonautonomously.
3D culture models of tissues under tension
Authors: Eyckmans Jeroen , Chen Christopher S. 
Published: December 2016

ABSTRACT
Cells dynamically assemble and organize into complex tissues during development, and the resulting three-dimensional (3D) arrangement of cells and their surrounding extracellular matrix in turn feeds back to regulate cell and tissue function. Recent advances in engineered cultures of cells to model 3D tissues or organoids have begun to capture this dynamic reciprocity between form and function. Here, we describe the underlying principles that have advanced the field, focusing in particular on recent progress in using mechanical constraints to recapitulate the structure and function of musculoskeletal tissues.
Letters
Authors: Willimott V. , Malloy Evelyn , Pope S. A. , Curry F. , Small J.F. , Morris A.M. , Urquhart C.L. , Hutchinson J. 
Published: December 2016

TOPICAL PREPARATIONS WOUND CARE SOCIETY PREVENTING PRESSURE SORES AFTER HIP FRACTURES LEG ULCER CLINIC DRESSING METHODS AFTER TOENAIL REMOVAL WOUND CARE IS NOT A GAME POINT OF STYLE JOURNAL BINDERS
From the Editor in Chief
Authors: Doğanay Ahmet 
Published: December 2016

Dear producers and consumers of knowledge,

I would like to share the happiness of being with you again with 6th Volume 4th Issue of Pegem Journal of Education and Instruction (PEGEGOG). I hope you could find time to have a rest after your busy schedule. Initially, I want to thank you for the increasing interest for our journal.

As mentioned before, we had applied to many indexes. Our belief in being accepted to these indexes that we are through evaluation process is increasing day by day. I would like to remind that our journal will have English and Turkish full papers from now on to fulfill the conditions of these indexes.

We shared with you in previous issues and announcements that our journal got high scores by many indexes. I'm pleased to inform you in this issue that the journal's h-index rose to 9. However, our aim is always to have much higher scores. Therefore, we invite you to share studies comprehensive, built on strong theoretical basis, innovative and bringing a vision on various fields of educational sciences increasing the number of readers.

There has been 13 articles sent for publication to our journal. This is good news for our journal and country. On the other hand, I have to indicate that there were critical problems in terms of format within these articles as stated in the previous issue. First of all, unfortunately we had to reject some articles as in many of them there were texts very similar to ones in different articles. At first step, we scan all articles in i-Thenticate program to determine the exact quotations from other resources. After this scan, we reject the articles detected to have exact quotations at a high rate without initiating peer-review process. Apart from that, we also send back the articles not written in an academic format not to disturb our reviewers unnecessarily.

One of the problems with the articles submitted to our journal and we had to reject was about data analysis. The data is the raw information collected from related resources through research aims. These should be analyzed in parallel with these aims. It is necessary to analyze them using statistics for quantitative data and methods such as content analysis or descriptive analysis for qualitative data. Analysis provides the data being transformed into findings and make sense. Especially, in some of document analysis and some qualitative studies, it is seen that data are presented as findings. In some others, data are presented being only described. It is essential that the studies are formed in an article format obeying the rules by the journal and presented for publication afterwards.

As always, we present the six articles got through peer-review process and given DOI number to you dear producers and consumers of knowledge. I wish these studies conducted in various fields of educational sciences will be useful and contribute to theoretical knowledge within the field. Hope to meet within the next issue.

Sincerely yours,
RECONSIDERING HOPE
Authors: Blanchet Clément 
Published: December 2016

Zusammenfassung:
Architektur und Urbanismus können wir als zwei Bereiche beschreiben, die versuchen durch einige ziemlich ernstzunehmende und gefährliche Phänomene immun zu werden, wie sie im folgenden Beitrag beschrieben werden. Die Widerständigkeit, die Nostalgie, der Zufall, das Bild, die Verführung, die Fragmentierung, die Verpflichtung zu Komplexität, das Unbekannte, die Überdosis sind einige der Beispiele, die ich ausführen werde, als mögliche Miszellaneen giftiger Substanzen heutiger Architektur. Einige Projekte versuchen, diese Themen aufzugreifen.
Die Zukunft der Architektur mag darin liegen, sich gegen ein Gift zu wehren, indem man sich verschiedene toxische Produkte zuführt. Immunität wird durch das wiederholte Einnehmen dieser schädlichen Substanzen und eine ständige Dosissteigerung erlangt.
On Dirichlet problem for fractionalp-Laplacian with singular non-linearity
Authors: Mukherjee Tuhina , Sreenadh Konijeti 
Published: December 2016

AbstractIn this article, we study the following fractionalp-Laplacian equation with critical growth and singular non-linearity:(-Δp)s⁢u=λ⁢u-q+uα,u>0 in ⁢Ω,u=0 in ⁢ℝn∖Ω,(-\Delta_{p})^{s}u=\lambda u^{-q}+u^{\alpha},\quad u>0\quad\text{in }\Omega,% \qquad u=0\quad\text{in }\mathbb{R}^{n}\setminus\Omega,where Ω is a bounded domain inℝn{\mathbb{R}^{n}}with smooth boundary∂⁡Ω{\partial\Omega},n>s⁢p{n>sp},s∈(0,1){s\in(0,1)},λ>0{\lambda>0},0<q≤1{0<q\leq 1}and1<p<α+1≤ps*{1<p<\alpha+1\leq p^{*}_{s}}. We use variational methods to show the existence and multiplicity of positive solutions of the above problem with respect to the parameter λ.
Existence via regularity of solutions for elliptic systems and saddle points of functionals of the calculus of variations
Authors: Boccardo Lucio , Orsina Luigi 
Published: December 2016

Abstract
The core of this paper concerns the existence (via regularity) of weak solutions in

W
0

1
,
2

${W_{0}^{1,2}}$

of a class of elliptic systems such as

{

-

div
⁡

(

(

A
+
φ

)

⁢

∇
⁡
u

)

=
f

,

-

div
⁡

(

M
⁢

(
x
)

⁢

∇
⁡
φ

)

=

1
2

⁢

|

∇
⁡
u

|

2

,

$\left\{\begin{aligned} \displaystyle-\operatorname{div}((A+\varphi)\nabla u)&%
\displaystyle=f,\\
\displaystyle-\operatorname{div}(M(x)\nabla\varphi)&\displaystyle=\frac{1}{2}%
\lvert\nabla u\rvert^{2},\end{aligned}\right.$

deriving from saddle points of integral functionals of the type

J
⁢

(
v
,
ψ
)

=

1
2

⁢

∫
Ω

(

A
+

ψ
+

)

⁢

|

∇
⁡
v

|

2

-

1
2

⁢

∫
Ω

M
⁢

(
x
)

⁢

∇
⁡
ψ

⁢

∇
⁡
ψ

-

∫
Ω

f
⁢
v

.

$J(v,\psi)=\frac{1}{2}\int_{\Omega}(A+\psi_{+})\lvert\nabla v\rvert^{2}-\frac{1%
}{2}\int_{\Omega}M(x)\nabla\psi\nabla\psi-\int_{\Omega}fv.$
Was fördert die nachhaltige Integration von Hauptschüler/innen in den Ausbildungsmarkt?
Authors: Kohlrausch Bettina , Richter Maria 
Published: December 2016

Zusammenfassung
Hauptschüler/innen haben besonders häufig Probleme damit, den Übergang in eine vollqualifizierende Ausbildung zu meistern. Um den Schüler/innen diesen Übergang zu erleichtern und Kontakte zu den Betrieben herzustellen, wurden in den letzten Jahren vermehrt Maßnahmen durchgeführt, die stärker auf betriebliche Praxiserfahrungen setzen. Im Beitrag wird am Beispiel eines Interventionsprojekts untersucht, wie nachhaltig solche Maßnahmen bezogen auf den Ausbildungsverlauf sind. Die Befunde zeigen, dass Maßnahmen, die darauf zielen, Diskreditierungsprozesse durch direkten und dauerhaften Kontakt zu den Betrieben abzubauen, für Jugendliche mit einem einfachen Hauptschulabschluss ein vielversprechender Weg sind.
From wood to food: Approaching stakeholder integration in forest-based biorefinery development / Vom Holz zum Lebensmittel: Ein Beitrag zur Integration von Stakeholdern bei der Entwicklung von Holz-Bioraffinerien
Authors: Höher Martin , Schwarzbauer Peter , Menrad Klaus , Hedeler Barbara , Peer Michael , Stern Tobias 
Published: December 2016

Summary
The expansion of existing pulp mills with additional technology processing concepts to forest-based biorefineries implies high risks. A stakeholder-integrated strategy development is therefore more likely to open up such new business opportunities. Therefore, this paper aims to develop and verify a feasible approach. For this purpose, Porter’s deliberate strategy was extended in context of a case study on the production of hemicelluloses for value-added food markets. Considering two different strategies based on technological approaches, the case of pre-extraction can be given preference considering the interests of involved stakeholders regarding food additive marketing. The implementation process of a forest biorefinery remains widely case dependent, but nonetheless this paper provides some guidance concerning realization steps. The study proved that vast concordance between three different stakeholder groups can be achieved in case of two complex options. Hence, coordination of stakeholder interests is feasible in context of technology implementation strategy development.
A Microwave Tunable Bandpass Filter for Liquid Crystal Applications
Authors: Cao Weiping , Jiang Di , Liu Yupeng , Yang Yuanwang , Gan Baichuan 
Published: December 2016

AbstractIn this paper, a novel microwave continuously tunable band-pass filter, based on nematic liquid crystals (LCs), is proposed. It uses liquid crystal (LC) as the electro-optic material to mainly realize frequency shift at microwave band by changing the dielectric anisotropy, when applying the bias voltage. According to simulation results, it achieves 840 MHz offset. Comparing to the existing tunable filter, it has many advantages, such as continuously tunable, miniaturization, low processing costs, low tuning voltage, etc. Thus, it has shown great potentials in frequency domain and practical applications in modern communication.
Body Culture, Play and Identity
Authors: Eichberg Henning , Kosiewicz Jerzy 
Published: December 2016

Abstract
This is the second article of the cycle of portraits of the members of the Editorial Board and Editorial Advisory Board of the journal Physical Culture and Sport. Studies and Research, who are eminent social scientists researching the issue of sport. Among them, there are many world-class professors, rectors and deans of excellent universities, founders, presidents and secretaries-general of continental and international scientific societies and editors of high-scoring journals related to social sciences focusing on sport. The journal Physical Culture and Sport. Studies and Research started its activities in 2008 and gathered many readers, distinguished authors and outstanding reviewers. It is worth taking a moment to present the profiles of the individual editors, thanks to whom the journal keeps getting better and better. The journal is increasingly appreciated internationally particular among the scientists from the humanist and social areas of investigations. The rapidly increasing number of its readers and its surprisingly wide reception, indicated by the number of visits and downloads in English-speaking countries, including hundreds of universities (up to 791 were interested in the content of issue 62 of our magazine), research institutes and related libraries, as well as academics, researchers and students, should be celebrated. These data are derived only from one bibliographic data base (EBSCO). It must be noted that the journal is indexed in 43 bases.
HEPA Promotion in the Environment of Academic Scientists - Preliminary Research
Authors: Cynarski Wojciech J. , Grzywacz Renata , Kubala Krzysztof , Kunysz-Rozborska Magdalena , Podolski Adam , Pawelec Przemysław 
Published: December 2016

Abstract
The theoretical framework for this research is the sociology of leisure and the sociology of health. Because sedentary behaviour (of employees) is a relevant new research area with important health risks, we decided to focus our attention on this subject. Moreover, sedentary behaviour in the workplace seems to be an important topic for the future.
The general aim of the research is to provide a platform for exchange on effective approaches for promoting health-enhancing physical activity among workers, to learn from experiences in different European countries and to promote the most effective approaches across Europe.
Two methods of qualitative research were used. The first was the method of expert judges. By way of direct interview, the statements of nine persons were collected, all of whom were recognised as competent judges. The second method was the analysis of the content of the literature (quality method). Using the computer program Atlas.ti, the respondents and their answers were examined.
Most of the indications (89%) concerned responses indicating physical activity. In general, the experts are quite physically active and keep a healthy (in their opinion) diet. They have both knowledge and appropriate skills in physical education. They point to the growing interest of younger academics in health and fitness, which may be associated with trends in popular culture, such as a sporty lifestyle, the cult of the body, various healthy diets and supplements, etc., that are becoming the universal fashion.
The aim of this work was to provide a platform for exchange on effective approaches to the promotion of health-enhancing physical activity among workers, to learn from experience in different European countries and to promote the most effective approaches across the region. Because the sedentary behaviour of employees is a relevant new research area with important health risks, we decided to focus our attention on this subject.