Miracle-dz/UniFAR-FTUs huggingface dataset:
Segregation analysis for hip and elbow dysplasia in the Finnish Rottweiler.

INTRODUCTION Canine hip and elbow dysplasia have been reported as quantitative traits (e.g. Leighton et al., 1977 ; Swenson et al., 1997). In addition to the quantitative inheritance, a possibility of a major gene or mitochondrial inheritance has been suggested (e.g. Janss and Brascamp, 1998 ; Todhunter et al., 1999). Mäki et al. (2002) studied the mode of inheritance in four Finnish dog populations. Existence of segregating major genes was preliminarily assessed based on frequency distributions of hip and elbow dysplasia of the offspring of individual sires. These family specific distributions did not show any sign of major genes, for example multimodality. This does not, however, rule out the possibility of a major gene in either of the traits, as the effect of a major gene would have to be very large to affect the distributions of the traits. In this study a segregation analysis was applied in order to assess the possible existence of major genes affecting hip and/or elbow dysplasia in the Finnish Rottweiler population.
Structures of RNA polymerase II complexes with Bye1, a chromatin-binding PHF3/DIDO homologue

Significance Transcription of protein-coding genes requires transient binding of many different factors to RNA polymerase II. Thus far, crystal structures of only two such factors in complex with RNA polymerase II are known. Here we report crystal structures of a third polymerase-binding protein, bypass of Ess1 (Bye1), in complex with RNA polymerase II in different functional states. We also show that Bye1 binds histone tails with posttranslational modifications that mark active chromatin and discuss models for Bye1 function in a chromatin context. Bypass of Ess1 (Bye1) is a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. Here we show that Bye1 binds with its TFIIS-like domain (TLD) to RNA polymerase (Pol) II, and report crystal structures of the Bye1 TLD bound to Pol II and three different Pol II–nucleic acid complexes. Like TFIIS, Bye1 binds with its TLD to the Pol II jaw and funnel. In contrast to TFIIS, however, it neither alters the conformation nor the in vitro functions of Pol II. In vivo, Bye1 is recruited to chromatin via its TLD and occupies the 5′-region of active genes. A plant homeo domain (PHD) in Bye1 binds histone H3 tails with trimethylated lysine 4, and this interaction is enhanced by the presence of neighboring posttranslational modifications (PTMs) that mark active transcription and conversely is impaired by repressive PTMs. We identify putative human homologs of Bye1, the proteins PHD finger protein 3 and death-inducer obliterator, which are both implicated in cancer. These results establish Bye1 as the founding member of a unique family of chromatin transcription factors that link histones with active PTMs to transcribing Pol II.
Stable three-dimensional metallic carbon with interlocking hexagons

Significance Carbon is an amazing material: it not only forms the chemical basis for all known life but also, because of its rich physics and chemistry, displays an array of structures: from the age-old graphite and diamond to more recent C60 fullerene, 1D nanotube, and 2D graphene. One of the unsolved issues in carbon science has been to find a 3D form of carbon that is metallic under ambient conditions. This paper addresses this important challenge. Using state-of-the-art theoretical calculations, we predict the existence of such a phase that is formed from interlocking hexagons and is dynamically, mechanically, and thermally stable. It is suggested that this new form of carbon may be synthesized chemically by using benzene or polyacenes molecules. Design and synthesis of 3D metallic carbon that is stable under ambient conditions has been a long-standing dream. We predict the existence of such phases, T6- and T14-carbon, consisting of interlocking hexagons. Their dynamic, mechanical, and thermal stabilities are confirmed by carrying out a variety of state-of-the-art theoretical calculations. Unlike the previously studied K4 and the simple cubic high pressure metallic phases, the structures predicted in this work are stable under ambient conditions. Equally important, they may be synthesized chemically by using benzene or polyacenes molecules.
Magnetic Nanocomposite Cilia Tactile Sensor

A multifunctional biomimetic nanocomposite tactile sensor is developed that can detect shear and vertical forces, feel texture, and measure flow with extremely low power consumption. The sensor's high performance is maintained within a wide operating range that can be easily adjusted. The concept works on rigid and flexible substrates and the sensors can be used in air or water without any modifications.
Recomendaciones de expertos sobre el diagnóstico y tratamiento de la hepatitis C crónica en el medio penitenciario

The prevalence of HCV infection in Spanish prisons is very high (38.5%). The characteristics of the infected patients, particularly the high rate of HIV coinfection, makes it very likely that the morbidity and mortality produced by serious liver disease secondary to this infection will increase considerably in the coming years. A group of Spanish experts with experience in patients who are inmates has been invited to establish a series of recommendations for the diagnosis and treatment of chronic hepatitis C infection in Spanish prisons.
Abdominal travmada değişim süreci: Ege Üniversitesi deneyimi

Amaç: Bu makale ile travmadaki değişim sürecinin kliniğimiz hastalarına olan yansımasını değerlendirmeyi amaçladık. Durum deðerlendirmesi: Abdominal travma, özellikle son 20 yılda, hem etiyolojik açıdan hem de travmaya tanısal ve tedavisel yaklaşım açısıdan önemli bir değişim süreci içerisindedir. Yöntem: Temmuz 1994 – Eylül 2005 tarihleri arasında kliniğimizde ameliyat edilen erişkin, künt ve penetran, toplam 601 abdominal travma olgusu, iki farklı zaman diliminde (Dönem I: Temmuz 1994 – Aralık 1999 ve Dönem II: Ocak 2000 – Eylül 2005), retroprospektif olarak değerlendirildi. Bulgular: Yaş ortalaması 33.4 ± 12 olan hastaların %82.6’sının erkek ve %17.4’ünü kadın hastalar oluşturmakta idi. Hastaların %50.7’sinin künt travmaya ve %49.3’unun penetran travmaya maruz kaldığı görüldü. Penetran travma hastalarında en sık kesicidelici alet yaralanması (%31.4) izlenirken künt travmanın en sık trafik kazası (%42) sonucu ortaya çıktığı gözlendi. Dönemler arasında penetran yaralanma oranında artış izlenirken (%41.5 %56, p<0.05), künt travma oranının azaldığı izlendi (%58.5 %44, p<0.05). Diagnostik periton lavajı kullanım sıklığı dönemler arası fark gösterdi (Dönem I: %31.3 – Dönem II: %10.6, p<0.05). Dönem II’de uygulanmaya başlanan nonoperatif yönetim toplam 65 (%24.7) hastaya uygulandı. Penetran travma olgularında Dönem II’de kullanılmaya başlanan diagnostik laparoskopi 153 hastadan 11 (%7.9) hastaya uygulandı. Sonuç: Gelişen teknoloji, alınan önlemler ve değişen algoritmalar ile abdominal travma değişim süreci içerisindedir. Bu değişimin cerrahi eğitimde ve cerrahın pratiğinde önemli etkilere neden olacağı açıktır. Anahtar Kelimeler: Abdominal travma, cerrahi, nonoperatif yaklaşım, diagnostik periton lavajı
Molecular-scale hydrophobic interactions between hard-sphere reference solutes are attractive and endothermic

Significance Hydrophobic interactions and other solvent-mediated noncovalent interactions are decisive for the stability and functionality of biomolecular structures over an extended range of conditions. A molecular theory should explain characteristic temperature dependences and help in modeling biomolecular structures and functions. So far, there has been just one theory of hydrophobic interactions, the Pratt–Chandler (PC) theory. The PC theory has not been definitively tested because of lack of quantitative correspondence between systems convenient for theory, simulation, and experiment. The present work adapts simulation results to atomic-scale hard-core models of the PC theory. Surprisingly, from the perspective of the PC theory, these results show that atomic-scale hydrophobic interactions between hard-sphere solutes are attractive and endothermic, thereby identifying a target for improved theories. The osmotic second virial coefficients, B2, for atomic-sized hard spheres in water are attractive (B2 < 0) and become more attractive with increasing temperature (ΔB2/ΔT < 0) in the temperature range 300 K ≤ T ≤ 360 K. Thus, these hydrophobic interactions are attractive and endothermic at moderate temperatures. Hydrophobic interactions between atomic-sized hard spheres in water are more attractive than predicted by the available statistical mechanical theory. These results constitute an initial step toward detailed molecular theory of additional intermolecular interaction features, specifically, attractive interactions associated with hydrophobic solutes.
Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis

Significance Stormorken syndrome is a rare autosomal-dominant genetic condition characterized by congenital miosis, bleeding diathesis, thrombocytopenia, and proximal muscle weakness. Other manifestations include functional or anatomical asplenia, ichthyosis, headaches, and dyslexia. A milder form of Stormorken syndrome is associated with muscle weakness and congenital miosis, but without hematologic abnormalities. Here we identify the gene mutations responsible for these syndromes and show that both conditions are caused by the hyperactivation of the Ca2+ release-activated Ca2+ (CRAC) channel. These findings contrast the pathologies associated with loss or diminished function of the CRAC channel, provide new molecular insights of the function of the CRAC channel, and suggest new approaches to combat these conditions by blocking CRAC channel activity. Signaling through the store-operated Ca2+ release-activated Ca2+ (CRAC) channel regulates critical cellular functions, including gene expression, cell growth and differentiation, and Ca2+ homeostasis. Loss-of-function mutations in the CRAC channel pore-forming protein ORAI1 or the Ca2+ sensing protein stromal interaction molecule 1 (STIM1) result in severe immune dysfunction and nonprogressive myopathy. Here, we identify gain-of-function mutations in the cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital miosis and tubular aggregate myopathy but without hematological abnormalities. Heterologous expression of STIM1 p.R304W results in constitutive activation of the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of Stormorken syndrome. p.P245L in ORAI1 does not make a constitutively active CRAC channel, but suppresses the slow Ca2+-dependent inactivation of the CRAC channel, thus also functioning as a gain-of-function mutation. These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca2+ entry in the treatment of patients with Stormorken syndrome and related pathologic conditions.
Acute inflammation primes myeloid effector cells for anti-inflammatory STAT6 signaling

The anti-inflammatory drug high-dose intravenous immunoglobulin, widely used to suppress inflammation, depends on a specific α-2,6-sialylated glycoform of IgG Fc to induce Interleukin 4 (IL-4) and Signal Transducer and Activator of Transcription 6 (STAT6) signaling for its activity. Here we show that anti-inflammatory activities of IL-4 can be attributed to the direct action of this cytokine on myeloid effector cells, depending on their expression of the IL-4 receptor alpha chain (IL-4Rα/CD124). However, in their basal state, these cells express low levels of IL-4Rα and would not be expected to result in significant signaling compared with other cell populations. This apparent paradox can be explained by the observation that during inflammation, triggered by a variety of stimuli (including autoantibodies, adjuvants, and TLR ligands), IL-4Rα is up-regulated specifically on these cells, priming them for STAT6 signaling. The regulation is mediated by a soluble, proteinase K-sensitive factor, released to the circulation by bone marrow-derived, non-B/non-T cells found in several organs, including the lungs, and fat. We propose that this regulation is part of a homeostatic mechanism to limit excessive inflammation and tissue damage. High-dose intravenous immunoglobulin thus exploits an endogenous feedback loop, general to inflammation, that could be further targeted for therapeutic purposes.
Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Significance High adjuvant doses are generally required to induce strong CD8+ T-cell immunity with subunit vaccines. Here we codeliver an antigen and an adjuvant coupled on separate ultrasmall polymeric nanoparticles. Because both payloads are attached to similarly sized nanoparticles, and as size is the principle determinant of nanoparticle drainage, this enhanced the dual uptake of antigen and adjuvant by cross-presenting dendritic cells resident in the draining lymph nodes. This cotargeting induced potent effector CD8+ T cells and a more powerful memory recall of these cytotoxic T cells compared with nanoparticle-conjugated antigen with free adjuvant. As such, nanoparticle conjugation enhanced the immunogenicity of adjuvants while maintaining a low dose, and thus limiting toxicity, affecting the design of future subunit vaccine formulations. In subunit vaccines, strong CD8+ T-cell responses are desired, yet they are elusive at reasonable adjuvant doses. We show that targeting adjuvant to the lymph node (LN) via ultrasmall polymeric nanoparticles (NPs), which rapidly drain to the LN after intradermal injection, greatly enhances adjuvant efficacy at low doses. Coupling CpG-B or CpG-C oligonucleotides to NPs led to better dual-targeting of adjuvant and antigen (codelivered on separate NPs) in cross-presenting dendritic cells compared with free adjuvant. This led to enhanced dendritic cell maturation and T helper 1 (Th1)-cytokine secretion, in turn driving stronger effector CD8+ T-cell activation with enhanced cytolytic profiles and, importantly, more powerful memory recall. With only 4 μg CpG, NP-CpG-B could substantially protect mice from syngeneic tumor challenge, even after 4 mo of vaccination, compared with free CpG-B. Together, these results show that nanocarriers can enhance vaccine efficacy at a low adjuvant dose for inducing potent and long-lived cellular immunity.
Flexible Nanogenerators for Energy Harvesting and Self‐Powered Electronics

Flexible nanogenerators that efficiently convert mechanical energy into electrical energy have been extensively studied because of their great potential for driving low‐power personal electronics and self‐powered sensors. Integration of flexibility and stretchability to nanogenerator has important research significance that enables applications in flexible/stretchable electronics, organic optoelectronics, and wearable electronics. Progress in nanogenerators for mechanical energy harvesting is reviewed, mainly including two key technologies: flexible piezoelectric nanogenerators (PENGs) and flexible triboelectric nanogenerators (TENGs). By means of material classification, various approaches of PENGs based on ZnO nanowires, lead zirconate titanate (PZT), poly(vinylidene fluoride) (PVDF), 2D materials, and composite materials are introduced. For flexible TENG, its structural designs and factors determining its output performance are discussed, as well as its integration, fabrication and applications. The latest representative achievements regarding the hybrid nanogenerator are also summarized. Finally, some perspectives and challenges in this field are discussed.
Cytogenetics of paediatric and adolescent acute lymphoblastic leukaemia

Cytogenetics has determined the incidence and prognostic significance of chromosomal abnormalities in acute lymphoblastic leukaemia (ALL). The development of fluorescence in situ hybridization (FISH) and array technologies has led to the discovery of novel aberrations. Five ‘hot topics’ are presented in which cytogenetics and related techniques have been instrumental in understanding the role of genetics in leukaemogenesis: (i) genetic changes are integral to the biology of T‐cell ALL; (ii) intrachromosomal amplification of chromosome 21 is a new recurrent abnormality in precursor‐B ALL (BCP‐ALL); (iii) the immunoglobulin heavy chain gene (IGH@) is significant in BCP‐ALL; (iv) alterations in genes involved in B‐cell development and cell cycle control contribute to the pathogenesis of BCP‐ALL; (v) age‐related cytogenetic profiles define ALL in children and adolescents as distinct biological entities. In this molecular era, cytogenetics continues to be integral to our understanding of the genetics of this disease.
Patients with chemotherapy‐refractory mantle cell lymphoma experience high response rates and identical progression‐free survivals compared with patients with relapsed disease following treatment with single agent bortezomib: results of a multicentre phase 2 clinical trial

The recent approval of bortezomib for the treatment of mantle cell lymphoma (MCL) by the US Food and Drug Administration is based on the results of the multicentre PINNACLE study with supportive data from a number of single and multicentre Phase 2 studies. This multicentre Phase 2 study enroled 40 patients with heavily pretreated MCL. The overall response rate (ORR) was 47%, including 5 complete remissions and 14 partial remissions. Overall, these remissions are relatively durable. The ORR in relapsed and refractory patients was 50% and 43% respectively (P = 0·74), while both populations of patients exhibited essentially similar progression‐free survival (PFS; 5·6 months vs. 3·9 months, P = 0·81). Responding patients experienced a PFS from bortezomib that was similar to their line of prior therapy (7·8 months vs. 8·4 months, respectively). The data showed similar responses in relapsed and refractory patients as well as remission durations similar to prior therapy, suggesting that there may be little cross‐resistance with other conventional cytotoxic agents. Importantly, these data suggest that MCL patients with refractory or poorly responsive disease may still derive meaningful clinical benefit from treatment with bortezomib.
Giant Nonlinearity of an Optically Reconfigurable Plasmonic Metamaterial

Metamaterial nanostructures actuated by light give rise to a large optical nonlinearity. Plasmonic metamolecules on a flexible support structure cut from a dielectric membrane of nanoscale thickness are rearranged by optical illumination. This changes the optical properties of the strongly coupled plasmonic structure and therefore results in modulation of light with light.
Visible‐Frequency Metasurface for Structuring and Spatially Multiplexing Optical Vortices

A multifocus optical vortex metalens, with enhanced signal-to-noise ratio, is presented, which focuses three longitudinal vortices with distinct topological charges at different focal planes. The design largely extends the flexibility of tuning the number of vortices and their focal positions for circularly polarized light in a compact device, which provides the convenience for the nanomanipulation of optical vortices.
Lesões coronarianas de bifurcação: classificação, estratégias de tratamento e perspectivas

The occurrence of coronary lesions that involve side branches, with greater or lesser risk of occlusion, is not a rare event. The percutaneous treatment of these bifurcation lesions is a challenge to interventional cardiology. Their extremely varied presentation, whether due to the arrangement of the branches, or to the plaque distribution in the branches, has resulted in the description of several classifications. When coronary angioplasty was performed only with balloon catheters, many techniques were described. Results at follow up were unsatisfactory. After the introduction of stents, other strategies, using one or two stents, were described. However, the rates of target lesion revascularization remained high. Although, the use of drug-eluting stents has shown better results than bare metal stents, they are not totally convincing yet, especially in regards to the occurrence of restenosis at the ostia of side branches. Despite of not being a new idea, other models of stents specially designed for the treatment of bifurcation lesions, called dedicated stents, are being tested and some are already on the market. The authors review the classifications of bifurcation lesions and of the proposed treatment strategies, analyze the main currently used techniques with their advantages and disadvantages, as well as comment on the devices being developed for the treatment of such coronary lesions.
What Matters for Education? Evidence for Catalonia

This paper studies the association between socioeconomic factors, school characteristics and children's cognitive and non-cognitive development in Catalonia. We find that children born later in the year, close to the December 31st cutoff date, persistently tend to have lower academic results than those born in the first two quarters. However, we do not observe any difference in non-cognitive development by quarter of birth. The analysis also shows that children who ever attended nursery school do generally better than those who first started at pre-school (P3) or later. Furthermore, we find that family structure matters since children raised in non-nuclear and low educated families tend to underperform others at school. Estimates also indicate that first generation immigrants, especially Africans, have worse academic performance than those born in Spain. There seem to be strong benefits associated to time spent reading and studying languages, computer science and music. Finally, there is inconclusive evidence that students who arrive late in the academic year and those with special needs generate negative peer effects in the classroom.