Miracle-dz/UniFAR-FTUs huggingface dataset:
Late-onset Cerebrotendinous Xanthomatosis with a Novel Mutation in the CYP27A1 Gene

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive, inborn disruption in bile acid synthesis characterized by severe systemic xanthomas, cataracts and neurological injuries occurring before adolescence without elevation of the serum cholesterol or triglyceride levels. CTX is caused by a deficiency of the mitochondrial enzyme sterol 27-hydroxylase, which is encoded by the CYP27A1 gene. We herein report a 50-year-old Japanese woman with late-onset CTX who had no relevant symptoms before the development of bilateral Achilles tendon xanthomas in middle age. A genetic analysis revealed a compound heterozygous mutation in the CYP27A1 gene with a previously known missense mutation (NM_000784.3:c.1421 G>A) and a novel frame shift mutation of NM_000784. 3:c. 1342_1343insCACC.
Occludin S471 Phosphorylation Contributes to Epithelial Monolayer Maturation

ABSTRACT Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size-reductive proliferation and differentiate, creating a dense, highly ordered monolayer with high resistance barriers. We provide evidence that the tight junction protein occludin contributes to the regulation of epithelial cell maturation upon phosphorylation of S471 in its coiled-coil domain. Overexpression of a phosphoinhibitory occludin S471A mutant prevents size-reductive proliferation and subsequent tight junction maturation in a dominant manner. Inhibition of cell proliferation in cell-contacted but immature monolayers recapitulated this phenotype. A kinase screen identified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction maturation. We conclude that occludin contributes to the regulation of size-reductive proliferation and epithelial cell maturation in a phosphorylation-dependent manner.
Non-Orthogonal Coded Access for Contention-Based Transmission in 5G

The fifth generation (5G) wireless network faces unprecedented massive concurrent random access requests in uplink (UL) contention-based (CB) transmission. In this paper, a non-orthogonal coded access (NOCA) UL transmission in combination with parallel interference cancellation (PIC) based reception scheme at base station is investigated. Non-orthonormal code generated by Zadoff-Chu (ZC) sequences is used to spread the data bits over orthogonal frequency division multiple (OFDM) symbols. It is shown through both link level and system level simulations that in dense urban scenario NOCA-PIC scheme is capable of working in highly overloaded system conditions. It can support more than 4 times concurrent random access number compared with OFDM based CB transmission.
Sharecropper’s Tuberculosis: Pathologies of Power in a Fatal Outbreak

ABSTRACT Tuberculosis Bacilli (TB) is a global scourge that affects poor people and regions. Drawing on Farmer’s (2003) pathologies of power, and a case study approach, we examine the sociostructural landscape of a fatal outbreak of Sharecropper’s TB among African Americans in rural Alabama. In a mixed-method qualitative approach involving oral history, surveys, interviews and documentary analysis, we identified three pathologies that contribute to TB susceptibility: corporate power, land wealth, and structural racism. While medicine can cure non-resistant forms of TB, control of future outbreaks will depend upon a social “cure” such as addressing structural inequality and building community trust in the health system. Video abstract Read the transcript Watch the video on Vimeo
Deposited in DRO : 01 February 2016 Version of attached le : Accepted Version Peer-review status of attached

13 The spatial pattern and morphometry of bedforms and their relationship to sediment thickness have 14 been analysed in the Marguerite Bay Palaeo-Ice Stream Trough, western Antarctic Peninsula. Over 15 17,000 glacial landforms were measured from geophysical datasets, and sediment thickness maps 16 were generated from acoustic sub-bottom profiler data. These analyses reveal a complex bedform 17 pattern characterised by considerable spatial diversity, influenced heavily by the underlying 18 substrate. The variability in length and density of mega-scale lineations indicates an evolving 19 bedform signature, whereby landforms are preserved at different stages of maturity. Lineation 20 generation and attenuation is associated with regions of thick, soft till where deformation was likely 21 to be greatest. The distribution of soft till and the localised extent of grounding-zone wedges (GZWs) 22 indicate a dynamic sedimentary system characterised by considerable spatio-temporal variability in 23 sediment erosion, transport and deposition. Formation of GZWs on the outer shelf of Marguerite 24 Trough, within the error range of the radiocarbon dates, requires large sediment fluxes (upwards of 25 1000 m yr per meter width of grounding line), and a >1 m thick mobile till layer, or rapid basal 26 sliding velocities (upwards of 6 km yr). 27
Experimental evidence that density mediates negative frequency‐dependent selection on aggression

Aggression can be beneficial in competitive environments if aggressive individuals are more likely to access resources than non-aggressive individuals. However, variation in aggressive behaviour persists within populations, suggesting that high levels of aggression might not always be favoured. The goal of this study was to experimentally assess the effects of population density and phenotypic frequency on selection on aggression in a competitive environment. We compared survival of two strains of Drosophila melanogaster that differ in aggression across three density treatments and five frequency treatments (single strain groups, equal numbers of each strain and strains mixed at 3:1 and 1:3 ratios) during a period of limited resources. While there was no difference in survival across single-strain treatments, survival was strongly density dependent, with declining survival as density increased. Furthermore, at medium and high densities, there was evidence of negative frequency-dependent selection, where rare strains experienced greater survival than common strains. However, there was no evidence of negative frequency-dependent selection at low density. Our results indicate that the benefits of aggression during periods of limited resources can depend on the interaction between the phenotypic composition of populations and population density, both of which are mechanisms that could maintain variation in aggressive behaviours within natural populations.
Bridged-T Coil for Miniature Dual-Band Branch-Line Coupler and Power Divider Designs

In this paper, a new design method for bridged-T coil (BTC) is proposed such that it can be made equivalent to two different transmission line sections at two different frequencies. In this way, on-chip dual-band branch-line coupler and dual-band power divider designs with very compact circuit sizes can be made possible through the use of BTCs. Specifically, the proposed 2.45/5.8-GHz dual-band branch-line coupler realized using the integrated passive device (IPD) process features a compact circuit size of only <inline-formula> <tex-math notation="LaTeX">$2.8~\text {mm} \times 1.4$ </tex-math></inline-formula> mm while the proposed 2.4/5.5-GHz dual-band power divider in IPD exhibits a very small circuit size of only <inline-formula> <tex-math notation="LaTeX">$1.8~\text {mm} \times 1.7$ </tex-math></inline-formula> mm. To the best of our knowledge, the proposed dual-band branch-line coupler is the smallest one ever reported while the circuit size of the proposed dual-band power divider is comparable to the smallest in the literature.
Disparity map refinement method using coarse-to-fine image segmentation

Stereo matching methods are used mainly to obtain the depth information in stereo images. Since stereo images are taken from two different viewpoints for the same scene, we have occlusion regions that are visible in only one image, but not in the other image. Because the occlusion region lacks information on corresponding points, disparity errors occur in the disparity map. In order to correct the occlusion region, we propose a disparity map refinement method based on coarse-to-fine (CTF) image segmentation. Experimental results show the proposed method generates a higher quality depth information than other methods; in particular the proposed method reduces disparity errors in discontinuity regions.
Altered macromolecular pattern and content in the aging human brain

The resonances originating from proteins underlie those of metabolites in brain 1H nuclear magnetic resonance (NMR) spectra. These resonances have different physical properties from those of metabolites, such as shorter T1 and T2 relaxation time constants. The age dependence of the macromolecular pattern and content in the human brain was investigated with a focus on adults over 66 years of age using ultrahigh‐field in vivo magnetic resonance spectroscopy. Eighteen young and 23 cognitively normal older adults were studied at 7 T. Metabolite spectra were acquired in the occipital cortex and the posterior cingulate cortex with single‐voxel stimulated echo acquisition mode (STEAM) spectroscopy in 14 young and 20 older adults. Macromolecular spectra were acquired in the occipital cortex using an inversion recovery STEAM sequence in four young and three older adults. The macromolecular pattern was apparent over the 0.5–4.5‐ppm range in the inversion recovery spectra and the 0.5–2‐ppm range in the metabolite spectra. Macromolecular content was quantified from metabolite spectra using LCModel and from inversion recovery spectra using integration. Age‐associated differences in the macromolecular pattern were apparent via both types of spectra, with the largest difference observed for the 1.7‐ and 2‐ppm macromolecular resonances. A higher macromolecular content was observed in the older adults for both brain regions. Age‐specific macromolecular spectra are needed when comparing metabolite spectra from subjects of differing ages because of age‐associated differences in macromolecular pattern. Age‐associated pattern and content differences may provide information about the aging process.
The structure of the binary methyltransferase-SAH complex from Zika virus reveals a novel conformation for the mechanism of mRNA capping

Zika virus, a flavivirus like Dengue and West Nile viruses, poses a significant risk as a pathogen in the category of emerging infectious diseases. Zika infections typically cause nonspecific, mild symptoms, but can also manifest as a neurological disorder like Guillain-Barré syndrome. Infection in pregnant women is linked to microcephaly in newborn infants. The methyltransferase domain of the non-structural protein 5 is responsible for two sequential methylations of the 5′-RNA cap. This is crucial for genome stability, efficient translation, and escape from the host immune response. Here we present the crystal structures of the Zika methyltransferase domain in complex with the methyl-donor SAM and its by-product SAH. The methyltransferase-SAH binary complex presents a new conformation of a “closed” or “obstructed” state that would restrict the binding of new RNA for capping. The combination and comparison of our new structures with recently published Zika methyltransferase structures provide a first glimpse into the structural mechanism of Zika virus mRNA capping.
Induction of Human Macrophage Vascular Endothelial Growth Factor and Intercellular Adhesion Molecule-1 by Ureaplasma urealyticum and Downregulation by Steroids

Chronic lung disease (CLD) remains a major cause of morbidity for the prematurely born infant. The pathogenesis of CLD is complex and has not been defined entirely. Infection and lung inflammatory events have been thought to play a key role in the development of CLD. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated and steroids produce some improvement in neonates with this disease. The aim of this study was to investigate if U. urealyticum could stimulate macrophages to produce vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in vitro, which are potentially associated with both early and later pathological changes in the lung during the development of CLD. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≧4 × 107 color-changing units/ml) stimulated human macrophages (phorbol 12-myristate 13-acetate-differentiated THP-1 cell line) to produce VEGF and soluble ICAM-1 in a dose-dependent manner (p < 0.05) measured by ELISA. Likewise, cell surface ICAM-1 (CD54) measured by flow cytometry was increased after stimulation with U. urealyticum. This effect was attenuated by budesonide and dexamethasone (p < 0.05). The mRNA expressions of VEGF and ICAM-1 detected by a semi-quantitative reverse transcriptase polymerase chain reaction were also induced in response to U. urealyticum and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-α production was neutralized with an anti-TNF-α antibody. Our findings imply that U. urealyticum might be involved in the development of CLD of prematurity.
A Novel Design of Membership Authentication and Group Key Establishment Protocol

A new type of authentication, called group authentication, has been proposed recently which can authenticate all users belonging to the same group at once in a group communication. However, the group authentication can only detect the existence of nonmembers but cannot identify who are the nonmembers. Furthermore, in a group communication, it needs not only to authenticate memberships but also to establish a group key among all members. In this paper, we propose a novel design to provide both membership authentication and group key establishment. Our proposed membership authentication can not only detect nonmembers but also identify who are the nonmembers. We first propose a basic membership authentication and key establishment protocol which can only support one-time group communication. Then, we extend the basic protocol to support multiple group communications. Our design is unique since tokens of users issued by a group manager (GM) during registration are used for both membership authentication and group key establishment.
British Thoracic Society Clinical Statement on Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations (PAVMs) are structurally abnormal vascular communications that provide a continuous right-to-left shunt between pulmonary arteries and veins. Their importance stems from the risks they pose (>1 in 4 patients will have a paradoxical embolic stroke, abscess or myocardial infarction while life-threatening haemorrhage affects 1 in 100 women in pregnancy), opportunities for risk prevention, surprisingly high prevalence and under-appreciation, thus representing a challenging condition for practising healthcare professionals. The driver for the current Clinical Statement was the plethora of new data since previous hereditary haemorrhagic telangiectasia (HHT) guidelines generated in 2006 and a systematic Cochrane Review for PAVM embolisation in 2011. The British Thoracic Society (BTS) identified key areas in which there is now evidence to drive a change in practice. Due to the paucity of data in children, this Statement focused on adults over 16 years. The Statement spans the management of PAVMs already known to be present (interventional and medical), screening and diagnosis (for PAVMs and HHT) and follow-up of patients following a first diagnosis, intervention or negative screen for PAVMs. The Good Practice Points (in bold) were generated for a target audience of general respiratory, medical and specialist clinicians and were approved by the BTS Standards of Care Committee, before formal peer review and public consultation. The Statement spans embolisation treatment, accessory medical management and issues related to the likelihood of underlying HHT.
Immune checkpoint inhibitors: new strategies to checkmate cancer

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte‐associated protein‐4 (CTLA‐4) or programmed cell death protein 1 (PD‐1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proved challenging. This review summarizes the mechanisms of action of ICIs and outlines important preclinical work that contributed to their development. We explore clinical data that has led to disease‐specific drug licensing, and highlight key clinical trials that have revealed ICI efficacy across a range of malignancies. We describe how ICIs have been used as part of combination therapies, and explore their future prospects in this area. We conclude by discussing the incorporation of these new immunotherapeutics into precision approaches to cancer therapy.
The MNS Blood Group Antigens, Vr (MNS12) and Mta (MNS14), Each Arise from an Amino Acid Substitution on Glycophorin A

Background and Objectives: The antigens, Vr (MNS12) and Mta (MNS14), are low–incidence antigens of the MNS blood group system. The Vr antigen has been found only on the red blood cells (RBCs) of persons of Dutch ancestry whereas the Mta antigen has been found on the RBCs of persons from a wide geographic distribution. The objective of this study was to determine the molecular basis of Vr and Mta. Materials and Methods: Following RT–PCR amplification of total RNA isolated from one Vr+ person (G488) and one Mt(a+) person (GH), the genes encoding glycophorin A (GYPA) and glycophorin B (GYPB) were cloned and sequenced. To confirm the point mutation observed in the cDNA from G488 (Vr+), GYPA exon 3 was cloned and sequenced from the genomic DNA of G488 and a second unrelated Vr+ person (MU). A restriction fragment length polymorphism (RFLP) assay was used to analyze genomic DNA from 11 Mt(a+) persons (10 unrelated) following PCR amplification of GYPA exon 3. Results: The coding sequence of GYPB was normal in both G488 (Vr+) and GH (Mt(a+)). Sequencing data from GYPA clones derived from G488 showed to full length GYPA sequences: A normal GYPA M allele and a GYPA M allele with a point mutation 197C→A. Sequencing of GYPA exon 3 from G488 and MU confirmed the point mutation. Sequencing data drom GYPA clones derived from GH showed two full length GYPA sequences: a normal GYPA M allele and a GYPA N allele with a point mutation 230C→T. RFLP analysis based on the point mutation showed that DNA from 11 Mt(a+) samples were heterozygous for the point mutation. Conclusion: The Vr antigen arises from a point mutation 197C→A on GYPA which is predicted to change serine at position 47 to tyrosine. This change introduces a new α–chymotrypsin cleavage site. The Mta antigen arises from a point mutation 230C→T which is predicted to change threonine at position 58 to isoleucine.
Validation of Digital Microscopy Compared With Light Microscopy for the Diagnosis of Canine Cutaneous Tumors

Integration of new technologies, such as digital microscopy, into a highly standardized laboratory routine requires the validation of its performance in terms of reliability, specificity, and sensitivity. However, a validation study of digital microscopy is currently lacking in veterinary pathology. The aim of the current study was to validate the usability of digital microscopy in terms of diagnostic accuracy, speed, and confidence for diagnosing and differentiating common canine cutaneous tumor types and to compare it to classical light microscopy. Therefore, 80 histologic sections including 17 different skin tumor types were examined twice as glass slides and twice as digital whole-slide images by 6 pathologists with different levels of experience at 4 time points. Comparison of both methods found digital microscopy to be noninferior for differentiating individual tumor types within the category epithelial and mesenchymal tumors, but diagnostic concordance was slightly lower for differentiating individual round cell tumor types by digital microscopy. In addition, digital microscopy was associated with significantly shorter diagnostic time, but diagnostic confidence was lower and technical quality was considered inferior for whole-slide images compared with glass slides. Of note, diagnostic performance for whole-slide images scanned at 200× magnification was noninferior in diagnostic performance for slides scanned at 400×. In conclusion, digital microscopy differs only minimally from light microscopy in few aspects of diagnostic performance and overall appears adequate for the diagnosis of individual canine cutaneous tumors with minor limitations for differentiating individual round cell tumor types and grading of mast cell tumors.
Area-efficient CMOS implementation of NCL gates for XOR-AND/OR dominated circuits

Null conventional logic units are the most important logic units in asynchronous circuits. This paper presents an area-efficient CMOS implementation of Null Conventional Logic (NCL) gates for XOR-AND/OR dominated asynchronous circuits. These optimization of logic gates are based on Binary Decision Diagram (BDD) that produces 25% and 14.29% fewer transistor counts for the proposed logic topology of XOR and AND/OR respectively. Thus, giving a reduced area of more than 14% compared with the conventional NCL logic circuits. The simulation results show the delay and energy consumption can give a reasonable result as compared to conventional approach.
Unusual way of feeding by the deutonymph of Neottialges evansi (Actinotrichida, Astigmata, Hypoderatidae), a subcutaneous parasite of cormorants, revealed by fine structural analyses

The parasitic deutonymphs of hypoderatid mites live within the subcutaneous layer of their avian hosts, where they become greatly engorged despite not having functional mouthparts. The method by which they take up nutrients has been mysterious up to now. Here, we report on the morphology of hypoderatid deutonymphs using scanning and transmission electron microscopy and describe structures that may resolve the mystery. The deutonymph of Neottialges evansi (Hypoderatidae) from the cormorant Phalacrocorax carbo is a simply organized stage lacking both mouthparts and a functional foregut. The structure of midgut and hindgut indicate that they are not capable of processing food. The midgut consists of highly branching flat cells and rarely shows a lumen. Almost the entire space between integument, gut remnants and other organs (synganglion, developing gonads) is filled by huge cells containing protein and glycogen granules and numerous lipid inclusions. The anal opening is minute. The structure of the cuticle and epidermis suggests that nutrients are not absorbed through the general integument. Thus the two main existing hypotheses about feeding modes in hypoderatid deutonymphs, anal vs. integumentary food absorbtion, are not supported. We suggest instead that two pairs of genital papillae showing peculiar microanatomical features are actively involved in movement of liquid materials between host and mite and most probably are the nutrient‐intake organs. J. Morphol. 277:1368–1389, 2016. © 2016 Wiley Periodicals, Inc.