Miracle-dz/UniFAR-FTUs huggingface dataset:
Leu432Val polymorphism in CYP1B1 as a susceptible factor towards predisposition to primary open-angle glaucoma

Purpose Defects in cytochrome P450 1B1 (CYP1B1) cause primary congenital glaucoma. However, defects in the gene have also been reported in primary open-angle glaucoma (POAG). Since POAG is primarily a complex disease, we examined the potential of coding single nucleotide polymorphisms (cSNPs) in the gene for association with the disease. Methods Five coding SNPs – c.514 C>G (Arg48Gly), c.727 G>T (Ala119Ser), c.1666 C>G (Leu432Val), c.1719 C>T (Asp449Asp), and c.1730 A>G (Asn453Ser) – were genotyped in 264 unrelated POAG patients and 95 controls. In addition, 542 normal individuals selected from various ethnic groups representing the Indian population were also genotyped for these cSNPs. The patterns of linkage disequilibrium between the SNPs and haplotype variations for comparison between POAG patients and controls as well as different ethnic groups of the Indian population were determined using Haploview. Allelic variants of Leu432Val were cloned by site-directed mutagenesis of normal CYP1B1 cDNA, which were used for transfection of retinal pigment epithelium (RPE) cells. The generation of reactive oxygen species (ROS) was quantified by measuring fluorescence emission by degradation of CM-H2DCFDA using a fluoremeter. Results The c.1666G allele of the Leu432Val in CYP1B1 showed a statistically significant higher representation among POAG patients compared to controls (p=0.0001; Odds ratio=6.027; 95% CI: 3.863–9.401) suggesting it to be a potential risk allele toward disease predisposition. Analysis of genotype frequencies of the polymorphism between the two groups demonstrated GG as a potential risk genotype (p=0.0001; Odds ratio=15.505; 95% CI: 5.529–43.474) for the disease. CYP1B1 Val432 was estimated to generate higher ROS in RPE cells compared to its allelic variant (Leu432; p=0.0245 for 15 min and p=0.0197 for 30 min). Comparison of haplotype diversities revealed CGGTA as the risk haplotype for the disease (p=0.0001, by Fisher’s exact test). Conclusions We report CYP1B1 c.1666G (Val432) as a susceptible allele for POAG and CGGTA as the risk haplotype for the disease. Higher ROS generation by Val432 in CYP1B1 might lead to apoptotic change that leads to glaucoma. Remarkable variation of the cSNPs observed among ethnic groups of India could provide insight for future epidemiological studies on POAG in these population groups.
Multiple Endocrine Neoplasia and Hyperparathyroid-Jaw Tumor Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood

Children and adolescents who present with neuroendocrine tumors are at extremely high likelihood of having an underlying germline predisposition for the multiple endocrine neoplasia (MEN) syndromes, including MEN1, MEN2A and MEN2B, MEN4, and hyperparathyroid-jaw tumor (HPT-JT) syndromes. Each of these autosomal dominant syndromes results from a specific germline mutation in unique genes: MEN1 is due to pathogenic MEN1 variants (11q13), MEN2A and MEN2B are due to pathogenic RET variants (10q11.21), MEN4 is due to pathogenic CDKN1B variants (12p13.1), and the HPT-JT syndrome is due to pathogenic CDC73 variants (1q25). Although each of these genetic syndromes share the presence of neuroendocrine tumors, each syndrome has a slightly different tumor spectrum with specific surveillance recommendations based upon tumor penetrance, including the age and location for which specific tumor types most commonly present. Although the recommended surveillance strategies for each syndrome contain similar approaches, important differences do exist among them. Therefore, it is important for caregivers of children and adolescents with these syndromes to become familiar with the unique diagnostic criteria for each syndrome, and also to be aware of the specific tumor screening and prophylactic surgery recommendations for each syndrome. Clin Cancer Res; 23(13); e123–e32. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.
Social Relations, Firms and Societies

Business systems theory holds that specific nations are locked onto a particular developmental trajectory reflecting differences in both institutional configuration and corresponding social agency; these variations are reflected in the role and structuring of firms and employment practices. This article uses an international survey of firms to test the extent to which specific national business systems are distinguished by the nature and extent of employer-employee interdependence and the degree of delegation to employees. The evidence provides empirical support for the theory, though with some need for subtle modification, showing continuing difference between the employment practices of nations and business systems.
ION CHANNELS , RECEPTORS AND TRANSPORTERS TRPC 6 channels modulate the response of pancreatic stellate cells to hypoxia

Pancreatic cancer is characterized by a massive fibrosis (desmoplasia), which is primarily caused by activated pancreatic stellate cells (PSCs). This leads to a hypoxic tumor microenvironment further reinforcing the activation of PSCs by stimulating their secretion of growth factors and chemokines. Since many of them elicit their effects via Gprotein-coupled receptors (GPCRs), we tested whether TRPC6 channels, effector proteins of many G-proteincoupled receptor pathways, are required for the hypoxic activation of PSCs. Thus far, the function of ion channels in PSCs is virtually unexplored. qPCR revealed TRPC6 channels to be one of the most abundant TRPC channels in primary cultures of murine PSCs. TRPC6 channel function was assessed by comparing PSCs from TRPC6 mice and wildtype (wt) littermates. Cell migration, Ca signaling, and cytokine secretion were analyzed as readout for PSC activation. Hypoxia was induced by incubating PSCs for 24 h in 1% O2 or chemically with dimethyloxalylglycine (DMOG). PSCs migrate faster in response to hypoxia. Due to reduced autocrine stimulation, TRPC6 PSCs fail to increase their rate of migration to the same level as wt PSCs under hypoxic conditions. This defect could not be overcome by the stimulation with plateletderived growth factor. In line with these results, calcium influx is increased in wt but not TRPC6 PSCs under hypoxia. We conclude that TRPC6 channels of PSCs are major effector proteins in an autocrine stimulation pathway triggered by hypoxia.
Pronounced climatic variations in Alaska during the last two millennia

Paired oxygen-isotopic analyses of abiotic carbonate and benthic-ostracode shells from lake sediments provide a continuous quantitative record of growing-season temperature for the past 2000 years in the northwestern foothills of the Alaska Range. This record reveals three time intervals of comparable warmth: anno Domini (A.D.) 0–300, 850-1200, and post-1800, the latter two of which correspond to the Medieval Climatic Anomaly and climatic amelioration after the end of the Little Ice Age. The Little Ice Age culminated at A.D. 1700, when the climate was ≈1.7°C colder than at present. A marked climatic cooling also occurred around A.D. 600, coinciding with extensive glacial advances in Alaska. Comparisons of this temperature record with ostracode trace-element ratios (Mg/Ca, Sr/Ca) further suggest that colder periods were wetter and vice versa during the past 2000 years.
Modeling security protocols using operational semantics

In this paper we develop a formal semantics of security protocols. Its main virtue is that it is a generic model, in the sense that it is parameterized over e.g. the intruder model. Further characteristics of the model are a straightforward handling of parallel execution of multiple protocols, locality of security claims, the binding of local constants to role instances, and explicitly defined initial intruder knowledge. We validate our framework by analyzing the Needham-Schroeder-Lowe protocol.
Unstimulated Primary CD4+ T Cells from HIV-1-Positive Elite Suppressors Are Fully Susceptible to HIV-1 Entry and Productive Infection

ABSTRACT Elite controllers or suppressors (ES) are a group of HIV-1-infected individuals who maintain viral loads below the limit of detection of commercial assays for many years. The mechanisms responsible for this remarkable control are under intense study, with the hope of developing therapeutic vaccines effective against HIV-1. In this study, we addressed the question of the intrinsic susceptibility of ES CD4+ T cells to infection. While we and others have previously shown that CD4+ T cells from ES can be infected by HIV-1 isolates in vitro, these studies were confounded by exogenous activation and in vitro culture of CD4+ T cells prior to infection. In order to avoid the changes in chemokine receptor expression that have been associated with such exogenous activation, we infected purified CD4+ T cells directly after isolation from the peripheral blood of ES, viremic patients, and uninfected donors. We utilized a green fluorescent protein (GFP)-expressing proviral construct pseudotyped with CCR5-tropic or CXCR4-tropic envelope to compare viral entry using a fluorescence resonance energy transfer-based, single-round virus-cell fusion assay. The frequency of productive infection was also compared by assessing GFP expression. CD4+ T cells from ES were as susceptible as or more susceptible than cells from viremic patients and uninfected donors to HIV-1 entry and productive infection. The results of this physiological study strongly suggest that differences in HIV-1 entry and infection of CD4+ T cells alone cannot explain the elite control of viral replication.
From cradle to grave: the relevance of a theology of natality for a theology of death and dying and pastoral care in the church

This thesis explores the relevance of a theology of natality for a theology of death and dying and pastoral care in the church. The concept of natality is drawn from the work of Grace M Jantzen and is characterised by beauty, creativity, newness, flourishing and birth. Following a survey of theological and pastoral approaches to death and dying, natality is expounded and the feminist practical theology research methodology employed described. Data from semi-structured interviews conducted with hospital chaplains, clinical staff, palliative care patients and their relatives/friends, coded according to Jantzen’s main features of natality of embodiment, engenderment, relationality and hope, is then presented and discussed. The data analysis shows that natality is strongly relevant to theology and pastoral care in death and dying, and, contrary to Jantzen, its most significant feature for research participants is not hope but, rather, relationality, as a vital source of hope. This indicates the importance of relationality for pastoral theology and care. Reflection upon this leads to the offering of holding as a metaphor for such theology and pastoral practice, and the recognition of the potential value of further qualitative research surrounding the concept of natality.
Implicit learning in infants with a familial risk of dyslexia: the effects of age and length of training

The current study is a follow-up study on the work of Kerkhoff, De Bree, De Klerk & Wijnen (2011; in press) in which the hypothesis was tested that developmental dyslexia is (partly) caused by a deficit in implicit sequential learning. With the help of a head-turn-experiment it was investigated whether 18-month-old infants at familial risk of dyslexia can track non-adjacent dependencies in an artificial language. A deficit in implicit learning can hinder the processing of such dependencies. For this experiment an artificial language is used to test the tracking of these NAD’s, in the form of a-X-c, b-X-d or a-X-d, b-X-c, with fixed first and third elements and 24 different X elements. Family risk (FR) and typically developing (TD) infants were exposed to one of two novel languages containing these dependencies. The results revealed that only the typically developing infants could discriminate between grammatical and ungrammatical sentences. This was in contrast with the results of the family risk infants, who showed no discrimination between the grammars. To test whether the FR group’s poor performance was due to a developmental delay, the current study exposed a group of 24-month-old FR-infants to the same task (Experiment 1). To investigate whether these children might benefit from an increased exposure to the artificial language, a pilot study also examined whether 18-month-old TD and FR infants are able to discriminate between the grammars after a prolonged familiarization phase (Experiment 2). The results show no evidence that the 24 month-old FR group is sensitive to NAD’s. This could be evidence for a delay in implicit sequence learning of at least six months. Furthermore, the TD infants in the pilot experiment showed a trend towards an unexpected change from a novelty preference to a familiarity preference.
On the Efficiency of Optimising Shallow Backtracking in Compiled Prolog

The cost of backtracking has been identified as one of the bottlenecks in achieving peak performance in compiled Prolog programs. Much of the backtracking in Prolog programs is shallow, i.e. is caused by unification failures in the head of a clause when there are more alternatives for the same procedure, and so special treatment of this form of backtracking has been proposed as a significant optimisation. This paper describes a modified WAM which optimises shallow backtracking. Four different implementation approaches are compared. A number of benchmark results are presented, measuring the relative tradeoffs between compilation time, code size, and run time. The results show that the speedup gained by this optimisation can be significant.
Detection and tracking using wireless sensor networks

Target detection and tracking is a well-established area of research. However, a majority of proposed solutions in existing literature rely on expensive and specialized sensors, which often have limited coverage. Using low cost sensor nodes is an attractive and complementary approach to scalable target detection and tracking applications. However, tracking with low cost Wireless Sensor Network (WSN), presents its own challenges, namely real time decision making, high frequency sampling, multi-modal sensing, complex signal processing, and data fusion. In this work, we investigate the use of inexpensive off-the-shelf WSN devices for ground surveillance. Our system estimates and tracks a target based on the spatial differences of the target object's signal strength detected by the monitoring sensors at different locations.
25 Insecticide Activity of Lectins and Secondary Metabolites

Proteins are polymers of amino acids (molecules containing an amino group, a carboxylic group and a hydrophobic or hydrophilic side chain) present in all organisms. Apolar, polar uncharged and electrically charged amino acids are covalently linked through peptide bonds (amide bonds) and the sequence they form in the polypeptide chain (primary structure) determines the tertiary or quaternary structures ultimately presenting some biological activity. Proteins can be formed by one or multiple polypeptides (subunits) with or without a non-amino acid molecule (carbohydrate, ion, lipid, etc) linked to them. Lectins comprise a heterogeneous group of non-immune proteins that interact with carbohydrates. This interaction is behind a number of biological properties, including antimicrobial, antitumoral, hemagglutinating, mitogenic and insecticide activities. The specificity of the carbohydrate binding site is determined by the amino acids forming the lectin molecule, as well as shape and the spatial arrangement of neighboring amino acids; additionally, metal ions may contribute for correct positioning of the amino acid residues for binding to the carbohydrate (Sharon and Lis, 2001). Lectins can be divided into those that bind monosaccharides as well as oligosaccharides, and those that recognize only oligosaccharides (Sharon and Lis, 2007). Depending on carbohydrate specificity, they can be classified as: glucose/mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, fucose and sialic acid-binding lectins (Wu et al., 2001). The hemagglutinating activity assay (Figure 1A) in presence of free carbohydrates (Figure 1B) has been proved to be a useful tool to characterize lectin specificity. Plant lectins have been isolated from bark, cladodes, flowers, leaves, rhizomes, roots and seeds. They differ from each other with respect to their molecular structures, carbohydratebinding specificities, and biological activities. The compact globular structures, molecular aggregation and glycosylation of lectins in general result in high structural stability (Kawsar et al., 2008; Moreno et al., 2008). In general, lectin isolation procedures include protein extraction steps with aqueous solvent, the production of a lectin-rich fraction, and separation of lectin from protein or non-protein
Application-layer traffic optimization in software-defined mobile networks: A proof-of-concept implementation

Integration of application layer traffic optimization (ALTO) in software-defined mobile networks could have several benefits for orchestration of endpoint selection for distributed services. ALTO can provide guidance, e.g., in the redirection of end users to appropriate in-network cache, content distribution network server or virtual network function instance during service chaining. ALTO service provides appropriate level of abstraction of network and cost maps, enforcing the policies of mobile network operator and optionally other actors, but keeping the privacy of network topology information. SDN controllers can enforce flow redirection and can dynamically provide abstracted network and cost maps to ALTO server. In this paper we present the operation of ALTO in software-defined networks from the point of view of mobile network operators, and describe our proof-of-concept implementation.
Performance Analysis of NOMA With Fixed Gain Relaying Over Nakagami- $m$ Fading Channels

This paper studies the application of cooperative techniques for non-orthogonal multiple access (NOMA). More particularly, the fixed gain amplify-and-forward (AF) relaying with NOMA is investigated over Nakagami-<inline-formula> <tex-math notation="LaTeX">$m$ </tex-math></inline-formula> fading channels. Two scenarios are considered insightfully: 1) the first scenario is that the base station (BS) intends to communicate with multiple users through the assistance of AF relaying, where the direct links are existent between the BS and users and 2) the second scenario is that the AF relaying is inexistent between the BS and users. To characterize the performance of the considered scenarios, new closed-form expressions for both exact and asymptomatic outage probabilities are derived. Based on the analytical results, the diversity orders achieved by the users are obtained. For the first and second scenarios, the diversity order for the <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>th user are <inline-formula> <tex-math notation="LaTeX">$\mu (n+1)$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$\mu \text{n}$ </tex-math></inline-formula>, respectively. Simulation results unveil that NOMA is capable of outperforming orthogonal multiple access (OMA) in terms of outage probability and system throughput. It is also worth noting that NOMA can provide better fairness compared with conventional OMA. By comparing the two scenarios, cooperative NOMA scenario can provide better outage performance relative to the second scenario.
A security infrastructure for distributed Java applications

We describe the design and implementation of a security infrastructure for a distributed Java application. This work is inspired by SDSI/SPKI, but has a few twists of its own. We define a logic for access control, such that access is granted iff a proof that it should be granted is derivable in the logic. Our logic supports linked local name spaces, privilege delegation across administrative domains, and attribute certificates. We use SSL to establish secure channels through which principals can "speak", and have implemented our access control system in Java. While we implemented our infrastructure for the Placeless Documents System, our design is applicable to other applications as well. We discuss general issues related to building secure, distributed Java applications that we discovered.
Lifting Object Detection Datasets into 3D

While data has certainly taken the center stage in computer vision in recent years, it can still be difficult to obtain in certain scenarios. In particular, acquiring ground truth 3D shapes of objects pictured in 2D images remains a challenging feat and this has hampered progress in recognition-based object reconstruction from a single image. Here we propose to bypass previous solutions such as 3D scanning or manual design, that scale poorly, and instead populate object category detection datasets semi-automatically with dense, per-object 3D reconstructions, bootstrapped from:(i) class labels, (ii) ground truth figure-ground segmentations and (iii) a small set of keypoint annotations. Our proposed algorithm first estimates camera viewpoint using rigid structure-from-motion and then reconstructs object shapes by optimizing over visual hull proposals guided by loose within-class shape similarity assumptions. The visual hull sampling process attempts to intersect an object's projection cone with the cones of minimal subsets of other similar objects among those pictured from certain vantage points. We show that our method is able to produce convincing per-object 3D reconstructions and to accurately estimate cameras viewpoints on one of the most challenging existing object-category detection datasets, PASCAL VOC. We hope that our results will re-stimulate interest on joint object recognition and 3D reconstruction from a single image.
Mitochondrial DNA Ligase Is Dispensable for the Viability of Cultured Cells but Essential for mtDNA Maintenance*

Background: Nonviability of cells lacking mitochondrial DNA ligase suggests essential function of this enzyme. Results: We report the isolation of viable Lig3−/− cells, which lack mtDNA. Conclusion: The lethality of the Lig3 knock-out is mediated by the ρ0 phenotype. Significance: This is definitive proof that the essential function of LIG3 in mitochondria is limited to DNA transactions. Multiple lines of evidence support the notion that DNA ligase III (LIG3), the only DNA ligase found in mitochondria, is essential for viability in both whole organisms and in cultured cells. Previous attempts to generate cells devoid of mitochondrial DNA ligase failed. Here, we report, for the first time, the derivation of viable LIG3-deficient mouse embryonic fibroblasts. These cells lack mtDNA and are auxotrophic for uridine and pyruvate, which may explain the apparent lethality of the Lig3 knock-out observed in cultured cells in previous studies. Cells with severely reduced expression of LIG3 maintain normal mtDNA copy number and respiration but show reduced viability in the face of alkylating and oxidative damage, increased mtDNA degradation in response to oxidative damage, and slow recovery from mtDNA depletion. Our findings clarify the cellular role of LIG3 and establish that the loss of viability in LIG3-deficient cells is conditional and secondary to the ρ0 phenotype.
TREC 2005 Genomics Track Experiments at IBM Watson

This paper describes our experiments in the TREC 2005 Genomics Track. For the ad-hoc retrieval task, we study synonym-based query expansion, as well as the eectiveness of a new pseudo-relevance feedback method which is derived from our recent work on semi-supervised learning. For the categorization task, we study various methods for estimating conditional class probability and determining the optimal threshold parameter — essential for obtaining high performance results for this task.