Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA sequence analysis of GJB2, encoding connexin 26: Observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls

Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of GJB2 in a cohort of hearing impaired patients and a multi‐ethnic control group is reported. Among 610 hearing impaired cases, 43 DNA sequence variations were identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms, 3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and 7 novel variants (G12C, N14D, V63A, T86M, L132V, D159, 592_600delinsCAGTGTTCATGACATTC). Sixteen non‐coding sequence variations were also identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13 novel variants. A diagnosis of GJB2‐associated hearing loss was confirmed for 63 cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases carrying novel or unclassified variants (1.8 %) and 18 cases carrying the controversial V37I variant were identified (3%). In addition, 294 control subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence variations in the coding region of GJB2 were identified among controls including 2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1 controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence variations were identified among controls in the non‐coding regions in and around GJB2 exon 2. Of particular interest among controls were the variability in carrier rates and ethnic stratification of alleles, and the complex genotypes among Asians, 47% of whom carried two to four sequence variations in the coding region of GJB2. These data provide new information about carrier rates for GJB2‐based hearing loss in various ethnic groups and contribute to evaluation of the pathogenicity of the controversial V37I variant. © 2006 Wiley‐Liss, Inc.
The Posttranscriptional Regulator RsmA Plays a Role in the Interaction between Pseudomonas aeruginosa and Human Airway Epithelial Cells by Positively Regulating the Type III Secretion System

ABSTRACT Posttranscriptional regulation of certain virulence-related genes in Pseudomonas aeruginosa is brought about by RsmA, a small RNA-binding protein. During interaction with airway epithelial cells, RsmA promoted actin depolymerization, cytotoxicity, and anti-internalization of P. aeruginosa by positively regulating the virulence-associated type III secretion system.
The Structure of Preferences and Attitudes towards the Timing of the Resolution of Uncertainty

This paper is concerned with the phenomenon of preference for timing in the temporal resolution of uncertainty and its implications for the structure of utility functionals defined on multiperiod consumption programs. Several postulates concerning attitudes towards timing are stated using a new definition of timing premium for early resolution of uncertainty. The analysis provides an axiomatic basis for the specifications of expected utility and the more general weighted utility and implicit weighted utility functionals in temporal models. Copyright 1989 by Economics Department of the University of Pennsylvania and the Osaka University Institute of Social and Economic Research Association.
Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats

Interactions with nucleoporins containing FxFG‐repeat cores are crucial for the nuclear import of RanGDP mediated by nuclear transport factor 2 (NTF2). We describe here the 1.9 Å resolution crystal structure of yeast NTF2‐N77Y bound to a FxFG‐nucleoporin core, which provides a basis for understanding this interaction and its role in nuclear trafficking. The two identical FxFG binding sites on the dimeric molecule are formed by residues from each chain of NTF2. Engineered mutants at the interaction interface reduce the binding of NTF2 to nuclear pores and cause reduced growth rates and Ran mislocalization when substituted for the wild‐type protein in yeast. Comparison with the crystal structure of FG‐nucleoporin cores bound to importin‐β and TAP/p15 identified a number of common features of their binding sites. The structure of the binding interfaces on these transport factors provides a rationale for the specificity of their interactions with nucleoporins that, combined with their weak binding constants, facilitates rapid translocation through NPCs during nuclear trafficking.
Enkephalins: Raman spectral analysis and comparison as function of pH 1-13.

Raman spectral studies are carried out on Leu- and Met-enkephalin as a function of the pH value in the range of 1-13. The molecules are dissolved in KCl solvent and the pH is controlled at each value. Spectral analyses reveal the dependence of the structural conformation on the pH, and a comparison of the two molecules is made in three frequency regions: the tyrosine Fermi doublet (850-830 cm(-1)), aromatic side chains (1650-1550 cm(-1)), and carboxylate (1430-1400 cm(-1)). All regions and frequencies are presented, discussed, and compared for the two molecules.
Fluency with information technology - skills, concepts, and capabilities (2. ed.)

Fluency with Information Technology: Skills, Concepts, and Capabilities, Fourth Edition, equips readers who are already familiar with computers, the Internet, and the World Wide Web with a deeper understanding of the broad capabilities of technology. Becoming Skilled at Information Technology: Terms of Endearment: Defining Information Technology; What the Digerati Know: Exploring the HumanComputer Interface; Making the Connection: The Basics of Networking; Marking Up with HTML: A Hypertext Markup Language Primer; Searching for Truth: Locating Information on the WWW; Searching for Guinea Pig B: Case Study in Online Research. Algorithms and Digitizing Information: To Err Is Human: An Introduction to Debugging; Bits and the "Why" of Bytes: Representing Information Digitally; Following Instructions: Principles of Computer Operation; What's the Plan? Algorithmic Thinking; Light, Sound, Magic: Representing Multimedia Digitally. Data and Information: Computers in Polite Society: Social Implications of IT; Shhh, It's a Secret: Privacy and Digital Security; Fill-in-the-Blank Computing: Basics of Spreadsheets; What If Thinking Helps: Advanced Spreadsheets for Planning; A Table with a View: Database Queries; iDiary: A Case Study in Database Design. Problem Solving: Get with the Program: Fundamental Concepts Expressed in JavaScript; The Bean Counter: A JavaScript Program; Thinking Big: Programming Functions; Once Is Not Enough: Iteration Principles; The Smooth Motion: Case Study in Algorithmic Problem Solving; Computers Can Do Almost {Everything, Nothing}: Limits to Computation; A Fluency Summary: Click to Close. For readers interested in computers, the Internet, the World Wide Web, and a deeper understanding of technology.
Global Health : Where to Now ?

The recently evolving global financial crisis reveals both the fragile state of the global economy and the major long-term implications of an increasingly unfair global economy for global health and human flourishing. We are also at a critical juncture in world history in relation to understanding and endeavoring to counteract the adverse effects of modern life on climate change and our natural environment. If the growing world-wide interest and apparent commitment to global health and environmental security are to have a significant impact it will be necessary for us be deeply introspective about our value system and reconsider what needs to be done to ensure long-term and secure human flourishing in an interdependent world. It is proposed that belief in endless economic growth and emphasis on an entirely medicalized approach to health needs to be replaced by a vision of healthy human life that is achievable and sustainable for a greater proportion of the world’s population.
Endocytic Recycling Proteins EHD1 and EHD2 Interact with Fer-1-like-5 (Fer1L5) and Mediate Myoblast Fusion*

The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved in vesicle trafficking. Myoferlin and dysferlin regulate myoblast fusion and muscle membrane resealing, respectively. Correspondingly, myoferlin is most highly expressed in singly nucleated myoblasts, whereas dysferlin expression is increased in mature, multinucleated myotubes. Myoferlin also mediates endocytic recycling and participates in trafficking the insulin-like growth factor receptor. We have now characterized a novel member of the ferlin family, Fer1L5, because of its high homology to dysferlin and myoferlin. We found that Fer1L5 protein is expressed in small myotubes that contain only two to four nuclei. We also found that Fer1L5 protein binds directly to the endocytic recycling proteins EHD1 and EHD2 and that the second C2 domain in Fer1L5 mediates this interaction. Reduction of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for normal translocation of Fer1L5 to the plasma membrane. The characterization of Fer1L5 and its interaction with EHD1 and EHD2 underscores the complex requirement of ferlin proteins and mediators of endocytic recycling for membrane trafficking events during myotube formation.
High Sucrose Intake at 3 Years of Age Is Associated with Increased Salivary Counts of Mutans Streptococci and Lactobacilli, and with Increased Caries Rate from 3 to 16 Years of Age

Objective: We aimed to study the long-term associations between sucrose intake (SI), selected representatives of the cariogenic oral flora, and the dental health of children from 3 to 16 years of age. Methods: At 7 months of age 1,062 infants (540 intervention; 522 controls) were included in the prospective, randomised STRIP-project aimed at restricting the child's saturated fat and cholesterol intake to prevent atherosclerosis when they become adults. At 3 years of age, every fifth child was invited (n = 178) to an oral sub-study, and 148 (78 boys) children attended. A restudy was conducted on 135 children aged 6, 127 aged 9, 114 aged 12 and 88 aged 16. SI using 4-day food records, plate-cultured mutans streptococci (MS), salivary lactobacilli (LB) and yeasts using commercial kits (Orion Diagnostica, Espoo Finland), toothbrushing frequency using fluoridated toothpaste and dental health expressed as d3mft/D3MFT were regularly recorded. Results: The SI of children whose intake was ≥10 E% (high SI) at 3 years remained high throughout the entire follow-up (p < 0.001, GLM for repeated measures) period, and they had higher salivary MS and LB counts (p = 0.024 and p = 0.068, respectively, GLM) than their counterparts whose SI was below 10 E% (low SI). No differences in toothbrushing habits were found between the high and low SI-groups. Caries-survival was strongly associated with low 6-year-counts of MS (p = 0.008, Cox regression analysis), and the d3mft/D3MFT-scores of the high SI-group were higher than those of the low SI-group (p = 0.046, GLM). Conclusions: High SI at 3 years was associated with high MS-counts (≥105 cfu/ml) and with a high risk for caries.
Novel lynx spider toxin shares common molecular architecture with defense peptides from frog skin

A unique 30‐residue cationic peptide oxyopinin 4a (Oxt 4a) was identified in the venom of the lynx spider Oxyopes takobius (Oxyopidae). Oxt 4a contains a single N‐terminally located disulfide bond, Cys4–Cys10, and is structurally different from any spider toxin studied so far. According to NMR findings, the peptide is disordered in water, but assumes a peculiar torpedo‐like structure in detergent micelles. It features a C‐terminal amphipathic α‐helical segment (body; residues 12–25) and an N‐terminal disulfide‐stabilized loop (head; residues 1–11), and has an unusually high density of positive charge in the head region. Synthetic Oxt 4a was produced and shown to possess strong and broad‐spectrum cytolytic and antimicrobial activity. cDNA cloning showed that the peptide is synthesized in the form of a conventional prepropeptide with an acidic prosequence. Unlike other arachnid toxins, Oxt 4a exhibits striking similarity with defense peptides from the skin of ranid frogs that contain the so‐called Rana‐box motif (a C‐terminal disulfide‐enclosed loop). Parallelism or convergence is apparent on several levels: the structure, function and biosynthesis of a lynx spider toxin are mirrored by those of Rana‐box peptides from frogs.
Integrin Leukocyte Function-associated Antigen-1-mediated Cell Binding Can Be Activated by Clustering of Membrane Rafts*

The leukocyte function-associated antigen-1 (LFA-1) integrin (CD11a/CD18) is an important adhesion molecule for lymphocyte migration and the initiation of an immune response. At the cell surface, LFA-1 activity can be regulated by divalent cations that enhance receptor affinity but also by membrane clustering induced by treatment of cells with substances such as phorbol esters. Membrane clustering leads to increased LFA-1 avidity. We report here that LFA-1-mediated binding of mouse thymocytes or activated T lymphocytes to intercellular adhesion molecule 1 can be rapidly induced by clustering of membrane rafts using antibodies to the glycosylphophatidylinositol-anchored molecule CD24 or cholera toxin (CTx). CD24 and CD18 were found to co-localize in rafts and cross-linking with CTx lead to enhanced LFA-1 clustering. We observed that disruption of raft integrity by lowering the membrane cholesterol content abolished the CTx and the phorbol 12-myristate 13-acetate-induced LFA-1 binding but left the ability to activate LFA-1 with Mg2+/EGTA unimpaired. In contrast to activation with Mg2+/EGTA, activation via raft clustering was dependent on PI3-kinase, required cytoskeletal mobility, and was accompanied by Tyr phosphorylation of a 18-kDa protein. Our results support the notion that rafts as preformed adhesion platforms could be important for the rapid regulation of lymphocyte adhesion.
Possible relationship between Staphylococcus aureus colonizing the respiratory tract and rectum and S. aureus isolated in a geriatric hospital environment.

tion, including molecular analysis, is available regarding the relationship between colonization and S. aureus environmental contamination in long-term care (LTC) institutions. In this study, we performed a 12-week prospective culture survey to investigate the possible relationship between S. aureus types colonizing the respiratory tract and rectum, and S. aureus types isolated from the hospital environment. The setting was an 8-bed room for the seriously ill patients in a geriatric LTC ward (180 beds) of Aino Memorial Hospital. The average length of hospital stay was 110 days. Ten patients (1 male and 9 females; mean age, 81.4 years) were admitted to the roombetween September and December 1996. Informed consent was obtained from either the patient or their families. Infection control measures included hand washing and disinfection of the upper respiratory tract
A multi-agent based load balancing system in IaaS cloud environment

Infrastructure as a service (IaaS) is a type of cloud computing in which a third-party provider hosts virtualized computing resources over the Internet for executing tasks in the cloud computing. Whenever some VMs are overloaded and some VMs are under loaded, this situation may cause to SLA violation and leads to the reduction of customer satisfaction level and further affects the cloud provider leading to penalty. However, in this study, we propose a Multiple Agent-based Load Balancing Algorithm (MA) in which shift the load in the IaaS to achieve well dynamic load balancing across virtual machines for maximizing the utilization. The proposed algorithm with regard to changing environment and characteristics of the VMs, perform both of sender-initiated and receiver-initiated approach to balances the load of an IaaS in such a way that the amount of waiting time of the tasks in the queue is minimal and at the same time the SLA is guaranteed.We have compared the proposed algorithm with existing load balancing and scheduling algorithms via simulation. The simulation results show that the proposed algorithm is more effective and there is a good improvement in the load-balance, response time and makespan.
Effect of Stress Level on Different Forms of Self-Touch in Pre- and Postadolescent Girls

ABSTRACT Self-touch serves for regulation of both hyper- and hypoarousal. It remains unclear if different forms of self-touch occur in different contexts, and if the regulatory mechanisms are learned or innate. The authors describe forms and context of self-touch, and explore age differences in stress processing. They analyzed hand movements of 10 pre- and 10 postadolescent girls in low-stress and high-stress settings and found 3 forms of self-touch. In postadolescent participants, self-touch 2 (irregular structure, rhythmical, medium intensity) and 3 (phasic structure, single accent, medium intensity) were used for self-regulation, whereas self-touch 1 (irregular structure, single accent, low intensity) had conversational reasons. Increasing immobility might represent the inward focus of stressed participants that tried to focus on the task. No differences were found for preadolescent participants. Differences between pre- and postadolescent participants might be due to brain development during adolescence.
Some puzzling situations in the onset, occurrence and future of coronary heart disease in developed and developing populations, particularly such in sub-Saharan Africa

Coronary heart disease (CHD) was rare in developed populations until the early 1900s; this prevailed even among the small segments who were prosperous and who, in measure, had most of the currently recognised risk factors. However, in the 1930s, with improved circumstances from general rises in socio-economic state, there were major increases in the occurrence and mortality rate from the disease, the latter reaching a third of the total mortality in some countries, as in the United Kingdom (UK). Puzzlingly, the inter-population diversity of the increases in CHD has been such that there are as much as five fold differences in CHD mortality rates, as, for example, between Poland and Spain. Within recent years, with appropriate treatments, the mortality rate has halved in some countries, again, as in the UK. However, the incidence rate of the disease has diminished little or hardly at all. Risk factors include a familial component and, nutritionally, over-eating, a high fat intake, relatively low intakes of plant foods, especially of vegetables and fruit and, non-nutritionally, smoking, excessive alcohol consumption and a low level of everyday physical activity. On the one hand, known risk factors, broadly, are considered to be capable of explaining only about half of the variation in the occurrence of the disease. Even at present, known risk factors far from fully explain the epidemiological differences in mortality rates. Yet, on the other hand, there is abundant evidence that in population groups, among whom risk factors are low or have been reduced, CHD incidence and mortality rates are lower. Notwithstanding this knowledge, broadly, there is very little interest in the general public in taking avoiding measures. As to the situation in developing populations, in sub-Saharan Africa, in urban Africans, as in Johannesburg, South Africa, despite considerable westernisation of life style and with rises in risk factors, CHD remains of very low occurrence, the situation thereby resembling, historically, its relatively slow emergence in developed populations. In most eastern countries, mortality rates remain relatively low, as in Russia and Japan. However, in major contrast, in India, rates have risen considerably in urban dwellers. Indeed, in Indian immigrants, as in those in the UK, their rate actually exceeds that in the country’s white population. In brief, much remains to be explained in the epidemiology of the disease.
Perinatal complications associated with maternal tobacco use.

The use of tobacco products by pregnant women is associated with placenta previa, abruptio placentae, premature rupture of the membranes, preterm birth, intrauterine growth restriction and sudden infant death syndrome. Approximately 15-20% of women smoke during pregnancy. It has been suggested that smoking is responsible for 15% of all preterm births, 20-30% of all infants of low birthweight, and a 150% increase in overall perinatal mortality. Cigarette smoking is one of the most important and modifiable risk factors associated with adverse perinatal outcomes.
A 4Kx8 dynamic RAM with self-refresh

A 4K/spl times/8 MOS dynamic RAM using a single transistor cell with on-chip self-refresh is described. The device uses a multiplexed address/data bus. Control of the reconfigurable data bus allows the RAM to operate on either an 8-bit or a 16-bit data bus. The memory cell is fabricated using a double polysilicon n-channel HMOS technology using polysilicon word lines and metal bit lines. Self-refresh is implemented with an on-chip timer, arbiter, counter and multiplexer. A high-speed arbiter resolves simultaneous memory and refresh requests. Redundant rows are used for increased manufacturing yields. Polysilicon fuses are electrically programmed to select redundant rows.
Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Abstract Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lungs 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.