Miracle-dz/UniFAR-FTUs huggingface dataset:
The fundamental and medical impacts of recent progress in research on hereditary hearing loss.

What would define real progress in the field of deafness research in fundamental and medical terms? In fundamental terms, progress would be measured by an improvement in our knowledge of the development and physiology of the ear. In medical terms, progress would lead to the division of the broad category of hearing defects into distinct clinical entities or subclasses, the collection of epidemiological data, the creation of molecular diagnostic tests, the improvement of genetic counselling services and the development of new therapeutics. In this review, we will introduce some general considerations on hereditary hearing loss and on the structure and function of the ear, present the rapidly emerging data on the molecular basis of syndromic and non-syndromic forms of hearing loss and comment on relevant recent progress in this field of research. Generally speaking, the isolation of genes underlying hereditary hearing loss has, as yet, had little impact on our understanding of the biology of the ear, whereas it has made major contributions to the medical field, in particular due to the recognition of two genes, Cx26 and mitochondrial 12S rRNA , as frequently underlying cases of non-syndromic hearing impairment.
Transgene Expression in a Syngeneic Bladder Tumor Model through Augmentation of Adenoviral Infection and Adenovirus-Mediated Cytosine Deaminase Gene Therapy Low-Dose Etoposide Enhances Telomerase-Dependent

The human telomerase reverse transcriptase (hTERT) promoter can selectively drive transgene expression in many telomerase-positive human cancer cells. Here we evaluated combination therapy of adenoviral vector Ad-hTERT-CD encoding E. coli cytosine deaminase (CD) driven by the hTERT promoter and low-dose etoposide (0.1 Mg/mL) for treating bladder cancer. Ad-hTERT-CD conferred sensitivity to 5fluorocytosine (5-FC) in bladder cancer cells, which could be enhanced by etoposide treatment, but not in normal cells. Such effect was correlated with up-regulation of hypoxia-inducible factor (HIF)-1A expression. By contrast, etoposide activated p53 and down-regulated hTERT promoter activity in normal cells. Etoposide also increased adenoviral infection via enhancement of coxsackie-adenovirus receptor expression on bladder cancer and normal cells. Combination index analysis revealed that combined therapy of Ad-hTERT-CD (10 plaqueforming units)/5-FC (200 mg/kg) with etoposide (2 mg/kg) synergistically suppressed tumor growth and prolonged survival in mice bearing syngeneic MBT-2 bladder tumors. This combination therapy regimen induced complete tumor regression and generated antitumor immunity in 75% of tumor-bearing mice. Furthermore, increased infiltrating CD4 and CD8 T cells and necrosis within tumors were found in mice receiving combination therapy of Ad-hTERT-CD and etoposide compared with those treated with either treatment alone. Thus, the potential high therapeutic index of the combination therapy may be an appealing therapeutic intervention for bladder cancer. Furthermore, because a majority of human tumors exhibit high telomerase activity, adenovirus-mediated CD gene therapy driven by the hTERT promoter in combination with low-dose etoposide may be applicable to a broad spectrum of cancers. (Cancer Res 2006; 66(20): 9957-66)
Novel Murine Dendritic Cell Lines: A Powerful Auxiliary Tool for Dendritic Cell Research

Research in vitro facilitates discovery, screening, and pilot experiments, often preceding research in vivo. Several technical difficulties render Dendritic Cell (DC) research particularly challenging, including the low frequency of DC in vivo, thorough isolation requirements, and the vulnerability of DC ex vivo. Critically, there is not as yet a widely accepted human or murine DC line and in vitro systems of DC research are limited. In this study, we report the generation of new murine DC lines, named MutuDC, originating from cultures of splenic CD8α conventional DC (cDC) tumors. By direct comparison to normal WT splenic cDC subsets, we describe the phenotypic and functional features of the MutuDC lines and show that they have retained all the major features of their natural counterpart in vivo, the splenic CD8α cDC. These features include expression of surface markers Clec9A, DEC205, and CD24, positive response to TLR3 and TLR9 but not TLR7 stimuli, secretion of cytokines, and chemokines upon activation, as well as cross-presentation capacity. In addition to the close resemblance to normal splenic CD8α cDC, a major advantage is the ease of derivation and maintenance of the MutuDC lines, using standard culture medium and conditions, importantly without adding supplementary growth factors or maturation-inducing stimuli to the medium. Furthermore, genetically modified MutuDC lines have been successfully obtained either by lentiviral transduction or by culture of DC tumors originating from genetically modified mice. In view of the current lack of stable and functional DC lines, these novel murine DC lines have the potential to serve as an important auxiliary tool for DC research.
Recent arecibo timing of the relativistic binary PSR B1534+12

We present a new timing solution for PSR B1534+12, based on coherently-dedispersed observations at Jodrell Bank and, recently, Arecibo. The new data have resulted in improved measurements of the post-Keplerian timing parameters, including the orbital period derivative. At present, the poorly-known distance to the pulsar limits the precision of the measurement of the intrinsic orbital period derivative, and hence the strength of the test of general relativity that results from this binary system. By assuming that general relativity is the correct theory of gravity, we may invert the test and find an improved value of the pulsar distance.
Building Security In

knowledge about vulnerabilities, threats, impacts, and probability. Established risk-analysis method-ologies possess distinct advantages and disadvantages, but almost all of them share some good principles as well as limitations when applied to modern software design. What separates a great software risk assessment from a merely mediocre one is its ability to apply classic risk definitions to software design and then generate accurate mitigation requirements. A high-level approach to iterative risk analysis should be deeply integrated throughout the software development life cycle. 1 In case you're keeping track, Figure 1 shows you where we are in our series of articles about software security's place in the software development life cycle. Traditional terminology Example risk-analysis methodolo-gies for software usually fall into two basic categories: commercial (including Microsoft's STRIDE, Sun's ACSM/SAR, Insight's CRAMM, and Cigital's SQM) and standards-based (from the National Institute of Standards and Technology's ASSET or the Software Engineering Insti-tute's OCTAVE). An in-depth analysis of all existing methodologies is beyond our scope, but we'll look at basic approaches, common features, strengths, weaknesses, and relative advantages and disadvantages. As a corpus, " traditional " method-ologies are varied and view risk from different perspectives. Examples of basic approaches include • financial loss methodologies that seek to provide a loss figure to balance against the cost of implementing various controls; • mathematically derived " risk ratings " that equate risk with arbitrary ratings for threat, probability, and impact; and • qualitative assessment techniques that base risk assessment on anec-dotal or knowledge-driven factors. Each basic approach has its distinctly different merits, but they almost all share some valuable concepts that should be considered in any risk analysis. We can capture these com-monalities in a set of basic definitions: • The asset, or object of the protection efforts, can be a system component , data, or even a complete system. • Risk, the probability that an asset will suffer an event of a given negative impact, is determined from various factors: the ease of executing an attack, the attacker's motivation and resources, a system's existing vul-nerabilities, and the cost or impact in a particular business context. • The threat, or danger source, is invariably the danger a malicious agent poses and that agent's motivations (financial gain, prestige, and so on). Threats manifest themselves as direct attacks on system security. • A vulnerability is a defect or weakness in system security procedure, design, implementation, or internal control that …
Gender differences in response to family crisis: changes in household composition and migration of widowed parents with minor children in the Netherlands, 1863–1910

ABSTRACT This article examines parental coping strategies in response to the death of a partner in the Netherlands in the period 1863–1910. The author concentrates on two largely neglected strategies in particular: separation of widowed parent and minor child and the outmigration of the entire household to another municipality. The rich population register data from the Historical Sample of the Netherlands is exploited which contains the life trajectories of more than 2800 half-orphaned children. The results derived from sequence analysis and event-history analysis reveal a high degree of family stability following the partner’s death but point to gender differences in coping strategies: Whereas widowers were more likely to split up with their young children, widows were more likely to migrate together with them. These gender differences can be explained by the fundamentally different positions of men and women concerning childcare, work and poor relief in Dutch society during the period under consideration. Additionally, no significant differences between nuclear and non-nuclear households were found with regard to parental separation from minor children. This finding challenges the nuclear hardship hypothesis which predicts that non-nuclear family systems are better able to cope with family crises.
An exemplar-theoretic account of word senses

This thesis offers an exploratory study of certain aspects of the psychological status of the senses of four polysemous words, over, under, above and below, using three sets of sentence-sorting experiments. The thesis assumes that word senses are examples of linguistic categories; therefore, it is further assumed that categorisation tasks will offer insights into their nature as categories, and that effects predicted by existing models of categorisation can be tested. The first set of experiments questions the representativity of linguists’ intuitions about the senses of these words. The results indicate that expert and naive speakers’ intuitions do not reliably coincide. This is consistent with existing research into the representativity of expert intuitions in syntax (e.g., Schutze, 1996). The possibility that this is due to individual differences is the subject of the second experiment. The data gathered suggest that there may be individual differences in word senses, consistent with observations of individual differences in other areas of language (e.g., Bates et al., 1995; Street and Dąbrowska, 2014). It is noted that lack of consensus may be a product of the task design, and that the scale of the task may have caused fatigue, forgetting, or semantic satiation. This was remedied in the final set of experiments. Further evidence of individual variation in word senses was found. In addition, the versatility of the methodology was exploited to test whether word senses are stored in memory, and in a manner compatible with the Generalised Context Model of Classification, or exemplar model (Nosofsky, 1986). Participants sorted the same stimuli twice, divided by a period of two months. In general, participants reached better consensus with themselves than with others. This indicates that word senses may have some form of mental representation. Effects of selective attention, a central prediction of the exemplar model, were observed in sorting behaviour. Four original contributions to knowledge are made: (1) there appear to be individual differences in word senses; (2) expert intuitions about what the senses of a given polysemous word are do not correspond to those of other speakers; (3) word senses do appear to have some form of mental representation, but not in the fixed form previously suggested (e.g., Tyler and Evans, 2001); and (4) selective attention effects are observed in this example of linguistic categorisation. The findings indicate that the exemplar model can account for the representation of word senses. This allows the conclusion that we may understand word senses as potential categories of exemplars.
Astrocyte-Specific Inactivation of the Neurofibromatosis 1 Gene (NF1) Is Insufficient for Astrocytoma Formation

ABSTRACT Individuals with the neurofibromatosis 1 (NF1) inherited tumor syndrome develop low-grade gliomas (astrocytomas) at an increased frequency, suggesting that the NF1 gene is a critical growth regulator for astrocytes. In an effort to determine the contribution of the NF1 gene product, neurofibromin, to astrocyte growth regulation and NF1-associated astrocytoma formation, we generated astrocyte-specific Nf1 conditional knockout mice (Nf1GFAPCKO) by using Cre/LoxP technology. Transgenic mice were developed in which Cre recombinase was specifically expressed in astrocytes by embryonic day 14.5. Successive intercrossing with mice bearing a conditional Nf1 allele (Nf1flox) resulted in GFAP-Cre Nf1flox/flox (Nf1GFAPCKO) animals. No astrocytoma formation or neurological impairment was observed in Nf1GFAPCKO mice after 20 months, but increased numbers of proliferating astrocytes were observed in several brain regions. To determine the consequence of Nf1 inactivation at different developmental times, the growth properties of embryonic day 12.5 and postnatal day 2 Nf1 null astrocytes were analyzed. Nf1 null astrocytes exhibited increased proliferation but lacked tumorigenic properties in vitro and did not form tumors when injected into immunocompromised mouse brains in vivo. Collectively, our results suggest that loss of neurofibromin is not sufficient for astrocytoma formation in mice and that other genetic or environmental factors might influence NF1-associated glioma tumorigenesis.
SyncProf: detecting, localizing, and optimizing synchronization bottlenecks

Writing concurrent programs is a challenge because developers must consider both functional correctness and performance requirements. Numerous program analyses and testing techniques have been proposed to detect functional faults, e.g., caused by incorrect synchronization. However, little work has been done to help developers address performance problems in concurrent programs, e.g., because of inefficient synchronization. This paper presents SyncProf, a concurrency-focused profiling approach that helps in detecting, localizing, and optimizing synchronization bottlenecks. In contrast to traditional profilers, SyncProf repeatedly executes a program with various inputs and summarizes the observed performance behavior. A key novelty is a graph-based representation of relations between critical sections, which is the basis for computing the performance impact of critical sections, for identifying the root cause of a bottleneck, and for suggesting optimization strategies to the developer. We evaluate SyncProf on 19 versions of eight C/C++ projects with both known and previously unknown synchronization bottlenecks. The results show that SyncProf effectively localizes the root causes of these bottlenecks with higher precision than a state of the art lock contention profiler and that it suggests valuable strategies to avoid the bottlenecks.
The scope for dynamic collection scheduling using remote asset monitoring: a case study in the charity sector

Many waste collection operations run on the traditional fixed round - fixed time service, where commercial and domestic customers have their bins serviced at agreed intervals. With remote sensing technology now coming onto the market that allows waste receptacles to report their fill levels at regular intervals (e.g. daily), there is the opportunity for dynamic optimisation of collection schedules to better meet their true servicing needs. This paper investigates this possibility using a case study involving collections of donated goods (e.g. clothing, books) from Oxfam charity banks and shops. Oxfam operates a network of around 1300 donation banks across the UK, currently serviced on a fixed schedule basis, and there is considerable interest in the transport cost reductions that could be realised through optimising collections using real-time feedback on donation rates (a dynamic and heterogeneous variant of the Vehicle Routing Problem (VRP) with time windows, working time restrictions and customer selection). The case study is based on one of Oxfam’s 33 defined operating areas in the UK comprising collections from 37 bank sites and 50 shops.
Answering Conjunctive Queries under Updates

We consider the task of enumerating and counting answers to k-ary conjunctive queries against relational databases that may be updated by inserting or deleting tuples. We exhibit a new notion of q-hierarchical conjunctive queries and show that these can be maintained efficiently in the following sense. During a linear time pre-processing phase, we can build a data structure that enables constant delay enumeration of the query results; and when the database is updated, we can update the data structure and restart the enumeration phase within constant time. For the special case of self-join free conjunctive queries we obtain a dichotomy: if a query is not q-hierarchical, then query enumeration with sublinear *) delay and sublinear update time (and arbitrary preprocessing time) is impossible. For answering Boolean conjunctive queries and for the more general problem of counting the number of solutions of k-ary queries we obtain complete dichotomies: if the query's homomorphic core is q-hierarchical, then size of the the query result can be computed in linear time and maintained with constant update time. Otherwise, the size of the query result cannot be maintained with sublinear update time. All our lower bounds rely on the OMv-conjecture, a conjecture on the hardness of online matrix-vector multiplication that has recently emerged in the field of fine-grained complexity to characterise the hardness of dynamic problems. The lower bound for the counting problem additionally relies on the orthogonal vectors conjecture, which in turn is implied by the strong exponential time hypothesis. *) By sublinear we mean O(n(1-ε) for some ε > 0, where n is the size of the active domain of the current database.
Traffic Control in Unicast ATM ABR Service using Adaptive Approsch

This paper addresses the problem of rate control for Available Bit Rate (ABR) service class in Asynchronous Transfer Mode (ATM) networks. An adaptive neurofuzzy mechanism based on Adaptive Network Fuzzy Inference System (ANFIS) for allocating rates in ABR service has been proposed and compared with the fuzzy technique called as Fuzzy Explicit Rate Marking (FERM). To achieve this, a neurofuzzy ANFIS controller has been built and its control actions are compared with FERM. Simulations are carried out. Network throughput and average cell delay at the terminal end; and percentage cell drop at the switches are calculated.
Seeing the bigger picture: a user perspective on 360° TV

Omnidirectional video (ODV) is a type of video in which viewers can look around in 360° as if turning the camera themselves. This type of video presents opportunities for new interactive television formats. The development of such new formats, however, is accompanied by challenges in terms of user experience and technical and creative development. In this paper, we discuss which issues and opportunities users anticipate. These findings are the result of a human-centered design study in which we first introduced potential users to ODV, gathering their feedback, and then encouraged them to envision suitable ODV-based enhancements of television genres.
Vegetation sensitivity to global anthropogenic carbon dioxide emissions in a topographically complex region

Anthropogenic increases in atmospheric carbon dioxide (CO2) concentrations may affect vegetation distribution both directly through changes in photosynthesis and water‐use efficiency, and indirectly through CO2‐induced climate change. Using an equilibrium vegetation model (BIOME4) driven by a regional climate model (RegCM2.5), we tested the sensitivity of vegetation in the western United States, a topographically complex region, to the direct, indirect, and combined effects of doubled preindustrial atmospheric CO2 concentrations. Those sensitivities were quantified using the kappa statistic. Simulated vegetation in the western United States was sensitive to changes in atmospheric CO2 concentrations, with woody biome types replacing less woody types throughout the domain. The simulated vegetation was also sensitive to climatic effects, particularly at high elevations, due to both warming throughout the domain and decreased precipitation in key mountain regions such as the Sierra Nevada of California and the Cascade and Blue Mountains of Oregon. Significantly, when the direct effects of CO2 on vegetation were tested in combination with the indirect effects of CO2‐induced climate change, new vegetation patterns were created that were not seen in either of the individual cases. This result indicates that climatic and nonclimatic effects must be considered in tandem when assessing the potential impacts of elevated CO2 levels.
Accuracy of the cosmic‐ray soil water content probe in humid forest ecosystems: The worst case scenario

Soil water content is one of the key state variables in the soil‐vegetation‐atmosphere continuum due to its important role in the exchange of water and energy at the soil surface. A new promising method to measure integral soil water content at the field or small catchment scale is the cosmic‐ray probe (CRP). Recent studies of CRP measurements have mainly presented results from test sites located in very dry areas and from agricultural fields with sandy soils. In this study, distributed continuous soil water content measurements from a wireless sensor network (SoilNet) were used to investigate the accuracy of CRP measurements for soil water content determination in a humid forest ecosystem. Such ecosystems are less favorable for CRP applications due to the presence of a litter layer. In addition, lattice water and carbohydrates of soil organic matter and belowground biomass reduce the effective sensor depth and thus were accounted for in the calibration of the CRP. The hydrogen located in the biomass decreased the level of neutron count rates and thus also decreased the sensitivity of the cosmic‐ray probe, which in turn resulted in an increase of the measurement uncertainty. This uncertainty was compensated by using longer integration times (e.g., 24 h). For the Wüstebach forest site, the cosmic‐ray probe enabled the assessment of integral daily soil water content dynamics with a RMSE of about 0.03 cm3/cm3 without explicitly considering the litter layer. By including simulated water contents of the litter layer in the calibration, a better accuracy could be achieved.