Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Chemistry — Per Ardua Ad …?

Selection for the Vickers Award is a considerable honour and carries an implication of personal achievement of some magnitude. It may take the form of a brilliant discovery or, if one is fortunate enough to be in the right position, achievement is simply part of everyday work. Here at the Clinical Research Centre (CRC) we are very conscious of being favourably placed to do interesting things, and indeed our remit is to make some sort of national and international impact in our various specialties. This happy and, as we find it, almost unique position in the world of clinical chemistry becomes a little difficult when, as has happened in the past, awards are bestowed on any member of staff. There was a time when brilliant work in our profession was done by individuals, but this is now rare and team work is required if progress is to be made in almost any area of our specialty; sometimes, because of cost and complexity, centres in several different countries need to be involved. Then again, with advancing years so many of us find we are increasingly concerned with the philosophies involved in the work, selecting areas of activity and creating the environment for that activity to be successful. I should like to cover to some extent the philosophy behind our approach at the CRC to the many problems we have in clinical chemistry, and then to give a few practical examples of how that philosophy is applied. It is a pleasure to take this opportunity to thank the many colleagues who have contributed in many ways, a few of which will be highlighted later. We in the Association of Clinical Biochemists are grateful to Vickers for funding this award for so many years. The Company and I have been associated for nearly four decades, from the war years when I flew their planes, to a more peaceful involvement in the late 1960s and early 1970s in the development of the M-300 and D-300 analysers. The results from both of these instruments must have formed the basis of a large number of papers from almost every research division at the CRe.
VoR-tree

A very important class of spatial queries consists of nearest-neighbor (NN) query and its variations. Many studies in the past decade utilize R-trees as their underlying index structures to address NN queries efficiently. The general approach is to use R-tree in two phases. First, R-tree's hierarchical structure is used to quickly arrive to the neighborhood of the result set. Second, the R-tree nodes intersecting with the local neighborhood (Search Region) of an initial answer are investigated to find all the members of the result set. While R-trees are very efficient for the first phase, they usually result in the unnecessary investigation of many nodes that none or only a small subset of their including points belongs to the actual result set. On the other hand, several recent studies showed that the Voronoi diagrams are extremely efficient in exploring an NN search region, while due to lack of an efficient access method, their arrival to this region is slow. In this paper, we propose a new index structure, termed VoR-Tree that incorporates Voronoi diagrams into R-tree, benefiting from the best of both worlds. The coarse granule rectangle nodes of R-tree enable us to get to the search region in logarithmic time while the fine granule polygons of Voronoi diagram allow us to efficiently tile or cover the region and find the result. Utilizing VoR-Tree, we propose efficient algorithms for various Nearest Neighbor queries, and show that our algorithms have better I/O complexity than their best competitors.
A Pleiotropically Acting Microrna, Mir-31, Inhibits Breast Cancer Metastasis Accessed Terms of Use Detailed Terms a Pleiotropically Acting Microrna, Mir-31, Inhibits Breast Cancer Metastasis

Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. SUMMARY MicroRNAs are well suited to regulate tumor metas-tasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a micro-RNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable micro-RNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis. For a video summary of this article, see the Paper-Flick file available with the online Supplemental Data.
An optimized round robin cpu scheduling algorithm with dynamic time quantum

CPU scheduling is one of the most crucial operations performed by operating system. Different algorithms are available for CPU scheduling amongst them RR (Round Robin) is considered as optimal in time shared environment. The effectiveness of Round Robin completely depends on the choice of time quantum. In this paper a new CPU scheduling algorithm has been proposed, named as DABRR (Dynamic Average Burst Round Robin). That uses dynamic time quantum instead of static time quantum used in RR. The performance of the proposed algorithm is experimentally compared with traditional RR and some existing variants of RR. The results of our approach presented in this paper demonstrate improved performance in terms of average waiting time, average turnaround time, and context switching.
Extended Critical Paths in Temporal Planning

Timed initial literals refer to a recently added feature to the problem domain description language PDDL. Besides the modelling perspective to express exogenous events, this language extension allows to impose deadlines to action execution and to select temporal plans of high quality. For efficiently solving problems with explicit timing requirements, the work in this paper extends a two-stage planning/scheduling system where the sequential plan is built followed by a critical path scheduling phase to find a parallel arrangement. Timed initial literals are included into the plan finding and scheduling process in form of time windows for action execution. Compared to earlier work, the temporal model is refined to include slack and to allow overlappings of dependent actions. The apparently simple scheduling phase is faster than other approaches to establish parallel plans, but expressive enough to cope with current benchmark problems. Through its efficiency, it applies not only to schedule complete plans, but also partial and relaxed plans. Correctness and optimality of the algorithms are shown, and limitations of the approach are discussed. Empirical evidence is given by providing plans for many temporal planning problems.
Riemannian metrics on locally projectively flat manifolds

The expression [inline-graphic xmlns:xlink="http://www.w3. org/1999/xlink" xlink:href="01i" /] transforms as a symmetric (0, 2) tensor under projective coordinate changes of a domain in R n so long as u transforms as a section of a certain line bundle. On a locally projectively flat manifold, the section u can be regarded as a metric potential analogous to the local potential in Kahlergeometry. Let M be a compact locally projectively flat manifold. We prove that if u is a negative section of the dual of the tautological bundle such that [inline-graphic xmlns:xlink="http://www.w3. org/1999/xlink" xlink:href="02i" /] is a Riemannian metric, then M is projectively equivalent to a quotient of a bounded convex domain in R n . The same is true for such manifolds M with boundary if u = 0 on the boundary. This theorem is an analog of a result of Schoen and Yau in locally conformally flat geometry. The proof involves affine differential geometry techniques developed by Cheng and Yau.
MRI methods for the evaluation of high intensity focused ultrasound tumor treatment: Current status and future needs

Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR‐guided HIFU system. The MR‐based evaluation of HIFU treatment is most often restricted to contrast‐enhanced T1‐weighted imaging, while it has been shown that the non‐perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU‐induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been—or could be—used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI‐based evaluation of HIFU treatment. Magn Reson Med 75:302–317, 2016. © 2015 Wiley Periodicals, Inc.
Delamination modelling using an element free galerkin approach

The prediction of delamination initiation, and propagation in composite structures is quite complex, and requires advanced modelling techniques. The main computational techniques currently used include the finite element method, the boundary integral method etc. While current computational tools are quite robust for the modelling of stationary cracks, the representation of crack evolution of arbitrary cracks is still yet to be addressed properly due to the difficulties in relating an evolving geometry to the discretization for each stage of the delamination propagation. The objective of the paper is to investigate the potential of the Element-Free Galerkin (EFG) [1-2] method coupled to a material cohesive zone damage model for simulating the steadystate evolution of delamination in composite structures for quasi-static loading of various single mode and mixed-mode. In particular, a single relative displacement-based damage parameter is applied in a softening law to track the damage state of the layers interface and to prevent the restoration of the undamaged cohesive state during unloading. The methodology developed was used to simulate delamination growth in a 24-ply unidirectional AS4/PEEK (APC2) carbon fibre reinforced composite for various single mode and mixed-mode delamination test specimens, i.e. the Double Cantilever Beam (DCB) specimen is used for Mode I, the End-Notched Flexure (ENF) or the End-Loaded Split (ELS) test specimens are used for Mode II. To demonstrate the accuracy of the proposed methodology, the results were compared with experimental data showing promising accuracy and robustness.
Querying GIS with animated spatial sketches

We present the design of the visual query system VISCO that offers a sketch-based query language for defining approximate spatial constellations of objects. VISCO smoothly integrates geometrical and topological querying with deductive spatial reasoning. It is based on a strong physical metaphor visualizing semantics of query elements. Approximate queries rely on combined topological and geometrical constraints enhanced with relaxations and "don't cares" that are visualized through live animations.
Expanding functional repertoires of fungal peroxisomes: contribution to growth and survival processes

It has long been regarded that the primary function of fungal peroxisomes is limited to the β-oxidation of fatty acids, as mutants lacking peroxisomal function fail to grow in minimal medium containing fatty acids as the sole carbon source. However, studies in filamentous fungi have revealed that peroxisomes have diverse functional repertoires. This review describes the essential roles of peroxisomes in the growth and survival processes of filamentous fungi. One such survival mechanism involves the Woronin body, a Pezizomycotina-specific organelle that plugs the septal pore upon hyphal lysis to prevent excessive cytoplasmic loss. A number of reports have demonstrated that Woronin bodies are derived from peroxisomes. Specifically, the Woronin body protein Hex1 is targeted to peroxisomes by peroxisomal targeting sequence 1 (PTS1) and forms a self-assembled structure that buds from peroxisomes to form the Woronin body. Peroxisomal deficiency reduces the ability of filamentous fungi to prevent excessive cytoplasmic loss upon hyphal lysis, indicating that peroxisomes contribute to the survival of these multicellular organisms. Peroxisomes were also recently found to play a vital role in the biosynthesis of biotin, which is an essential cofactor for various carboxylation and decarboxylation reactions. In biotin-prototrophic fungi, peroxisome-deficient mutants exhibit growth defects when grown on glucose as a carbon source due to biotin auxotrophy. The biotin biosynthetic enzyme BioF (7-keto-8-aminopelargonic acid synthase) contains a PTS1 motif that is required for both peroxisomal targeting and biotin biosynthesis. In plants, the BioF protein contains a conserved PTS1 motif and is also localized in peroxisomes. These findings indicate that the involvement of peroxisomes in biotin biosynthesis is evolutionarily conserved between fungi and plants, and that peroxisomes play a key role in fungal growth.
Attribute Relation Extraction from Template-inconsistent Semi-structured Text by Leveraging Site-level Knowledge

A variety of methods have been proposed for attribute-value extraction from semistructured text with consistent templates (strict semi-text). However, when the templates in semi-structured text are inconsistent (weak semi-text), these methods will work poorly. To overcome the templateinconsistent problem, in this paper, we proposed a novel method to leverage sitelevel knowledge for attribute-value extraction. First, we use a graph-based random walk model to acquire site-level knowledge. Then we utilize such knowledge to identify weak semi-text in each page and extract attribute-value pairs. The experiments show that, comparing to the baseline method which does not utilize sitelevel knowledge, our method can improve the extraction performance significantly.
Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

Significance Understanding the genetic mechanisms that control lifespan is essential for the development of regenerative therapies that seek to reverse the aging process. In the nematode Caenorhabditis elegans, long-lived mutants that are defective in insulin signaling up-regulate a number of stress response genes to promote survival. A study published in 2009 reported that these long-lived mutants also express in their somatic cells factors that are normally restricted to germ cells and that these mutants rely on germ-line factors for some of their lifespan extension. Our studies call these findings into question and instead suggest that expression of certain germ-line factors in the somatic cells of worms is detrimental to the health of worms and reduces lifespan. The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2’s long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2’s long lifespan.
Assortative Mating by Ethnicity in Longevous Families

Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human longevity: the Long Life Family Study (LLFS), and the New England Centenarian Study (NECS). In the LLFS, we identified 890 spouse pairs spanning two generations, while in the NECS we used data from 102 spouse pairs including offspring of centenarians. We used principal components of genome-wide genotype data to demonstrate strong evidence of ancestry-based assortative mating in spouse pairs of the older generation and also confirm the decreasing trend of endogamy in more recent generations. These findings in studies of human longevity suggest that spouses marrying into longevous families may not be powerful controls for genetic association studies, and that there may be important ethnicity-specific, genetic influences and/or gene–environment interactions that influence extreme survival in old generations. In addition, the decreasing trend of genetic similarity of more recent generations might have ramifications for the incidence of homozygous rare variants necessary for survival to the most extreme ages.
Exposure to PFOA and PFOS and fetal growth: a critical merging of toxicological and epidemiological data

Abstract Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed. Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure. Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was −12.8 g (95% CI −23.2; 2.4), and −27.1 g (95% CI −50.6; −3.6) for an increase of 1 loge ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was −0.92 g (95%CI −3.4; 1.6), and for an increase of 1 loge ng/mL was −46.1(95% CI −80.3; −11.9). No consistent pattern emerged for study location or timing of blood sampling. Conclusions: Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 102–103 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.
A multi‐service link layer architecture for the wireless Internet

The performance of Internet applications over wireless links is disappointing due to the adverse effects of wireless errors on higher layer protocols and applications. This paper focuses on link layer enhancement mechanisms which attempt to hide these wireless impairments. We simulate file transfer and WWW browsing over TCP and continuous media distribution over UDP, in conjunction with various link layer schemes. Our results reveal that WWW browsing behaves differently than bulk file transfer, that some TCP aware enhancements have limited applicability and that UDP applications are best served by schemes inappropriate for TCP. We then describe a multi‐service link layer architecture that simultaneously enhances the performance of diverse applications by supporting multiple error recovery schemes in parallel. In order to evaluate our architecture, we repeat our previous simulations with all applications executing simultaneously. The results reveal that with our approach each application achieves similar improvements as when it operates alone over its preferred link layer. Copyright © 2004 John Wiley & Sons, Ltd.
The Relative Timing of Mutations in a Breast Cancer Genome

Many tumors have highly rearranged genomes, but a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. Chromosome instability might arise early, be a late event contributing little to cancer development, or happen as a single catastrophic event. Another unknown is which of the point mutations and rearrangements are selected. To address these questions we show, using the breast cancer cell line HCC1187 as a model, that we can reconstruct the likely history of a breast cancer genome. We assembled probably the most complete map to date of a cancer genome, by combining molecular cytogenetic analysis with sequence data. In particular, we assigned most sequence-level mutations to individual chromosomes by sequencing of flow sorted chromosomes. The parent of origin of each chromosome was assigned from SNP arrays. We were then able to classify most of the mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome, endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided earlier and later, suggesting that genetic instability was relatively constant throughout the life of this tumor, and chromosome instability was not a late event. Mutations that caused chromosome instability would be in the earlier set. Strikingly, the great majority of inactivating mutations and in-frame gene fusions happened earlier. The non-random timing of some of the mutations may be evidence that they were selected.
Towards robust phoneme classification with hybrid features

In this paper, we investigate the robustness of phoneme classification to additive noise with hybrid features using support vector machines (SVMs). In particular, the cepstral features are combined with short term energy features of acoustic waveform segments to form a hybrid representation. The energy features are then taken into account separately in the SVM kernel, and a simple subtraction method allows them to be adapted effectively in noise. This hybrid representation contributes significantly to the robustness of phoneme classification and narrows the performance gap to the ideal baseline of classifiers trained under matched noise conditions.