Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonal evolution of high‐grade serous ovarian carcinoma from primary to recurrent disease

High‐grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum‐ and taxane‐based chemotherapy, the majority of patients experience recurrence of treatment‐resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.
The intestinal microflora in allergic Estonian and Swedish 2‐year‐old children

The prevalence of allergic diseases seems to have increased particularly over the past 35–40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1‐ and TH2‐like immunity.
How cells (might) sense microgravity

This article is a summary of a lecture presented at an ESA/NASA Workshop on Cell and Molecular Biology Research in Space that convened in Leuven, Belgium, in June 1998. Recent studies are reviewed which suggest that cells may sense mechanical stresses, including those due to gravity, through changes in the balance of forces that are transmitted across transmembrane adhesion receptors that link the cytoskeleton to the extracellular matrix and to other cells (e.g., integrins, cadherins, selectins). The mechanism by which these mechanical signals are transduced and converted into a biochemical response appears to be based, in part, on the finding that living cells use a tension‐dependent form of architecture, known as tensegrity, to organize and stabilize their cytoskeleton. Because of tensegrity, the cellular response to stress differs depending on the level of pre‐stress (pre‐existing tension) in the cytoskeleton and it involves all three cytoskeletal filament systems as well as nuclear scaffolds. Recent studies confirm that alterations in the cellular force balance can influence intracellular biochemistry within focal adhesion complexes that form at the site of integrin binding as well as gene expression in the nucleus. These results suggest that gravity sensation may not result from direct activation of any single gravioreceptor molecule. Instead, gravitational forces may be experienced by individual cells in the living organism as a result of stress‐dependent changes in cell, tissue, or organ structure that, in turn, alter extracellular matrix mechanics, cell shape, cytoskeletal organization, or internal pre‐stress in the cell‐tissue matrix. —Ingber, D. How cells (might) sense microgravity. FASEB J. 13 (Suppl.), S3–S15 (1999)
Chemokines and the Signaling Modules Regulating Integrin Affinity

Integrin-mediated adhesion is a general concept referring to a series of adhesive phenomena including tethering–rolling, affinity, valency, and binding stabilization altogether controlling cell avidity (adhesiveness) for the substrate. Arrest chemokines modulate each aspect of integrin activation, although integrin affinity regulation has been recognized as the prominent event in rapid leukocyte arrest induced by chemokines. A variety of inside-out and outside-in signaling mechanisms have been related to the process of integrin-mediated adhesion in different cellular models, but only few of them have been clearly contextualized to rapid integrin affinity modulation by arrest chemokines in primary leukocytes. Complex signaling processes triggered by arrest chemokines and controlling leukocyte integrin activation have been described for ras-related rap and for rho-related small GTPases. We summarize the role of rap and rho small GTPases in the regulation of rapid integrin affinity in primary leukocytes and provide a modular view of these pro-adhesive signaling events. A potential, albeit still speculative, mechanism of rho-mediated regulation of cytoskeletal proteins controlling the last step of integrin activation is also discussed. We also discuss data suggesting a functional integration between the rho- and rap-modules of integrin activation. Finally we examine the universality of signaling mechanisms regulating integrin triggering by arrest chemokines.
The Acquisition of Temporal Patterns

Speech can be defined in terms of the signal, as a time varying acoustic waveform. We associate speech segments with abrupt spectral or amplitude changes in that waveform. Some of the variation in the temporal aspects of segments can be ascribed to the inherent durations of different articulatory configurations. Other variation is contextually-driven. For instance, the order in which segments are sequenced has consequences for coarticulation, which has consequences for segmental duration. The relative speed with which segment sequences are executed also interacts with coarticulation, and so with patterns of segmental duration. Still other variation is linguistically specified. For example, at the segmental level, different languages will use different patterns of inter-articulatory timing to execute the “same” sound (e.g., Spanish /p/ is more similar to English /b/ than English /p/). At the suprasegmental level, there is prosody, which has extensive effects on segmental durations through reduction and lengthening processes. The focus of this chapter is on the acquisition of temporal patterns that are defined by all of these influences. In keeping with the continuity hypothesis, we assume that the motor factors that constrain the shape of pre-speech vocalizations also influence the realization of temporal patterns in children’s fluent speech. That said, we recognize that the transition from vocal play and imitation (pre-speech) to concept-driven communication (speech) represents an important discontinuity in development. We propose that this transition marks the development of a speech plan; a representation that guides speech action. Overall, our thesis is that the acquisition of temporal patterns reflects motor skill development; but some patterns are planned, in that they reflect remembered speech action (i.e., stored acoustically-linked articulatory schema), while others emerge during fluent speech from the practiced execution of serially ordered schemas (i.e., multi-word plans). Our thesis structures the content presented in this chapter, which is a review of research on early vocalizations, first words, and developmental changes in children’s fluent speech.
Acoustic Fault Detection Technique for High-Power Insulators

Insulators are important equipment used to electrically isolate and mechanically hold wires in high-voltage power transmission systems. Faults caused by the deterioration of the insulators induce very serious problems to the power transmission line. Techniques were introduced for the acoustic detection of insulator faults by acoustic radiation noises. Radiation noises were measured from normal state insulators and fault state insulators in an anechoic chamber. The insulators used were two porcelain insulators, a cut-out switch, two line posters, and a lightning arrester. A new acoustic technique determines the direction of the insulator faults using source localization with three-dimensional microphone arrays. The advantage is to classify the fault state insulators without human inspection by considering the amount of total noises and 120-Hz harmonic components. The fault detection was determined by neural network to diagnose the state automatically. The proposed technique was evaluated by distinct, real datasets and the efficacy was validated. The noise source was detected with 100.0% accuracy and the classification ratio achieved 96.7% for three typical conditions.
Preparation and properties of polysulfone–clay composite membranes

Porous membranes and dense films were prepared from polysulfone solutions in N-methyl-2-pyrrolidone (NMP) containing different types and amounts of clay. Commercial clays supplied by Southern Clay, either unmodified (Cloisite Na) or organically modified (Cloisite 30B and Cloisite 93A), were used. The clay behavior in the organic solvent was dependent on the presence and type of the organic compatibilizer: Cloisite containing Na ions did not swell in NMP, whereas those with the organic compatibilizer swelled, though to a different degree. Electron microscopy observations were made to examine the clay dispersion in the membrane structure. At variance with Cloisite Na and Cloisite 93A formed microaggregates, Cloisite 30B yielded nanostructures composed of both single sheets and well-ordered multilayer silicate clusters, which were characterized by an interlayer distance higher than that of the neat clay. The increase in the distance between the layers of Cloisite 30B was related to the formation of intercalated nanocomposites, whereas the presence of single sheets well distributed in the polymer matrix supported the occurrence of delaminated nanocomposites. The intercalation of the polymer into clay layers was confirmed with wide-angle X-ray diffractometry. The addition of Cloisite 30B to the casting solution influenced the phase-separation process in the coagulation bath. Therefore, by the variation of the layered-silicate concentration in the casting solution, membranes with different morphological structures and ultrafiltration properties were obtained. Cloisite 30B was also found to improve the wettability and mechanical properties of dense films. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3637–3644, 2007
Deriving a lazy abstract machine

We derive a simple abstract machine for lazy evaluation of the lambda calculus, starting from Launchbury's natural semantics. Lazy evaluation here means non-strict evaluation with sharing of argument evaluation, i.e. call-by-need. The machine we derive is a lazy version of Krivine's abstract machine, which was originally designed for call-by-name evaluation. We extend it with datatype constructors and base values, so the final machine implements all dynamic aspects of a lazy functional language.
Imputation of orofacial clefting data identifies novel risk loci and sheds light on the genetic background of cleft lip ± cleft palate and cleft palate only

Abstract Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is among the most common human birth defects with multifactorial etiology. Here, we present results from a genome-wide imputation study of nsCL/P in which, after adding replication cohort data, four novel risk loci for nsCL/P are identified (at chromosomal regions 2p21, 14q22, 15q24 and 19p13). On a systematic level, we show that the association signals within this high-density dataset are enriched in functionally-relevant genomic regions that are active in both human neural crest cells (hNCC) and mouse embryonic craniofacial tissue. This enrichment is also detectable in hNCC regions primed for later activity. Using GCTA analyses, we suggest that 30% of the estimated variance in risk for nsCL/P in the European population can be attributed to common variants, with 25.5% contributed to by the 24 risk loci known to date. For each of these, we identify credible SNPs using a Bayesian refinement approach, with two loci harbouring only one probable causal variant. Finally, we demonstrate that there is no polygenic component of nsCL/P detectable that is shared with nonsyndromic cleft palate only (nsCPO). Our data suggest that, while common variants are strongly contributing to risk for nsCL/P, they do not seem to be involved in nsCPO which might be more often caused by rare deleterious variants. Our study generates novel insights into both nsCL/P and nsCPO etiology and provides a systematic framework for research into craniofacial development and malformation.
Chemical Composition and Nutritive Benefits of Chicory (Cichorium intybus) as an Ideal Complementary and/or Alternative Livestock Feed Supplement

Chicory is a perennial plant grown in different parts of the world, used as forage for livestock, as folklore remedies, or as a vegetable addition in human diets. There are several varieties of the chicory plant, known differently globally due to its numerous medicinal, culinary, and nutritional qualities. Most parts of the plant contain a potpourri of nutrients ranging within carbohydrates, proteins, vitamins, minerals, soluble fiber, trace elements, and bioactive phenolic compounds, which are responsible for the various nutritive, prophylactic, and therapeutic qualities of chicory. Inulin, coumarins, tannins, monomeric flavonoids, and sesquiterpene lactones are some of the major phytocompounds mostly found in chicory plants. The health-promoting activities attributed to chicory comprise, among others, anti-inflammatory, anticarcinogenic, antiviral, antibacterial, antimutagenic, antifungal, anthelmintic, immune-stimulating, and antihepatotoxic and its antioxidative qualities. As a versatile plant, chicory's chemical composition and use as a suitable livestock feed supplement or as an alternative feed ingredient (AFI) are thus reviewed.
Characterization of microstructure and residual stress in a 3D H13 tool steel component produced by additive manufacturing

H13 tool steel was deposited using the additive manufacturing technique Direct Metal Deposition to produce a part having a wedge geometry. The wedge was characterized both in terms of microstructure and residual stress. It was found that phase transformations were significantly influencing the microstructure, which was then linked to the residual stress distribution as seen in Fig. 8. The residual stress distribution was found to be opposite to that reported in the literature. This was attributed to the low temperature martensitic phase transformation of the H13 tool steel and the subsequent tempering of the microstructure with an increasing number of layers of deposited material. The high hardness and compressive residual stress of the top 4 mm of the wedge are ideal in die casting and forging dies, as it will resist thermal fatigue. It also has a hardness higher than that produced by typical heat treatment processes.
Lipid Interventions in Aortic Valvular Disease

Abstract:Aortic valve stenosis is the most common valvular disease in the elderly population. Presently, there is increasing evidence that aortic stenosis (AS) is an active process of lipid deposition, inflammation, fibrosis and calcium deposition. The pathogenesis of AS shares many similarities to that of atherosclerosis; therefore, it was hypothesized that certain lipid interventions could prevent or slow the progression of aortic valve stenosis. Despite the early enthusiasm that statins may slow the progression of AS, recent large clinical trials did not consistently demonstrate a decrease in the progression of AS. However, some researchers believe that statins may have a benefit early on in the disease process, where inflammation (and not calcification) is the predominant process, in contrast to severe or advanced AS, where calcification (and not inflammation) predominates. Positron emission tomography using 18F-fluorodeoxyglucose and 18F-sodium fluoride can demonstrate the relative contributions of valvular calcification and inflammation in AS, and thus this method might potentially be useful in providing the answer as to whether lipid interventions at the earlier stages of AS would be more effective in slowing the progression of the disease. Currently, there is a strong interest in recombinant apolipoprotein A-1 Milano and in the development of new pharmacological agents, targeting reduction of lipoprotein (a) levels and possibly reduction of the expression of lipoprotein-associated phospholipase A2, as potential means to slow the progression of aortic valvular stenosis.
Comments on 'The valid generic names for the fish species usually placed in Cyclocheilichthys' (KOTTELAT 2013) and a correction of Pasco-viel et al. (2012).

As authors of the study demonstrating the non-monophyly of the genus previously called Cyclocheilichthys (Pasco-Viel et al . 2012), which included nine species, we acknowledge Kottelat’s (2013: this issue) conclusions with regard to the generic names for the species we investigated: cu� o������g pincer-shaped suckers, is described for the first time using scanning electron microscopy. In scolex morphology, M. ficta closely resembles phyllobothriidean cestodes, parasites of elasmobranchs. However, this similarity does not reflect phylogenetic relatedness of these cestodes but instead presents an example of convergent morphological evolution of attachment organs of unrelated groups of cestodes that parasitize different groups of vertebrates. Besides scolex morphology, the genus is characterised by the possession of a very large cirrus-sac, which may reach up to the midline of proglottides, few testes (less than 60), vitelline follicles limited to the dorsal side of proglottides, a large vaginal sphincter, and eggs with a three-layered embryophore covered with rounded projections. Numerous errors in the diagnosis of M. ficta , which appeared in the literature as a result of uncritical compilation of data without examination of original material, are corrected. Multilocus phylogenetic analysis of nuclear ribosomal RNA genes ssr - and lsrDNA and mitochondrial genes rrnL and cox1 place this species among other snake-parasitizing proteocephalideans of the genus Ophiotaenia . The convergent evolution of scolex morphology across distantly related taxa is discussed.
Predicting active slip systems in β-Sn from ideal shear resistance

We analyse the ideal shear resistances of 15 nonequivalent slip systems in β-Sn using first-principles density functional theory. From the ideal shear resistance and Schmid's law, the orientation dependence of active slip systems in a β-Sn single crystal subjected to uniaxial tension is investigated. We find that has the lowest ideal shear resistance among the 15 slip systems. Our calculations indicate that, depending on crystal orientation, uniaxial tension activates seven nonequivalent groups of slip systems. The active slip systems for [1 0 0] and [1 1 0] orientations determined in this study agree with the experimental results.
Disfiguring organic residues on industrially produced sheet metal coupons simulating copper and brass works of art by Donald Judd: Attenuated total reflectance Fourier transform infrared spectroscopy analysis and treatment recommendations

Abstract The Minimalist work of Donald Judd exemplifies modern and contemporary works of art that utilize the appearance of bare metal as an integral component of the artist's intent. Decades after fabrication, disfiguring patterns have appeared on the surfaces of many such works. These patterns are not related to the formation of tarnish or other corrosion effects caused by improper storage, display, or transportation and handling; rather, they are associated with the initial processing of the metal sheets and subsequent fabrication of the art objects. Due to the challenges of obtaining analytical data directly from works of art, the authors present results from industrial sheet metal coupons prepared to simulate materials and techniques used in Donald Judd's copper and brass artworks. Attenuated total reflectance Fourier transform infrared spectroscopy carried out on each side of 55 coupons indicated the presence of organic materials such as long-chain aliphatic hydrocarbons, esters, and ethers, consistent with the types of compounds used in industrial lubricants. In addition to conducting the first systematic instrumental analysis of these residues, the authors propose the use of specific solvents for their removal as an alternative to abrasive methods, which cause removal of original surface from the objects.
Freezing transition of the random bond RNA model: Statistical properties of the pairing weights.

To characterize the pairing specificity of RNA secondary structures as a function of temperature, we analyze the statistics of the pairing weights as follows: for each base (i) of the sequence of length N , we consider the (N-1) pairing weights w{i}(j) with the other bases (j not equal i) of the sequence. We numerically compute the probability distributions P1(w) of the maximal weight w[{i}{max}=max{j}[w{i}(j)] , the probability distribution Pi(Y(2)) of the parameter Y2(i)= summation operator{j}w{i}{2}(j) , as well as the average values of the moments Y{k}(i)= summation operator_{j}w_{i}{k}(j) . We find that there are two important temperatures T_{c}<T_{gap} . For T>T_{gap} , the distribution P1(w) vanishes at some value w{0}(T)<1 , and accordingly the moments Y{k}(i) decay exponentially as [w{0}(T)]{k} in k . For T<T{gap} , the distributions P1(w) and Pi(Y2) present the characteristic Derrida-Flyvbjerg singularities at w=1n and Y{2}=1/n for n=1,2,. In particular, there exists a temperature-dependent exponent mu(T) that governs the singularities P1(w) approximately (1-w){mu(T)-1} and Pi(Y2) approximately (1-Y{2}){mu(T)-1} as well as the power-law decay of the moments Y{k}(i) approximately 1k{mu(T)} . The exponent mu(T) grows from the value mu(T=0)=0 up to mu(T{gap}) approximately 2 . The study of spatial properties indicates that the critical temperature T{c} where the large-scale roughness exponent changes from the low temperature value zeta approximately 0.67 to the high temperature value zeta approximately 0.5 corresponds to the exponent mu(T{c})=1 . For T<T{c} , there exists frozen pairs of all sizes, whereas for T{c}<T<T{gap} , there exists frozen pairs, but only up to some characteristic length diverging as xi(T) approximately 1(T{c}-T){nu} with nu approximately 2 . The similarities and differences with the weight statistics in Lévy sums and in Derrida's random energy model are discussed.