Miracle-dz/UniFAR-FTUs huggingface dataset:
AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.
Monarch butterfly population decline in North America: identifying the threatening processes

The monarch butterfly (Danaus plexippus) population in North America has sharply declined over the last two decades. Despite rising concern over the monarch butterfly's status, no comprehensive study of the factors driving this decline has been conducted. Using partial least-squares regressions and time-series analysis, we investigated climatic and habitat-related factors influencing monarch population size from 1993 to 2014. Potential threats included climatic factors, habitat loss (milkweed and overwinter forest), disease and agricultural insecticide use (neonicotinoids). While climatic factors, principally breeding season temperature, were important determinants of annual variation in abundance, our results indicated strong negative relationships between population size and habitat loss variables, principally glyphosate use, but also weaker negative effects from the loss of overwinter forest and breeding season use of neonicotinoids. Further declines in population size because of glyphosate application are not expected. Thus, if remaining threats to habitat are mitigated we expect climate-induced stochastic variation of the eastern migratory population of monarch butterfly around a relatively stationary population size.
Clustering fully and partially observable graphs via nonconvex optimization

The problem of clustering unweighted graphs either in the case of fully or partially observable adjacency matrices is considered in this paper. Both these subproblems have been recently considered in the literature and have been tackled based on convex optimization techniques related to the problems of matrix completion and robust principal component analysis that fall into the general compressive sensing framework. We revisit these approaches and extend them by proposing ways to obtain more accurate clustering results based on better approximations for the ℓ0-norm of a matrix than the ℓ1-norm. The current state-of-art methods correspond to special instances of the proposed extensions. Although nonconvex, the proposed methods can be approximately decomposed into sequences of ℓ1-norm minimization problems, thus pertaining the efficiency of convex formulations. The methods are compared using graphs that are built upon the classical stochastic blockmodel. These comparisons provide a good indication that the proposed methods can improve the accuracy of state-of-art clustering methods applied to currently popular applications such as that of community detection in social networks.
Ahead-of-Time Compilation of Stack-Based JVM Bytecode on Resource-Constrained Devices

Many virtual machines have been developed for tiny devices with only a few KB of RAM and tens to a few hundred KB of flash memory. They pack an impressive set of features in a very limited space, but suffer from a large performance penalty: a slowdown of one to two orders of magnitude compared to optimised native code is typical for most VMs, reducing throughput and increasing power consumption. Compiling the VM’s bytecode to native code to improve performance has been studied extensively for larger devices, but has not received much attention in the context of sensor networks, where the restricted resources mean most modern techniques cannot be applied. Simply replacing each VM instruction with a predefined sequence of native instructions is known to improve performance, but there is still a large gap to native C performance and the trade off is that the resulting code is several times larger than the compiled C equivalent, limiting the amount of code that can be loaded onto a device. This paper presents techniques to mitigate this code size overhead, making translation to native code a more attractive option, and to further improve performance. We start by analysing the overhead resulting from the basic approach using a set of benchmarks with different characteristics: sort, binary search, fft, rc5, xxtea and md5. We identify three distinct sources of overhead, two of which are related to the JVM’s stack-based architecture, and propose a set of optimisations to target each of them. Combined these optimisations reduce code size overhead by 59%. While they do increase the size of the VM, the break even point at which this fixed cost is compensated for is well within the range of memory typically available on a sensor device, allowing us to load more code on a device. Performance overhead is reduced by 79%, resulting in an average performance that is only 68% slower than optimised C.
Pathophysiology of human ventilatory control

We review the substantial recent progress made in understanding the underlying mechanisms controlling breathing and the applicability of these findings to selected human diseases. Emphasis is placed on the sites of central respiratory rhythm and pattern generation as well as newly described functions of the carotid chemoreceptors, the integrative nature of the central chemoreceptors, and the interaction between peripheral and central chemoreception. Recent findings that support critical contributions from cortical central command and muscle afferent feedback to exercise hyperpnoea are also reviewed. These basic principles, and the evidence supporting chemoreceptor and ventilatory control system plasticity during and following constant and intermittent hypoxaemia and stagnant hypoxia, are applied to: 1) the pathogenesis, consequences and treatment of obstructive sleep apnoea; and 2) exercise hyperpnoea and its control and limitations with ageing, chronic obstructive pulmonary disease and congestive heart failure. We review control of breathing in humans and how new findings lead to novel treatments in sleep apnoea, CHF and COPD http://ow.ly/weJ7A
Effects of ATP on cultured smooth muscle cells from rat aorta

1 Membrane ionic currents provoked by externally applied ATP were studied by patch‐clamp techniques in cultured aortic smooth muscle cells of the rat. 2 Using standard bath and pipette solutions and whole‐cell voltage‐clamp, ATP evoked an inward current when the cell membrane potential was held at −50 mV and an outward current when the potential was held at 30 mV, with a reversal potential near −10 mV. 3 Application of ATPγS gave results similar to those obtained with ATP, while adenosine, AMP and α,β‐methylene ATP were ineffective. The ATP‐activated current was inhibited by suramin, 100 μm. 4 ATP also induced a biphasic rise in internal free Ca levels as shown directly by Fura‐2 measurements and by the increase in Ca‐dependent K single‐channel activity in cell‐attached patches. 5 With outward current through K channels blocked by internal Cs and TEA, modification of the ionic composition of bath and pipette solutions revealed that the reversal potential for the ATP‐induced whole‐cell current closely followed ECl, the chloride equilibrium potential, and was insensitive to manipulations of the monovalent cation gradient. 6 These results indicate that in rat cultured aortic smooth muscle cells, ATP binding to P2‐purinoceptors produces increases of internal free Ca levels and subsequent activation of both Ca‐dependent K and Cl currents.
The role of l+h* pitch accent in discourse construction

L+H* is claimed to evoke contrast between discourse entities in English. To test whether this prominent accent projects a contrastive relation for the discourse foreground, spontaneous continuations of short stories were examined. For both subject and object positions, participants mentioned contrastive alternatives more often when the corresponding discourse entity was introduced with L+H* in the context. Also, the presence of L+H* on a discourse marker (e.g., And NEXT) that preceded the continuation facilitated the mention of the contrastive subject/object. These results do not merely confirm the function of L+H* on arguments in projecting contrastive relations, but also uncovers the facilitative mediation of the contrastive relation by L+H* on a discourse marker.
Mining Search Engine Query Log for Evaluating Content and Structure of a Web Site

Mining search engine query log is a new method for evaluating web site link structure and information architecture. In this paper we propose a new query-URL co-clustering for a web site useful to evaluate information architecture and link structure. Firstly, all queries and clicked URLs corresponding to particular web site are collected from a query log as bipartite graph, one side for queries and the other side for URLs. Then a new content free clustering is applied to cluster queries and URLs concurrently. Afterwards, based on information entropy, clusters of URLs and queries will be used for evaluating link structure and information architecture respectively. Data sets of different web sites have been extracted from a huge query log to evaluate our method, and experiments show promising result.
Design and Implementation of a Microfluidic Logic Gate Chip Based on Double-Stranded DNA

Since the traditional computer based on semiconductor technology is hard to meet people's requirements in information storage and processing, and the development of integrated circuit has been close to its technical limit, explore new calculation model to replace traditional electronic computing is extremely urgent. DNA computing has gained significant research interest, the design of a biochip with DNA computing as a carrier has become a key area in the development of a DNA molecular computer. Logic operation is the basic function in computer operation system, therefore, the research of logic operation in DNA computing system is the key to the realization of DNA computing functions. In this study, logic AND and OR gates on microfluidic chip is developed by means of bio-reaction. This technology is combined with biochip and adopts PMMA (polymethylmecrylate) and PET (polyethylene terephthalate) to fabricate a microscale hybrid chip. Using a DNA strand as an operand, realization of logic AND and OR operation on microfluidic chip is achieved by controlling the annealing of double-stranded DNA. The computing results are rapidly and accurately obtained by detecting the presence of double-stranded DNA in a solution by agarose gel electrophoresis. The microfluidic logic chip accurately realizes logic computations, and it provides a new way for the computation of DNA computer.
Notes on specifying systems in EST

EST is a tool for formal verication of systems. A system to be veried should be specied in a CCS-like syntax. CCS has been chosen because it is widely used in theoretical approaches due to a relatively small set of operators and nice laws valid for them. In this paper we make an overview of operators supported by EST. They can be classied into two groups: standard CCS operators and additional operators which we introduced to shorten specications and to facilitate traslations from other formalisms.
Analysis of Forecasting Indexes for Dental Caries  in 3- to 6-year-old Children.

OBJECTIVE To analyse a possible predictive index for dental caries in 3 to 6 year old children in urban Beijing. METHODS Using random cluster sampling, 2,333 participants from six kindergartens, comprised of 35.7% 3-year-olds, 32.4% 4-year-olds and 31.9% 5-year-olds in urban Beijing were selected. At baseline, questionnaires were administered to about half of the parents. Children's oral health condition was examined at baseline and 6, 12 and 18 months later. In total there were 1,094 children who completed the 18-month evaluation. RESULTS The baseline caries prevalence was 56.4%, and the mean dmft (decayed, missing and filled primary teeth) and dmfs (decayed, missing and filled primary surfaces) were 2.66 and 5.60, respectively. There were 62.3% parents who were aware of oral health knowledge, and amongst which the accuracy rate for attitudes regarding oral healthcare was 82.1%. The caries incidence in children who completed the evaluation was 55.3%, and mean increases in dmft and dmfs were 1.62 and 3.93, respectively. Predictive factors related to caries incidence were "past caries experience" [odds ratio (OR) = 4.969, P < 0.001], "parents help children brush teeth daily" (OR = 0.851, P = 0.046), and "parents consider that primary caries need to be treated" (OR = 1.270, P = 0.031). The sensitivity and specificity of "past caries experience" were 69.4% and 73.2%, respectively, and the sensitivity of the three indices combined was 88.4%. CONCLUSION "Past caries experience" was an important predictor for primary caries incidence, and can be used in combination with "parents help children brush teeth daily" and "parents consider that primary caries need to be treated" as a predictive index.
HW3D: A tool for interactive real-time 3D visualization in GIS supported flood modelling

Large numerical calculations are made to get a prediction what damage a possible flood would cause. These results of the simulation are used to prevent further flood catastrophes. The more realistic a visualization of these calculations is the more precaution will be taken by the local authority and the citizens. This paper describes a tool and techniques to get a realistic looking, three-dimensional, easy to use, realtime visualization despite of the huge amount of data given from the flood simulation process.
Quantifying retinal nerve fiber layer thickness histologically: a novel approach to sectioning of the retina.

PURPOSE To present a technique of ocular sectioning that enables continuous histologic measurements of peripapillary retinal nerve fiber layer (RNFL) thickness in a concentric ring around the optic disc, corresponding to similar regions measured by in vivo imaging techniques. METHODS Two pig eyes and two normal human eyes were processed using the "umbrella" technique, in which peripapillary concentric ring sections were obtained, at increasing diameters, all centered on the optic disc. Each histologic ring section contains a continuous circumferential 360 degrees retinal slice, oriented approximately perpendicular to the retinal surface. Every histologic slice contains each axon of the retina, sectioned perpendicular to each axon's long axis and at an equal set distance from the disc margin. RESULTS Ring sections from pig and human eyes are presented and correlated to known RNFL anatomy. For the two human eyes, peripapillary RNFL thickness was quantified and plotted, resulting in the expected double-hump pattern. CONCLUSIONS The umbrella technique provides, on a single histologic section, all necessary information for quantifying the entire RNFL layer of that eye, in a standardized fashion. This technique can simplify the process of analyzing the RNFL thickness histologically, assist in obtaining a normative database of RNFL thickness in humans, and be implemented as a histologic end point in animal studies evaluating new treatment modalities for glaucoma.
COMPUTATION OF GENERATIVE FAMILIES OF POSITIVE SEMI-FLOWS IN TWO TYPES OF COLOURED NETS

It is well known that a generative family of positive flows provides a more accurate information than a generative family of ordinary ones. For instance with the help of positive flows one can decide the structural boundness of the nets and detect the structural implicit places. Up to now, no computation of positive flows has been developed for coloured nets. In this paper, we present a computation of positive flows for two basic families of coloured nets: unary regular nets and unary Predicate/Transition nets. First of all, we show that these two computations are based on the resolution of the parametrized equation A.X1=A.X2=. =A.Xn where A is a matrix and X i, the unknowns are vectors. Thus an algorithm is presented to solve this equation and at last we show how this algorithm can be used to compute the generative family of semi-flows in the unary regular nets and unary Predicate/Transition nets.
A comparison of worldwide phonemic and genetic variation in human populations

Significance Linguistic data are often combined with genetic data to frame inferences about human population history. However, little is known about whether human demographic history generates patterns in linguistic data that are similar to those found in genetic data at a global scale. Here, we analyze the largest available datasets of both phonemes and genotyped populations. Similar axes of human geographic differentiation can be inferred from genetic data and phoneme inventories; however, geographic isolation does not necessarily lead to the loss of phonemes. Our results show that migration within geographic regions shapes phoneme evolution, although human expansion out of Africa has not left a strong signature on phonemes. Worldwide patterns of genetic variation are driven by human demographic history. Here, we test whether this demographic history has left similar signatures on phonemes—sound units that distinguish meaning between words in languages—to those it has left on genes. We analyze, jointly and in parallel, phoneme inventories from 2,082 worldwide languages and microsatellite polymorphisms from 246 worldwide populations. On a global scale, both genetic distance and phonemic distance between populations are significantly correlated with geographic distance. Geographically close language pairs share significantly more phonemes than distant language pairs, whether or not the languages are closely related. The regional geographic axes of greatest phonemic differentiation correspond to axes of genetic differentiation, suggesting that there is a relationship between human dispersal and linguistic variation. However, the geographic distribution of phoneme inventory sizes does not follow the predictions of a serial founder effect during human expansion out of Africa. Furthermore, although geographically isolated populations lose genetic diversity via genetic drift, phonemes are not subject to drift in the same way: within a given geographic radius, languages that are relatively isolated exhibit more variance in number of phonemes than languages with many neighbors. This finding suggests that relatively isolated languages are more susceptible to phonemic change than languages with many neighbors. Within a language family, phoneme evolution along genetic, geographic, or cognate-based linguistic trees predicts similar ancestral phoneme states to those predicted from ancient sources. More genetic sampling could further elucidate the relative roles of vertical and horizontal transmission in phoneme evolution.
A Possible Influence of the Spindle Fibre on Crossing-Over in Drosophila.

The distribution of genes in the second and third chromosomes of Drosophila melanogaster suggests that crossing-over may be influenced by the spindle fibre at least in neighboring regions. The disparity between the genetic and cytological maps of these chromosomes especially in the spindle fibre regions (Dobzhanzky 2,3) is consistent with such a view.
The role of the primary auditory cortex in the neural mechanism of auditory verbal hallucinations

Auditory verbal hallucinations (AVHs) are a subjective experience of “hearing voices” in the absence of corresponding physical stimulation in the environment. The most remarkable feature of AVHs is their perceptual quality, that is, the experience is subjectively often as vivid as hearing an actual voice, as opposed to mental imagery or auditory memories. This has lead to propositions that dysregulation of the primary auditory cortex (PAC) is a crucial component of the neural mechanism of AVHs. One possible mechanism by which the PAC could give rise to the experience of hallucinations is aberrant patterns of neuronal activity whereby the PAC is overly sensitive to activation arising from internal processing, while being less responsive to external stimulation. In this paper, we review recent research relevant to the role of the PAC in the generation of AVHs. We present new data from a functional magnetic resonance imaging (fMRI) study, examining the responsivity of the left and right PAC to parametrical modulation of the intensity of auditory verbal stimulation, and corresponding attentional top-down control in non-clinical participants with AVHs, and non-clinical participants with no AVHs. Non-clinical hallucinators showed reduced activation to speech sounds but intact attentional modulation in the right PAC. Additionally, we present data from a group of schizophrenia patients with AVHs, who do not show attentional modulation of left or right PAC. The context-appropriate modulation of the PAC may be a protective factor in non-clinical hallucinations.
Perceived Synchronization of Mulsemedia Services

Multimedia synchronization involves a temporal relationship between audio and visual media components. The presentation of “in-sync” data streams is essential to achieve a natural impression, as “out-of-sync” effects are often associated with user quality of experience (QoE) decrease . Recently , multi-sensory media (mulsemedia) has been demonstrated to provide a highly immersive experience for its users. Unlike traditional multimedia, mulsemedia consists of other media types (i.e., haptic, olfaction, taste, etc.) in addition to audio and visual content. Therefore, the goal of achieving high quality mulsemedia transmission is to present no or little synchronization errors between the multiple media components. In order to achieve this ideal synchronization, there is a need for comprehensive knowledge of the synchronization requirements at the user interface. This paper presents the results of a subjective study carried out to explore the temporal boundaries within which haptic and air-flow media objects can be successfully synchronized with video media. Results show that skews between sensorial media and multimedia might still give the effect that the mulsemedia sequence is “in-sync” and provide certain constraints under which synchronization errors might be tolerated. The outcomes of the paper are used to provide recommendations for mulsemedia service providers in order for their services to be associated with acceptable user experience levels, e.g. haptic media could be presented with a delay of up to 1 s behind video content, while air-flow media could be released either 5 s ahead of or 3 s behind video content.