Miracle-dz/UniFAR-FTUs huggingface dataset:
Subnetwork State Functions Define Dysregulated Subnetworks in Cancer

Emerging research demonstrates the potential of protein-protein interaction (PPI) networks in uncovering the mechanistic bases of cancers, through identification of interacting proteins that are coordinately dysregulated in tumorigenic and metastatic samples. When used as features for classification, such coordinately dysregulated subnetworks improve diagnosis and prognosis of cancer considerably over single-gene markers. However, existing methods formulate coordination between multiple genes through additive representation of their expression profiles and utilize fast heuristics to identify dysregulated subnetworks, which may not be well suited to the potentially combinatorial nature of coordinate dysregulation. Here, we propose a combinatorial formulation of coordinate dysregulation and decompose the resulting objective function to cast the problem as one of identifying subnetwork state functions that are indicative of phenotype. Based on this formulation, we show that coordinate dysregulation of larger subnetworks can be bounded using simple statistics on smaller subnetworks. We then use these bounds to devise an efficient algorithm, Crane, that can search the subnetwork space more effectively than existing algorithms. Comprehensive cross-classification experiments show that subnetworks identified by Crane outperform those identified by additive algorithms in predicting metastasis of colorectal cancer (CRC).
Bayesian Additive Regression Tree Calibration of Complex High-Dimensional Computer Models

Complex natural phenomena are increasingly investigated by the use of a complex computer simulator. To leverage the advantages of simulators, observational data need to be incorporated in a probabilistic framework so that uncertainties can be quantified. A popular framework for such experiments is the statistical computer model calibration experiment. A limitation often encountered in current statistical approaches for such experiments is the difficulty in modeling high-dimensional observational datasets and simulator outputs as well as high-dimensional inputs. As the complexity of simulators seems to only grow, this challenge will continue unabated. In this article, we develop a Bayesian statistical calibration approach that is ideally suited for such challenging calibration problems. Our approach leverages recent ideas from Bayesian additive regression Tree models to construct a random basis representation of the simulator outputs and observational data. The approach can flexibly handle high-dimensional datasets, high-dimensional simulator inputs, and calibration parameters while quantifying important sources of uncertainty in the resulting inference. We demonstrate our methodology on a CO2 emissions rate calibration problem, and on a complex simulator of subterranean radionuclide dispersion, which simulates the spatial–temporal diffusion of radionuclides released during nuclear bomb tests at the Nevada Test Site. Supplementary computer code and datasets are available online.
Identification of a unique domain essential for Escherichia coli DNA topoisomerase III‐catalysed decatenation of replication intermediates

A 17‐amino‐acid residue domain has been identified in Escherichia coli DNA topoisomerase III (Topo III) that is essential for Topo III‐mediated resolution of DNA replication intermediates in vitro. Deletion of this domain reduced Topo III‐catalysed resolution of DNA replication intermediates and decatenation of multiply linked plasmid DNA dimers by four orders of magnitude, whereas reducing Topo III‐catalysed relaxation of negatively supercoiled DNA substrates only 20‐fold. The presence of this domain has been detected in multiple plasmid‐encoded topoisomerases, raising the possibility that these enzymes may also be decatenases.
Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein.

BACKGROUND The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution. METHODS Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via delta-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after > or =7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2-4 days of therapy) due to MRSA. RESULTS The 2 groups had comparable baseline characteristics but differed in their clinical courses (e.g., endocarditis was more frequent in patients with PB than in those with RB [43% vs. 0%, respectively; P=.0016]); isolates from patients with PB exhibited higher rates of (1) survival in vitro after exposure to tPMP (22.4+/-14.8% vs. 11.6+/-6.5%, respectively; P=.005); (2) defective delta-lysin production (71.4% vs. 38.9%, respectively; P=.057); (3) non-agr genotype II profile (100% vs. 77.8%, respectively; P=.037); and (4) overrepresentation of a specific PFGE genotype (85.7% vs. 44.4%, respectively; P=.015). CONCLUSIONS Isolates from patients with PB differed from those in patients with RB, in several in vitro characteristics. Further studies will be necessary to define how these factors might affect clinical outcome.
The Influence of Tone Inventory on ERP without Focal Attention: A Cross-Language Study

This study investigates the effect of tone inventories on brain activities underlying pitch without focal attention. We find that the electrophysiological responses to across-category stimuli are larger than those to within-category stimuli when the pitch contours are superimposed on nonspeech stimuli; however, there is no electrophysiological response difference associated with category status in speech stimuli. Moreover, this category effect in nonspeech stimuli is stronger for Cantonese speakers. Results of previous and present studies lead us to conclude that brain activities to the same native lexical tone contrasts are modulated by speakers' language experiences not only in active phonological processing but also in automatic feature detection without focal attention. In contrast to the condition with focal attention, where phonological processing is stronger for speech stimuli, the feature detection (pitch contours in this study) without focal attention as shaped by language background is superior in relatively regular stimuli, that is, the nonspeech stimuli. The results suggest that Cantonese listeners outperform Mandarin listeners in automatic detection of pitch features because of the denser Cantonese tone system.
The Cell Population of Dorsal Root Ganglia in Children with Neurospinal Dysraphism

The number and apparent maturation of nerve cells in the dorsal root ganglia at the level of T7 in children dying with neurospinal dysraphism (myelomeningocele with hydrocephalus) appears to be within normal limits, and the cell count may be normal at cord levels associated with myelomeningoceles when the child shows no evidence of paralysis.
Control Flow Analysis Can Find New Flaws Too

A previous study [6] showed how control flow analysis can be applied to analyse key distribution protocols based on symmetric key cryptography. We have extended both the theoretical treatment and our fully automatic verifier to deal with protocols based on asymmetric cryptography. This paper reports on the application of our technique – exemplified on the Beller-Chang-Yacobi MSR protocol, which uses both symmetric and asymmetric cryptography – and show how we discover an undocumented flaw.
The mammalian target of rapamycin pathway as a therapeutic target in multiple myeloma

The mammalian target of rapamycin (mTOR) is centrally located, linking proximal oncogenic cascades to critical downstream pathways that drive tumor growth. mTOR regulates such diverse functions as protein translation, proliferation, viability, autophagy, metabolism homeostasis, monitoring of energy reserves, and induction of angiogenesis. Given its fundamental role in tumorigenesis, it is not surprising that a huge effort is being made to develop mTOR inhibitors. The existence of feedback pathways that become activated subsequent to mTOR inhibition has complicated these efforts. However, the fact that mTOR exists in two separate complexes, TORC1 and TORC2, and rapalogs primarily inhibit only TORC1 and TORC2 is actually a key activator of AKT, has injected new energy into the quest to find inhibitors that can inhibit both complexes. In myeloma models, preclinical studies confirm the activity of rapalogs as well as newer TORC1/TORC2 inhibitors, and early phase clinical trials have begun. In addition, the recent finding of up-regulated myeloma cell expression of DEPTOR, an mTOR binding protein that restricts mTOR activity, suggests an additional future therapeutic target specific to the myeloma tumor model.
Scaling Variables and Stability of Hyperbolic Fronts

We consider the damped hyperbolic equation $$ \epsilon u_{tt} + u_t \,=\, u_{xx} + \FF(u) , \quad x \in \mathbf{R} , \quad t \ge 0 , \leqno(1) $$ where $\epsilon$ is a positive, not necessarily small parameter. We assume that $\FF(0) = \FF(1) = 0$ and that $\FF$ is concave on the interval [0,1]. Under these hypotheses, (1) has a family of monotone traveling wave solutions (or propagating fronts) connecting the equilibria u=0 and u=1. This family is indexed by a parameter $c \ge c_*$ related to the speed of the front. In the critical case $c=c_*$, we prove that the traveling wave is asymptotically stable with respect to perturbations in a weighted Sobolev space. In addition, we show that the perturbations decay to zero like $t^{-3/2}$ as $t \to +\infty$ and approach a universal self-similar profile, which is independent of $\epsilon$, F, and the initial data. In particular, our solutions behave for large times like those of the parabolic equation obtained by setting $\epsilon = 0$ in (1). The proof of our .
At the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathways

The metabolic syndrome is becoming increasingly prevalent in the general population and carries significant incremental morbidity and mortality. It is associated with multi‐organ involvement and increased all‐cause mortality, resembling a precocious aging process. The mechanisms that account for this phenomenon are incompletely known, but it is becoming clear that longevity genes might be involved. Experiments with overactivation or disruption of key lifespan determinant pathways, such as silent information regulator (SIR)T1, p66Shc, and mammalian target of rapamycin (TOR), lead to development of features of the metabolic syndrome in mice. These genes integrate longevity pathways and metabolic signals in a complex interplay in which lifespan appears to be strictly dependent on substrate and energy bioavailability. Herein, we describe the roles and possible interconnections of selected lifespan determinant molecular networks in the development of the metabolic syndrome and its complications, describing initial available data in humans. Additional pathways are involved in linking nutrient availability and longevity, certainly including insulin and Insulin‐like Growth Factor‐1 (IGF‐1) signaling, as well as FOXO transcription factors. The model described in this viewpoint article is therefore likely to be an oversimplification. Nevertheless, it represents one starting platform for understanding cell biology of lifespan in relation to the metabolic syndrome.
Status, guild and diversity of avian fauna from a wetland site and surroundings, in Krishnagar, a City beside tropic of cancer, West Bengal, India

A total of 98 taxa of avifauna belonging to 46 families has been recorded in a survey carried out from November 2012 to March 2016 at a wetland site (Sadhanpara Beel) and surroundings located in Krishnagar Block II, West Bengal, beside tropic of cancer. This is the first report of the avian diversity from the area. The site provided habitat to 59 species of resident, 16 species of winter migratory, 15 species of local migratory and 8 species of summer migratory bird. Among the feeding guilds, insectivores dominate in species strength (31.63%) closely followed by carnivores (25.51%), omnivores (19.38%), frugivore and grainivore (8.16%), piscivore (5.10%) and nectarivores (2.04%). Survey shows that the landscape is visited by one Near threatened (Black headed Ibis), one Vulnerable (Lesser Adjutant stork) and one Critically endangered (Indian vulture) occasionally. The results of relative diversity (RD) index showed that Accipitridae (RD value = 7.14) was the dominant family in the area. This is the first report of avifaunal diversity from the area. The present check list will provide baseline information for the bird diversity in and around the area.
The Developing Bone: Slave or Master of Its Cells and Molecules?

A large number of molecular, cellular, and epidemiologic factors have been implicated in the regulation of bone development. A major unsolved problem is how to integrate these disparate findings into a concept that explains the development of bone as an organ. Often events on the organ level are simply presented as the cumulative effect of all factors that individually are known to influence bone development. In such a cumulative model it must be assumed that each bone cell carries the construction plan of the entire skeletal anatomy in its genes. This scenario is implausible, because it would require an astronomical amount of positional information. We therefore propose a functional model of bone development, which is based on Frost's mechanostat theory. In this model the genome only provides positional information for the basic outline of the skeleton as a cartilaginous template. Thereafter, bone cell action is coordinated by the mechanical requirements of the bone. When mechanical challenges exceed an acceptable level (the mechanostat set point), bone tissue is added at the location where it is mechanically necessary. The main mechanical challenges during growth result from increases in bone length and in muscle force. Hormones, nutrition, and environmental factors exert an effect on bone either directly by modifying the mechanostat system or indirectly by influencing longitudinal bone growth or muscle force. Predictions based on this model are in accordance with observations on prenatal, early postnatal, and pubertal bone development. We propose that future studies on bone development should address topics that can be derived from the mechanostat model.
The neuronal architecture of the mushroom body provides a logic for associative learning

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell–MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory. DOI: http://dx.doi. org/10.7554/eLife.04577. 001
Culture and Context: An Empirical Study for the Development of a Framework for the Elicitation of Cultural Influence in Product Usage

The globalization of the economy is leading to greater diversification among user groups. Product designers will therefore have to take account of the cultural differences between these user groups. This article first defines the construct of culture with regard to human-computer interaction and presents various possible cultural influences. It then considers how the concept of culture is defined in psychological theories on human-computer interaction. This information is then used as a basis for drawing up requirements to be met by methods for recording cultural influences. Qualitative methods seem to be particularly promising. Empirical work was carried out to identify factors that influence the use of products in foreign cultures. A total of 35 Indian households in Bombay and New Delhi were selected for a qualitative study in which a washing machine developed in Germany was used for a period of 3 weeks. From observations and interviews it was possible to identify 8 factors that need to be taken into consideration when defining requirements in different cultures.
Combined RLS-LMS initialization for per tone equalizers in DMT-receivers

In classical discrete multi tone receivers, the equalizer structure consists of a (real) time domain equalizer (TEQ) combined with (complex) 1-taps frequency domain equalizers. Recently, an alternative receiver was introduced based on a separate per tone equalization, where the SNR on each tone and hence the bitrate is maximized. In this paper, a new adaptive initialization scheme for this per tone equalizer (PTEQ) is introduced, based on a combination of Least Mean Squares (LMS) and Recursive Least Squares (RLS) with inverse updating. It will be shown that the proposed method exhibits only slightly slower convergence compared to full RLS with inverse updating, while complexity as well as memory cost are reduced considerably.
Antioxidant and Hepatoprotective Effects of Silibinin in a Rat Model of Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease related to the metabolic syndrome, obesity and diabetes. The rising prevalence of NASH and the lack of efficient treatments have led to the exploration of different therapeutic approaches. Milk thistle (Silibum marianum) is a medicinal plant used for its hepatoprotective properties in chronic liver disease since the 4th century BC. We explored the therapeutic effect of silibinin, the plant's most biologically active extract, in an experimental rat NASH model. A control group was fed a standard liquid diet for 12 weeks. The other groups were fed a high-fat liquid diet for 12 weeks without (NASH) or with simultaneous daily supplement with silibinin–phosphatidylcholine complex (Silibinin 200 mg kg−1) for the last 5 weeks. NASH rats developed all key hallmarks of the pathology. Treatment with silibinin improved liver steatosis and inflammation and decreased NASH-induced lipid peroxidation, plasma insulin and TNF-α. Silibinin also decreased O2 ∙− release and returned the relative liver weight as well as GSH back to normal. Our results suggest that milk thistle's extract, silibinin, possesses antioxidant, hypoinsulinemic and hepatoprotective properties that act against NASH-induced liver damage. This medicinal herb thus shows promising therapeutic potential for the treatment of NASH.
Cloning and Functional Characterization of a β-Pinene Synthase from Artemisia annua That Shows a Circadian Pattern of Expression1

Artemisia annua plants produce a broad range of volatile compounds, including monoterpenes, which contribute to the characteristic fragrance of this medicinal species. A cDNA clone, QH6, contained an open reading frame encoding a 582-amino acid protein that showed high sequence identity to plant monoterpene synthases. The prokaryotically expressed QH6 fusion protein converted geranyl diphosphate to (−)-β-pinene and (−)-α-pinene in a 94:6 ratio. QH6 was predominantly expressed in juvenile leaves 2 weeks postsprouting. QH6 transcript levels were transiently reduced following mechanical wounding or fungal elicitor treatment, suggesting that this gene is not directly involved in defense reaction induced by either of these treatments. Under a photoperiod of 12 h/12 h (light/dark), the abundance of QH6 transcripts fluctuated in a diurnal pattern that ebbed around 3 h before daybreak (9th h in the dark phase) and peaked after 9 h in light (9th h in the light phase). The contents of (−)-β-pinene in juvenile leaves and in emitted volatiles also varied in a diurnal rhythm, correlating strongly with mRNA accumulation. WhenA. annua was entrained by constant light or constant dark conditions, QH6 transcript accumulation continued to fluctuate with circadian rhythms. Under constant light, advanced cycles of fluctuation of QH6 transcript levels were observed, and under constant dark, the cycle was delayed. However, the original diurnal pattern could be regained when the plants were returned to the normal light/dark (12 h/12 h) photoperiod. This is the first report that monoterpene biosynthesis is transcriptionally regulated in a circadian pattern.
Oxygen-linked hydrogen ion binding of human hemoglobin. Effects of carbon dioxide and 2,3-diphosphoglycerate.

The Bohr coefficient, b, and the Haldane coefficient, h, were measured simultaneously in erythrolysates in the presence and absence of CO2and 2,3-diphosphoglycerate. We found b—h=—0.04 (—0.023 to —0.054) although b—h=—0 according to the linkage equation. The cause of the observed difference seems to be that his measured as the mean value for oxygen saturation fractions (zHbO2) between 0 and 1, while brefers to a zHbO2of 0.54. Apparently b(and h) varies with zHbO2and reaches a numerical maximum at an intermediate zHbO2value.
Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat H9c2(2-1) Cardiomyocytes

This study was aimed at preliminarily assessing the cytoprotective and antioxidative effects of rice bran extracts (RBEs) from a Sarawak local rice variety (local name: “BJLN”) and a commercial rice variety, “MR219,” on oxidative stress in rat H9c2(2-1) cardiomyocytes. The cardiomyocytes were incubated with different concentrations of RBE and hydrogen peroxide (H2O2), respectively, to identify their respective IC50 values and safe dose ranges. Two nonlethal and close-to-IC50 doses of RBE were selected to evaluate their respective effects on H2O2 induced oxidative stress in cardiomyocytes. Both RBEs showed dose-dependent cytotoxicity effects on cardiomyocytes. H2O2 induction of cardiomyocytes pretreated with RBE further revealed the dose-dependent cytoprotective and antioxidative effects of RBE via an increase in IC50 values of H2O2. Preliminary analyses of induction effects of RBE and H2O2 on cellular antioxidant enzyme, catalase (CAT), also revealed their potential in regulating these activities and expression profile of related gene on oxidative stress in cardiomyocytes. Pretreated cardiomyocytes significantly upregulated the enzymatic activity and expression level of CAT under the exposure of H2O2 induced oxidative stress. This preliminary study has demonstrated the potential antioxidant effects of RBE in alleviating H2O2-mediated oxidative injuries via upregulation in enzymatic activities and expression levels of CAT.