Miracle-dz/UniFAR-FTUs huggingface dataset:
The Plastid Protein THYLAKOID FORMATION1 and the Plasma Membrane G-Protein GPA1 Interact in a Novel Sugar-Signaling Mechanism in Arabidopsis[W]

Mutations in genes encoding components of the heterotrimeric G-protein complex were previously shown to confer altered sensitivity to increased levels of d-glucose. This suggests that G-protein coupling may be a novel sugar-signaling mechanism in Arabidopsis thaliana. THYLAKOID FORMATION1 (THF1) is here demonstrated in vivo as a Gα interaction partner that functions downstream of the plasma membrane–delimited heterotrimeric G-protein (GPA1) in a d-glucose signaling pathway. THF1 is a plastid protein localized to both the outer plastid membrane and the stroma. Contact between root plastidic THF1 and GPA1 at the plasma membrane occurs at sites where the plastid membrane abuts the plasma membrane, as demonstrated by Förster resonance energy transfer (FRET). A probable role for THF1 in sugar signaling is demonstrated by both biochemical and genetic evidence. Root growth in the thf1-1 null mutant is hypersensitive to exogenous d-glucose, and THF1-overexpressing roots are resistant to inhibition of growth rate by high d-glucose. Additionally, THF1 levels are rapidly degraded by d-glucose but not l-glucose. The interaction between THF1 and GPA1 has been confirmed by in vitro and in vivo coimmunoprecipitation, FRET analysis, and genetic epistasis and provides evidence of a sugar-signaling mechanism between plastids and the plasma membrane.
Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer

Background This study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment. Methods Female Fischer 344 rats were fed either a control diet for the entire study (control), or switched to a diet containing fish oil (2.0 g /100 g of diet) one week prior to tumor implantation (long term fish oil) or at the start of chemotherapy (adjuvant fish oil). Chemotherapy (irinotecan plus 5-fluorouracil) was initiated 2 weeks after tumor implantation (cycle-1) and 1 week thereafter (cycle-2). Reference animals received no tumor or treatment and only consumed the control diet. All skeletal muscle measures were conducted in the gastrocnemius. To assess myosteatosis, lipids were assessed histologically by Oil Red O staining and total triglyceride content was quantified by gas chromatography. Expression of adipogenic transcription factors were assessed at the mRNA level by real-time RT-PCR. Results Feeding a diet containing fish oil significantly reduced tumor- and subsequent chemotherapy-associated increases in skeletal muscle neutral lipid (p<0.001) and total triglyceride content (p<0.03), and expression of adipogenic transcription factors (p<0.01) compared with control diet fed animals. The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p<0.01). Conclusion Long term and adjuvant fish oil diets are equally efficacious in reducing chemotherapy-associated myosteatosis that may be occurring by reducing expression of transcription factors involved in adipogenesis/lipogenesis, and improving tumor-response to chemotherapy in a neoplastic model.
Bayesian statistical model checking with application to Stateflow/Simulink verification

We address the problem of model checking stochastic systems, i.e., checking whether a stochastic system satisfies a certain temporal property with a probability greater (or smaller) than a fixed threshold. In particular, we present a Statistical Model Checking (SMC) approach based on Bayesian statistics. We show that our approach is feasible for a certain class of hybrid systems with stochastic transitions, a generalization of Simulink/Stateflow models. Standard approaches to stochastic discrete systems require numerical solutions for large optimization problems and quickly become infeasible with larger state spaces. Generalizations of these techniques to hybrid systems with stochastic effects are even more challenging. The SMC approach was pioneered by Younes and Simmons in the discrete and non-Bayesian case. It solves the verification problem by combining randomized sampling of system traces (which is very efficient for Simulink/Stateflow) with hypothesis testing (i.e., testing against a probability threshold) or estimation (i.e., computing with high probability a value close to the true probability). We believe SMC is essential for scaling up to large Stateflow/Simulink models. While the answer to the verification problem is not guaranteed to be correct, we prove that Bayesian SMC can make the probability of giving a wrong answer arbitrarily small. The advantage is that answers can usually be obtained much faster than with standard, exhaustive model checking techniques. We apply our Bayesian SMC approach to a representative example of stochastic discrete-time hybrid system models in Stateflow/Simulink: a fuel control system featuring hybrid behavior and fault tolerance. We show that our technique enables faster verification than state-of-the-art statistical techniques. We emphasize that Bayesian SMC is by no means restricted to Stateflow/Simulink models. It is in principle applicable to a variety of stochastic models from other domains, e.g., systems biology.
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences

The heterogeneous collection of nucleosome remodelling and deacetylation (NuRD) complexes can be grouped into the MBD2- or MBD3-containing complexes MBD2–NuRD and MBD3–NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here, we show that MBD2–NuRD, in contrast to MBD3–NuRD, converts open chromatin with euchromatic histone modifications into tightly compacted chromatin with repressive histone marks. Genome-wide, a strong enrichment for MBD2 at methylated CpG sequences is found, whereas CpGs bound by MBD3 are devoid of methylation. MBD2-bound genes are generally lower expressed as compared with MBD3-bound genes. When depleting cells for MBD2, the MBD2-bound genes increase their activity, whereas MBD2 plus MBD3-bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes.
Uncovering transcriptional regulators by combined relevance analysis of genome-wide transcription-factor binding data and gene expression

We present a method for integrating data from genome-wide location of DNA-binding proteins and gene expression to uncover relevant transcriptional regulators without any previous biological knowledge. We show that this method correctly identifies known regulators for the biological processes under study in three expression datasets. While other computational methods have been proposed to suggest transcriptional regulators, most have not integrated genome-wide binding data, which describes physical interactions between transcription factors and the regions upstream from a gene. Our method suggests likely regulators of the biological process under study in an expression dataset and is not limited to coexpressed regulators. The method comprises three steps: (i) assign a relevance score to the binding information of a transcription factor with respect to the correlation of all genes under study in the expression dataset; (ii) calculate the significance of the score; (iii) analyze the over-representation of the number of such significant interactions for a given transcription factor when compared to randomized datasets. This tool allows researchers to uncover those regulators whose genome-wide binding events are predictive of an expression dataset. It suggests the biological processes in which the regulators are active. The synergistic approach of this work represents a valuable tool for researchers in functional genomics. Thesis Supervisor: David K. Gifford Title: Professor
A sequential dual method for large scale multi-class linear svms

Efficient training of direct multi-class formulations of linear Support Vector Machines is very useful in applications such as text classification with a huge number examples as well as features. This paper presents a fast dual method for this training. The main idea is to sequentially traverse through the training set and optimize the dual variables associated with one example at a time. The speed of training is enhanced further by shrinking and cooling heuristics. Experiments indicate that our method is much faster than state of the art solvers such as bundle, cutting plane and exponentiated gradient methods.
Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri

Cervical cancer is strongly associated with infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear an HPV infection, some develop persistent infections that may lead to cancer. The determinants of persistent infection are largely unknown. We have previously shown that women developing carcinoma in situ of the cervix uteri have higher titers of HPV 16 long before development of cervical neoplasia, indicating that the immune response to HPV is important in determining the outcome of an infection. The HLA class II alleles DRB1*1501 and DQB1*0602 have previously been associated with an increased risk of HPV infection, and carriers of these alleles also tend to have more long‐term infections. Together these results indicate that certain HLA alleles may affect the ability to control the HPV copy number. To evaluate this possibility, we studied the HLA class II DRB1*1501‐DQB1*0602 haplotype, as well as the alleles individually, and the HPV 16 titer in 928 women from a retrospective case‐control study (441 cases and 487 controls). Carriers of the haplotype DRB1*1501‐DQB1*0602 allele have a significantly higher HPV 16 titer compared to noncarriers (t‐test with unequal variance, p = 0.017). An association was found between the HLA haplotype carrier frequency and HPV 16 titer (Mantel‐Haenszel statistics p = 0.005). To study whether titer is related to the persistency of infection, women were divided into groups with long‐term and short‐term infection. A strong correlation is seen between long‐term infection and high viral load and between short‐term infection and low viral load. These results show that host genetic factors, e.g., variation at the HLA class II loci studied, may affect the immune reaction to the virus and thereby indirectly increase the susceptibility to carcinoma in situ of the cervix uteri. © 2002 Wiley‐Liss, Inc.
A point is normal for almost all maps βx+α mod 1 or generalized β-transformations

Abstract We consider the map Tα,β(x):=βx+α mod 1, which admits a unique probability measure μα,β of maximal entropy. For x∈[0,1], we show that the orbit of x is μα,β-normal for almost all (α,β)∈[0,1)×(1,∞) (with respect to Lebesgue measure). Nevertheless, we construct analytic curves in [0,1)×(1,∞) along which the orbit of x=0 is μα,β-normal at no more than one point. These curves are disjoint and fill the set [0,1)×(1,∞). We also study the generalized β-transformations (in particular, the tent map). We show that the critical orbit x=1 is normal with respect to the measure of maximal entropy for almost all β.
Aura alphavirus subgenomic RNA is packaged into virions of two sizes

The alphavirus genome is 11.8 kb in size. During infection, a 4.2-kb subgenomic RNA is also produced. Most alphaviruses package only the genomic RNA into virions, which are enveloped particles with icosahedral symmetry, having a triangulation number (T) = 4. Aura virus, however, packages both the genomic RNA and the subgenomic RNA into virions. The genomic RNA is primarily packaged into a virion that has a diameter of 72 nm and which appears to be identical to the virions produced by other alphaviruses. The subgenomic RNA is packaged into two major, regular particles with diameters of 72 and 62 nm. The 72-nm-diameter particle appears to be identical in construction to virions containing genomic RNA. The 62-nm-diameter particle probably has T = 3. The large and small Aura virions can be partially separated in sucrose gradients. In addition to these two major classes of particles, there are other particles produced that appear to arise from abortive assembly. From these results and from previous studies of alphavirus assembly, we suggest that during assembly of alphavirus nucleocapsids in the infected cell there is a specific initiation event followed by recruitment of additional capsid subunits into the complex, that the triangulation number of the complex is not predetermined but depends upon the size of the RNA and interactions that occur during assembly, and that budding of assembled nucleocapsids results in the acquisition of an envelope containing glycoproteins arranged in a manner determined by the nucleocapsid.
What are Emotional States, and Why Do We Have Them?

An approach to emotion is described in which emotions are defined as states elicited by instrumental reinforcers, that is, by stimuli that are the goals for action. This leads to a theory of the evolutionary adaptive value of emotions, which is that different genes specify different goals in their own self-interest, and any actions can then be learned and performed by instrumental learning to obtain the goals. The brain mechanisms for emotion in brain regions such as the orbitofrontal and anterior cingulate cortex provide a foundation for understanding the neural basis of emotion. Classically conditioned effects may modulate the actions initiated by this system. In addition to this instrumental learning system, some stimuli may elicit responses, for example approach, withdrawal, or fixed action patterns, but intervening states are not required for this type of adaptive response. In addition, a rational thought system involved in multistep planning can allow gene-specified goals to be deferred or avoided in order to achieve longer-term types of goals that may be more advantageous to the individual than to the genes.
Sec61p contributes to signal sequence orientation according to the positive-inside rule.

Protein targeting to the endoplasmic reticulum is mediated by signal or signal-anchor sequences. They also play an important role in protein topogenesis, because their orientation in the translocon determines whether their N- or C-terminal sequence is translocated. Signal orientation is primarily determined by charged residues flanking the hydrophobic core, whereby the more positive end is predominantly positioned to the cytoplasmic side of the membrane, a phenomenon known as the "positive-inside rule. " We tested the role of conserved charged residues of Sec61p, the major component of the translocon in Saccharomyces cerevisiae, in orienting signals according to their flanking charges by site-directed mutagenesis by using diagnostic model proteins. Mutation of R67, R74, or E382 in Sec61p reduced C-terminal translocation of a signal-anchor protein with a positive N-terminal flanking sequence and increased it for signal-anchor proteins with positive C-terminal sequences. These mutations produced a stronger effect on substrates with greater charge difference across the hydrophobic core of the signal. For some of the substrates, a charge mutation in Sec61p had a similar effect as one in the substrate polypeptides. Although these three residues do not account for the entire charge effect in signal orientation, the results show that Sec61p contributes to the positive-inside rule.
Adaptive Bas‐relief Generation from 3D Object under Illumination

Bas‐relief is designed to provide 3D perception for the viewers under illumination. For the problem of bas‐relief generation from 3D object, most existing methods ignore the influence of illumination on bas‐relief appearance. In this paper, we propose a novel method that adaptively generate bas‐reliefs with respect to illumination conditions. Given a 3D object and its target appearance, our method finds an adaptive surface that preserves the appearance of the input. We validate our approach through a variety of applications. Experimental results indicate that the proposed approach is effective in producing bas‐reliefs with desired appearance under illumination.
Implicit and Explicit Parallel Programming in Haskell

It has often been suggested that functional languages provide an excellent basis for programming parallel computer systems. This is largely a result of the lack of side effects which makes it possible to evaluate the subexpressions of a given term without any risk of interference. On the other hand, the lack of side-effects has also been seen as a weakness of functional languages since it rules out many features of traditional imperative languages such as state, I/O and exceptions. These ideas can be simulated in a functional language but the resulting programs are sometimes unnatural and inefficient. On the bright side, recent work has shown how many of these features can be naturally incorporated into a functional language without compromising efficiency by expressing computations in terms of monads or continuations. Unfortunately, the “single-threading” implied by these techniques often destroys many opportunities for parallelism. In this paper, we describe a simple extension to the Haskell I/O monad that allows a form of explicit high-level concurrency. It is a simple matter to incorporate these features in a sequential implementation, and genuine parallelism can be obtained on a parallel machine. In addition, the inclusion of constructs for explicit concurrency enhances the use of Haskell as an executable specification language, since some programs are most naturally described as a composition of parallel processes. ∗This research was supported by ARPA via a subcontract to Intermetrics, Inc.
Neoclassical Models of Imperfectly Competitive Labor Markets

The scenario of perfect competition, as augmented by human capital theory, yields a large body of testable hypotheses concerning labor market outcomes. These hypotheses, overviewed in the first chapter of this volume, might all be understood as applications of three more fundamental implications of perfectly competitive equilibrium conditions: no unemployment or vacancies, the law of one wage, and compensating wage differentials. The hypothesis of no equilibrium unemployment or job vacancies (NUV) follows immediately from the assumption that wage rates flexibly adjust to clear markets, so that the only reason for actors not to be engaged as employees or employers is because they choose not to participate in labor markets at going wage rates. The law of one wage (LOW) asserts that employees with equal (marginal) productivities facing identical working conditions receive the same wage rates, and follows from the assumption of frictionless exchange. Complementarily, the hypothesis of compensating wage differentials (CWD) asserts, broadly speaking, that variations in wage rates across workers are explained by either variations in labor productivity arising from costly investments by workers or variations in working conditions that are costly for employers to modify. These fundamental implications of competitive theory are challenged by both casual observation and careful empirical analysis. The NUV hypothesis conflicts with the appearance of persistently positive unemployment and vacancy rates. The LOW hypothesis is tested by manifestations of labor market " duality " or segmentation (Dickens and Lang 1993), persistent inter-and intraindustry wage differentials (Krueger and Summers 1988, Groshen 1991b) discrimination by ethnicity, gender, or race (Cain 1986; Jacobsen 2007, Chapter 9), and other indications that workers who are seemingly identical from the standpoint of competitive theory 2 nonetheless receive unequal wages. Indeed, such indications motivated the initial emergence of labor economics as a distinct field (Kerr 1988). Finally, consistent evidence of CWD has been notoriously hard to establish (Dorman 1996, Chapter 4). Such inconsistencies help motivate the study of models of imperfect competition in labor markets. Consistently with the observation that employers typically set wage levels, the chapter's primary focus will be on two cases of imperfect competition in which equilibrium wage levels are set by firms, monopsony and efficiency wages. In one sense, these cases reflect contrary views of employers' wage-setting power, in that the former scenario is generally associated with equilibria in which wages are below their corresponding perfectly competitive levels, while the latter are generally associated with supra-competitive wage …
Effects of low birth weight on insulin resistance syndrome in caucasian and African-American children.

OBJECTIVE To examine the effects of low birth weight (LBW) on the components of insulin resistance syndrome (IRS) in Caucasian and African-American children aged 4-14 years (n = 560 observations among 139 subjects). RESEARCH DESIGN AND METHODS A linear random-effects modeling analysis with repeated measures (average four annual visits per child) was conducted to examine the associations between LBW and the components of IRS and their developmental trends over age. Fasting glucose, insulin, and lipids were assessed after an overnight fast; insulin action and secretion were determined by the tolbutamide-modified frequently sampled intravenous glucose tolerance test; and body composition was assessed by dual energy X-ray absorptiometry and computed tomography. RESULTS LBW was significantly associated with increased fasting insulin concentration and visceral fat mass, decreased acute insulin response, beta-cell function, and HDL cholesterol among African-American children. Among children with LBW, there were significant differences in fasting insulin, insulin sensitivity, acute insulin response, and HDL cholesterol between Caucasians and African-Americans. LBW was significantly associated with faster decrease in acute insulin response and increase in triglycerides with regard to age. The hyperbolic function between insulin sensitivity and beta-cell function was retarded among children with LBW (P = 0.04). In addition, there was a significant interaction between LBW and ethnicity in relation to fasting insulin (P < 0.05) and visceral fat (P = 0.05). CONCLUSIONS LBW may predict the risk of the IRS and its progression over age in childhood, and this effect may be more pronounced among African-American children.
Guaranteed quality-of-service wireless access to ATM networks

In this paper, we study the problem of wireless access to ATM. We consider three classes of ATM sources: constant bit rate (CBR), variable bit rate (VBR) and available bit rate (ABR). We propose a polling scheme with nonpreemptive priority. Under such a scheme, we derive sufficient conditions such that all the CBR sources satisfy their jitter constraints and all the VBR sources satisfy their delay constraints. The remaining bandwidth is used by the ABR sources, for which we adapt a random access scheme proposed by Chen and Lee (1994). For this random access scheme, we derive the throughput-offer load characteristic, and thus the capacity. Based on this, we propose adaptive random access schemes that track the offer load to its optimal value. Our simulations show that our adaptive schemes maintain a high throughput with respect to the whole range of system load.