Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational Analyses of Synergism in Small Molecular Network Motifs

Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli. The present study investigates how variations in pairs of parameters affect responses in a series of ten common network motifs, identifying concurrent variations that act synergistically (or antagonistically) to alter the responses of the motifs to stimuli. Synergism (or antagonism) was quantified using degrees of nonlinear blending and additive synergism. Simulations identified concurrent variations that maximized synergism, and examined the ways in which it was affected by stimulus protocols and the architecture of a motif. Only a subset of architectures exhibited synergism following paired changes in parameters. The approach was then applied to a model describing interlocked feedback loops governing the synthesis of the CREB1 and CREB2 transcription factors. The effects of motifs on synergism for this biologically realistic model were consistent with those for the abstract models of single motifs. These results have implications for the rational design of combination drug therapies with the potential for synergistic interactions.
Morphological diversity of blastula formation and gastrulation in temnopleurid sea urchins

ABSTRACT Embryos of temnopleurid sea urchins exhibit species-specific morphologies. While Temnopleurus toreumaticus has a wrinkled blastula and then invaginates continuously at gastrulation, others have a smooth blastula and their invagination is stepwise. We studied blastula and gastrula formation in four temnopleurids using light and scanning electron microscopy to clarify the mechanisms producing these differences. Unlike T. toreumaticus, blastomeres of mid-blastulae in T. reevesii, T. hardwickii and Mespilia globulus formed pseudopods. Before primary mesenchyme cells ingressed, embryos developed an area of orbicular cells in the vegetal plate. The cells surrounding the orbicular cells extended pseudopods toward the orbicular cell area in three Temnopleurus species. In T. toreumaticus, the extracellular matrix was well-developed and developed a hole-like structure that was not formed in others. Gastrulation of T. reevesii, T. hardwickii and M. globulus was stepwise, suggesting that differences of gastrulation are caused by all or some of the following factors: change of cell shape, rearrangement, pushing up and towing of cells. We conclude that (1) many aspects of early morphogenesis differ even among very closely related sea urchins with indirect development and (2) many of these differences may be caused by the cell shape and structure of blastomeres or by differences in extracellular matrix composition. Summary: Closely related temnopleurid sea urchins exhibit diversity in blastula formation and gastrulation during early morphogenesis.
DRAFT Statistical Models for Linguistic Variation in Social Media

Language on the Internet and social media varies due to time, geography and social factors. For example, consider an online chat forum where people from different regions across the world interact. In such scenarios, it is important to track and detect regional variation in language. A person from the UK, who is in conversation with someone from the USA could say “he is stuck in the lift” to mean ”he is stuck in an elevator”, since the word lift means an elevator in the UK. Note that in the US, lift does not refer to an elevator. Modeling such variation can allow for applications to prompt or suggest the intended meaning to the other participants of the conversation. In this thesis I conduct two related lines of inquiry focusing on (a) language itself and the variation it manifests and (b) the user and what we can infer about them based on their language use on social media. First I develop computational methods to track and detect changes in word usage, including semantic and syntactic variation. I examine two modalities: time and geography. Specifically I outline methods to use distributional word representations (word embeddings) to detect semantic variation in word usage. Our methods are scalable to large datasets, making them particularly suited for social media. Second, I turn my attention towards users. In particular, I seek to model latent personality traits of users based on their language use on social media. I propose to develop generative latent factor models, that explicitly seek to build representations of each user based on their inferred latent personality traits. These models seek to capture latent personality traits that serve as useful co-variates for a wide variety of tasks like predicting what topics users like on social media and the number of friends in their social circle. This work has broad applications in several fields like information retrieval, semantic web applications, socio-variational linguistics, computational social science including digital health care, psycho-linguistics and ad-targeting. April 18, 2016 DRAFT
How to Adjust for Nonignorable Nonresponse: Calibration, Heckit or FIML?

When a survey response mechanism depends on the variable of interest measured within the same survey and observed for only part of the sample, the situation is one of nonignorable nonresponse. Ignoring the nonresponse is likely to generate significant bias in the estimates. To solve this, one option is the joint modelling of the response mechanism and the variable of interest. Another option is to calibrate each observation with weights constructed from auxiliary data. In an application where earnings equations are estimated these approaches are compared to reference estimates based on large a Swedish register based data set without nonresponse.
Voter Mobilization Meets eGovernment: Turnout and Voting by Mail From Online or Paper Ballot Request

During the past two decades, the movement toward eGoverment has shifted many government services online. Despite initial hopes that the Internet could be leveraged to increase voter participation, eGovernment has changed little about the voting process. Our field experiment compares two treatments sent to voters via postal mail prior to the 2010 general election in Maine: (1) recruitment to request a mail ballot via Maine's new online system and (2) recruitment to request a mail ballot using Maine's traditional paper application. We find that recruitment to vote by mail using a traditional paper ballot application significantly increased turnout. Contrary to the expectations of advocates of eGovernment, the mailer encouraging voters to use Maine's innovative new online ballot request system generated no significant increase in overall voter turnout. Our findings indicate why eGovernment continues to contribute less to democratic participation than anticipated.
Strategies and clinical outcome of 250 cycles of Preimplantation Genetic Diagnosis for single gene disorders.

BACKGROUND We report on our experience with preimplantation genetic diagnosis (PGD) for single gene disorders (SGDs), from 1999 to 2004, describing strategies and overall clinical outcome of 250 cycles in 174 couples for 23 different genetic conditions. METHODS PGD cycles included 15 for autosomal dominant, 148 for autosomal recessive and 19 for X-linked SGDs. In addition, 68 cycles of PGD for SGDs were performed in combination with HLA matching. The strategy in each case used an initial multiplex PCR, followed by minisequencing to identify the mutation(s) combined with multiplex PCR for closely linked informative markers to increase accuracy. Linkage analysis, using intragenic and/or extragenic polymorphic microsatellite markers, was performed in cases where the disease-causing mutation(s) was unknown or undetectable. RESULTS In 250 PGD cycles, a total of 1961 cleavage stage embryos were biopsied. PCR was successful in 3409 out of 3149 (92.4%) biopsied blastomeres and a diagnosis was possible in 1849 (94.3%) embryos. Four hundred and twenty-seven embryos were transferred in 211 cycles, resulting in 71 pregnancies (33.6% per embryo transfer), including 15 biochemical pregnancies, six spontaneous miscarriages, two ectopic pregnancies, which were terminated, and nine pregnancies which are still ongoing. The remaining pregnancies were confirmed to be unaffected and went to term without complications, resulting in the birth of 35 healthy babies. CONCLUSIONS Minisequencing for mutation detection combined with multiplex fluorescence PCR for linkage analysis is an efficient, accurate and widely applicable strategy for PGD of SGDs. Our experience provides a further demonstration that PGD is an effective clinical tool and a useful option for many couples with a high risk of transmitting a genetic disease.
Emotion regulation strategy mediates both positive and negative relationships between music uses and well-being

The mediating effects of emotion regulation (reappraisal and suppression) were examined in the relationship between music engagement and well-being. Emotion regulation strategies (Emotion Regulation Questionnaire; Gross & John, 2003) and styles of music engagement (Music Use questionnaire; Chin & Rickard, 2012) were assessed in a large diverse sample of 637 participants. A battery of hedonic and eudaimonic well-being measures (International Positive and Negative Affect Schedule Short Form; Thompson, 2007; Satisfaction With Life Scale; Diener, Emmons, Larsen, & Griffin, 1985; Mental Health Continuum-Short Form; Keyes et al., 2008) was also administered. Results demonstrated that the path of mediation was dependent on the type of emotion regulation strategy utilized, as well as the way in which one engages with music. Findings provide initial evidence that engaging with music for the purposes of cognitive and emotion regulation may enhance well-being primarily through the habitual use of cognitive reappraisal. In contrast, various other aspects of music engagement (music listening, engaged production, and social connection) if coupled with a tendency to regulate emotions and thoughts by expressive suppression may yield undesirable well-being outcomes. This study highlights the important role emotion regulation plays in the complex relationship between music engagement and well-being.
Concurrent Performance of Cognitive and Motor Tasks in Neurological Rehabilitation

Although in many circumstances motor control and cognitive tasks can be performed simultaneously without significant decrement to either, there is evidence that performance is impaired under certain conditions. This study set out to investigate the effects of concomitant demands from cognitive and motor control tasks on patients recovering from acquired brain injury. In line with findings in ageing and physical rehabilitation we found significant interference from a motor tracking task on a simultaneously performed spatial reasoning task among seven subjects undergoing neurological rehabilitation, with lesser interference to a category generation and a number addition task. Tracking performance was also affected by concurrent performance of the spatial reasoning task. We suggest these effects may arise because motor control tasks become less automatic, and require increased cognitive processing resources, following acquired brain injury. This leads to potential interference with other cognitive tasks. Finally, we argue that this dual-task interference may be clinically relevant, as it may determine patients' responsiveness to rehabilitation.
Large and small artery endothelial function in patients with essential hypertension – Effect of ACE inhibition and beta‐blockade

Hypertension has been associated with changes in endothelial function in both large muscular arteries and small resistance arteries. We evaluated the relationship between blood flow velocity and dilatation of the brachial artery following transient forearm ischemia and acetylcholine‐induced relaxation in subcutaneous small arteries and the influence of antihypertensive therapy on both in patients with essential hypertension. Thirty‐one previously untreated hypertensive patients were randomized in a double‐blind fashion to treatment with either the angiotensin‐converting enzyme (ACE) inhibitor perindopril or the beta‐blocker atenolol and compared with 17 healthy normotensive controls. Before and after 1 year of treatment, while still on active medication, flow‐mediated dilatation (FMD) was measured in the brachial artery using ultrasound while relaxation to acetylcholine in small arteries was tested in vitro in a myograph. FMD correlated inversely to resting brachial artery diameter (r = −0.38, p<0.05). FMD corrected for resting diameter (FMDcorr) was lower in patients (3.0±0.2%) compared with controls (4.2±0.3%, p<0.01). In both patients and controls, FMDcorr was related to flow velocity in a non‐linear way with FMDcorr reaching a maximum despite increasing flow velocities, and in the patients, FMDcorr was only reduced at high flow velocities. Furthermore, patients had a reduced acetylcholine‐induced relaxation in small arteries (p = 0.04). Perindopril and atenolol reduced blood pressure to similar levels and both drugs improved FMDcorr to a similar degree without any effects on relaxation to acetylcholine in small arteries. The present study demonstrates the role of correcting for differences in baseline diameter during measurements of FMD and a non‐linear relationship between flow velocity and FMD in the brachial artery. Furthermore, the results suggest different effects of antihypertensive treatment on endothelial function in large and small arteries.
Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly. This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index >30 kg·m−2). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied. The study found that obese and nonobese patients showed different in vitro geniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients. These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.
Local inhibitory action of BMPs and their relationships with activators in feather formation: implications for periodic patterning.

The formation of periodic patterns is fundamental in biology. Theoretical models describing these phenomena have been proposed for feather patterning; however, no molecular candidates have been identified. Here we show that the feather tract is initiated by a continuous stripe of Shh, Fgf-4, and Ptc expression in the epithelium, which then segregates into discrete feather primordia that are more strongly Shh and Fgf-4 positive. The primordia also become Bmp-2 and Bmp-4 positive. Bead-mediated delivery of BMPs inhibits local feather formation in contrast with the activators, SHH and FGF-4, which induce feather formation. Both FGF-4 and SHH induce local expression of Bmp-4, while BMP-4 suppresses local expression of both. FGF-4 also induces Shh. Based on these findings, we propose a model that involves (1) homogeneously distributed global activators that define the field, (2) a position-dependent activator of competence that propagates across the field, and (3) local activators and inhibitors triggered in sites of individual primordia that act in a reaction-diffusion mechanism. A computer simulation model for feather pattern formation is also presented.
MPC-based shared steering control for automated driving systems

This paper describes the design of a new haptic shared steering control framework for automated driving systems. In this framework, the shared control problem is formulated as a constrained optimization problem which is solved online by a model predictive controller. Without driver's intervention, the system assumes automatic lane-keeping control. When the driver takes over control, by adapting the weight on the stage cost and implementing dynamic constraints, the framework ensures seamless control transfer from the system to the driver while conveying potential hazards through haptic feedback. Simulation results are presented to demonstrate the ability of this framework to handle control allocation and hazard warning.
The relationship between organized violence, family violence and mental health: findings from a community-based survey in Muhanga, Southern Rwanda

Background The relationship between organized violence and family violence, and their cumulative effect on mental health in post-conflict regions remains poorly understood. Objective The aim of the present study was to establish prevalence rates and predictors of family violence in post-conflict Rwanda. And to examine whether higher levels of war-related violence and its socio-economic consequences would result in higher levels of violence within families and whether this would be related to an increase of psychological distress in descendants. Method One hundred and eighty-eight parent–child pairs from four sectors of the district Muhanga, Southern Province of Rwanda, were randomly selected for participation in the study. Trained local psychologists administered structured diagnostic interviews. A posttraumatic stress disorder (PTSD) diagnosis was established using the PTSD Symptom Scale Interview (PSS-I) and child maltreatment was assessed by means of the Childhood Trauma Questionnaire (CTQ). Additionally, the Hopkins Symptom Checklist (HSCL-25) assessed symptoms of depression and anxiety in descendants. Results Prevalence rates of child abuse and neglect among descendants were below 10%. Ordinal regression analyses revealed that the level of child maltreatment in descendants was predicted by female sex, poverty, loss of the mother, exposure to war and genocide as well as parents’ level of PTSD and reported child maltreatment. Poor physical health, exposure to war and genocide, parental PTSD symptoms, and reported childhood trauma were significantly associated with depressive and anxious symptoms, while only exposure to war and genocide and poor physical health predicted the level of PTSD. Conclusion The results indicate that cumulative stress such as exposure to organized violence and family violence in Rwandan descendants poses a risk factor for the development of depressive and anxious symptoms. Besides the support for families to cope with stress, awareness-raising initiatives challenging the current discourse of discipline toward children in schools or at home need to be fostered.
FINITE STATE AUTOMATA BASED FAULT TOLERANT AND ENERGY EFFICIENT ROUTING ( FSA-FTEER ) IN WIRELESS SENSOR NETWORKS

With the availability of low power, tiny and inexpensive devices, wireless sensor networks have been used for a wide variety of applications ranging from industrial to environmental monitoring and military uses. Wireless Sensor nodes are mainly used in mission critical applications and deployed in sensitive areas due to which they can’t be replaced frequently. Certain situations may arise where the nodes in network may not function properly due to failures, and they become unavailable to the network. There is much need to develop energy efficient and fault tolerant routing for wireless sensor networks. We propose a (FSA-FTEER) protocol which creates multiple node-disjoint paths from source to destination and ensures that paths don’t interfere with each other. Residual energy of sensor nodes is taken in to consideration as heterogeneous nodes are deployed in network. KeywordsFinite State Automata, Probability, Congestion, Interference, Faulty Nodes
DNA bending and unbending by MutS govern mismatch recognition and specificity

DNA mismatch repair is central to the maintenance of genomic stability. It is initiated by the recognition of base–base mismatches and insertion/deletion loops by the family of MutS proteins. Subsequently, ATP induces a unique conformational change in the MutS–mismatch complex but not in the MutS–homoduplex complex that sets off the cascade of events that leads to repair. To gain insight into the mechanism by which MutS discriminates between mismatch and homoduplex DNA, we have examined the conformations of specific and nonspecific MutS–DNA complexes by using atomic force microscopy. Interestingly, MutS–DNA complexes exhibit a single population of conformations, in which the DNA is bent at homoduplex sites, but two populations of conformations, bent and unbent, at mismatch sites. These results suggest that the specific recognition complex is one in which the DNA is unbent. Combining our results with existing biochemical and crystallographic data leads us to propose that MutS: (i) binds to DNA nonspecifically and bends it in search of a mismatch; (ii) on specific recognition of a mismatch, undergoes a conformational change to an initial recognition complex in which the DNA is kinked, with interactions similar to those in the published crystal structures; and (iii) finally undergoes a further conformational change to the ultimate recognition complex in which the DNA is unbent. Our results provide a structural explanation for the long-standing question of how MutS achieves mismatch repair specificity.
The influence of predator--prey population dynamics on the long-term evolution of food web structure.

We develop a set of equations to describe the population dynamics of many interacting species in food webs. Predator-prey interactions are nonlinear, and are based on ratio-dependent functional responses. The equations account for competition for resources between members of the same species, and between members of different species. Predators divide their total hunting/foraging effort between the available prey species according to an evolutionarily stable strategy (ESS). The ESS foraging behaviour does not correspond to the predictions of optimal foraging theory. We use the population dynamics equations in simulations of the Webworld model of evolving ecosystems. New species are added to an existing food web due to speciation events, whilst species become extinct due to coevolution and competition. We study the dynamics of species-diversity in Webworld on a macro-evolutionary time-scale. Coevolutionary interactions are strong enough to cause continuous overturn of species, in contrast to our previous Webworld simulations with simpler population dynamics. Although there are significant fluctuations in species diversity because of speciation and extinction, very large-scale extinction avalanches appear to be absent from the dynamics, and we find no evidence for self-organized criticality.