Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Inhomogeneous DNA Replication Kinetics

In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.
A numerical method for simulating the dynamics of 3 D axisymmetric vesicles suspended in viscous flows February

We extend the efficient high-order method of [Veerapaneni et al., 2008] to the axisymmetric flows with immersed vesicles of spherical or toroidal topology. In this case, the bending and fluid forces require a siginficantly different (for bending forces, nonlinear, vs. linear in arclength in the 2D case) computation. The qualitative numerical behavior of the problem is also different: with a nonlinear implicit scheme needed to eliminate the CFL-type restriction in the toroidal case. We present an unconditionally stable scheme with low cost per time step, and spectrally accurate in space and third-order accurate in time. We also present a novel numerical scheme for evaluation of the 3D Stokes single-layer potential on an axisymmetric surface. As an application, we explore the motion of axisymmetric vesicles under gravity.
Control of Schistosoma mansoni egg‐induced inflammation by IL‐4‐responsive CD4+CD25−CD103+Foxp3− cells is IL‐10‐dependent

Host protection to helminth infection requires IL‐4 receptor α chain (IL‐4Rα) signalling and the establishment of finely regulated Th2 responses. In the current study, the role of IL‐4Rα‐responsive T cells in Schistosoma mansoni egg‐induced inflammation was investigated. Egg‐induced inflammation in IL‐4Rα‐responsive BALB/c mice was accompanied with Th2‐biased responses, whereas T‐cell‐specific IL‐4Rα‐deficient BALB/c mice (iLckcreIl4ra−/lox) developed Th1‐biased responses with heightened inflammation. The proportion of Foxp3+ Treg in the draining LN of control mice did not correlate with the control of inflammation and was reduced in comparison to T‐cell‐specific IL‐4Rα‐deficient mice. This was due to IL‐4‐mediated inhibition of CD4+Foxp3+ Treg conversion, demonstrated in adoptively transferred Rag2−/− mice. Interestingly, reduced footpad swelling in Il4ra−/lox mice was associated with the induction of IL‐4 and IL‐10‐secreting CD4+CD25−CD103+Foxp3− cells, confirmed in S. mansoni infection studies. Transfer of IL‐4Rα‐responsive CD4+CD25−CD103+ cells, but not CD4+CD25high or CD4+CD25−CD103− cells, controlled inflammation in iLckcreIl4ra−/lox mice. The control of inflammation depended on IL‐10, as transferred CD4+CD25−CD103+ cells from IL‐10‐deficient mice were not able to effectively downregulate inflammation. Together, these results demonstrate that IL‐4 signalling in T cells inhibits Foxp3+ Treg in vivo and promotes CD4+CD25−CD103+Foxp3− cells that control S. mansoni egg‐induced inflammation via IL‐10.
The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis

Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target.
Identification of RNA partners of viral proteins in infected cells

RNA viruses exhibit small-sized genomes encoding few proteins, but still establish complex networks of protein-protein and RNA-protein interactions within a cell to achieve efficient replication and spreading. Deciphering these interactions is essential to reach a comprehensive understanding of the viral infection process. To study RNA-protein complexes directly in infected cells, we developed a new approach based on recombinant viruses expressing tagged viral proteins that were purified together with their specific RNA partners. High-throughput sequencing was then used to identify these RNA molecules. As a proof of principle, this method was applied to measles virus nucleoprotein (MV-N). It revealed that in addition to full-length genomes, MV-N specifically interacted with a unique population of 5′ copy-back defective interfering RNA genomes that we characterized. Such RNA molecules were able to induce strong activation of interferon-stimulated response element promoter preferentially via the cytoplasmic pattern recognition receptor RIG-I protein, demonstrating their biological functionality. Thus, this method provides a new platform to explore biologically active RNA-protein networks that viruses establish within infected cells.
Interactive typed tactic programming in the Coq proof assistant

Interactive Typed Tactic Programming in the Coq Proof Assistant Beta Ziliani 2015 In order to allow for the verification of realistic problems, Coq provides a language for tactic programming, therefore enabling general-purpose scripting of automation routines. However, this language is untyped, and as a result, tactics are known to be difficult to compose, debug, and maintain. In this thesis, I develop two different approaches to typed tactic programming in the context of Coq: Lemma Overloading and Mtac. The first one utilizes the existing mechanism of overloading, already incorporated into Coq, to build typed tactics in a style that resembles that of dependently typed logic programming. The second one, Mtac, is a lightweight yet powerful extension to Coq that supports dependently typed functional tactic programming, with additional imperative features. I motivate the different characteristics of Lemma Overloading and Mtac through a wide range of examples, mainly coming from program verification. I also show how to combine these approaches in order to obtain the best of both worlds, resulting in extensible, typed tactics that can be programmed interactively. Both approaches rely heavily on the unification algorithm of Coq, which currently suffers from two main drawbacks: it incorporates heuristics not appropriate for tactic programming, and it is undocumented. In this dissertation, in addition to the aforementioned approaches to tactic programming, I build and describe a new unification algorithm better suited for tactic programming in Coq.
The piezoelectric thin film device

PROBLEM TO BE SOLVED: To enhance characteristics of a piezoelectric thin film device including a single or a plurality of piezoelectric thin film resonators by suppressing the sub-resonance of the piezoelectric thin film resonator. SOLUTION: A piezoelectric thin film resonator 1 has such a structure as an adhesive layer 12, a cavity forming film 13, a lower surface electrode 15, a piezoelectric thin film 16 and an upper surface electrode 17 are laminated in this order on a supporting substrate 11. The upper surface electrode 171 is opposed to the lower surface electrode 15 while sandwiching the piezoelectric thin film 16 in an opposite region E1 becoming a vibrating portion. When the periphery of the opposite region E1 is fixed to the piezoelectric thin film resonator 1, the cavity forming film 13 is deposited to cover a range continuous from the periphery of the flat surface 15p of the lower surface electrode 15 to the lower surface of the piezoelectric thin film 16 via the end face 15s of the lower surface electrode 15 at a part constituted of the end face 15s of the lower surface electrode 15 out of the contour of the opposite region E1, and the range is fixed to the supporting substrate 11 through the adhesive layer 12 and the cavity forming film 13. COPYRIGHT: (C)2008,JPO&INPIT
2D Study of Inclusion Shape Effect on the Effective Permittivity of Random Inhomogeneous Media

The effective properties of composite materials are closely related to the shape and arrangement of its constituent phases. In the quasi-static limit, we use the finite element method as a numerical tool to evaluate the effective permittivity of loss-less random composite materials with small grains and short fibers as fillers. The effect of the inclusion shapes as a function of surface fraction is highlighted. The numerical tool used to extract the exact value of the effective permittivity takes into account all internal multipolar interactions which contribute to the polarization of the material medium. The Maxwell-Garnett theory fails to predict the effective permittivity of the studied hetero structures for high permittivity contrast, but, Looyenga and Böttcher mixing rules predict more accurately the short fiber and granular fillers of the composite materials respectively.
What Are Youth Asking About Drugs? A Report of NIDA Drug Facts Chat Day

The current study analyzes a sample of questions about drugs asked online by youth who participated in the National Institute on Drug Abuse’s (NIDA) “Drug Facts Chat Day. ” The types of drugs youth asked about were coded into 17 substance categories, and the topics they raised were coded into seven thematic categories. The top five queried drugs were marijuana (16.4%), alcohol (8.5%), tobacco (6%), cocaine (5.7), and pharmaceutical drugs (4.5%). The effects of drug use, experience of being high, the addictiveness of drugs, pharmacology, and drug sales were among the more common types of questions to emerge but varied depending on the substance. These findings show the types of information young people are seeking about drugs and have clear implications to inform youth drug education programs.
Clock Trees: Logical Clocks for Programs with Nested Parallelism

A vector clock is a valuable tool for maintaining run time concurrency information in parallel programs. A novel method is presented for modifying vector clocks to make them suitable for programs with nested fork join parallelism (having a variable number of tasks). The resulting kind of clock is called a clock tree, due to its tree structure. The clock tree method compares favorably with other timestamping methods for variable parallelism: task identifier reuse and task recycling. The worst case space requirements of clock trees equals the best case for the latter two methods, and the average size of a clock tree is much smaller than the size of a vector with task recycling. Furthermore, the algorithm for maintaining clock trees does not require a shared data structure and thus avoids the serialization bottleneck that task recycling suffers from.
The Open University ’ s repository of research publications and other research outputs Mining for Social Serendipity Conference Item

A common social problem at an event in which people do not personally know all of the other participants is the natural tendency for cliques to form and for discussions to mainly happen between people who already know each other. This limits the possibility for people to make interesting new acquaintances and acts as a retarding force in the creation of new links in the social web. Encouraging users to socialize with people they don’t know by revealing to them hidden surprising links could help to improve the diversity of interactions at an event. The goal of this paper is to propose a method for detecting ”surprising” relationships between people attending an event. By ”surprising” relationship we mean those relationships that are not known a-priori, and that imply shared information not directly related with the local context of the event (location, interests, contacts) at which the meeting takes place. To demonstrate and test our concept we used the Flickr community. We focused on a community of users associated with a social event (a computer science conference) and represented in Flickr by means of a photo pool devoted to the event. We use Flickr metadata (tags) to mine for user similarity not related to the context of the event, as represented in the corresponding Flickr group. For example, we look for two group members who have been in the same highly specific place (identified by means of geo-tagged photos), but are not friends of each other and share no other common interests or, social neighborhood.
Rats Repeatedly Exposed to Toluene Diisocyanate Exhibit Immune Reactivity against Methyl Isocyanate-Protein Conjugates

Background: Volatile monoisocyanates are formed through thermal degradation when products containing polyurethane are heated. Repeated exposure to diisocyanates, such as toluene diisocyanate (TDI) are a well-known cause of occupational asthma. However, although monoisocyanates are abundant in occupational settings, there are few data concerning their ability to provoke immune reactions and asthma. We compared immune reactivity and respiratory disease following single or repeated inhalation exposures to the monoisocyanates methyl isocyanate (MIC) and isocyanic acid (ICA) with the effects of TDI. Methods:Isocyanates were administrated either as single vapor exposures or as repeated intranasal instillations in rats. Adverse health effects were monitored by analyzing airway inflammation, respiratory function and weight gain. Immune reactivity caused by repeated exposures was studied by analysis of isocyanate-specific antibodies and airway infiltration of immune competent cells. Results: Repeated exposures to TDI induced airway infiltration of neutrophils and lymphocytes, while neither MIC nor ICA provoked a detectable inflammatory response. Antibodies against isocyanate-albumin conjugates were detected in serum after both exposures to TDI and MIC, but not to ICA. TDI-exposed rats also displayed IgG antibodies against MIC-albumin conjugates. Even though MIC did not induce airway inflammation, single exposure provoked an increase in airway resistance and repeated exposures caused weight loss similar to that of TDI. Conclusions: Airway exposure to TDI produces an antibody response not only against TDI but also against MIC-protein conjugates. This indicates that immune reactivity against abundant monoisocyanates in occupational environments can occur in individuals pre-sensitized with low abundance but highly sensitizing diisocyanates.
The HIT-LTRC machine translation system for IWSLT 2012

In this paper, we describe HIT-LTRC's participation in the IWSLT 2012 evaluation campaign. In this year, we took part in the Olympics Task which required the participants to translate Chinese to English with limited data. Our system is based on Moses [1] , which is an open source machine translation system. We mainly used the phrase-based models to carry out our experiments, and factored-based models were also performed in comparison. All the involved tools are freely available. In the evaluation campaign, we focus on data selection, phrase extraction method comparison and phrase table combination.
Adenine‐induced chronic kidney disease in rats

Many animal models have been developed to study the causes and treatments of chronic kidney disease (CKD) in humans, an insidious disease resulting from kidney injury and characterized by persistent functional decline for more than 3 months, with or without evidence of structural deficit. The eventual outcome of CKD may be end‐stage kidney disease (ESKD), where patients need dialysis or transplantation to survive. Cardiovascular disease is accelerated in patients with CKD and contributes to increased mortality, with the relationship between CKD and cardiovascular disease being bi‐directional. Most animal models do not mimic the complexity of the human disease as many do not develop CKD‐associated cardiovascular disease. The adenine diet model of CKD in rodents is an exception. The original adenine diet model produced rapid‐onset kidney disease with extensive tubulointerstitial fibrosis, tubular atrophy, crystal formation and marked vessel calcification. Since then, lower adenine intake in rats has been found to induce slowly progressive kidney damage and cardiovascular disease. These chronic adenine diet models allow the characterization of relatively stable kidney and cardiovascular disease, similar to CKD in humans. In addition, interventions for reversal can be tested. Here the key features of the adenine diet model of CKD are noted, along with some limitations of other available models. In summary, the data presented here support the use of chronic low‐dose adenine diet in rats as an easy and effective model for understanding human CKD, especially the links with cardiovascular disease, and developing potential therapeutic interventions.
Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction

An exhaustive real-time reverse transcriptase-polymerase chain reaction (PCR) quantification method was used to determine 15 of the catalytically active human UDP-glucuronosyltransferase (UGT) isoforms (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, and 2B17). The specific primers for respective human UGTs were developed for differential determination. The cDNA derived from the 1A7 isoform was detected in the esophagus, the 1A8 and 1A10 isoforms were detected in the small intestine, and all other isoforms were detected in at least the liver by PCR. In all cases, single bands of the expected size on the agarose gel were confirmed to correspond with the predicted UGT isoform sequences. Each calibration curve showed linearity between the PCR crossing point and the calibrator copy number. The correlation coefficients were greater than 0.9957 with high reproducibility. This exhaustive measurement method was applied to UGT expression in 23 human tissue types. UGT was mostly expressed in the alimentary system and liver. We were surprised to find that extremely high expression in the liver was found for UGT2B4 and UGT2B15, which had, respectively, 8.98 and 4.38 times greater expression than UGT2B7 in the liver. In addition, even though expressed at low levels, several UGT isoforms were expressed in steroidogenic tissues, such as the breast, prostate, heart, and adrenal. Therefore, this quantification method may provide valuable information about the medical efficacy or pharmacokinetic characteristics of a wide variety of UGT-metabolized drugs.
Factors associated with long-term survival of diabetics.

Three hundred and seventy diabetics and an equal number of matched controls were followed up over a ten-year period to compare the mortality of diabetics with that of nondiabetics, and to determine how the longevity of diabetics is affected by various complicating conditions and by the severity of the diabetes. During the ten-year study period, the death rate of the diabetics was 25.4% compared to 9.7% among the controls, a ratio of about 2.6. Some of the excess mortality was accounted for by (1) a higher prevalence of hypertension, overweight, coronary heart disease, and kidney disease, and (2) the severity of the diabetes, as indicated by a high insulin dosage, early onset, and recurrent glycosuria. However, the mortality of those with mild diabetes and those without complicating diseases was also substantially greater than that of the nondiabetics.
Detecting digital audio forgeries by checking frame offsets

MP3 is the most popular compressed audio format in our daily life but it can be doctored very easily by pervasive audio editing software. Thus it is necessary to develop authentication methods for MP3. Different from JPEG compression for image, MP3 compression has its own characteristics. Thus existing forensics methods for JPEG compression is unable to be applied to MP3 compression directly. In this paper, we propose a passive approach to detect doctored MP3 audio by checking frame offsets. As the audio samples are divided into frames to encode, each frame has its own frame offset after encoding. Forgeries lead to the broken of frame grids. So the frame offsets are good indication for locating forgeries, and the frame offsets can be detected by the identification of quantization characteristic. In this way, the doctored positions can be automatically located. Experimental results demonstrate the validity of the proposed approach on detecting some common forgeries, such as deletion, insertion, substitution and splicing. Under different bitrates, the detection ratios are above 94%. To the best of our knowledge, this piece of work is the first one to investigate digital forensics on MP3 format.
Preliminary Study of Trong Clay – HA Bone Scaffold Fabrication Using Solvent Casting/Particulate Leaching Method and Indirect 3D-Printing Technique

This paper is about the feasibility of using the combination of Trong clay and hydroxyapatite for the fabrication of bone tissue scaffold. Trong clay is one of Perak’s (a state in Malaysia) natural resources which can be potentially used as a biomaterial. Two methods were involved in the scaffold fabrication: the solvent casting/particulate leaching method and the indirect three-dimensional printing method. It is found that the solvent casting/particulate leaching method was not able to produce tissue scaffold as intended. However, tissue scaffolds made using indirect three-dimensional printing were able to be fabricated using the 9:1 Trong clay-HA ratio. It was found also that the scaffolds with lower percentage of Trong clay were more fragile and brittle. In this study, the scaffolds produced using this technique have an interconnected porous structure with approximately 500μm pores diameter observed using Field Emission Scanning Electron Microscope (FESEM).