Miracle-dz/UniFAR-FTUs huggingface dataset:
The Grand National: a review of factors associated with non-completion and horse-falls, 1990 to 2012

The Grand National (GN) attracts high profile press and subsequent public attention. This study aimed to establish if factors influential to non-completion, horse-falls and specific fence risk in the GN supported the measures implemented by the British Horseracing Authority (BHA) to improve equine welfare in the GN. Horse, jockey, trainer and race related factors associated with non-completion, horse-falls and horse-falls at specific fences of the GN were collated over a 22 year period from 1990 to 2012. Descriptive analysis calculated non-completion rates per year, according to age and reason for non-completion. The distribution of fallers during the race in relation to fence number, design and key feature fences were also determined. Univariable analysis informed multivariable model building to identify factors associated with non-completion (n=840) and horse-falls (n=514) in the GN. Two final logistic regression models were refined through a backward stepwise process with variables retained if likeliho.
The Role of Communication Complexity in Adaptive Contextualization

Research problem: Adding contextual information to a core message has been shown to be critical in improving communication quality, especially in computer mediated communication. This paper models how people contextualize messages in the face of changing communication complexity. Research question: Can changes in communication complexity that occur during the communication process explain and predict contextualization? Literature review: Theories of human communication and studies of computer supported collaboration suggest that communication complexity reflects potentially problematic conditions resulting from 1) the difference in perspective and context held by the collaborators; 2) the incompatibility between the message representation and the way it is interpreted and used by the receiver; and 3) the intensity of information exchanged between communicators. We use this definition as a basis of for developing a measure of cognitive communication complexity. The literature further suggests that higher communication complexity induces higher contextualization. Methodology: First, we conducted a pilot study to develop and validate measures of communication complexity. Second, we conducted a laboratory experiment, in which 258 participants working in pairs collaborated on a sixteen-step assembly task. They used a tailored system that structured each message as core (the essence of the message) and context (additional information that explains the core and the sender's perspective). We used unbalanced panel data analysis to examine the repeated measures of contextualization and communication complexity associated with each step of the task. Results and discussion: We found that collaborators respond to changes in communication complexity at the expense of higher collaborative effort. We offer a cost-benefit framework in which, at the step level, people contextualize to reduce the communication complexity, and at the task level, they additionally consider the impact of contextualization on task performance. The main limitation of this study was the need to structure the communication between collaborators, to control and measure contextualization. Future research can adapt and extend our measure of communication complexity to less structured communication.
Role for CysJ Flavin Reductase in Molybdenum Cofactor-Dependent Resistance of Escherichia coli to 6-N-Hydroxylaminopurine

ABSTRACT We have previously described a novel Escherichia coli detoxification system for the removal of toxic and mutagenic N-hydroxylated nucleobases and related compounds that requires the molybdenum cofactor. Two subpathways (ycbX and yiiM) were identified, each employing a novel molybdo activity capable of inactivating N-hydroxylated compounds by reduction to the corresponding amine. In the present study, we identify the cysJ gene product as one additional component of this system. While the CysJ protein has been identified as the NADPH:flavin oxidoreductase component of the CysJI sulfite reductase complex (CysJ8I4), we show that the role of CysJ in base analog detoxification is unique and independent of CysI and sulfite reductase. We further show that CysJ functions as a specific partner of the YcbX molybdoenzyme. We postulate that the function of CysJ in this pathway is to provide, via its NADPH:flavin reductase activity, the reducing equivalents needed for the detoxification reaction at the YcbX molybdocenter. In support of the proposed interaction of the CysJ and YcbX proteins, we show that an apparent CysJ-YcbX “hybrid” protein from two Vibrio species is capable of compensating for a double cysJ ycbX defect in E. coli.
A Systemic Network for Chlamydia pneumoniae Entry into Human Cells

ABSTRACT Bacterial entry is a multistep process triggering a complex network, yet the molecular complexity of this network remains largely unsolved. By employing a systems biology approach, we reveal a systemic bacterial-entry network initiated by Chlamydia pneumoniae, a widespread opportunistic pathogen. The network consists of nine functional modules (i.e., groups of proteins) associated with various cellular functions, including receptor systems, cell adhesion, transcription, and endocytosis. The peak levels of gene expression for these modules change rapidly during C. pneumoniae entry, with cell adhesion occurring at 5 min postinfection, receptor and actin activity at 25 min, and endocytosis at 2 h. A total of six membrane proteins (chemokine C-X-C motif receptor 7 [CXCR7], integrin beta 2 [ITGB2], platelet-derived growth factor beta polypeptide [PDGFB], vascular endothelial growth factor [VEGF], vascular cell adhesion molecule 1 [VCAM1], and GTP binding protein overexpressed in skeletal muscle [GEM]) play a key role during C. pneumoniae entry, but none alone is essential to prevent entry. The combination knockdown of three genes (coding for CXCR7, ITGB2, and PDGFB) significantly inhibits C. pneumoniae entry, but the entire network is resistant to the six-gene depletion, indicating a resilient network. Our results reveal a complex network for C. pneumoniae entry involving at least six key proteins.
Role of Accessory DNA Polymerases in DNA Replication in Escherichia coli: Analysis of the dnaX36 Mutator Mutant

ABSTRACT The dnaX36(TS) mutant of Escherichia coli confers a distinct mutator phenotype characterized by enhancement of transversion base substitutions and certain (−1) frameshift mutations. Here, we have further investigated the possible mechanism(s) underlying this mutator effect, focusing in particular on the role of the various E. coli DNA polymerases. The dnaX gene encodes the τ subunit of DNA polymerase III (Pol III) holoenzyme, the enzyme responsible for replication of the bacterial chromosome. The dnaX36 defect resides in the C-terminal domain V of τ, essential for interaction of τ with the α (polymerase) subunit, suggesting that the mutator phenotype is caused by an impaired or altered α-τ interaction. We previously proposed that the mutator activity results from aberrant processing of terminal mismatches created by Pol III insertion errors. The present results, including lack of interaction of dnaX36 with mutM, mutY, and recA defects, support our assumption that dnaX36-mediated mutations originate as errors of replication rather than DNA damage-related events. Second, an important role is described for DNA Pol II and Pol IV in preventing and producing, respectively, the mutations. In the system used, a high fraction of the mutations is dependent on the action of Pol IV in a (dinB) gene dosage-dependent manner. However, an even larger but opposing role is deduced for Pol II, revealing Pol II to be a major editor of Pol III mediated replication errors. Overall, the results provide insight into the interplay of the various DNA polymerases, and of τ subunit, in securing a high fidelity of replication.
YlxM Is a Newly Identified Accessory Protein That Influences the Function of Signal Recognition Particle Pathway Components in Streptococcus mutans

ABSTRACT Streptococcus mutans is a cariogenic oral pathogen whose virulence is determined largely by its membrane composition. The signal recognition particle (SRP) protein-targeting pathway plays a pivotal role in membrane biogenesis. S. mutans SRP pathway mutants demonstrate growth defects, cannot contend with environmental stress, and exhibit multiple changes in membrane composition. This study sought to define a role for ylxM, which in S. mutans and numerous other bacteria resides directly upstream of the ffh gene, encoding a major functional element of the bacterial SRP. YlxM was observed as a produced protein in S. mutans. Its predicted helix-turn-helix motif suggested that it has a role as a transcriptional regulator of components within the SRP pathway; however, no evidence of transcriptional regulation was found. Instead, capture enzyme-linked immunosorbent assay (ELISA), affinity chromatography, and bio-layer interferometry (BLI) demonstrated that S. mutans YlxM interacts with the SRP components Ffh and small cytoplasmic RNA (scRNA) but not with the SRP receptor FtsY. In the absence of FtsY, YlxM increased the GTP hydrolysis activity of Ffh alone and in complex with scRNA. However, in the presence of FtsY, YlxM caused an overall diminution of net GTPase activity. Thus, YlxM appears to modulate GTP hydrolysis, a process necessary for proper recycling of SRP pathway components. The presence of YlxM conferred a significant competitive growth advantage under nonstress and acid stress conditions when wild-type and ylxM mutant strains were cultured together. Our results identify YlxM as a component of the S. mutans SRP and suggest a regulatory function affecting GTPase activity.
Archaeal ApbC/Nbp35 Homologs Function as Iron-Sulfur Cluster Carrier Proteins

ABSTRACT Iron-sulfur clusters may have been the earliest catalytic cofactors on earth, and most modern organisms use them extensively. Although members of the Archaea produce numerous iron-sulfur proteins, the major cluster assembly proteins found in the Bacteria and Eukarya are not universally conserved in archaea. Free-living archaea do have homologs of the bacterial apbC and eukaryotic NBP35 genes that encode iron-sulfur cluster carrier proteins. This study exploits the genetic system of Salmonella enterica to examine the in vivo functionality of apbC/NBP35 homologs from three archaea: Methanococcus maripaludis, Methanocaldococcus jannaschii, and Sulfolobus solfataricus. All three archaeal homologs could correct the tricarballylate growth defect of an S. enterica apbC mutant. Additional genetic studies showed that the conserved Walker box serine and the Cys-X-X-Cys motif of the M. maripaludis MMP0704 protein were both required for function in vivo but that the amino-terminal ferredoxin domain was not. MMP0704 protein and an MMP0704 variant protein missing the N-terminal ferredoxin domain were purified, and the Fe-S clusters were chemically reconstituted. Both proteins bound equimolar concentrations of Fe and S and had UV-visible spectra similar to those of known [4Fe-4S] cluster-containing proteins. This family of dimeric iron-sulfur carrier proteins evolved before the archaeal and eukaryal lineages diverged, representing an ancient mode of cluster assembly.
Genome Sequence of the Welan Gum-Producing Strain Sphingomonas sp. ATCC 31555

ABSTRACT Sphingomonas sp. strain ATCC 31555 can produce an anionic heteropolysaccharide, welan gum, which shows excellent stability and viscosity retention even at high temperatures. Here we present a 4.0-Mb assembly of its genome sequence. We have annotated 10 coding sequences (CDSs) responsible for the welan gum biosynthesis and 55 CDSs related to monosaccharide metabolism.
Xer1-Mediated Site-Specific DNA Inversions and Excisions in Mycoplasma agalactiae

ABSTRACT Surface antigen variation in Mycoplasma agalactiae, the etiologic agent of contagious agalactia in sheep and goats, is governed by site-specific recombination within the vpma multigene locus encoding the Vpma family of variable surface lipoproteins. This high-frequency Vpma phase switching was previously shown to be mediated by a Xer1 recombinase encoded adjacent to the vpma locus. In this study, it was demonstrated in Escherichia coli that the Xer1 recombinase is responsible for catalyzing vpma gene inversions between recombination sites (RS) located in the 5′-untranslated region (UTR) in all six vpma genes, causing cleavage and strand exchange within a 21-bp conserved region that serves as a recognition sequence. It was further shown that the outcome of the site-specific recombination event depends on the orientation of the two vpma RS, as direct or inverted repeats. While recombination between inverted vpma RS led to inversions, recombination between direct repeat vpma RS led to excisions. Using a newly developed excision assay based on the lacZ reporter system, we were able to successfully demonstrate under native conditions that such Xer1-mediated excisions can indeed also occur in the M. agalactiae type strain PG2, whereas they were not observed in the control xer1-disrupted VpmaY phase-locked mutant (PLMY), which lacks Xer1 recombinase. Unless there are specific regulatory mechanisms preventing such excisions, this might be the cost that the pathogen has to render at the population level for maintaining this high-frequency phase variation machinery.
Contextual Resource Negotiation-Based Task Allocation and Load Balancing in Complex Software Systems

In the complex software systems, software agents always need to negotiate with other agents within their physical and social contexts when they execute tasks. Obviously, the capacity of a software agent to execute tasks is determined by not only itself but also its contextual agents; thus, the number of tasks allocated on an agent should be directly proportional to its self-owned resources as well as its contextual agents' resources. This paper presents a novel task allocation model based on the contextual resource negotiation. In the presented task allocation model, while a task comes to the software system, it is first assigned to a principal agent that has high contextual enrichment factor for the required resources; then, the principal agent will negotiate with its contextual agents to execute the assigned task. However, while multiple tasks come to the software system, it is necessary to make load balancing to avoid overconvergence of tasks at certain agents that are rich of contextual resources. Thus, this paper also presents a novel load balancing method: if there are overlarge number of tasks queued for a certain agent, the capacities of both the agent itself and its contextual agents to accept new tasks will be reduced. Therefore, in this paper, the task allocation and load balancing are implemented according to the contextual resource distribution of agents, which can be well suited for the characteristics of complex software systems; and the presented model can reduce more communication costs between allocated agents than the previous methods based on self-owned resource distribution of agents.
The LiaFSR System Regulates the Cell Envelope Stress Response in Streptococcus mutans

ABSTRACT Maintaining cell envelope integrity is critical for bacterial survival, including bacteria living in a complex and dynamic environment such as the human oral cavity. Streptococcus mutans, a major etiological agent of dental caries, uses two-component signal transduction systems (TCSTSs) to monitor and respond to various environmental stimuli. Previous studies have shown that the LiaSR TCSTS in S. mutans regulates virulence traits such as acid tolerance and biofilm formation. Although not examined in streptococci, homologs of LiaSR are widely disseminated in Firmicutes and function as part of the cell envelope stress response network. We describe here liaSR and its upstream liaF gene in the cell envelope stress tolerance of S. mutans strain UA159. Transcriptional analysis established liaSR as part of the pentacistronic liaFSR-ppiB-pnpB operon. A survey of cell envelope antimicrobials revealed that mutants deficient in one or all of the liaFSR genes were susceptible to Lipid II cycle interfering antibiotics and to chemicals that perturbed the cell membrane integrity. These compounds induced liaR transcription in a concentration-dependent manner. Notably, under bacitracin stress conditions, the LiaFSR signaling system was shown to induce transcription of several genes involved in membrane protein synthesis, peptidoglycan biosynthesis, envelope chaperone/proteases, and transcriptional regulators. In the absence of an inducer such as bacitracin, LiaF repressed LiaR-regulated expression, whereas supplementing cultures with bacitracin resulted in derepression of liaSR. While LiaF appears to be an integral component of the LiaSR signaling cascade, taken collectively, we report a novel role for LiaFSR in sensing cell envelope stress and preserving envelope integrity in S. mutans.
Evaluation of illness severity scoring systems and risk prediction in vascular intensive care admissions

Introduction This study examines the predictive value of intensive care unit (ICU) scoring systems in a vascular ICU population. Methods From April 2005 to September 2011, we examined 363 consecutive ICU admissions. Simplified Acute Physiology Score II (SAPS II), Acute Physiology and Chronic Health Evaluation II (APACHE II), APACHE IV, Multiple Organ Dysfunction Score (MODS), organ dysfunctions and/or infection (ODIN), mortality prediction model (MPM) and physiologic and operative severity score for the enumeration of mortality and morbidity (POSSUM) were calculated. The Glasgow Aneurysm Score (GAS) was calculated for patients with aneurysm-related admissions. Results Overall mortality for complex vascular intervention was 11.6%. At admission, the areas under the receiver operating characteristic curve (AUCs) was 0.884 for SAPS II, 0.894 for APACHE II, 0.895 for APACHE IV, 0.902 for MODS, 0.891 for ODIN and 0.903 for MPM. At 24 h, model discrimination was best for POSSUM (AUC = 0.906) and MPM (AUC = 0.912). Conclusion The good discrimination of these scoring systems indicates their value as an adjunct to clinical assessment but should not be used on an individual basis as a clinical decision-making tool.
Utilization of Lactose and Galactose by Streptococcus mutans: Transport, Toxicity, and Carbon Catabolite Repression

ABSTRACT Abundant in milk and other dairy products, lactose is considered to have an important role in oral microbial ecology and can contribute to caries development in both adults and young children. To better understand the metabolism of lactose and galactose by Streptococcus mutans, the major etiological agent of human tooth decay, a genetic analysis of the tagatose-6-phosphate (lac) and Leloir (gal) pathways was performed in strain UA159. Deletion of each gene in the lac operon caused various alterations in expression of a PlacA -cat promoter fusion and defects in growth on either lactose (lacA, lacB, lacF, lacE, and lacG), galactose (lacA, lacB, lacD, and lacG) or both sugars (lacA, lacB, and lacG). Failure to grow in the presence of galactose or lactose by certain lac mutants appeared to arise from the accumulation of intermediates of galactose metabolism, particularly galatose-6-phosphate. The glucose- and lactose-PTS permeases, EIIMan and EIILac, respectively, were shown to be the only effective transporters of galactose in S. mutans. Furthermore, disruption of manL, encoding EIIABMan, led to increased resistance to glucose-mediated CCR when lactose was used to induce the lac operon, but resulted in reduced lac gene expression in cells growing on galactose. Collectively, the results reveal a remarkably high degree of complexity in the regulation of lactose/galactose catabolism.
HupB, a Nucleoid-Associated Protein of Mycobacterium tuberculosis, Is Modified by Serine/Threonine Protein Kinases In Vivo

ABSTRACT HU, a widely conserved bacterial histone-like protein, regulates many genes, including those involved in stress response and virulence. Whereas ample data are available on HU-DNA communication, the knowledge on how HU perceives a signal and transmit it to DNA remains limited. In this study, we identify HupB, the HU homolog of the human pathogen Mycobacterium tuberculosis, as a component of serine/threonine protein kinase (STPK) signaling. HupB is extracted in its native state from the exponentially growing cells of M. tuberculosis H37Ra and is shown to be phosphorylated on both serine and threonine residues. The STPKs capable of modifying HupB are determined in vitro and the residues modified by the STPKs are identified for both in vivo and the in vitro proteins through mass spectrometry. Of the identified phosphosites, Thr65 and Thr74 in the DNA-embracing β-strand of the N-terminal domain of HupB (N-HupB) are shown to be crucial for its interaction with DNA. In addition, Arg55 is also identified as an important residue for N-HupB–DNA interaction. N-HupB is shown to have a diminished interaction with DNA after phosphorylation. Furthermore, hupB is shown to be maximally expressed during the stationary phase in M. tuberculosis H37Ra, while HupB kinases were found to be constitutively expressed (PknE and PknF) or most abundant during the exponential phase (PknB). In conclusion, HupB, a DNA-binding protein, with an ability to modulate chromatin structure is proposed to work in a growth-phase-dependent manner through its phosphorylation carried out by the mycobacterial STPKs.
TLIA: Efficient Reconfigurable Architecture for Control-Intensive Kernels with Triggered-Long-Instructions

Coarse-Grained Reconfigurable Architectures (CGRAs), which provide high performance, low power and flexibility, is viewed as a promising trend for computing. CGRAs are mostly employed to process compute-intensive kernels because of their inefficiency for control flows. Various methods have been proposed to alleviate this problem, and triggered instruction is one of the state-of-the-art techniques. In this paper, a reconfigurable architecture called Triggered-Long-Instruction Architecture (TLIA) is proposed to enhance the triggered instructions with parallel condition method. In the proposed architecture, triggered instruction set is employed on processing elements (PEs). In this way, over-serialized execution and branch instructions are both eliminated. In the meanwhile, each PE has an improved data-path with three ALUs which is inspired by the parallel condition method. In this way, the amount of parallelism inside each control flow is increased by paralleling predicate computations and predicated operations. Moreover, multiple triggered instructions, which may have internal control dependence, can be executed on PEs in parallel. The strategy of issuing instructions is implemented in hardware, and verified by FPGA. Experimental results show that the performance is improved by 20.9 to 140.0 percent, the area is reduced by 24.5 percent, and the power is reduced by 32.5 percent over the equivalent Triggered Instruction Architecture (TIA).