Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Systems Biology Peer Review Process File a Comprehensive Genome-scale Reconstruction of Escherichia Coli Metabolism -2011 Transaction Report

(Note: With the exception of the correction of typographical or spelling errors that could be a source of ambiguity, letters and reports are not edited. The original formatting of letters and referee reports may not be reflected in this compilation.) Thank you again for submitting your work to Molecular Systems Biology. We have now heard back from the three referees who agreed to evaluate your manuscript. As you will see from the reports below, the referees generally agreed that this updated model of E. coli metabolism could provide a useful resource to the community, but they raised a series of substantial concerns, which, I am afraid to say, preclude its publication in its present form. The reviewers main concerns feel broadly into two categories. 1. They indicated that this work currently lacked a clear and direct comparison of the performance of this new model to its predecessor (iAF1260). In fact, reviewer #1 notes that comparison with your previous work may even suggest that this model shows a small performance decrease compared to iAF1260. Similarly, the editor notes Fig. 4C as compared to Fig. 3E in Feist et al. (2007) which appears to suggest a slight decrease in the accuracy of the model predictions. In addition, all three reviewers has concerns about the appropriateness of the Schaub et al. (2008) flux data used for the flux prediction comparisons. 2. More broadly, the reviewers found the current work overly-long and indicated that many of the analyses presented could be condensed, and some could be entirely removed. Indeed, the second reviewer recommended dramatically reformatted this work using a shorter format (e.g. our Report format). We now encourage reviewers to comment on each other's reviews and during this process reviewer #1 supported this suggestion, writing: "I think that the idea of reviewer #2 to make this work some kind of short communication/letter to the editor [is] very valuable. The model itself will
Metric learning for graph-based label propgation

The efficiency of graph-based semi-supervised algorithms depends on the graph of instances on which they are applied. The instances are often in a vectorial form before a graph linking them is built. The construction of the graph relies on a metric over the vectorial space that help define the weight of the connection between entities. The classic choice for this metric is usually a distance measure or a similarity measure based on the euclidean norm. We claim that in some cases the euclidean norm on the initial vectorial space might not be the more appropriate to solve the task efficiently. We propose an algorithm that aims at learning the most appropriate vectorial representation for building a graph on which the task at hand is solved efficiently.
Exploring Small-Scale and Large-Scale CMP Architectures for Commercial Java Servers

As we enter the era of chip multiprocessor (CMP) architectures, it is important that we explore the scaling characteristics of mainstream server workloads on these platforms. In this paper, we analyze the performance of an Enterprise Java workload (SPECjbb2005) on two important classes of CMP architectures. One class of CMP platforms comprise of "small-scale" CMP (SCMP) processors with a few large out-of order cores on the die. Another class of CMP platforms comprise of "large-scale" CMP (LCMP) processors) with several small in-order cores on the die. For these classes of CMP architectures to succeed, it is important that there are sufficient resources (cache, memory and interconnect) to allow for a balanced scalable platform. In this paper, we focus on evaluating the resource scaling characteristics (cores, caches and memory) of SPECjbb2005 on these two architectures and understanding architectural trade-offs that may be required in future CMP offerings. The overall evaluation is uniquely conducted using four different methodologies (measurements on latest platforms, trace-based cache simulation, trace-based platform simulation and execution-driven emulation). Based on our findings, we summarize the architectural recommendations for future CMP server platforms (e.g. the need for large DRAM caches)
Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study

Objective Chromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletion's impact on survival and its clinical manifestations in a large cohort of Chilean patients. Design Demographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death. Setting Genetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion. Outcomes Fatality rate and associated factors. Results 59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects. Conclusions In this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival.
Multiresolution modeling of point-sampled geometry

We present a framework and algorithms for multiresolution modeling of point-sampled geometry. Most of our techniques extend the key ingredients of recent multiresolution editing concepts, including geometry smoothing, simplification, and offset computation, to point clouds. Using these building blocks, we designed a powerful and versatile hierarchical representation for point-based modeling. An intuitive editing metaphor along with dynamic resampling techniques facilitates modeling operations at different scales and enables us to effectively handle very large model deformations. In our approach all processing is performed directly on point-sampled geometry without the need for intermediate local triangulation or meshing.
Is the Firm-Level Relationship between Uncertainty and Irreversible Investment Non- Linear?

Abel and Eberly (1994, 1999) suggest that the relationship between uncertainty and investment is non-linear and can be represented by an inverted Ucurve: at low levels of uncertainty, investment and uncertainty show a positive relationship whereas at high levels of uncertainty the relationship is a negative one. We empirically test this hypothesis using panel data on 459 US manufacturing industries (4-digit level) for the period 1958 to 1996 for different sources of uncertainty: (i) output price, (ii) productivity, and (iii) factor costs. Our results tend to support Abel and Eberly's hypothesis and are robust with respect to different specifications of the investment model. Furthermore, this non-monotonic (inverted "U shaped") relationship was significant for almost all the various sources of uncertainty that were tested and for varying degrees of irreversibility. We further distinguish between the components of uncertainty: industry-wide and firm-specific. This distinction demonstrates that the investment-uncertainty relationship remains nonlinear and significant only in certain cases: when uncertainty is firm specific and arises from output prices or productivity, or when uncertainty is aggregate and arises
Skull Base Inverted Papilloma: A Comprehensive Review

Skull base inverted papilloma (IP) is an unusual entity for many neurosurgeons. IP is renowned for its high rate of recurrence, its ability to cause local destruction, and its association with malignancy. This paper is a comprehensive review of the reports, studies, and reviews published in the current biomedical literature from 1947 to September 2010 and synthesize this information to focus on its potential invasion to the base of the skull and possible intradural extension. The objective is to familiarize the clinician with the different aspects of this unusual disease. The role of modern diagnostic tools in medical imaging in order to assess clearly the limits of the tumors and to enhance the efficiency and the safety in the choice of a surgical approach is pointed out. The treatment guidelines for IP have undergone a complex evolution that continues today. Radical excision of the tumour is technically difficult and often incomplete. Successful management of IP requires resection of the affected mucosa which could be achieved with open surgery, endoscopic, or combined approach. Radio and chemotherapy were used for certain indications. More optimally research would be a multicenter randomized trials with large size cohorts.
Constructing Conflict-Free Schedules in Space and Time

This paper addresses the problem of constructing plans and schedules for resources that must obey spatial constraints in addition to time and capacity constraints. Spatial constraints are relevant in environments that involve mobile resources whose movements must be coordinated to avoid collisions and near-misses. In air-campaign planning, for example, aircraft are allocated to missions that must be flown concurrently within a localized and often heavily populated environment. Mission routes tend to be generated dynamically and must ensure that sufficient spatial separation is maintained at all times among all aircraft. We present a solution to this class of problems that treats the standard resource-allocation problem as a four-dimensional one, where the space in which resources must maneuver is itself managed as a capacitated resource. Underlying our approach is a representation of spatial capacity that uses a linear octree structure for indexing vector-based vehicle routes. Generalizing the notion of contention-based search heuristics, we present an algorithm that first solves a relaxed version of the problem to construct a spatial capacity profile (represented as an octree), and then uses spatio-temporal regions where demand exceeds capacity to make conflict-avoiding vehicle routing and scheduling decisions. To demonstrate the viability of the approach we present experimental results using data from a realistically sized air-campaign planning domain.
Cross-Domain Bootstrapping for Named Entity Recognition

propose a general cross-domain bootstrapping algorithm for domain adaptation in the task of named entity recognition. We first generalize the lexical features of the source domain model with word clusters generated from a joint corpus. We then select target domain instances based on multiple criteria during the bootstrapping process. Without using annotated data from the target domain and without explicitly encoding any target-domain- specific knowledge, we were able to improve the source model's F-measure by 7 points on the target domain.
Decorin binding by DbpA and B of Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu Stricto.

BACKGROUND Decorin adherence is crucial in the pathogenesis of Lyme borreliosis. Decorin-binding proteins (Dbp) A and B are the adhesins that mediate this interaction. DbpA and B of Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto (ss) differ in their amino acid sequence, but little attention has been paid to the potential difference in their decorin binding. METHODS We expressed recombinant DbpA and DbpB of B. garinii, B. afzelii, and B. burgdorferi ss and studied their binding to decorin. We also generated recombinant Borrelia strains to study the role of DbpA and DbpB in the adhesion of live spirochetes to decorin and decorin-expressing cells. RESULTS. Recombinant DbpA of B. garinii and DbpB of B. garinii and B. burgdorferi ss showed strong binding to decorin, whereas DbpA of B. burgdorferi ss and both DbpA and DbpB of B. afzelii exhibited no or only minor binding activity. DbpA and DbpB of B. garinii and B. burgdorferi ss also supported the adhesion of whole spirochetes to decorin and decorin-expressing cells, whereas DbpA and DbpB of B. afzelii did not exhibit this activity. CONCLUSIONS Dbp A and B of B. garinii and B. burgdorferi ss mediate the interaction between the spirochete and decorin, whereas the same adhesins of B. afzelii show only negligible activity.
Dysregulation of Cav1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

Mutations in the gene encoding Cav1.4, CACNA1F, are associated with visual disorders including X-linked incomplete congenital stationary night blindness type 2 (CSNB2). In mice lacking Cav1.4 channels, there are defects in the development of “ribbon” synapses formed between photoreceptors (PRs) and second-order neurons. However, many CSNB2 mutations disrupt the function rather than expression of Cav1.4 channels. Whether defects in PR synapse development due to altered Cav1.4 function are common features contributing to the pathogenesis of CSNB2 is unknown. To resolve this issue, we profiled changes in the subcellular distribution of Cav1.4 channels and synapse morphology during development in wild-type (WT) mice and mouse models of CSNB2. Using Cav1.4-selective antibodies, we found that Cav1.4 channels associate with ribbon precursors early in development and are concentrated at both rod and cone PR synapses in the mature retina. In mouse models of CSNB2 in which the voltage-dependence of Cav1.4 activation is either enhanced (Cav1.4I756T) or inhibited (CaBP4 KO), the initial stages of PR synaptic ribbon formation are largely unaffected. However, after postnatal day 13, many PR ribbons retain the immature morphology. This synaptic abnormality corresponds in severity to the defect in synaptic transmission in the adult mutant mice, suggesting that lack of sufficient mature synapses contributes to vision impairment in Cav1.4I756T and CaBP4 KO mice. Our results demonstrate the importance of proper Cav1.4 function for efficient PR synapse maturation, and that dysregulation of Cav1.4 channels in CSNB2 may have synaptopathic consequences.
Rapid, efficient functional characterization and recovery of HIV-specific human CD8+ T cells using microengraving

The nature of certain clinical samples (tissue biopsies, fluids) or the subjects themselves (pediatric subjects, neonates) often constrain the number of cells available to evaluate the breadth of functional T-cell responses to infections or therapeutic interventions. The methods most commonly used to assess this functional diversity ex vivo and to recover specific cells to expand in vitro usually require more than 106 cells. Here we present a process to identify antigen-specific responses efficiently ex vivo from 104–105 single cells from blood or mucosal tissues using dense arrays of subnanoliter wells. The approach combines on-chip imaging cytometry with a technique for capturing secreted proteins—called “microengraving”—to enumerate antigen-specific responses by single T cells in a manner comparable to conventional assays such as ELISpot and intracellular cytokine staining. Unlike those assays, however, the individual cells identified can be recovered readily by micromanipulation for further characterization in vitro. Applying this method to assess HIV-specific T-cell responses demonstrates that it is possible to establish clonal CD8+ T-cell lines that represent the most abundant specificities present in circulation using 100- to 1,000-fold fewer cells than traditional approaches require and without extensive genotypic analysis a priori. This rapid (<24 h), efficient, and inexpensive process should improve the comparative study of human T-cell immunology across ages and anatomic compartments.
Antimicrobial Resistance or Delayed Appropriate Therapy—Does One Influence Outcomes More Than the Other Among Patients With Serious Infections Due to Carbapenem-Resistant Versus Carbapenem-Susceptible Enterobacteriaceae?

Abstract Background The relative contribution of antimicrobial resistance versus delayed appropriate treatment to the clinical and economic burden of Enterobacteriaceae infections is not well understood. Methods Using a large US hospital database, we identified all admissions between July 2011 and September 2014 with evidence of serious Enterobacteriaceae infection. The “index date” was the earliest date on which a culture positive for Enterobacteriaceae was drawn. Infections were classified as carbapenem-resistant (CRE) or carbapenem-susceptible (CSE). Receipt of antimicrobials with activity against all index pathogens on the index date or ≤2 days thereafter was deemed as “timely”; all other instances were “delayed. ” Associations between CRE status and delayed appropriate therapy on outcomes were estimated using inverse probability weighting and multivariate regression models (ie, logistic model for discharge destination and composite mortality [in-hospital death or discharge to hospice] or generalized linear model for duration of antibiotic therapy, hospital length of stay [LOS], and costs). Results A total of 50 069 patients met selection criteria; 514 patients (1.0%) had CRE. Overall, 67.5% of CSE patients (vs 44.6%, CRE) received timely appropriate therapy (P < .01). Irrespective of CRE status, patients who received delayed appropriate therapy had longer durations of antibiotic therapy and LOS, higher costs, lower likelihood of discharge to home, and greater likelihood of the composite mortality outcome (P for trend < .01). Conclusions Delayed appropriate therapy is a more important driver of outcomes than CRE, although the 2 factors are somewhat synergistic. Better methods of early CRE identification may improve outcomes in this patient population.
New caching techniques for web search engines

This paper proposes a cache hierarchy that enables Web search engines to efficiently process user queries. The different caches in the hierarchy are used to store pieces of data which are useful to solve frequent queries. Cached items range from specific data such as query answers to generic data such as segments of index retrieved from secondary memory. The paper also presents a comparative study based on discrete-event simulation and bulk-synchronous parallelism. The studied performance metrics include overall query throughput, single-user query latency and power consumption. In all cases, the results show that the proposed cache hierarchy leads to better performance than a baseline approach built on state of the art caching techniques.
Incremental sensor fusion in factor graphs with unknown delays

Sensor fusion by incremental smoothing in factor graphs allows the easy incorporation of asynchronous and delayed measurements, which is one of the main advantages of this approach compared to the ubiquitous filtering techniques. While incorporating delayed measurements into the factor graph representation is in principle easy when the delay is known, handling unknown delays is a non-trivial task that has not been explored before in this context. Our paper addresses the problem of performing incremental sensor fusion in factor graphs when some of the sensor information arrive with a significant unknown delay. We develop and compare two techniques to handle such delayed measurements under mild conditions on the characteristics of that delay: We consider the unknown delay to be bounded and quantizable into multiples of the state transition cycle time. The proposed methods are evaluated using a simulation of a dynamic 3-DoF system that fuses odometry and GPS measurements.
Environmental Regulation and the Eco-Industry

This paper re-examines environmental regulation, under the assumption that pollution abatement technologies and services are provided by an imperfectly competitive environment industry. It is shown that each regulatory instrument (emission taxes and quotas; design standards; and voluntary agreements) has a specific impact on the price-elasticity of the polluters’ demand for abatement services, hence on the market power of the eco-industry and the resulting cost of abatement. This implies that the optimal pollution tax will be higher than the marginal social cost of pollution, while a voluntary approach to pollution abatement may fail unless the eco-industry itself is willing to participate.
How does the chain extension of poly (acrylic acid) scale in aqueous solution? A combined study with light scattering and computer simulation

This work addresses the question of the scaling behavior of polyelectrolytes in solution for a realistic prototype. We show results of a combined experimental (light scattering) and theoretical (computer simulations) investigation of structural properties of the sodium salt of poly (acrylic acid) (Na-PAA). Experimentally, we determined the molecular weight (MW) and the hydrodynamic radius (RH) by static and dynamic light scattering for six different Na-PAA samples in aqueous NaCl-containing solution (0.1–1 mol/l) of polydispersity DP between 1.5 and 1.8. On the computational side, three different variants of a newly developed mesoscopic force field for Na-PAA were employed to determine RH for monodisperse systems of the same MW as in the experiments. The force field effectively incorporates atomistic information and one coarse-grained bead corresponds to one PAA monomer. We find that RH matches with the experimental data for all investigated samples. The effective scaling exponent for RH is found to be ar.
Surveillance in Barrett Esophagus

The only known precursor of the esophageal adenocarcinoma (EAC) is represented by the Barrett’s esophagus (BE). EAC incidence has increased sharply in the last 4 decades. The annual conversion rate of BE to cancer is small but significant; therefore the identification of patients at a higher risk of cancer represents a dilemma. The endoscopic surveillance of BE aims to detect dysplasia and in particular high-grade dysplasia and intramucosal cancers that can be endoscopically treated before progressing to invasive cancer with lymph node metastases. Using standard white light endoscopy (WLE), these high-risk lesions are often subtle and hard to detect. In addition to high-definition standard endoscopy, chromoendoscopy (CE), virtual chromoendoscopy (e.g. narrow band imaging), and confocal laser endomicroscopy might increase the diagnostic efficiency for the detection of dysplastic lesions and can also increase the diagnostic efficiency for the detection of BE dysplasia or cancer. This ability to detect subtle mucosal abnormalities that harbor high-grade dysplasia (HGD) or intramucosal carcinoma might enable endoscopists skilled in the assessment of BE to perform targeted rather than random biopsies. The standard protocol will remain the careful examination by using conventional high-resolution endoscopes, combined with a longer inspection time, which is associated with an increased detection of dysplasia until these modalities have been demonstrated to enhance efficiency or be cost effective. Many of the limitations of the current clinical standard may be overcome in the future by the use of multi-modal imaging combined with molecular information.