Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Systems Biology Peer Review Process File Synthetic Incoherent Feed-forward Circuits Show Adaptation to the Amount of Their Genetic Template. 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 whom we asked to evaluate your manuscript. As you will see from the reports below, the referees find the topic of your study of potential interest. However, they raise several concerns, which should be convincingly addressed in a revision of the present work. The main concerns noted by the reviewers refer to the following aspects:-the need to characterize better the relationship between DNA copy number input and measured fluorescence output. -additional clarifications are required with regard to the FACS data and the observed behavior of the negative control circuits. In addition to our capacity to host datasets in our supplementary in formation section, we provide a new functionality on our website, which allows readers to directly download the 'source data' associated with selected figure panels (eg <http://tinyurl.com/365zpej>), for the purpose of alternative visualization, re-analysis or integration with other data. These files are separate from the traditional supplementary information files and are directly linked to specific figure panels. In the case of this study, we would strongly encourage you to submit the source data files corresponding to the quantitative measurements presented in the figures included in this manuscript. We provide below some general guidelines with regard to the format of such data tables. Systems Biology will publish online a Review Process File to accompany accepted manuscripts. When preparing your letter of response, please be aware that in the event of acceptance, your cover letter/point-by-point document will be included as part of this File, which will be available to the scientific community. More information about this initiative is available in our Instructions to
Venous Elastography: Validation of a Novel High‐Resolution Ultrasound Method for Measuring Vein Compliance Using Finite Element Analysis

Ultrasonography for the noninvasive assessment of tissue properties has enjoyed widespread success. With the growing emphasis in recent years on arteriovenous fistulae (AVFs) for dialysis vascular access in patients with end‐stage renal disease, and on reducing AVF failures, there is increasing interest in ultrasound for the preoperative evaluation of the mechanical and elastic properties of arteries and veins. This study used high‐resolution ultrasound with phase‐sensitive speckle tracking to obtain in vivo vein elasticity measurements during dilation. The results of this novel ultrasound technique were then compared to a computer model of venous strain. The computer model and ultrasound analysis of the vessel wall demonstrated internally consistent positive and negative longitudinal strain values as the vein wall underwent dilation. These results support further investigation of the use of phase‐sensitive speckle tracking for ultrasound venous mapping for preoperative vascular access evaluation.
Adult Current Smoking: Differences in Definitions and Prevalence Estimates—NHIS and NSDUH, 2008

Objectives. To compare prevalence estimates and assess issues related to the measurement of adult cigarette smoking in the National Health Interview Survey (NHIS) and the National Survey on Drug Use and Health (NSDUH). Methods. 2008 data on current cigarette smoking and current daily cigarette smoking among adults ≥18 years were compared. The standard NHIS current smoking definition, which screens for lifetime smoking ≥100 cigarettes, was used. For NSDUH, both the standard current smoking definition, which does not screen, and a modified definition applying the NHIS current smoking definition (i.e., with screen) were used. Results. NSDUH consistently yielded higher current cigarette smoking estimates than NHIS and lower daily smoking estimates. However, with use of the modified NSDUH current smoking definition, a notable number of subpopulation estimates became comparable between surveys. Younger adults and racial/ethnic minorities were most impacted by the lifetime smoking screen, with Hispanics being the most sensitive to differences in smoking variable definitions among all subgroups. Conclusions. Differences in current cigarette smoking definitions appear to have a greater impact on smoking estimates in some sub-populations than others. Survey mode differences may also limit intersurvey comparisons and trend analyses. Investigators are cautioned to use data most appropriate for their specific research questions.
A controlled experiment to assess the effectiveness of inspection meetings

Software inspection is one of the best practices for detecting and removing defects early in the software development process. In a software inspection, review is first performed individually and then by meeting as a team. In the last years, some empirical studies have shown that inspection meetings do not improve the effectiveness of the inspection process with respect to the number of true discovered defects. While group synergy allows inspectors to find some new defects, these meeting gains are offset by meeting losses, that is defects found by individuals but not reported as a team. We present a controlled experiment with more than one hundred undergraduate students who inspected software requirements documents as part of a university course. We compare the performance of nominal and real teams, and also investigate the reasons for meeting losses. Results show that nominal teams outperformed real teams, there were more meeting losses than meeting gains, and that most of the losses were defects found by only one individual in the inspection team.
Diversifying Product Review Rankings: Getting the Full Picture

E-commerce Web sites owe much of their popularity to consumer reviews provided together with product descriptions. On-line customers spend hours and hours going through heaps of textual reviews to build confidence in products they are planning to buy. At the same time, popular products have thousands of user-generated reviews. Current approaches to present them to the user or recommend an individual review for a product are based on the helpfulness or usefulness of each review. In this paper we look at the top-k reviews in a ranking to give a good summary to the user with each review complementing the others. To this end we use Latent Dirichlet Allocation to detect latent topics within reviews and make use of the assigned star rating for the product as an indicator of the polarity expressed towards the product and the latent topics within the review. We present a framework to cover different ranking strategies based on theuser's need: Summarizing all reviews, focus on a particular latent topic, or focus on positive, negative or neutral aspects. We evaluated the system using manually annotated review data from a commercial review Web site.
Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer

Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of lung cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA methylation in the bronchoalveolar lavage (BAL) samples of lung cancer patients. Experimental Design: We examined the tumor and the matched BAL DNA for aberrant methylation of eight gene promoters (CDH1, APC, MGMT, RASSF1A, GSTP1, p16, RAR-β2, and ARF) from 31 patients with primary lung tumors by quantitative fluorogenic real-time PCR. BAL from 10 age-matched noncancer patients was used as a control. Results: Promoter hypermethylation of at least one of the genes studied was detected in all 31 lung primary tumors; 27 (87%) CDH1, 17 (55%) APC, 14 (45%) RASSF1A, 12 (39%) MGMT, 7 (23%) p16, 3 (10%) GSTP1, 3 (10%) RAR-β2, and 0 (0%) ARF. Methylation was detected in CDH1 (48%), APC (29%), RASSF1A (29%), MGMT (58%), p16 (14%), GSTP1 (33%), RAR-β2 (0%), and ARF (0%) of BAL samples from matched methylation-positive primary tumors, and in every case, aberrant methylation in BAL DNA was accompanied by methylation in the matched tumor samples. BAL samples from 10 controls without evidence of cancer revealed no methylation of the MGMT, GSTP1, p16, ARF, or RAR-β2 genes whereas methylation of RASSF1, CDH1, and APC was detected at low levels. Overall, 21 (68%) of 31 BAL samples from cancer patients were positive for aberrant methylation. Conclusion: Our findings suggest that promoter hypermethylation in BAL can be detected in the majority of lung cancer patients. This approach needs to be evaluated in large early detection and surveillance studies of lung cancer.
A Cyclophilin Homology Domain-Independent Role for Nup358 in HIV-1 Infection

The large nucleoporin Nup358/RanBP2 forms eight filaments that project from the nuclear pore into the cytoplasm where they function as docking platforms for nucleocytoplasmic transport receptors. RNAi screens have implicated Nup358 in the HIV-1 life cycle. The 164 C-terminal amino acids of this 3,224 amino acid protein are a cyclophilin homology domain (Nup358Cyp), which has potential to bind the HIV-1 capsid and regulate viral progress to integration. Here we examined the virological role of Nup358 in conditional knockout mouse cells and in RNAi-depleted human CD4+ T cells. Cre-mediated gene knockout was toxic and diminished HIV-1 infectivity. However, cellular health and HIV-1 susceptibility were coordinately preserved if, prior to gene inactivation, a transposon was used to express all of Nup358 or only the N-terminal 1340 amino acids that contain three FG repeats and a Ran-binding domain. HIV-1, but not N74D capsid-mutant HIV-1, was markedly sensitive to TNPO3 depletion, but they infected 1–1340 segment-complemented Nup358 knockout cells equivalently. Human and mouse CypA both rescued HIV-1 in CypA gene −/− Jurkat cells and TRIM-Nup358Cyp fusions derived from each species were equally antiviral; each also inhibited both WT and N74D virus. In the human CD4+ T cell line SupT1, abrupt Nup358 depletion reduced viral replication but stable Nup358-depleted cells replicated HIV-1 normally. Thus, human CD4+ T cells can accommodate to loss of Nup358 and preserve HIV-1 susceptibility. Experiments with cylosporine, viruses with capsids that do not bind cyclophilins, and growth arrest did not uncover viral dependency on the C-terminal domains of Nup358. Our data reinforce the virological importance of TNPO3 and show that Nup358 supports nuclear transport functions important for cellular homeostasis and for HIV-1 nuclear import. However, the results do not suggest direct roles for the Nup358 cyclophilin or SUMO E3 ligase domains in engaging the HIV-1 capsid prior to nuclear translocation.
Space-Efficient Framework for Top-k String Retrieval Problems

Given a set ${\cal D}=\{d_1, d_2,. , d_D\}$ of $D$strings of total length $n$, our task is to report the "most relevant"strings for a given query pattern $P$. This involves somewhat more advanced query functionality than the usual pattern matching, as some notion of "most relevant" is involved. In information retrieval literature, this task is best achieved by using inverted indexes. However, inverted indexes work only for some predefined set of patterns. In the pattern matching community, the most popular pattern-matching data structures are suffix trees and suffix arrays. However, a typical suffix tree search involves going through all the occurrences of the pattern over the entire string collection, which might be a lot more than the required relevant documents. The first formal framework to study such kind of retrieval problems was given by [Muthukrishnan, 2002]. He considered two metrics for relevance: frequency and proximity. He took a threshold-based approach on these metrics and gave data structures taking $O(n \logn)$ words of space. We study this problem in a slightly different framework of reporting the top $k$ most relevant documents (in sorted order) under similar and more general relevance metrics. Our framework gives linear space data structure with optimal query times for arbitrary score functions. As a corollary, it improves the space utilization for the problems in [Muthukrishnan, 2002] while maintaining optimal query performance. We also develop compressed variants of these data structures for several specific relevance metrics.
Epigenetic DNA Demethylation Causes Inner Ear Stem Cell Differentiation into Hair Cell-Like Cells

The DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) causes genomic demethylation to regulate gene expression. However, it remains unclear whether 5-aza affects gene expression and cell fate determination of stem cells. In this study, 5-aza was applied to mouse utricle sensory epithelia-derived progenitor cells (MUCs) to investigate whether 5-aza stimulated MUCs to become sensory hair cells. After treatment, MUCs increased expression of hair cell genes and proteins. The DNA methylation level (indicated by percentage of 5-methylcytosine) showed a 28.57% decrease after treatment, which causes significantly repressed DNMT1 protein expression and DNMT activity. Additionally, FM1-43 permeation assays indicated that the permeability of 5-aza-treated MUCs was similar to that of sensory hair cells, which may result from mechanotransduction channels. This study not only demonstrates a possible epigenetic approach to induce tissue specific stem/progenitor cells to become sensory hair cell-like cells, but also provides a cell model to epigenetically modulate stem cell fate determination.
Predicting the Evolution of Sex on Complex Fitness Landscapes

Most population genetic theories on the evolution of sex or recombination are based on fairly restrictive assumptions about the nature of the underlying fitness landscapes. Here we use computer simulations to study the evolution of sex on fitness landscapes with different degrees of complexity and epistasis. We evaluate predictors of the evolution of sex, which are derived from the conditions established in the population genetic literature for the evolution of sex on simpler fitness landscapes. These predictors are based on quantities such as the variance of Hamming distance, mean fitness, additive genetic variance, and epistasis. We show that for complex fitness landscapes all the predictors generally perform poorly. Interestingly, while the simplest predictor, ΔVarHD, also suffers from a lack of accuracy, it turns out to be the most robust across different types of fitness landscapes. ΔVarHD is based on the change in Hamming distance variance induced by recombination and thus does not require individual fitness measurements. The presence of loci that are not under selection can, however, severely diminish predictor accuracy. Our study thus highlights the difficulty of establishing reliable criteria for the evolution of sex on complex fitness landscapes and illustrates the challenge for both theoretical and experimental research on the origin and maintenance of sexual reproduction.
A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly.

CONTEXT Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases. EVIDENCE ACQUISITION We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review was designed to document and stratify data by study design, summarize therapeutic regimens and patient characteristics, assess the percentage of patients showing changes in tumor size, and calculate the weighted average effect on size reduction. EVIDENCE SYNTHESIS Overall, for patients who experience significant shrinkage, an approximately 50% decrease in pituitary mass is achieved when a somatostatin analog is used exclusively or before surgery or radiotherapy. Fourteen studies (n = 424) provided a definition of significant tumor shrinkage, and the results showed that 36.6% (weighted mean percentage) of patients receiving primary SRL therapy for acromegaly experienced a significant reduction in tumor size. The weighted mean percent reduction in tumor size was 19.4% for those studies in which all patients received SRLs and change in tumor size was reported for all patients. CONCLUSIONS Clinical implications are discussed for patients in whom tumor size control with SRLs is an important objective, typically those who have failed surgery or are being treated with primary medical therapy with large tumors.
Brains with different degrees of dysplasia show different patterns of neurodegenerative changes following pilocarpine-induced seizures. Histologic evidence of tissue damage correlated with MRI data

Abstract Objective: Brain dysplasias produced by irradiation with gamma rays at various stages of prenatal development cause different post-natal susceptibility to seizures. To detect possible determinants of this difference, patterns of degenerative changes in the dysplastic brains following pilocarpine-induced epilepsy were analysed. Methods: Pregnant Wistar rats were exposed to a 1.0 Gy dose of gamma rays on gestation days 15 (E15) or 17 (E17). On post-natal day 60, their offspring received pilocarpine injections to evoke status epilepticus. Motor manifestations of seizure activity were observed continuously for 6 hours and rated. Six days following the status epilepticus, the rats were anesthetized and T2-weighted magnetic resonance (MR) images were obtained. Frontal sections of the brains were immunostained for immunoglobulins G (IgGs) to detect blood–brain barrier damage and IgG cell uptake and glial fibrillary acidic protein (GFAP) or S-100-β protein to visualize astrocytes. Bandeiraea simplicifolia isolectin-B4 (BSI-B4) isolectin histochemistry was also performed to detect microglia/macrophages. Results: Tissue damages within epileptic brains as observed by light microscopy generally reflected changes in magnetic resonance imaging (MRI) at similar locations. Brains of rats irradiated on E15 or E17 and showing epileptic symptoms at comparable intensity also displayed different distribution of the pathologic changes. Among other post-epileptic changes, in rats irradiated on E17 as well as controls, the laterodorsal and ventrolateral thalamic nuclei showed signs of severe degeneration. In rats irradiated on E15, the nuclei were free of such changes. Conclusions: The obtained data point to important differences in the pattern of propagation of epileptic activity in the dysplastic brains suffering from neuronal loss in functionally different structures.
Applications of error data in traffic safety evaluation

Most efforts, projects and measures dealing with the development of new information/control strategies and technologies in vehicle equipment aim at an improvement of traffic safety (e.g. PROMETHEUS, DRIVE). Therefore, it has to be highlighted that there is a need for supplying criteria and methods for an evaluation of possible safety effects, because all measures have to be applied and approved under real traffic conditions. Research indicates evidence that an evaluation of safety effects completely relying on accident data will not provide reliable future safety assessments. Without aiming at a detailed discussion about the pros and cons of the accident criterion, one important fact should be taken into account in any case: accident data will not be at our disposal at that time when new technologies are available and ready for use in real world traffic. Therefore, it is necessary to develop a set of criteria and methods to be used for a quick and efficient road safety evaluation without having to rely on retrospective accident data analysis.
The Diurnal Cycle and Its Depiction in the Community Climate System Model

Abstract To evaluate the performance of version 2 of the Community Climate System Model (CCSM2) in simulating the diurnal cycle and to diagnose the deficiencies in underlying model physics, 10 years of 3-hourly data from a CCSM2 control run are analyzed for global and large-scale features of diurnal variations in surface air temperature, surface pressure, upper-air winds, cloud amount, and precipitation. The model-simulated diurnal variations are compared with available observations, most of which were derived from 3-hourly synoptic reports and some new results are reported for surface air temperatures. The CCSM2 reproduces most of the large-scale tidal variations in surface pressure and upper-air winds, although it overestimates the diurnal pressure tide by 20%–50% over low-latitude land and underestimates it over most oceans, the Rockies, and other midlatitude land areas. The CCSM2 captures the diurnal amplitude (1°–6°C) and phase [peak at 1400–1600 local solar time (LST)] of surface air temperature ove.
Comparison of Proteome Profiling of Two Sensitive and Resistant Field Iranian Isolates of Leishmania major to Glucantime® by 2- Dimensional Electrophoresis

Background: In this study, two-dimensional gel electrophoresis (2-DE) method was applied to determine and compare the protein spots expressed in the two field isolates of Leishmania major and recovered from the patients who were clinically sensitive and resistant to Glucantime® treatment. Methods: Leishmania parasites were isolated from the cutaneous lesions of two CL infected patients in Shiraz, south of Iran. The species of the two isolates were identified as L. major using Nested-PCR. Sensitivity (Sh-214S) and resistance (Sh-120R) of the two isolates to meglumine antimonite were checked by the standard in vitro assays. Both sensitive and resistant L. major isolates were harvested in RPMI 1640 medium. Protein extractions were performed using TCA/Acetone method and the protein spots were determined by a two-dimensional gel electrophoresis (2-DE). The gels were stained with silver nitrate and analyzed by Image Master 2D Melanie-6 software. Results: About 2967 protein spots were detected. Overall, 89 protein spots represented considerable changes of expression in the resistant isolate of L. major compared to the sensitive isolate. Of these, 60 and 29 protein spots were up-and down regulated, respectively. In addition, 11 protein spots present in the resistant isolate were noticed to be absent in the sensitive isolate. Conclusion: A number of proteins showed significant changes of expression in the drug-resistant L. major; moreover, the roles of these proteins probably enhanced the parasite resistance to the drug and increased parasite survival in the cells.