Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor-Derived Cell Lines as Molecular Models of Cancer Pharmacogenomics

Compared with normal cells, tumor cells have undergone an array of genetic and epigenetic alterations. Often, these changes underlie cancer development, progression, and drug resistance, so the utility of model systems rests on their ability to recapitulate the genomic aberrations observed in primary tumors. Tumor-derived cell lines have long been used to study the underlying biologic processes in cancer, as well as screening platforms for discovering and evaluating the efficacy of anticancer therapeutics. Multiple -omic measurements across more than a thousand cancer cell lines have been produced following advances in high-throughput technologies and multigroup collaborative projects. These data complement the large, international cancer genomic sequencing efforts to characterize patient tumors, such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). Given the scope and scale of data that have been generated, researchers are now in a position to evaluate the similarities and differences that exist in genomic features between cell lines and patient samples. As pharmacogenomics models, cell lines offer the advantages of being easily grown, relatively inexpensive, and amenable to high-throughput testing of therapeutic agents. Data generated from cell lines can then be used to link cellular drug response to genomic features, where the ultimate goal is to build predictive signatures of patient outcome. This review highlights the recent work that has compared -omic profiles of cell lines with primary tumors, and discusses the advantages and disadvantages of cancer cell lines as pharmacogenomic models of anticancer therapies. Mol Cancer Res; 14(1); 3–13. ©2015 AACR.
Human iPS cell models of Jervell and Lange-Nielsen syndrome

Recessive mutations in the ion channel-encoding KCNQ1 gene may cause Jervell and Lange-Nielsen syndrome (JLNS), a fatal cardiac disease leading to arrhythmia and sudden cardiac death in young patients. Mutations in KCNQ1 may also cause a milder and dominantly inherited form of the disease, long QT syndrome 1 (LQT1). However, why some mutations cause LQT1 and others cause JLNS can often not be understood a priori. In a recent study,1 we have generated human induced pluripotent stem cell (hiPSC) models of JLNS. Our work mechanistically revealed how distinct classes of JLNS-causing genetic lesions, namely, missense and splice-site mutations, may promote the typical severe features of the disease at the cellular level. Interestingly, the JLNS models also displayed highly sensitive responses to pro-arrhythmic stresses. We hence propose JLNS hiPSCs as a powerful system for evaluating both phenotype-correcting as well as cardiotoxicity-causing drug effects.
Bone strength is maintained after 8 months of inactivity in hibernating golden-mantled ground squirrels, Spermophilus lateralis

SUMMARY Prolonged inactivity leads to disuse atrophy, a loss of muscle and bone mass. Hibernating mammals are inactive for 6–9 months per year but must return to full activity immediately after completing hibernation. This necessity for immediate recovery presents an intriguing conundrum, as many mammals require two to three times the period of inactivity to recover full bone strength. Therefore, if hibernators experience typical levels of bone disuse atrophy during hibernation, there would be inadequate time available to recover during the summer active season. We examined whether there were mechanical consequences as a result of the extended inactivity of hibernation. We dissected femur and tibia bones from squirrels in various stages of the annual hibernation cycle and measured the amount of force required to fracture these bones. Three groups were investigated; summer active animals were captured during the summer and immediately killed, animals in the 1 month detraining group were captured in the summer and killed following a 1-month period of restricted mobility, hibernating animals were killed after 8 months of inactivity. A three-point bend test was employed to measure the force required to break the bones. Apparent flexural strength and apparent flexural modulus (material stiffness) were calculated for femurs. There were no differences between groups for femur fracture force, tibia fracture force, or femur flexural strength. Femur flexural modulus was significantly less for the 1 month detraining group than for the hibernation and summer active groups. Thus, hibernators seem resistant to the deleterious effects of prolonged inactivity during the winter. However, they may be susceptible to immobilization-induced bone loss during the summer.
A regional scale modeling analysis of aerosol and trace gas distributions over the eastern Pacific during the INTEX-B field campaign

Abstract. The Sulfur Transport and dEposition Model (STEM) is applied to the analysis of observations obtained during the Intercontinental Chemical Transport Experiment-Phase B (INTEX-B), conducted over the eastern Pacific Ocean during spring 2006. Predicted trace gas and aerosol distributions over the Pacific are presented and discussed in terms of transport and source region contributions. Trace species distributions show a strong west (high) to east (low) gradient, with the bulk of the pollutant transport over the central Pacific occurring between ~20° N and 50° N in the 2–6 km altitude range. These distributions are evaluated in the eastern Pacific by comparison with the NASA DC-8 and NSF/NCAR C-130 airborne measurements along with observations from the Mt. Bachelor (MBO) surface site. Thirty different meteorological, trace gas and aerosol parameters are compared. In general the meteorological fields are better predicted than gas phase species, which in turn are better predicted than aerosol quantities. PAN is found to be significantly overpredicted over the eastern Pacific, which is attributed to uncertainties in the chemical reaction mechanisms used in current atmospheric chemistry models in general and to the specifically high PAN production in the SAPRC-99 mechanism used in the regional model. A systematic underprediction of the elevated sulfate layer in the eastern Pacific observed by the C-130 is another issue that is identified and discussed. Results from source region tagged CO simulations are used to estimate how the different source regions around the Pacific contribute to the trace gas species distributions. During this period the largest contributions were from China and from fires in South/Southeast and North Asia. For the C-130 flights, which operated off the coast of the Northwest US, the regional CO contributions range as follows: China (35%), South/Southeast Asia fires (35%), North America anthropogenic (20%), and North Asia fires (10%). The transport of pollution into the western US is studied at MBO and a variety of events with elevated Asian dust, and periods with contributions from China and fires from both Asia and North America are discussed. The role of heterogeneous chemistry on the composition over the eastern Pacific is also studied. The impacts of heterogeneous reactions at specific times can be significant, increasing sulfate and nitrate aerosol production and reducing gas phase nitric acid levels appreciably (~50%).
[Antimicrobial resistance of Bartonella bacilliformis strains from regions endemic to bartonellosis in Peru].

OBJECTIVES To evaluate in vitro antimicrobial susceptibility to chloramphenicol (CHL) and ciprofloxacin (CIP) in strains of Bartonella bacilliformis from areas that are endemic to Bartonellosis in Peru, through three laboratory methods. MATERIALS AND METHODS Antimicrobial susceptibility to CHL and CIP from 100 strains of Bartonella bacilliformis isolated in patients from the regions of Ancash, Cusco, Cajamarca, Lima and La Libertad were evaluated. Strains were evaluated by: disk diffusion, E-test and agar dilution. RESULTS 26% of the strains of Bartonella bacilliformis evaluated were resistant to CIP and 1% to CHL. Similar patterns of antimicrobial sensitivity / resistance were obtained in all three methods. CONCLUSIONS Bartonella bacilliformis strains circulating in Peru have high levels of in vitro resistance to CIP, so it is advisable to expand research on the use of drug treatment regimens of the Bartonellosis. The methods of E-test and disk diffusion were the most suitable for assessment in vitro of antimicrobial susceptibility of the microorganism.
Inhibition of T4ss Gene Legionella pneumophila with Catalytical Ozonization

Legionella bacteria are aerobic gram-negative rods associated with respiratory infections. Of the 52 known species legionella , 20 have been linked to pneumonia infections in humans. The species L.pneumophila (particularly serogroups 1-6) has been accepted as the principal cause of human outbreaks of legionellosis, which includes both legionnaires, disease and Pontiac fever. Legionella are ubiquitous in natural aquatic environments, capable of existing in waters with varied temperature, PH levels, and nutrient and oxygen contents. Contamination by legionella has occurred in the distribution systems of many hospitals. Their widespread survival in nature can be attribute to their relationships with other microorganisms in the environment. Symbiotic existence with algae and other bacteria , particularly in biofilms, increases the availability of nutrients. They also are able to infect protozoans and subsequently reproduce within these organisms. These relationships provide protection against adverse environmental conditions, including standard water disinfection techniques. Consequently, legionella are also prevent in anthropogenic waters such as potable water, cooling tower reservoirs, water distribution systems and whirlpools. Aerosol-generating systems such as fauceta, shower heads, cooling towers, and nebolizers aid in the transmission of legionella from water to air. Human inhalation of contaminated aerosols leads to legionella infections and disease outbreaks. Collection of legionella was done from hospital water . These samples are typically concentrated by filtration, treated with an acid buffer and temperature , and isolated on a BCYE agar culture medium. Legionella pneumophila was treated with concentration of MIC catalytical ozonation then evaluated t4ss gene expression by RT-PCR technique. The results indicated that catalytical ozonation have inhibitory effects on virulence genes Legionella pneumophila . So we can use it as an active disinfectant in hospital distribution systems.
Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery

Objectives Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology. Setting 107 secondary and tertiary cardiac surgery centres across the USA. Participants We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included. Primary and secondary outcome measures The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution. Results Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10−5 in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10−3 for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10−6 for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation. Conclusions Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.
Journal of Geophysical Research: Atmospheres Emissions and topographic effects on column CO2 (XCO2) variations, with a focus on the Southern California Megacity

Within the California South Coast Air Basin (SoCAB), XCO2 varies significantly due to atmospheric dynamics and the nonuniform distribution of sources. XCO2 measurements within the basin have seasonal variation compared to the “background” due primarily to dynamics, or the origins of air masses coming into the basin. We observe basin-background differences that are in close agreement for three observing systems: Total Carbon Column Observing Network (TCCON) 2.3 ± 1.2 ppm, Orbiting Carbon Observatory-2 (OCO-2) 2.4 ± 1.5 ppm, and Greenhouse gases Observing Satellite 2.4 ± 1.6 ppm (errors are 1σ). We further observe persistent significant differences (∼0.9 ppm) in XCO2 between two TCCON sites located only 9 km apart within the SoCAB. We estimate that 20% (±1σ confidence interval (CI): 0%, 58%) of the variance is explained by a difference in elevation using a full physics and emissions model and 36% (±1σ CI: 10%, 101%) using a simple, fixed mixed layer model. This effect arises in the presence of a sharp gradient in any species (here we focus on CO2) between the mixed layer (ML) and free troposphere. Column differences between nearby locations arise when the change in elevation is greater than the change in ML height. This affects the fraction of atmosphere that is in the ML above each site. We show that such topographic effects produce significant variation in XCO2 across the SoCAB as well. Plain Language Summary Cities persistently have elevated carbon dioxide (CO2) levels as compared to surrounding regions. Within a city CO2 levels can also vary significantly at different locations for reasons such as more CO2 being emitted in some parts than others. Elevated column CO2 levels in the South Coast Air Basin (SoCAB) are in agreement for three observation systems (two satellite and one ground-based) systems and vary with regional wind patterns throughout the year. In Pasadena, California, within the SoCAB, a significant fraction (about 25%) of variation in the column-averaged CO2 can be explained by differences in surface altitude. This is important to understand so that all variations in column CO2 within an urban region are not mistakenly interpreted as being from CO2 surface fluxes.
The Transcriptome of Streptococcus pneumoniae Induced by Local and Global Changes in Supercoiling

The bacterial chromosome is compacted in a manner optimal for DNA transactions to occur. The degree of compaction results from the level of DNA-supercoiling and the presence of nucleoid-binding proteins. DNA-supercoiling is homeostatically maintained by the opposing activities of relaxing DNA topoisomerases and negative supercoil-inducing DNA gyrase. DNA-supercoiling acts as a general cis regulator of transcription, which can be superimposed upon other types of more specific trans regulatory mechanism. Transcriptomic studies on the human pathogen Streptococcus pneumoniae, which has a relatively small genome (∼2 Mb) and few nucleoid-binding proteins, have been performed under conditions of local and global changes in supercoiling. The response to local changes induced by fluoroquinolone antibiotics, which target DNA gyrase subunit A and/or topoisomerase IV, involves an increase in oxygen radicals which reduces cell viability, while the induction of global supercoiling changes by novobiocin (a DNA gyrase subunit B inhibitor), or by seconeolitsine (a topoisomerase I inhibitor), has revealed the existence of topological domains that specifically respond to such changes. The control of DNA-supercoiling in S. pneumoniae occurs mainly via the regulation of topoisomerase gene transcription: relaxation triggers the up-regulation of gyrase and the down-regulation of topoisomerases I and IV, while hypernegative supercoiling down-regulates the expression of topoisomerase I. Relaxation affects 13% of the genome, with the majority of the genes affected located in 15 domains. Hypernegative supercoiling affects 10% of the genome, with one quarter of the genes affected located in 12 domains. However, all the above domains overlap, suggesting that the chromosome is organized into topological domains with fixed locations. Based on its response to relaxation, the pneumococcal chromosome can be said to be organized into five types of domain: up-regulated, down-regulated, position-conserved non-regulated, position-variable non-regulated, and AT-rich. The AT content is higher in the up-regulated than in the down-regulated domains. Genes within the different domains share structural and functional characteristics. It would seem that a topology-driven selection pressure has defined the chromosomal location of the metabolism, virulence and competence genes, which suggests the existence of topological rules that aim to improve bacterial fitness.
Journal of Stem Cell Research

Benzodiazepines (BZDs) are some of the most commonly prescribed medications in the United States and are currently classified as schedule IV-controlled substances. Originally patented in 1958, Librium became the first BZD synthesized and set the stage for what would become a major change in medical practice. Since their introduction, BZDs were meant to replace barbiturates, a precursor family with highly addictive properties and lethal overdose consequences. Within the past twenty years, it has been found that BZDs can also cause physical dependence, sometimes in as little as two weeks
Mu suppression and human movement responses to the Rorschach test

Electroencephalographic &mgr; wave suppression was investigated using all 10 static, ambiguous Rorschach stimuli. In an earlier study using four Rorschach stimuli, the two stimuli that elicited feelings of movement were associated with &mgr; suppression. In this study, we replicated this relationship using all 10 Rorschach stimuli while overcoming a number of other earlier limitations. The results strongly support the hypothesis that internal representation of the feeling of movement is sufficient to suppress the &mgr; rhythm even when minimal external cues are present. This outcome increases the generalizability and ecological validity of this approach and gives support to the traditional interpretation of the Rorschach human movement responses as being associated with cognitive functioning, empathy, and social cognition.
Diversity of Hepatitis B virus infecting Malaysian candidate blood donors is driven by viral and host factors

Summary. Malaysia is a medium endemic country for hepatitis B virus (HBV) infection but little is known about HBV strains circulating in Malaysian blood donors. Viral load, HBsAg concentrations and nested PCR products from 84 HBV surface antigen (HBsAg) positive samples were analysed in detail. Median viral load was 3050 IU/mL and median HBsAg 1150 IU/mL. Fifty‐six full genome, 20 pre‐S/S, 1 S gene and six basic core promoter/precore‐only sequences were obtained. Genotypes B and C were present at a ratio of 2:1, and two genotype D samples were obtained, both from donors of Indian background. Phylogenetically, genotype B was more diverse with subgenotypes B2‐5, B7 and B8 present, while most genotype C strains were from subgenotype C1. Genotypes B and C were equally frequent in ethnic Malays, but 80% of strains from Chinese were genotype B. HBsAg concentrations were higher in genotype C than in genotype B, in Chinese than Malays and in donors under the age of 30. HBV vaccine escape substitutions (P120S/T, I126N and G145G) were present in six strains. In the large surface protein, immuno‐inactive regions were more mutated than CD8 epitopes and the major hydrophilic region. Strains of genotype B or from ethnic Malays had higher genetic diversity than strains of genotype C or from Chinese donors. Hence HBV strains circulating in Malaysia are phylogenetically diverse reflecting the ethnic mix of its population. Ethnic Malays carry lower HBsAg levels and higher genetic diversity of the surface antigen, possibly resulting in more effective immune control of the infection.
Space-Time Aware Behavioral Topic Modeling for Microblog Posts

Off-the-Shelf (OTS), relational databases can be challenging when deployed in the cloud. Given their architectures, limitations arise regarding performance (because of virtualization), scalability (because of multi-tenancy), and elasticity (because existing engines cannot easily take advantage of the application migration possibilities of virtualized environments). As a result, many database engines tailored to cloud computing differ from conventional engines in functionality, consistency levels, support for queries or transactions, and even interfaces. Efficiently supporting Off-the-Shelf databases in the cloud would allow to port entire application stacks without rewriting them. In this paper we present a system that combines snapshot isolation (SI) replication with virtualization to provide a flexible solution for running unmodified databases in the cloud while taking advantage of the opportunities cloud architectures provide. Unlike replication-only solutions, our system works well both within larger servers and across clusters. Unlike virtualization only solutions, our system provides better performance and more flexibility in the deployment.
Reliable Broadcasting in Hypercubes with Random Link and Node Failures

We consider the problem of broadcasting in an n–node hypercube whose links and nodes fail independently with given probabilities p < 1 and q < 1, respectively. Information held in a fault-free node, called the source, has to reach all other fault-free nodes. Messages may be directly transmitted to adjacent nodes only, and every node may communicate with at most one neighbour in a unit of time. A message can be transmitted only if both communicating neighbours and the link joining them are fault-free. For parameters p and q satisfying (1 – p)(1 – q) ≽ 0.99 (e.g. p = q = 0.5%), we give an algorithm working in time O(log n) and broadcasting source information to all fault-free nodes with probability exceeding 1 – cn-e for some positive constant ε, c depending on p and q but not depending on n.
Symmetrization and Mass Comparison for Degenerate Nonlinear Parabolic and Related Elliptic Equations

Abstract We consider the solutions to various nonlinear parabolic equations and their elliptic counterparts and prove comparison results based on two main tools, symmetrization and mass concentration comparison. The work focuses on equations like the porous medium equation, the filtration equation and the p-Laplacian equation. The results will be used in a companion work in combination with a detailed knowledge of special solutions to obtain sharp a priori bounds and decay estimates for wide classes of solutions of those equations.