Miracle-dz/UniFAR-FTUs huggingface dataset:
A positive selection for plasmid loss in Saccharomyces cerevisiae using galactose‐inducible growth inhibitory sequences

Counter‐selections for the loss of introduced plasmid sequences are useful for gene manipulations in yeast. We have used GAL10 promoter‐mediated overexpression of GIN sequences, which inhibit the growth of cells, to develop a novel counter‐selection system. Yeast cells carrying a GIN sequence grow normally on glucose medium but are unable to grow on galactose medium, whereas derivatives that have lost the GIN sequence are able to grow in the presence of galactose. We constructed autonomously replicating, integrating, and disruption plasmids carrying GIN sequences and tested their use to select for loss of the plasmid. The results showed that the GIN sequences provide a selection for efficient loss of plasmids or integrated constructs from yeast during growth on galactose medium, indicating that this system can be used for plasmid shuffling, gene replacements and marker gene recycling. This counter‐selection system has wide application, because any Gal+ strain and a wide variety of marker genes can be used. In addition, counter‐selection systems using growth‐inhibitory sequences should be applicable to other yeasts and possibly to other organisms. Copyright © 1999 John Wiley & Sons, Ltd.
The TRAPPIII complex activates the GTPase Ypt1 (Rab1) in the secretory pathway

Rab GTPases serve as molecular switches to regulate eukaryotic membrane trafficking pathways. The transport protein particle (TRAPP) complexes activate Rab GTPases by catalyzing GDP/GTP nucleotide exchange. In mammalian cells, there are two distinct TRAPP complexes, yet in budding yeast, four distinct TRAPP complexes have been reported. The apparent differences between the compositions of yeast and mammalian TRAPP complexes have prevented a clear understanding of the specific functions of TRAPP complexes in all cell types. In this study, we demonstrate that akin to mammalian cells, wild-type yeast possess only two TRAPP complexes, TRAPPII and TRAPPIII. We find that TRAPPIII plays a major role in regulating Rab activation and trafficking at the Golgi in addition to its established role in autophagy. These disparate pathways share a common regulatory GTPase Ypt1 (Rab1) that is activated by TRAPPIII. Our findings lead to a simple yet comprehensive model for TRAPPIII function in both normal and starved eukaryotic cells.
The use and limits of scientific names in biological informatics

Abstract Scientific names serve to label biodiversity information: information related to species. Names, and their underlying taxonomic definitions, however, are unstable and ambiguous. This negatively impacts the utility of names as identifiers and as effective indexing tools in biological informatics where names are commonly utilized for searching, retrieving and integrating information about species. Semiotics provides a general model for describing the relationship between taxon names and taxon concepts. It distinguishes syntactics, which governs relationships among names, from semantics, which represents the relations between those labels and the taxa to which they refer. In the semiotic context, changes in semantics (i.e., taxonomic circumscription) do not consistently result in a corresponding and reflective change in syntax. Further, when syntactic changes do occur, they may be in response to semantic changes or in response to syntactic rules. This lack of consistency in the cardinal relationship between names and taxa places limits on how scientific names may be used in biological informatics in initially anchoring, and in the subsequent retrieval and integration, of relevant biodiversity information. Precision and recall are two measures of relevance. In biological taxonomy, recall is negatively impacted by changes or ambiguity in syntax while precision is negatively impacted when there are changes or ambiguity in semantics. Because changes in syntax are not correlated with changes in semantics, scientific names may be used, singly or conflated into synonymous sets, to improve recall in pattern recognition or search and retrieval. Names cannot be used, however, to improve precision. This is because changes in syntax do not uniquely identify changes in circumscription. These observations place limits on the utility of scientific names within biological informatics applications that rely on names as identifiers for taxa. Taxonomic systems and services used to organize and integrate information about taxa must accommodate the inherent semantic ambiguity of scientific names. The capture and articulation of circumscription differences (i.e., multiple taxon concepts) within such systems must be accompanied with distinct concept identifiers that can be employed in association with, or in replacement of, traditional scientific names.
Diet Quality Is Associated with Higher Nutrient Intake and Self-Rated Health in Mid-Aged Women

Objective: To develop a diet quality score reflecting adherence to national dietary recommendations for the Australian Longitudinal Study on Women's Health (ALSWH) and to compare this against energy standardized nutrient intakes and indices of health. Design: Cross-sectional survey in a nationally representative sample of mid-aged women participating in a cohort study. Subjects: Data from 9,895 women aged 50–55 who participated in the 2001 survey and had four or less missing values on their food frequency questionnaires were used to calculate the Australian Recommended Food Score (ARFS) based on adherence to Australian Dietary Guidelines. Measure of Outcome: Correlates of ARFS were investigated including, mean nutrient intakes and indices of self-rated health and health service use. Associations were examined using ANOVA for continuous variables and Chi-squared tests for categorical variables. Area of residence and educational attainment were used as covariates in all modeling, to adjust for sampling frame and socioeconomic status. Results: The maximum ARFS was 74, with a mean of 33.0 ± 9.0 and 21% achieving a score > 40. Higher ARFS was associated with indicators of higher socio-economic status, better self-rated health and lower health service use, p<0.0001, higher intakes of micronutrients and lower percentage of energy as total or saturated fat, p<0.0001. Conclusions: The Australian Recommended Food Score can be used to rank mid-aged women in terms of diet quality and nutrient intake and is associated with indices of self-rated health and health service use. The ARFS can be used to measure future associations with health outcomes and mortality.
Potential role for 8‐oxoguanine DNA glycosylase in regulating inflammation

OGG‐1 DNA glycosylase (OGG‐1) is an enzyme involved in DNA repair. It excises 7,8‐dihydro‐8‐oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG‐1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG‐1−/− mice are resistant to endotoxin (lipopolysaccharide, LPS)‐induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild‐type controls (OGG+/+). Furthermore, the deletion of the OGG‐1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low‐dose streptozotocin treatment. OGG‐1−/− mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG‐1+/+ mice. Biochemical analysis of the pancreas showed that OGG‐1−/− mice had greater insulin content, indicative of a greater β‐cell mass coupled with lower levels of the chemokine MIP‐1α and Th1 cytokines IL‐12 and TNF‐α. Levels of protective Th2 cytokines, IL‐4 and IL‐10 were significantly higher in the pancreata of OGG‐1−/− mice as compared with the levels measured in wild‐type mice. In the contact hypersensitivity induced by oxazolone, the OGG‐1−/− mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG‐1 in the regulation of inflammation.
Further localization of X-linked hydrocephalus in the chromosomal region Xq28.

X-linked hydrocephalus (HSAS) is the most frequent genetic form of hydrocephalus. Clinical symptoms of HSAS include hydrocephalus, mental retardation, clasped thumbs, and spastic paraparesis. Recently we have assigned the HSAS gene to Xq28 by linkage analysis. In the present study we used a panel of 18 Xq27-q28 marker loci to further localize the HSAS gene in 13 HSAS families of different ethnic origins. Among the Xq27-q28 marker loci used, DXS52, DXS15, and F8C gave the highest combined lod scores, of 14.64, 6.53 and 6.33, respectively, at recombination fractions of . 04, 0, and . 05, respectively. Multipoint linkage analysis localizes the HSAS gene in the telomeric part of the Xq28 region, with a maximal lod score of 20.91 at 0.5 cM distal to DXS52. Several recombinations between the HSAS gene and the Xq28 markers DXS455, DXS304, DXS305, and DXS52 confirm that the HSAS locus is distal to DXS52. One crossover between HSAS and F8C suggests that HSAS gene to be proximal to F8C. Therefore, data from multipoint linkage analysis and the localization of key crossovers indicate that the HSAS gene is most likely located between DXS52 and F8C. This high-resolution genetic mapping places the HSAS locus within a region of less than 2 Mb in length, which is now amenable to positional cloning.
A peak-shift control method for charging and discharging of the battery in an ultrabook

As the electricity rates during peak hours are higher, this paper proposes a method for an ultrabook to automatically shift the charging period to an off-peak period. In addition this design sets an upper limit for the battery which thus protects the battery and avoids its remaining in a state of continued high voltage. We use a low-power embedded controller (EC) as the main control part together with RTC ICs. The sensing value of the EC and the presetting of parameters are used to control the conversion of the AC/DC module. Our user interface design allows the user to set the peak/off-peak period and the upper limit of the battery. The design also controls dynamically both the charging current and the charging voltage, in accordance with the temperature of the battery. In this way our design extends the life of the battery.
Ras Activation Is Necessary for Integrin-mediated Activation of Extracellular Signal-regulated Kinase 2 and Cytosolic Phospholipase A2 but Not for Cytoskeletal Organization*

Cell adhesion to the extracellular matrix triggers a cascade of intracellular biochemical signals regulated by the integrin family of receptors. Recent evidence suggests that integrin engagement may activate a mitogen-activated protein (MAP) kinase cascade that may cooperate with more clearly defined mitogenic signaling pathways to regulate cell proliferation, adhesion, and migration. Here we report that the adhesion-dependent activation of the MAP kinase Erk2 (extracellular signal-regulated kinase 2) occurs in serum-starved NIH3T3 cells, and that this activation of Erk2 is preceded by the activation of the small GTP-binding protein Ras in fibronectin-adherent cells. Inhibition of Ras signaling by expression of a dominant-inhibitory mutant of Ras (N17Ras) in NIH3T3 cells blocked adhesion-dependent activation of Erk2, although the focal adhesion kinase (FAK) was still activated in these cells. Furthermore, activation of this Ras-MAP kinase pathway activated cytosolic phospholipase A2, leading to the release of arachidonic acid metabolites, and N17Ras also inhibited these events. However, N17Ras expression does not inhibit cell adhesion, spreading, or focal contact and stress fiber formation. These results suggest that, while integrin-dependent activation of this MAP kinase pathway is Ras-dependent, the integrin-dependent activation of FAK and several morphological events are Ras-independent. Thus, integrin-mediated signals involved in regulating cell morphology appear to diverge from those regulating MAP kinase activation at a level upstream of Ras activation.
Real time angular velocity and vibration monitoring using fiber Bragg grating interrogation system

We present a fiber Bragg grating sensing system which combined with fiber Bragg grating (FBG) vibration sensors and fiber optic gyroscope (FOG) in a fiber loop to achieve the ability of real time angular velocity measurement and mechanical monitoring. The FBG sensing system is consisted by a fiber ring laser structure which is pumped by an erbium doped fiber amplifier (EDFA). The FBG which its wavelength can be perturbed by physical vibration and is used for the reflective filter of the fiber ring laser. The principle of the angular velocity measurement is based on Sagnac effect to form the interference due to two counter-propagating propagation, CW and CCW along the fiber loops. Real time vibrational measurement as high as 1 kHz with accuracy of 1 Hz, and minimum angular velocity measurement of 0.105 rad/s (1 rpm) was achieved. It shows that this FBG sensing system is efficient to real time safety monitoring for the civil engineering object and geodesic landscape.
Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy.

BACKGROUND Amplification or deletion of the topoisomerase II alpha (TOP2A) gene in breast cancers has been postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than amplification of the human epidermal growth factor receptor type 2 (HER2) gene. METHODS We studied 438 tumors from 710 premenopausal women with node-positive breast cancer who received cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy in the randomized National Cancer Institute of Canada Clinical Trials Group Mammary 5 (MA.5) trial. TOP2A alterations and HER2 amplification were quantified by fluorescence in situ hybridization. The association of TOP2A and HER2 status with recurrence-free survival (RFS) and overall survival (OS) in the two treatment groups was analyzed using Kaplan-Meier curves, the log-rank test, and Cox proportional hazard models. All statistical tests were two-sided. RESULTS In patients whose tumors showed TOP2A alterations (either amplifications or deletions), treatment with CEF was statistically significantly superior to treatment with CMF in terms of RFS (adjusted hazard ratio [HR] = 0.35, 95% confidence interval [CI] = 0.17 to 0.73, P = .005) and OS (adjusted HR = 0.33, 95% CI = 0.15 to 0.75, P = .008). In patients without TOP2A amplification or deletion, the corresponding adjusted hazard ratios for RFS and OS were 0.90 (95% CI = 0.66 to 1.23, P = .49) and 1.09 (95% CI = 0.77 to 1.56, P = .62). Adjusted tests of interaction between treatment and TOP2A status were P = . 09 for RFS and P = . 02 for OS. Adjusted tests of interaction between treatment and HER2 status were P = . 008 for RFS and P = . 02 for OS. CONCLUSION TOP2A gene alterations (amplifications or deletions) are associated with an increase in responsiveness to anthracycline-containing chemotherapy regimens relative to non-anthracycline regimens that is similar to that seen in patients with HER2 amplification.
Heterogeneous Breast Tumoroids: An In Vitro Assay for Investigating Cellular Heterogeneity and Drug Delivery

Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell and cell-matrix interactions during tumor development. This article presents an in vitro coculture-based 3-dimensional heterogeneous breast tumor model that can be used in drug resistance and drug delivery investigations. Breast cancer cell lines of different phenotypes (MDAMB231, MCF7, and ZR751) were cocultured in a rotating wall vessel bioreactor to form a large number of heterogeneous tumoroids in a single cell culture experiment. Cells in the rotating vessels were labeled with Cell Tracker fluorescent probes to allow for time course fluorescence microscopy to monitor cell aggregation. Histological sections of tumoroids were stained with hematoxylin and eosin, progesterone receptor, E-cadherin (E-cad), and proliferation marker ki67. In vitro tumoroids developed in this study recapture important features of the temporal-spatial organization of solid tumors, including the presence of necrotic areas at the center and higher levels of cell division at the tumor periphery. E-cad-positive MCF7 cells form larger tumoroids than E-cad-negative MDAMB231 cells. In heterogeneous tumors, the irregular surface roughness was mainly due to the presence of MDAMB231 cells, whereas MCF7 cells formed smooth surfaces. Moreover, when heterogeneous tumoroids were placed onto collagen gels, highly invasive MDAMB231 cell-rich surface regions produced extensions into the matrix, whereas poorly invasive MCF7 cells did not. The fact that one can form a large number of 1-mm tumoroids in 1 coculture attests to the potential use of this system at high-throughput investigations of cancer drug development and drug delivery into the tumor.
Is Cupressus sempervirens native in Italy? An answer from genetic and palaeobotanical data

This study represents the first large‐scale analysis using nuclear molecular markers to assess genetic diversity and structure of Cupressus sempervirens L. Genetic and fossil data were combined to infer the possible role of human activity and evolutionary history in shaping the diversity of cypress populations. We analysed 30 populations with six polymorphic nuclear microsatellite markers. Dramatic reductions in heterozygosity and allelic richness were observed from east to west across the species range. Structure analysis assigned individuals to two main groups separating central Mediterranean and eastern populations. The two main groups could be further divided into five subgroups which showed the following geographical distributions: Turkey with the Greek islands Rhodes and Samos, Greece (Crete), Southern Italy, Northern Italy, Tunisia with Central Italy. This pattern of genetic structure is also supported by samova and Barrier analyses. Palaeobotanical data indicated that Cupressus was present in Italy in the Pliocene, Pleistocene and Holocene. Furthermore, our molecular survey showed that Italian cypress populations experienced bottlenecks that resulted in reduced genetic diversity and allelic richness and greater genetic differentiation. Recent colonization or introduction may also have influenced levels of diversity detected in the Italian populations, as most individuals found in this range today have multilocus genotypes that are also present in the eastern range of the species. The data reveal a new interpretation of the history of cypress distribution characterized by ancient eastern populations (Turkey and Greek islands) and a mosaic of recently introduced trees and remnants of ancient, depauperate populations in the central Mediterranean range.
Survival without Common Toxicity Criteria Grade 3/4 Toxicity for Pemetrexed Compared with Docetaxel in Previously Treated Patients with Advanced Non-small Cell Lung Cancer (NSCLC): A Risk-Benefit Analysis

Background: In a recent large phase III study, previously treated patients with advanced non-small cell lung cancer who received pemetrexed demonstrated a survival time similar to patients who received docetaxel (median, 8.3 months with pemetrexed versus 7.9 months with docetaxel), with a more favorable toxicity profile, and significantly fewer Common Toxicity Criteria grade 3/4 toxicities. This is a retrospective risk-benefit analysis of survival without grade 3/4 toxicity, defined as the time to the first occurrence of Common Toxicity Criteria grade 3 or 4 toxicity or death, in the prospective phase III study comparing pemetrexed with docetaxel. Methods: A total of 541 patients (of 571 randomized) received either pemetrexed (500 mg/m2 intravenously [IV]) supplemented with vitamin B12 injections and oral folic acid or docetaxel (75 mg/m2 IV) on day 1 of 21-day cycles. Survival without grade 3/4 toxicity was analyzed using Kaplan-Meier and Cox methods. Results: Pemetrexed demonstrated a statistically significantly longer survival without grade 3/4 toxicity compared with docetaxel (hazard ratio = 0.60, 95% confidence interval: 0.50–0.72; p < 0.0001). A supportive analysis based on selected grade 3/4 toxicities (neutropenia lasting >5 days, febrile neutropenia, infection with neutropenia, anemia, thrombocytopenia, fatigue, nausea, vomiting, diarrhea, stomatitis, and neurosensory events) also demonstrated an advantage for pemetrexed (hazard ratio = 0.53; 95% confidence interval: 0.44–0.64; p < 0.0001). Conclusion: This analysis of survival without grade 3/4 toxicity suggests a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of patients with non-small cell lung cancer.
Analytical and clinical evaluation of biomarkers assays: When are biomarkers ready for prime time?

Background Biomarker assays can be evaluated for analytical performance (ability of assay to measure the biomarker quantity) and clinical performance (ability of assay result to inform of the clinical condition of interest). Additionally, a biomarker assay is said to have clinical utility if it ultimately improves patient outcomes when used as intended. Purpose This article reviews analytical and clinical performance studies of biomarker assay tests and also some designs of clinical utility studies. Results Appropriate design and statistical analysis of analytical and clinical evaluation studies depend on the intended clinical use of the test. Some key aspects to valid performance studies include using subjects who are independent of those used to develop the test, masking users of the test to any other available test or reference results, and including in the primary statistical analysis subjects with unavailable results in an intention-to-diagnose analysis. Ingenuity in study design and analysis may be required for efficient and unbiased estimation of performance. Limitations Performance studies need to be carefully planned as they can be prone to many sources of bias. Analytical inaccuracy can hamper the clinical performance of biomarkers. Conclusions As biomedical research and technology advance, challenges in study design and statistical analysis will continue to emerge for analytical and clinical performance studies of biomarker assays. Although not emphasized in some circles, the analytical performance of a biomarker assay is important to characterize. Analytical performance studies have many study design and statistical analysis challenges that deserve further attention.