Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative genomic analysis of primary versus metastatic colorectal carcinomas.

PURPOSE To compare the mutational and copy number profiles of primary and metastatic colorectal carcinomas (CRCs) using both unpaired and paired samples derived from primary and metastatic disease sites. PATIENTS AND METHODS We performed a multiplatform genomic analysis of 736 fresh frozen CRC tumors from 613 patients. The cohort included 84 patients in whom tumor tissue from both primary and metastatic sites was available and 31 patients with pairs of metastases. Tumors were analyzed for mutations in the KRAS, NRAS, BRAF, PIK3CA, and TP53 genes, with discordant results between paired samples further investigated by analyzing formalin-fixed, paraffin-embedded tissue and/or by 454 sequencing. Copy number aberrations in primary tumors and matched metastases were analyzed by comparative genomic hybridization (CGH). RESULTS TP53 mutations were more frequent in metastatic versus primary tumors (53.1% v 30.3%, respectively; P < .001), whereas BRAF mutations were significantly less frequent (1.9% v 7.7%, respectively; P = .01). The mutational status of the matched pairs was highly concordant (> 90% concordance for all five genes). Clonality analysis of array CGH data suggested that multiple CRC primary tumors or treatment-associated effects were likely etiologies for mutational and/or copy number profile differences between primary tumors and metastases. CONCLUSION For determining RAS, BRAF, and PIK3CA mutational status, genotyping of the primary CRC is sufficient for most patients. Biopsy of a metastatic site should be considered in patients with a history of multiple primary carcinomas and in the case of TP53 for patients who have undergone interval treatment with radiation or cytotoxic chemotherapies.
Immune Modulation by the Human Cytomegalovirus-Encoded Molecule UL18, a Mystery Yet to Be Solved

Human cytomegalovirus infects human populations at a high frequency worldwide. During the long coevolution of virus and host, a fine balance has developed between viral immune evasion strategies and defense mechanisms of the immune system. Human cytomegalovirus encodes multiple proteins involved in the evasion of immune recognition, among them UL18, a MHC class I homologue. Despite almost 20 years of research and the discovery of a broadly expressed inhibitory receptor for this protein, its function in immune modulation is not clear yet. Recent data suggest that besides inhibitory effects on various immune cells, UL18 may also act as an activating component during CMV infection. In this review, we provide an overview of the biology of UL18 and discuss several attempts to shed light on its function.
Constraint Satisfaction mit Petri-Netzen

Ein Constraint Satisfaction Problem (CSP) besteht aus Variablen, Wertebereichen und Constraints, die die Belegungskombinationen der Variablen einschranken. Wir zeigen, wie man CSPs mit Hilfe von Pr/T-Netzen modellieren und losen kann. In den verwendeten Netzen gibt es neben den konventionellen Stellenmarken Transitionsmarken, die sich entgegen der Kantenrichtung bewegen, wenn Stellen schalten. Auch wenn es offensichtliche Parallelen zwischen den Prozessen in diesen Pr/T-Netzen und den CSP-Losungsprozessen gibt, sind grundlegende Unterschiede zwischen den beiden Paradigmen zu uberwinden.
Impact of the ocean acoustic transfer function on the coherence of undersea propagations

Multipath propagation, in conjunction with source motion, creates a splitting and spreading of the received source-signal energy over the time register, time scale-factor (ambiguity) plane. This splitting of the received signal energy is manifested as correlation interactions between both; the set of eigenray signal arrivals (comprising the multipaths) at each receiving sensor, and the set of eigenray signal correlation-pairs comprising two (or more) sensors. The more tightly the sets of eigenray signals are clustered in the ambiguity plane, the stronger will be the signal component interactions at each sensor and the less will be the expected correlation degradation between sensors. However, the greater will be the variance. Conversely, the more diffuse the clustering, the weaker will be the signal component interactions and the greater will be the expected intersensor coherence degradation. Also, the less will be the variance. Criteria which define the degree of signal component interactions in terms of the system parameters have been defined and are displayed in graphical form.
[Different expression of protein in the supernatant of heat injured keratinocytes].

OBJECTIVE To compare the difference of protein expression in the supernatant of heat injured keratinocytes (KC) and normal KC. METHODS A model of heat injured KC was produced in vitro. The supernatant of normal KC and heat injured KC was collected after culture for 12 hours, and was ultrafiltered and lyophilized to get the protein. The protein sample was separated by immobilized pH gradient based two dimensional gel electrophoresis (2-DE). The gel was stained and the different expression of protein was analyzed using ImageMaster 2D analysis software. RESULTS (1) Average protein spots were 1,898 +/- 113, 1,877 +/- 97 in the supernatant of normal and heat injured KC and 1,118 protein spots could be used for statistical analysis. (2) Statistical result showed that 26 protein spots were significantly different between the two groups. 16 protein spots were higher in the supernatant of normal KC and then 10 protein spots were lower in the normal group. (3) 16 protein spots, which included 10 kinds of proteins, were identified successfully as different spots. Lower expression proteins were alpha-enolase, actin cytoplasmic 2, peroxiredoxin-4, phosphoglycerate mutase 1, G protein-regulated inducer of neurite outgrowth l in the supernatant of heat injured KC. Higher expression proteins in heat KC were purine nucleoside phosphorylase, tumor necrosis factor ligand superfamily member 10, proteasome subunit alpha type-7, UDP-glucose 6-dehydrogenase in the supernatant of heat injured KC. CONCLUSIONS The result indicated that there are some significant different expression proteins in the supernatant of normal KC and heat injured KC. These findings provide new data for screening major molecules of tissue repair and finding the mechanism of wound repair.
Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

Chemical modification of oligonucleotides came to prominence in the early 1990s with the advent of the antisense approach to control gene expression. Whilst the antisense field suffered to some extent from unrealistically high expectations for clinical applications, in some quarters, efforts to develop modified oligonucleotides and nucleic acid mimic has continued at a pace. Further impetus for the field came with the discovery of RNA interference, which has reinvigorated research into chemical modification of oligonucleotides to stabilise and improve the efficacy of siRNAs. In addition to this, modified oligonucleotides and mimics have found a wide range of other applications. Whilst clinical development of antisense oligonucleotides (ASOs) has been slow, the use of ASOs to probe gene function, for fundamental studies, which do not necessarily have therapeutic applications, has accelerated considerably. For example, one of the earliest examples of an oligonucleotide mimic, the PMO, is now widely used in gene functional analysis, in a range of organisms from human cells through to zebrafish. Many conjugation strategies have been developed to aid delivery, localisation and imaging of modified oligonucleotides. Notably nanoparticles have proven to be very useful not only as transfection agents, but also as a means to aid the detection of specific sequences, such as in their use with surface plasmon resonance and nanoflares. In addition to this, modified oligonucleotides and mimics are finding wide-spread applications as bioanalytical and diagnostic tools, allowing more stringent detection of SNPs from increasingly small concentrations of sample DNA. Finally, modified oligonucleotides and mimics are proving useful as building blocks in the assembly of higher-order nanostructures. In this review we cover the main developments of the chemistry and biology of modified oligonucleotides, including recent examples of chemical modifications, conjugation and derivatisation, antisense, RNAi and other applications, such as gene functional analysis and bioanalysis. This review is not intended to present an exhaustive account of all the chemical modifications, targets and applications for modified oligonucleotides, but rather highlights the recent and ever increasing diversity and possibilities that such oligonucleotides and derivatives possess. This review also highlights how well-known limitations, such as stability, transfection, targeting etc. , are being overcome. To a large extent the review covers the most recent literature and the reader is referred to our previous review of this field for details of earlier work in this area. 2. Chemical Modifications
Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study.

BACKGROUND Suboptimal dietary intake during pregnancy may have long-term health implications in children. These effects may be mediated by fetal growth. We investigated the associations of early pregnancy and umbilical cord total homocysteine (tHcy), folate, and total and active vitamin B12 concentrations with fetal growth parameters repeatedly measured in pregnancy and at birth. METHODS This study was performed in 5890 pregnant women, participating in a population-based prospective cohort study. Blood samples were obtained from women in early pregnancy and from the umbilical vein at delivery. Fetal size parameters were repeatedly measured by ultrasound. Information about birth anthropometrics was retrieved from medical records. RESULTS High early pregnancy maternal tHcy (≥8.31 μmol/L), as compared with low maternal homocysteine (≤5.80 μmol/L), and low early pregnancy maternal folate (≤9.10 nmol/L), as compared with high maternal folate (≥25.81 nmol/L) concentrations, were associated with reduced weight growth patterns throughout pregnancy, resulting in birthweight differences of -102.3 g (95% CI -139.6, -65.0) and -113.0 g (95% CI -159.6, -66.3), respectively. Low umbilical cord folate concentrations (≤15.20 nmol/L) as compared with high umbilical cord folate concentrations (≥28.41 nmol/L) were also associated with a lower birthweight and birth length (P < 0.001). Interestingly, compared with higher umbilical cord vitamin B12 , lower vitamin B12 concentrations were associated with a higher weight, length, and head circumference at birth (P < 0.01). CONCLUSION Early pregnancy maternal and umbilical cord markers of the homocysteine pathway are significantly associated with fetal growth patterns. These differences arise from mid-pregnancy onwards.
Coronary Atherosclerosis and Myocardial Infarction in Autopsied Patients in Gondar, Ethiopia

Autopsy study of 124 Ethiopian patients for athero-sclerotic lesions and myocardial infarction revealed aortic lesions in 58 (47%), coronary lesions in 26 (21%) and myocardial infarction in 8 (6.5%) cases. Fatty streaks in the coronary arteries were detected after the age of 19 years. Thereafter the frequency increased gradually with age reaching a peak of 33.3% by the age group of 50–59 years. Fibrous plaque appeared at the age of 40 years and progressed with age reaching a maximum of 44.4% by the age of 60–69 years. Myocardial infarction was the cause of sudden death in two cases. Six of the patients with myocardial infarction had moderate to severe lesions. Calcification with narrowing of the left anterior descending coronary artery was found in a 60–year-old female. The significance of the increasing incidence of CHD in black Africans and particularly in Ethiopians is discussed.
p53 expression in breast cancer is more likely to predict survival in African-American than Hispanic or white women.

10001 Background: Abnormal nuclear accumulation of p53 protein may predict poorer survival & aggressive tumor biology in African-American (AA) women with breast cancer. We hypothesized that compared to Hispanics or whites, survival would be worse for AA women with p53 positive tumors. METHODS Tumors from 195 consecutive AA, 46 Hispanic & 52 white women were evaluated for p53 expression with IHC, using antibody Pab1801 on paraffin embedded tissue, at the SHCC MBCCOP, in Chicago. Staining was scored on the UK Receptor Group 0-8 system with score ≥2 read as positive. Survival was computed by the Kaplan-Meier method & correlated with p53 expression. Univariate analyses were done with two-sided log-rank test & multivariate analysis was done with Cox proportional-hazards model. RESULTS There were no significant differences between racial groups regarding tumor size, grade, node status, stage, estrogen receptor (ER) status, treatment & p53 expression. Hispanics were significantly younger (p=0.014). For AA, Hispanic & white women respectively, p53 expression was 29.2%, 34.8% & 18.8%. High grade (p=0.0001) & negative ER status (p=0.006) were significantly associated with p53 expression in AA women; similar results were seen in whites (p=0.014 & p=0.031 respectively), however although the trend for grade was similar, only negative ER status was significantly associated with p53 expression in Hispanics. AA women with p53 positive tumors had significantly worse survival compared to AA women with p53 negative tumors (Hazard Ratio=1.945; 95% CI=1.040-3.638; p=0.037). However, comparison of survival between races for women with p53 positive tumors (p=0.793) and also for women with p53 negative tumors (p=0.4027) was not different. Multivariate analysis demonstrated that there was no interaction (p=0.523) between p53 expression & stage as predictors of poor survival in AA women. CONCLUSIONS Analyses between racial groups demonstrated that AA, Hispanic & white women with breast tumors with abnormal p53 expression had similar associations with high tumor grade, negative ER status and survival. However within racial groups, abnormal p53 expression was only able to predict significantly worse survival in AA women. This association appeared to be independent of stage. [Table: see text].
Contribution of T-Cell Receptor Repertoire Breadth to the Dominance of Epitope-Specific CD8+ T-Lymphocyte Responses

ABSTRACT Dominant epitope-specific CD8+ T-lymphocyte responses play a central role in controlling viral spread. We explored the basis for the development of this focused immune response in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys through the use of two dominant (p11C and p199RY) and two subdominant (p68A and p56A) epitopes. Using real-time PCR to quantitate T-cell receptor (TCR) variable region beta (Vβ) family usage, we show that CD8+ T-lymphocyte populations specific for dominant epitopes are characterized by a diverse Vβ repertoire, whereas those specific for subdominant epitopes employ a dramatically more focused Vβ repertoire. We also demonstrate that dominant epitope-specific CD8+ T lymphocytes employ TCRs with multiple CDR3 lengths, whereas subdominant epitope-specific cells employ TCRs with a more restricted CDR3 length. Thus, the relative dominance of an epitope-specific CD8+ T-lymphocyte response reflects the clonal diversity of that response. These findings suggest that the limited clonal repertoire of subdominant epitope-specific CD8+ T-lymphocyte populations may limit the ability of these epitope-specific T-lymphocyte populations to expand and therefore limit the ability of these cell populations to contribute to the control of viral replication.
Identification and characterization of four bacterial strains isolated from a bioaugmented sequencing batch reactor.

Intermediates for the synthesis of a variety of chemicals are one of the major groups of substances responsible for environmental contamination and ecological imbalance (Liu et al., 2012). O-Nitrobenzaldehyde (ONBA), an important intermediate for the synthesis of a lot of pharmaceuticals, agrochemicals, dyes and other organic compounds, is one of them (Yu et al., 2010). Though no definite acceptable limits of ONBA have been formulated, it is necessary to treat these wastewaters prior to their discharge. Recently, relevant environmental issues have been attracting greater public attention, with substantial manpower and financial resources invested in counteracting these problems. In China, however, the situation is getting worse with the rapid growth of the national economy. Although integrated physical and chemical methods seem to be feasible for the treatment of such wastewater, biological methods are receiving serious attention and should be used preferably considering cost and technical advantages (Silveira et al., 2009). Microbial metabolism plays a very important role in the degradation or detoxification of recalcitrant pollutants in the environment. Moreover, bioaugmentation is recognized as a promising and attractive operational means to enhance wastewater treatment performance (Ivanov et al., 2006; Karn et al., 2010; Mohan et al., 2009) and has been demonstrated to successfully accelerate the removal of ONBA (Yu et al., 2010). In previous research, the feasibility of using a functional strain, Pseudomonas putida ONBA-17 (Yu et al., 2006), which was chromosomally marked with gfp, to bioaugment SBR treating ONBA synthetic wastewater has been reported. After a transient adaptation, almost 100% removal of ONBA was achieved within 8 days as compared with to 23.47% of a non-inoculated control (Yu et al., 2010). The bioaugmented reactor exhibited a better chemical oxygen demand removal performance (96.28%) than that of the control (79.26%). The bioaugmentation not only enhanced the removal capability of the target compound, but shortened system start-up time. Functional dissection of microbial communities based on structure information represents an ongoing effort in the field of microbial ecology (Torsvik and Ovreas, 2002). Although developed molecular techniques such as denaturing gel electrophoresis including DGGE, temperature gradient gel electrophoresis and temporal temperature gradient gel electrophoresis, analysis of the polymerase chain reaction (PCR)amplified ribosomal DNA sequences and in situ green fluorescent protein fluorescence detection have been employed as powerful tools for monitoring specific miJ. Gen. Appl. Microbiol. , 59, 251‒256 (2013)
Use of water cluster detector for preventing drunk and drowsy driving

Implementing safety measures to prevent drunk and drowsy driving is a major technical challenge for the car industry. We have developed a system that involves a non-contact breath sensor to do this. The breath sensor detects breath by measuring electric currents of positively or negatively charged water clusters in breath that are separated by using an electric field. Our device couples a breath sensor with an alcohol sensor, and simultaneously detects the electrical signals of both breath and alcohol in the breath. This ensures that the sample is from a person's breath, not an artificial source. Furthermore, our breath sensor can detect breath from about 50 cm, and can also test the level of alertness of a subject sitting in the driver's seat. This is done by measuring the point of time the breathing changes from conscious, such as in pursed-lip breathing, to unconscious when the driver becomes drowsy. This is the first time that one device has been used to detect both drunk and drowsy driving.
Enzymatic Oxidation of Cholesterol Aggregates in Supercritical Carbon Dioxide

Fundamental studies of enzyme-solvent interactions can be conducted with supercritical fluids because small changes in pressure or temperature may bring about great changes in the properties of a single solvent near its critical point. Cholesterol oxidase is active in supercritical carbon dioxide and supercritical carbon dioxide-cosolvent mixtures. Variations in solvent power caused by pressure changes or by the addition of dopants affected the rate of enzymatic oxidation of cholesterol by altering the structure of cholesterol aggregates.
The Analysis of Mind

THE title of Mr. Russell's book may raise expectations that it is an exposition or development of his philosophical theory. It cannot, however, take rank with his great works. It is a course of lectures, to all appearance a verbatim report, which has been subjected to the very minimum of revision. It is brimming over with casual witty remarks which pass well with an audience, but will not bear reflection. The lectures show Mr. Russell under the influence of two comparatively recent popular movements in philosophy and psychology, both of which seem to have attracted him powerfully, and neither to have convinced him completely, namely, William James's Neutral Monism and Prof. J. B. Watson's Behaviourism. One lecture deals at some length with the question, “Does Consciousness exist? ” The answer reminds one of the famous pronouncement that Shakespeare's plays were not written by Shakespeare but by some one else of the same name. It is easy enough to argue that consciousness does not exist, but then there is something we are talking about when we affirm its non-existence, and it is difficult to find any other name for it. In regard to Behaviourism Mr. Russell thinks it a beautiful theory and an ideal method, but then—there are images, and the theory cannot account for them.The Analysis of Mind.BertrandRussellBy. (Library of Philosophy.) Pp. 310. (London: George Allen and Unwin, Ltd.; New York: The Macmillan Company, 1921.) 16s. net.