Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Analysis of HER2-mediated Effects on HER2 and Epidermal Growth Factor Receptor Endocytosis

Endocytic trafficking plays an important role in the regulation of the epidermal growth factor receptor (EGFR) family. Many cell types express multiple EGFR family members (including EGFR, HER2, HER3, and/or HER4) that interact to form an array of homo- and heterodimers. Differential trafficking of these receptors should strongly affect signaling through this system by changing substrate access and heterodimerization efficiency. Because of the complexity of these dynamic processes, we used a quantitative and computational model to understand their integrated operation. Parameters characterizing EGFR and HER2 interactions were determined using experimental data obtained from mammary epithelial cells constructed to express different levels of HER2, enabling us to estimate receptor-specific internalization rate constants and dimer uncoupling rate constants. Significant novel results obtained from this work are as follows: first, that EGFR homodimerization and EGFR/HER2 heterodimerization occur with comparable affinities; second, that EGFR/HER2 heterodimers traffic as single entities. Furthermore, model predictions of the relationship of HER2 expression levels to consequent distribution of EGFR homodimers and EGFR/HER2 heterodimers suggest that the levels of HER2 found on normal cells are barely at the threshold necessary to drive efficient heterodimerization. Thus, altering HER2 concentrations, either overall or local, could provide an effective mechanism for regulating EGFR/HER2 heterodimerization and may explain why HER2 overexpression found in some cancers has such a profound effect on cell physiology.
Does Trauma‐Linked Dissociation Vary Across Ethnic Groups?

This investigation assessed the relationship between traumatic stress exposure and dissociation in male Vietnam theater veterans from three ethnic groups. Subjects were African-American (N = 61), Caucasian (N = 91), and Hispanic (N = 73) veterans who completed the Dissociative Experiences Scale and a measure of war zone stress exposure, and who were rated on the Peritraumatic Dissociative Experiences Questionnaire-Rater Version. Greater exposure to war zone stress was associated with reports of more dissociation at the time of trauma and with more general dissociative experiences both when the data were pooled and when examined separately for each group. After controlling for the effects of war zone stress exposure, the significant differences found in peritraumatic and general dissociative experiences across the three ethnic groups no longer were evident. This investigation demonstrated that among American Vietnam veterans, greater exposure to traumatic stress is related to more dissociative experiences, regardless of ethnicity.
Epigenetic Gene Regulation in the Bacterial World

SUMMARY Like many eukaryotes, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Unlike eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of diverse pathogens of humans and livestock animals, including pathogenic Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression. Transcriptional repression by Dam methylation appears to be more common than transcriptional activation. Certain promoters are active only during the hemimethylation interval that follows DNA replication; repression is restored when the newly synthesized DNA strand is methylated. In the E. coli genome, however, methylation of specific GATC sites can be blocked by cognate DNA binding proteins. Blockage of GATC methylation beyond cell division permits transmission of DNA methylation patterns to daughter cells and can give rise to distinct epigenetic states, each propagated by a positive feedback loop. Switching between alternative DNA methylation patterns can split clonal bacterial populations into epigenetic lineages in a manner reminiscent of eukaryotic cell differentiation. Inheritance of self-propagating DNA methylation patterns governs phase variation in the E. coli pap operon, the agn43 gene, and other loci encoding virulence-related cell surface functions.
Chromosomal rearrangement as the basis for human tumourigenesis

Purpose: To develop a model for the initiation of human tumourigenesis that is consistent with various observations that are difficult to reconcile with current models. Conclusions: A novel model of tumourigenesis was developed that includes three basic postulates: (1) tumourigenesis is initiated by recombinogenic DNA lesions, (2) potentially recombinogenic DNA lesions in transcribed regions of the genome can be converted into chromosomal rearrangements and (3) chromosomal rearrangements alone are insufficient for tumourigenesis but can initiate a mutator/recombinator phenotype.
Viability of clathrin heavy-chain-deficient Saccharomyces cerevisiae is compromised by mutations at numerous loci: implications for the suppression hypothesis

The gene encoding clathrin heavy chain in Saccharomyces cerevisiae (CHC1) is not essential for growth in most laboratory strains tested. However, in certain genetic backgrounds, a deletion of CHC1 (chc1) results in cell death. Lethality in these chc1 strains is determined by a locus designated SCD1 (suppressor of clathrin deficiency) which is unlinked to CHC1 (S. K. Lemmon and E. W. Jones, Science 238:504-509, 1987). The lethal allele of SCD1 has no effect on cell growth when the wild-type version of CHC1 is present. This result led to the proposal that most yeast strains are viable in the absence of clathrin heavy chain because they possess the SCD1 suppressor. Discovery of another yeast strain that cannot grow without clathrin heavy chain has allowed us to perform a genetic test of the suppressor hypothesis. Genetic crosses show that clathrin-deficient lethality in the latter strain is conferred by a single genetic locus (termed CDL1, for clathrin-deficient lethality). By constructing strains in which CHC1 expression is regulated by the GAL10 promoter, we demonstrate that the lethal alleles of SCD1 and CDL1 are recessive. In both cases, very low expression of CHC1 can allow cells to escape from lethality. Genetic complementation and segregation analyses indicate that CDL1 and SCD1 are distinct genes. The lethal CDL1 allele does not cause a defect in the secretory pathway of either wild-type or clathrin heavy-chain-deficient yeast. A systematic screen to identify mutants unable to grow in the absence of clathrin heavy chain uncovered numerous genes similar to SCD1 and CDL1. These findings argue against the idea that viability of chc1 cells is due to genetic suppression, since this hypothesis would require the existence of a large number of unlinked genes, all of which are required for suppression. Instead, lethality appears to be a common, nonspecific occurrence when a second-site mutation arises in a strain whose cell growth is already severely compromised by the lack of clathrin heavy chain.
ANTIBIOTIC SUSCEPTIBILITY OF P . AERUGINOSA 981 A comparison of growth of strain Ps 15 in carbenicillin or gentamicin with and without

A chelating agent, triethylenetetramine dihydrochloride, interacted synergistically in vitro with both gentamicin and carbenicillin against a clinical isolate of Pseudomonas aeruginosa designated Ps 15. The minimal inhibitory concentrations of carbenicillin and gentamicin for Ps 15 in a 50% serum-Trypticase soy broth were 250 and 72.9 ,ig/ml, respectively. However, addition of triethylenetetramine dihydrochloride to the 50% serum-Trypticase soy broth reduced the minimal inhibitory concentration of both antibiotics approximately 10-fold. A comparison of the growth of Ps 15 in 50% serum-Trypticase'soy broth containing either of the antibiotics showed that a rapid decrease in the percentage of survivors only occurred when the chelating agent was present.
Propagation path loss models for LTE-advanced urban relaying systems

Relaying technology - a key technical enhancement in 3GPP LTE-Advanced (3rd Generation Partnership Project Long Term Evolution - Advanced) - has attracted much research interest over the last few years. However, propagation path loss models dedicated to relaying systems are yet to be properly validated. Moreover, the impact of relay antenna height on propagation channel has not yet been adequately studied. This paper presents a measurement-based study which aims to analyze the impact of relay antenna height on path loss channel models. The analysis results demonstrate that BS-RS (Base Station - Relay Station) link path loss decreases with the increase in relay antenna height. Moreover, different propagation models which could be applied for BS-RS link are verified. The analyses show that these models are not completely adequate for relaying deployment. Finally, a new propagation model for relaying deployment which takes into account the impact of relay antenna height is proposed.
A principal components analysis of the factors effecting personal exposure to air pollution in urban commuters in Dublin, Ireland

Principal component analysis was used to examine air pollution personal exposure data of four urban commuter transport modes for their interrelationships between pollutants and relationships with traffic and meteorological data. Air quality samples of PM2.5 and VOCs were recorded during peak traffic congestion for the car, bus, cyclist and pedestrian between January 2005 and June 2006 on a busy route in Dublin, Ireland. In total, 200 personal exposure samples were recorded each comprising 17 variables describing the personal exposure concentrations, meteorological conditions and traffic conditions. The data reduction technique, principal component analysis (PCA), was used to create weighted linear combinations of the data and these were subsequently examined for interrelationships between the many variables recorded. The results of the PCA found that personal exposure concentrations in non-motorised forms of transport were influenced to a higher degree by wind speed, whereas personal exposure concentrations in motorised forms of transport were influenced to a higher degree by traffic congestion. The findings of the investigation show that the most effective mechanisms of personal exposure reduction differ between motorised and non-motorised modes of commuter transport.
Painting in air

For several years I have been editing a series of computer-generated images that I created on the Cal Tech Workbench, using Stephen Schkölne's proprietary Surface Drawing program. Schkölne, who recently completed his Ph.D. in computer science at Cal Tech, is one of a small number of computer scientists interested in spontaneous 3D freehand drawing in immersive space. As far as I know, there are only a few Ph.D. students who are continuing research in this direction-Art and Design in Helsinki. When other 3D CGI inventors focused their research on integrating CAD-based drawing with 3D immersive systems, Schkölne had the vision to understand that there is not yet a computer based drawing system that affords artists the full range of kinesthetic expression. How the artist moves in space is an issue of major concern in the creative process, as it is integral to tangible and intangible elements of expression in the creative act and object. Drawing in the semi-immersive space of the Caltech Workbench for the first time in 1999 was exhilarating. I felt like a child again, able to make forms floating in space by the simple act of waving my hand in the air. " An art like painting is itself a language – a language of form and color in which complex intuitions are expressed. The necessity for the plastic symbols of the art of painting is to some extent distanced by the inadequacy of our linguistic means of communication.To explain art, therefore, is often to give words to nameless process, to actions otherwise confined to instinctive gestures. "
Substance use and psychiatric symptoms in subjects referred to the Drug Addiction Services by the Prefecture

La diffusione dell'uso di sostanze stupefacenti tra i giovani ha raggiunto livelli preoccupanti. Dalla Relazione annuale al Parlamento sullo stato delle tossicodipendenze in Italia nel 2005 realizzata dal Dipartimento Nazionale per le Politiche Antidroga emerge che il 31% della popolazione generale tra i 15 e i 54 anni ha fatto uso di cannabis almeno una volta nella vita, con un consumo negli ultimi 12 mesi piu elevato nei maschi tra i 15 e 23 anni. Inoltre, l'uso almeno una volta nella vita di cocaina o crack, di allucinogeni e di eroina si attesta rispettivamente intorno al 6.7%, al 3.4 % e al 1.3%, con un aumento dell'uso combinato di sostanze negli ultimi 5 anni. Dati paragonabili sono riportati anche da Siliquini et al. (2001) in uno studio su di una popolazione di diciottenni.
Reconfigurable printed antenna arrays for mm-wave applications

This work presents a numerical investigation of high-gain reconfigurable printed antenna arrays for mm-waves wireless applications of broadband mobile communication. Two compact structures with reconfigurable radiation based on four broadside microstrip arrays of six elements are presented: the first one is a planar array with gain up to 20dBi; the second is tree-dimensional printed array with gain up to 15dBi. In order to estimate the electromagnetic performance of these antennas, a numerical analyzes were performed by ANSYS HFSS, which employs the Finite Element Method (FEM).
Responses of vascular endothelial cells to angiogenic signaling are important for tumor cell survival

Neoplastic cells overexpress several angiogenic cytokines, which stimulate neovascularization. Whether the responses of the host endothelial cells to these signaling molecules affect tumor cells during early tumorigenesis has not been investigated. We investigated pre‐angiogenic tumor cell survival and angiogenesis initiation by two murine tumor lines (4T1 mammary carcinoma and B16 melanoma), which constitutively expressed GFP, in dorsal skin‐fold window chambers of mice treated with extracellular domain of Tie‐2 (ExTek) or bFGF. ExTek reduced tumor cell survival, retarded tumor growth, and inhibited angiogenesis onset compared with controls. bFGF increased tumor cell survival and promoted earlier angiogenesis and tumor growth. Neither bFGF nor ExTek affected cell proliferation in vitro. RT‐PCR showed mRNA expression of bFGF receptor 2 (FGFR2) IIIb, which does not bind bFGF efficiently, by 4T1 cells and B16 cells express FGFR1 but not FGFR2. B16 cells expressed angiopoietin (Ang) 2, but neither cell line expresses Ang1. Both tumor lines express VEGF. These findings suggested that effects of bFGF and ExTek on tumor cell survival and angiogenesis were not due to direct action but were instead a result of paracrine factors secreted by endothelial cells. These subsequent signals from endothelial cells promote early survival and proliferation of disseminated tumor cells before onset of angiogenesis.
Detection of EHV-1 and EHV-4 DNA in unweaned Thoroughbred foals from vaccinated mares on a large stud farm.

REASONS FOR PERFORMING STUDY A silent cycle of equine herpesvirus 1 infection has been described following epidemiological studies in unvaccinated mares and foals. In 1997, an inactivated whole virus EHV-1 and EHV-4 vaccine was released commercially in Australia and used on many stud farms. However, it was not known what effect vaccination might have on the cycle of infection of EHV-1. OBJECTIVE To investigate whether EHV-1 and EHV-4 could be detected in young foals from vaccinated mares. METHODS Nasal and blood samples were tested by PCR and ELISA after collection from 237 unvaccinated, unweaned foals and vaccinated and nonvaccinated mares during the breeding season of 2000. RESULTS EHV-1 and EHV-4 DNA was detected in nasal swab samples from foals as young as age 11 days. CONCLUSIONS These results confirm that EHV-1 and EHV-4 circulate in vaccinated populations of mares and their unweaned, unvaccinated foals. POTENTIAL RELEVANCE The evidence that the cycle of EHV-1 and EHV-4 infection is continuing and that very young foals are becoming infected should assist stud farms in their management of the threat posed by these viruses.
Screening and counseling for thalassemia.

The demography of patients with thalassemia syndromes in North America has changed. [1][1],[2][2] In the past 6 months, we were asked to diagnose 4 infants, ages 1 month to 4 years, who were born with β-thalassemia major ([Table 1][3]). Included were a pair of twins (family no. 3), both of whom had
Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

Significance Dogs have an integral role in human society, and recent evidence suggests they have a unique bond that elicits a beneficial hormonal response in both dogs and human handlers. Here, we show this relationship has a dark side. Small population size during domestication and strong artificial selection for breed-defining traits has unintentionally increased the numbers of deleterious genetic variants. Our findings question the overly typological practice of breeding individuals that best fit breed standards, a Victorian legacy. This practice does not allow selection to remove potentially deleterious variation associated with genes responsible for breed-specific traits. Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.
Bone marrow karyotypes in 94 children with acute leukemia

Abstract: During the last 10 years, we have cytogenetically analyzed at diagnosis bone marrow cells from a total of 94 children with acute leukemia. Of the 78 children with acute lymphatic leukemia (ALL), 53 (68%) had clonal acquired chromosome abnormalities; in the group with acute nonlymphatic leukemia (ANLL), the corresponding proportion was 13 out of 16 (81%). Among the cytogenetically abnormal ALL patients, the most numerous subset was the hyperdiploid cases with stemlines containing 51 or more chromosomes (26 of 53 abnormal cases; 49%). This is a clearly higher proportion than has been reported in large series from other centers. Deletions of 6q were present in 8 cases and rearrangements of 12p in 5. Of the 7 T‐cell ALLs, 3 had translocations of the distal part of 7q, i.e., of the region where the beta T‐cell receptor is encoded. Only 2 of 26 (8%) patients with leukemic stemlines with more than 50 chromosomes have relapsed; the remainder are still in first remission (mean observation time 42 months). This may be contrasted with 6 of 25 (24%) relapses among the cytogenetically normal (observation time 41 months), and 8 of 27 (30%) relapses among ALL patients with aberrations but with less than 51 chromosomes (observation time 26 months). Our results support the conclusion that the finding of a markedly hyperdiploid leukemia karyotype is indicative of good prognosis in ALL.
[GLUT-1 is the receptor of retrovirus HTLV].

Le rôle pathogène de l’opsine non liée Ainsi, les photorécepteurs des souris Rpe65-/sont soumis à un phénomène ambigu: du fait de la très faible quantité de rhodopsine, ils sont protégés contre les fortes expositions de lumière, mais l’activité de l’opsine, correspondant à une exposition faible en permanence, entraîne une dégénérescence irréversible. Le phénomène est d’autant plus intéressant que les souris Rpe65-/sont aussi un modèle pour la carence en vitamine A dans laquelle les bâtonnets, privés de rétinal mais contenant de l’opsine, subissent aussi une dégénérescence. C’est la première fois qu’un tel mécanisme physiopathologique est démontré en pathologie humaine: en l’absence de mutation, un trouble fonctionnel d’un récepteur couplé à une protéine G est capable de produire des lésions. Il sera intéressant de rechercher si d’autres récepteurs couplés à des protéines G peuvent également être à l’origine de maladies humaines. ◊ spontaneous activity of opsin, one of the causes of Leber congenital amaurosis