Miracle-dz/UniFAR-FTUs huggingface dataset:
The length of homology required for gene targeting in embryonic stem cells

Homologous recombination has been used to introduce site-specific mutations into murine embryonic stem (ES) cells with both insertion and replacement vectors. In this study, we compared the frequency of gene targeting with various lengths of homology and found a dramatic increase in targeting with an increase in homology from 1.3 to 6.8 kb. We examined in detail the relationship between the length of homology and the gene-targeting frequency for replacement vectors and found that a critical length of homology is needed for targeting. Adding greater lengths of homology to this critical length has less of an effect on the targeting frequency. We also analyzed the lengths of homology necessary on both arms of the vector for gene replacement events and found that 472 bp of homology is used as efficiently as 1.2 kb in the formation and resolution of crossover junctions.
One-Shot Coresets: The Case of k-Clustering

Scaling clustering algorithms to massive data sets is a challenging task. Recently, several successful approaches based on data summarization methods, such as coresets and sketches, were proposed. While these techniques provide provably good and small summaries, they are inherently problem dependent - the practitioner has to commit to a fixed clustering objective before even exploring the data. However, can one construct small data summaries for a wide range of clustering problems simultaneously? In this work, we affirmatively answer this question by proposing an efficient algorithm that constructs such one-shot summaries for k-clustering problems while retaining strong theoretical guarantees.
Multiple Functional Domains of AML1: PU.1 and C/EBPα Synergize with Different Regions of AML1

ABSTRACT Control elements of many genes are regulated by multiple activators working in concert to confer the maximal level of expression, but the mechanism of such synergy is not completely understood. The promoter of the human macrophage colony-stimulating factor (M-CSF) receptor presents an excellent model with which we can study synergistic, tissue-specific activation for two reasons. First, myeloid-specific expression of the M-CSF receptor is regulated transcriptionally by three factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPα. Second, these proteins interact in such a way as to demonstrate at least two examples of synergistic activation. We have shown that AML1 and C/EBPα activate the M-CSF receptor promoter in a synergistic manner. As we report here, AML1 also synergizes, and interacts physically, with PU.1. Detailed analysis of the physical and functional interaction of AML1 with PU.1 and C/EBPα has revealed that the proteins contact one another through their DNA-binding domains and that AML1 exhibits cooperative DNA binding with C/EBPα but not with PU.1. This difference in DNA-binding abilities may explain, in part, the differences observed in synergistic activation. Furthermore, the activation domains of all three factors are required for synergistic activation, and the region of AML1 required for synergy with PU.1 is distinct from that required for synergy with C/EBPα. These observations present the possibility that synergistic activation is mediated by secondary proteins contacted through the activation domains of AML1, C/EBPα, and PU.1.
The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research

The investigation of genetic alterations that may be related to the prognosis of patients with malignant disease has become a frequently used strategy in recent years. Although some conclusions have been reached in certain studies, the complexity and the multifactorial nature of most neoplastic diseases makes it difficult to identify clinically relevant information, and the results of some studies have been of borderline significance or have been conflicting. In contrast, the identification and the study of patients or families with very characteristic phenotypes have yielded outstanding results in the identification of the genetic characteristics underlying such phenotypes. Although, in most cases, the individuals who are selected for these types of studies are characterized by a negative phenotype (i.e., individuals who are at increased risk for developing a specific disease), a few studies have been directed toward individuals with phenotypes that imply an unusually good prognosis (i.e., individuals who present with a decreased risk for developing specific diseases despite an important exposure to well‐known risk factors). Therefore, it seems logical to develop this strategy further as a valid methodology for the study of other diseases, such as cancer. The study of individuals with phenotypes that imply an extremely good prognosis, such as long‐term survivors of theoretically incurable malignancies or individuals who seem to be protected against a certain neoplastic disorder despite having a markedly increased risk for its development, may unveil genetic alterations that explain such characteristic phenotypes and may provide potentially useful therapeutic targets against these diseases. Cancer 2002;95:1605–10. © 2002 American Cancer Society.
Messenger RNA processing is altered in autosomal dominant leukodystrophy

Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by autonomic dysfunction, followed by cerebellar and pyramidal features. ADLD is caused by duplication of the lamin B1 gene ( LMNB1 ), which leads to its increased expression. The molecular pathways involved in the disease are still poorly understood. Hence, we analyzed global gene expression in ﬁ broblasts and whole blood of LMNB1 duplication carriers and used Gene Set Enrichment Analysis to explore their gene signatures. We found that LMNB1 duplication is associated with dysregulation of genes involved in the immune system, neuronal and skeletal development. Genes with an altered transcriptional pro ﬁ le clustered in speci ﬁ c genomic regions. Among the dysregulated genes, we further studied the role of RAVER2 , which we found to beoverexpressedat mRNAand proteinlevel. RAVER2 encodesaputativetrans regulatorof the splicing repressorpolypyrimidine tract binding protein (PTB) and is likely implicated in alternative splicing regulation. Functional studies demonstrated an abnormal splicing pattern of several PTB-target genes and of the myelin protein gene PLP1 , previously demonstrated to be involved in ADLD. Mutant mice with different lamin B1 expression levels con ﬁ rmed that Raver2 expression is dependent on lamin B1 in neural tissue and determines an altered splicing pattern of PTB-target genes and Plp1 . Overall our results demonstrate that deregulation of lamin B1 expression induces modi ﬁ ed splicing of several genes, likely driven by raver-2 overexpression, and suggest that an alteration of mRNA processing could be a pathogenic mechanism in ADLD. Tx-100. Equal amounts of proteins were separated on NuPage 10% bis-tris polyacrylamide gels (Invi-trogen, Thermo Scienti ﬁ c) and analyzed (14) using primary rabbit polyclonal antibodies against lamin B1 (Abcam, Cambridge, Eng-land, UK), γ -tubulin (Sigma), actin (Sigma) and raver-2 (Abcam). Densitometric analysis was performed using the NIH ImageJ pro-gram (65). The protein levels were normalized on γ -tubulin or actin content.
The Effect of Gasket Creep-Relaxation on the Leakage Tightness of Bolted Flanged Joints

The loss of tightness of bolted flanged joints is primarily due to the relaxation of the joint; in particular, the clamping load is affected by the amount of relaxation that a gasket exhibits over time. Test methods are available for evaluating the ability of a gasket to maintain a given compressive stress. It is necessary, however, to evaluate the response of the joint members to a small change in gasket thickness produced by the effect of creep-relaxation. This paper presents an analytical evaluation of the effect of gasket creep-relaxation on the remaining gasket stress taking into account the flexibility of all joint members, thus allowing the evaluation of the required tightening load on the gasket. The results obtained by this approach are shown to agree with those determined on an experimental rig made up of 4-in. class-600-lb pair of flanges. Axisymmetric finite element models of larger flange assemblies are also used for comparison. The results show that creep-relaxation of gaskets has a major influence on the remaining compression load on the gasket.
Statistical network analysis for functional MRI: summary networks and group comparisons

Comparing networks in neuroscience is hard, because the topological properties of a given network are necessarily dependent on the number of edges in that network. This problem arises in the analysis of both weighted and unweighted networks. The term density is often used in this context, in order to refer to the mean edge weight of a weighted network, or to the number of edges in an unweighted one. Comparing families of networks is therefore statistically difficult because differences in topology are necessarily associated with differences in density. In this review paper, we consider this problem from two different perspectives, which include (i) the construction of summary networks, such as how to compute and visualize the summary network from a sample of network-valued data points; and (ii) how to test for topological differences, when two families of networks also exhibit significant differences in density. In the first instance, we show that the issue of summarizing a family of networks can be conducted by either adopting a mass-univariate approach, which produces a statistical parametric network (SPN). In the second part of this review, we then highlight the inherent problems associated with the comparison of topological functions of families of networks that differ in density. In particular, we show that a wide range of topological summaries, such as global efficiency and network modularity are highly sensitive to differences in density. Moreover, these problems are not restricted to unweighted metrics, as we demonstrate that the same issues remain present when considering the weighted versions of these metrics. We conclude by encouraging caution, when reporting such statistical comparisons, and by emphasizing the importance of constructing summary networks.
Olive oil-based lipid emulsion's neutral effects on neutrophil functions and leukocyte-endothelial cell interactions.

BACKGROUND Infection remains a drawback of parenteral nutrition (PN), probably related, among other factors, to immunosuppressive effects of its lipid component. Newer preparations may have lesser immunosuppressive impact. This study examines the effects of an olive oil-based lipid emulsion (long-chain triacylglycerols-monounsaturated fatty acids [LCT-MUFA]; ClinOleic) on various functions of human neutrophils in vitro and on rat leukocyte-endothelial cell interactions in vivo compared with LCT (Intralipid) and 50% LCT-50% medium-chain triacylglycerols (MCT; Lipofundin) mixture. METHODS Neutrophils isolated from healthy donors were incubated with concentrations (0.03-3 mmol/L) of lipid emulsions encompassing clinically relevant levels. In vivo leukocyte recruitment was studied with intravital microscopy within rat mesenteric microcirculation. RESULTS LCT-MUFA (3 mmol/L) did not alter the N-formyl-Met-Leu-Phe (FMLP)-induced rise in [Ca2+]i, oxidative burst, chemotaxis, and elastase release, whereas LCT-MCT decreased [Ca2+]i and chemotaxis and increased oxidative burst. FMLP-induced LTB4 production was augmented by lipid emulsions. Serum-opsonized zymosan-induced phagocytosis was unaltered by lipid emulsions. Basal and FMLP-induced CD11b expression was unaffected by lipid emulsions. Lipopolysaccharide (LPS)-induced TNF-alpha, IL-1beta and IL-8 mRNA, and protein expression was unaltered by LCT-MUFA, whereas LCT and LCT-MCT decreased IL-1beta mRNA and protein. LCT-MUFA did not alter apoptosis, but LCT increased apoptosis in absence and presence of GM-CSF. LPS (1 microg/mL)-induced increase in leukocyte rolling flux, adhesion, and emigration was inhibited by LCT and LCT-MCT but unaffected in LCT-MUFA-treated rats. Immunohistochemistry showed LPS-induced increase in P-selectin expression attenuated by LCT and LCT-MCT but not LCT-MUFA. CONCLUSIONS LCT-MUFA showed lower in vitro and in vivo impact on neutrophil function compared with LCT and LCT-MCT.
GM-CSF in the lung protects against lethal influenza infection.

RATIONALE Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza. OBJECTIVES To determine if increased expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the lung increases resistance to influenza. METHODS Wild-type mice and transgenic mice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus. MEASUREMENTS AND MAIN RESULTS Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showed histologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza. CONCLUSIONS GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.
Aggressors and Victims in Bullying and Cyberbullying: A Study of Personality Profiles using the Five-Factor Model

Abstract Bullying and cyberbullying are highly prevalent in today’s society. However, the personality profiles of different roles involved in this phenomenon remain little known. This study aims (1) to examine the association between bullying and cyberbullying in adolescents; and (2) to analyze the relationship between bullying and cyberbullying in terms of the domains and facets of the five-factor model (FFM). A total of 910 adolescents aged 12 to 19 years old participated. They were administered self-report assessments of aggression and victimization in bullying and cyberbullying, as well as the JS-NEO-S questionnaire. The results provide evidence of co-occurrence between bullying and cyberbullying (p < .001). We observed higher neuroticism in victims and aggressor-victims, higher openness in victims, higher agreeableness in victims and non-aggressor non-victims and higher conscientiousness in non-aggressor non-victims as compared with the rest of the groups (p < .001). Comparison of the four cyberbullying groups showed that cybervictims score higher in neuroticism and openness, cybervictims and non-cybervictims non-cyberaggressors score higher in agreeableness and non-cybervictims non-cyberaggressors score higher in conscientiousness (p < .001) In conclusion, this study provides a broad, systematic view of the personality traits associated with different roles implicated in traditional bullying and cyberbullying.
Collisions through liquid layers

The initial collision (see pp. 571–2). The instantaneous velocity change of the hammer (from V0 to V) when it first strikes the liquid film should be calculated from energy and not momentum considerations, since the hammer has momentum in the vertical direction whilst the liquid is expressed in a horizontal direction and its total momentum is, by symmetry, zero at every instant. The kinetic energy dE of an annulus of liquid of radius r will be ½mc2, where m = 2πrhρdr, and c, the radial velocity of flow, is ½rV/h, since the liquid starts moving in plug flow. Integrating from r = 0 to r = R, we find that the total kinetic energy E imparted to the liquid film is . Assuming that extraneous energy losses, including any energy imparted to the anvil, are negligible, we may equate this to the energy loss of the hammer . Hence To a first approximation this yields The term at the right-hand side of the denominator is one-half that given in the original derivation (equation (20)), so that the instantaneous decrease in the velocity of the hammer is even less marked. For the given case where M = 400g. , R = 1 cm. , ρ = 1.6 and h = 5 × 10−2 cm. , the velocity decrease is less than 2%. Vol. 44 (1948), pp. 566–80.
Economics and Identity

This paper considers how identity, a person's sense of self, affects economic outcomes. We incorporate the psychology and sociology of identity into an economic model of behavior. In the utility function we propose, identity is associated with different social categories and how people in these categories should behave. We then construct a simple game-theoretic model showing how identity can affect individual interactions. The paper adapts these models to gender discrimination in the workplace, the economics of poverty and social exclusion, and the household division of labor. In each case, the inclusion of identity substantively changes conclusions of previous economic analysis.
THE PATHOGENESIS OF ALOPECIA AREATA

SUMMARY. — The pathogenesis of alopecia areata was studied by plucking hairs from each of a series of concentric zones, using felt patterns placed over lesions. It was possible to group lesions according to the zone with the greatest proportion of club hairs. The results are logically interpreted to mean that a wave of hair follicle damage or arrest moves centrifugally from a focal point beyond the area of alopecia.
A weak gravitational lensing recalibration of the scaling relations linking the gas properties of dark haloes to their mass

We use weak gravitational lensing to measure mean mass profiles around locally brightest galaxies (LBGs). These are selected from the Seventh Data Release of the Sloan Digital Sky Survey spectroscopic and photometric catalogues to be brighter than any neighbour projected within 1.0 Mpc and differing in redshift by 83 per cent) are expected to be the central galaxies of their dark matter haloes. Previous stacking analyses have used this LBG sample to measure mean Sunyaev–Zeldovich flux and mean X-ray luminosity as a function of LBG stellar mass. In both cases, a simulation of the formation of the galaxy population was used to estimate effective halo mass for LBGs of given stellar mass, allowing the derivation of scaling relations between the gas properties of haloes and their mass. By comparing results from a variety of simulations to our lensing data, we show that this procedure has significant model dependence reflecting: (i) the failure of any given simulation to reproduce observed galaxy abundances exactly; (ii) a dependence on the cosmology underlying the simulation; and (iii) a dependence on the details of how galaxies populate haloes. We use our lensing results to recalibrate the scaling relations, eliminating most of this model dependence and explicitly accounting both for residual modelling uncertainties and for observational uncertainties in the lensing results. The resulting scaling relations link the mean gas properties of dark haloes to their mass over an unprecedentedly wide range, 1012.5 < M500/M⊙ < 1014.5, and should fairly and robustly represent the full halo population.
Comfort care for terminally ill patients. The appropriate use of nutrition and hydration.

OBJECTIVE To determine the frequency of symptoms of hunger and thirst in a group of terminally ill patients and determine whether these symptoms could be palliated without forced feeding, forced hydration, or parenteral alimentation. DESIGN Prospective evaluation of consecutively admitted terminally ill patients treated in a comfort care unit. SETTING Ten-bed comfort care unit in a 471-bed long-term care facility. PARTICIPANTS Mentally aware, competent patients with terminal illnesses monitored from time of admission to time of death while residing in the comfort care unit. MAIN OUTCOME MEASURES Symptoms of hunger, thirst, and dry mouth were recorded, and the amounts and types of food and fluids necessary to relieve these symptoms were documented. The subjective level of comfort was assessed longitudinally in all patients. RESULTS Of the 32 patients monitored during the 12 months of study, 20 patients (63%) never experienced any hunger, while 11 patients (34%) had symptoms only initially. Similarly, 20 patients (62%) experienced either no thirst or thirst only initially during their terminal illness. In all patients, symptoms of hunger, thirst, and dry mouth could be alleviated, usually with small amounts of food, fluids, and/or by the application of ice chips and lubrication to the lips. Comfort care included use of narcotics for relief of pain or shortness of breath in 94% of patients. CONCLUSIONS In this series, patients terminally ill with cancer generally did not experience hunger and those who did needed only small amounts of food for alleviation. Complaints of thirst and dry mouth were relieved with mouth care and sips of liquids far less than that needed to prevent dehydration. Food and fluid administration beyond the specific requests of patients may play a minimal role in providing comfort to terminally ill patients.
Breath condenser coatings affect measurement of biomarkers in exhaled breath condensate

Exhaled breath condensate collection is not yet standardised and biomarker measurements are often close to lower detection limits. In the current study, it was hypothesised that adhesive properties of different condenser coatings interfere with measurements of eicosanoids and proteins in breath condensate. In vitro, condensate was derived from a collection model using two test solutions (8-isoprostane and albumin) and five condenser coatings (silicone, glass, aluminium, polypropylene and Teflon). In vivo, condensate was collected using these five coatings and the EcoScreen® condenser to measure 8-isoprostane, and three coatings (silicone, glass, EcoScreen®) to measure albumin. In vitro, silicone and glass coatings had significantly higher albumin recovery compared with the other coatings. A similar trend was observed for 8-isoprostane recovery. In vivo, median (interquartile range) 8-isoprostane concentrations were significantly higher using silicone (9.2 (18.8) pg·mL-1) or glass (3.0 (4.5) pg·mL-1) coating, compared with aluminium (0.5 (2.4) pg·mL-1), polypropylene (0.5 (0.5) pg·mL-1), Teflon (0.5 (0.0) pg·mL-1), and EcoScreen® (0.5 (2.0) pg·mL-1). Albumin in vivo was mainly detectable using glass coating. In conclusion, a condenser with silicone or glass coating is more efficient for measurement of 8-isoprostane or albumin in exhaled breath condensate, than EcoScreen®, aluminium, polypropylene or Teflon. Guidelines for exhaled breath condensate standardisation should include the most valid condenser coating to measure a specific biomarker.