A hipster's heaven in regional Queensland is putting the sword to counterculture capitals such as Sydney and Melbourne by embracing its man buns, skinny jeans and coffee shops.

(United States Third Circuit) - In this action alleging that defendants infringed upon plaintiff's trade dress in violation of the Lanham Act and unjustly enriched themselves by copying plaintiff's business, dismissal of plaintiff's trade dress and unjust enrichment claims and subsequent award of attorneys' fees to defendants is: 1) affirmed as to the trade dress and unjust enrichment claims, where plaintiff failed to adequately explain what "dress" it sought to protect, and plaintiff did not plead with sufficient particularity in what manner defendants had been unjustly enriched; and 2) vacated and remanded as to the award of attorneys' fees, where the award of reasonable fees would have been appropriate only to the extent that this was an "exceptional" case under section 35(a) of the Lanham Act.

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La marca de moda urbana DPStreet, filial del corporativo GrupoDP, ha dado a conocer su intención de transformar el modelo comercial y de negocio apoyados en la habilitación de distintas estrategias digitales, una de las principales es una tienda virtual desarrollada por IBM (Digital Commerce) e implementada por Solemti S.A. de C.V., su asociado de negocios en el área digital.

Jeffrey Epstein was found dead in his cell on Saturday morning, allegedly by suicide. While the media announced that the sex offender and financier had hung himself, the internet is not as convinced. Most people share the sentiment that he was in fact killed by someone with a whole lot of power. Here are the best conspiracy theory memes that play largely on Epstein's connections with the Clinton and Trump administration, the Clinton body count, and the accusations that many more people were involved in the wealthy man's sex trafficking operation. You don't need to drink the conspiracy theory Kool-Aid to find these funny memes entertaining, so make up your minds for yourselves.

There's no evidence that Bill Gates ever visited Jeffrey Epstein's private island in the Caribbean, contrary to a viral Facebook post claiming he went there numerous times. The "flight records" cited do not show that.

The post False Claim Targets Gates Using Epstein Connection appeared first on FactCheck.org.

Chicago real estate experts bust myths portrayed by home improvement shows, from actors subbing in as buyers to unrealistically low renovation costs.

Gustavo Oliveira was last seen near Tallow Wood Drive in Clifton Park around 1 a.m. with his father, 41-year-old Nivaldo Oliveira, police said.

Gustavo Oliveira was last seen near Tallow Wood Drive in Clifton Park around 1 a.m. with his father, 41-year-old Nivaldo Oliveira, police said.

Gustavo Oliveira was last seen near Tallow Wood Drive in Clifton Park around 1 a.m. with his father, 41-year-old Nivaldo Oliveira, police said.

There's sloppy play and misfires. At times, it's like you're watching a blooper reel. But L.A. Wildcats games are a Lambeau-leaping hoot. And a great value.

His department has ignored visas for trafficking victims.

Hear about traveling the Dempster Highway as the Amateur Traveler talks to Lisa from TheHotFlashPacker.com about this iconic drive into the Arctic Circle in Canada. 

• Upstream Color review
• The Kings of Summer review
• Blackfish review
• What We Watched: Fruitvale Station, At World's End, The Spectacular Now, Elysium, Only God Forgives, and The ABCs of Death
• Grand Theft Auto 5 talk

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24^–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the "prelamin A–only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.

London : King's Fund Institute, 1989.

Maddalena Cavicchioli.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 605--631.

Abstract:
The paper treats the modeling of stationary multivariate stochastic processes via a frequency domain model expressed in terms of cepstrum theory. The proposed model nests the vector exponential model of [20] as a special case, and extends the generalised cepstral model of [36] to the multivariate setting, answering a question raised by the last authors in their paper. Contemporarily, we extend the notion of generalised autocovariance function of [35] to vector time series. Then we derive explicit matrix formulas connecting generalised cepstral and autocovariance matrices of the process, and prove the consistency and asymptotic properties of the Whittle likelihood estimators of model parameters. Asymptotic theory for the special case of the vector exponential model is a significant addition to the paper of [20]. We also provide a mathematical machinery, based on matrix differentiation, and computational methods to derive our results, which differ significantly from those employed in the univariate case. The utility of the proposed model is illustrated through Monte Carlo simulation from a bivariate process characterized by a high dynamic range, and an empirical application on time varying minimum variance hedge ratios through the second moments of future and spot prices in the corn commodity market.

In a public-private partnership to develop housing, resident services and hope for 102 working families in Haster Orangewood community, Jamboree Housing Corporation and the City of Anaheim announce...

(PRWeb April 27, 2020)

Read the full story at https://www.prweb.com/releases/jamboree_begins_construction_on_capstone_development_to_change_trajectory_of_neighborhood_in_anaheim_ca/prweb17073166.htm

Highway 8, otherwise known as the Dempster Highway, will be closed to all traffic at 5 p.m. on Friday, according to the government of the Northwest Territories.

Urinary tract infection (UTI) is the most common bacterial infection in febrile infants aged 1 to 90 days. It is unclear if urine microscopy offers significant benefit beyond urine dipstick as a screening test for UTI in this population.

Dipstick may be an adequate screening test for UTI in infants aged 1 to 90 days with a negative predictive value (NPV) of 98.7%. Adding microscopy increases the NPV to 99.2% but results in 8 false-positives for every UTI missed by dipstick. (Read the full article)

Urinary tract infection is the most common serious bacterial illness among febrile infants and young children. Automated urine cytometry may supplant traditional urinalysis, but diagnostic performance at unique pediatric cutpoints has not been described for this labor-saving technique.

We describe new, clinically useful cutpoints for automated leukocyte and bacterial counts. The sensitivity and specificity of bacterial counts ≥250 cells/μL exceed those of other methods. However, point-of-care dipstick tests for leukocyte esterase or nitrite have acceptable performance. (Read the full article)

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After months of hard work and preparation, nearly a dozen Penn State Hazleton seniors are now one step closer to graduating after presenting their Capstone Research and Design Thesis projects.

Anglers encouraged to practice responsible social distancing. Trout streams closed March 21 until opening.

Fleet companies, RWAs, hospitals, logistics providers, private and public bus owners, hotels that offer commute, garages, dealerships, can all avail Droom's Jumpstart service.

Capstone is a multi-architecture, multi-platform disassembly framework. It has a simple and lightweight architecture-neutral API, thread-safe by design, provides details on disassembled instruction, and more.

In its decision of 27. June 2019 (Ref. 6 U 6/19), the Higher Regional Court of Frankfurt am Main ruled that participation in a sweepstakes can be made dependent on participants giving their consent to receive future marketing via e-mail or calls. In...

Usually the kingdom of water tanks and satellite dishes, Lebanon's rooftops have recently been graced by unlikely scenes of locked-down residents fleeing their flats.

Nigerian comedian Maryam Apaokagi has a sure-fire way of getting people to listen to her coronavirus health advice - she delivers it with a hard slap in the face.

Title: Lipsticks, Glosses Contain Toxic Metals: Report
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM

ABSTRACT

Recognition modes of individual T cell receptors (TCRs) are well studied, but factors driving the selection of TCR repertoires from primary through persistent human virus infections are less well understood. Using deep sequencing, we demonstrate a high degree of diversity of Epstein-Barr virus (EBV)-specific clonotypes in acute infectious mononucleosis (AIM). Only 9% of unique clonotypes detected in AIM persisted into convalescence; the majority (91%) of unique clonotypes detected in AIM were not detected in convalescence and were seeming replaced by equally diverse "de novo" clonotypes. The persistent clonotypes had a greater probability of being generated than nonpersistent clonotypes due to convergence recombination of multiple nucleotide sequences to encode the same amino acid sequence, as well as the use of shorter complementarity-determining regions 3 (CDR3s) with fewer nucleotide additions (i.e., sequences closer to germ line). Moreover, the two most immunodominant HLA-A2-restricted EBV epitopes, BRLF1₁₀₉ and BMLF1₂₈₀, show highly distinct antigen-specific public (i.e., shared between individuals) features. In fact, TCRα CDR3 motifs played a dominant role, while TCRβ played a minimal role, in the selection of TCR repertoire to an immunodominant EBV epitope, BRLF1. This contrasts with the majority of previously reported repertoires, which appear to be selected either on TCRβ CDR3 interactions with peptide/major histocompatibility complex (MHC) or in combination with TCRα CDR3. Understanding of how TCR-peptide-MHC complex interactions drive repertoire selection can be used to develop optimal strategies for vaccine design or generation of appropriate adoptive immunotherapies for viral infections in transplant settings or for cancer.

IMPORTANCE Several lines of evidence suggest that TCRα and TCRβ repertoires play a role in disease outcomes and treatment strategies during viral infections in transplant patients and in cancer and autoimmune disease therapy. Our data suggest that it is essential that we understand the basic principles of how to drive optimum repertoires for both TCR chains, α and β. We address this important issue by characterizing the CD8 TCR repertoire to a common persistent human viral infection (EBV), which is controlled by appropriate CD8 T cell responses. The ultimate goal would be to determine if the individuals who are infected asymptomatically develop a different TCR repertoire than those that develop the immunopathology of AIM. Here, we begin by doing an in-depth characterization of both CD8 T cell TCRα and TCRβ repertoires to two immunodominant EBV epitopes over the course of AIM, identifying potential factors that may be driving their selection.

Decades of rallying cries from professional societies, medical education and training programs, and government stakeholders have distilled the conversation of social determinants of health (SDOH) from theoretical proposals into practical solutions [1-3]. No longer standing on the precipice of change, we are now in the trenches. The nation's health care system recognizes SDOH as important drivers of health and is taking steps to address them in the practice environment.

More widespread action and attention by the health care system drives the need to train the next generation of physicians in the concepts and actions related to SDOH. This includes SDOH as a core part of the medical curriculum, offering clinical and research experiences and service in the community [4-5]. Unfortunately, to date only a handful of programs have brought this vision to fruition. Across the country, most programs offer educational content that is largely didactic and provided in short or one-time sessions [6]. Though a start, such approaches are insufficient to prepare the next generation of physicians for their important work ahead.

In New Orleans, the NOLA Hotspotters are an interdisciplinary group of medical, public health, nursing, and pharmacy students inspired by the work out of Camden, New Jersey, to "hot spot" patients with high utilization, which is often related to social needs [7]. While the results of the Camden program have been widely discussed following publication of their work, we argue the benefit of such a program exists beyond reduced emergency department visits or health care spending [8]. The...

Epstein-Barr virus (EBV) causes B cell lymphomas and transforms B cells in vitro. The EBV protein EBNA3A collaborates with EBNA3C to repress p16 expression and is required for efficient transformation in vitro. An EBNA3A deletion mutant EBV strain was recently reported to establish latency in humanized mice but not cause tumors. Here, we compare the phenotypes of an EBNA3A mutant EBV (3A) and wild-type (WT) EBV in a cord blood-humanized (CBH) mouse model. The hypomorphic 3A mutant, in which a stop codon is inserted downstream from the first ATG and the open reading frame is disrupted by a 1-bp insertion, expresses very small amounts of EBNA3A using an alternative ATG at residue 15. 3A caused B cell lymphomas at rates similar to their induction by WT EBV but with delayed onset. 3A and WT tumors expressed equivalent levels of EBNA2 and p16, but 3A tumors in some cases had reduced LMP1. Like the WT EBV tumors, 3A lymphomas were oligoclonal/monoclonal, with typically one dominant IGHV gene being expressed. Transcriptome sequencing (RNA-seq) analysis revealed small but consistent gene expression differences involving multiple cellular genes in the WT EBV- versus 3A-infected tumors and increased expression of genes associated with T cells, suggesting increased T cell infiltration of tumors. Consistent with an impact of EBNA3A on immune function, we found that the expression of CLEC2D, a receptor that has previously been shown to influence responses of T and NK cells, was markedly diminished in cells infected with EBNA3A mutant virus. Together, these studies suggest that EBNA3A contributes to efficient EBV-induced lymphomagenesis in CBH mice.

IMPORTANCE The EBV protein EBNA3A is expressed in latently infected B cells and is important for efficient EBV-induced transformation of B cells in vitro. In this study, we used a cord blood-humanized mouse model to compare the phenotypes of an EBNA3A hypomorph mutant virus (3A) and wild-type EBV. The 3A virus caused lymphomas with delayed onset compared to the onset of those caused by WT EBV, although the tumors occurred at a similar rate. The WT EBV and EBNA3A mutant tumors expressed similar levels of the EBV protein EBNA2 and cellular protein p16, but in some cases, 3A tumors had less LMP1. Our analysis suggested that 3A-infected tumors have elevated T cell infiltrates and decreased expression of the CLEC2D receptor, which may point to potential novel roles of EBNA3A in T cell and NK cell responses to EBV-infected tumors.

The Epstein-Barr virus (EBV) causes human cancers, and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81, which was isolated from a Chinese patient with nasopharyngeal carcinoma, induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one-third of the viruses hardly replicated, the remaining viruses showed variable levels of replication, with three isolates replicating at levels close to that of M81 in B cells. We cloned one strongly replicating virus into a bacterial artificial chromosome (BAC); the resulting recombinant virus (MSHJ) retained the properties of its nonrecombinant counterpart and showed similarities to M81, undergoing lytic replication in vitro and in vivo after 3 weeks of latency. In contrast, B cells infected with the nonreplicating Western B95-8 virus showed early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a Western virus, being genetically much closer to B95-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B cells, it is ideal to perform genetic analyses of all viral functions in Western strains and their associated diseases.

IMPORTANCE The Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far Eastern nasopharyngeal carcinomas replicate strongly in B cells. We show here that some viruses isolated from Western patients, including the MSHJ strain, share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and is much closer to nonreplicating Western viruses. We conclude that Western EBV strains are heterogeneous, with some viruses being able to replicate more strongly and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property.

Serological testing for nasopharyngeal carcinoma (NPC) has recently been reinvigorated by the implementation of novel Epstein-Barr virus (EBV)-specific IgA and IgG antibodies from a proteome array. Although proteome arrays are well suited for comprehensive antigen selection, they are not applicable for large-scale studies. We adapted a 13-marker EBV antigen signature for NPC risk identified by proteome arrays to multiplex serology to establish an assay for large-scale studies. Taiwanese NPC cases (n = 175) and matched controls (n = 175) were used for assay validation. Spearman’s correlation was calculated, and the diagnostic value of all multiplex markers was assessed independently using the area under the receiver operating characteristic curve (AUC). Two refined signatures were identified using stepwise logistic regression and internally validated with 10-fold cross validation. Array and multiplex serology showed strong correlation for each individual EBV marker, as well as for a 13-marker combined model on continuous data. Two refined signatures with either four (LF2 and BGLF2 IgG, LF2 and BMRF1 IgA) or two (LF2 and BGLF2 IgG) antibodies on dichotomous data were identified as the most parsimonious set of serological markers able to distinguish NPC cases from controls with AUCs of 0.992 (95% confidence interval [CI], 0.983 to 1.000) and 0.984 (95% CI, 0.971 to 0.997), respectively. Neither differed significantly from the 13-marker model (AUC, 0.992; 95% CI, 0.982 to 1.000). All models were internally validated. Multiplex serology successfully validated the original EBV proteome microarray data. Two refined signatures of four and two antibodies were capable of detecting NPC with 99.2% and 98.4% accuracy.

High-constitutive activity of the DNA damage response protein checkpoint kinase 1 (CHK1) has been shown in glioblastoma (GBM) cell lines and in tissue sections. However, whether constitutive activation and overexpression of CHK1 in GBM plays a functional role in tumorigenesis or has prognostic significance is not known. We interrogated multiple glioma patient cohorts for expression levels of CHK1 and the oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A), a known target of high-CHK1 activity, and examined the relationship between these two proteins in GBM. Expression levels of CHK1 and CIP2A were independent predictors for reduced overall survival across multiple glioma patient cohorts. Using siRNA and pharmacologic inhibitors we evaluated the impact of their depletion using both in vitro and in vivo models and sought a mechanistic explanation for high CIP2A in the presence of high-CHK1 levels in GBM and show that; (i) CHK1 and pSTAT3 positively regulate CIP2A gene expression; (ii) pSTAT3 and CIP2A form a recursively wired transcriptional circuit; and (iii) perturbing CIP2A expression induces GBM cell senescence and retards tumor growth in vitro and in vivo. Taken together, we have identified an oncogenic transcriptional circuit in GBM that can be destabilized by targeting CIP2A.