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Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases.

Oxidative stress including decreased antioxidant enzyme activities, elevated lipid peroxidation, and accumulation of advanced glycation end products in the blood from children with autism spectrum disorders (ASD) has been reported. The mechanisms affecting the development of ASD remain unclear; however, toxic environmental exposures leading to oxidative stress have been proposed to play a significant role. The BTBRT⁺Itpr3tf /J (BTBR) strain provides a model to investigate the markers of oxidation in a mouse strain exhibiting ASD-like behavioral phenotypes. In the present study, we investigated the level of oxidative stress and its effects on immune cell populations, specifically oxidative stress affecting surface thiols (R-SH), intracellular glutathione (iGSH), and expression of brain biomarkers that may contribute to the development of the ASD-like phenotypes that have been observed and reported in BTBR mice. Lower levels of cell surface R-SH were detected on multiple immune cell subpopulations from blood, spleens, and lymph nodes and for sera R-SH levels of BTBR mice compared to C57BL/6 J (B6) mice. The iGSH levels of immune cell populations were also lower in the BTBR mice. Elevated protein expression of GATA3, TGM2, AhR, EPHX2, TSLP, PTEN, IRE1α, GDF15, and metallothionein in BTBR mice is supportive of an increased level of oxidative stress in BTBR mice and may underpin the pro-inflammatory immune state that has been reported in the BTBR strain. Results of a decreased antioxidant system suggest an important oxidative stress role in the development of the BTBR ASD-like phenotype.

Email is one of the most prolific forms of communication in the world. As colleges and universities move more student experiences online, faculty members and advisors need to understand how to best communicate with students. In an attempt to understand how faculty and advisors write, and, more importantly, how students read, I developed this two-phase mixed methods investigation. In Phase I, I collected nine writing samples from 19 faculty and advisor participants and dissected the samples with Pennebaker Conglomerate’s 2015 Linguistic Inquiry and Word Count (LIWC) program. In a transition phase, I leveraged Phase I data to create an instrument for Phase II. The 37 student participants in Phase II offered insight into their communication preferences through the completion of a questionnaire, writing prompts, and focus groups. Through synthesis of the Phase I and Phase II data, I drew conclusions about differences in students’ perceptions of professor and advisor emails and made recommendations for how university personnel can better communicate with students via email. While results indicated few differences in faculty and advisor participants, student participants favored social communication with faculty members and focused on impersonal objectives when communicating with advisors. Student participants also vocalized a desire for concise, bulleted communication from both faulty members and advisors.

Contracting out However, as long as the lease is for a fixed term, the parties can contract out of the 1954 Act. Since 2004, the contracting out process has been governed by the Regulatory Reform (Business Tenancies) (England and Wales) Order 2003. There is also authority from that era that a \"substantial\" change to the terms of the lease appended to the court order could invalidate the contracting out. The Civil Procedure Rules allow for service of documents relating to court proceedings by email, so long as: the party receiving the document has confirmed that it is willing to accept service by email and specified the email address(es) to use for that purpose; and the party serving the notice has asked the receiving party if there are any limitations to its agreement to accept service by email (such as file size or format) and complied with any such requirements. A court may be influenced by the CPR when deciding if email service of a warning notice under the 1954 Act is valid and so it would seem prudent for the above steps to be followed.

Truce Street Tales is a short story collection that explores the racial, class, and gender tensions on a boarder street in an American city through the Chaucerian perceptions of ten narrators.

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases.

Accurately measuring the performance characteristics of web applications under realistic loads is a difficult task. Manley presents an Internet Server API filter for Microsoft IIS that offers hooks for extending functionality.

Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, which is categorized by deficiency of social contact and communication, and stereotyped forms of performance. Meningeal immunity conditions the immune reflection and immune defense in the meningeal area involving meningeal lymphatic organization, glymphatic structure, immune cells, and cytokines. The development of meningeal immunity dysfunction might be the leading cause for many neural diseases including ASD. The inbred mouse strain BTBRT+Itpr3tf/J (BTBR) shows multiple ASD-like behavioral phenotypes, thus making this strain a widely used animal model for ASD. In our previous study, we reported an altered peripheral immune profile in BTBR mice. Herein, we are investigating immunological and neural interactions associated with the aberrant behavior of BTBR mice. BTBR mice have an increased level of immune cell deposition in the meninges along with a higher level of CD4+ T cells expressing CD25 and of B and myeloid cells expressing more MHCII than C57BL/6 (B6) mice, which have normal behaviors. BTBR mice also have higher levels of autoantibodies to dsDNA, Aquaporin-4, NMDAR1, Pentraxin/SAP and Caspr2 than B6 mice, which may affect neural functions. Interestingly, the T regulatory (Treg) cell population and their function was significantly reduced in the meninges and brain draining lymph nodes, which may explain the increased level of activated B and T cells in the meninges of BTBR mice. A low level of Treg cells, less IL-10 production by Treg, and activated T and B cells in meninges together with higher autoantibody levels might contribute to the development of autism-like behavior through neuroinflammation, which is known to be increased in BTBR mice. BTBR mice have higher level of immune cell deposition in the meninges compared to C57BL/6 (B6) mice. Meningeal T cells and B cells of BTBR mice express a higher level of CD25 and MHCII, respectively, than those of B6 mice. BTBR mice have a higher level of serum autoantibodies to dsDNA and brain antigens (Aquaporin-4, NMDAR1, Pentraxin/SAP and Caspr2) than B6 mice. T regulatory (Treg) cell population was reduced in the meninges and brain draining lymph nodes of BTBR mice with lower cytokine production of IL-10. Fewer Treg cells and more activated meningeal T and B cells together with higher autoantibody levels might contribute to the development of the autism-like behavior of BTBR mice.

In this paper we generalize the discrete Fourier-Ricatti-Bessel transform, allowing, via choice of several appropriate parameters, the recovery of the discrete Fourier sine transform, the discrete Hankel transform, and the discrete Fourier-Ricatti-Bessel transform for all three classes of boundary conditions, and the associated asymptotic inversion formulas. We then numerically and analytically estimate the error in our discrete inversion formula, finding that the error decreases as the square of the size of the transform matrix. Finally, we apply our new transform to selected functions for which the continuous transform is known, compute the discrete backward transform, and asymptotically recover the original function.