Dimensional Crossover and Effective Exponents

We investigate the critical behavior of the lambda phi^4 theory defined on S^1 x R^d having two finite length scales beta, the circumference of S^1, and k^{-1}, the blocking scale introduced by the renormalization group transformation. By numerically solving the coupled differential RG equations for the finite-temperature blocked potential U_{beta,k}(Phi) and the wavefunction renormalization constant Z_{beta,k}(Phi), we demonstrate how the finite-size scaling variable betabar = beta k determines whether the phase transition is (d+1)- or d-dimensional in the limits betabar >> 1 and betabar << 1, respectively. For the intermediate values of betabar, finite-size effects play an important role. We also discuss the failure of the polynomial expansion of the effective potential near criticality.Comment: 24 pages, TeX, 8 figures in separate file, Updated version to appear in Nucl. Phys.

Coordinate enhancement of transgene transcription and translation in a lentiviral vector

BACKGROUND: Coordinate enhancement of transgene transcription and translation would be a potent approach to significantly improve protein output in a broad array of viral vectors and nonviral expression systems. Many vector transgenes are complementary DNA (cDNA). The lack of splicing can significantly reduce the efficiency of their translation. Some retroviruses contain a 5' terminal post-transcriptional control element (PCE) that facilitates translation of unspliced mRNA. Here we evaluated the potential for spleen necrosis virus PCE to stimulate protein production from HIV-1 based lentiviral vector by: 1) improving translation of the internal transgene transcript; and 2) functionally synergizing with a transcriptional enhancer to achieve coordinate increases in RNA synthesis and translation. RESULTS: Derivatives of HIV-1 SIN self-inactivating lentiviral vector were created that contain PCE and cytomegalovirus immediate early enhancer (CMV IE). Results from transfected cells and four different transduced cell types indicate that: 1) PCE enhanced transgene protein synthesis; 2) transcription from the internal promoter is enhanced by CMV IE; 3) PCE and CMV IE functioned synergistically to significantly increase transgene protein yield; 4) the magnitude of translation enhancement by PCE was similar in transfected and transduced cells; 5) differences were observed in steady state level of PCE vector RNA in transfected and transduced cells; 6) the lower steady state was not attributable to reduced RNA stability, but to lower cytoplasmic accumulation in transduced cells. CONCLUSION: PCE is a useful tool to improve post-transcriptional expression of lentiviral vector transgene. Coordinate enhancement of transcription and translation is conferred by the combination of PCE with CMV IE transcriptional enhancer and increased protein yield up to 11 to 17-fold in transfected cells. The incorporation of the vector provirus into chromatin correlated with reduced cytoplasmic accumulation of PCE transgene RNA. We speculate that epigenetic modulation of promoter activity altered cotranscriptional recruitment of RNA processing factors and reduced the availability of fully processed transcript or the efficiency of export from the nucleus. Our results provide an example of the dynamic interplay between the transcription and post-transcription steps of gene expression and document that introduction of heterologous gene expression signals can yield disparate effects in transfected versus transduced cells

Human T lymphotropic virus type-1 p30(II )alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

BACKGROUND: Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13(II )and p30(II), which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30(II )differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. RESULTS: Herein, we further characterized the role of p30(II )in regulation of cellular gene expression, using stable p30(II )expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30(II )expressing Jurkat T cells. In all categories, p30(II )appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. CONCLUSIONS: We are the first to demonstrate that p30(II), while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo

Digital Orthopaedics: A Glimpse Into the Future in the Midst of a Pandemic.

BackgroundThe response to COVID-19 catalyzed the adoption and integration of digital health tools into the health care delivery model for musculoskeletal patients. The change, suspension, or relaxation of Medicare and federal guidelines enabled the rapid implementation of these technologies. The expansion of payment models for virtual care facilitated its rapid adoption. The authors aim to provide several examples of digital health solutions utilized to manage orthopedic patients during the pandemic and discuss what features of these technologies are likely to continue to provide value to patients and clinicians following its resolution.ConclusionThe widespread adoption of new technologies enabling providers to care for patients remotely has the potential to permanently change the expectations of all stakeholders about the way care is provided in orthopedics. The new era of Digital Orthopaedics will see a gradual and nondisruptive integration of technologies that support the patient's journey through the successful management of their musculoskeletal disease

Gauge-ball spectrum of the four-dimensional pure U(1) gauge theory

We investigate the continuum limit of the gauge-ball spectrum in the four-dimensional pure U(1) lattice gauge theory. In the confinement phase we identify various states scaling with the correlation length exponent $\nu \simeq 0.35$. The square root of the string tension also scales with this exponent, which agrees with the non-Gaussian fixed point exponent recently found in the finite size studies of this theory. Possible scenarios for constructing a non-Gaussian continuum theory with the observed gauge-ball spectrum are discussed. The $0^{++}$ state, however, scales with a Gaussian value $\nu \simeq 0.5$. This suggests the existence of a second, Gaussian continuum limit in the confinement phase and also the presence of a light or possibly massless scalar in the non-Gaussian continuum theory. In the Coulomb phase we find evidence for a few gauge-balls, being resonances in multi-photon channels; they seem to approach the continuum limit with as yet unknown critical exponents. The maximal value of the renormalized coupling in this phase is determined and its universality confirmed.Comment: 46 pages, 12 figure

Improvement in Chronic Hepatocerebral Degeneration Following Liver Transplantation

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation