CSRR Loaded 2x1 Triangular MIMO Antenna for LTE Band Operation

A 2´1 (two-element) multiple-input multiple-output (MIMO) patch antenna system is designed and fabricated for (2.43 – 2.57) GHz LTE band 7 operation. It uses comple-mentary split -ring resonator (CSRR) loading on its ground plane for antenna miniaturization. This reduces the single-element antenna size by 76%. The total board size of the proposed MIMO antenna system, including the GND plane is 50´50´0.8mm3, while the single-patch antenna element has a size of 18.5 ´16mm2. The antenna is fabricated and tested. Measured results are in good agreement with simulations. A minimum measured isolation of 10 dB is obtained given the close interelement spacing of 0.17λ

CSRR Loaded 2x1 Triangular MIMO Antenna for LTE Band Operation

A 2´1 (two-element) multiple-input multiple-output (MIMO) patch antenna system is designed and fabricated for (2.43 – 2.57) GHz LTE band 7 operation. It uses comple-mentary split -ring resonator (CSRR) loading on its ground plane for antenna miniaturization. This reduces the single-element antenna size by 76%. The total board size of the proposed MIMO antenna system, including the GND plane is 50´50´0.8mm3, while the single-patch antenna element has a size of 18.5 ´16mm2. The antenna is fabricated and tested. Measured results are in good agreement with simulations. A minimum measured isolation of 10 dB is obtained given the close interelement spacing of 0.17λ

Bandwidth Enhanced MIMO antenna for LTE bands using Split Ring Resonators and Stubs

In this work, an array of circular patch antenna loaded with a partial split ring and a pair of stubs each with same dimensions, on each of the antenna. Patch of the radius (r) = 7.5mm. The split ring is of the width 1.35mm. the split ring not only accounts for a newer operating band, but also tend to reduce the isolation and the stubs are tends to increase the bandwidth which results in change by 44.92% compared to array of antennas without split rings. The substrate dimensions are 55´30´0.8mm3 and the ground of 55´9mm2. The proposed antennas are simulated using high frequency structural simulator and the results compared with the circular patch antenna without split ring resonators. The results obtained clearly show that, bandwidth of circular micro strip antenna without split ring can be enhanced. The proposed antennas may find applications in LTE band 1, 2, 3, 4, 7, 9, 10, 11, 15, 16, 21, 22, 23, 24, 25, 30, 33, 34, 35, 37, 38, 39, 40, 41, 42, 43 GHz covering a broadband width of 2500MHz

A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21((-/-))) and were examined with respect to growth and migration. p21((-/-) )and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21((-/-) )FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21((-/-) )FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21((-/-) )FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p &lt; 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant

Ribonuclease L (RNase L) is an important effector of the innate antiviral response. Mutations or variants that impair function of RNase L, particularly R462Q, have been proposed as susceptibility factors for prostate cancer. Given the role of this gene in viral defense, we sought to explore the possibility that a viral infection might contribute to prostate cancer in individuals harboring the R462Q variant. A viral detection DNA microarray composed of oligonucleotides corresponding to the most conserved sequences of all known viruses identified the presence of gammaretroviral sequences in cDNA samples from seven of 11 R462Q-homozygous (QQ) cases, and in one of eight heterozygous (RQ) and homozygous wild-type (RR) cases. An expanded survey of 86 tumors by specific RT-PCR detected the virus in eight of 20 QQ cases (40%), compared with only one sample (1.5%) among 66 RQ and RR cases. The full-length viral genome was cloned and sequenced independently from three positive QQ cases. The virus, named XMRV, is closely related to xenotropic murine leukemia viruses (MuLVs), but its sequence is clearly distinct from all known members of this group. Comparison of gag and pol sequences from different tumor isolates suggested infection with the same virus in all cases, yet sequence variation was consistent with the infections being independently acquired. Analysis of prostate tissues from XMRV-positive cases by in situ hybridization and immunohistochemistry showed that XMRV nucleic acid and protein can be detected in about 1% of stromal cells, predominantly fibroblasts and hematopoietic elements in regions adjacent to the carcinoma. These data provide to our knowledge the first demonstration that xenotropic MuLV-related viruses can produce an authentic human infection, and strongly implicate RNase L activity in the prevention or clearance of infection in vivo. These findings also raise questions about the possible relationship between exogenous infection and cancer development in genetically susceptible individuals

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92443/1/bjh9173.pd

RNase L Mediated Protection from Virus Induced Demyelination

IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL−/−) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL−/− mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination