Bit-wise Unequal Error Protection for Variable Length Block Codes with Feedback

The bit-wise unequal error protection problem, for the case when the number of groups of bits $\ell$ is fixed, is considered for variable length block codes with feedback. An encoding scheme based on fixed length block codes with erasures is used to establish inner bounds to the achievable performance for finite expected decoding time. A new technique for bounding the performance of variable length block codes is used to establish outer bounds to the performance for a given expected decoding time. The inner and the outer bounds match one another asymptotically and characterize the achievable region of rate-exponent vectors, completely. The single message message-wise unequal error protection problem for variable length block codes with feedback is also solved as a necessary step on the way.Comment: 41 pages, 3 figure

Interface driven magnetoelectric effects in granular CrO2

Antiferromagnetic and magnetoelectric Cr2O3-surfaces strongly affect the electronic properties in half metallic CrO2. We show the presence of a Cr2O3 surface layer on CrO3 grains by high-resolution transmission electron microscopy. The effect of these surface layers is demonstrated by measurements of the temperature variation of the magnetoelectric susceptibility. A major observation is a sign change at about 100 K followed by a monotonic rise as a function of temperature. These electric field induced moments in CrO3 are correlated with the magnetoelectric susceptibility of pure Cr2O3. This study indicates that it is important to take into account the magnetoelectric character of thin surface layers of Cr2O3 in granular CrO2 for better understanding the transport mechanism in this system. The observation of a finite magnetoelectric susceptibility near room temperature may find utility in device applications.Comment: Figure 1 with strongly reduced resolutio

HEART RATE VARIABILITY PARAMETERS IN PATIENTS WITH ARTERIAL HYPERTENSION IN DEPENDENCE ON THE TYPE OF DAILY BLOOD PRESSURE PROFILE

Violation of functioning of the autonomic nervous system is an important factor in the formation and progression of arterial hypertension (AH). Abnormal nocturnal blood pressure (BP) reduction is regarded as an independent prognostic factor for cardiovascular complications in patients with AH. One of the possible factors that determine the violation of BP circadian rhythm can be imbalance of different parts of autonomic nervous system. The aim of our study was to study heart rate variability (HRV) in patients with AH, dependently of BP profile. 72 patients with AH were examined. Average age was 57 ± 11 years. All patients underwent ambulatory BP (ABPM) and ECG monitoring. To define the daily profile the nocturnal BP dip was quantified and for HRV evaluation the frequency analysis method was used. HRV changes in patients with AH present with reduced total power and with a violation in the ratio of the powers of very low, low and high frequencies, enhanced sympathycotension and influence of humoral factors. Violations of systolic BP (SBP) daily profile was mainly characterized by an increase in the power of low frequency waves, which indicates an intensification of sympathetic and decreased parasympathetic influences. Violations of diastolic BP (DBP) daily profile were mainly characterized by a relative increase in the power of very low frequency waves. The obtained results showed that in the management of patients with AH it is important not only to control the circadian SBP and DBP profiles, but the evaluation of HRV also

Afatinib and Temozolomide Combination Inhibits Tumorigenesis by Targeting EGFRvIII-cMet Signaling in Glioblastoma Cells

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The recurrence is largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are amplified in ~ 60% and ~ 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation of tyrosine kinase receptor, cMET, regulates GBM CSC maintenance and promote tumor recurrence. Here, we evaluated the efficacy of pan-EGFR inhibitor afatinib and Temozolomide (TMZ) combination on GBM in vitro and in vivo. METHODS: We analyzed the effect of afatinib and temozolomide (TMZ) combination on GBM cells U87MG and U251 engineered to express wild type (WT) EGFR, EGFRvIII or EGFRvIII dead kinase, CSCs isolated from U87 and U87EGFRvIII in vitro. The therapeutic utility of the drug combination was investigated on tumor growth and progression using intracranially injected U87EGFRvIII GBM xenografts. RESULTS: Afatinib and TMZ combination synergistically inhibited the proliferation, clonogenic survival, motility, invasion and induced senescence of GBM cells compared to monotherapy. Mechanistically, afatinib decreased U87EGFRvIII GBM cell proliferation and motility/invasion by inhibiting EGFRvIII/AKT, EGFRvIII/JAK2/STAT3, and focal adhesion kinase (FAK) signaling pathways respectively. Interestingly, afatinib specifically inhibited EGFRvIII-cMET crosstalk in CSCs, resulting in decreased expression of Nanog and Oct3/4, and in combination with TMZ significantly decreased their self-renewal property in vitro. More interestingly, afatinib and TMZ combination significantly decreased the xenograft growth and progression compared to single drug alone. CONCLUSION: Our study demonstrated significant inhibition of GBM tumorigenicity, CSC maintenance in vitro, and delayed tumor growth and progression in vivo by combination of afatinib and TMZ. Our results warrant evaluation of this drug combination in EGFR and EGFRvIII amplified GBM patients

A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg- PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma MG. At sixteen-seventeen weeks post infection, cardiac ejection fraction and fractional shortening also declined by 26 and 35%, and plasma MG increased to four-fold higher than uninfected controls. Histopathological and biochemical analyses of cardiac tissues from Hu-mice 17 weeks post-infection affirmed MG increase with a concomitant decrease in expression of the MG-degrading enzyme glyoxalase-1 (Glo1). The endothelial cell marker CD31 was found to be lower, and coronary microvascular leakage and myocardial fibrosis were prominent. Increasing expression of Glo1 in Hu-mice five weeks post-infection using a single dose of an engineered AAV2/9 (1.7 × 1012 virion particles/kg), attenuated the increases in plasma and cardiac MG levels. Increasing Glo1 also blunted microvascular leakage, fibrosis, and HF seen at sixteen weeks post-infection, without changes in plasma viral loads. In plasma fromvirally suppressed PLWH,MG was also 3.7-fold higher. In autopsied cardiac tissues from seropositive, HIV individuals with low viral log, MG was 4.2-fold higher and Glo1 was 50% lower compared to uninfected controls. These data show for the first time a causal link between accumulation of MG and HF in the setting of HIV infection

Immune Activations and Viral Tissue Compartmentalization During Progressive HIV-1 Infection of Humanized Mice

Human immunodeficiency virus type one (HIV-1) tissue compartments are established soon after viral infection. However, the timing in which virus gains a permanent foothold in tissue and the cellular factors that control early viral-immune events are incompletely understood. These are critical events in studies of HIV-1 pathogenesis and in the development of viral reservoirs after antiretroviral therapy. Moreover, factors affecting the permanence of viral-tissue interactions underlie barriers designed to eliminate HIV-1 infection. To this end we investigated the temporal and spatial viral and host factors during HIV-1 seeding of tissue compartments. Two humanized NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ mouse models were employed. In the first, immune deficient mice were reconstituted with human CD34+ cord blood hematopoietic stem cells (HSC) (hu-HSC) and in the second mice were transplanted with adult mature human peripheral lymphocytes (hu-PBL). Both, in measure, reflect relationships between immune activation and viral infection as seen in an infected human host. Following humanization both mice models were infected with HIV-1ADA at 104 50% tissue culture infective doses. Viral nucleic acids and protein and immune cell profiles were assayed in brain, lung, spleen, liver, kidney, lymph nodes, bone marrow, and gut from 3 to 42 days. Peripheral CD4+ T cell loss began at 3 days together with detection of HIV-1 RNA in both mouse models after initiation of HIV-1 infection. HIV-1 was observed in all tested tissues at days 3 and 14 in hu- PBL and HSC mice, respectively. Immune impairment was most prominent in hu-PBL mice. T cell maturation and inflammation factors were linked directly to viral tissue seeding in both mouse models. We conclude that early viral tissue compartmentalization provides a roadmap for investigations into HIV-1 elimination

Efficacy of labral repair, biceps tenodesis, and diagnostic arthroscopy for SLAP Lesions of the shoulder: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Surgery for type II SLAP (superior labral anterior posterior) lesions of the shoulder is a promising but unproven treatment. The procedures include labral repair or biceps tenodesis. Retrospective cohort studies have suggested that the benefits of tenodesis include pain relief and improved function, and higher patient satisfaction, which was reported in a prospective non-randomised study. There have been no completed randomised controlled trials of surgery for type II SLAP lesions. The aims of this participant and observer blinded randomised placebo-controlled trial are to compare the short-term (6 months) and long-term (2 years) efficacy of labral repair, biceps tenodesis, and placebo (diagnostic arthroscopy) for alleviating pain and improving function for type II SLAP lesions.</p> <p>Methods/Design</p> <p>A double-blind randomised controlled trial are performed using 120 patients, aged 18 to 60 years, with a history for type II SLAP lesions and clinical signs suggesting type II SLAP lesion, which were documented by MR arthrography and arthroscopy. Exclusion criteria include patients who have previously undergone operations for SLAP lesions or recurrent shoulder dislocations, and ruptures of the rotator cuff or biceps tendon. Outcomes will be assessed at baseline, three, six, 12, and 24 months. Primary outcome measures will be the clinical Rowe Score (1988-version) and the Western Ontario Instability Index (WOSI) at six and 24 months. Secondary outcome measures will include the Shoulder Instability Questionnaire (SIQ), the generic EuroQol (EQ-5 D and EQ-VAS), return to work and previous sports activity, complications, and the number of reoperations.</p> <p>Discussion</p> <p>The results of this trial will be of international importance and the results will be translatable into clinical practice.</p> <p>Trial Registration</p> <p><b>[ClinicalTrials.gov NCT00586742]</b></p

Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice

Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible