EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis

<p>Abstract</p> <p>Background</p> <p>About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (<it>EBER</it>s) are presented in all EBV-infected cells, but their functions are still less understood.</p> <p>Results</p> <p><it>EBER1 </it>was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for <it>EBER1</it>-induced changes. We found that <it>EBER1 </it>suppressed <it>p21</it>^cip1/waf1transcription in HL cell lines. In addition, positive regulators of <it>p21</it>^cip1/waf1transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of <it>p21</it>^cip1/waf1in the <it>EBER1</it>⁺HL cell lines was associated with increased resistance to histone deacetylase inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing p21^cip1/waf1levels. On biopsy specimens, EBV⁺HLs had weaker expression of both p21^cip1/waf1and active caspase 3. Clinically, suppression of p21^cip1/waf1in EBV⁺HLs was associated with a worse 2-year disease-free survival rate (45% for EBV⁺HLs <it>vs</it>. 77% for EBV^-HLs, <it>p </it>= 0.002).</p> <p>Conclusion</p> <p>Although the underlying mechanisms are still relatively unclear, <it>EBER1 </it>inhibits <it>p21</it>^cip1/waf1transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1. The anti-apoptotic activity of <it>EBER1 </it>may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV⁺HLs.</p

Generation of heralded optical `Schroedinger cat' states by photon-addition

Optical "Schr\"odinger cat" states, the non-classical superposition of two quasi-classical coherent states, serve as a basis for gedanken experiments testing quantum physics on mesoscopic scales and are increasingly recognized as a resource for quantum information processing. Here, we report the first experimental realization of optical "Schr\"odinger cats" by adding a photon to a squeezed vacuum state, so far only photon-subtraction protocols have been realized. Photon-addition gives us the advantage of using heralded signal photons as experimental triggers, and we can generate "Schr\"odinger cats" at rates exceeding $8.5 \times 10^4$ counts per second; at least one order of magnitude higher than all previously reported realizations. Wigner distributions with pronounced negative parts are demonstrated at down to -8.89 dB squeezing, even when the initial squeezed vacuum input state has low purity. Benchmarking against such a degraded squeezed input state we report a maximum fidelity of more than 80% with a maximum cat amplitude of $|\alpha| \approx 1.66$. Our experiment uses photon-addition from pairs, one of those photons is used for monitoring, giving us enhanced control; moreover the pair production rates are high and should allow for repeated application of photon-addition via repeat-stages.Comment: 5 pages, 2 figures, 1 tabl

UPANets: Learning from the Universal Pixel Attention Networks

Among image classification, skip and densely-connection-based networks have dominated most leaderboards. Recently, from the successful development of multi-head attention in natural language processing, it is sure that now is a time of either using a Transformer-like model or hybrid CNNs with attention. However, the former need a tremendous resource to train, and the latter is in the perfect balance in this direction. In this work, to make CNNs handle global and local information, we proposed UPANets, which equips channel-wise attention with a hybrid skip-densely-connection structure. Also, the extreme-connection structure makes UPANets robust with a smoother loss landscape. In experiments, UPANets surpassed most well-known and widely-used SOTAs with an accuracy of 96.47% in Cifar-10, 80.29% in Cifar-100, and 67.67% in Tiny Imagenet. Most importantly, these performances have high parameters efficiency and only trained in one customer-based GPU. We share implementing code of UPANets in https://github.com/hanktseng131415go/UPANets

Adaptive Synaptic Memory via Lithium Ion Modulation in RRAM Devices

Biologically plausible computing systems require fine- grain tuning of analog synaptic characteristics. In this study, lithium- doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state- dependent decay to be reliably achieved. As a result, this device offers multi- bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short- term memory and long- term memory are emulated across dynamical timescales. Spike- timing- dependent plasticity and paired- pulse facilitation are also demonstrated. These mechanisms are capable of self- pruning to generate efficient neural networks. Time- dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human’s higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.In this study, lithium- doped silicate resistive random access memory with a titanium nitride (TiN) electrode is shown to mimic biological synapses. The TiN electrode effectively stores lithium ions, a principle widely adopted from battery construction, and enables reliable state- dependent decay. This device offers multi- bit functionality and synaptic plasticity, short- term memory and long- term memory, spike- timing- dependent plasticity and paired- pulse facilitation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163426/3/smll202003964-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163426/2/smll202003964_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163426/1/smll202003964.pd

Association Between Net Vertebral Artery Flow Volume and Non-AF Stroke: A Retrospective 2-Year Analysis

Objectives: Association between net vertebral artery flow volume (NVAFV) and stroke types remains unclear. We hypothesize NVAFV is low in patients with posterior circulation infarction (PCI) and an ideal cut-off value for discriminating PCI from anterior circulation infarction (ACI) and controls may be present.Materials and Methods: As study candidates, we retrospectively enrolled hospitalized patients with first-time non-AF stroke within 2-years period. Consecutive non-AF, non-stroke subjects were enrolled as the control group. We compared NVAFV values among the PCI, ACI, and control groups.Results: Overall, 866 candidates—213, 418, and 235 candidates in the PCI, ACI, and control groups, respectively—were enrolled. NVAFV (mean ± SD) values were 134.8 ± 52.7, 152.3 ± 59.2, and 172.0 ± 54.7 mL/min in the PCI, ACI, and control groups, respectively. Statistics revealed significant difference (p &lt; 0.001) among three groups. To use NVAFV as a diagnostic parameter, the AUC of any two groups should be between 0.58 and 0.69. Most (93.6%) of the controls had NVAFV above 100 mL/min. The odds ratio of any non-AF stroke is 3.48 if the NVAFV is below 100 mL/min.Conclusions: NVAFV is lowest in non-AF PCI group. Low NVAFV is associated with both non-AF ACI and PCI. No ideal cut-off value is available to discriminate PCI from other two conditions. We agree that an NVAFV of 100 mL/min is the lower limit of a normal value. Any value below 100 mL/min indicates high stroke risk and implies diffuse cerebral atherosclerosis and impaired cerebral perfusion

The Estimation of First-Phase Insulin Secretion by Using Components of the Metabolic Syndrome in a Chinese Population

Aims. There are two phases of insulin secretion, the first (FPIS) and second phase (SPIS). In this study, we built equations to predict FPIS with metabolic syndrome (MetS) components and fasting plasma insulin (FPI). Methods. Totally, 186 participants were enrolled. 75% of participants were randomly selected as the study group to build equations. The remaining 25% of participants were selected as the external validation group. All participants received a frequently sampled intravenous glucose tolerance test, and acute insulin response after the glucose load (AIRg) was obtained. The AIRg was considered as FPIS. Results. When MetS components were only used, the following equation was built: log (FPIS) = 1.477 − 0.119 × fasting plasma glucose (FPG) + 0.079 × body mass index (BMI) − 0.523 × high-density lipoprotein cholesterol (HDL-C). After FPI was added, the second equation was formulated: log (FPIS) = 1.532 − 0.127 × FPG + 0.059 × BMI - 0.511 × HDL-C + 0.375 × log (FPI), which provided a better accuracy than the first one. Conclusions. Using MetS components, the FPIS could be estimated accurately. After adding FPI into the equation, the predictive power increased further. We hope that these equations could be widely used in daily practice

Association Between Acid-Sensing Ion Channel 3 Gene Variants and Balance Impairment in People With Mild Traumatic Brain Injury

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown.Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test.Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01).Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance