Novel low power CAM architecture

One special type of memory use for high speed address lookup in router or cache address lookup in a processor is Content Addressable Memory (CAM). CAM can also be used in pattern recognition applications where a unique pattern needs to be determined if a match is found. CAM has an additional comparison circuit in each memory bit compared to Static Random Access Memory. This comparison circuit provides CAM with an additional capability for searching the entire memory in one clock cycle. With its hardware parallel comparison architecture, it makes CAM an ideal candidate for any high speed data lookup or for address processing applications. Because of its high power demand nature, CAM is not often used in a mobile device. To take advantage of CAM on portable devices, it is necessary to reduce its power consumption. It is for this reason that much research has been conducted on investigating different methods and techniques for reducing the overall power. The objective is to incorporate and utilize circuit and power reduction techniques in a new architecture to further reduce CAM’s energy consumption. The new CAM architecture illustrates the reduction of both dynamic and static power dissipation at 65nm sub-micron environment. This thesis will present a novel CAM architecture, which will reduce power consumption significantly compared to traditional CAM architecture, with minimal or no performance losses. Comparisons with other previously proposed architectures will be presented when implementing these designs under 65nm process environment. Results show the novel CAM architecture only consumes 4.021mW of power compared to the traditional CAM architecture of 12.538mW at 800MHz frequency and is more energy efficient over all other previously proposed designs

Aberrant Transferrin and Ferritin Upregulation Elicits Iron Accumulation and Oxidative Inflammaging Causing Ferroptosis and Undermines Estradiol Biosynthesis in Aging Rat Ovaries by Upregulating NF-Κb-Activated Inducible Nitric Oxide Synthase: First Demonstration of an Intricate Mechanism

We report herein a novel mechanism, unraveled by proteomics and validated by in vitro and in vivo studies, of the aberrant aging-associated upregulation of ovarian transferrin and ferritin in rat ovaries. The ovarian mass and serum estradiol titer plummeted while the ovarian labile ferrous iron and total iron levels escalated with age in rats. Oxidative stress markers, such as nitrite/nitrate, 3-nitrotyrosine, and 4-hydroxy-2-nonenal, accumulated in the aging ovaries due to an aberrant upregulation of the ovarian transferrin, ferritin light/heavy chains, and iron regulatory protein 2(IRP2)-mediated transferrin receptor 1 (TfR1). Ferritin inhibited estradiol biosynthesis in ovarian granulosa cells in vitro via the upregulation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p65/p50-induced oxidative and inflammatory factor inducible nitric oxide synthase (iNOS). An in vivo study demonstrated how the age-associated activation of NF-κB induced the upregulation of iNOS and the tumor necrosis factor α (TNFα). The downregulation of the keap1-mediated nuclear factor erythroid 2-related factor 2 (Nrf2), that induced a decrease in glutathione peroxidase 4 (GPX4), was observed. The aberrant transferrin and ferritin upregulation triggered an iron accumulation via the upregulation of an IRP2-induced TfR1. This culminates in NF-κB-iNOS-mediated ovarian oxi-inflamm-aging and serum estradiol decrement in naturally aging rats. The iron accumulation and the effect on ferroptosis-related proteins including the GPX4, TfR1, Nrf2, Keap1, and ferritin heavy chain, as in testicular ferroptosis, indicated the triggering of ferroptosis. In young rats, an intraovarian injection of an adenovirus, which expressed iron regulatory proteins, upregulated the ovarian NF-κB/iNOS and downregulated the GPX4. These novel findings have contributed to a prompt translational research on the ovarian aging-associated iron metabolism and aging-associated ovarian diseases

Qigong Exercise Alleviates Fatigue, Anxiety, and Depressive Symptoms, Improves Sleep Quality, and Shortens Sleep Latency in Persons with Chronic Fatigue Syndrome-Like Illness

Objectives:. To evaluate the effectiveness of Baduanjin Qigong exercise on sleep, fatigue, anxiety, and depressive symptoms in chronic fatigue syndrome- (CFS-) like illness and to determine the dose-response relationship. Methods:. One hundred fifty participants with CFS-like illness (mean age = 39.0, SD = 7.9) were randomly assigned to Qigong and waitlist. Sixteen 1.5-hour Qigong lessons were arranged over 9 consecutive weeks. Pittsburgh Sleep Quality Index (PSQI), Chalder Fatigue Scale (ChFS), and Hospital Anxiety and Depression Scale (HADS) were assessed at baseline, immediate posttreatment, and 3-month posttreatment. The amount of Qigong self-practice was assessed by self-report. Results:. Repeated measures analyses of covariance showed a marginally nonsignificant (P = 0.064) group by time interaction in the PSQI total score, but it was significant for the “subjective sleep quality” and “sleep latency” items, favoring Qigong exercise. Improvement in “subjective sleep quality” was maintained at 3-month posttreatment. Significant group by time interaction was also detected for the ChFS and HADS anxiety and depression scores. The number of Qigong lessons attended and the amount of Qigong self-practice were significantly associated with sleep, fatigue, anxiety, and depressive symptom improvement. Conclusion:. Baduanjin Qigong was an efficacious and acceptable treatment for sleep disturbance in CFS-like illness. This trial is registered with Hong Kong Clinical Trial Register: HKCTR-1380

Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients

Evaluation of the ClearVoice Strategy in Adults Using HiResolution Fidelity 120 Sound Processing

ObjectivesThis study aimed to evaluate the benefits of ClearVoice strategy on speech perception in noise and in everyday listening situations in Cantonese-speaking cochlear implant users.MethodsTwelve experienced adult users of the Harmony implant and HiRes 120 sound processing participated in the study. The study employed a prospective within-subjects design wherein speech recognition in adults using HiRes 120 without ClearVoice turned on (control option) was compared to their performance with HiRes 120 with ClearVoice turned on. Each subject was evaluated with two different ClearVoice gain settings: -12 dB (ClearVoice medium) and -18 dB (ClearVoice high) after one-week of use. The Cantonese hearing in noise test and a questionnaire were used as the outcome measures.ResultsSubjects performed significantly better with ClearVoice medium than with control option in noise. No significant difference in performance was noted among the 3 settings in quiet. Most subjects reported high level of satisfaction with ClearVoice in daily listening situations and preferred to keep ClearVoice on.ConclusionClearVoice can help cochlear implant recipients to hear better in noise

Dense Cranial Electroacupuncture Stimulation for Major Depressive Disorder—A Single-Blind, Randomized, Controlled Study

BACKGROUND: Previous studies suggest that electroacupuncture possesses therapeutic benefits for depressive disorders. The purpose of this study was to determine whether dense cranial electroacupuncture stimulation (DCEAS) could enhance the antidepressant efficacy in the early phase of selective serotonin reuptake inhibitor (SSRI) treatment of major depressive disorder (MDD). METHODS: In this single-blind, randomized, controlled study, patients with MDD were randomly assigned to 9-session DCEAS or noninvasive electroacupuncture (n-EA) control procedure in combination with fluoxetine (FLX) for 3 weeks. Clinical outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), Clinical Global Impression-severity (CGI-S), and Self-rating Depression Scale (SDS) as well as the response and remission rates. RESULTS: Seventy-three patients were randomly assigned to n-EA (n = 35) and DCEAS (n = 38), of whom 34 in n-EA and 36 in DCEAS group were analyzed. DCEAS-treated patients displayed a significantly greater reduction from baseline in HAMD-17 scores at Day 3 through Day 21 and in SDS scores at Day 3 and Day 21 compared to patients receiving n-EA. DCEAS intervention also produced a higher rate of clinically significant response compared to n-EA procedure (19.4% (7/36) vs. 8.8% (3/34)). The incidence of adverse events was similar in the two groups. CONCLUSIONS: DCEAS is a safe and effective intervention that augments the antidepressant efficacy. It can be considered as an additional therapy in the early phase of SSRI treatment of depressed patients. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN88008690

Erratum to: Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma cell lines and biomarkers of response

published_or_final_versionSpringer Open Choice, 01 Dec 201

Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development

Background: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. © 2011 Yip et al.published_or_final_versio

Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study

OBJECTIVE: The risk of seizure following BNT162b2 and CoronaVac vaccinations has been sparsely investigated. This study aimed to evaluate this association. METHOD: Patients who had their first seizure-related hospitalization between February 23, 2021 and January 31, 2022 were identified in Hong Kong. All seizure episodes happening on the day of vaccination (day 0) were excluded since clinicians validated that most of the cases on day 0 were syncopal episodes. Within-individual comparison using a modified self-controlled case series analysis was applied to estimate the incidence rate ratio (IRR) with 95% confidence intervals (CI) of seizure using conditional Poisson regression. RESULTS: We identified 1656 individuals who had their first seizure-related hospitalization (BNT162b2: 426; CoronaVac: 263; unvaccinated: 967) within the observation period. The incidence of seizure was 1.04 (95% CI: 0.80-1.33) and 1.11 (95% CI: 0.80-1.50) per 100,000 doses of BNT162b2 and CoronaVac administered respectively. 16 and 17 individuals received second dose after having first seizure within 28 days after first dose of BNT162b2 and CoronaVac vaccinations, respectively. None had recurrent seizures after the second dose. There was no increased risk during day 1-6 after the first (BNT162b2: IRR=1.39, 95% CI=0.75-2.58; CoronaVac: IRR=1.19, 95% CI=0.50-2.83) and second doses (BNT162b2: IRR=1.36, 95% CI 0.72-2.57; CoronaVac: IRR=0.71, 95% CI=0.22-2.30) of vaccinations. During 7-13, 14-20- and 21-27-days post-vaccination, no association was observed for both vaccines. SIGNIFICANCE: The findings demonstrated no increased risk of seizure following BNT162b2 and CoronaVac vaccinations. Future studies will be warranted to evaluate the risk of seizure following COVID-19 vaccinations in different populations with subsequent doses to ensure the generalizability

Dissecting the effects of METTL3 on alternative splicing in prostate cancer

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker