A Multimode 28 GHz CMOS Fully Differential Beamforming IC for Phased Array Transceivers.

A 28 GHz fully differential eight-channel beamforming IC (BFIC) with multimode operations is implemented in 65 nm CMOS technology for use in phased array transceivers. The BFIC has an adjustable gain and phase control on each channel to achieve fine beam steering and beam pattern. The BFIC has eight differential beamforming channels each consisting of the two-stage bi-directional amplifier with a precise gain control circuit, a six-bit phase shifter, a three-bit digital step attenuator, and a tuning bit for amplitude and phase variation compensation. The Tx and Rx mode overall gains of the differential eight-channel BFIC are around 11 dB and 9 dB, respectively, at 27.0-29.5 GHz. The return losses of the Tx mode and Rx mode are >10 dB at 27.0-29.5 GHz. The maximum phase of 354° with a phase resolution of 5.6° and the maximum attenuation of 31 dB, including the gain control bits with an attenuation resolution of 1 dB, is achieved at 27.0-29.5 GHz. The root mean square (RMS) phase and amplitude errors are <3.2° and <0.6 dB at 27.0-29.5 GHz, respectively. The chip size is 3.0 × 3.5 mm2, including pads, and Tx mode current consumption is 580 mA at 2.5 V supply voltage.

Auto-Tiler: Variable-Dimension Autoencoder with Tiling for Compressing Intermediate Feature Space of Deep Neural Networks for Internet of Things.

Due to limited resources of the Internet of Things (IoT) edge devices, deep neural network (DNN) inference requires collaboration with cloud server platforms, where DNN inference is partitioned and offloaded to high-performance servers to reduce end-to-end latency. As data-intensive intermediate feature space at the partitioned layer should be transmitted to the servers, efficient compression of the feature space is imperative for high-throughput inference. However, the feature space at deeper layers has different characteristics than natural images, limiting the compression performance by conventional preprocessing and encoding techniques. To tackle this limitation, we introduce a new method for compressing DNN intermediate feature space using a specialized autoencoder, called auto-tiler. The proposed auto-tiler is designed to include the tiling process and provide multiple input/output dimensions to support various partitioned layers and compression ratios. The results show that auto-tiler achieves 18% to 67% higher percent point accuracy compared to the existing methods at the same bitrate while reducing the process latency by 73% to 81%. The dimension variability of an auto-tiler also reduces the storage overhead by 62% with negligible accuracy loss.

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

Ribosomal protein S6 (RPS6) is a component of the 40S small ribosomal subunit and participates in the control of mRNA translation. Additionally, phospho (p)-RPS6 has been recognized as a surrogate marker for the activated PI3K/AKT/mTORC1 pathway, which occurs in many cancer types. However, downstream mechanisms regulated by RPS6 or p-RPS remains elusive, and the therapeutic implication of RPS6 is underappreciated despite an approximately half a century history of research on this protein. In addition, substantial evidence from RPS6 knockdown experiments suggests the potential role of RPS6 in maintaining cancer cell proliferation. This motivates us to investigate the current knowledge of RPS6 functions in cancer. In this review article, we reviewed the current information about the transcriptional regulation, upstream regulators, and extra-ribosomal roles of RPS6, with a focus on its involvement in cancer. We also discussed the therapeutic potential of RPS6 in cancer.

The effects of personality and aging attitudes on well-being in different life domains.

OBJECTIVES: Personality plays a major role in determining the way people adjust to life experiences, ultimately affecting life satisfaction. Aging attitudes also impact well-being, but there is little research on whether these personality and attitudinal effects reflect the same mechanism. The purpose of this study was to examine whether aging attitudes mediate the relationship between personality and well-being across seven different domains of everyday functioning, and whether this effect depends on age. METHODS: Data from 563 adults ranging in age from 30 to 89 were used. Sociodemographic information as well as the Big Five Inventory, aging attitudes, and well-being (i.e. current self-views and life satisfaction) in seven different life domains was assessed. RESULTS: The mediating effect of aging attitudes in the relationship between personality and well-being was strong for neuroticism, conscientiousness, and agreeableness and varied across domains. Significant mediation effects were limited for openness and extraversion. Significant moderated mediations were rather limited but the effects were stronger in later life. DISCUSSION: These results suggest that personality influences aging attitudes, which in turn affect well-being. Further, our results indicate that such relationships are context-specific, suggesting that the global assessments of attitudes and well-being may not fully characterize significant aging outcomes.

Generalized Nonlinear Least Squares Method for the Calibration of Complex Computer Code Using a Gaussian Process Surrogate.

The approximated nonlinear least squares (ALS) method has been used for the estimation of unknown parameters in the complex computer code which is very time-consuming to execute. The ALS calibrates or tunes the computer code by minimizing the squared difference between real observations and computer output using a surrogate such as a Gaussian process model. When the differences (residuals) are correlated or heteroscedastic, the ALS may result in a distorted code tuning with a large variance of estimation. Another potential drawback of the ALS is that it does not take into account the uncertainty in the approximation of the computer model by a surrogate. To address these problems, we propose a generalized ALS (GALS) by constructing the covariance matrix of residuals. The inverse of the covariance matrix is multiplied to the residuals, and it is minimized with respect to the tuning parameters. In addition, we consider an iterative version for the GALS, which is called as the max-minG algorithm. In this algorithm, the parameters are re-estimated and updated by the maximum likelihood estimation and the GALS, by using both computer and experimental data repeatedly until convergence. Moreover, the iteratively re-weighted ALS method (IRWALS) was considered for a comparison purpose. Five test functions in different conditions are examined for a comparative analysis of the four methods. Based on the test function study, we find that both the bias and variance of estimates obtained from the proposed methods (the GALS and the max-minG) are smaller than those from the ALS and the IRWALS methods. Especially, the max-minG works better than others including the GALS for the relatively complex test functions. Lastly, an application to a nuclear fusion simulator is illustrated and it is shown that the abnormal pattern of residuals in the ALS can be resolved by the proposed methods.

Expectation-Maximization Algorithm for the Calibration of Complex Simulator Using a Gaussian Process Emulator.

The approximated non-linear least squares (ALS) tunes or calibrates the computer model by minimizing the squared error between the computer output and real observations by using an emulator such as a Gaussian process (GP) model. A potential defect of the ALS method is that the emulator is constructed once and it is no longer re-built. An iterative method is proposed in this study to address this difficulty. In the proposed method, the tuning parameters of the simulation model are calculated by the conditional expectation (E-step), whereas the GP parameters are updated by the maximum likelihood estimation (M-step). These EM-steps are alternately repeated until convergence by using both computer and experimental data. For comparative purposes, another iterative method (the max-min algorithm) and a likelihood-based method are considered. Five toy models are tested for a comparative analysis of these methods. According to the toy model study, both the variance and bias of the estimates obtained from the proposed EM algorithm are smaller than those from the existing calibration methods. Finally, the application to a nuclear fusion simulator is demonstrated.

Pharmacokinetic and bioequivalence study of a fixed-dose combination of amlodipine besylate and rosuvastatin calcium compared to co-administration of separate tablets in healthy Korean subjects
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CONTEXT: A fixed-dose combination (FDC) tablet of amlodipine and rosuvastatin was recently developed for the treatment of concomitant hypertension and dyslipidemia and is anticipated to improve medication compliance. OBJECTIVE: This study was performed to compare the single-dose pharmacokinetic properties and safety of DP-R212 (FDC of amlodipine and rosuvastatin) to those of each agent co-administered in healthy Korean subjects. MATERIALS AND METHODS: A total of 36 healthy Korean subjects were enrolled in this randomized, open-label, single-dose, two-treatment, two-way crossover study. During each treatment period, subjects received the test drug (FDC tablet containing amlodipine and rosuvastatin) or reference drugs (individual tablets). Plasma samples were collected pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours post-dose. Safety was assessed by the evaluation of adverse events (AEs), laboratory assessments, 12-lead electrocardiograms (ECGs), physical examinations, and vital sign measurements. RESULTS: The 90% confidence intervals (CIs) of the geometric least-square mean ratios of AUClast and Cmax were 0.9796 - 1.0590 and 1.0135 - 1.0981 for amlodipine, and 0.9156 - 1.0490 and 0.8400 - 1.0306 for rosuvastatin, respectively. All AEs were of mild to moderate intensity, and no significant difference was observed in the incidence of AEs between the treatments. Moreover, the pharmacokinetic properties of the test and reference drugs were bioequivalent to each other, satisfying the regulatory criteria (0.8 - 1.25). DISCUSSION AND CONCLUSION: Both drugs were safe and well tolerated, and the pharmacokinetic profiles were comparable between the treatments.

The ageing systemic milieu negatively regulates neurogenesis and cognitive function.

In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines--including CCL11 (also known as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.

Radiogenomic correlation in lung adenocarcinoma with epidermal growth factor receptor mutations: Imaging features and histological subtypes.

OBJECTIVES: To correlate imaging features of resected lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation and the IASLC/ATS/ERS classification histological subtypes. METHODS: In 250 consecutive patients with resected lung adenocarcinoma, EGFR mutation status was correlated with demographics, imaging features including ground-glass opacity (GGO) proportion and the IASLC/ATS/ERS classification histological subtypes. RESULTS: EGFR mutations were significantly more frequent in women (54.5 % vs. 38.1 %, p = 0.011) and in never-smokers (54.7 % vs. 35.3 %, p = 0.003). GGO proportion was significantly higher in tumours with EGFR mutation than in those without (30.3 ± 33.8 % vs. 19.0 ± 29.3 %, p = 0.005). EGFR mutation was significantly more frequent in tumours with GGO ≥ 50 % and tumours with any GGO (p = 0.026 and 0.008, respectively). Adenocarcinomas with exon 19 or 21 mutation showed significantly higher GGO proportion than that in EGFR wild-type tumours (p = 0.009 and 0.029, respectively). Absence of GGO was an independent predictor of negative EGFR mutation (odds ratio, 1.81; 95 % confidence interval, 1.16-3.04; p = 0.018). CONCLUSIONS: GGO proportion in adenocarcinomas with EGFR mutation was significantly higher than that in EGFR wild-type tumours, and the absence of GGO on CT was an independent predictor of negative EGFR mutation. KEY POINTS: • Ground-glass opacity (GGO) proportion is significantly higher in EGFR-mutated adenocarcinomas • Exon 19 or 21 mutated adenocarcinomas shows significantly higher GGO proportion • GGO absence is an independent predictor of negative EGFR mutation in lung adenocarcinomas.

A Randomized Comparison of Remifentanil Target-Controlled Infusion Versus Dexmedetomidine Single-Dose Administration: A Better Method for Smooth Recovery From General Sevoflurane Anesthesia.

Remifentanil target-controlled infusion and dexmedetomidine single-dose administration are known to reduce airway response and hemodynamic stimulation during anesthetic recovery. We compared the effects of 2 drugs on the prevention of cough during emergence. We enrolled 70 female patients aged 20-60 years with American Society of Anesthesiologists (ASA) I-II who underwent general anesthesia for elective thyroidectomy. The patients were randomly assigned to remifentanil (group R) or dexmedetomidine (group D). Anesthesia was maintained with sevoflurane and effect-site target-controlled infusion of remifentanil. In group D, remifentanil was discontinued, and dexmedetomidine 0.5 µg/kg was given 10 minutes before the end of surgery. In group R, remifentanil target-controlled infusion at an effective-site concentration of 2.0 ng/mL was maintained during emergence until extubation. The cough grade, hemodynamic values, respiration, and other recovery profiles were evaluated during the periextubation period. The proportion of patients with no cough or just a single cough during extubation was significantly higher in group R than in group D (96.8% vs. 55.9%). The change of mean arterial pressure and heart rate were not significantly different during extubation in both groups. Respiratory rate and the incidence of residual sedation after extubation were lower in group R. There were no desaturation events and no differences in time to extubation or duration of postanesthesia care unit stay in both groups. Remifentanil target-controlled infusion reduces emergence cough from general anesthesia more effectively than single-dose dexmedetomidine. However, a single-dose of dexmedetomidine has the effect with respect to respiratory and hemodynamic stability during emergence.

The 27 to 29-year outcomes of the PCA total hip arthroplasty in patients younger than 50 years old.

We previously reported our six and 19.4-year results of arthroplasty with the PCA total hip prosthesis. We now report on the performance of this prosthesis at 27-29years. Eighty-eight consecutive primary THAs using a PCA total hip system were performed in 70 patients (mean age, 45.6±11.1years). The mean follow-up was 28.4years (27-29). The mean Harris hip score was 89 points at final follow-up. Thigh pain was reported in 22 hips (25%). The mean annual polyethylene wear was 0.182±0.03mm. There were 75 acetabular (85%) and 40 femoral (45%) osteolysis. The rate of survival after 28.4years as the end point of revision was 66% for the acetabular component and 90% for the femoral component.

Selective Engagement in Preparations for Aging.

OBJECTIVES: Preparing for old age is an adaptive behavior with positive consequences on well-being. This study examined; (a) the degree to which the importance associated with positive outcomes within specific domains of everyday functioning (e.g., social relationships, health) varies across ages and cultures; (b) the impact of importance on preparing for old age; and (c) whether the effects of importance were greater in later life. METHODS: Using data from adults aged 30-85 years in Germany (n = 623), Hong Kong (n = 317), and the United States (n = 313) collected over 5 years, we examined variations in importance ratings across age, cultures, and behavioral domains, and the extent to which age and importance predicted preparations. RESULTS: Importance ratings were found to vary with age, time of test, domains, and culture, reflecting the expected contextual effects. Importance also was a positive predictor of preparations, with the strength of prediction being somewhat greater in old age. DISCUSSION: The results provide evidence that the perceived importance of functioning within domains is affected by a number of contextual factors, including the domain of everyday function and culture. Given that importance also predicts preparations, such variation may help explain differences in preparations across contexts. In line with selective engagement theory, some support was also obtained for the prediction that older adults are more selective in engaging resources in support of preparations. Such selectivity can be viewed as an adaptive response to diminishing personal resources in later life.

A deep dive into burn-mediated ARDS severity assessment: a retrospective study on hematological markers.

Acute Respiratory Distress Syndrome (ARDS) is a critical form of Acute Lung Injury (ALI), challenging clinical diagnosis and severity assessment. This study evaluates the potential utility of various hematological markers in burn-mediated ARDS, including Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), MPV-to-Lymphocyte Ratio (MPVLR), Platelet count, and Platelet Distribution Width (PDW). Employing a retrospective analysis of data collected over 12 years, this study focuses on the relationship between these hematological markers and ARDS diagnosis and severity in hospitalized patients. The study establishes NLR as a reliable systemic inflammation marker associated with ARDS severity. Elevated MPV and MPVLR also emerged as significant markers correlating with adverse outcomes. These findings suggest these economical, routinely measured markers can enhance traditional clinical criteria, offering a more objective approach to ARDS diagnosis and severity assessment. Hematological markers such as NLR, MPV, MPVLR, Platelet count, and PDW could be invaluable in clinical settings for diagnosing and assessing ARDS severity. They offer a cost-effective, accessible means to improve diagnostic accuracy and patient stratification in ARDS. However, further prospective studies are necessary to confirm these findings and investigate their integration with other diagnostic tools in diverse clinical settings.

Suicidality is most centrally situated within network of depression symptom criteria in unipolar depression patients with mood stabilizer in Asia.

Lithium and mood stabilizers are considered effective augmentation agents of antidepressants for treatment-resistant depression. Thus, this study aimed to estimate the network structure of depression symptom criteria among unipolar depression patients with mood stabilizers, using data from the Research on Asian Psychotropic Prescription Patterns for mood stabilizers (REAP-MS). We estimated a network of the 9 depression symptom criteria among 411 unipolar depression patients in Asia. Each of the depression symptom criteria was considered to be a dichotomous categorical variable. Suicidality (suicidal ideation or attempt) was the most centrally situated within the network of depression symptoms, followed by depressed mood, loss of energy, anhedonia and weight loss or gain. Contrastingly, concentration problem was the least interconnected. The depression symptom criteria were organized into 4 clusters by the community detection method. The findings suggest that suicidality may be one of the significant therapeutic target symptoms in unipolar depression patients with mood stabilizers.

Predicting the spatio-temporal distribution of the invasive alien plant Andropogon virginicus, in the South Korean peninsula considering long-distance dispersal capacities.

The spread of invasive alien species is a major threat to biodiversity. Estimating the long-distance dispersal capacity of invasive alien plants is vital for understanding their population dynamics and community composition. We predicted the spatial-temporal distribution of the alien plant Andropogon virginicus, in the Korean peninsula under climate change scenario using Random Forest (RF) and Cellular Automaton (CA) methods. Land use, barriers to dispersal, long-distance dispersal frequency, and maximum long-distance dispersal range were considered in our analysis. Our results showed that, among the five selected environmental variables, annual mean temperature and Human Foot-Printing (HFP) were positively associated with the occurrence probability of A. virginicus. This suggests that A. virginicus is likely to spread to the disturbed northern part of the Korean Peninsula due to climate change and habitat preference. When comparing modeling results for dispersal to field survey data, the modeling raster sets drawn from the long-distance dispersal frequency of 0.05 and maximum long-distance dispersal distance of 30 km y-1 had the most similar spatial expansion among the six long-distance dispersal parameter sets. The dispersal directions were associated with the landscape. Specifically, seeds dispersed by wind (anemochorous seeds) could propagate into open landscapes more easily than in forests. Regarding A. virginicus management, this grass can quickly invade bare ground with their wind-dispersed seeds, therefore habitat destruction, such as excessive logging and weeding, should be restrained.

Mental Healthcare through Cognitive Emotional Regulation Strategies among Prisoners.

Prisoners are exposed to a deprived environment, which triggers mental illness and psychological problems. Abundant research has reported that mental illness problems, suicide, aggression, and violent behaviors occur in incarcerated people. Although the mental healthcare system for incarcerated people is emphasized, little research has been conducted due to their limited environment. In particular, the regulation of negative emotion is significantly associated with mental illness and anti-social and violent behaviors. However, mental healthcare through cognitive emotional regulation based on cognitive behavioral therapy has not been fully investigated. This study identified four different patterns in cognitive strategies for regulating negative emotions. Cognitive emotional regulation strategies (i.e., self-blame, other-blame, rumination, catastrophizing, putting into perspective, positive refocusing, positive reappraisal, acceptance, and refocus on planning) were examined and addressed their vulnerable psychological factors. We analyzed a total of 500 prisoners' responses to the cognitive emotional regulation questionnaire (CERQ) by latent class profiling analysis. A four-class model was identified based on the responses of CERQ. In addition, the significant effect of depression on classifying the four classes was found. Furthermore, differences in the average number of incarcerations were also shown across four classes. In conclusion, Class 2 (Negative Self-Blamer) uses dysfunctional/negative strategies that may place the group at a high risk of psychological disorder symptoms, including depression and post-traumatic stress. Class 3 (Distorted Positivity) uses positive/functional strategies but seems to utilize the positive strategies in distorted manners to rationalize their convictions. Class 1 (Strong Blamer) and Class 4 (Moderator Blamer) showed similar patterns focused on the "other-blame" strategy for regulating negative emotion, but they are at different levels, indicating that they attribute incarceration to external factors. These findings provide useful information for designing mental healthcare interventions for incarcerated people and psychological therapy programs for clinical and correctional psychologists in forensic settings.

Learning quadrupedal locomotion on deformable terrain.

Simulation-based reinforcement learning approaches are leading the next innovations in legged robot control. However, the resulting control policies are still not applicable on soft and deformable terrains, especially at high speed. The primary reason is that reinforcement learning approaches, in general, are not effective beyond the data distribution: The agent cannot perform well in environments that it has not experienced. To this end, we introduce a versatile and computationally efficient granular media model for reinforcement learning. Our model can be parameterized to represent diverse types of terrain from very soft beach sand to hard asphalt. In addition, we introduce an adaptive control architecture that can implicitly identify the terrain properties as the robot feels the terrain. The identified parameters are then used to boost the locomotion performance of the legged robot. We applied our techniques to the Raibo robot, a dynamic quadrupedal robot developed in-house. The trained networks demonstrated high-speed locomotion capabilities on deformable terrains: The robot was able to run on soft beach sand at 3.03 meters per second although the feet were completely buried in the sand during the stance phase. We also demonstrate its ability to generalize to different terrains by presenting running experiments on vinyl tile flooring, athletic track, grass, and a soft air mattress.

Penalized likelihood approach for the four-parameter kappa distribution.

The four-parameter kappa distribution (K4D) is a generalized form of some commonly used distributions such as generalized logistic, generalized Pareto, generalized Gumbel, and generalized extreme value (GEV) distributions. Owing to its flexibility, the K4D is widely applied in modeling in several fields such as hydrology and climatic change. For the estimation of the four parameters, the maximum likelihood approach and the method of L-moments are usually employed. The L-moment estimator (LME) method works well for some parameter spaces, with up to a moderate sample size, but it is sometimes not feasible in terms of computing the appropriate estimates. Meanwhile, using the maximum likelihood estimator (MLE) with small sample sizes shows substantially poor performance in terms of a large variance of the estimator. We therefore propose a maximum penalized likelihood estimation (MPLE) of K4D by adjusting the existing penalty functions that restrict the parameter space. Eighteen combinations of penalties for two shape parameters are considered and compared. The MPLE retains modeling flexibility and large sample optimality while also improving on small sample properties. The properties of the proposed estimator are verified through a Monte Carlo simulation, and an application case is demonstrated taking Thailand's annual maximum temperature data.

Synapto-protective effect of lithium on HIV-1 Tat-induced synapse loss in rat hippocampal cultures.

Human immunodeficiency virus type I (HIV-1) infection of the CNS produces synapse loss which correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). Lithium is mood stabilizer of unknown mechanism used to treat bipolar disorder and is known to exhibit neuroprotective properties. Here, we studied the effects of lithium on HIV-1 Tat-induced synapses between rat hippocampal neurons. The number of synapses was quantified to detect clusters of the scaffold protein postsynaptic density 95 (PSD95) which is clustered at glutamatergic synapses on cultured rat hippocampal neurons in vitro. Lithium protected synapses from HIV-1 Tat-induced synapse loss and subsequent neuronal death. This synaptic protection was prevented by both the activation of NMDA receptor leading to intracellular signaling and the regulatory pathway of lithium including inositol depletion and glycogen synthase kinase-3ß (GSK-3ß). These results suggest that mood stabilizers might be effective drugs to treat neurodegenerative disorders including HAND.

Biases in Retrospective Perceptions of Changes in Well-Being Associated With Aging Attitudes.

OBJECTIVES: Aging attitudes have important consequences on functioning in later life. A critical question concerns whether such attitudes may bias perceptions of one's own aging, with potentially negative effects on important outcomes. METHODS: Using data from adults aged 30-85 years in Germany (n = 623), Hong Kong (n = 317), and the United States (n = 313), we examined the impact of age and aging attitudes on accuracy of perceptions of change in well-being over 5 years in different domains of functioning. RESULTS: Across contexts, comparisons revealed good correspondence between retrospective reports and actual change. However, older adults and those with negative attitudes retrospectively reported less positive change over this period. Inconsistent with expectations, attitudes did not consistently bias accuracy of retrospective reports over cultures and domains of functioning, nor did age have a consistent moderating effect on the impact of attitudes on accuracy. DISCUSSION: The results highlight the complex relationship between various personal characteristics and perceptions of change in well-being, as well as the potentially insidious effects of attitudes on the accuracy of these perceptions.