Progress in Oligometastatic Prostate Cancer: Emerging Imaging Innovations and Therapeutic Approaches.

Prostate cancer (PCa) exhibits a spectrum of heterogeneity, from indolent to highly aggressive forms, with approximately 10-20% of patients experiencing metastatic PCa. Oligometastatic PCa, characterized by a limited number of metastatic lesions in specific anatomical locations, has gained attention due to advanced imaging modalities. Although patients with metastatic PCa typically receive systemic therapy, personalized treatment approaches for oligometastatic PCa are emerging, including surgical and radiotherapeutic interventions. This comprehensive review explores the latest developments in the field of oligometastatic PCa, including its biological mechanisms, advanced imaging techniques, and relevant clinical studies. Oligometastatic PCa is distinct from widespread metastases and presents challenges in patient classification. Imaging plays a crucial role in identifying and characterizing oligometastatic lesions, with new techniques such as prostate-specific membrane antigen positron emission tomography demonstrating a remarkable efficacy. The management strategies encompass cytoreductive surgery, radiotherapy targeting the primary tumor, and metastasis-directed therapy for recurrent lesions. Ongoing clinical trials are evaluating the effectiveness of these approaches. Oligometastatic PCa occupies a unique position between locally advanced and high-volume metastatic diseases. While a universally accepted definition and standardized diagnostic criteria are still evolving, emerging imaging technologies and therapeutic strategies hold promise for improving the patient outcomes in this intermediate stage of PCa.

Safety, Tolerability, and Pharmacokinetics of a Novel Oral Phosphodiesterase 4 Inhibitor, ME3183: First-in-Human Phase 1 Study.

A novel, oral phosphodiesterase 4 (PDE4) inhibitor, ME3183, is under development for the treatment of psoriasis, atopic dermatitis, and other inflammatory diseases. To evaluate its safety, tolerability, and pharmacokinetics, double-blind, placebo-controlled, single ascending dose (SAD), and multiple ascending dose (MAD) phase 1 studies were conducted in 126 healthy adults. The food effect was evaluated in a randomized, open-label, crossover manner (n = 5). ME3183 was safe and tolerable up to 25 mg in the SAD part and up to 10 mg twice daily in the MAD part. Frequently observed treatment-emergent adverse events included diarrhea and headache, as commonly reported for approved PDE4 inhibitors, providing no novel safety concerns. Pharmacokinetic analysis showed dose-dependent increases in Cmax and AUC, with later tmax and longer t1/2 than apremilast, an approved PDE4 inhibitor. The food effect study showed slightly decreased systemic exposure. In the MAD part, plasma exposure levels of ME3183 were higher even at the minimal dose (2.5 mg twice daily) than the estimated therapeutically effective level. These results show the safe profile of ME3183 and support further studies to confirm the safety and efficacy of the drug in patients with psoriasis and other inflammatory diseases.

Laparoscopic adrenalectomy for adrenal tumors with endocrine activity: Perioperative management pathways for reduced complications and improved outcomes.

The major adrenal tumors with endocrine activity are primary aldosteronism, Cushing's syndrome/mild autonomous cortisol secretion, and pheochromocytoma/paraganglioma. Excessive aldosterone secretion in primary aldosteronism causes cardiovascular, renal, and other organ damage in addition to hypertension and hypokalemia. Cortisol hypersecretion in Cushing's syndrome/mild autonomous cortisol secretion causes obesity, hypertension, impaired glucose tolerance, and cardiometabolic syndrome. Massive secretion of catecholamines in pheochromocytoma/paraganglioma causes hypertension and cerebrocardiovascular disease due to rapid blood pressure fluctuation. Moreover, pheochromocytoma multi-system crisis is a feared and possibly fatal presentation of pheochromocytoma/paraganglioma. Thus, adrenal tumors with endocrine activity are considered an indication for adrenalectomy, and perioperative management is very important. They have a risk of perioperative complications, either due to direct hemodynamic effects of the hormone hypersecretion or due to hormone-related comorbidities. In the last decades, deliberate preoperative evaluation and advanced perioperative management have significantly reduced complications and improved outcomes. Furthermore, improvements in anesthesia and surgical techniques with the feasibility of laparoscopic adrenalectomy have contributed to reduced morbidity and mortality. However, there are still several challenges to be considered in the perioperative care of these patients. There are very few data available prospectively to guide clinical management, due to the rarity of adrenal tumors with endocrine activity. Therefore, most guidelines are based on retrospective data analyses or small case series. In this review, the latest knowledge is summarized, and practical pathways to reduce perioperative complications and improve outcomes in adrenal tumors with endocrine activity are presented.

Arterial Transit Time-Based Multidelay Combination Strategy Improves Arterial Spin Labeling Cerebral Blood Flow Measurement Accuracy in Severe Steno-Occlusive Diseases.

BACKGROUND: Although perfusion imaging plays a key role in the management of steno-occlusive diseases, the clinical usefulness of arterial spin labeling (ASL) is limited by technical issues. PURPOSE: To examine the effect of arterial transit time (ATT) prolongation on cerebral blood flow (CBF) measurement accuracy and identify the best CBF measurement protocol for steno-occlusive diseases. STUDY TYPE: Prospective. POPULATION: Moyamoya (n = 10) and atherosclerotic diseases (n = 8). FIELD STRENGTH/SEQUENCE: A 3.0T/3DT1 -weighted and ASL. ASSESSMENT: Hadamard-encoded multidelay ASL scans with/without vessel suppression (VS) and single-delay ASL scans with long-label duration (LD) and long postlabeling delay (PLD), referred to as long-label long-delay (LLLD), were acquired. CBF measurement accuracy and its ATT dependency, measured as the correlation between the relative CBF measurement difference (ASL-single-photon emission computed tomography [SPECT]) and ATT, were compared among 1) Combo (incorporating multidelay and LLLD data based on ATT), 2) standard (LD/PLD = 1333/2333 msec), and 3) LLLD (LD/PLD = 4000/4000 msec) protocols, using whole-brain voxel-wise correlation with reference standard SPECT CBF. The effect of VS on CBF measurement accuracy was also assessed. STATISTICAL TESTS: Pearson's correlation coefficient, repeated-measures analysis of variance, t-test. P< 0.05 was considered significant. RESULTS: Pearson's correlation coefficients between ASL and SPECT CBF measurements were as follows: Combo = 0.55 ± 0.09; standard = 0.52 ± 0.12; LLLD = 0.41 ± 0.10. CBF measurement was least accurate in LLLD and most accurate in Combo. VS significantly improved overall CBF measurement accuracy in the standard protocol and in moyamoya patients for the Combo. ATT dependency analysis revealed that, compared with Combo, the standard and LLLD protocols showed significantly lower and negative and significantly higher and positive correlations, respectively (standard = -0.12 ± 0.04, Combo = -0.04 ± 0.03, LLLD = 0.17 ± 0.03). DATA CONCLUSION: By using ATT-corrected CBF derived from LD/PLD = 1333/2333 msec as a base and by compensating underestimation in delayed regions using multidelay scans, the ATT-based Combo strategy improves CBF measurement accuracy compared with single-delay protocols in severe steno-occlusive diseases. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Reliability and Sensitivity to Longitudinal CBF Changes in Steno-Occlusive Diseases: ASL Versus 123 I-IMP-SPECT.

BACKGROUND: Noninvasive cerebral blood flow (CBF) monitoring using arterial spin labeling (ASL) magnetic resonance imaging is useful for managing large cerebral artery steno-occlusive diseases. However, knowledge about its measurement characteristics in comparison with reference standard perfusion imaging is limited. PURPOSE: To evaluate perfusion in a longitudinal manner in patients with steno-occlusive disease using ASL and compare with single-photon emission computed tomography (SPECT). STUDY TYPE: Prospective. POPULATION: Moyamoya (n = 10, eight females) and atherosclerotic diseases (n = 2, two males). FIELD STRENGTH/SEQUENCE: 3.0 T; gradient-echo three-dimensional T1 -weighted and spin-echo ASL. ASSESSMENT: Multi-delay ASL and [123 I]-iodoamphetamine SPECT CBF measurements were performed both before and within 9 days of anterior-circulation revascularization. Reliability and sensitivity to whole-brain voxel-wise CBF changes (ΔCBF) and their postlabeling delay (PLD) dependency with varied PLDs (in milliseconds) of 1000, 2333, and 3666 were examined. STATISTICAL TESTS: Reliability and sensitivity to ΔCBF were examined using within-subject standard deviation (Sw) and intraclass correlation coefficients (ICCs). For statistical comparisons, standard deviation of longitudinal ΔCBF within the hemisphere contralateral to surgery, and the ratio between it and average ΔCBF within the ipsilateral regions of interest were subjected to paired t tests, respectively. P < 0.05 was considered statistically significant. RESULTS: ASL test-retest time interval was 31 ± 18 days. Test-retest reliability was significantly lower for SPECT (0.16 ± 0.02) than ASL (0.13 ± 0.04). Sensitivity to postoperative changes was significantly higher for ASL (2.71 ± 2.79) than SPECT (0.27 ± 0.62). Test-retest reliability was significantly higher for a PLD of 2333 (0.13 ± 0.04) than 3666 (0.19 ± 0.05), and sensitivity to ΔCBF was significantly higher for PLDs of 1000 (2.53 ± 2.50) and 2333 than 3666 (0.79 ± 1.88). ICC maps also showed higher reliability for ASL than SPECT. DATA CONCLUSION: Higher test-retest reliability led to better ASL sensitivity than SPECT for postoperative ΔCBF. ASL test-retest reliability and sensitivity to ΔCBF were higher with a PLD of 2333. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Risk assessment of multi-factorial complications after transrectal ultrasound-guided prostate biopsy: a single institutional retrospective cohort study.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TRUSPB) is widely used to diagnose prostate cancer (PCa). The aim of this study was to evaluate the risk of multi-factorial complications (febrile genitourinary tract infection (GUTI), rectal bleeding, and urinary retention) after TRUSPB. METHODS: N = 2053 patients were Japanese patients undergoing transrectal or transperineal TRUSPB for suspicious of PCa. To assess risk of febrile GUTI adequately, the patients were divided into four groups: low-risk patients before starting a rectal culture, low-risk patients after starting a rectal culture, high-risk patients, and patients undergoing transperineal TRUSPB. Furthermore, to identify risk of rectal bleeding and urinary retention, patients were divided into transrectal and transperineal group. RESULTS: Febrile GUTI significantly decreased owing to risk classification. The frequency of rectal bleeding was 1.43% (transrectal: 25/1742), while it did not happen in transperineal group. The patients with rectal bleeding had a significantly lower body mass index (BMI) (P < 0.01). The frequency of urinary retention was 5.57% (transrectal: 97/1742), while it did not happen in transperineal group. The patients with urinary retention had a significantly higher prostate-specific antigen (PSA) (P = 0.01) in transrectal group. CONCLUSIONS: Risk classification, rectal swab culture, and selected antimicrobial prophylaxis for transrectal TRUSPB were extremely effective to reduce the risk of febrile GUTI. Furthermore, lower BMI and higher PSA were novel clinical predictors for rectal bleeding and urinary retention, respectively. When urologists perform transrectal TRUSPB to their patients, they can correctly understand and explain each complication risk to their patients based on these novel risk factors.

Imaging approaches for chromosome structures.

This review describes image analyses for chromosome visible structures, focusing on the chromosome imaging system CHIAS (Chromosome Image Analyzing System). CHIAS is the first comprehensive imaging system for the analysis and characterization of plant chromosomes. A simulation method for human vision for capturing band positive regions was developed and used for the image analysis of large plant chromosomes with bands. Applying this method to C-banded Crepis chromosomes enabled recognition of band positive regions as seen by human vision. Furthermore, a new image parameter, condensation pattern was developed and successfully applied to identify small plant chromosomes such as rice and brassicas. Condensation profile (CP) derived from condensation pattern was also effective in developing quantitative chromosome maps. The result was quantitative chromosomal maps of several plants with small chromosomes, including Arabidopsis, diploid brassicas, rapeseed, rice, spinach, and sugarcane. In the final chapter, various applications of imaging techniques to the analysis of pachytene chromosomes, improved visibility of multicolor FISH images, 3D reconstruction of a human chromosome based on cross-section images obtained by a FIB/SEM, automatic extraction of chromosomal regions by machine learning, etc. are described.

[SIGNIFICANCE OF IgG4 IN IDIOPATHIC RETROPERITONEAL FIBROSIS].

(Objective)Retroperitoneal fibrosis is largely divided into the idiopathic and secondary types. Some idiopathic cases include IgG4-related diseases, which are often similar to malignant diseases, such as lymphoma and sarcoma. The diagnostic criteria for IgG4-related disease are used and pathologic examination is necessary for a definitive diagnosis of IgG4-related retroperitoneal fibrosis. The first choice of treatment for IgG4-related retroperitoneal fibrosis is steroid administration, but no consensus has been established regarding its dose and tapering schedule. We investigated the significance of IgG4 in diagnosis and treatment of idiopathic retroperitoneal fibrosis. (Patients and methods)We examined 14 cases diagnosed as idiopathic retroperitoneal fibrosis between April 2013 and March 2019. Serum IgG4 was measured at the time of diagnosis in 13 cases, and changes over time in serum IgG4 before and after the induction of steroid therapy were measured in 6 cases. Computed tomography-guided biopsy was performed on 4 cases. (Results)Of all cases, 1 patient was diagnosed as IgG4-related retroperitoneal fibrosis and 5 patients were classified as possible group. Ten patients were administered steroid therapy. Percutaneous nephrostomy tube was placed in 3 patients and was removed in 2 of these patients after steroid therapy. The serum high levels of IgG4 were confirmed in all 4 patients who were classified into the possible group and who were treated with steroids. (Conclusion)Although histologic examination is necessary for the diagnosis of retroperitoneal fibrosis, tissue collection by open or laparoscopic surgery is highly invasive. CT-guided biopsy may be useful in high-risk cases, such as elderly patients on anticoagulation. After excluding other diseases in high-risk cases, response to empiric steroid therapy may be diagnostic. In the possible group, changes in serum IgG4 levels may reflect the disease condition and might be useful in determining the maintenance dose of steroids.

Blood group antigen A on von Willebrand factor is more protective against ADAMTS13 cleavage than antigens B and H.

BACKGROUND: ADAMTS13 specifically cleaves the peptide bond between Y1605 and M1606 within the VWF-A2 domain. OBJECTIVE: The VWF contains ABO(H) blood group antigens, which may influence the susceptibility of VWF to ADAMTS13. METHODS: Using a unique monoclonal antibody recognizing the Y1605 residue, we have developed a sandwich ELISA to analyze the generation of a VWF-DP by ADAMTS13 quantitatively. RESULTS: Production of VWF-DP after exposure to four different degrees of high shear stress was validated in comparison to the reduction in high-molecular-weight multimers using VWF multimer analysis. In analysis of plasma from 259 healthy individuals, plasma levels of VWF antigen (VWF:Ag) were significantly lower in blood group O than in the other groups and were significantly correlated with plasma VWF-DP levels. The ratio between VWF-DP and VWF:Ag was significantly higher in blood group O than in blood groups A and AB. The ratio in blood group B was also significantly higher than those in A and AB, but did not differ from blood group O. Finally, to examine whether ABO(H) blood group antigens contributed to VWF cleavage, 82 plasma samples were exposed to high shear stress using a cone-plate shear stress inducer. The difference in the VWF-DP/VWF:Ag ratio before and after high shear stress in blood group O was significantly greater than those in groups A and AB. CONCLUSION: These results indicate that blood group antigen A on VWF was more protective against ADAMTS13 cleavage than antigens B and H.

The cloud-free global energy balance and inferred cloud radiative effects: an assessment based on direct observations and climate models.

In recent studies we quantified the global mean Earth energy balance based on direct observations from surface and space. Here we infer complementary reference estimates for its components specifically under cloud-free conditions. While the clear-sky fluxes at the top of atmosphere (TOA) are accurately known from satellite measurements, the corresponding fluxes at the Earth's surface are not equally well established, as they cannot be directly measured from space. This is also evident in 38 global climate models from CMIP5, which are shown to greatly vary in their clear-sky surface radiation budgets. To better constrain the latter, we established new clear-sky reference climatologies of surface downward shortwave and longwave radiative fluxes from worldwide distributed Baseline Surface Radiation Network sites. 33 out of the 38 CMIP5 models overestimate the clear-sky downward shortwave reference climatologies, whereas both substantial overestimations and underestimations are found in the longwave counterparts in some of the models. From the bias structure of the CMIP5 models we infer best estimates for the global mean surface downward clear-sky shortwave and longwave radiation, at 247 and 314 Wm-2, respectively. With a global mean surface albedo of 13.5% and net shortwave clear-sky flux of 287 Wm-2 at the TOA this results in a global mean clear-sky surface and atmospheric shortwave absorption of 214 and 73 Wm-2, respectively. From the newly-established diagrams of the global energy balance under clear-sky and all-sky conditions, we quantify the cloud radiative effects not only at the TOA, but also within the atmosphere and at the surface.

CiApex1 has AP endonuclease activity and abrogated AP site repair disrupts early embryonic development in Ciona intestinalis.

Apurinic/apyrimidinic (AP) sites are the most common form of cytotoxic DNA damage. Since AP sites inhibit DNA replication and transcription, repairing them is critical for cell growth. However, the significance of repairing AP sites during early embryonic development has not yet been clearly determined. Here, we focused on APEX1 from the ascidian Ciona intestinalis (CiApex1), a homolog of human AP endonuclease 1 (APEX1), and examined its role in early embryonic development. Recombinant CiApex1 protein complemented the drug sensitivities of an AP endonuclease-deficient Escherichia coli mutant, and exhibited Mg2+-dependent AP endonuclease activity, like human APEX1, in vitro. Next, the effects of abnormal AP site repair on embryonic development were investigated. Treatment with methyl methanesulfonate, which alkylates DNA bases and generates AP sites, induced abnormal embryonic development. This abnormal phenotype was also caused by treatment with methoxyamine, which inhibits AP endonuclease activity. Furthermore, we constructed dominant-negative CiApex1, which inhibits CiApex1 action, and found that its expression impaired embryonic growth. These results suggested that AP site repair is essential for embryonic development and CiApex1 plays an important role in AP site repair during early embryonic development in C. intestinalis.

Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population.

We aimed to test the hypothesis that selenoprotein P (SELENOP), a hepatokine involved in the development of both insulin resistance and impaired insulin production in mice, is related to future onset of hyperglycemia in humans. 76 healthy non-pregnant human subjects without diabetes underwent oral glucose tolerance test (OGTT) at baseline and 4-years follow-up. Nine subjects developed either impaired glucose tolerance or type 2 diabetes at follow-up. At baseline, SELENOP concentrations correlated negatively with insulinogenic index, but not with homeostasis model assessment-estimated insulin resistance (HOMA-IR). Multivariate analysis showed that baseline SELENOP predicted fasting plasma glucose at follow-up independently of the other parameters. The receiver operating characteristic (ROC) curve analysis showed that baseline concentrations of serum SELENOP, but not of selenium, were a reliable test to predict future onset of glucose intolerance. In conclusion, elevation of circulating SELENOP, but not of circulating selenium, was positively and independently associated with future onset of glucose intolerance in a general Japanese population.

Quantitative evaluation of the relative apparent diffusion coefficient values on multiparametric magnetic resonance imaging to predict higher Gleason score prostate cancer.

INTRODUCTION: Apparent diffusion coefficient (ADC) values on multiparametric magnetic resonance imaging (mpMRI) have been reported to correlate with high-Gleason score (GS) prostate cancer. However, the relative ADC values between tumor lesions and normal tissue have been suggested as more suitable than the absolute ADC values for evaluation of diffusion abnormalities, because absolute ADC values are susceptible to differences in scanners or scanner settings. The present study evaluated the usefulness of the relative assessment of ADC values between tumor lesions and normal tissue on preoperative mpMRI for the prediction of high-risk prostate cancer on radical prostatectomy specimens. MATERIALS AND METHODS: A retrospective analysis of 48 men who underwent radical prostatectomy between January 2013 and December 2014 was conducted. MpMRI was performed with a 3.0-T scanner using b-values of 0 and 1500 s/mm2. ADC values of the tumor (ADCTUMOR) and normal prostate and the relative ADC tumor/normal ratio (ADCTNR) were evaluated by two radiologists. RESULTS: The inter-rater reliability between two radiologists for ADCTUMOR measurement was high, with Pearson's r = 0.982. There was no difference in ADCTUMOR between GS ≤7 and GS ≥8. In contrast, ADCTNR was significantly lower in GS ≥8 than in GS ≤7. ROC curves of ADCTNR to predict higher GS (≥8) showed better classification performance (AUC = 0.8243, p = .0012 by radiologist A and AUC = 0.7961, p = .0031 by radiologist B) than of ADCTUMOR. CONCLUSIONS: The relative assessment of ADC values between tumor lesions and normal tissue could improve the detection rate of high-risk prostate cancers.

Development of a quantitative pachytene chromosome map and its unification with somatic chromosome and linkage maps of rice (Oryza sativa L.).

A quantitative pachytene chromosome map of rice (Oryza sativa L.) was developed using imaging methods. The map depicts not only distribution patterns of chromomeres specific to pachytene chromosomes, but also the higher order information of chromosomal structures, such as heterochromatin (condensed regions), euchromatin (decondensed regions), the primary constrictions (centromeres), and the secondary constriction (nucleolar organizing regions, NOR). These features were image analyzed and quantitatively mapped onto the map by Chromosome Image Analyzing System ver. 4.0 (CHIAS IV). Correlation between H3K9me2, an epigenetic marker and formation and/or maintenance of heterochromatin, thus was, clearly visualized. Then the pachytene chromosome map was unified with the existing somatic chromosome and linkage maps by physically mapping common DNA markers among them, such as a rice A genome specific tandem repeat sequence (TrsA), 5S and 45S ribosomal RNA genes, five bacterial artificial chromosome (BAC) clones, four P1 bacteriophage artificial chromosome (PAC) clones using multicolor fluorescence in situ hybridization (FISH). Detailed comparison between the locations of the DNA probes on the pachytene chromosomes using multicolor FISH, and the linkage map enabled determination of the chromosome number and short/long arms of individual pachytene chromosomes using the chromosome number and arm assignment designated for the linkage map. As a result, the quantitative pachytene chromosome map was unified with two other major rice chromosome maps representing somatic prometaphase chromosomes and genetic linkages. In conclusion, the unification of the three rice maps serves as an indispensable basic information, not only for an in-depth comparison between genetic and chromosomal data, but also for practical breeding programs.

Observation-Based Decomposition of Radiative Perturbations and Radiative Kernels.

The Clouds and the Earth's Radiant Energy System (CERES)-partial radiative perturbation [PRP (CERES-PRP)] methodology applies partial-radiative-perturbation-like calculations to observational datasets to directly isolate the individual cloud, atmospheric, and surface property contributions to the variability of the radiation budget. The results of these calculations can further be used to construct radiative kernels. A suite of monthly mean observation-based inputs are used for the radiative transfer, including cloud properties from either the diurnally resolved passive-sensor-based CERES synoptic (SYN) data or the combination of the CloudSat cloud radar and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) lidar. The CloudSat/CALIPSO cloud profiles are incorporated via a clustering method that obtains monthly mean cloud properties suitable for accurate radiative transfer calculations. The computed fluxes are validated using the TOA fluxes observed by CERES. Applications of the CERES-PRP methodology are demonstrated by computing the individual contributions to the variability of the radiation budget over multiple years and by deriving water vapor radiative kernels. The calculations for the former are used to show that an approximately linear decomposition of the total flux anomalies is achieved. The observation-based water vapor kernels were used to investigate the accuracy of the GCM-based NCAR CAM3.0 water vapor kernel. Differences between our observation-based kernel and the NCAR one are marginally larger than those inferred by previous comparisons among different GCM kernels.

On the Lessons Learned from the Operations of the ERBE Nonscanner Instrument in Space and the Production of the Nonscanner TOA Radiation Budget Dataset.

Monitoring the flow of radiative energy at top-of-atmosphere (TOA) is essential for understanding the Earth's climate and how it is changing with time. The determination of TOA global net radiation budget using broadband nonscanner instruments has received renewed interest recently due to advances in both instrument technology and the availability of small satellite platforms. The use of such instruments for monitoring Earth's radiation budget was attempted in the past from satellite missions such as the Nimbus 7 and the Earth Radiation Budget Experiment (ERBE). This paper discusses the important lessons learned from the operation of the ERBE nonscanner instrument and the production of the ERBE nonscanner TOA radiation budget data set that have direct relevance to current nonscanner instrument efforts.

Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle.

Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP) causes exercise resistance through its muscle receptor low-density lipoprotein receptor-related protein 1 (LRP1). SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a) expression in skeletal muscle. Supplementation with the anti-oxidant N-acetylcysteine (NAC) reduced ROS production and the endurance capacity in SeP-deficient mice. SeP treatment impaired hydrogen-peroxide-induced adaptations through LRP1 in cultured myotubes and suppressed exercise-induced AMPK phosphorylation and Ppargc1a gene expression in mouse skeletal muscle-effects which were blunted in mice with a muscle-specific LRP1 deficiency. Furthermore, we found that increased amounts of circulating SeP predicted the ineffectiveness of training on endurance capacity in humans. Our study suggests that inhibitors of the SeP-LRP1 axis may function as exercise-enhancing drugs to treat diseases associated with a sedentary lifestyle.

Cloud Occurrences and Cloud Radiative Effects (CREs) from CCCM and CloudSat Radar-Lidar Products.

Two kinds of radar-lidar synergy cloud products are compared and analyzed in this study; CERES-CALIPSO-CloudSat-MODIS (CCCM) product and CloudSat radar-lidar (RL) product such as GEOPROF-LIDAR and FLXHR-LIDAR. Compared to GEOPROF-LIDAR, CCCM has more low-level (< 1 km) clouds over tropical oceans because CCCM uses a more relaxed threshold of Cloud-Aerosol Discrimination (CAD) score for Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical feature mask (VFM) product. In contrast, GEOPROF-LIDAR has more mid-level (1-8 km) clouds than CCCM at high latitudes (> 40°). The difference occurs when hydrometeors are detected by CALIPSO lidar but are undetected by CloudSat radar, which may be related to precipitation. In the comparison of cloud radiative effects (CREs), global mean differences between CCCM and FLXHR-LIDAR are mostly smaller than 5 W m-2, while noticeable regional differences are found over three regions. First, CCCM has larger shortwave (SW) and longwave (LW) CREs than FXLHR-LIDAR along the west coasts of Africa and America. This might be caused by missing small-scale marine boundary layer clouds in FLXHR-LIDAR. Second, over tropical oceans where precipitation frequently occurs, SW and LW CREs from FLXHR-LIDAR are larger than those from CCCM partly because FLXHR-LIDAR algorithm includes the contribution of rainwater to total liquid water path. Third, over midlatitude storm-track regions, CCCM shows larger SW and LW CREs than FLXHR-LIDAR, due to CCCM biases caused by larger cloud optical depth or higher cloud effective height.

Spectrally Dependent CLARREO Infrared Spectrometer Calibration Requirement for Climate Change Detection.

Detecting climate trends of atmospheric temperature, moisture, cloud, and surface temperature requires accurately calibrated satellite instruments such as the Climate Absolute Radiance and Reflectivity Observatory (CLARREO). Wielicki et al. have studied the CLARREO measurement requirements for achieving climate change accuracy goals in orbit. Our study further quantifies the spectrally dependent IR instrument calibration requirement for detecting trends of atmospheric temperature and moisture profiles. The temperature, water vapor, and surface skin temperature variability and the associated correlation time are derived using Modern Era Retrospective-Analysis for Research and Applications (MERRA) and European Center for Medium-Range Weather Forecasts (ECMWF) reanalysis data. The results are further validated using climate model simulation results. With the derived natural variability as the reference, the calibration requirement is established by carrying out a simulation study for CLARREO observations of various atmospheric states under all-sky. We derive a 0.04 K (k=2, or 95% confidence) radiometric calibration requirement baseline using a spectral fingerprinting method. We also demonstrate that the requirement is spectrally dependent and some spectral regions can be relaxed due to the hyperspectral nature of the CLARREO instrument. We further discuss relaxing the requirement to 0.06 K (k=2) based on the uncertainties associated with the temperature and water vapor natural variability and relatively small delay in time-to-detect for trends relative to the baseline case. The methodology used in this study can be extended to other parameters (such as clouds and CO2) and other instrument configurations.

Examining Impacts of Mass-Diameter (m-D) and Area-Diameter (A-D) Relationships of Ice Particles on Retrievals of Effective Radius and Ice Water Content from Radar and Lidar Measurements.

Mass-diameter (m-D) and projected area-diameter (A-D) relations are often used to describe the shape of nonspherical ice particles. This study analytically investigates how retrieved effective radius (r eff ) and ice water content (IWC) from radar and lidar measurements depend on the assumption of m-D [m(D) = a D b ] and A-D [A(D) = γD s ] relationships. We assume that unattenuated reflectivity factor (Z) and visible extinction coefficient (k ext ) by cloud particles are available from the radar and lidar measurements, respectively. A sensitivity test shows that r eff increases with increasing a, decreasing b, decreasing γ, and increasing δ. It also shows that a 10% variation of a, b, γ, and δ induces more than a 100% change of r eff . In addition, we consider both gamma and lognormal particle size distributions (PSDs), and examine the sensitivity of r eff to the assumption of PSD. It is shown that r eff increases by up to 10% with increasing dispersion (µ) of the gamma PSD by 2, when large ice particles are predominant. Moreover, r eff decreases by up to 20% with increasing the width parameter (ω) of the lognormal PSD by 0.1. We also derive an analytic conversion equation between two effective radii when different particle shapes and PSD assumptions are used. When applying the conversion equation to nine types of m-D and A-D relationships, r eff easily changes up to 30%. The proposed r eff -convertion method can be used to eliminate the inconsistency of assumptions that made in a cloud retrieval algorithm and a forward radiative transfer model.