Aerosol Loading and Radiation Budget Perturbations in Densely Populated and Highly Polluted Indo-Gangetic Plain by COVID-19: Influences on Cloud Properties and Air Temperature.

Aerosols emitted in densely populated and industrialized Indo-Gangetic Plain, one of the most polluted regions in the world, modulate regional climate, monsoon, and Himalayan glacier retreat. Thus, this region is important for understanding aerosol perturbations and their resulting impacts on atmospheric changes during COVID-19 lockdown period, a natural experimental condition created by the pandemic. By analyzing 5 years (2016-2020) data of aerosols and performing a radiative transfer calculation, we found that columnar and near-surface aerosol loadings decreased, leading to reductions in radiative cooling at the surface and top of the atmosphere and atmospheric warming during lockdown period. Further, satellite data analyses showed increases in cloud optical thickness and cloud-particle effective radius and decrease in lower tropospheric air temperature during lockdown period. These results indicate critical influences of COVID-19 lockdown on regional climate and water cycle over Indo-Gangetic Plain, emphasizing need for further studies from modeling perspectives.

Development of Algorithm for Discriminating Hydrometeor Particle Types with a Synergistic Use of CloudSat and CALIPSO.

We developed a method for classifying hydrometeor particle types, including cloud and precipitation phase and ice crystal habit, by a synergistic use of CloudSat/Cloud Profiling Radar (CPR) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO)/Cloud-Aerosol LIdar with Orthogonal Polarization (CALIOP). We investigated how the cloud phase and ice crystal habit characterized by CALIOP globally relate with radar reflectivity and temperature. The global relationship thus identified was employed to develop an algorithm for hydrometeor type classification with CPR alone. The CPR-based type classification was then combined with CALIPSO-based type characterization to give CPR-CALIOP synergy classification. A unique aspect of this algorithm is to exploit and combine the lidar's sensitivity to thin ice clouds and the radar's ability to penetrate light precipitation to offer more complete picture of vertically resolved hydrometeor type classification than has been provided by previous studies. Given the complementary nature of radar and lidar detections of hydrometeors, our algorithm delivers thirteen hydrometeor types: warm water, supercooled water, randomly-oriented ice crystal (3D-ice), horizontally-oriented plate (2D-plate), 3D-ice+2D-plate, liquid drizzle, mixed-phase drizzle, rain, snow, mixed-phase cloud, water+liquid drizzle, water+rain and unknown. The global statistics of three-dimensional occurrence frequency of each hydrometeor type revealed that 3D-ice contributes the most to the total cloud occurrence frequency (53.8%), followed by supercooled water (14.3%), 2D-plate (9.2%), rain (5.9%), warm water (5.7%), snow (4.8%), mixed-phase drizzle (2.3%), and the remaining types (4.0%). This hydrometeor type classification provides useful observation-based information for climate model diagnostics in representation of cloud phase and their microphysical characteristics.

Imaging mass spectrometry detects dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia.

BACKGROUND AND PURPOSE: The initial steps in the cascade leading to cell death are still unknown because of the limitations of the existing methodology, strategy, and modalities used. METHODS: Imaging mass spectrometry (IMS) was used to measure dynamic molecular changes of phosphatidylcholine (PC) species in the rat hippocampus after transient global ischemia (TGI) for 6min. Fresh frozen sections were obtained after euthanizing the rats on Days 1, 2, 4, 7, 10, 14, and 21. Histopathology and IMS of adjacent sections compared morphological and molecular changes, respectively. RESULTS: Histopathological changes were absent immediately after TGI (at Day 1, superacute phase). At Days 2-21 after TGI (from subacute to chronic phases), histopathology revealed neuronal death associated with gliosis, inflammation, and accumulation of activated microglia in CA1. IMS detected significant molecular changes after TGI in the same CA1 domain: increase of PC (diacyl-16:0/22:6) in the superacute phase and increase of PC (diacyl-16:0/18:1) in the subacute to chronic phases. CONCLUSIONS: Histopathology and IMS can provide comprehensive and complementary information on cell death mechanisms in the hippocampal CA1 after global ischemia. IMS provided novel data on molecular changes in phospholipids immediately after TGI. Increased level of PC (diacyl-16:0/22:6) in the pyramidal cell layer of hippocampal CA1 prior to the histopathological change may represent an early step in delayed neuronal death mechanisms.

Reductions of docosahexaenoic acid-containing phosphatidylcholine levels in the anterior horn of an ALS mouse model.

In this study, we analyzed the spatiotemporal alterations of phospholipid composition in the spinal cord of an amyotrophic lateral sclerosis (ALS) mouse model (G93A-mutated human superoxide dismutase 1 transgenic mice [SOD1(G93A) mice]) using imaging mass spectrometry (IMS), a powerful method to visualize spatial distributions of various types of molecules in situ. Using this technique, we deciphered the phospholipid distribution in the pre-symptomatic stage, early stage after disease onset, and terminal stages of disease in female SOD1(G93A) mouse spinal cords. These experiments revealed a significant decrease in levels of docosahexaenoic acid (DHA)-containing phosphatidylcholines (PCs), such as PC (diacyl-16:0/22:6), PC (diacyl-18:0/22:6), and PC (diacyl-18:1/22:6) in the L5 anterior horns of terminal stage (22-week-old) SOD1(G93A) mice. The reduction in PC (diacyl-16:0/22:6) level could be reflecting the loss of motor neurons themselves in the anterior horn of the spinal cord in ALS model mice. In contrast, other PCs, such as PC (diacyl-16:0/16:0), were observed specifically in the L5 dorsal horn gray matter, and their levels did not vary between ALS model mice and controls. Thus, our study showed a significant decrease in DHA-containing PCs, but not other PCs, in the terminal stage of ALS in model mice, which is likely to be a reflection of neuronal loss in the anterior horns of the spinal cords. Given its enrichment in dorsal sensory regions, the preservation of PC (diacyl-16:0/16:0) may be the result of spinal sensory neurons being unaffected in ALS. Taken together, these findings suggest that ALS spinal cords show significant alterations in PC metabolism only at the terminal stage of the disease, and that these changes are confined to specific anatomical regions and cell types.

Blockade of IL-6 signaling by MR16-1 inhibits reduction of docosahexaenoic acid-containing phosphatidylcholine levels in a mouse model of spinal cord injury.

The interleukin (IL)-6 pathway plays an important role in recovery after spinal cord injury (SCI). The anti-IL-6 receptor antibody MR16-1 has been shown to suppress inflammation after SCI and promote recovery of motor function. The purpose of this study was to analyze the effects of MR16-1 on the expression patterns of phospholipids in the spinal cord in a mouse model of SCI. Eight-week-old C57BL/6JJmsSlc mice were used in this study. Laminectomy was performed at the ninth and tenth thoracic levels (T9-T10), and contusion injury of the spinal cord was induced at level T10. Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (MR16-1 group) or a single dose of phosphate-buffered saline of the same volume (control group). Imaging mass spectrometry was performed to visualize phosphatidylcholine (PC) expression in the spinal cord 7 days after SCI. We found that MR16-1 treatment suppressed the infiltration of immune cells after SCI, and was able to increase the locomotor function post-injury. Phospholipid imaging revealed that the MR16-1 was able to prevent the reduction of docosahexaenoic acid (DHA)-containing PC in comparison with the control group. We also observed high levels of glial fibrillary acidic protein (GFAP) at the site of DHA-containing PC expression in the MR16-1 group. These results suggest that MR16-1 treatment influences the DHA-containing PC composition of GFAP-positive cells at the injury site as early as 7 days post-SCI.

(ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease.

Genetic and epidemiologic evidence suggests that cellular energy homeostasis is critically associated with Parkinson's disease (PD) pathogenesis. Here we demonstrated that genetic deletion of Poly (ADP-ribose) polymerase 1 completely blocked 6-hydroxydopamine-induced dopaminergic neurodegeneration and related PD-like symptoms. Hyperactivation of PARP-1 depleted ATP pools in dopaminergic (DA) neurons, thereby activating AMP-activated protein kinase (AMPK). Further, blockade of AMPK activation by viral infection with dominant-negative AMPK strongly inhibited DA neuronal atrophy with moderate suppression of nuclear translocation of apoptosis-inhibiting factor (AIF), whereas overactivation of AMPK conversely strengthened the 6-OHDA-induced DA neuronal degeneration. Collectively, these results suggest that manipulation of PARP-1 and AMPK signaling is an effective therapeutic approach to prevent PD-related DA neurodegeneration.

Imaging mass spectrometry reveals unique lipid distribution in primary varicose veins.

BACKGROUND: The lipid metabolism of varicose veins (VVs) remains unknown. To elucidate the pathogenesis of VV, we utilized the novel technique of imaging mass spectrometry (IMS). MATERIALS AND METHODS: We obtained VV tissues from 10 limbs of 10 VV patients who underwent great saphenous vein stripping. As control vein samples, we harvested segmental vein tissues from 6 limbs of 6 patients with peripheral artery occlusive disease who underwent infra-inguinal bypass with reversed saphenous vein grafting. To identify the localisation of lipid molecules in the VV tissues, we performed matrix-assisted laser desorption/ionization IMS (MALDI-IMS). We also performed MS/MS analyses to identify the structure of each molecule. RESULTS: We obtained mass spectra directly from control vein tissues and VV tissues and found a unique localisation of lipid molecules in the VV tissues. We localised lysophosphatidylcholine (LPC) (1-acyl 16:0), phosphatidylcholine (PC) (1-acyl 36:4) and sphingomyelin (SM) (d18:1/16:0) at the site of the VV valve. CONCLUSION: MALDI-IMS revealed the distribution of various lipid molecules in normal veins and VVs both. Accumulation of LPC (1-acyl 16:0), PC (1-acyl 36:4) and SM (d18:1/16:0) in the VV tissues suggested that inflammation associated with abnormal lipid metabolism may contribute to the development of VV.

Imaging mass spectrometry revealed the production of lyso-phosphatidylcholine in the injured ischemic rat brain.

To develop an effective neuroprotective strategy against ischemic injury, it is important to identify the key molecules involved in the progression of injury. Direct molecular analysis of tissue using mass spectrometry (MS) is a subject of much interest in the field of metabolomics. Most notably, imaging mass spectrometry (IMS) allows visualization of molecular distributions on the tissue surface. To understand lipid dynamics during ischemic injury, we performed IMS analysis on rat brain tissue sections with focal cerebral ischemia. Sprague-Dawley rats were sacrificed at 24 h after middle cerebral artery occlusion, and brain sections were prepared. IMS analyses were conducted using matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) in positive ion mode. To determine the molecular structures, the detected ions were subjected to tandem MS. The intensity counts of the ion signals of m/z 798.5 and m/z 760.5 that are revealed to be a phosphatidylcholine, PC (16:0/18:1) are reduced in the area of focal cerebral ischemia as compared to the normal cerebral area. In contrast, the signal of m/z 496.3, identified as a lyso-phosphatidylcholine, LPC (16:0), was clearly increased in the area of focal cerebral ischemia. In IMS analyses, changes of PC (16:0/18:1) and LPC (16:0) are observed beyond the border of the injured area. Together with previous reports--that PCs are hydrolyzed by phospholipase A(2) (PLA(2)) and produce LPCs,--our present results suggest that LPC (16:0) is generated during the injury process after cerebral ischemia, presumably via PLA(2) activation, and that PC (16:0/18:1) is one of its precursor molecules.

Comparison of phospholipid molecular species between terminal and stem villi of human term placenta by imaging mass spectrometry.

Placental villi play pivotal roles in the feto-maternal transportation and phospholipids constitute major part of villous membrane. However, the functional contributions as well as pathological roles of placental phospholipids are yet to be fully clarified, because tissue distribution of phospholipids in the placental villi has not been identified. Recently, we have been developing and optimizing an imaging system based on a matrix-assisted laser desorption ionization (MALDI)-based mass spectrometer, which provides clear two-dimensional molecular identification with highly sensitive mass spectrometry from mixtures of ions generated on tissue surfaces. In the present study, we applied this technology to the molecular identification of phospholipids in the human term placenta and found that sphingomyelin (d18:1/16:0) and phosphatidylcholine (16:0/20:4) were distributed differently between stem and terminal villi. This methodology detected a distinct tissue distribution of phosphatidylcholine (16:0/20:4) of terminal villi, coupling with arachidonic acid (AA), which might be a clue leading to the future investigation of the possible involvement the synthetic cascade of eicosanoids in the physiology as well as pathological development of terminal villi, such as fetal growth restriction and/or fetal hypoxia, since terminal villi plays the central roles for nutrient and oxygen supply from maternal to fetal circulation.

An internet-based wearable watch-over system for elderly and disabled utilizing EMG and accelerometer.

An effective way for preventing injuries and diseases among the elderly is to monitor their daily lives. In this regard, we propose the use of a "Hyper Hospital Network", which is an information support system for elderly people and patients. In the current study, we developed a wearable system for monitoring electromyography (EMG) and acceleration using the Hyper Hospital Network plan. The current system is an upgraded version of our previous system for gait analysis (Yoshida et al. [13], Telemedicine and e-Health 13 703-714), and lets us monitor decreases in exercise and the presence of a hemiplegic gait more accurately. To clarify the capabilities and reliability of the system, we performed three experimental evaluations: one to verify the performance of the wearable system, a second to detect a hemiplegic gait, and a third to monitor EMG and accelerations simultaneously. Our system successfully detected a lack of exercise by monitoring the iEMG in healthy volunteers. Moreover, by using EMG and acceleration signals simultaneously, the reliability of the Hampering Index (HI) for detecting hemiplegia walking was improved significantly. The present study provides useful knowledge for the development of a wearable computer designed to monitor the physical conditions of older persons and patients.

The role of silicon in preventing appressorial penetration by the rice blast fungus.

To test the hypothesis that silicon (Si) confers resistance against appressorial penetration of the rice blast fungus, the proportion of appressorial penetration into the leaf epidermis to total appressoria formed was compared among rice plants amended with various rates of silica gel to those plants nonamended. The amounts of Si in the youngest leaves were consistent with the amounts of silica gel applied to the rice plants. Relative Si levels on the adaxial surface of leaves as detected by energy dispersive X-ray analysis also increased with the amounts of silica gel applied. Based on light microscopic observation of the adaxial surface of rice leaves, the proportion of appressorial penetration was reduced by increasing amounts of silica gel applied and increased with the length of period after spray inoculation. Consequently, these results strongly support the hypothesis and suggest that Si in the leaf epidermis may confer resistance against appressorial penetration. Meanwhile, the number of lesions per leaf also decreased with the amount of Si applied, while only a certain part of penetrated appressoria could become sporulating susceptible lesions. This suggests that Si also confers physiological resistance against blast infection after the penetration.

Development of a wearable computer system with a hands-free operation interface for the use of home health caregiver.

We previously developed a network-based medical care support system called the Hyper Hospital, a computer network with an interface that is dedicated to patient care. In this study, we developed a wearable information system that is designed so that a caregiver can obtain information and control various support devices within the home-care environment. In our system, the wearable computer itself consists of a computer network built into a jacket. Each required function is implemented by a dedicated small computer connected to the in-jacket network. A new function may easily be added to the system by connecting additional computers. A network comprising such a set of single-function computers becomes a highly efficient information system when applied to health care support.

Upper bound of the expected training error of neural network regression for a Gaussian noise sequence.

In neural network regression problems, often referred to as additive noise models, NIC (Network Information Criterion) has been proposed as a general model selection criterion to determine the optimal network size with high generalization performance. Although NIC has been derived using asymptotic expansion, it has been pointed out that this technique cannot be applied under the assumption that a target function is in a family of assumed networks and the family is not minimal for representing the target true function, i.e. the overrealizable case, in which NIC reduces to the well-known AIC (Akaike Information Criterion) and others depending on a loss function. Because NIC is the unbiased estimator of generalization error based on training error, it is required to derive the expectations of errors for neural networks for such cases. This paper gives upper bounds of the expectations of training errors with respect to the distribution of training data, which we call the expected training error, for some types of networks under the squared error loss. In the overrealizable case, because the errors are determined by fitting properties of networks to noise components, including in data, the target set of data is taken to be a Gaussian noise sequence. For radial basis function networks and 3-layered neural networks with bell shaped activation function in the hidden layer, the expected training error is bounded above by sigma2* - 2nsigma2*logT/T, where sigma2* is the variance of noise, n is the number of basis functions or the number of hidden units and T is the number of data. Furthermore, for 3-layered neural networks with sigmoidal activation function in the hidden layer, we obtained the upper bound of sigma2* - O(log T/T) when n > 2. If the number of data is large enough, these bounds of the expected training error are smaller than sigma2* - N(n)sigma2*/T as evaluated in NIC, where N(n) is the number of all network parameters.

Ranitidine clearance during hemodialysis with high-flux membrane: comparison of polysulfone and cellulose acetate hemodialyzers.

OBJECTIVE: To compare the effect of hemodialysis using two different types of dialyzer membranes, polysulfone (PS), a high-flux membrane, and cuprophane (CP), a conventional membrane, on blood ranitidine concentration. BACKGROUND: Recent advances in hemodialyzer membranes have improved the removal of small and middle size uremic toxins, while little is known about the change of drug removal by new membranes. METHODS: Eight patients with chronic renal failure who received ranitidine (150 mg/day) on a chronic basis were included. During the dialysis, blood samples were obtained from both the arterial and venous sides (before and after, respectively) of the dialyzer. RESULTS: Serum concentration of ranitidine decreased more on PS [54 +/- 3% (+/- SEM) reduction after 3 h] than on CP (35 +/- 4%). The dialyzer clearance of ranitidine on PS membrane (67.2 +/- 4.4 ml/min/m2) was significantly higher than that on CP (43.1 +/- 3.8 ml/min/m2, P < 0.001). Elimination fraction (EF) of the drug during the dialysis with PS was also significantly higher than that with CP (72 +/- 2% versus 44 +/- 3%). Apparent half-life of ranitidine during dialysis with PS (2.9 +/- 0.4 h) was shorter than that with CP (5.1 +/- 0.7 h). However, the amount of ranitidine removed by a single dialysis with PS membrane was less than 20 mg. CONCLUSION: Ranitidine clearance by hemodialysis is significantly higher with PS than with CP. Although additional dose adjustment may not be needed for ranitidine, the type of dialyzer membrane can affect drug elimination and should be taken into account for consideration of drug removal by hemodialysis.

Optical properties and size distribution of aerosols derived from simultaneous measurements with lidar, a sunphotometer, and an aureolemeter.

A new method is proposed to derive the optical properties and size distribution of aerosol in an air column from simultaneous measurements of the backscattering coefficient, the optical thickness, and the solar aureole intensity with lidar, a sunphotometer, and an aureolemeter. Inasmuch as the backscattering properties and the optical thickness depend on both the complex refractive index and the size distribution, whereas the forward-scattering properties depend mainly on the size distribution, real and imaginary indices of refraction and size distributions of aerosol are retrieved from these measurements. The real and the imaginary parts of the complex refractive index of an aerosol at a wavelength of 500 nm during the period from November 1991 to March 1992 obtained in Tsukuba, Japan, were estimated to be 1.46-1.48 and 0.005-0.014, respectively. It is inferred from the size distribution and an optical thickness fraction of stratospheric aerosols in the total columnar aerosols that these results reflect the influences of stratospheric aerosols that originated from the Mt. Pinatubo eruption.

Stratification and Size Distribution of Aerosols Retrieved from Simultaneous Measurements with Lidar, a SunPhotometer, and an Aureolemeter.

Vertical profiles of backscattering coefficients, optical thicknesses, and columnar size distributions of aerosols were obtained by simultaneous measurements with lidar, a sunphotometer, and an aureolemeter in Tsukuba, Japan, from November 1991 to December 1992. Several conspicuous characteristics were found in the relationship between aerosol size distribution and stratification. In summer an accumulation mode is dominant, and aerosols were heavily loaded in the planetary boundary layer. Turbid atmospheres with an abundance of large particles are observed in the middle troposphere in the spring. In autumn and winter the troposphere is clear so that columnar aerosol size distributions reflect stratospheric aerosols. During the observation period, volcanic aerosols that are due to the Mt. Pinatubo eruption were being loaded in the stratosphere. The mode radius in the volume size distribution of the stratospheric aerosol was observed to increase from 0.45 mum in November 1991 to 0.6 mum in October 1992, and decreased after October 1992. Total aerosol loading in the stratosphere was estimated to be maximum in the spring of 1992, minimum in the autumn of 1992, and increased again after the autumn of 1992.

Simultaneous determination of the aerosol complex index of refraction and size distribution from scattering measurements of polarized light.

In this study we attempt to determine the aerosol complex index of refraction and size distribution from scattering measurements of polarized light. We illustrate that the scattering matrix elements M(2)(100 degrees ) and D(21) (150 degrees ) can be selected as an optimum set of matrix elements for determination of the complex index of refraction. We also illustrate that errors increase if we include insensitive scattering matrix elements in the determination of the complex index of refraction. A method is developed for the simultaneous determination of the complex index of refraction and the size distribution. In our method, we selected two sets of matrix elements, M (2) (100 degrees ) and D (21) (150 degrees ), for the determination of the complex index of refraction and others, which are much less sensitive to the complex index of refraction than M(2) (100 degrees ) and D(21) (150 degrees ), for the determination of the size distribution, based on their sensitivity analyses. A modified inversion library algorithm is adopted to solve the coupled system. Numerical experiments show that both the complex index of refraction and the size distribution can be determined with reasonable accuracy when we apply our method to scattering measurements of polarized light.

[MR venography using 3D-fast STIR sequence for lower extremities].

Venography of the lower extremities performed by injecting iodinated contrast material requires a complicated technique. Veins of lower-flow-speed such as varices are scarcely outlined by using the time-of-flight MR angiography technique. On the other hand, the 2D fast SE technique has proven itself unsuccessful when used with medium magnetic field MRI equipment in which a very long TR is unavailable. We obtained images of lower extremity veins by using the 3D fast STIR technique and medium magnetic field MRI equipment of 0.5 Tesla. The results were crisp angiographic images of lower-flow-speed veins including varices.