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Aim: To describe the genomic characteristics of seawater-borne hemolytic Shewanella algae and its resistance genes. Materials & methods: Whole genome sequence of S. algae SYT3 was determined using llumina MiSeq platform. Multiple-database-based analysis was performed to identify the genetic background of its hemolytic activity and the antibiotic resistance genes. Results: S. algae SYT3 possesses a homolog of the hly operon involved in the synthesis of hemolysin. We also identified candidate genes associated with resistance to β-lactam antibiotics (bla OXA-55) and fluoroquinolone (qnrA3). Conclusion: The study provides an insight into the hemolytic activity of S. algae. Our findings also suggested S. algae as a potential reservoir of antimicrobial resistance determinants.

Observations of atmospheric carbon monoxide (CO) can only be made on continental and global scales by remote sensing instruments situated in space. One such instrument is the Infrared Atmospheric Sounding Interferometer (IASI), producing spectrally resolved, top-of-atmosphere radiance measurements from which CO vertical layers and total columns can be retrieved. This paper presents a technique for intercomparisons of satellite data with low vertical resolution. The example in the paper also generates the first intercomparison between an IASI CO data set, in this case that produced by the University of Leicester IASI Retrieval Scheme (ULIRS), and the V3 and V4 operationally retrieved CO products from the Measurements Of Pollution In The Troposphere (MOPITT) instrument. The comparison is performed for a localised region of Africa, primarily for an ocean day-time configuration, in order to develop the technique for instrument intercomparison in a region with well defined a priori. By comparing both the standard data and a special version of MOPITT data retrieved using the ULIRS a priori for CO, it is shown that standard intercomparisons of CO are strongly affected by the differing a priori data of the retrievals, and by the differing sensitivities of the two instruments. In particular, the differing a priori profiles for MOPITT V3 and V4 data result in systematic retrieved profile changes as expected. An application of averaging kernels is used to derive a difference quantity which is much less affected by smoothing error, and hence more sensitive to systematic error. These conclusions are confirmed by simulations with model profiles for the same region. This technique is used to show that for the data that has been processed the systematic bias between MOPITT V4 and ULIRS IASI data, at MOPITT vertical resolution, is less than 7 % for the comparison data set, and on average appears to be less than 4 %. The results of this study indicate that intercomparisons of satellite data sets with low vertical resolution should ideally be performed with: retrievals using a common a priori appropriate to the geographic region studied; the application of averaging kernels to compute difference quantities with reduced a priori influence; and a comparison with simulated differences using model profiles for the target gas in the region.

We use GPS radio occultation (RO) data to investigate the structure and temporal behavior of extremely dry, high-ozone tropospheric air in the tropical western Pacific during the 6-week period of the CONTRAST (CONvective TRansport of Active Species in the Tropics) experiment (January and February 2014). Our analyses are aimed at testing whether the RO method is capable of detecting these extremely dry layers and evaluating comparisons with in situ measurements, satellite observations, and model analyses. We use multiple data sources as comparisons, including CONTRAST research aircraft profiles, radiosonde profiles, AIRS (Atmospheric Infrared Sounder) satellite retrievals, and profiles extracted from the ERA (ERA-Interim reanalysis) and the GFS (US National Weather Service Global Forecast System) analyses, as well as MTSAT-2 satellite images. The independent and complementary radiosonde, aircraft, and RO data provide high vertical resolution observations of the dry layers. However, they all have limitations. The coverage of the radiosonde data is limited by having only a single station in this oceanic region; the aircraft data are limited in their temporal and spatial coverage; and the RO data are limited in their number and horizontal resolution over this period. However, nearby observations from the three types of data are highly consistent with each other and with the lower-vertical-resolution AIRS profiles. They are also consistent with the ERA and GFS data. We show that the RO data, used here for the first time to study this phenomenon, contribute significant information on the water vapor content and are capable of detecting layers in the tropics and subtropics with extremely low humidity (less than 10 %), independent of the retrieval used to extract moisture information. Our results also verify the quality of the ERA and GFS data sets, giving confidence to the reanalyses and their use in diagnosing the full four-dimensional structure of the dry layers.

The spatial and temporal variability of the marine boundary layer (MBL) over the southeastern Pacific is studied using high-resolution radiosonde data from the VAMOS Ocean–Cloud–Atmosphere–Land Study Regional Experiment (VOCALS-REx), lidar cloud measurements from the CALIOP instrument on the CALIPSO satellite, radio occultation (RO) data from the COSMIC satellites, and the ERA-Interim. The height of the MBL (MBLH) is estimated using three RO-derived parameters: the bending angle, refractivity, and water vapor pressure computed from the refractivity derived from a one-dimensional variational data inversion (1D-VAR) procedure. Two different diagnostic methods (minimum gradient and break point method) are compared. The results show that, although a negative bias in the refractivity exists as a result of superrefraction, the spatial and temporal variations of the MBLH determined from the RO observations are consistent with those from CALIOP and the radiosondes. The authors find that the minimum gradient in the RO bending angle gives the most accurate estimation of the MBL height.

We use the NCAR TIEGCM (Thermosphere Ionosphere Electrodynamics General Circulation Model) model to investigate the eddy diffusion and tidal effects on the ionosphere SAO (semiannual oscillation). We also use the COSMIC (Constellation Observing System for Meteorology, Ionosphere, and Climate) satellite GPS radio occultation (RO) observations to validate the simulation results. The TIEGCM is driven at the 97 km lower boundary by tidal and gravity wave (eddy diffusion coefficient) inputs. The eddy diffusion input can be constant or with a SAO modulation [Qian et al., 2009] and the tidal input has on and off options. The TIEGCM simulation with a SAO modulated eddy diffusion (with tidal input) agrees better with the COSMIC observation than that without the SAO. Turning off the tides at the lower boundary makes the TIEGCM simulated ionospheric density much higher than the COSMIC observation. The simulations showed two results: 1) the need to add the SAO modulation to the eddy diffusion, and 2) how tides reduce the ionospheric density and SAO. As to how much of the SAO should be added to the eddy diffusion is dependent on the amplitudes of the tides since both can have effects on the ionospheric density. The TIEGCM results also demonstrate that the ionospheric density diurnal signal is mostly in-situ excited, while the semidiurnal signal comes from lower atmosphere.

We compare atmospheric total precipitable water (TPW) derived from the SSM/I (Special Sensor Microwave Imager) and SSMIS (Special Sensor Microwave Imager/Sounder) radiometers and WindSat to collocated TPW estimates derived from COSMIC (Constellation System for Meteorology, Ionosphere, and Climate) radio occultation (RO) under clear and cloudy conditions over the oceans from June 2006 to December 2013. Results show that the mean microwave (MW) radiometer – COSMIC TPW differences range from 0.06 to 0.18 mm for clear skies, from 0.79 to 0.96 mm for cloudy skies, from 0.46 to 0.49 mm for cloudy but non-precipitating conditions, and from 1.64 to 1.88 mm for precipitating conditions. Because RO measurements are not significantly affected by clouds and precipitation, the biases mainly result from MW retrieval uncertainties under cloudy and precipitating conditions. All COSMIC and MW radiometers detect a positive TPW trend over these 8 years. The trend using all COSMIC observations collocated with MW pixels for this data set is 1.79 mm decade−1, with a 95 % confidence interval of (0.96, 2.63), which is in close agreement with the trend estimated by the collocated MW observations (1.78 mm decade−1 with a 95 % confidence interval of 0.94, 2.62). The sample of MW and RO pairs used in this study is highly biased toward middle latitudes (40–60∘ N and 40–65∘ S), and thus these trends are not representative of global average trends. However, they are representative of the latitudes of extratropical storm tracks and the trend values are approximately 4 to 6 times the global average trends, which are approximately 0.3 mm decade−1. In addition, the close agreement of these two trends from independent observations, which represent an increase in TPW in our data set of about 6.9 %, are a strong indication of the positive water vapor–temperature feedback on a warming planet in regions where precipitation from extratropical storms is already large.

The effect of quasi-biennial oscillation (QBO) on the temperature of cold point tropopause (T-CPT) and its height (H-CPT) is being investigated using radio occultation measurements by COSMIC/FORMOSAT-3. Observations comprising of 935,863 numbers of occultations have been used to study the zonal mean seasonal variability in T-CPT and H-CPT from January 2007 to December 2011. Results are shown over 30°N–30°S geographic latitudes. In general, T-CPT is found to be the coldest in February and the warmest in August. H-CPT attains maximum height during December–February and minimum during July–August. Interestingly, H-CPT shows maxima at off-equator region (around 20°N or 20°S) during all the seasons in both hemispheres. H-CPT at off-equatorial region, in reference to the equatorial region, is slightly higher (~ 1.0 km) during winter as compared to monsoon season (~ 0.5 km) in Northern Hemisphere (NH). Inter-annual variation in T-CPT and H-CPT found to be clearly influenced by the QBO. Westerly (easterly) phase generates warm (cold) T-CPT, which consequently results a decrease (increase) in H-CPT. It is concluded that QBO induces the changes in T-CPT by as much as 2 °C and in H-CPT by 0.5 km.

The Global Navigation Satellite System (GNSS) Radio Occultation (RO) is a key technique for obtaining thermodynamic profiles of temperature, humidity, pressure, and density in the Earth’s troposphere. However, due to refraction effects of both the dry air and water vapor at low altitudes, retrieval of accurate profiles is challenging. Here we introduce a new moist air retrieval algorithm aiming to improve the quality of RO-retrieved profiles in moist air and including uncertainty estimation in a clear sequence of steps. The algorithm first uses RO dry temperature and pressure and background temperature/humidity and their uncertainties to retrieve humidity/temperature and their uncertainties. These temperature and humidity profiles are then combined with their corresponding background profiles by optimal estimation employing inverse-variance weighting. Finally, based on the optimally estimated temperature and humidity profiles, pressure and density profiles are computed using hydrostatic and equation-of-state formulas. The input observation and background uncertainties are dynamically estimated, accounting for spatial and temporal variations. We show results from applying the algorithm on test datasets, deriving insights from both individual profiles and statistical ensembles, and from comparison to independent 1D-Variational (1DVar) algorithm-derived moist air retrieval results from Radio Occultation Meteorology Satellite Application Facility Copenhagen (ROM-SAF) and University Corporation for Atmospheric Research (UCAR) Boulder RO processing centers. We find that the new scheme is comparable in its retrieval performance and features advantages in the integrated uncertainty estimation that includes both estimated random and systematic uncertainties and background bias correction. The new algorithm can therefore be used to obtain high-quality tropospheric climate data records including uncertainty estimation.

[1] Radio occultation (RO) observations of precipitable water (PW) from the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) are compared with ground-based Global Positioning System (GPS) PW for 6 years (2007–2012). From comparisons of more than 120,000 collocated samples, differences in PW between RO and GPS exhibit a standard deviation of less than 3 mm with a global correlation of 0.96 to 0.97. The monthly mean RO PW is also compared to the National Centers for Environmental Prediction (NCEP) reanalyses. PWs over land for RO, GPS, and reanalyses are highly correlated in each hemisphere. We also used the RO data to explore the variation of the monthly mean PW in four regions (Tibetan Plateau, central Australia, Amazon Basin, and central Africa) where ground stations are few. This study highlights the characteristics of these PW climatologies, suggesting that the RO data are useful complements to global reanalyses and other data sets.

[1] Precipitable water (PW) retrievals from FORMOSAT-3/Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) Global Positioning System (GPS) radio occultation (RO) measurements were analyzed and compared with those derived from Special Sensor Microwave/Imager (SSM/I) and Advanced Microwave Scanning Radiometer for Earth Observation System (AMSR-E) during the El Nino-Southern Oscillation (ENSO) events from 2007 to 2011. For the three ENSO events in 2007–2011, monthly mean binned COSMIC PW results are in a very high correlation (up to 0.98) with those of SSM/I and AMSR-E over the ocean, generally with root-mean-square differences less than 4 mm. PW retrievals from the three satellites are also of similar latitudinal variations. However, the PW is slightly underestimated by GPS RO, in particular, in the tropical regions. This underestimate may be caused partially by the fact that not all RO measurements can reach the surface. Inter-satellite PW anomaly comparisons for the winter months in the ENSO events, with respect to those during the neutral (non-ENSO) months, show consistent ENSO signals with major PW anomaly near the central Pacific in the warm event and near the Indonesian region and east of Australia in the two cold events. However, the 2007/2008 La Nina is somewhat less correlated for COSMIC with AMSR-E and SSM/I. For the stronger 2010/2011 La Nina, their PW anomalies are in higher correlations of about 0.8.

[1] The accurate determination of tropical cyclone (TC) cloud-top height and its vertical thermal structure using the GPS radio occultation (RO) technique is demonstrated in this study. Cloud-top heights are determined by using the bending angle anomaly and the temperature anomaly profiles during the TC events, and the results are compared to near-coincident cloud-top heights determined by Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements. Based on 34 closely located RO-CALIOP pairs during 2006 to 2009, TC cloud-top heights from RO are highly correlated with CALIOP (r = 0.84), with a mean RO-CALIOP cloud-top height difference of approximately 500 m and a root-mean-square difference near 1 km. GPS RO data also allow analysis of the TC thermal structure, showing warm anomalies in the middle troposphere and cold anomalies in the upper levels, with a strong inversion near cloud top. We further investigate the thermal structure of the TCs from collocated radiosondes, and identify 246 RO-radiosonde pairs from 2001 to 2009. Radiosonde data confirm the thermal structure identified in GPS RO, with a strong inversion near the inferred cloud top. The mean difference between RO-derived inversion heights and those from radiosonde temperature profiles is approximately 500 m. Results show that, while cloud-top height detected from nadir-viewing satellites can be easily biased by a few kilometers, the biases of RO-derived cloud-top height are within ~500 m.

Epstein-Barr virus (EBV) is a ubiquitous human oncovirus. Previous studies by us and others have indicated that pet dogs frequently encounter EBV or EBV-related viral infection. In this study, we explored whether EBV is involved in canine malignancies in dogs. EBV-specific BamHI W sequence was detected by polymerase chain reaction (PCR) in 10 of 12 canine tumor specimens, including 8 of 10 oral tumors. Using reverse transcription-PCR, gene expressions of latent membrane protein 1 (LMP 1) and BamHI H rightward reading frame 1 (BHRF1) were identified in 8 and 7 of 12 specimens, respectively. A novel LMP1 variant, T0905, was predominant in 5 canine tumor specimens and found to exist in EBV positive human BC-2 cells. Another LMP1 variant, T0902, was similar to human tumor variant JB7. The BHRF1 sequence identified from these canine tumors was identical to that of the B95-8 viral strain. LMP1 protein and EBV-encoded RNA (EBER) were detected by immunohistochemistry and fluorescent in situ hybridization, respectively, in several tumors, particularly in tumor nests of oral amelanotic melanomas. Furthermore, EBV-like virions adopting a herpesvirus egress pathway were detected in a canthal fibroblastic osteosarcoma and an oral amelanotic melanoma. In conclusion, we report the expressions of BHRF1 transcript (a viral anti-apoptotic protein), LMP1 (a viral oncoprotein) transcript and protein, EBER (a viral oncogenic RNA), and EBV-like virions in multiple canine tumors. The identity of BHRF1 and the resemblance of LMP1 variants between canine and human tumors indicate either a close evolutionary relationship between canine and human EBV, or the possibility of zoonotic transmission.

Radiosonde observations (RAOBs) have provided the only long-term global in situ temperature measurements in the troposphere and lower stratosphere since 1958. In this study, we use consistently reprocessed Global Positioning System (GPS) radio occultation (RO) temperature data derived from COSMIC and Metop-A/GRAS missions from 2006 to 2014 to characterize the inter-seasonal and inter-annual variability of temperature biases in the lower stratosphere for different sensor types. The results show that the RAOB temperature biases for different RAOB sensor types are mainly owing to i) uncorrected solar zenith angle dependent errors, and ii) change of radiation correction. The mean daytime temperature difference (ΔT) for Vaisala RS92 is equal to 0.18 K in Australia, 0.20 K in Germany, 0.10 K in Canada, 0.13 K in England, and 0.33 K in Brazil. The mean daytime ΔT is equal to −0.06 K for Sippican, 0.71 K for VIZ-B2, 0.66 K for AVK-MRZ, and 0.18 K for Shanghai. The daytime trend of anomalies for Vaisala RS92 and RO temperature at 50 hPa is equal to 0.00 K/5 yrs over United States, −0.02 K/5 yrs over Germany, 0.17 K/5 yrs over Australia, 0.23 K/5 yrs over Canada, 0.26 K/5 yrs over England, and 0.12 K/5 yrs over Brazil, respectively. Although there still exist uncertainties for Vaisala RS92 temperature measurements over different geographical locations, the global trend of temperature anomaly between Vaisala RS92 and RO from June 2006 to April 2014 is within +/−0.09 K/5 yrs globally. Comparing with Vaisala RS80, Vaisala RS90 and sondes from other manufacturers, the Vaisala RS92 seems to provide the best RAOB temperature measurements, which can potentially be used to construct long term temperature CDRs. Results from this study also demonstrate the feasibility to use RO data to correct RAOB temperature biases for different sensor types.

We use GPS Radio Occultation (RO) data to investigate the structure and temporal behavior of extremely dry, high-ozone tropospheric air in the Tropical Western Pacific during the six-week period of the CONTRAST (CONvective TRansport of Active Species in the Tropics) experiment (January and February 2014). Our analyses are aimed at testing if the RO method is capable of detecting these extremely dry layers, and evaluating comparisons with in situ measurements, satellite observations, and model analyses. We use multiple data sources as comparisons, including CONTRAST research aircraft profiles, radiosonde profiles, AIRS (Atmospheric Infrared Sounder) satellite retrievals, and profiles extracted from the ERA (ERA-Interim Reanalysis) and the GFS (US National Weather Service Global Forecast System) analyses, as well as MTSAT-2 satellite images. The independent and complementary radiosonde, aircraft, and RO data provide high vertical resolution observations of the dry layers. However, they all have limitations. The coverage of the radiosonde data is limited by having only a single station in this oceanic region; the aircraft data are limited in their temporal and spatial coverage; and the RO data are limited in their number and horizontal resolution over this period. However, nearby observations from the three types of data are highly consistent with each other and with the lower-vertical resolution AIRS profiles. They are also consistent with the ERA and GFS data. We show that the RO data, used here for the first time to study this phenomenon, contribute significant information on the water vapor content and are capable of detecting layers in the tropics and subtropics with extremely low humidity (less than 10 %), independent of the retrieval used to extract moisture information. Our results also verify the quality of the ERA data set, giving confidence to the reanalysis and its use in diagnosing the full four-dimensional structure of the dry layers.

Background In humans, the presence of antiphospholipid antibodies (aPL) is frequently found in immune thrombocytopenia. The present study investigated whether aPL and any aPL subtypes are associated with canine thrombocytopenia, in particular, immune-mediated thrombocytopenia (immune thrombocytopenia) that usually manifests with severe thrombocytopenia. Results Sera were collected from 64 outpatient dogs with thrombocytopenia (Group I, platelet count 0 – 80 × 103/uL), and 38 of which having severe thrombocytopenia (platelet count

A project for deriving temperature and humidity profiles from High-resolution Infrared Radiation Sounder (HIRS) observations is underway to build a long-term dataset for climate applications. The retrieval algorithm development of the project includes a neural network retrieval scheme, a two-tiered cloud screening method, and a calibration using radiosonde and Global Positioning System Radio Occultation (GPS RO) measurements. As atmospheric profiles over high surface elevations can differ significantly from those over low elevations, different neural networks are developed for three classifications of surface elevations. The significant impact from the increase of carbon dioxide in the last several decades on HIRS temperature sounding channel measurements is accounted for in the retrieval scheme. The cloud screening method added one more step from the HIRS-only approach by incorporating the Advanced Very High Resolution Radiometer (AVHRR) observations to assess the likelihood of cloudiness in HIRS pixels. Calibrating the retrievals with radiosonde and GPS RO reduces biases in retrieved temperature and humidity. Except for the lowest pressure level which exhibits larger variability, the mean biases are within ±0.3 °C for temperature and within ±0.2 g/kg for specific humidity at standard pressure levels, globally. Overall, the HIRS temperature and specific humidity retrievals closely align with radiosonde and GPS RO observations in providing measurements of the global atmosphere to support other relevant climate dataset development.

BACKGROUND Statins have therapeutic benefits for the management of several disorders. A short-term course of a high-dose statin pretreatment has demonstrated neuroprotective effects against neurological diseases. However, the molecular basis underlying the neuroprotective action of statins remains unclear. OBJECTIVE We investigated whether a short-term course of high-dose atorvastatin pretreatment has beneficial effects in protecting sciatic nerve from crush injury. METHODS Atorvastatin (5 mg/kg) or saline was given orally to Sprague-Dawley rats for 7 days before injury. The rats were subjected to crush injury in the left sciatic nerve with a vessel clamp. Biochemical, functional, electrophysiological, and morphological alterations occurring during injury-induced degeneration/regeneration were examined. RESULTS Atorvastatin improved injury-induced neurobehavioral/electrophysiological changes and axonal loss. Damage-associated alterations, including structural disruption, oxidative stress, inflammation, and apoptosis, were attenuated by atorvastatin. After injury, regeneration-associated genes, including growth-associated protein-43, myelin basic protein, ciliary neurotrophic factor, and collagen, were upregulated by atorvastatin. The suppression of extracellular signal-regulated kinase, AKT, signal transducer and activators of transcription-1, and necrosis factor-kappaB and the elevated activation of c-Jun N-terminal kinase, Smad2/3, and activating protein-1 were associated with the neuroprotective action of atorvastatin. CONCLUSION These findings suggest that a short-term course of high-dose atorvastatin pretreatment can protect against sciatic nerve crush injury through modifying intracellular or extracellular environments, making it favorable for regeneration.

In this study, we compare specific humidity profiles derived from Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) from August to November 2006 with those from different types of radiosonde and from ECMWF global analysis. Comparisons show that COSMIC specific humidity data agree well with ECMWF analysis over different regions of the world for both day and night times. On the contrary, evaluation against COSMIC specific humidity shows a distinct dry bias of Shang-E radiosonde (China) and an obvious wet bias of VIZ-type (USA). No obvious specific humidity biases are found for MRZ (Russia) and MEISEI (Japan) radiosondes. These results demonstrate the usefulness of COSMIC water vapor for quantifying the dry/wet biases among different sensor types.

Object Human amniotic fluid–derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regeneration capacity. The present study evaluates whether the transplantation of glia cell line–derived neurotrophic factor (GDNF)–modified human AFMSCs may enhance regeneration of sciatic nerve after a crush injury. Methods Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. Either GDNF-modified human AFMSCs or human AFMSCs were embedded in Matrigel and delivered to the injured nerve. Motor function and electrophysiological studies were conducted after 1 and 4 weeks. Early or later nerve regeneration markers were used to evaluate nerve regeneration. The expression of GDNF in the transplanted human AFMSCs and GDNF-modified human AFMSCs was monitored at 7-day intervals. Results Human AFMSCs were successfully transfected with adenovirus, and a significant amount of GDNF was detected in human AFMSCs or the culture medium supernatant. Increases in the sciatic nerve function index, the compound muscle action potential ratio, conduction latency, and muscle weight were found in the groups treated with human AFMSCs or GDNF-modified human AFMSCs. Importantly, the GDNF-modified human AFMSCs induced the greatest improvement. Expression of markers of early nerve regeneration, such as increased expression of neurofilament and BrdU and reduced Schwann cell apoptosis, as well as late regeneration markers, consisting of reduced vacuole counts, increased expression of Luxol fast blue and S100 protein, paralleled the results of motor function. The expression of GDNF in GDNF-modified human AFMSCs was demonstrated up to 4 weeks; however, the expression decreased over time. Conclusions The GDNF-modified human AFMSCs appeared to promote nerve regeneration. The consecutive expression of GDNF was demonstrated in GDNF-modified human AFMSCs up to 4 weeks. These findings support a nerve regeneration scenario involving cell transplantation with additional neurotrophic factor secretion.

Purpose Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Methods Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Results Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. Conclusion AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

The radio occultation (RO) technique, which makes use of radio signals transmitted by the global positioning system (GPS) satellites, has emerged as a powerful and relatively inexpensive approach for sounding the global atmosphere with high precision, accuracy, and vertical resolution in all weather and over both land and ocean. On 15 April 2006, the joint Taiwan-U.S. Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC)/Formosa Satellite Mission 3 (COSMIC/FORMOSAT-3, hereafter COSMIC) mission, a constellation of six microsatellites, was launched into a 512-km orbit. After launch the satellites were gradually deployed to their final orbits at 800 km, a process that took about 17 months. During the early weeks of the deployment, the satellites were spaced closely, offering a unique opportunity to verify the high precision of RO measurements. As of September 2007, COSMIC is providing about 2000 RO soundings per day to support the research and operational communities. COSMIC RO dat...

Amniotic fluid mesenchymal stem cells have the ability to secrete neurotrophic factors that are able to promote neuron survival in vitro. The purpose of this study was to evaluate the effects of neurotrophic factors secreted by rat amniotic fluid mesenchymal stem cells on regeneration of sciatic nerve after crush injury. Fifty Sprague-Dawley rats weighing 250-300 g were used. The left sciatic nerve was crushed with a vessel clamp. Rat amniotic fluid mesenchymal stem cells embedded in fibrin glue were delivered to the injured nerve. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect neurotrophic factors secreted by the amniotic fluid mesenchymal stem cells. Nerve regeneration was assessed by motor function, electrophysiology, histology, and immunocytochemistry studies. Positive CD29/44, and negative CD11b/45, as well as high levels of expression of brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, ciliary neurotrophic factor (CNTF), nerve growth factor, and neurotrophin-3 (NT-3) were demonstrated in amniotic fluid mesenchymal stem cells. Motor function recovery, the compound muscle action potential, and nerve conduction latency showed significant improvement in rats treated with amniotic fluid mesenchymal stem cells. ELISA measurement in retrieved nerves displayed statistically significant elevation of CNTF and NT-3. The immunocytochemical studies demonstrated positive staining for NT-3 and CNTF in transplanted cells. The histology and immunocytochemistry studies revealed less fibrosis and a high level of expression of S-100 and glial fibrillary acid protein at the crush site. Rat amniotic fluid mesenchymal stem cells may facilitate regeneration in the sciatic nerve after crush injury. The increased nerve regeneration found in this study may be due to the neurotrophic factors secreted by amniotic fluid mesenchymal stem cells.

Accurate temperature and water vapor profiles in the middle and lower troposphere (LT) are crucial for understanding the water cycle, cloud systems, and energy balance. Global positioning system (GPS) radio occultation (RO) is the first technique that can provide a high-vertical-resolution all-weather refractivity profile, which is a function of pressure, temperature, and moisture. However, in the moist LT over the Tropics, the refractivity retrievals from GPS RO data are often significantly negatively biased because of tracking errors and propagation effects related to sharp vertical moisture gradients that may result in superrefraction (SR). The Atmospheric Infrared Sounder (AIRS) is a nadir-viewing sounder that can measure vertical temperature and moisture profiles with about 1–2-km vertical resolution. However, AIRS observations cannot usually obtain accurate temperature and water vapor profiles in the planetary boundary layer (PBL) because of the poor resolving power in the LT. This study uses simulations based on radiosonde profiles by combining the AIRS and the GPS RO measurements to obtain the best temperature and moisture retrievals in the LT. Different approaches are used for the drier LT and the moist LT. For the drier LT, where GPS RO data are not affected by SR errors, a multivariable regression algorithm for inverting the combined AIRS and GPS RO measurements is used. In the moist LT (e.g., SR on top of PBL), the combined AIRS and GPS RO regression inversion above the LT is used as the first guess for AIRS-only physical retrieval, which is extended into the LT. The results show that combining AIRS and GPS RO data effectively constrains the individual solutions, and therefore significantly improves inversion results. The algorithm is also applied for all available radiosonde profiles (19 profiles) over a 1-month period from the site characterized by strong SR on top of the PBL. Retrieved temperature and water vapor profiles yield unbiased low-resolution refractivity profiles in the PBL.

To understand the effect of thuringiensin on the lungs tissues, male Sprague-Dawley rats were administrated with thuringiensin by intratracheal instillation at doses 0.8, 1.6 and 3.2 mg/kg of body weight, respectively. The rats were sacrificed 4 h after treatment, and lungs were isolated and examined. Subsequently, an effective dose of 1.6 mg/kg was selected for the time course study (4, 8, 12, and 24 h). Intratracheal instillation of thuringiensin resulted in lung damage, as evidenced by increase in lung weight and decrease in alkaline phosphatase (10-54%), an enzyme localized primarily in pulmonary alveolar type II epithelial cells. Furthermore, the administration of thuringiensin caused increases in lipid peroxidation (21-105%), the indices of lung injury. In addition, the superoxide dismutase (SOD) and glutathione (GSH) activities of lung tissue extracts were measured to evaluate the effect of thuringiensin on antioxidant defense system. The SOD activity and GSH content in lung showed significant decreases in a dose-related manner with 11-21% and 15-37%, respectively. Those were further supported by the release of proinflammatory cytokines, as indicated by increases in IL-1beta (229-1017%) and TNF-alpha (234%) levels. Therefore, the results demonstrated that changes in the pulmonary oxidative-antioxidative status might play an important role in the thuringiensin-induced lung injury.

The purpose of this work is to evaluate the effect of thuringiensin on the adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3'5'-monophosphate (cAMP) levels were shown to be dose-dependently elevated 17-450% or 54-377% by thuringiensin at concentrations of 10 microM-100 mM or 0.5-4 mM, due to the activation of basal adenylate cyclase activity of rat cerebral cortical membrane preparation. Thuringiensin also activated basal activity of a commercial adenylate cyclase from Escherichia coli. However, the forskolin-stimulated adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin at concentrations of 1-100 microM, thus cAMP production decreased. Furthermore, thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin (10 microM)-stimulated adenylate cyclase activity at concentrations of 10 microM, 49% or 43% inhibition, respectively. In conclusion, this study demonstrated that thuringiensin could activate basal adenylate cyclase activity and increase cAMP concentrations in rat cerebral cortex or in a commercial adenylate cyclase. Comparing the dose-dependent effects of thuringiensin on the basal and forskolin-stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate cyclase.

The purpose of this work is to evaluate the pulmonary toxicity of purified thuringiensin in Sprague–Dawley rats. Rats were intratracheally instillated with 0, 0.4, 0.8, 1.6, 3.2, 6.4 and 9.6 mg/kg body weight of thuringiensin. The results indicated that the acute pulmonary LD 50 of thuringiensin for rats was 4.4 mg/kg. The total number of inflammatory cells and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage (BAL) fluid increased in a dose-dependent manner after thuringiensin instillation. Furthermore, an effective dose of 1.6 mg/kg was selected for the time course study of pulmonary toxicity. The treated animals showed a significant increase in the weights of the lungs, hydroxyproline levels in the lungs and total number of cells in BAL fluid 2, 4, 7, 14, 28 and 56 days after treatment. In comparison with the control, the total protein concentrations in BAL fluid were increased by 361, 615, 116, 41, 34 and 41%, after 2, 4, 7, 14, 28 and 56 days, respectively. The LDH activity in BAL fluid showed a significant increase after 1, 2, 4, 7, 14, 28 and 56 days. The increases in fibronectin levels were 164, 552, 490, 769, 335, 257 and 61% at the corresponding times, but neither tumor necrosis factor nor interleukin-1 increased. The treated rats presented abnormal histology including distributed inflammation in the bronchioles and alveoli, bronchial cellular necrosis on days 1 and 2, and areas of septal thickening with cellular infiltration and collagen deposit in the intestinal and alveolar spaces on days 4–56. Based on these biochemical and pathological parameters, intratracheal instillation of purified thuringiensin might cause significant pulmonary toxicity in rats.

Endoscopic argon plasma coagulation (APC) and hemoclip were used for the treatment of bleeding peptic ulcers. There are wide ranges of hemostatic doses (power and flow) of APC used in previous studies. The aim of our study was to assess the efficacy and safety of "intermediate dose" APC compared to hemoclips for hemostasis from bleeding peptic ulcer.The present study was designed as a retrospective study using historical controls. One hundred and ninety-four consecutive upper GI bleeding patients with bleeding visible vessel lesions were treated with either APC or hemoclips. There are 110 patients received APC treatment and 84 patients received hemoclip hemostasis. The main outcome measurements were one week rebleeding rate, one month rebleeding rate, surgery, morality, amount of blood transfusion and durations of hospital stay.There were no significant differences between the two groups in 1 week rebleeding rate (1.8% vs. 2.4%, p = 1.0), 1 month rebleeding rate (0% vs. 1.2%, p = 0.433), mortality, surgery and amount of blood transfusion (2.67 +/- 3.27 vs. 3.04 +/- 2.75 units, p = 0.322). However, the hospital stay was longer in hemoclip group (5.38 +/- 6.76 vs. 8.49 +/- 11.19 days p = 0.011).APC and hemoclip are with different hemostatic mechanisms, but the hemostatic outcomes were not significantly different between the two groups. APC is an effective, safe, and easily applicable endoscopic hemostatic modality as hemoclip for patients with non-variceal bleeding.

The pharmacokinetics of sarafloxacin applied by oral gavage at a dose of 15 mg/kg b.w. was studied in eel (Anguilla anguilla) at water temperature of 24 degrees C. Sarafloxacin levels were determined using high performance liquid chromatography with a quantitation limit of 0.07 microg/ml or gram. The time to peak plasma concentration, Tmax, was 12 hr and peak concentration, Cmax, was 2.64 microg/ml. The absorption rate constant (k(a)) was 0.23 hr(-1) (r=0.996). The drug disposition curve after Tmax was fitted to a two-compartment open model. The distribution rate constant (alpha) was 0.085 hr(-1) (r=0.972), and the half-life (t(1,2alpha)) was 8.15 hr. The elimination rate constant (beta) was 0.023 hr(-1) (r=0.909), and the half-life (t(1/2beta)) was 30.13 hr. The estimated area under the curve, AUC, was 56.7 microg.hr/ml. The peak concentrations of drug in liver, kidney, muscle, and skin were 13.39 (12 hr), 5.53 (12 hr), 1.82 (24 hr), and 0.78 microg/g (40 hr), respectively. The time for sarafloxacin mean levels to fall below detectable limits in the plasma, muscle, and skin were 7 days but for the liver and kidney were 14 days.

We present a new high-fidelity method of calibrating a cross-track scanning microwave radiometer using Global Positioning System (GPS) radio occultation (GPSRO) measurements. The radiometer and GPSRO receiver periodically observe the same volume of atmosphere near the Earth's limb, and these overlapping measurements are used to calibrate the radiometer. Performance analyses show that absolute calibration accuracy better than 0.25 K is achievable for temperature sounding channels in the 50-60-GHz band for a total-power radiometer using a weakly coupled noise diode for frequent calibration and proximal GPSRO measurements for infrequent (approximately daily) calibration. The method requires GPSRO penetration depth only down to the stratosphere, thus permitting the use of a relatively small GPS antenna. Furthermore, only coarse spacecraft angular knowledge (approximately one degree rms) is required for the technique, as more precise angular knowledge can be retrieved directly from the combined radiometer and GPSRO data, assuming that the radiometer angular sampling is uniform. These features make the technique particularly well suited for implementation on a low-cost CubeSat hosting both radiometer and GPSRO receiver systems on the same spacecraft. We describe a validation platform for this calibration method, the Microwave Radiometer Technology Acceleration (MiRaTA) CubeSat, currently in development for the National Aeronautics and Space Administration (NASA) Earth Science Technology Office. MiRaTA will fly a multiband radiometer and the Compact TEC/Atmosphere GPS Sensor in 2015., United States. Dept. of Defense. Assistant Secretary of Defense for Research & Engineering (United States. Air Force Contract FA8721-05-C-0002)

[1] The atmospheric temperature and specific humidity profiles derived from 4 years of Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) measurements during the boreal winter (November thru April in 2006–2010) were employed to study the large-scale vertical structure of the Madden-Julian Oscillation (MJO). In a composited MJO cycle, both RO temperature and moisture anomalies propagate eastward along with the enhanced MJO convection over the Indo-Pacific region. In the same region, the RO temperature anomaly is positively correlated with the convection (Tropical Rainfall Measuring Mission (TRMM) rainfall) anomaly in the middle and upper troposphere (800 hPa–200 hPa) and negatively correlated in the lower troposphere and at the tropopause. A positive RO moisture anomaly has a westward tilt below 300 hPa and is well associated with the convection anomaly. RO bending angle and refractivity anomalies show vertical structure similar to that of temperature MJO anomaly above ∼300 hPa and to that of the moisture anomaly below that. These salient MJO features agree well with those revealed by global reanalysis data and meteorological satellite observations, such as the Atmospheric Infrared Sounder (AIRS), even though RO anomalies exhibit sharper structure at the tropopause region due to the higher vertical resolution of the RO. Investigation of the cold-point tropopause anomaly indicates that the enhanced convection is preceded by cooling of the tropopause and followed by lowering of the tropopause height. The MJO moisture structures during two boreal winters, November 2007–April 2008 (La Nina) and November 2009–April 2010 (El Nino), are individually presented to demonstrate the El Nino-Southern Oscillation (ENSO) effect on the MJO structure.

[1] To examine the claim that Global Positioning System (GPS) radio occultation (RO) data are useful as a benchmark data set for climate monitoring, the structural uncertainties of retrieved profiles that result from different processing methods are quantified. Profile-to-profile comparisons of CHAMP (CHAllenging Minisatellite Payload) data from January 2002 to August 2008 retrieved by six RO processing centers are presented. Differences and standard deviations of the individual centers relative to the inter-center mean are used to quantify the structural uncertainty. Uncertainties accumulate in derived variables due to propagation through the RO retrieval chain. This is reflected in the inter-center differences, which are small for bending angle and refractivity increasing to dry temperature, dry pressure, and dry geopotential height. The mean differences of the time series in the 8 km to 30 km layer range from −0.08% to 0.12% for bending angle, −0.03% to 0.02% for refractivity, −0.27 K to 0.15 K for dry temperature, −0.04% to 0.04% for dry pressure, and −7.6 m to 6.8 m for dry geopotential height. The corresponding standard deviations are within 0.02%, 0.01%, 0.06 K, 0.02%, and 2.0 m, respectively. The mean trend differences from 8 km to 30 km for bending angle, refractivity, dry temperature, dry pressure, and dry geopotential height are within ±0.02%/5 yrs, ±0.02%/5 yrs, ±0.06 K/5 yrs, ±0.02%/5 yrs, and ±2.3 m/5 yrs, respectively. Although the RO-derived variables are not readily traceable to the international system of units, the high precision nature of the raw RO observables is preserved in the inversion chain.

Infection of gastric epithelial cells by Helicobacter pylori stimulates the activation of nuclear factor-κB (NF-κB) and the upregulation of interleukin-8 (IL-8) expression. Activation of NF-κB can occur through classical (p50/p65) and alternative (p52/RelB) pathways. The role of the bacterial cag pathogenicity island (PAI) in these events is controversial. This study aimed to evaluate the hypothesis that the CagA protein is required for H. pylori-induced activation of NF-κB and upregulation of IL-8 expression, and for clarithromycin (CAM) to exert its molecular effects. Cultured KATO-III human gastric cancer cells were treated with extracts of H. pylori strains ATCC43504 (cag PAI(+)) and ATCC51932 (cag PAI(-)) for 24 h. NF-κB and phospho-IκB protein expression was then evaluated using western blotting. IL-8 mRNA expression was evaluated using the reverse transcription polymerase chain reaction. Following the separation of the proteins using two-dimensional gel electrophoresis, proteomes of the two bacterial extracts were compared using nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) analysis. Although the protein profiles of the two extracts differed, both extracts induced IκBα phosphorylation, upregulation of IL-8 expression, and NF-κB activation through classical and alternative pathways. In cells treated with either of the bacterial extracts, CAM inhibited H. pylori-induced activation of NF-κB and upregulation of IL-8 expression. These results suggested that CagA is not required for H. pylori-induced activation of NF-κB and upregulation of IL-8 expression in gastric epithelial cells. H. pylori-induced NF-κB signaling can occur through classical and alternative activation pathways, and that CAM inhibits these two pathways.

Large-scale climate patterns influenced temperature and weather patterns around the globe in 2011. In particular, a moderate-to-strong La Niña at the beginning of the year dissipated during boreal spring but reemerged during fall. The phenomenon contributed to historical droughts in East Africa, the southern United States, and northern Mexico, as well the wettest two-year period (2010-11) on record for Australia, particularly remarkable as this follows a decade-long dry period. Precipitation patterns in South America were also influenced by La Niña. Heavy rain in Rio de Janeiro in January triggered the country's worst floods and landslides in Brazil's history. The 2011 combined average temperature across global land and ocean surfaces was the coolest since 2008, but was also among the 15 warmest years on record and above the 1981-2010 average. The global sea surface temperature cooled by 0.1°C from 2010 to 2011, associated with cooling influences of La Niña. Global integrals of upper ocean heat content for 2011 were higher than for all prior years, demonstrating the Earth's dominant role of the oceans in the Earth's energy budget. In the upper atmosphere, tropical stratospheric temperatures were anomalously warm, while polar temperatures were anomalously cold. This led to large springtime stratospheric ozone reductions in polar latitudes in both hemispheres. Ozone concentrations in the Arctic stratosphere during March were the lowest for that period since satellite records began in 1979. An extensive, deep, and persistent ozone hole over the Antarctic in September indicates that the recovery to pre-1980 conditions is proceeding very slowly. Atmospheric carbon dioxide concentrations increased by 2.10 ppm in 2011, and exceeded 390 ppm for the first time since instrumental records began. Other greenhouse gases also continued to rise in concentration and the combined effect now represents a 30% increase in radiative forcing over a 1990 baseline. Most ozone depleting substances continued to fall. The global net ocean carbon dioxide uptake for the 2010 transition period from El Niño to La Niña, the most recent period for which analyzed data are available, was estimated to be 1.30 Pg C yr-1, almost 12% below the 29-year long-term average. Relative to the long-term trend, global sea level dropped noticeably in mid-2010 and reached a local minimum in 2011. The drop has been linked to the La Nina conditions that prevailed throughout much of 2010-11. Global sea level increased sharply during the second half of 2011. Global tropical cyclone activity during 2011 was wellbelow average, with a total of 74 storms compared with the 1981-2010 average of 89. Similar to 2010, the North Atlantic was the only basin that experienced abovenormal activity. For the first year since the widespread introduction of the Dvorak intensity-estimation method in the 1980s, only three tropical cyclones reached Category 5 intensity level-all in the Northwest Pacific basin. The Arctic continued to warm at about twice the rate compared with lower latitudes. Below-normal summer snowfall, a decreasing trend in surface albedo, and aboveaverage surface and upper air temperatures resulted in a continued pattern of extreme surface melting, and net snow and ice loss on the Greenland ice sheet. Warmerthan- normal temperatures over the Eurasian Arctic in spring resulted in a new record-low June snow cover extent and spring snow cover duration in this region. In the Canadian Arctic, the mass loss from glaciers and ice caps was the greatest since GRACE measurements began in 2002, continuing a negative trend that began in 1987. New record high temperatures occurred at 20 m below the land surface at all permafrost observatories on the North Slope of Alaska, where measurements began in the late 1970s. Arctic sea ice extent in September 2011 was the second-lowest on record, while the extent of old ice (four and five years) reached a new record minimum that was just 19% of normal. On the opposite pole, austral winter and spring temperatures were more than 3°C above normal over much of the Antarctic continent. However, winter temperatures were below normal in the northern Antarctic Peninsula, which continued the downward trend there during the last 15 years. In summer, an all-time record high temperature of -12.3°C was set at the South Pole station on 25 December, exceeding the previous record by more than a full degree. Antarctic sea ice extent anomalies increased steadily through much of the year, from briefly setting a record low in April, to well above average in December. The latter trend reflects the dispersive effects of low pressure on sea ice and the generally cool conditions around the Antarctic perimeter. © 2012 American Meteorological Society.

Thermal structure associated with deep convective clouds is investigated using Global Positioning System (GPS) radio occultation measurements. GPS data are insensitive to the presence of clouds, and provide high vertical resolution and high accuracy measurements to identify associated temperature behavior. Deep convective systems are identified using International Satellite Cloud Climatology Project (ISCCP) satellite data, and cloud tops are accurately measured using Cloud-Aerosol Lidar with Orthogonal Polarization (CALIPSO) lidar observations; we focus on 53 cases of near-coincident GPS occultations with CALIPSO profiles over deep convection. Results show a sharp spike in GPS bending angle highly correlated to the top of the clouds, corresponding to anomalously cold temperatures within the clouds. Above the clouds the temperatures return to background conditions, and there is a strong inversion at cloud top. For cloud tops below 14 km, the temperature lapse rate within the cloud often approaches a moist adiabat, consistent with rapid undiluted ascent within the convective systems.

Background Matrix metalloproteinases (MMPs) are involved in acute myocardial dysfunction by degrading several intracellular contractile proteins, including cardiac troponin I (cTnI). Here, we examined the temporal profiles of MMPs and cTnI in plasma and myocardial tissue in the acute stage of subarachnoid hemorrhage (SAH). Materials and methods SAH was induced by the endovascular suture method in rats. Intracranial pressure and left ventricular (LV) function were recorded. Plasma cTnI and MMPs were measured at 0, 5, 15, 30, 60, 120, and 180 minutes after SAH. Myocardial cTnI and MMP activities were quantified at 30, 60 and 180 min after SAH from homogenized hearts. Results SAH-induced rats showed a marked decline in -LV dP/dt max (index of LV diastolic function). Plasma samples revealed a noticeable increase in cTnI and pro-MMP-9 activities over the course of 180 minutes. In myocardial tissue, there was a marked increase in pro-MMP-9, pro-MMP-2 activities and expression of activated MMP-2. Western blot analysis revealed a striking decrease in cTnI content and increase in cTnI degradation in myocardium. Simultaneous cTnI depletion and MMP-2 expression in myocardium was detected by immunohistochemistry as early as 30 minutes after SAH. MMPs correlated with -LV dP/dt max (% of baseline) both in plasma and in myocardial tissue. Furthermore, activated MMP-2 activity correlated positively with cTnI degradation in myocardium. Conclusions Early activation of MMPs was observed in myocardium and plasma following SAH. Activated MMP-2 may regulate proteolytic cTnI and contribute to myocardium stunning injury in SAH rats.

DNA repair has been suggested to be a major cause of spontaneous drug resistance in patients with lung adenocarcinomas (LADC). Among the DNA repair-related proteins, excision repair cross-complementation group 1 (ERCC1) has been shown to be essential for repairing cisplatin-induced interstrand cross-linkage. However, the role of other DNA repair-related proteins in drug resistance has not been clearly elucidated. In this study, we used suppression subtractive hybridization and microarray analysis to identify the DNA repair-related genes associated with cisplatin resistance. We focused on the association of XPC protein expression, which plays a pivotal role in the earliest response to global genomic repair, with the survival of LADC patients. Using suppression subtractive hybridization and a microarray analysis to identify drug resistance-associated DNA repair-related genes, we found that the mRNA levels of ERCC1, MSH-3, MSH-6 and XPC were significantly increased in LADC patients. Since the results of ERCC1 mRNA expression corresponded well with those in previous reports, in this study we focused on the clinical correlation between XPC expression and patient survival. The level of XPC protein was determined by immunohistochemical and immunoblotting analyses. We detected the XPC protein in 46 (43%) of 107 pathological LADC samples. XPC protein expression correlated with tumor stage, cigarette smoking and poor survival. In the in vitro experiments with LADC cell lines, increased XPC expression was associated with elevated drug resistance, and silencing of XPC expression reduced cisplatin resistance. Our results suggest that XPC expression predicts drug resistance in LADC.

DNA repair is one of the major causes of spontaneous drug and radiation resistance in patients with lung adenocarcinomas (LADC). 53BP1 is a mediator that relays signals from DNA damage sensors and activates various effectors for the DNA repair and cell survival. In this study we investigated the clinical and biological significance of 53BP1. Expression of 53BP1 was detected by immunoblotting and immunohistochemistry. Our data showed that 53BP1 was detected in 166 (75.8%) of 219 LADC patients. Expression of 53BP1 correlated with tumor stage, cigarette smoking, lymphovascular invasion and poor clinical outcome. In vitro, increased 53BP1 expression elevated drug resistance, and silencing of 53BP1 expression reduced cisplatin resistance. Our results suggest that 53BP1 expression plays an important role in cisplatin resistance and predicts the prognosis for LADC.

[1] Vertical profiles of carbon monoxide (CO) concentration and corresponding total column values derived from measurements made by the Measurements of Pollution in the Troposphere (MOPITT) satellite instrument are now being processed operationally with the “version 4” (V4) retrieval algorithm. This algorithm exploits the results of analyses of in situ data, chemical transport modeling, and radiative transfer modeling in the MOPITT postlaunch era. Improvements in the V4 product are evident in both clean and polluted conditions. The new products are validated using CO in situ measurements acquired from aircraft from 2000 to 2007. As determined by both retrieval simulations and observations, retrieval bias drift is typically about 1 ppbv/yr for levels in the middle troposphere and about 2 ppbv/yr in the upper troposphere. Retrieval simulations indicate that observed bias drift may be the result of gradual on-orbit changes in the instrument's modulation cell parameters.