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This research aimed to study the application of magnetic resonance imaging (MRI) under three-dimensional mark point positioning algorithm in stereotactic surgery for Parkinson’s disease (PD) and improve clinical treatment effect. Eighty patients with PD in Tianjin Medical University General Hospital were selected as the research objects and randomly divided into two groups. The three-dimensional mark point positioning algorithm was applied to perform feature positioning on the MRI images of PD patients, and the international unified Parkinson’s disease rating scale (UPDRS) was assessed before and after single-target surgery of the two groups. There was a significant difference in the postoperative treatment effect between the two groups compared with the preoperative one ( P < 0.05 ). Among the patients in the observation group, 37 cases were marked as markedly effective, accounting for 92.5% of the total group; 1 case was ineffective and 2 cases were improved, accounting for 2.5% and 5%, respectively. In the control group, 35, 2, and 3 cases were assessed as markedly effective, ineffective, and improved, accounting for 87.5%, 5%, and 7.5%, respectively. The overall curative effect of the observation group was better than that of the control group, and the difference was significant ( P < 0.05 ). The MRI manifestations of PD patients were diversified. MRI under the three-dimensional mark point positioning algorithm had a high value for the stereotactic treatment of PD patients, which was beneficial to the clinical surgery.

We describe the design and synthesis of OFS-1, an Osteoadsorptive Fluorogenic Sentinel imaging probe that is adsorbed by hydroxyapatite (HAp) and bone mineral surfaces, where it generates an external fluorescent signal in response to osteoclast-secreted cathepsin K (Ctsk). The probe consists of a bone-anchoring bisphosphonate moiety connected to a Forster resonance energy transfer (FRET) internally quenched fluorescent (IQF) dye pair, linked by a Ctsk peptide substrate, GHPGGPQG. Key structural features contributing to the effectiveness of OFS-1 were defined by structure-activity relationship (SAR) and modeling studies comparing OFS-1 with two cognates, OFS-2 and OFS-3. In solution or when preadsorbed on HAp, OFS-1 exhibited strong fluorescence when exposed to Ctsk (2.5-20 nM). Time-lapse photomicrographs obtained after seeding human osteoclasts onto HAp-coated well plates containing preadsorbed OFS-1 revealed bright fluorescence at the periphery of resorbing cells. OFS-1 administered systemically detected early osteolysis colocalized with orthotopic engraftment of RPMI-8226-Luc human multiple myeloma cells at a metastatic skeletal site in a humanized mouse model. OFS-1 is thus a promising new imaging tool for detecting abnormal bone resorption.

Given a still photograph, one can imagine how dynamic objects might move against a static background. This idea has been actualized in the form of cinemagraphs, where the motion of particular objects within a still image is repeated, giving the viewer a sense of animation. In this paper, we learn computational models that can generate cinemagraph sequences automatically given a single image. To generate cinemagraphs, we explore combining generative models with a recurrent neural network and deep Q-networks to enhance the power of sequence generation. To enable and evaluate these models we make use of two datasets, one synthetically generated and the other containing real video generated cinemagraphs. Both qualitative and quantitative evaluations demonstrate the effectiveness of our models on the synthetic and real datasets., Comment: WACV2018

As two of the five traditional human senses (sight, hearing, taste, smell, and touch), vision and sound are basic sources through which humans understand the world. Often correlated during natural events, these two modalities combine to jointly affect human perception. In this paper, we pose the task of generating sound given visual input. Such capabilities could help enable applications in virtual reality (generating sound for virtual scenes automatically) or provide additional accessibility to images or videos for people with visual impairments. As a first step in this direction, we apply learning-based methods to generate raw waveform samples given input video frames. We evaluate our models on a dataset of videos containing a variety of sounds (such as ambient sounds and sounds from people/animals). Our experiments show that the generated sounds are fairly realistic and have good temporal synchronization with the visual inputs., Project page: http://bvision11.cs.unc.edu/bigpen/yipin/visual2sound_webpage/visual2sound.html

Poly(β-l-malic acid) (PMA) is a biodegradable polymer with many potential biomedical applications. PMA can be readily hydrolyzed to malic acid (MA), which is widely used as an acidulant in foods and pharmaceuticals. PMA production from sucrose and sugarcane juice by Aureobasidium pullulans ZX-10 was studied in shake-flasks and bioreactors, confirming that sugarcane juice can be used as an economical substrate without any pretreatment or nutrients supplementation. A high PMA titer of 116.3g/L and yield of 0.41g/g were achieved in fed-batch fermentation. A high productivity of 0.66g/L·h was achieved in repeated-batch fermentation with cell recycle. These results compared favorably with those obtained from glucose and other biomass feedstocks. A process economic analysis showed that PMA could be produced from sugarcane juice at a cost of $1.33/kg, offering a cost-competitive bio-based PMA for industrial applications.

Polymalic acid (PMA) production by Aureobasidium pullulans ZX-10 from soybean hull hydrolysate supplemented with corn steep liquor (CSL) gave a malic acid yield of ∼0.4g/g at a productivity of ∼0.5g/L·h. ZX-10 can also ferment soy molasses, converting all carbohydrates including the raffinose family oligosaccharides to PMA, giving a high titer (71.9g/L) and yield (0.69g/g) at a productivity of 0.29g/L·h in fed-batch fermentation under nitrogen limitation. A higher productivity of 0.64g/L·h was obtained in repeated batch fermentation with cell recycle and CSL supplementation. Cost analysis for a 5000 MT plant shows that malic acid can be produced at $1.10/kg from soy molasses, $1.37/kg from corn, and $1.74/kg from soybean hull. At the market price of $1.75/kg, malic acid production from soy molasses via PMA fermentation offers an economically competitive process for industrial production of bio-based malic acid.

Based on life-long observations of physical, chemical, and biologic phenomena in the natural world, humans can often easily picture in their minds what an object will look like in the future. But, what about computers? In this paper, we learn computational models of object transformations from time-lapse videos. In particular, we explore the use of generative models to create depictions of objects at future times. These models explore several different prediction tasks: generating a future state given a single depiction of an object, generating a future state given two depictions of an object at different times, and generating future states recursively in a recurrent framework. We provide both qualitative and quantitative evaluations of the generated results, and also conduct a human evaluation to compare variations of our models.

Background The hemoglobin of the Earthworm Lumbricus terrestris (also known as erythrocruorin, or LtEc) is a naturally occurring high molecular weight protein assembly (3.6 MDa) that is extremely stable, resistant to oxidation, and transports oxygen similarly to human whole blood. Therefore, LtEc may serve as an alternative to donated human red blood cells, however, a suitable purification process must be developed to produce highly pure LtEc on a large scale that can be evaluated in an animal model to determine the safety and efficacy of LtEc.

This study analyzes the changes of NO2 vertical tropospheric columns (VTCs) over Europe during the period 2004–2009 using a statistical model, based on a homogeneous high-quality data set of observations of the Ozone Monitoring Instrument OMI. At each point of a regular grid, a Generalized Additive regression Model (GAM) with non-parametric model terms was fitted to the observed columns to describe the most relevant factors contributing to the observed variability in NO2 VTCs. These factors include annual cycle, day of week, wind, precipitation, retrieved cloud radiance fraction, and trend. Significant negative changes are found in areas with large anthropogenic sources over Western Europe (mostly from −4 to −8% year−1). The overall negative changes are consistent with EMEP/CEIP (European Monitoring and Evaluation Programme/Center on Emission Inventories and Projections) emission estimations and previous trend studies. However, we found remarkably large spatial variations in NO2 column changes within individual regions. Our analysis shows that in particular the NOx emissions from Spanish power plants (from −10 to approx. −20% year−1) and over the center of England (up to approx. −12% year−1) have been strongly reduced in the past few years, at a rate exceeding the reported emission changes averaged over the individual country. A number of other features of the temporal behavior of the time series of tropospheric NO2 distributions over Europe were quantified, including clear annual and weekly cycles. Modeling the influence of wind considering both wind direction and wind speed not only improves the accuracy of the trend results, but can be particularly interesting for identifying the sources of the NO2 VTCs and the transport pathways of air pollutants. The effects of precipitation are observed to vary obviously during warm and cold months, due to the strong seasonal dependence of soil NOx emissions.

We present an improved tropospheric nitrogen dioxide column retrieval algorithm (DOMINO v2.0) for OMI based on better air mass factors (AMFs) and a correction for across-track stripes resulting from calibration errors in the OMI backscattered reflectances. Since October 2004, NO2 retrievals from the Ozone Monitoring Instrument (OMI), a UV/Vis nadir spectrometer onboard NASA's EOS-Aura satellite, have been used with success in several scientific studies focusing on air quality monitoring, detection of trends, and NOx emission estimates. Dedicated evaluations of previous DOMINO tropospheric NO2 retrievals indicated their good quality, but also suggested that the tropospheric columns were susceptible to high biases (by 0–40%), probably because of errors in the air mass factor calculations. Here we update the DOMINO air mass factor approach. We calculate a new look-up table (LUT) for altitude-dependent AMFs based on more realistic atmospheric profile parameters, and include more surface albedo and surface pressure reference points than before. We improve the sampling of the TM4 model, resulting in a priori NO2 profiles that are better mixed throughout the boundary layer. We evaluate the NO2 profiles simulated with the improved TM4 sampling as used in the AMF calculations and show that they are highly consistent with in situ NO2 measurements from aircraft during the INTEX-A and INTEX-B campaigns in 2004 and 2006. Our air mass factor calculations are further updated by the implementation of a high-resolution terrain height and a high-resolution surface albedo climatology based on OMI measurements. Together with a correction for across-track stripes, the overall impact of the improved terrain height and albedo descriptions is modest (

Recent data suggest that transitions between the relaxed (R) and tense (T) state of hemoglobin control the reduction of nitrite to nitric oxide (NO) by deoxyhemoglobin. This reaction may play a role in physiologic NO homeostasis and be a novel consideration for the development of the next generation of hemoglobin-based blood oxygen carriers (HBOCs, i.e. artificial blood substitutes). Herein we tested the effects of chemical stabilization of bovine hemoglobin in either the T- (THb) or R-state (RHb) on nitrite-reduction kinetics, NO-gas formation and ability to stimulate NO-dependent signaling. These studies were performed over a range of fractional saturations that is expected to mimic biological conditions. The initial rate for nitrite-reduction decreased in the following order RHb > bHb > THb, consistent with the hypothesis that the rate constant for nitrite reduction is faster with R-state Hb and slower with T-state Hb. Moreover, RHb produced more NO-gas and inhibited mitochondrial respiration more potently than both bHb and THb. Interestingly, at low oxygen fractional saturations, THb produced more NO and stimulated nitrite-dependent vasodilation more potently than bHb despite both derivatives having similar initial rates for nitrite reduction and a more negative reduction potential in THb versus bHb. These data suggest that cross-linking of bovine hemoglobin in the T-state conformation leads to a more effective coupling of nitrite reduction to NO-formation. Our results support the model of allosteric regulation of nitrite reduction by deoxyhemoglobin and show that cross-linking hemoglobins in distinct quaternary states can generate products with increased NO yields from nitrite reduction that could be harnessed to promote NO-signaling in vivo.

We attempt for the first time to retrieve lower-tropospheric vertical profile information for 8 quantities from ground-based Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) observations. The components retrieved are the aerosol extinction coefficients at two wavelengths, 357 and 476 nm, and NO2, HCHO, CHOCHO, H2O, SO2, and O3 volume mixing ratios. A Japanese MAX-DOAS profile retrieval algorithm, version 1 (JM1), is applied to observations performed at Cabauw, the Netherlands (51.97° N, 4.93° E), in June–July 2009 during the Cabauw Intercomparison campaign of Nitrogen Dioxide measuring Instruments (CINDI). Of the retrieved profiles, we focus here on the lowest-layer data (mean values at altitudes 0–1 km), where the sensitivity is usually highest owing to the longest light path. In support of the capability of the multi-component retrievals, we find reasonable overall agreement with independent data sets, including a regional chemical transport model (CHIMERE) and in situ observations performed near the surface (2–3 m) and at the 200-m height level of the tall tower in Cabauw. Plumes of enhanced HCHO and SO2 were likely affected by biogenic and ship emissions, respectively, and an improvement in their emission strengths is suggested for better agreement between CHIMERE simulations and MAX-DOAS observations. Analysis of air mass factors indicates that the horizontal spatial representativeness of MAX-DOAS observations is about 3–15 km (depending mainly on aerosol extinction), comparable to or better than the spatial resolution of current UV-visible satellite observations and model calculations. These demonstrate that MAX-DOAS provides multi-component data useful for the evaluation of satellite observations and model calculations and can play an important role in bridging different data sets having different spatial resolutions.

We present an approach to reduce topography-related errors of vertical tropospheric columns (VTC) of NO2 retrieved from the Ozone Monitoring Instrument (OMI) in the vicinity of mountainous terrain. This is crucial for reliable estimates of air pollution levels over our particular area of interest, the Alpine region and the adjacent planes, where the Dutch OMI NO2 product (DOMINO) exhibits significant biases due to the coarse resolution of surface parameters used in the retrieval. Our approach replaces the coarse-gridded surface pressures by accurate pixel-average values using a high-resolution topography data set, and scales the a priori NO2 profiles accordingly. NO2 VTC reprocessed in this way for the period 2006–2007 suggest that NO2 over the Po Valley in Italy and over the Swiss plateau is underestimated by DOMINO by about 15–20% in winter and 5% in summer under clear-sky conditions (cloud radiance fraction

New marine bacterium Zooshikella sp. SY01, producer of prodigiosin, was isolated from the seawaters of Sanya Bay. The culture conditions of this bacterium were investigated. Zooshikella sp. SY01 was cultured in 2216E media which contained tryptophan, histidine, lactonic acid, camphor, limonene, casein, diphenyl guanidine, coumarin and 1,3-dinitrobenzene, respectively. After 5 days cultivation, the extracts of different culture broths were detected by direct infusion mass spectroscopy using positive ESI mode. As the results, tryptophan, histidine and casein didn’t show any observable influences on the biosynthesis of prodigiosin. Lactonic acid, camphor, limonene, diphenyl guanidine, coumarin could inhibit the bacterium growth and prodigiosin biosynthesis to a certain extent, slower the culture broth to turn red. However, 1,3-dinitrobenzene inhibited the bacteria to produce prodigiosin completely. MS data suggested that various metabolites with chemodiversity were produced in different culture media. In particular, a series of high-molecular-weight compounds with high relative abundances were observed in the medium containing limonene. To further optimize the culture condition, more new prodigiosin analogues and lead compounds can be obtained and the goal of “one strain-many compounds” can be achieved.

In situ flying height testing technology is becoming more and more important in slider–disk interaction analysis and manufacturing quality control of disk drives and head-related components. Triple harmonic method is a quite promising choice for in situ flying height analysis, compared with other in situ methods reported up to now. This paper reports results of investigations on engineering issues of applying triple harmonic method for in situ flying height analysis. The paper reports results of analysis on the effects of various testing conditions on flying height testing repeatability and accuracy. Results suggest that working at reasonable high channel density and working on the ratio between third and first harmonics will be an advantage in terms of both flying height testing sensitivity and testing repeatability. Comparing with media thickness effect, the gap-length variation among different heads will be important if it is to study flying height difference among different heads and the testing is at high channel density. Also, it is suggested to work at AC erased track, in order to reduce the non-linearity caused by hard transition.

Gap length (GL) of reading head is one of the most critical parameters for high-density magnetic recording systems. A novel method is proposed for quantitative evaluation of the GL fluctuation among a batch of magneto-resistive/giant magneto-resistive heads with same structure design. The method works at head-gimbal assembly level and the evaluation can be done with any read/write analysis equipment. The testing process is based on harmonic analysis of the readback signal. The testing system consists of a selected reference head and sample heads for evaluation. A GL variation function is introduced for the evaluation of GL deviation between the reference head and sample head. This method proved to be easy for implementation and results suggest that variation of GL is considerable and has obvious effect on recording performance in high recording density systems.

D-Limonene was effectively biotransformed by marine bacteria, Vibrio cholerae, Listonella damsela and Vibrio alginolyticus which collected from the Daya Bay of the South China Sea. These bacterial strains were fermented in the liquid medium 2216E, D- limonene was distributed among the culture flasks (200 mg/L). The flasks were incubated at 28 degrees C on a rotary shaker (r/min = 120) for 5 days. On completion, the culture broth were successively extracted with EtOAc. The extract was quantitatively measured by gas chromatography-mass spectrometry (GC-MS) analysis. The results showed that biocatalytic reactions were comprised of oxidation, including hydroxylation and ketonization which occurred at different positions of the D-limonene, as well as hydrogenation, hydrolyzation, esterification and cyclic cleavage. These bacteria strains possess the distinctive biocatalytic capacities towards the D-limonene. A series of terpenoids, including sesqui-, di- and tri terpenoids were also observed, which was accounted for D-limonene had influence on the metabolites of marine bacteria. Biotransformation is a valuable tool, with the advantages of the simple manipulation, working under mild reaction conditions, high efficiency, being reaction-, regio-, and stereoselective, and friendly. Microorganisms biotransformation definitely represents a new powerful approach to the development and the utilization of monoterpene, the abundant natural resource and provides the endless opportunities to obtain some significant compounds which can be used in the fields of medicine, organic synthesis and fine chemistry.

International audience; In this paper we propose a general MAP-estimation framework for blind image deconvolution that allows the incorporation of powerful priors regarding predicting the edges of the latent image, which is known to be a crucial factor for the success of blind deblurring. This is achieved in a principled, robust and unified manner through the use of a global energy function that can take into account multiple constraints. Based on this framework, we show how to successfully make use of a particular prior of this type that is quite strong and also applicable to a wide variety of cases. It relates to the strong structural regularity that is exhibited by many scenes, and which affects the location and distribution of the corresponding image edges. We validate the excellent performance of our approach through an extensive set of experimental results and comparisons to the state-of-the-art.

Malic acid is a dicarboxylic acid widely used in the food industry and also a potential C4 platform chemical that can be produced from biomass. However, microbial fermentation for direct malic acid production is limited by low product yield, titer, and productivity due to end-product inhibition. In this work, a novel process for malic acid production from polymalic acid (PMA) fermentation followed by acid hydrolysis was developed. First, a PMA-producing Aureobasidium pullulans strain ZX-10 was screened and isolated. This microbe produced PMA as the major fermentation product at a high-titer equivalent to 87.6 g/L of malic acid and high-productivity of 0.61 g/L h in free-cell fermentation in a stirred-tank bioreactor. Fed-batch fermentations with cells immobilized in a fibrous-bed bioreactor (FBB) achieved the highest product titer of 144.2 g/L and productivity of 0.74 g/L h. The fermentation produced PMA was purified by adsorption with IRA-900 anion-exchange resins, achieving a ∼100% purity and a high recovery rate of 84%. Pure malic acid was then produced from PMA by hydrolysis with 2 M sulfuric acid at 85°C, which followed the first-order reaction kinetics. This process provides an efficient and economical way for PMA and malic acid production, and is promising for industrial application. Biotechnol. Bioeng. 2013; 110: 2105–2113. © 2013 Wiley Periodicals, Inc.

Hemoglobin (Hb)-based oxygen carriers (HBOCs) represent a class of biological therapeutics that have been studied in multiple disease state clinical trials when blood volume replacement and oxygen delivery are required (Silverman and Weiskopf, 2009). Disease states studied include traumatic and surgical blood loss, cardiac bypass, stroke, myocardial infarction, and sickle cell anemia. Additionally, these agents are approved in certain countries for use in lieu of blood transfusion due to either shortage or donor blood safety concerns. In the United States, several HBOCs have been evaluated clinically under regulatory supervision; however, none have been approved for licensure. The primary regulatory issues with HBOCs stem from unacceptable safety profiles in clinical trials that indicate an increased risk to benefit ratio (Silverman and Weiskopf, 2009). The primary safety signals observed suggest increased severe adverse events associated with the cardiovascular system, central nervous system, and kidneys. The mechanisms of these toxicities are not well defined; however, the primary focus has been on the nitric oxide (NO)–depleting effects of Hb, which can lead to hypertension and vascular dysfunction (Yu et al., 2009). An equally important mechanism of Hb toxicity involves oxidation of heme within the protein, which can lead to free radical generation and finally heme and iron release (Buehler et al., 2007; Butt et al., 2010). The primary effects can be acute and localized tissue injury, particularly in organ systems experiencing extensive exposures. HBOCs were often developed as single entity molecules for intended use in multiple and diverse indications. Development strategies have focused on chemical and recombinant modification of Hb, however, limited examples exist where in vivo studies were employed in a multicandidate down selection process. In a series of papers focused on recombinant-based heme pocket re-engineering intended to minimize heme iron's interaction with NO, one can find a description of extensive recombinant and biochemical efforts followed by a limited in vivo screening analysis (Doherty et al., 1998; Dou et al., 2002; Olson et al., 2004). As part of these studies, libraries of modified proteins were evaluated and down selected based on hemodynamic response in rats. Particular focus was placed on systemic vasoconstriction, and the choice of engineered Hb was based on the rate of NO dioxygenation determined in vitro and vascular resistance determined in vivo. The down selection of an appropriate product candidate for preclinical and later clinical trial evaluation may further benefit from initial evaluation of libraries of product candidates to include early assessment of pharmacokinetics (PKs), hemodynamics, oxidation, and toxicological responses in vivo. We have developed and evaluated a library of four molecular sized bovine hemoglobins (bHb) polymerized with glutaraldehyde and collectively termed PolybHb. PolybHbs were synthesized with cross-link densities (i.e., molar ratio of glutaraldehyde to bHb) of 10:1, 20:1, 30:1, and 40:1 according to a previously described methodology reported in the literature (Zhou et al., 2011). Within the context of this study, the PolybHbs function as a group of identically prepared HBOCs with the single variable in their preparation being the glutaraldehyde to bHb polymerization ratio. This allowed us to study the effects of modified Hbs with identical starting material and modifying agent on a priori determined in vivo characteristics. In the present set of experiments, the four PolybHbs were evaluated for PK characteristics (metabolism, distribution, and excretion), safety pharmacology (systemic blood pressure response), in vitro and in vivo oxidation, and potential for tissue-based toxicity (acute renal toxicity). Our criteria for meeting selection included a long circulating modified Hb with minimal breakdown in circulation, no renal excretion, limited hypertensive response, minimal potential for oxidation, and no initial evidence of renal tissue toxicity (renal iron deposition, histological changes, or increases in serum creatinine). We additionally suggest that this type of approach could serve as a novel method to down select HBOCs early in their development using a priori determined in vivo attributes that may be applicable to use specific indications.

The hemoglobin of the earthworm Lumbricus terrestris (also known as erythrocruorin, or LtEc) is a naturally occurring high-molecular-weight protein assembly (3.6 MDa) that is extremely stable, resistant to oxidation, and transports oxygen similarly to human whole blood. Therefore, LtEc may serve as an alternative to donated human red blood cells. However, a suitable purification process must be developed to produce highly pure LtEc on a large scale that can be evaluated in an animal model to determine the safety and efficacy of LtEc.We used tangential-flow filtration (TFF), an easily scalable and affordable technique, to produce highly pure LtEc from earthworms. The purity, yield, methemoglobin level, viscosity, colloid osmotic pressure, O(2) binding equilibria, and ligand-binding kinetics of the purified LtEc were measured in vitro. The purified LtEc product was then evaluated in hamsters using a hypervolemic infusion model to establish its basic biocompatibility and detect any changes in microcirculatory and systemic variables.TFF was able to produce LtEc with high purity and yield (5-10 g/1000 worms). The purified LtEc product did not elicit hypertension or vasoconstriction when infused into hamsters.LtEc may be easily purified and safely transfused into hamsters in small amounts (0.5-1.5 g/dL final concentration in blood) without any noticeable side effects. Therefore, LtEc may serve as a very promising oxygen carrier for use in transfusion medicine.

From June to July 2009 more than thirty different in-situ and remote sensing instruments from all over the world participated in the Cabauw Intercomparison campaign for Nitrogen Dioxide measuring Instruments (CINDI). The campaign took place at KNMI's Cabauw Experimental Site for Atmospheric Research (CESAR) in the Netherlands. Its main objectives were to determine the accuracy of state-of-the-art ground-based measurement techniques for the detection of atmospheric nitrogen dioxide (both in-situ and remote sensing), and to investigate their usability in satellite data validation. The expected outcomes are recommendations regarding the operation and calibration of such instruments, retrieval settings, and observation strategies for the use in ground-based networks for air quality monitoring and satellite data validation. Twenty-four optical spectrometers participated in the campaign, of which twenty-one had the capability to scan different elevation angles consecutively, the so-called Multi-axis DOAS systems, thereby collecting vertical profile information, in particular for nitrogen dioxide and aerosol. Various in-situ samplers and lidar instruments simultaneously characterized the variability of atmospheric trace gases and the physical properties of aerosol particles. A large data set of continuous measurements of these atmospheric constituents has been collected under various meteorological conditions and air pollution levels. Together with the permanent measurement capability at the CESAR site characterizing the meteorological state of the atmosphere, the CINDI campaign provided a comprehensive observational data set of atmospheric constituents in a highly polluted region of the world during summertime. First detailed comparisons performed with the CINDI data show that slant column measurements of NO2, O4 and HCHO with MAX-DOAS agree within 5 to 15%, vertical profiles of NO2 derived from several independent instruments agree within 25% of one another, and MAX-DOAS aerosol optical thickness agrees within 20–30% with AERONET data. For the in-situ NO2 instrument using a molybdenum converter, a bias was found as large as 5 ppbv during day time, when compared to the other in-situ instruments using photolytic converters.

A mathematical model was developed to study nitric oxide (NO) and oxygen (O(2)) transport in an arteriole and surrounding tissues exposed to a mixture of red blood cells (RBCs) and hemoglobin (Hb)-based O(2) carriers (HBOCs). A unique feature of this model is the inclusion of blood vessel wall shear stress-induced production of endothelial-derived NO, which is very sensitive to the viscosity of the RBC and HBOC mixture traversing the blood vessel lumen. Therefore in this study, a series of polymerized bovine Hb (PolyHb) solutions with high viscosity, varying O(2) affinities, NO dioxygenation rate constants and O(2) dissociation rate constants that were previously synthesized and characterized by our group was evaluated via mathematical modeling, in order to investigate the effect of these biophysical properties on the transport of NO and O(2) in an arteriole and its surrounding tissues subjected to anemia with the commercial HBOC Oxyglobin® and cell-free bovine Hb (bHb) serving as appropriate controls. The computer simulation results indicated that transfusion of high viscosity PolyHb solutions promoted blood vessel wall shear stress dependent generation of the vasodilator NO, especially in the blood vessel wall and should transport enough NO inside the smooth muscle layer to activate vasodilation compared to the commercial HBOC Oxyglobin® and cell-free bHb. However, NO scavenging in the arteriole lumen was unavoidable due to the intrinsic high NO dioxygenation rate constant of the HBOCs being studied. This study also observed that all PolyHbs could potentially improve tissue oxygenation under hypoxic conditions, while low O(2) affinity PolyHbs were more effective in oxygenating tissues under normoxic conditions compared with high O(2) affinity PolyHbs. In addition, all ultrahigh molecular weight PolyHbs displayed higher O(2) transfer rates than the commercial HBOC Oxyglobin® and cell-free bHb. Therefore, these results suggest that ultrahigh molecular weight PolyHb solutions could be used as safe and efficacious O(2) carriers for use in transfusion medicine. It also suggests that future generations of PolyHb solutions should possess lower NO dioxygenation reaction rate constants in order to reduce NO scavenging, while maintaining high solution viscosity to take advantage of wall shear stress-induced NO production. Taken together, we suggest that this mathematical model can be used to predict the vasoactivity of HBOCs and help guide the design and optimization of the next generation of HBOCs for use in transfusion medicine.

Background: The objective of this study was to determine the role of plasma oxygen carrying capacity during resuscitation from hemorrhagic shock (HS). Methods: Hemodynamic responses to small-volume resuscitation from HS with hypertonic saline followed by infusion of ultrahigh-molecular-weight tense-state polymerized hemoglobins (PolyHbs) were studied in the hamster window chamber model. HS was induced by withdrawing 50% of the blood volume (BV), and hypovolemic state was maintained for 1 hour. Resuscitation was implemented by infusion of hypertonic saline (3.5% of BV) followed by 10% of BV infusion of polymerized human Hb (PolyHbhum, P50 = 49 mm Hg), polymerized bovine Hb (PolyHbbov, P50 = 40 mm Hg), or human serum albumin (HSA), all at 10 g/dL. Resuscitation was monitored over 90 minutes. Results: PolyHbhum elicited higher arterial pressure, produced vasoconstriction, and decreased perfusion. In contrast, PolyHbbov and HSA exhibited lower blood pressure and partially restored perfusion and functional capillary density compared with PolyHbhum. Blood gas parameters showed a pronounced recovery after resuscitation with PolyHbbov compared with both PolyHbhum and HSA. Tissue Po2 was significantly improved in the PolyHbbov group, showing that the moderate increase in P50 of PolyHbbov compared with hamster blood (P50 = 32 mm Hg) was beneficial during resuscitation. However, an excessive increase in oxygen release between the central and peripheral circulation, as induced by PolyHbhum produced vasoconstriction and hypoperfusion, limiting the benefits of additional oxygen carrying capacity. Conclusions: Appropriately engineered PolyHb will enhance/reinstate oxygenation, without hypertension or vasoconstriction, to be used in situations where blood transfusion is not logistically feasible.

In a recent study, ultrahigh molecular weight (Mw ) glutaraldehyde-polymerized bovine hemoglobins (PolybHbs) were synthesized with low O2 affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top-load model.(1) In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G:Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O2 affinity state. Our results showed that the Mw of the resulting PolybHbs increased with increasing G:Hb molar ratio. For low O2 affinity PolybHbs, increasing the G:Hb molar ratio reduced the O2 affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O2 affinity PolybHbs, increasing the G:Hb molar ratio led to increased O2 affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O2 affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G:Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G:Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G:Hb molar ratio. To preliminarily evaluate the ability of low and high O2 affinity PolybHbs to potentially oxygenate tissues in vivo, an O2 transport model was used to simulate O2 transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O2 affinity PolybHbs oxygenated the bioreactor better than high O2 affinity PolybHbs. This result points to the suitability of low O2 affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G:Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin-based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications.

Surface reflectance is a key parameter in satellite trace gas retrievals in the UV/visible range and in particular for the retrieval of nitrogen dioxide (NO2) vertical tropospheric columns (VTCs). Current operational retrievals rely on coarse-resolution reflectance data and do not account for the generally anisotropic properties of surface reflectance. Here we present a NO2 VTC retrieval that uses MODIS bi-directional reflectance distribution function (BRDF) data at high temporal (8 days) and spatial (1 km × 1 km) resolution in combination with the LIDORT radiative transfer model to account for the dependence of surface reflectance on viewing and illumination geometry. The method was applied to two years of NO2 observations from the Ozone Monitoring Instrument (OMI) over Europe. Due to its wide swath, OMI is particularly sensitive to BRDF effects. Using representative BRDF parameters for various land surfaces, we found that in July (low solar zenith angles) and November (high solar zenith angles) and for typical viewing geometries of OMI, differences between MODIS black-sky albedos and surface bi-directional reflectances are of the order of 0–10% and 0–40%, respectively, depending on the position of the OMI pixel within the swath. In the retrieval, black-sky albedo was treated as a Lambertian (isotropic) reflectance, while for BRDF effects we used the kernel-based approach in the MODIS BRDF product. Air Mass Factors were computed using the LIDORT radiative transfer model based on these surface reflectance conditions. Differences in NO2 VTCs based on the Lambertian and BRDF approaches were found to be of the order of 0–3% in July and 0–20% in November with the extreme values found at large viewing angles. The much larger differences in November are mainly due to stronger BRDF effects at higher solar zenith angles. To a smaller extent, they are also caused by the typically more pronounced maximum of the NO2 a priori profiles in the boundary layer during the cold season, which make the retrieval more sensitive to radiation changes near the surface. However, BRDF impacts vary considerably across Europe due to differences in land surface type and increasing solar zenith angles at higher latitude. Finally, we compare BRDF-based NO2 VTCs with those retrieved using the GOME/TOMS Lambertian equivalent reflectance (LER) data set. The relative differences are mostly below 15% in July but in November the NO2 VTCs from TOMS/GOME are lower by 20–60%. Our results indicate that the specific choice of albedo data set is even more important than accounting for surface BRDF effects, and this again demonstrates the strong requirement for more accurate surface reflectance data sets.

Hemoglobin (Hb)-based O2 carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O2 deficit under conditions of anemia and traumatic blood loss. The O2 transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O2 delivery during extreme anemia. The anemic state was induced by hemodilution with a plasma expander (70-kDa dextran). After an initial moderate hemodilution to 18% hematocrit, animals were randomly assigned to exchange transfusion groups based on the type of PolybHb solution used (namely, T-state PolybHb and R-state PolybHb groups). Measurements of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O2 levels were performed at 11% hematocrit. Both PolybHbs were infused at 10 g/dl, and their viscosities were higher than nondiluted blood. Restitution of the O2 carrying capacity with T-state PolybHb exhibited lower arterial pressure and higher functional capillary density compared with R-state PolybHb. Central arterial O2 tensions increased significantly for R-state PolybHb compared with T-state PolybHb; conversely, microvascular O2 tensions were higher for T-state PolybHb compared with R-state PolybHb. The increased tissue Po2 attained with T-state PolybHb results from the larger amount of O2 released from the PolybHb and maintenance of macrovascular and microvascular hemodynamics compared with R-state PolybHb. These results suggest that the extreme high O2 affinity of R-state PolybHb prevented O2 bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O2 carrier, is a quintessential example of an appropriately engineered O2 carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs.

Despite recent advances in the design of hemoglobin (Hb)-based oxygen carriers (HBOCs), vasoconstriction, presumably caused by nitric oxide (NO) scavenging, vessel wall hyperoxygenation, and/or extravasation, has been identified as the principal road block hampering commercial development of HBOCs. This study was designed to analyze systemic and microvascular responses to the molecular mass and plasma concentration of tense (T)-state polymerized bovine Hb (PolybHb) solutions. Experiments were performed using the hamster window chamber model subjected to successive hypervolemic infusions of T-state PolybHb solutions. PolybHb plasma concentrations were evaluated, namely, 0.5, 1.0 and 1.5 g/dl, respectively. Infusion of PolybHb solutions with molecular mass >500 kDa elicited hypertension and vasoconstriction proportional to the plasma concentration and inversely proportional to the PolybHb cross-link density. However, two high-molecular mass PolybHb solutions, PolybHb(40:1)highPolybHb(50:1)high, did not elicit vasoconstriction at all concentrations studied, whereas PolybHb(50:1)highonly elicited moderate hypertension at the highest concentration studied. In contrast, infusion of PolybHb solutions with molecular mass 500 kDa that was proportional to the plasma concentration and inversely proportional to the PolybHb cross-link density. We present promising results for highly cross-linked T-state PolybHb solutions with molecular mass >500 kDa [PolybHb(40:1)highPolybHb(50:1)high], which supports the concept that HBOC size/molecular mass influences its proximity to the vascular endothelium and molecular diffusivity. The hemodynamics of HBOC within the plasma layer surrounding the abluminal side endothelium regulates NO production and consumption, vessel oxygen flux, and extravasation. Although mechanistically attractive, neither of these hypotheses can be directly tested in vivo and will require further investigation.

The data retrieval resolution of spin-valve reading head is a function of the spacing between the shield layer and the free layer of the spin-valve head - the head gap. Spin-valve head is of multi-layer structure. The layer thickness variation among different wafers leads to the variation of the gap length. Therefore it is important to develop a suitable methodology for testing and evaluating the gap length fluctuation not only during the head fabrication process but also at the magnetic integration level. This paper reports a novel method for the quantitative evaluation of the gap length fluctuation among different heads. The proposed method proved to be simple and easy for implementation.