Improvement of Raman lidar algorithm for quantifying aerosol extinction

Aerosols are particles of different composition and origin and influence the formation of clouds which are important in atmospheric radiative balance. At the present there is high uncertainty on the effect of aerosols on climate and this is mainly due to the fact that aerosol presence in the atmosphere can be highly variable in space and time. Monitoring of the aerosols in the atmosphere is necessary to better understanding many of these uncertainties. A lidar (an instrument that uses light to detect the extent of atmospheric aerosol loading) can be particularly useful to monitor aerosols in the atmosphere since it is capable to record the scattered intensity as a function of altitude from molecules and aerosols. One lidar method (the Raman lidar) makes use of the different wavelength changes that occur when light interacts with the varying chemistry and structure of atmospheric aerosols. One quantity that is indicative of aerosol presence is the aerosol extinction which quantifies the amount of attenuation (removal of photons), due to scattering, that light undergoes when propagating in the atmosphere. It can be directly measured with a Raman lidar using the wavelength dependence of the received signal. In order to calculate aerosol extinction from Raman scattering data it is necessary to evaluate the rate of change (derivative) of a Raman signal with respect to altitude. Since derivatives are defined for continuous functions, they cannot be performed directly on the experimental data which are not continuous. The most popular technique to find the functional behavior of experimental data is the least-square fit. This procedure allows finding a polynomial function which better approximate the experimental data. The typical approach in the lidar community is to make an a priori assumption about the functional behavior of the data in order to calculate the derivative. It has been shown in previous work that the use of the chi-square technique to determine the most likely functional behavior of the data prior to actually calculating the derivative eliminates the need for making a priori assumptions. We note that the a priori choice of a model itself can lead to larger uncertainties as compared to the method that is validated here. In this manuscript, the chi-square technique that determines the most likely functional behavior is validated through numerical simulation and by application to a large body of Raman lidar measurements. In general, we show that the chi-square approach to evaluate aerosol extinction yields lower extinction uncertainty than the traditional technique. We also use the technique to study the feasibility of developing a general characterization of the extinction uncertainty that could permit the uncertainty in Raman lidar aerosol extinction measurements to be estimated accurately without the use of the chi-square technique

Characterizing the Vertical Processes of Ozone in Colorado's Front Range Using the GSFC Ozone Dial

Although characterizing the interactions of ozone throughout the entire troposphere are important for health and climate processes, there is a lack of routine measurements of vertical profiles within the United States. In order to monitor this lower ozone more effectively, the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center TROPospheric OZone DIfferential Absorption Lidar (GSFC TROPOZDIAL) has been developed and validated within the Tropospheric Ozone Lidar Network (TOLNet). Two scientifically interesting ozone episodes are presented that were observed during the 2014 Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER AQ) campaign at Ft. Collins,Colorado.The first case study, occurring between 22-23 July 2014, indicates enhanced concentrations of ozone at Ft. Collins during nighttime hours, which was due to the complex recirculation of ozone within the foothills of the Rocky Mountain region. Although quantifying the ozone increase a loft during recirculation episodes has been historically difficult, results indicate that an increase of 20 -30 ppbv of ozone at the Ft. Collins site has been attributed to this recirculation. The second case, occurring between Aug 4-8th 2014, characterizes a dynamical exchange of ozone between the stratosphere and the troposphere. This case, along with seasonal model parameters from previous years, is used to estimate the stratospheric contribution to the Rocky Mountain region. Results suggest that a large amount of stratospheric air is residing in the troposphere in the summertime near Ft. Collins, CO. The results also indicate that warmer tropopauses are correlated with an increase in stratospheric air below the tropopause in the Rocky Mountain Region

Impaired oxidative stress response characterizes HUWE1-promoted X-linked intellectual disability.

Mutations in the HECT, UBA and WWE domain-containing 1 (HUWE1) E3 ubiquitin ligase cause neurodevelopmental disorder X-linked intellectual disability (XLID). HUWE1 regulates essential processes such as genome integrity maintenance. Alterations in the genome integrity and accumulation of mutations have been tightly associated with the onset of neurodevelopmental disorders. Though HUWE1 mutations are clearly implicated in XLID and HUWE1 regulatory functions well explored, currently much is unknown about the molecular basis of HUWE1-promoted XLID. Here we showed that the HUWE1 expression is altered and mutation frequency increased in three different XLID individual (HUWE1 p.R2981H, p.R4187C and HUWE1 duplication) cell lines. The effect was most prominent in HUWE1 p.R4187C XLID cells and was accompanied with decreased DNA repair capacity and hypersensitivity to oxidative stress. Analysis of HUWE1 substrates revealed XLID-specific down-regulation of oxidative stress response DNA polymerase (Pol) λ caused by hyperactive HUWE1 p.R4187C. The subsequent restoration of Polλ levels counteracted the oxidative hypersensitivity. The observed alterations in the genome integrity maintenance may be particularly relevant in the cortical progenitor zones of human brain, as suggested by HUWE1 immunofluorescence analysis of cerebral organoids. These results provide evidence that impairments of the fundamental cellular processes, like genome integrity maintenance, characterize HUWE1-promoted XLID

Recurrent Hypoglycaemia in a Patient with Metastatic Pancreatic Carcinoma

The patient's recurrent hypoglycaemia was found to be due to non-islet cell tumour hypoglycaemia

A vertically integrated pixel readout device for the Vertex Detector at the International Linear Collider

3D-Integrated Circuit technology enables higher densities of electronic circuitry per unit area without the use of nanoscale processes. It is advantageous for mixed mode design with precise analog circuitry because processes with conservative feature sizes typically present lower process dispersions and tolerate higher power supply voltages, resulting in larger separation of a signal from the noise floor. Heterogeneous wafers (different foundries or different process families) may be combined with some 3D integration methods, leading to the optimization of each tier in the 3D stack. Tracking and vertexing in future High-Energy Physics (HEP) experiments involves construction of detectors composed of up to a few billions of channels. Readout electronics must record the position and time of each measurement with the highest achievable precision. This paper reviews a prototype of the first 3D readout chip for HEP, designed for a vertex detector at the International Linear Collider. The prototype features 20 x 20 {micro}m{sup 2} pixels, laid out in an array of 64 x 64 elements and was fabricated in a 3-tier 0.18 {micro}m Fully Depleted SOI CMOS process at MIT-Lincoln Laboratory. The tests showed correct functional operation of the structure. The chip performs a zero-suppressed readout. Successive submissions are planned in a commercial 3D bulk 0.13 {micro}m CMOS process to overcome some of the disadvantages of an FDSOI process

Vertically integrated pixel readout chip for high energy physics

We report on the development of the vertex detector pixel readout chips based on multi-tier vertically integrated electronics for the International Linear Collider. Some testing results of the VIP2a prototype are presented. The chip is the second iteration of the silicon implementation of the prototype, data-pushed concept of the readout developed at Fermilab. The device was fabricated in the 3D MIT-LL 0.15 {micro}m fully depleted SOI process. The prototype is a three-tier design, featuring 30 x 30 {micro}m{sup 2} pixels, laid out in an array of 48 x 48 pixels

Weak-strong uniqueness property for the full Navier-Stokes-Fourier system

The Navier-Stokes-Fourier system describing the motion of a compressible, viscous, and heat conducting fluid is known to possess global-in-time weak solutions for any initial data of finite energy. We show that a weak solution coincides with the strong solution, emanating from the same initial data, as long as the latter exists. In particular, strong solutions are unique within the class of weak solutions

Relative entropies, suitable weak solutions, and weak strong uniqueness for the compressible Navier-Stokes system

We introduce the notion of relative entropy for the weak solutions of the compressible Navier-Stokes system. We show that any finite energy weak solution satisfies a relative entropy inequality for any pair of sufficiently smooth test functions. As a corollary we establish weak-strong uniqueness principle for the compressible Navier-Stokes system

Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients

The aim of the present study was to define the activity and tolerability of a triplet regimen including oxaliplatin 130 mg m−2 (2 h i.v. infusion) and raltitrexed 3.0 mg m−2 (15 min i.v. infusion) given on day 1, followed by levo-folinic acid 250 mg m−2 (2 h i.v. infusion) and 5-fluorouracil 1050 mg m−2 i.v. bolus on day 2, every 2 weeks, in pretreated colorectal cancer patients. From April 1999 to December 2000, 50 patients were enrolled: 26 were males and 24 females, their median age was 63 (range, 43–79) years; ECOG performance status was 0 in 26 patients, ⩾1 in 24 patients; 26 patients had received previous adjuvant chemotherapy, 40 patients had been exposed to one or two lines of palliative chemotherapy (including irinotecan in 31 cases); 18 patients were considered chemo-refractory. A total of 288 cycles were administered, with a median number of 6 (range 1–12) courses per patient. A complete response was obtained in three patients, and a partial response in nine patients, giving a major response rate of 24% (95% confidence interval, 13–38%), while 15 further patients showed a stable disease, for an overall control of tumour growth in 60% of patients. Three complete responses and three partial responses were obtained in patients pretreated with irinotecan (response rate, 19%); among refractory patients, three achieved partial responses (response rate, 13%). After a median follow-up of 18 (range, 10–30) months, 40 patients showed a progression of disease: the growth modulation index ranged between 0.2 and 2.5: it was ⩾1.33 (showing a significant delay of tumour growth) in 16 (40%) patients. Actuarial median progression-free survival time was 7.6 months, and median survival time was 13.6 months: estimated probability of survival was 55% at 1 year. Main severe toxicity was neutropenia: World Health Organisation grade 4 affected 32% of patients; non-haematological toxicity was mild: World Health Organisation grade 3 diarrhoea was complained of by 8%, and grade 3 stomatitis by 4% of patients; neurotoxicity (according to Lévi scale) was scored as grade 3 in 8% of patients. In conclusion, this regimen was manageable and active as salvage treatment of advanced colorectal cancer patients; it showed incomplete cross-resistance with irinotecan-based treatments, and proved to delay the progression of disease in a relevant proportion of treated patients

Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer

BACKGROUND: The combination of capecitabine and gemcitabine at Fixed Dose Rate (FDR) has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. FDR gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. The goals of this phase I study were to determine the maximum-tolerated dose (MTD) of chronomodulated capecitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT), the safety profile of this way of administration. METHODS: Patients with advanced solid tumours who had failed to response to standard therapy or for whom no standard therapy was available were elegible for this study. Capecitabine was administered orally according to following schedule: 1/4 of dose at 8:00 a.m.; 1/4 of dose at 6:00 p.m. and 1/2 of dose at 11:00 p.m. each day for 14 consecutive days, followed by a 7-day rest period. RESULTS: All 27 patients enrolled onto the study were assessable for toxicity. The most common toxicities during the first two cycles of chemotherapy were fatigue, diarrhoea and hand foot syndrome (HFS). Only one out of the nine patients treated at capecitabine dose of 2,750 mg/m(2 )met protocol-specified DLT criteria (fatigue grade 4). However, at these doses the majority of cycles of therapy were delivered without dose reduction or delay. No other episodes of DLT were observed at the same dose steps and at the lower dose steps of capecitabine (1,500/1,750/2,000/2,250/2,500 mg/m(2)). The dose of 2,750 mg/m(2 )is recommended for further study. Tumor responses were observed in patients with metastatic breast and colorectal cancer. CONCLUSION: High doses of chronomodulated capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies