ABSTRACT We study the link between an expanding coronal shock and the energetic particles measured near Earth during the ground level enhancement of 2012 May 17. We developed a new technique based on ...multipoint imaging to triangulate the three-dimensional (3D) expansion of the shock forming in the corona. It uses images from three vantage points by mapping the outermost extent of the coronal region perturbed by the pressure front. We derive for the first time the 3D velocity vector and the distribution of Mach numbers, MFM, of the entire front as a function of time. Our approach uses magnetic field reconstructions of the coronal field, full magnetohydrodynamic simulations and imaging inversion techniques. We find that the highest MFM values appear near the coronal neutral line within a few minutes of the coronal mass ejection onset; this neutral line is usually associated with the source of the heliospheric current and plasma sheet. We illustrate the variability of the shock speed, shock geometry, and Mach number along different modeled magnetic field lines. Despite the level of uncertainty in deriving the shock Mach numbers, all employed reconstruction techniques show that the release time of GeV particles occurs when the coronal shock becomes super-critical (MFM > 3). Combining in situ measurements with heliospheric imagery, we also demonstrate that magnetic connectivity between the accelerator (the coronal shock of 2012 May 17) and the near-Earth environment is established via a magnetic cloud that erupted from the same active region roughly five days earlier.
The Greater Everglades Region of South Florida is one of the largest natural wetlands and the only subtropical ecosystem found in the continental United States. Mosquitoes are seasonally abundant in ...the Everglades where several potentially pathogenic mosquito-borne arboviruses are maintained in natural transmission cycles involving vector-competent mosquitoes and reservoir-competent vertebrate hosts. The fragile nature of this ecosystem is vulnerable to many sources of environmental change, including a wetlands restoration project, climate change, invasive species and residential development. In this study, we obtained baseline data on the distribution and abundance of both mosquitos and arboviruses occurring in the southern Everglades region during the summer months of 2013, when water levels were high, and in 2014, when water levels were low. A total of 367,060 mosquitoes were collected with CO2-baited CDC light traps at 105 collection sites stratified among the major landscape features found in Everglades National Park, Big Cypress National Preserve, Fakahatchee State Park Preserve and Picayune State Forest, an area already undergoing restoration. A total of 2,010 pools of taxonomically identified mosquitoes were cultured for arbovirus isolation and identification. Seven vertebrate arboviruses were isolated: Everglades virus, Tensaw virus, Shark River virus, Gumbo Limbo virus, Mahogany Hammock virus, Keystone virus, and St. Louis encephalitis virus. Except for Tensaw virus, which was absent in 2013, the remaining viruses were found to be most prevalent in hardwood hammocks and in Fakahatchee, less prevalent in mangroves and pinelands, and absent in cypress and sawgrass. In contrast, in the summer of 2014 when water levels were lower, these arboviruses were far less prevalent and only found in hardwood hammocks, but Tensaw virus was present in cypress, sawgrass, pinelands, and a recently burned site. Major environmental changes are anticipated in the Everglades, many of which will result in increased water levels. How these might lead to the emergence of arboviruses potentially pathogenic to both humans and wildlife is discussed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The biotech industry is, nowadays, facing unparalleled challenges due to the enhanced demand for biotechnology-based human therapeutic products, such as monoclonal antibodies (mAbs). This has led ...companies to improve substantially their upstream processes, with the yield of monoclonals increasing to titers never seen before. The downstream processes have, however, been overlooked, leading to a production bottleneck. Although chromatography remains the workhorse of most purification processes, several limitations, such as low capacity, scale-related packing problems, low chemical and proteolytic stability and resins' high cost, have arisen. Aqueous two-phase extraction (ATPE) has been successfully revisited as a valuable alternative for the capture of antibodies. One of the important remaining questions for this technology to be adopted by the biotech industries is, now, how it compares to the currently established platforms in terms of costs and environmental impact. In this report, the economical and environmental sustainability of the aqueous two-phase extraction process is evaluated and compared to the currently established protein A affinity chromatography. Accordingly, the ATPE process was shown to be considerably advantageous in terms of process economics, especially when processing high titer cell culture supernatants. This alternative process is able to purify continuously the same amount of mAbs reducing the annual operating costs from 14.4 to 8.5 million (US$/kg) when cell culture supernatants with mAb titers higher than 2.5g/L are processed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Nairovirus, one of five bunyaviral genera, includes seven species. Genomic sequence information is limited for members of the Dera Ghazi Khan, Hughes, Qalyub, Sakhalin, and Thiafora nairovirus ...species. We used next-generation sequencing and historical virus-culture samples to determine 14 complete and nine coding-complete nairoviral genome sequences to further characterize these species. Previously unsequenced viruses include Abu Mina, Clo Mor, Great Saltee, Hughes, Raza, Sakhalin, Soldado, and Tillamook viruses. In addition, we present genomic sequence information on additional isolates of previously sequenced Avalon, Dugbe, Sapphire II, and Zirqa viruses. Finally, we identify Tunis virus, previously thought to be a phlebovirus, as an isolate of Abu Hammad virus. Phylogenetic analyses indicate the need for reassignment of Sapphire II virus to Dera Ghazi Khan nairovirus and reassignment of Hazara, Tofla, and Nairobi sheep disease viruses to novel species. We also propose new species for the Kasokero group (Kasokero, Leopards Hill, Yogue viruses), the Ketarah group (Gossas, Issyk-kul, Keterah/soft tick viruses) and the Burana group (Wēnzhōu tick virus, Huángpí tick virus 1, Tǎchéng tick virus 1). Our analyses emphasize the sister relationship of nairoviruses and arenaviruses, and indicate that several nairo-like viruses (Shāyáng spider virus 1, Xīnzhōu spider virus, Sānxiá water strider virus 1, South Bay virus, Wǔhàn millipede virus 2) require establishment of novel genera in a larger nairovirus-arenavirus supergroup.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve ...clinical outcomes of patients admitted to the hospital with severe COVID-19.
We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio OR greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT mITT population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278.
447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 95% CI 0·94–1·97, p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups.
In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19.
COALITION COVID-19 Brazil and EMS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Over the last decade, nanocellulose-based nanocomposite hydrogels have emerged as promising materials in different fields of application such as medicine, food, and agriculture. The present review ...addresses the advances in the synthesis methods and technological applications of these hydrogels. Different chemical and physical cross-linking methods used for the design of cellulose nanocrystals, cellulose nanofibrils, and bacterial cellulose hydrogels are discussed in detail. Nanocomposite hydrogels based on nanocellulose or reinforced with nanocellulose have good mechanical properties, biocompatibility, and biodegradability and allow the incorporation of several molecules or solutes, which can provide a slow and controlled release profile. The major advances exploring these hydrogels in biomedicine, food, and agriculture are reviewed. Finally, challenges and environmental issues related to their production are briefly discussed.
Nanocellulose-based nanocomposite hydrogels are promising materials in different fields of application such as medicine, food, and agriculture.
The crystallization mechanisms of a series of fourteen 7-chloro-4-substituted-quinolines (substituents: (
1
) OCH
3
, (
2
) OCH
2
CH
3
, (
3
) OCH
2
CH&z.dbd;CH
2
, (
4
) O(CH
2
)
2
OH, (
5
) O(CH
2
...)
3
OH, (
6
) NH(CH
2
)
2
CH
3
, (
7
) NH(CH
2
)
3
CH
3
, (
8
) NH(CH
2
)
2
OH, (
9
) NHCH(CH
2
CH
3
)CH
2
OH, (
10
) NH(CH
2
)
2
Cl, (
11
) NHN&z.dbd;CH(C
6
H
5
), (
12
) NHN&z.dbd;CH(2-FC
6
H
4
), (
13
) NHN&z.dbd;CH(3-FC
6
H
4
), and (
14
) NHN&z.dbd;CH(4-FC
6
H
4
)) were proposed based on a retrocrystallization approach using the supramolecular cluster as demarcation. Crystallization mechanism stage parameters -
N
CG
% and NG/NC - were determined. The 4-substituents present in quinolines caused six different mechanisms, starting from the monomers in solution to dimers, 1D nuclei, and 2D nuclei (
6
,
11
,
12
); 2D nucleus formation (
5
); 1D nuclei to 2D nuclei (
7
,
9
); concomitant dimers and 1D nuclei to a 3D crystal (
8
); 1D nuclei directly to a 3D crystal lattice (
1-4
,
10
,
14
), and dimers to 2D nuclei and then to a 3D crystal (
13
). Analysis of
G
AI
showed atom atom intermolecular interactions in the proposed first nuclei for compounds
4
and
5
. The nucleation process inferred in the solid state was partially confirmed during the formation of the proto-crystal in solution due to the changes of the hydrogen chemical shift in variable-concentration
1
H-NMR experiments. Results revealed that the size of the alkyl chain and the presence of different functional groups in the 4-substituents influenced the crystallization process.
The crystallization mechanisms of a series of fourteen 7-chloro-4-substituted-quinolines were proposed based on a retrocrystallization approach using the supramolecular cluster as demarcation.
ABSTRACT Recent intensive Swift monitoring of the Seyfert 1 galaxy NGC 5548 yielded 282 usable epochs over 125 days across six UV/optical bands and the X-rays. This is the densest extended active ...galactic nucleus (AGN) UV/optical continuum sampling ever obtained, with a mean sampling rate <0.5 day. Approximately daily Hubble Space Telescope UV sampling was also obtained. The UV/optical light curves show strong correlations ( ) and the clearest measurement to date of interband lags. These lags are well-fit by a wavelength dependence, with a normalization that indicates an unexpectedly large disk radius of lt-day at 1367 , assuming a simple face-on model. The U band shows a marginally larger lag than expected from the fit and surrounding bands, which could be due to Balmer continuum emission from the broad-line region as suggested by Korista and Goad. The UV/X-ray correlation is weaker ( ) and less consistent over time. This indicates that while Swift is beginning to measure UV/optical lags in general agreement with accretion disk theory (although the derived size is larger than predicted), the relationship with X-ray variability is less well understood. Combining this accretion disk size estimate with those from quasar microlensing studies suggests that AGN disk sizes scale approximately linearly with central black hole mass over a wide range of masses.
Golden hamsters (Mesocricetus auratus) experimentally infected with West Nile virus (WNV) developed chronic renal infection and persistent shedding of virus in urine for up to 8 months, despite ...initial rapid clearance of virus from blood and the timely appearance of high levels of specific neutralizing antibodies. Infectious WNV could be recovered by direct culture of their urine and by cocultivation of kidney tissue for up to 247 days after initial infection. Only moderate histopathologic changes were observed in the kidneys or brain of the chronically infected hamsters, although WNV antigen was readily detected by immunohistochemistry within epithelium, interstitial cells, and macrophages in the distal renal tubules. Comparison of WNV isolates from serial urine samples from individual hamsters over several months indicated that the virus underwent both genetic and phenotypic changes during persistent infection. These findings are similar to previous reports of persistent infection with tickborne encephalitis and Modoc viruses
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
This practice-based retrospective study evaluated the survival of resin composite restorations in posterior teeth, focusing on the influence of potential patient risk factors. In total, 306 posterior ...composite restorations placed in 44 adult patients were investigated after 10 to 18 yrs. The history of each restoration was extracted from the dental records, and a clinical evaluation was performed with those still in situ. The patient risk status was assessed for caries and “occlusal-stress” (bruxism-related). Statistical analysis was performed by the Kaplan–Meier method and Cox-regression multivariate analysis. In total, 30% of the restorations failed, of which 82% were found in patients with 1 or 2 risk factors. Secondary caries was the main reason of failure within caries-risk patients, whereas fracture was the main reason in “occlusal-stress-risk” patients. The patient variables gender and age did not significantly affect survival, but risk did (p < .001). Tooth type (p < .001), arch (p = .013), and pulpal vitality (p = .003) significantly affected restoration survival. Within the limits of this retrospective evaluation, the survival of restorations is affected by patient risk factors, which should be included in survival analyses of restorations.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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