Study of underlying particle spectrum during huge X-ray flare of Mkn 421 in April 2013

Context: In April 2013, the nearby (z=0.031) TeV blazar, Mkn 421, showed one of the largest flares in X-rays since the past decade. Aim: To study all multiwavelength data available during MJD 56392 to 56403, with special emphasis on X-ray data, and understand the underlying particle energy distribution. Methods: We study the correlations between the UV and gamma bands with the X-ray band using the z-transformed discrete correlation function. We model the underlying particle spectrum with a single population of electrons emitting synchrotron radiation, and do a statistical fitting of the simultaneous, time-resolved data from the Swift-XRT and the NuSTAR. Results: There was rapid flux variability in the X-ray band, with a minimum doubling timescale of $1.69 \pm 0.13$ hrs. There were no corresponding flares in UV and gamma bands. The variability in UV and gamma rays are relatively modest with $\sim 8 \%$ and $\sim 16 \%$ respectively, and no significant correlation was found with the X-ray light curve. The observed X-ray spectrum shows clear curvature which can be fit by a log parabolic spectral form. This is best explained to originate from a log parabolic electron spectrum. However, a broken power law or a power law with an exponentially falling electron distribution cannot be ruled out either. Moreover, the excellent broadband spectrum from $0.3-79$ keV allows us to make predictions of the UV flux. We find that this prediction is compatible with the observed flux during the low state in X-rays. However, during the X-ray flares, the predicted flux is a factor of $2-50$ smaller than the observed one. This suggests that the X-ray flares are plausibly caused by a separate population which does not contribute significantly to the radiation at lower energies. Alternatively, the underlying particle spectrum can be much more complex than the ones explored in this work.Comment: 11 pages, 7 figures, Accepted in A&

Poly(ethylene glycol) Hydrogels to Engineer the Mesenchymal Stromal Cell Secretome

Bone marrow derived mesenchymal stem/stromal cells (MSCs) are widely used in clinical trials. In addition to their multipotency, MSC therapeutic efficacy relies on their secretory abilities; specifically, their secretion of growth factors, chemokines, and cytokines can influence endogenous cell behaviors and direct wound healing. Because MSCs only constitute 0.001-0.01% of all mononuclear cells in the bone marrow, their in vitro expansion is required to achieve clinically relevant cell numbers. Unfortunately, expansion of MSCs on tissue culture polystyrene (TCPS) can significantly reduce their in vivo regenerative capacities. Additionally, when injected intravenously or delivered carrier-free to a defect site, MSCs have low survival and engraftment. To begin to address these challenges, this thesis focused on developing hydrogel platforms to direct and maintain MSC secretory properties during in vitro expansion and in vivo delivery. We used PEG-based synthetic macromers reacted via bio-click reactions to create hydrogel environments to direct matrix mechanics, MSC-matrix interactions, and MSC-MSC contacts. First, by controlling MSC exposure to matrix mechanics, we designed a 2D soft hydrogel intervention to increase MSC cytokine secretion during in vitro TCPS expansion. Next, we designed a granular hydrogel system, comprised of micron-scale PEG-based hydrogels, to promote MSC secretion in 3D. By modulating scaffold porosity and including integrin and cadherin binding epitopes, we controlled MSC cell-cell and cell-matrix interactions. Pore-directed cell clustering increased MSC trophic factor secretion, specifically through N-cadherin mediated interactions. Exploiting our understanding of the influence of cell clustering and the inclusion of N-cadherin peptide mimetics on MSC secretion, we next evaluated the capacity of MSC-laden porous scaffolds to direct bone regeneration in critical-sized rat calvarial defects. Finally, we used these scaffolds to better understand how MSC secretion is changed in osteoporotic environments. Large clusters of osteoporotic MSCs had a pro-resorptive secretory profile, which was reduced by blocking N-cadherin interactions. Overall, we designed multiple hydrogel platforms to exert precise control over the in vitro MSC microenvironment and increased our understanding of how biophysical factors can be tuned to influence MSC secretory properties.</p

A novel NGS library preparation method to characterize native termini of fragmented DNA.

Biological and chemical DNA fragmentation generates DNA molecules with a variety of termini, including blunt ends and single-stranded overhangs. We have developed a Next Generation Sequencing (NGS) assay, XACTLY, to interrogate the termini of fragmented DNA, information traditionally lost in standard NGS library preparation methods. Here we describe the XACTLY method, showcase its sensitivity and specificity, and demonstrate its utility in in vitro experiments. The XACTLY assay is able to report relative abundances of all lengths and types (5' and 3') of single-stranded overhangs, if present, on each DNA fragment with an overall accuracy between 80-90%. In addition, XACTLY retains the sequence of each native DNA molecule after fragmentation and can capture the genomic landscape of cleavage events at single nucleotide resolution. The XACTLY assay can be applied as a novel research and discovery tool for fragmentation analyses and in cell-free DNA

Heterosis and heterobeltiosis in bell pepper (Capsicum annuum var. grossum) for growth and yield parameters

The magnitude of heterosis over commercial check and better parent was estimated to identify best crosses for growth and yield traits in bell pepper. Experimental material included 21 F1 hybrids developed by crossing seven diverse parents in half diallel mating design. The findings revealed that Arka Mohini X CW308 showed best heterotic cross combinations, recorded significantly higher heterosis and high per se value over commercial check with respect to number of primary branches, number of secondary branches, plant height, days to 50% flowering, days to first harvest, fruit length, fruit width, number of lobes per fruit, number of fruits per plant and average fruit weight. The cross Arka Mohini X CW308 also showed high heterobeltiosis for traits like fruit length, number of fruits per plant, average fruit weight and average yield per plant. Hence, this hybrid with high per se value and heterosis can be utilized to obtain desirable segregates for development of superior genotype for improvement of horticultural traits in bell pepper

Post-surgical giant pseudo meningocele in a patient with cervical neurofibroma: Case report and literature review

A patient aged 48-year-old, presented to the outpatient department with neck pain and weakness of all the limbs for three months. On examination, he had power 3/5 in all the limbs with bilateral hand grip weakness of 50%. Neuroimaging study showed a dumbell shaped lesion with compression of the spinal cord in the cervical region that was identified as a C4/C5 neurofibroma. Cervical laminectomy and excision of the tumour and unilateral lateral mass screw and rod fixation was done. Post operatively patient was discharged with improved motor power. One month after surgery, he presented with bulging at the operative site, which was diagnosed as a pseudo meningocele that did not respond to conservative therapy. As swelling was increasing size and becoming tense and also complaining of severe neck pain and postural hypotension, it was managed surgically, three months after first surgery, by excision of pseudo meningocele with primary repair of dural defect with muscle graft and lumbar drain inserted intraoperatively which was removed after five days. Patient’s neck pain and hypotensive episode were improved after repair. Possible causes for the development of post-operative pseudo meningocele can be soft tissue and paravertebral muscle damage or high intradural pressures that causes leakage of cerebrospinal fluid from a very small dural defect. Shunt insertion should be reserved for patients with impaired cerebrospinal fluid absorption or those with a refractory fistula, despite medical therapies and direct surgical repairs

Schwannoma of intermediate supraclavicular nerve: Case report

Schwannoma of supraclavicular nerve is very rare tumour occurring in head and neck region. This case is reported as a rare case of intermediate supraclavicular nerve schwannoma. A 48-year-old female patient presented to the outpatient department with right supraclavicular swelling for 5 years. She was diagnosed differently initially as having connective tissue neoplasm, tuberculous lymphadenitis, and granulomatous lymphadenitis by different surgeons. After all investigations, she was subjected to enucleation of mass and the histopathological report was suggestive of schwannoma. Post-op no neurological deficit was observed. She was discharged on fourth post-operative day

Natural ergot alkaloids in ocular pharmacotherapy: known molecules for novel nanoparticle-based delivery systems

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) granted to I.B. (88887.368385/2019-00), by the Portuguese Science and Technology Foundation (FCT) and co-financed by FEDER, under the Partnership Agreement PT2020, granted to E.B.S. (UIDB/04469/2020 strategic fund), by the Nutraceutica come supporto nutrizionale nel paziente oncologico, project granted to A.S. (CUP: B83D18000140007), and by Foundation of Research Support of the São Paulo State (FAPESP) for the funded projects 2011/10333-1, 2012/03427-2, and 2018/26069-0 and for the National Council for Scientific and Technological Development (CNPq) granted to W.P.O.info:eu-repo/semantics/publishedVersio

A SINFONI Integral Field Spectroscopy Survey for Galaxy Counterparts to Damped Lyman-alpha Systems - III. Three Additional Detections

We report three additional SINFONI detections of H-alpha emission line from quasar absorbers, two of which are new identifications. These were targeted among a sample of systems with log N(HI)>19.0 and metallicities measured from high-resolution spectroscopy. The detected galaxies are at impact parameters ranging from 6 to 12 kpc from the quasar's line-of-sight. We derive star formation rates (SFR) of a few solar masses per year for the two absorbers at z_abs~1 and SFR=17 solar masses per year for the DLA at z_abs~2. These three detections are found among a sample of 16 DLAs and sub-DLAs (5 at z_abs~1 and 7 at z_abs~2). For the remaining undetected galaxies, we derive flux limits corresponding to SFR<0.1--11.0 solar masses per year depending on redshift of the absorber and depth of the data. When combined with previous results from our survey for galaxy counterparts to HI-selected absorbers, we find a higher probability of detecting systems with higher metallicity as traced by dust-free [Zn/H] metallicity. We also report a higher detection rate with SINFONI for host galaxies at z_abs~1 than for systems at z_abs~2. Using the NII/H-alpha ratio, we can thus compare absorption and emission metallicities in the same high-redshift objects, more than doubling the number of systems for which such measures are possible.Comment: 16 pages, 8 figures, accepted for publication in MNRA