Mutations in spike protein T cell epitopes of SARS-COV-2 variants: Plausible influence on vaccine efficacy.

With emerging SARS-CoV-2 variants, vaccines approved so far are under scrutiny for long term effectiveness against the circulating strains. There is a prevalent obsession with humoral immunity as in vitro studies have indicated diminished effects of vaccine-induced neutralizing antibodies. However, this need not clinically translate to vaccine resistance as immune response against all forms of present vaccine preparations is T dependent unlike that against native viral particles which can induce T independent immune responses. Thus, we focused on this major correlate of protection against infections, T cell response. Using bioinformatics tools, we analyzed SARS-CoV-2 Spike protein T cell epitopes and their diversity across Delta plus/B.1.617.2.1, Gamma/P.1 (variant of concern), B.1.1.429, Zeta/P.2 and Mink cluster 5/B.1.1.298 variants as well as Omicron/B.1.1.529 (variant of concern). We also compared HLA restriction profiles of the mutant epitopes with that of the native epitopes (from Wuhan_hu_1 strain, used in vaccine formulations). Our observations show ~90% conservation of CD4+ and CD8+ epitopes across Delta plus/B.1.617.2.1, Gamma/P.1 (variant of concern), B.1.1.429, Zeta/P.2 and Mink cluster 5/B.1.1.298. For the Omicron/B.1.1.529 variant, ~75% of CD4+ and ~ 87% CD8+ epitopes were conserved. Majority of the mutated CD4+ and CD8+ epitopes of this variant were predicted to retain the HLA restriction pattern as their native epitopes. The results of our bioinformatics analysis suggest largely conserved T cell responses across the studied variants, ability of T cells to tackle new SARS-CoV-2 variants and aid in protection from COVID-19 post vaccination. In conclusion, the results suggest that current vaccines may not be rendered completely ineffective against new variants.

Graphene overcoats for ultra-high storage density magnetic media.

Hard disk drives (HDDs) are used as secondary storage in digital electronic devices owing to low cost and large data storage capacity. Due to the exponentially increasing amount of data, there is a need to increase areal storage densities beyond ~1 Tb/in2. This requires the thickness of carbon overcoats (COCs) to be <2 nm. However, friction, wear, corrosion, and thermal stability are critical concerns below 2 nm, limiting current technology, and restricting COC integration with heat assisted magnetic recording technology (HAMR). Here we show that graphene-based overcoats can overcome all these limitations, and achieve two-fold reduction in friction and provide better corrosion and wear resistance than state-of-the-art COCs, while withstanding HAMR conditions. Thus, we expect that graphene overcoats may enable the development of 4-10 Tb/in2 areal density HDDs when employing suitable recording technologies, such as HAMR and HAMR+bit patterned media.

Nanoscale Critical Phenomena in a Complex Fluid Studied by X-Ray Photon Correlation Spectroscopy.

The advent of high-speed x-ray photon correlation spectroscopy now allows the study of critical phenomena in fluids to much smaller length scales and over a wider range of temperatures than is possible with dynamic light scattering. We present an x-ray photon correlation spectroscopy study of critical fluctuation dynamics in a complex fluid typical of those used in liquid-liquid extraction (LLE) of ions, dodecane-DMDBTDMA with extracted aqueous Ce(NO_{3})_{3}. We observe good agreement with both static and dynamic scaling without the need for significant noncritical background corrections. Critical exponents agree with 3D Ising values, and the fluctuation dynamics are described by simple exponential relaxation. The form of the dynamic master curve deviates somewhat from the Kawasaki result, with a more abrupt transition between the critical and noncritical asymptotic behavior. The concepts of critical phenomena thus provide a quantitative framework for understanding the structure and dynamics of LLE systems and a path forward to new LLE processes.

Strong Size Dependency on the Carrier and Photon Dynamics in InGaN/GaN Single Nanowalls Determined Using Photoluminescence and Ultrafast Transient Absorption Spectroscopy.

Here, we have demonstrated strong size dependency of quasi-equilibrium and nonequilibrium carrier and photon dynamics in InGaN/GaN single nanowalls using photoluminescence and transient absorption spectroscopy. We demonstrate that two-dimensional carrier confinement, strain relaxation, and modified density of states lead to a reduced Stokes shift, smaller full width at half-maxima, increased exciton binding energy, and reduced nonradiative recombination. The ultrafast transient spectroscopy shows that carrier capture is a two-step process dominated by optical phonons and carrier-carrier scattering in succession. The carrier capture is a strongly size-dependent process and becomes slower due to modulation of the density of available states for progressively decreasing nanowall sizes. The slowest process is the electron-hole recombination, which is also extremely size-dependent and the rate increases by almost an order of magnitude in comparison to that of quantum-well structures. Electron-hole wave function overlap and modified density of states are among the key aspects in determining all the properties of these structures.

Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction.

Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor.

Mandibular Reconstruction in Ameloblastoma Using Allogeneic Cord Stem Cells and Alloplastic Graft Material - Case Report.

Ameloblastoma is a histologically benign odontogenic tumour and has a tendency of locally aggressive behaviour. This is second most prevalent odontogenic tumour and most common in the molar-ramus-angle region and surgical resection is only treatment option. In this article, we propose an innovative approach to deal with these cases by using alloplastic graft with cord stem cells. Over 2.5 years follow-up, we could demonstrate bone regeneration using this technique with no recurrence. To the best of our knowledge, this is the first report of successful regeneration of part of ramus and body of mandible using allogeneic cord stem cells in cases of Ameloblastoma.

Prevention of graft-tunnel mismatch during anatomical anterior cruciate ligament reconstruction using a bone-patellar tendon-bone graft.

Graft-tunnel mismatch of the bone-patellar tendon-bone (BPTB) graft is a major concern during anatomical anterior cruciate ligament (ACL) reconstruction if the femoral tunnel is positioned using a far medial portal technique, as the femoral tunnel tends to be shorter compared with that positioned using a transtibial portal technique. This study describes an accurate method of calculating the ideal length of bone plugs of a BPTB graft required to avoid graft-tunnel mismatch during anatomical ACL reconstruction using a far medial portal technique of femoral tunnel positioning. Based on data obtained intra-operatively from 60 anatomical ACL reconstruction procedures, we calculated the length of bone plugs required in the BPTB graft to avoid graft-tunnel mismatch. When this was prevented in all the 60 cases, we found that the mean length of femoral bone plug that remained in contact with the interference screw within the femoral tunnel was 14 mm (12 to 22) and the mean length of tibial bone plug that remained in contact with the interference screw within the tibial tunnel was 23 mm (18 to 28). These results were used to validate theoretical formulae developed to predict the required length of bone plugs in BPTB graft during anatomical ACL reconstruction using a far medial portal technique.

Determination of personalized diabetes treatment plans using a two-delay model.

Diabetes cases worldwide have risen steadily over the past few decades, lending urgency to the search for more efficient, effective, and personalized ways to treat the disease. Current treatment strategies, however, may fail to maintain oscillations in blood glucose concentration that naturally occur multiple times per day, an important element of normal human physiology. Building upon recent successes in mathematical modeling of the human glucose-insulin system, we show that both food intake and insulin therapy likely demand increasingly precise control over insulin sensitivity if oscillations at a healthy average glucose concentration are to be maintained. We then model and describe personalized treatment options for patients with diabetes that maintain these oscillations. We predict that for a person with type II diabetes, both blood glucose levels can be controlled and healthy oscillations maintained when the patient gets an hour of daily exercise and is placed on a combination of Metformin and sulfonylurea drugs. We note that insulin therapy and an additional hour of exercise will reduce the patient׳s need for sulfonylureas. Results of a modeling analysis suggest that, with constant nutrition and controlled exercise, the blood glucose levels of a person with type I diabetes can be properly controlled with insulin infusion between 0.45 and 0.7µU/mlmin. Lastly, we note that all suggested strategies rely on existing clinical techniques and established treatment measures, and so could potentially be of immediate use in the design of an artificial pancreas.

Treatment of osteoradionecrosis of mandible with bone marrow concentrate and with dental pulp stem cells.

Osteoradionecrosis (ORN) is a noninfectious, necrotic condition of the bone occurring as a complication of radiotherapy. Most cases occur following trauma or surgical manipulation of the irradiated site. Mandible is the most common bone to be affected following head and neck irradiation. The aim was to develop a successful therapeutic approach for ORN. A spectrum of treatment modalities is practiced for ORN with variable success rate that includes simple irrigation of the affected bone to the partial or complete resection of the jaw bone. In this paper, we present two cases which had successful therapeutic approach for ORN of mandible with autologous bone marrow concentrate stem cells and allogeneic dental pulp stem cells (DPSC) with platelet rich plasma (PRP) following failure of conventional methods. Autologous bone marrow aspirate concentrate (BMAC) was injected around the socket and into the periosteum for one case, and DPSC were mixed with tricalcium phosphate and inserted at the site of the defect in one case. The patient treated with BMAC remained asymptomatic and complete bone remodeling was noticed after 1 year. The extraoral sinus was excised, and healing was uneventful without recurrence in the patient treated with allogeneic DPSC and PRP. Periodic panoramic radiographs revealed an appreciable bone formation from the 2(nd) month onward. We have successfully treated two cases of ORN with BMAC and DPSC, respectively.

"Hybrid" lesion of the maxilla.

Juvenile ossifying fibroma is an uncommon benign but aggressive fibroosseous lesion that affects the craniofacial skeleton. Their distinct clinical and histopathological features warrant the lesion to be considered as a separate entity from other fibro-osseous group of lesions such as fibrous dysplasia and cemento ossifying fibroma. Concomitant development of secondary aneurysmal bone cyst may rarely occur, which makes the lesion more aggressive and difficult to treat. We report a case of a 6 year old girl who was diagnosed with aneurysmal bone cyst during her earlier presentation at a private hospital and was treated for the same. The lesion recurred within 6 months. The second incisional biopsy specimen revealed features of trabecular variant of juvenile ossifying fibroma along with areas of aneurysmal bone cyst.

Optically directed assembly of continuous mesoscale filaments.

We demonstrate irreversible continuous filament formation when a weak laser focus is positioned near the edge of an evaporating colloidal droplet containing carbon and gold nanoparticles. Optical trapping, hydrothermal, and chemical interactions lead to controlled colloidal synthesis of stable, irreversible mesoscale filaments of arbitrary shape and size. Mechanisms for this optically directed assembly are discussed with fluid dynamics, molecular dynamics, and lattice kinetic Monte Carlo calculations.

Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.

BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.

Isolation and characterization of bioactive and antibacterial compound from Helianthus annuus linn.

A bioactive compound with antibacterial activity was isolated and purified from the extract of leaves of sunflower, Helianthus annuus. The bioactive compound was characterized using 1H and 13C NMR. The compound induced auxin, gibberellins and cytokinin in Oryza sativa and Phaseolus mungo. It also showed activity against Xanthomonas oryzae pv. oryzae.

Hydrogen bond directed highly regioselective palladium-catalyzed allylic substitution.

The palladium-catalyzed allylic substitution of 5-vinyloxazolidinones and derivatives was investigated. Unusual and high regioselectivity for the branched product was observed. The regioselectivity was influenced by the type of substrate, the solvents, and the nucleophile. Imide-type nucleophiles were found to be directed to the internal carbon (branched:linear, 75:25 to >98:2), whereas sulfonamides, amines, and malonates added only to the terminal carbon of the allyl complex. Relatively nonpolar solvents such as toluene and THF favored the branched product (97:3 and 95:5, respectively). Acetonitrile and dichloromethane afforded lower regioselectivity (50:50 and 67:33, respectively), and the use of the protic solvent ethanol resulted in reversal of the regioselectivity (12:88). The directing group on the substrate was important. Amides afforded almost complete formation of the branched product, and carbamates gave a 50:50 mixture of regioisomers with phthalimide as the nucleophile. Evidence for direction of the nucleophile via hydrogen bonding was obtained by replacing the hydrogen of the amide with a methyl, resulting in the production of only the normal linear product.

Palladium-mediated regiodivergent kinetic resolution.

[reaction: see text]. The allylic substitution of racemic 5-vinyloxazolidinones with phthalimide and a chiral palladium catalyst afforded optically enriched regioisomeric products. Optimal divergence was found by employing chiral DIOP ligands in toluene. These results demonstrate the influence of chiral ligand/chiral substrate matching on the regioselectivity in a novel resolution strategy.

Calcium accelerates endocytosis of vSNAREs at hippocampal synapses.

A pH-sensitive form of green-fluorescent protein (GFP) fused to the lumenal domain of VAMP (synapto-pHluorin) provides a sensitive optical probe to track the net balance between exocytosis and endocytosis of this protein at small synaptic terminals of the central nervous system. Here we used a reversible proton-pump blocker that prevents vesicle re-acidification upon endocytosis to trap vesicles in the alkaline state during recycling. In combination with optical measurements of synapto-pHluorin, we used alkaline trapping to examine the kinetic components of exocytosis and endocytosis separately at synaptic terminals. Using this approach, we show that, in addition to controlling exocytosis, intracellular calcium levels tightly regulate the speed of endocytosis, increasing it to a maximal speed of approximately one vesicle per second.