•First report on the current information on the effects of ultrasonic treatment on rice grain and rice starch.•Ultrasound imparts morphological, textural, and physicochemical changes in rice rain and ...rice starch.•Ultrasonication enhances the formation of metabolites, uptake of fortificants, and softening of rice texture.•Ultrasonic treatment can be used for applications towards the improvement of rice functional properties.
As a green, nonthermal, and innovative technology, ultrasonication generates acoustic cavitation in an aqueous medium, developing physical forces that affect the starch chemistry and rice grain characteristics. This review describes the current information on the effect of ultrasonication on the morphological, textural, and physicochemical properties of rice starch and grain. In a biphasic system, ultrasonication introduced fissures and cracks, which facilitated higher uptake of water and altered the rice starch characteristics impacting textural properties. In wholegrain rice, ultrasonic treatment stimulated the production of health-related metabolites, facilitated the higher uptake of micronutrient fortificants, and enhanced the palatability by softening the rice texture. This review provides insights into the future direction on the utilization of ultrasonication for the applications towards the improvement of rice functional properties.
The axial coupling of the nucleon, g
, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength ...of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of g
makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome
: contamination of g
from excited states must be controlled in the calculations and statistical precision must be improved markedly
. Here we use an unconventional method
inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a g
value of 1.271 ± 0.013, which has a precision of about one per cent.
A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the ...central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.
Observation of neutrinoless double beta decay, a lepton number violating process that has been proposed to clarify the nature of neutrino masses, has spawned an enormous world-wide experimental ...effort. Relating nuclear decay rates to high-energy, beyond the standard model (BSM) physics requires detailed knowledge of nonperturbative QCD effects. Using lattice QCD, we compute the necessary matrix elements of short-range operators, which arise due to heavy BSM mediators, that contribute to this decay via the leading order π^{-}→π^{+} exchange diagrams. Utilizing our result and taking advantage of effective field theory methods will allow for model-independent calculations of the relevant two-nucleon decay, which may then be used as input for nuclear many-body calculations of the relevant experimental decays. Contributions from short-range operators may prove to be equally important to, or even more important than, those from long-range Majorana neutrino exchange.
Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a ...single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development.
Twenty-eight patients with metastatic melanoma received monthly intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to determine recommended monthly phase II dose. During phase II, 89 patients received tremelimumab 10 mg/kg once every month or 15 mg/kg every 3 months.
No dose-limiting toxicity was observed in phase I once every month dosing. In phase II, 8 (10%) of 84 response-assessable patients attained objective antitumor responses; best overall objective response was one complete response and three partial responses in each dosing regimen. Most responses were durable (range, 3 to 30+ months). Most frequent treatment-related adverse events (AEs) were diarrhea, rash, and pruritus. Frequency of grade 3/4 AEs was 13% in the 15 mg/kg every 3 months arm and 27% in the 10 mg/kg once every month. Serious AEs were also less frequent in the 15 mg/kg once every 3 months cohort (9% v 23% in 10 mg/kg arm).
Multiple infusions of tremelimumab were generally tolerable and demonstrated single-agent antitumor activity. Both phase II regimens generated durable tumor responses. Based on its more favorable safety profile, 15 mg/kg every 3 months was selected for further clinical testing.
•First report on structural change in κ-carrageenan under ultrasonic condition.•Sonication decreased the average molecular weight of κ-carrageenan.•Sonication afforded minor modification in the ...structure of the κ-carrageenan repeating units.
Degradation of polysaccharides to afford low-molecular-weight oligosaccharides have been shown to produce new bioactivities that are not present in the starting material. The simplicity of ultrasonic treatment in the degradation of a polysaccharide, such as κ-carrageenan, offers practical advantage in producing degraded products with lower molecular weight that may have new interesting potential activities. This study embarked on investigating the effects in molecular weights and structural changes of κ-carrageenan under varying ultrasonic conditions. Molecular weight (MW) monitoring of ultrasonically-treated κ-carrageenan at various conditions were done by gel permeation chromatography. The product formed using the optimized condition was characterized using FTIR and NMR. The decrease in MW has been shown to be dependent on low concentration (5.0 mg mL−1), high amplitude (85%), and long treatment time (180 mins) to afford a degraded κ-carrageenan with average molecular weight (AMW) of 41,864 Da, which is a 96.33% reduction from the raw sample with initial AMW of 1,139,927 Da. Structural analysis reveals that most of the peaks of the raw κ-carrageenan was retained with minor change. 1D and 2D NMR analyses showed that the sonic process afforded a product where the sulfate group at the G4S-4 position was cleaved forming a methylene in the G4S ring. The results would be useful in the structure–activity relationship of κ-carrageenan oligosaccharides and in understanding the effect in the various potential applications of degraded κ-carrageenan.
Tivantinib (ARQ 197) is an orally available, non-adenosine triphosphate competitive, selective c-MET inhibitor. The primary objective of this study was to evaluate the safety, tolerability and to ...establish the recommended phase II dose (RP2D) of tivantinib and gemcitabine combination.
Patients with advanced or metastatic solid tumors were treated with escalating doses of tivantinib (120–360mg capsules) in combination with gemcitabine (1000mg/m2 weekly for 3 of 4 weeks). Different schedules of administration were tested and modified based on emerging preclinical data. Tivantinib was given continuously, twice a day (b.i.d.) for 2, 3 or 4 weeks of a 28-day cycle or on a 5-day on, 2-day off schedule (the day before and day of gemcitabine administration).
Twenty-nine patients were treated with gemcitabine and escalating doses of tivantinib: 120mg b.i.d. (n = 4), 240mg b.i.d. (n = 6) and 360mg b.i.d. (n = 19). No dose-limiting toxicities were observed in escalation. The RP2D was 360mg b.i.d. daily, and 45 additional patients were enrolled in the expansion cohort. Grade ≥3 treatment-related toxicities were observed in 54 of 74 (73%) patients with the most common being neutropenia (43%), anemia (30%), thrombocytopenia (28%) and fatigue (15%). There was one treatment-related death due to neutropenia. Administration of gemcitabine did not affect tivantinib concentration. Fifty-six patients were assessable for response. Eleven (20%) patients achieved a partial response and 26 (46%) had stable disease (SD), including 15 (27%) who achieved SD for over 4 months. Ten of 37 patients with clinical benefit had prior exposure to gemcitabine.
The combination of tivantinib at its monotherapy dose and standard dose gemcitabine was safe and tolerable. Early signs of antitumor activity may warrant further development of this combination in nonsmall-cell lung cancer, ovarian, pancreatic and cholangiocarcinoma.
NCT00874042.
Better by design: Exploitation of the macrocyclic architecture of a cyclophane‐based ligand provides new highly active catalysts with improved thermal stability for ethylene polymerization. The ...strategic positioning of the metal center at the core of the cyclophane‐based ligand is the key to the observed high activity and thermal stability, and to the high molecular weight of the polyethylene (see picture; red: Pd, green: Cl, blue: N, gray: C).
Silver nanoparticles (AgNP) are important materials in developing novel devices owing to their unique physical and chemical properties. It attracted much interest because it exhibits a prominent ...Surface Plasmon Resonance (SPR) property that is dependent on its nanodimension and nanostructure. Its green synthesis using biological extracts offers a cheap and benign process to afford AgNPs. However, natural extracts contain thousands of metabolites that affect the formation of the desired AgNP. Other factors such as temperature, pH, time, and volume also influence the formation of the nanometal hence, optimization is always carried out to afford sufficient amounts of the nanometals. To eliminate further trials and errors, this work reports the optimization of AgNP using the aqueous extract from Laxitextum bicolor, a wild type of mushroom from the family of Stereacea. Using central composite design (CCD) under Response Surface Methodology (RSM), five levels from each of the five independent parameters (pH, temperature, time, volume of extract, and volume of AgNO3) in a single-block mode afforded 32 experimental runs where SPR at 420 nm of the formed AgNP was measured as the dependent variable. ANOVA evaluation revealed that the p-value of the refined model is significant (p-value = 0.00) and the p-value of lack-of-fit is insignificant (LoF = 0.223). Model statistics displayed acceptable goodness of fit (R2 = 98.54%, adjusted R2 = 97.34, predicted R2 = 92.50%). The predicted optimal condition to synthesize AgNP from aqueous extract of L. bicolor were determined to be pH = 10, Temperature = 55 °C, Time = 180 min, Vol. Ext = 1.5 mL, and Vol. AgNO3 = 20 mL. To check the accuracy and repeatability of predicted optimal synthesis conditions, the UV-Vis analysis was employed. It showed that the peak intensity has a narrow peak with an absorbance of 3.40 at around 420 nm, which was the set criteria for choosing the optimal synthesis condition.
Background. Safety and immunogenicity of heat-treated zoster vaccine (ZV HT ) were assessed in immunocompromised adults. Methods. In a randomized, double-blind, placebo–controlled, multicenter study, ...4 doses ZV HT or placebo were administered approximately 30 days apart to adults with either solid tumor malignancy (STM); hematologic malignancy (HM); human immunodeficiency virus (HIV) with CD4⁺ ≤200; autologous hematopoietic stem-cell transplant (HCT) or allogeneic-HCT recipients. Varicella-zoster virus (VZV) T-cell responses by interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) and VZV antibody concentrations by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and approximately 28 days after each dose. Results. No safety signals were found in any group. IFN-γ ELISPOT geometric mean fold rises (GMFR) after dose 4 in STM, HM, HIV, and autologous-HCT patients were 3.00 (P<.0001), 2.23 (P = .004), 1.76 (P = .026), and 9.01 (P = NA), respectively. Similarly, antibody GMFR were 2.35 (P<. 0001), 1.28 (P = . 003), 1.37 (P = .017), and 0.90 (P = NA), respectively. T-cell and antibody responses were poor after 4 doses of ZV HT m allogeneic-HCT patients. Conclusion. ZV HT was generally safe and immunogenic through 28 days post-dose 4 in adults with STM, HM, and HIV. Autologous-HCT but not allogeneic-HCT patients had a rise in T-cell response; antibody responses were not increased in either HCT population. Study identification. V212-002 Clinical Trials Registration. NCT00535236