ABSTRACT
HYPOTHESIS: Colloidal cubic silica shells, prepared from cuprous oxide cubes, with a typical size of 100 nm are promising model particles for scattering studies on dilute, as well as concentrated fluids, of non-spherical colloids. EXPERIMENTS: Small angle X-ray scattering, and static light scattering are employed to determine form factors of cubic silica shells and silica covered cuprous oxide cubes. Contrast variation experiments are performed to assess the refractive index and optical homogeneity of the cubic silica shells, which is important for the extension of the scattering study to concentrated dispersions of cubic shells in Part II (Dekker, submitted for publication). RESULTS: The experimental form factors, which compare well to theoretical form factors, manifest cubic silica shells that are dispersed as single stable colloids with a shape intermediate between a sphere and a perfect cube. Contrast variation demonstrates that the silica shells are optically homogeneous, with a refractive index that is independent of the shell thickness. The results presented here open up the possibility to extract structure factors from light scattering measurements on concentrated cube dispersions in Part II.
ABSTRACT
Chimeric antigen receptor-modified T-cell therapy (CAR-T therapy) is one of the fastest developing areas of immuno-oncology. Over the past decade, it has revolutionized the cell therapy modality and expedited its pace of development, from optimization of the structure of chimeric antigen receptors and animal model experiments to successful clinical application. The initial designs of the CAR configuration focused on increasing T-cell activation, cytotoxicity, and persistence. However, the first attempts to treat patients with CAR T cells have demonstrated the need for increased safety and controlled activation of genetically modified T cells. Herein, we summarize the different molecular approaches to engineering chimeric antigen receptors for reducing the potential clinical risks of T-cell therapy.
ABSTRACT
The rheological properties of petrolatum are dependent on both temperature and thermal history. How this thermal dependency can be explained is unclear. In the past it has been suggested that the structure of petrolatum consists of a three-dimensional crystalline network. This has been established using old microscopic techniques only. Therefore a study on the microstructure of petrolatum was conducted using rheometry, DSC, pulsed NMR, polarized light microscopy and synchrotron X-ray. The combination of these techniques show that petrolatum is composed of 21% solid material at room temperature. This consists of partly crystalline lamellar sheets which are packed in stacks. The occurrence of these lamellar sheets is temperature dependent and the number of lamellar stacks is dependent on thermal history. It was shown that rheological differences in petrolatum can be explained by the number of lamellar stacks present, where more lamellar stacks result in more rigid petrolatum.
Subject(s)
Excipients/chemistry , Petrolatum/chemistry , Rheology , Technology, Pharmaceutical/methods , Calorimetry, Differential Scanning , Crystallization , Drug Compounding , Magnetic Resonance Spectroscopy , Microscopy, Polarization , Molecular Structure , Scattering, Small Angle , Structure-Activity Relationship , Synchrotrons , Temperature , X-Ray DiffractionABSTRACT
X-ray free-electron lasers (XFELs) provide extremely bright and highly spatially coherent x-ray radiation with femtosecond pulse duration. Currently, they are widely used in biology and material science. Knowledge of the XFEL statistical properties during an experiment may be vitally important for the accurate interpretation of the results. Here, for the first time, we demonstrate Hanbury Brown and Twiss (HBT) interferometry performed in diffraction mode at an XFEL source. It allowed us to determine the XFEL statistical properties directly from the Bragg peaks originating from colloidal crystals. This approach is different from the traditional one when HBT interferometry is performed in the direct beam without a sample. Our analysis has demonstrated nearly full (80%) global spatial coherence of the XFEL pulses and an average pulse duration on the order of ten femtoseconds for the monochromatized beam, which is significantly shorter than expected from the electron bunch measurements.
ABSTRACT
We present results of a coherent x-ray diffractive imaging experiment performed on a single colloidal crystal grain. The full three-dimensional (3D) reciprocal space map measured by an azimuthal rotational scan contained several orders of Bragg reflections together with the coherent interference signal between them. Applying the iterative phase retrieval approach, the 3D structure of the crystal grain was reconstructed and positions of individual colloidal particles were resolved. As a result, an exact stacking sequence of hexagonal close-packed layers including planar and linear defects were identified.
ABSTRACT
The black honeybee Apis mellifera mellifera L. is today the only subspecies of honeybee which is suitable for commercial breeding in the climatic conditions of Northern Europe with long cold winters. The main problem of the black honeybee in Russia and European countries is the preservation of the indigenous gene pool purity, which is lost as a result of hybridization with subspecies, A. m. caucasica, A. m. carnica, A. m. carpatica, and A. m. armeniaca, introduced from southern regions. Genetic identification of the subspecies will reduce the extent of hybridization and provide the gene pool conservation of the black honeybee. Modern classification of the honeybee mitotypes is mainly based on the combined use ofthe DraI restriction endonuclease recognition site polymorphism and sequence polymorphism of the mtDNA COI-COII region. We performed a comparative analysis of the mtDNA COI-COII region sequence polymorphism in the honeybees ofthe evolutionary lineage M from Ural and West European populations of black honeybee A. m. mellifera and Spanish bee A. m. iberiensis. A new approach to the classification of the honeybee M mitotypes was suggested. Using this approach and on the basis of the seven most informative SNPs of the mtDNA COI-COII region, eight honeybee mitotype groups were identified. In addition, it is suggested that this approach will simplify the previously proposed complicated mitotype classification and will make it possible to assess the level of the mitotype diversity and to identify the mitotypes that are the most valuable for the honeybee breeding and rearing.
Subject(s)
Bees/genetics , Genome, Mitochondrial , Genotype , Polymorphism, Single Nucleotide , Animals , Bees/classification , Gene PoolABSTRACT
Local populations of the black honeybee Apis mellifera mellifera from the Urals and the Volga region were examined in comparison with local populations of southern honeybee subspecies A. m. caucasica and A. m. carpatica from the Caucasus and the Carpathians. Genetic analysis was performed on the basis of the polymorphism of nine microsatellite loci of nuclear DNA and the mtDNA COICOII locus. On the territory of the Urals and the Volga region, five extant populations (reserves) of the black honeybee A. m. mellifera were identified, including the Burzyanskaya, Tatyshlinskaya, Yuzhno-Prikamskaya, Visherskaya, and Kambarskaya populations. These five populations are the basis of the modern gene pool of the black honeybee A. m. mellifera from the Urals and the Volga region. The greatest proportion of the remaining indigenous gene pool of A. m. mellifera (the core of the gene pool of the population of A. m. mellifera) is distributed over the entire territory of Perm krai and the north of the Republic of Bashkortostan. For the population of A. m. mellifera from the Urals and the Volga region, the genetic standards were calculated, which will be useful for future population studies of honeybees.
Subject(s)
Bees/genetics , DNA, Mitochondrial/genetics , Phylogeny , Animals , RussiaABSTRACT
For the last two centuries, beekeepers in Russia and Europe have been introducing bees from the southern regions to the northern ones, subjecting the genetic pool of the dark European bee Apis mellifera mellifera L. subspecies to extensive hybridization. In order to reconfirm on the genetic level the previously published morphological data on the native bee population in the Urals, the Bashkortostan Republic, and the Perm Krai, we analyzed the polymorphism of the mitochondrial (mtDNA COI-COII intergenic locus) and nuclear (two microsatellite loci, ap243 and 4a110) DNA markers. Four local populations of the dark European bee A. m. mellifera surviving in the Urals have been identified, and their principal genetic characteristics have been determined. Data on the genetic structure and geographical localization of the areals of the dark European bee local populations in the Urals may be of use in restoring the damaged genetic pool of A. m. mellifera in Russia and other northern countries.
Subject(s)
Bees/genetics , DNA, Mitochondrial , Genetics, Population , Microsatellite Repeats , Animals , Bashkiria , DNA, Intergenic , Electron Transport Complex IV/genetics , Gene Frequency , Hybridization, Genetic , Polymorphism, Genetic , RussiaABSTRACT
P53 protein is considered to be the major tumor suppressor in human cells. Cancer cells do not survive if the p53-mediated signaling pathways function properly. However, about half of all malignancies still express wild type p53. One of the explanations to this is that p53 is suppressed by overexpression of p53-specific E3-ubiquitin ligases: Mdm2, MdmX, Pirh2 and Cop1. Pharmacological inhibition of protein-protein interactions between p53 and these negative regulators is a promising therapeutic approach to treat cancers retaining wild type p53. To date, a series of chemical inhibitors of p53 interactions with Mdm2 and MdmX E3-ubiquitin ligases have been discovered and characterized. Several of them are in the early stages of clinical trials. Despite this fact, their clinical efficacy may be hampered by a number of reasons, including tumor-specific expression of multiple isoforms of the target E3-ligases, which become inert to treatment with small molecules. This and other biochemical mechanisms of possible resistance of tumor cells with wild type p53 to small molecules against its negative regulators will be discussed in this review.
Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression Regulation, Neoplastic , Neoplasms/drug therapy , Nuclear Proteins/genetics , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Protein p53/genetics , Cell Cycle Proteins , Humans , Imidazoles/pharmacology , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/metabolism , Piperazines/pharmacology , Protein Binding/drug effects , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors , Proto-Oncogene Proteins c-mdm2/metabolism , Signal Transduction , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/metabolism , Ubiquitin-Protein Ligases/antagonists & inhibitors , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Transcription factor p63 is a member of the p53 protein family. Due to the high degree of structural similarity p53, p63, and p73 are known to have overlapping functions relating to cell cycle regulation, apoptosis and tumor transformation. Furthermore, p63 plays crucial role in epidermal tissue development and differentiation. Pirh2 (product of RCHY1 gene) is an E3 ubiquitin ligase modifying all three members of the p53 family resulting in their subsequent proteasomal degradation. Our results demonstrate that p63, similar to p53, is able to regulate expression levels of Pirh2. Importantly, Pirh2 expression is activated only by transcriptionally active isoform of p63--TAp63, but not the N-terminally truncated ΔNp63.
Subject(s)
Gene Expression Regulation , Proteasome Endopeptidase Complex/metabolism , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin/genetics , Amino Acid Sequence , Apoptosis/genetics , Cell Cycle Checkpoints/genetics , Cell Differentiation , Cell Line, Tumor , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , HCT116 Cells , Humans , Molecular Sequence Data , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein Binding , Proteolysis , Sequence Deletion , Signal Transduction , Transcription Factors/chemistry , Transcription Factors/metabolism , Transcription, Genetic , Tumor Protein p73 , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/chemistry , Tumor Suppressor Proteins/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism , UbiquitinationABSTRACT
Cryogenic transmission electron microscopy (cryo-TEM) is utilized to determine the second virial coefficient of osmotic pressure of PbSe quantum dots (QDs) dispersed in apolar liquid. Cryo-TEM images from vitrified samples provide snapshots of the equilibrium distribution of the particles. These snapshots yield radial distribution functions from which second virial coefficients are calculated, which agree with second virial coefficients determined with analytical centrifugation and small-angle X-ray scattering. The size dependence of the second virial coefficient points to an interparticle interaction that is proportional to the QD surface area. A plausible cause for this attraction is the interaction between the surface ions on adjacent QDs.
ABSTRACT
Oriented attachment of synthetic semiconductor nanocrystals is emerging as a route for obtaining new semiconductors that can have Dirac-type electronic bands such as graphene, but also strong spin-orbit coupling. The two-dimensional (2D) assembly geometry will require both atomic coherence and long-range periodicity of the superlattices. We show how the interfacial self-assembly and oriented attachment of nanocrystals results in 2D metal chalcogenide semiconductors with a honeycomb superlattice. We present an extensive atomic and nanoscale characterization of these systems using direct imaging and wave scattering methods. The honeycomb superlattices are atomically coherent and have an octahedral symmetry that is buckled; the nanocrystals occupy two parallel planes. Considerable necking and large-scale atomic motion occurred during the attachment process.
ABSTRACT
The structural evolution of colloidal crystals made of polystyrene hard spheres has been studied in situ upon incremental heating of a crystal in a temperature range below and above the glass transition temperature of polystyrene. Thin films of colloidal crystals having different particle sizes were studied in transmission geometry using a high-resolution small-angle X-ray scattering setup at the P10 Coherence Beamline of the PETRA III synchrotron facility. The transformation of colloidal crystals to a melted state has been observed in a narrow temperature interval of less than 10â K.
ABSTRACT
OBJECTIVES: 1) To show the role and place of endovenous radiofrequency obliteration (RFO) in removing the vertical reflux in the varicose major superficial large-diameter veins. 2) To assess the outcomes of treatment of patients with varicose disease and to determine their correlation with the scales VCSS, VSDS and CEAP. MATERIAL AND METHODS: Endovascular methods, the technique of endovascular radiofrequency (RFO) ClosureFAST belongs to, are intended to within the shortest terms remove reflux without disturbing the patient's habitual way of life and along with it to improve the main aspects of quality of life.From 2009 to 2011, we operated on 110 patients (a total of 135 extremities). The mean age amounted to 41 years. Patients with an ostium-adjacent venous diameter of less than 1.3 cm were excluded from the sample, 37% of patients had various trophic impairments, 41% of patients had various concomitant somatic pathology, and 17% of patients had the body weight index (BWI) exceeding 30. Diagnosis and severity of the disease were formed with due regard for the scales of disease severity VCSS, VSDS and CEAP, as well as the worked out diagnostic algorithm. The venous status was evaluated by the findings of the objective examination and triplex angioscanning. The groups of patients with reflux along the altered venous segments were distributed as follows: 32.6% of patients - the superior vena cava with the classical course, 8% - the inferior vena cava, 7% - vein of Giacomini, 16% - the anterior accessory vein, 8% - the anterior lateral inflow, 28.4% - the extrafascial course of the vessel. The pain factor according to the analogue scale amounted to 0.8. In the postoperative period, the patients were followed up and examined on day 3, day 10 and then after 1, 3, 6, 12 months and more. RESULTS: RFO was successfully used in patients in all venous basins irrespective of the diameter and anatomical course of the venous structures. In 98% of cases we managed to achieve occlusion with the removal of the reflux within the terms of up to one year. Regress of clinical symptoms and improvement of quality of life were reflected in the VCSS. 100% of patients returned to the habitual activity on the day of operation. CONCLUSION: RFO with obvious efficacy may be used in various topographical areas of lower limbs regardless of the veins' diameter and their anatomical course. RFO is a method of choice in patients with high BMI and accompanying somatic pathology. Ambulatory follow up of patients with severe somatic pathology is possible, independently of decompensation of venous pathology. Clinical scales of the disease severity VCSS and VSDS are convenient in use, clearly reflecting the dynamics of the disease in the pre- and postoperative periods, which makes it possible to recommend them for wide application along with other scales on studying quality of life.
Subject(s)
Catheter Ablation/methods , Endovascular Procedures/methods , Varicose Veins/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Phlebography , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Ultrasonography, Doppler, Color , Varicose Veins/diagnosis , Young AdultABSTRACT
Using microradian x-ray scattering and polarized light microscopy the rich liquid crystalline phase behaviour of a polydisperse system of chromium-modified goethite particles has been studied for five years. We observe that the particles stay highly mobile over years and the rich phase behaviour keeps developing in novel and even surprising ways. While in many other colloidal systems particle size polydispersity suppresses the formation of ordered phases, goethite particles form multiple coexisting ordered phases. The particle polydispersity problem is then solved by particle exchange between coexisting phases. One usually expects that a less ordered phase (e.g., nematic) is formed first while crystallization of the smectic and columnar crystals might take a longer time. For goethite particles we find the opposite, i.e. the nematic phase grows over years at the expense of a better ordered smectic phase. Moreover, SAXS patterns revealed peak splitting for both the smectic and the columnar phase, meaning that the system displays fractionated crystallization. We further discovered that the centred rectangular columnar phase spontaneously forms out of the simple rectangular columnar phase. The reverse transition is observed as well. We explain the ease of these martensitic transitions by showing how slight rotation and translation of the particles triggers the transition.
ABSTRACT
Active dissemination implementation of endovascular methods has during the past decade been a progressive tendency of the development of surgical treatment management of varicose disease.Amongst these methods, endovasal laser obliteration in Russia occupies the leading place. Despite widespread implementation of this method into clinical practice still there are neither common concepts on the mechanisms of action of laser energy, inducing lesions of the venous wall followed by obliteration, nor, consequently,criteria for administration thereof The search for an optimal method and mode of intravascular intervention is based on study-ing the mechanisms of the damaging action of laser energy on the venous wall. The article contains a literature review of the studies dedicated to investigating the mechanisms of action of endovasal methods of treatment for varicose disease.
Subject(s)
Angioplasty, Laser , Catheter Ablation , Lasers/adverse effects , Varicose Veins , Veins/radiation effects , Angioplasty, Laser/adverse effects , Angioplasty, Laser/instrumentation , Angioplasty, Laser/methods , Animals , Catheter Ablation/adverse effects , Catheter Ablation/instrumentation , Catheter Ablation/methods , Disease Models, Animal , Humans , Models, Cardiovascular , Patient Selection , Subcutaneous Tissue/blood supply , Varicose Veins/physiopathology , Varicose Veins/therapy , Veins/physiopathologyABSTRACT
We report on detailed measurements of the core structure of Shockley partial dislocations in colloidal crystals. In crystalline arrays of micrometer sized thermosensitive particles, the interactions between the colloidal building blocks were tuned by changing the temperature. Individual dislocation cores were observed in a confocal microscope and their behavior as a function of temperature was studied. The obtained results qualitatively agree with the Peierls theory and are promising for further studies in which both Peierls stress and dislocation core width are measured simultaneously.
ABSTRACT
We present small angle x-ray scattering data of single-domain nematic and columnar liquid crystal phases in suspensions of sterically stabilized gibbsite platelets. The measurements are performed with different sample orientations to obtain information about the three-dimensional structure of the liquid crystalline phases. With the x-ray beam incident along the director of the nematic phase a strong correlation peak is observed corresponding to the side-to-side interparticle correlations, which suggests a columnar nematic structure. Upon sample rotation this side-to-side correlation peak of the nematic shifts to higher Q-values, suggesting the presence of strong fluctuations of small stacks of particles with different orientations, while the overall particle orientation is constant. In the hexagonal columnar phase, clear Bragg intercolumnar reflections are observed. Upon rotation, the Q-value of these reflections remains constant while their intensity monotonically decreases upon rotation. This indicates that the column orientation fluctuates together with the particle director in the columnar phase. This difference between the behaviour of the columnar and the nematic reflections upon sample rotation is used to assign the liquid crystal phase of a suspension consisting of larger platelets, where identification can be ambiguous due to resolution limitations.
Subject(s)
Colloids/chemistry , Liquid Crystals/chemistry , X-Ray Diffraction/methods , Birefringence , Crystallization , Microscopy, Electron, Transmission/methods , Particle Size , Scattering, Small AngleABSTRACT
We have discovered that the long-term aging of the hexagonal columnar liquid-crystal phase of polydisperse gibbsite platelets leads to fractionated crystallization, that is, to the formation of coexisting columnar crystals with different periods. This process was revealed by microradian X-ray diffraction demonstrating the splitting of the Bragg intercolumnar reflections into sequences of sharper reflections. The fractionated crystallization was observed in a number of samples of sterically stabilized as well as charge-stabilized polydisperse gibbsite platelets.
Subject(s)
Colloids/chemistry , Crystallization , Particle Size , Surface PropertiesABSTRACT
Biaxial nematic and biaxial smectic phases were found in a colloidal model system of goethite (alpha-FeOOH) particles with a simple boardlike shape and short-range repulsive interaction. The macroscopic domains were oriented by a magnetic field and their structure was revealed by small angle x-ray scattering. In accordance with theoretical predictions, biaxiality appears in a system with particles that have a shape almost exactly in between rodlike and platelike. Our results suggest that biaxial phases can be readily obtained by a proper choice of the particle shape.