bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical applications of aptamers and nucleic acid therapeutics in haematological malignancies
Authors: Shigdar Sarah , Ward Alister C. , De Abhijit , Yang Chaoyong J. , Wei Mingqian , Duan Wei 
Published: August 2011

SummaryHaematological malignancies result from a heterogeneous mix of genetic mutations and chromosome aberrations and translocations. Targeted therapies, such as the anti‐CD20 antibody rituximab, or the BCR‐ABL1 inhibitor imatinib, have proven to be effective treatments in the management of some of these malignancies, though relapsing or refractory disease is still common. Nucleic acid‐based therapies have also entered the clinical arena, providing an alternative, complementary approach. The forerunner of these therapies were the antisense oligonucleotides, but their scope has expanded to include short‐interfering RNA (siRNA), microRNA, decoy oligonucleotides and aptamers. These can be used either as mono‐therapeutics, in conjunction with current chemotherapy regimens, or in combination with each other to improve therapeutic efficacy. Not only can these nucleic acid‐based therapies silence target genes, they also have the potential of restoring gene function. While challenges remain in delivering effective doses of nucleic acid in vivo, these are steadily being met, suggesting an optimistic future in the treatment of haematological malignancies. This review summarizes the application of nucleic acid‐based therapeutics, particularly aptamers, in the diagnosis and treatment of haematological malignancies.
Deregulation of FGFR1 and CDK6 oncogenic pathways in acute lymphoblastic leukaemia harbouring epigenetic modifications of the MIR9 family
Authors: Rodriguez‐Otero Paula , Román‐Gómez José , Vilas‐Zornoza Amaia , José‐Eneriz Edurne San , Martín‐Palanco Vanesa , Rifón José , Torres Antonio , Calasanz María José , Agirre Xabier , Prosper Felipe 
Published: August 2011

SummaryThe role of epigenetic mechanisms in the regulation of microRNAs (miRNAs) with a tumour‐suppressor function in human neoplasms has recently been established. Several miRNAs have been found to be inappropriately regulated by DNA methylation in patients with acute lymphoblastic leukaemia (ALL). We analysed the methylation status of the three members of the MIR9 family (MIR9‐1, MIR9‐2 and MIR9‐3) in a uniformly treated cohort of 200 newly diagnosed ALLs. MIR9 was methylated in 54% of the patients and was associated with downregulation of MIR9 (P < 0·01). Hypermethylation of MIR9 was an independent prognostic factor for disease‐free survival, overall survival and event‐free survival in a multivariate analysis (P < 0·01). Epigenetic downregulation of MIR9 induced upregulation of its targets, FGFR1 and CDK6, while treatment of ALL cells with FGFR1 (PD‐173074) and CDK6 (PD‐0332991) inhibitors induced a decrease in cell proliferation and an increase in apoptosis of ALL cells. Our results indicate that the MIR9 family is involved in the pathogenesis and clinical behaviour of ALL and provide the basis for new therapeutic strategies in the treatment of ALL, targeting the epigenetic regulation of miRNAs and/or the FGFR1 or CDK6‐RB pathway directly.
One Mouse per Child: interpersonal computer for individual arithmetic practice
Authors: Alcoholado C. , Nussbaum M. , Tagle A. , Gomez F. , Denardin F. , Susaeta H. , Villalta M. , Toyama K. 
Published: August 2011

AbstractSingle Display Groupware (SDG) allows multiple people in the same physical space to interact simultaneously over a single communal display through individual input devices that work on the same machine. The aim of this paper is to show how SDG can be used to improve the way resources are used in schools, allowing students to work simultaneously on individual problems at a shared display, and achieve personalized learning with individual feedback within different cultural contexts. We used computational fluency to apply our concept of ‘One Mouse per Child’. It consists of a participatory approach that makes use of personal feedback on an interpersonal computer for the whole classroom. This allows for N simultaneous intelligent tutoring systems, where each child advances at his or her own pace, both within a lecture and throughout the curricular units. Each student must solve a series of mathematical exercises, generated according to his or her performance through a set of pedagogical rules incorporated into the system. In this process, the teacher has an active mediating role, intervening when students require attention. Two exploratory studies were performed. The first study was a multicultural experience between two such distanced socio‐economic realities as Chile and India. It showed us that even in different environmental conditions, it is possible to implement this technology with minimal equipment (i.e. a computer, a projector, and one mouse per child). The second study was carried out in a third grade class in a low‐income school in Santiago de Chile. The students were asked to solve mainly addition exercises. We established statistically relevant results and observed that the software proved most beneficial for the students with the lowest initial results. This happens because the system adapts to the students' needs, reinforcing the content they most need to work on, thus generating a personalized learning process.
Detection of dichroism with the microscope
Authors: Goldstein D. J. 
Published: August 2011

SUMMARYTwo simple, sensitive, visual methods are described for the detection of dichroism in microscopic objects.1. The object is oriented at ±45° between crossed polars, and either the polarizer or the analyser is rotated through an equal angle alternately clockwise and anti‐clockwise. A dichroic object will brighten as the polar is rotated in one direction and darken as the polar is rotated in the other. If the optic axis of the object lies north‐east to south‐west and the transmission axes of polarizer and analyser respectively east‐west and north‐south, a positively dichroic object will darken as the polarizer is rotated anti‐clockwise, or the analyser is rotated clockwise.2. A formally similar method, which avoids the need to rotate either polar, is to orient the object at ± 45° between crossed polars, and insert a Nakamura plate between the polars in an optical plane conjugate with the specimen. Dichroism is indicated by inequality of the apparent brightness of the specimen on either side of the dividing line of the plate.Both methods are more sensitive than visual techniques traditionally used in microscopy.The sign of the dichroism of polished smears of dye particles is discussed. It is suggested that polishing in the dry state orients individual dye molecules, while polishing of a damp smear orients dye molecule aggregates.The relation of dichroism to the colour of stained histological structures, as seen either between crossed polars or with bright‐field illumination, is discussed, and the elementary optical theory of dichroism is summarized.
Demonstration of β‐glucuronidase with naphthol AS‐BI‐β‐D‐glucosiduronic acid by simultaneous coupling
Authors: Jeffree Grace M. 
Published: August 2011

SUMMARYUsing unfixed cryostat sections, well‐localized staining for β‐glucuronidase with Naphthol AS‐BI‐βD‐glucosiduronic acid as substrate was obtained by simultaneous coupling at pH 5·0 with Fast Bordeaux OL and Fast Red Violet LB salts and with diazotized pararosanilin. With some other diazonium salts, enzyme inhibition or background staining led to unsatisfactory results.
A simplified time‐lapse cinemicrographic unit
Authors: Burton Alexis L. 
Published: August 2011

SUMMARYTime‐lapse mechanisms, specially intended for use in conjunction with the microscope, are described. They are extremely simplified and of very low cost. An unmodified camera is driven continuously at low speed and the exposure is made by means of an electronic flashlight. Synchronization of the flash is secured by a microswitch which activates the flashlight when the shutter of the camera is open. Two equipments (for 35 mm and 16 mm film) of this type were built and found very satisfactory.
Stereology, or the quantitative evaluation of microstructures
Authors: Underwood E. E. 
Published: August 2011

SUMMARYA general survey is presented of the basic equations of stereology, that is, the quantitative relationships that exist between quantities measured on the two‐dimensional plane of polish or section and the magnitudes of microstructural features that occur in three‐dimensional space. A new and important branch of stereology concerns the quantitative relationships between structures in a thin foil and their projected images. Basic equations are given in the absence of overlap and truncation; then overlap and truncation corrections are indicated for simple cases. The methods of determining the size distribution of particles or grains are outlined. Finally, other important parameters are described, such as the mean free distance and the mean intercept length.The subject of stereology is not completely new to some, but there are still many experiments to be run and methods to be perfected. It is hoped that microscopists dealing with microstructures will be encouraged to apply quantitative methods in their work in order to advance our knowledge in this fascinating field.
Measurements from electron micrographs of organelle size in relation to their shape: A refinement applied to the epidermal melanosome and basal lamella
Authors: Waterhouse J. P. , Squier C. A. 
Published: August 2011

SUMMARYThe mean value of measurements of organelles made from electron‐microscope sections cut in random planes is not an accurate expression of any important dimension of a nonspherical organelle; realistic measurements of organelles in electron micrographs must take into account the three‐dimensional shape of the organelle. Stereological methods offer ways of calculating surface areas and volumes of organelles in electron‐microscope sections but do not provide an easy means of deriving three‐dimensional structures. If, however, the three‐dimensional shape of an organelle is known, it is possible to select profiles which contain what is approximately a major or a minor axis. The frequency distribution of the values from profiles so chosen are skewed, and the median provides the best estimate of the dimension of the organelle. The median and the interquartile range (P25–P75) are presented for measurements made in this way of melanosomes and the basal lamella and lamina lucida of mammalian oral epithelium.
A method of processing third‐stage larvae of the nematode Trichostrongylus colubriformis for electron microscopy
Authors: Smith K. 
Published: August 2011

SUMMARYA method for processing third‐stage larvæ for electron microscopy is described. Using simple apparatus larvæ are separated from fæcal material by migration to a warmed area; they are then immobilized and chopped up in agar prior to fixation. No cellular distortion is observed in ultra‐thin sections.
The use of liquid photographic emulsion for demonstrating blood vessels in histological sections
Authors: Olson Ian A. , Skuse Dorothy E. 
Published: August 2011

SUMMARYAutoradiographic liquid coating emulsion was exposed to strong light and then injected at body temperature into the right or left ventricle of 400–1000 g guineapigs. Bouin‐ or Zenker‐fixed tissues were processed routinely, embedded in ester wax and sections mounted on standard glass slides. These were developed in photographic developer before staining by a variety of methods. The sections were examined under incident‐light illumination which demonstrated the general microcirculation of the tissue at low magnifications as a shining silver pattern displaying many vessels not visible in transmitted light. It was thereafter possible to examine and identify the vessels so demonstrated, as the fine grains of silver did not obscure the histological detail under high magnification in standard transmitted light.
Visibility and resolution of periodic structure in oblique dark‐ground illumination: Images of diatoms with rectangulate and triangulate arrays of fine structure
Authors: Hewlett P. S. 
Published: August 2011

SUMMARYDark‐ground images of selected diatoms have been investigated and the resolution attained has been found compatible throughout with the Abbe theory of image formation when correctly applied. At the same time, resolution beyond that indicated by the formula conventionally quoted for dark ground is frequently possible. This is because the conventional formula is based on the imaging of a line grating, but additional diffraction maxima permitting increased resolution occur when certain other forms of periodic structure are examined under dark‐ground illumination. Some suspect claims made in the past for resolution of diatoms in dark ground are examined. Several are undoubtedly justified, though the general statement that dark‐ground resolution is equal to that in bright field is not.
Increasing the camera constant of the EM6 microscope
Authors: Duggan B. J. , Greene G. W. 
Published: August 2011

SUMMARYWhen identifying compounds by electron diffraction it is necessary to consider the error introduced in the calculated lattice spacings (‘d‐values’) during measurement of the patterns. This becomes particularly important for very complex patterns with large d‐values such as 4PbO. PbSO4, where only spots very close to the centre spot are characteristic. There are several methods for increasing the camera constant to reduce this error, but the one described has the advantage of retaining the required facility of selected‐area diffraction. The method was developed on an AEI EM6 microscope.
An electron‐optical lens effect as a possible source of contrast in biological preparations
Authors: Haydon Glen B. 
Published: August 2011

SUMMARYHeavy‐metal stain aggregates on the surface of thin sections of biological material have higher contrast than those embedded within the sections and both have greater contrast than can be accounted for by the amplitude image. Disturbances of the incident illumination by a specimen in both light‐ and electron‐optical systems and their possible contribution to image contrast are considered. The hypothesis is proposed that a lens effect produced by the stain aggregates may account for their contrast in the electron microscope in a similar manner to the contrast of glass beads in the light microscope with a low numerical aperture.
Quantitative studies on the preservation of choline and ethanolamine phosphatides during tissue preparation for electron microscopy
Authors: Cope G. H. , Williams M. A. 
Published: August 2011

SUMMARYThe loss of 14C ethanolamine‐ and 3H choline‐labelled phospholipids from rat liver during tissue preparation for electron microscopy has been examined. Column and thin‐layer chromatography combined with double‐label scintillation spectrometry were used to analyse the radioactive phospholipid content of the livers of rats injected simultaneously with 14C aminoethanol and 3H choline chloride. After 4 h (in vivo) the 14C and 3H labels were mainly incorporated into phosphatidyl ethanolamine and phosphatidyl choline respectively but some 14C label had been incorporated into phosphatidyl choline. Chopped rat liver was fixed in glutaraldehyde or osmium tetroxide or both sequentially and tissues were dehydrated in ethanol and embedded in Araldite. In each procedure examined the choline label proved more labile than the ethanolamine. After glutaraldehyde fixation alone complete loss of phosphatidyl choline occurred and half of the phosphatidyl ethanolamine was also lost. Following osmium tetroxide fixation negligible loss of either phosphatide occurred. In terms of phospholipid retention, no advantage was gained by glutaraldehyde fixation prior to osmium tetroxide fixation. The results show that both ethanols and embedding monomers are potent phospholipid solvents. The data also suggests that EM autoradiography of these two phosphatides may be carried out with reasonable confidence although it must be pointed out that a high degree of retention does not necessarily imply retention in situ.
An apparatus for fixation and continuous dehydration of specimens for paraffin sections
Authors: Turler Sonia , Frei Ulrich 
Published: August 2011

SUMMARYStimulated by the paper describing an apparatus for continuous dehydration by Evans (1966) we have developed an apparatus of our own. The chief differences between this and that mentioned above are:(1) The use of a hypodermic needle which assures an absolutely constant flow of dehydrating fluid. Any given speed is reproducible by a simple change of needle and is not influenced by normal changes of temperature or by the quantity of liquid in the reservoir.(2) The elimination of a stirrer shaft, whereby space is gained and the use of one large basket is made possible.(3) The apparatus can be connected to a vacuum pump for fixation, or to a water tap for rinsing.(4) The apparatus can be placed in an oven.One of our aims was to eliminate handling of the specimens as far as possible. The apparatus, which has now been successfully in use for over a year, allows us to leave the specimens untouched from the fresh state right up to the transfer to paraffin.
High‐voltage electron microscopy of inorganic particles in intact blood cells
Authors: Clarke J. A. , Cosslett V. E. , Salsbury A. J. 
Published: August 2011

SUMMARYPreliminary results obtained by examining intact fixed human red and white blood cells containing inorganic particles under the high‐voltage transmission electron microscope are described. Iron filings and ferritin ingested in vitro by granulocytes were observed as were inorganic particles in red cells from a case of lead poisoning. The nature of the particles in red cells is discussed. A faint intracellular network was seen in normal red cells and in cells from a case of lead poisoning. It was found possible to focus the electron microscope at different planes within the cell. The optimum accelerating voltage for red cells appeared to be around 750 kV, whereas a clear image of granulocytes was obtained at voltages between 750 and 1000 kV. The first results indicate that it is possible to examine intact blood cells under the high‐voltage electron microscope. Further work is in progress to determine if more information can be acquired by this technique.
The effect of the electron beam on various mounting and coating media in scanning electron microscopy
Authors: Muir M. D. , Rampley D. N. 
Published: August 2011

SUMMARYEight commonly used specimen adhesives were examined under the ‘Stereo‐scan’ scanning electron microscope to determine the effects of the electron beam on their surface topography. The adhesives were initially examined uncoated, and then coated variously with carbon, and seven different metals and alloys. The effect of the beam on the coated and uncoated adhesives was recorded. The results are presented in tabular form. The purpose of the experiments was to determine the extent of the damage, if any, produced by the beam, on the adhesive, and to try to discover the most damage‐resistant combinations. While combinations are damage‐free, some of the more easily damaged adhesives are regarded as being suitable for certain specialized purposes, where their special properties over‐ride their susceptibility to beam damage.
A roll film camera for the AEI‐EM6 electron microscope
Authors: Pedler C. M. H. , Mould G. 
Published: August 2011

SUMMARYThe currently available plate camera for the AEI EM6 and 6B microscopes is inconvenient for the photography of large numbers of serial sections: firstly because it has to be reloaded relatively frequently and secondly because the restricted format of 70 mm film does not allow a large enough field to be examined at low power. The camera described was designed and built in these laboratories to obviate these problems.
The dimensions and numbers of small vesicles in cells, endothelial and mesothelial and the significance of these for endothelial permeability*
Authors: Casley‐Smith J. R. 
Published: August 2011

SUMMARYMeasurements were made of the diameters, numbers and other parameters of small, smooth‐surfaced vesicles in the endothelium of blood capillaries and lymphatics, and in the mesothelial cells of the diaphragms of mice. Some measurements were also made on the aortic endothelium. With a few exceptions, there were no morphological differences between the various sites.It was found that between 25% and 35% of the non‐nuclear cell volume was composed of vesicles, whose membranes accounted for about 55% of their volumes. Their internal volumes were ∼ 70,000 nm3, totalling ∼ 0·04 μm3/μm2 of luminal surface area. For each 1 μm2 there were ∼ 135 vesicles attached to each surface membrane of the cell, and between ∼ 200 and ∼ 350 vesicles lying free in the cytoplasm. There was probably a slight amount of shrinkage during the preparation of the material, and the true linear dimensions were probably ∼ 105% of those actually observed. Thus the values for the internal volumes were probably ∼ 85,000 nm3 and ∼005 μm3 respectively; the vesicular numbers were probably ∼ 125 attached to each surface and between ∼ 175 and ∼ 300 free.The vesicles attached to the plasma membranes often had quite long stalks; these were estimated to be ∼ 30 nm at the moment of rupture. Thus the vesicles must be released an appreciable distance away from the membrane. This modifies the conclusions of Shea & Karnovsky (1966), since it can now be shown that Brownian movement alone is capable of accounting for the release of the vesicles, their movements within the cells and their transportation of material.By combining these results with others estimating the endothelial permeability coefficients, it can be calculated that the average free lifetime of a vesicle is ∼1½ sec, from union with one plasma membrane to the next. It can also be shown that the average time of such an attachment is ∼ 2½ sec. There are many possible sources of error relating to these measurements; they must only be regarded as tentative. It appears likely, however, that they are of about the correct order of magnitude as they accord well with other data.
Computer‐generated distribution functions as an aid to the quantitative interpretation of electron micrographs of shadowed macromolecules
Authors: Rowe A. J. , Rowe H. J. 
Published: August 2011

SUMMARYUsing the mica‐replication technique of Hall, it is possible to visualize small, metal‐shadowed biological macromolecules. Consideration is given to the interpretation of micrographs obtained in this way, in order that molecular dimensions may be inferred.It is shown that the width of the shadow cast by a macromolecule can be measured precisely. A method is developed whereby the histogram of the experimentally determined shadow widths is interpreted by reference to computer‐generated histograms, based upon models of assumed dimensions. Results are presented illustrating the use of this new method.