339,683 research outputs found
KIT mutation analysis in mast cell neoplasms: recommendations of the European competence network on mastocytosis
No full textAlthough acquired mutations in KIT are commonly detected in various categories of mastocytosis, the methodologies applied to detect and quantify the mutant type and allele burden in cells and various tissues are poorly defined. We here propose a consensus on methodologies used to detect KIT mutations in patients with mastocytosis at diagnosis and during follow up with sufficient precision and sensitivity in daily practice. In addition, we provide recommendations for sampling and storage of diagnostic material as well as a robust diagnostic algorithm. Using highly-sensitive assays, KIT D816V can be detected in peripheral blood leukocytes from most patients with systemic mastocytosis (SM) which is a major step forward in screening and SM diagnosis. In addition, the KIT D816V allele burden can be followed quantitatively during the natural course or during therapy. Our recommendations should greatly facilitate diagnostic and follow up investigations in SM in daily practice as well as in clinical trials. In addition, the new tools and algorithms proposed should lead to a more effective screen, early diagnosis of SM, and help to avoid unnecessary referral
Identifying domestic and family violence - a resource kit
No full textAdapted from the Identifying family violence 1999 resource kit for general practitioners, produced by the Domestic Violence and Incest Resource Centre Inc., Vic.A resource kit for identifying domestic and family violence. Includes contact numbers for services available to give advice and support
Sammons Preston Basic Assistive Device Kit II
No full textThe Basic Assistive Device Kit II is used to help avoid bending at the hip after surgery or hip fracture while performing household activities. The sock aid can assist with pulling on socks where reaching down to the feet is difficult and shoehorns can assist putting on shoes on without bending. Each tool has an extended handle that is comfortable to hold for those with arthritis or poor hand function. Kit includes: Easireach II Reacher 26" (081306398), or 32" (081306406), Cord-Style Sock Notch (081289792), and Therafin E-Z Slide Shoehorn (081288422). Designed to assist those with reduced reaching capabilities, the kit is packaged in a plastic bag for transportation and storage
G-quadruplexes: Kinetic stability and effects on the c-KIT promoter
No full textIn addition to the famous Watson & Crick model for B-form duplex DNA, guanine-rich DNA sequences can self-assemble under certain conditions to form a four-stranded structure known as a G-quadruplex. G-quadruplexes are composed of stacks of Gquartets, in which four guanines are arranged in a square planar array, interacting via eight hydrogen bonds. Monovalent cations especially K+ and Na+ but not Li+ stabilize this structure by binding with the central carbonyl O6 atoms. Bioinformatic databases have revealed potential quadruplex-forming sequences throughout the genome and tandem repeats of guanines are found to accumulate upstream of the transcription initiation site of several proto-oncogenes. The promoter region of the c-kit proto-oncogene contains two potential quadruplex forming sequences. The first part of this work focuses on understanding how the c-kit promoter is regulated by potential G-quadruplex forming structures. We have incorporated 165 base pairs of the c-kit promoter region into a luciferase reporter vector and have constructed several mutant variants of this sequence. Determining the level of luciferase expression of these constructed vectors in HeLa and HCT 116 cells have allowed us to elucidate the effect of quadruplex formation on gene expression. Our results reveal that a decrease in gene expression level is observed from the constructed vectors that carry a very stable quadruplex-forming sequence. In genomic DNA, these putative quadruplex-forming G-rich sequences are normally base paired with their complementary C-rich strands to generate duplex DNA. Structural transitions of B-form DNA (duplex) to non-B-form DNA (quadruplex) require local melting, which is facilitated by negative superhelical tension. We have examined in vitro the effect of DNA supercoiling on the reaction of the c-kit promoter (and some variants of the natural sequences) with three chemical probes KMnO4, DEPC, and DMS. The results demonstrated that negative superhelicity did not significantly affect the formation of G-quadruplex. For the first time, we have used two-dimensional agarose gel electrophoresis to probe topology-dependent structural transitions in the c-kit promoter and some of its modified versions. Our results showed that the constructed vectors that carried the very stable quadruplex-forming sequence undergo unusual structural transition. Finally, we have used a gel based assay to understand the dynamic equilibrium between quadruplex and duplex DNA under defined conditions. The results show that at elevated temperatures, the formation of duplex DNA with these G-rich sequences is kinetically reversible and we have measured the rate at which the duplex strand exchanges with single-stranded DNA. The formation of both quadruplex and duplex DNA are cation and concentration-dependent
Kit Kat Club group portrait
No full textGroup portrait of the members of the Kit Kat Club, 1946. The Kit Kat Club of Columbus, Ohio, has its roots in a literary publication titled "The Honey Jar: A Receptacle for Literary Preserves." The magazine began in 1898 in Columbus, but it had a limited circulation. When it ceased publication in 1911, Charles C. Pavey, an attorney and contributor, offered to start a new publication to be called the "Kit-Kat Magazine." The title came from an article in "The Honey Jar" concerning a famous 18th century literary club in London, England, whose namesake was Christopher “Kit” Kat, the owner of an English tavern in the 1700s where members such as writer and critic Samuel Johnson reportedly met.
Pavey invited 19 men to assemble and discuss underwriting the publishing of the new magazine on October 5, 1911. The Kit Kat Club was formed as a result of this meeting, and their first regular meeting was held on November 3, 1911. The club's mission is to "promote social intercourse among congenial men who are interested in literature, art, and other matters of broad human concern." They also published the monthly magazine from 1912 to 1920.
Membership in the club is limited to 39 men. Nominations for new members are made by a three-man committee when a member dies or resigns, and voted on by members. Many noted Columbus men were members of the Kit Kat Club, including John W. Bricker, Charles Y. Lazarus, Edward Orton Jr., Edward S. Thomas, John M. Vorys, and many men from The Ohio State University, including four of its presidents. An accompanying description of this photograph lists the members pictured as follows: Front row: Adolph E. Waller, James R. Hopkins, Howard Dwight Smith, John F. Cunningham, Howard L. Bevis, Otto Mees, George W. Rightmire and E.J. Crane. Second row: Carl V. Weygandt, Claris Addams, Robert G. Patterson, Hugh Huntington, James E. Pollard, H.E. Cherrington, Boynton Merrill, Robert E. Pfeiffer, Dr. Jonathan Forman, H.C. Shetrone, Harlan H. Hatcher, Dr. George M. Curtis, George Washburne and C.E. MacQuigg. Additional members who were not pictured include Landon C. Bell, James I. Boulger, John W. Bricker, Dr. W.O. Doescher, Dr. Leroy Johnson, Richard B. Bean (who took the photograph), George R. Roudebush, Harrison M. Sayre, Samuel Shellabarger, George K. Smith, Edward S. Thomas, Henry A. Williams, and John M. Vorys
denghuilu/deepmd-kit: optimized version of deepmd-kit for CPC
No full textIn order to reproduce the results of the paper "86 PFLOPS Deep Potential Molecular Dynamics simulation of 100 million atoms with ab initio accuracy", please follow the next steps: The following modules must be loaded for the compilation and running of the optimized deepmd-kit code.
cuda/10.1.168 gcc/4.8.5 spectrum-mpi/10.3.1.2-20200121 ibm-wml-ce/1.6.2-2
Install the DeePMD-kit's C++ interface
Download all the dependent packages according to the DOI of the artifacts. Check the download packages:
ls
cub-v2.0.0.zip cutlass-v2.0.1.zip deepmd-kit-v2.2.0.zip lammps-v2.0.0.zip
Then unzip all the packages, and rename them as cub, cutlass, deepmd-kit, and lammps accordingly.
ls
cub cutlass deepmd-kit lammps
For convenience, you may want to record the location of source to a variable, saying deepmd_source_dir by
cd deepmd-kit
deepmd_source_dir=`pwd`
Now, copy the submodules cub and cutlass into the deepmd-kit
cd ../cub
cp -r * deepmd_source_dir/source/op/cuda/cutlass
Now go to the source code directory of DeePMD-kit and make a build place.
cd tensorflow_root -DCMAKE_INSTALL_PREFIX=deepmd_root/lib
libdeepmd.so libdeepmd_op.so libdeepmd_op_cuda.so
Install LAMMPS's DeePMD-kit module
DeePMD-kit provide module for running MD simulation with LAMMPS. Now make the DeePMD-kit module for LAMMPS.
cd lammps. Now go into the LAMMPS code, and copy the DeePMD-kit module like this
cd deepmd_source_dir/source/build/USER-DEEPMD ./
Now build LAMMPS
make yes-kspace
make yes-user-deepmd
make mpi -j4
The option -j4 means using 4 processes in parallel. You may want to use a different number according to your hardware. If everything works fine, you will end up with an executable lmp_mpi.
Reproduce the results
For example, Go to the deepmd_source_dir/test/1_water: Change the system size by change the following line in the file 'water.in': replicate 64 32 32 then change the number of nodes (GPUs/CPUs) and run it.
The following is an example job script:
#!/bin/bash
# Begin LSF Directives
#BSUB -P projectname
#BSUB -W 0:10
#BSUB -nnodes 80
#BSUB -J deepmd
#BSUB -o deepmd.%J
#BSUB -e deepmd.%J
#BSUB -alloc_flags gpudefault
cd LS_SUBCWD
echo lammps/src/lmp_mpi < water.in
Please remember not to include GPU in the resource set when running the CPU version of code
denghuilu/deepmd-kit: baseline version of deepmd-kit for sc20 conference
No full textIn order to reproduce the results of pap183, please follow the next steps:
The following modules must be loaded for the compilation and running of the optimized/baseline deepmd-kit code.
gcc/4.8.5
spectrum-mpi/10.3.1.2-20200121
ibm-wml-ce/1.6.2-2
Install the DeePMD-kit's C++ interface
Download all the dependent packages according to the DOI of the artifacts. Check the download packages:
ls
deepmd-kit-v1.4.0.zip lammps-v2.0.0.zip
Then unzip all the packages, and rename them as deepmd-kit and lammps accordingly.
ls
deepmd-kit lammps
For convenience, you may want to record the location of source to a variable, saying deepmd_source_dir by
cd deepmd-kit
deepmd_source_dir=`pwd`
Now go to the source code directory of DeePMD-kit and make a build place.
cd tensorflow_root -DCMAKE_INSTALL_PREFIX=deepmd_root/lib
libdeepmd.so libdeepmd_op.so
Install LAMMPS's DeePMD-kit module
DeePMD-kit provide module for running MD simulation with LAMMPS. Now make the DeePMD-kit module for LAMMPS.
cd lammps. Now go into the LAMMPS code and copy the DeePMD-kit module like this
cd deepmd_source_dir/source/build/USER-DEEPMD ./
Now build LAMMPS
make yes-kspace
make yes-user-deepmd
make mpi -j4
The option -j4 means using 4 processes in parallel. You may want to use a different number according to your hardware.
If everything works fine, you will end up with an executable lmp_mpi.
Reproduce the results
For example, Go to the deepmd_source_dir/test/1_water:
Change the system size by change the following line in the file 'water.in':
replicate 64 32 32
then change the number of nodes (GPUs/CPUs) and run it.
The following is an example job script:
#!/bin/bash
# Begin LSF Directives
#BSUB -P projectname
#BSUB -W 0:10
#BSUB -nnodes 80
#BSUB -J deepmd
#BSUB -o deepmd.%J
#BSUB -e deepmd.%J
#BSUB -alloc_flags gpudefault
cd LS_SUBCWD
echo lammps/src/lmp_mpi < water.in
Please remember not to include GPU in the resource set when running the CPU version of cod
Automated detection of slum area change in Hyderabad, India using multitemporal satellite imagery
No full textThis paper presents an approach to automated identification of slum area change patterns in Hyderabad, India, using multi-year and multi-sensor very high resolution satellite imagery. It relies upon a lacunarity-based slum detection algorithm, combined with Canny- and LSD-based imagery pre-processing routines. This method outputs plausible and spatially explicit slum locations for the whole urban agglomeration of Hyderabad in years 2003 and 2010. The results indicate a considerable growth of area occupied by slums between these years and allow identification of trends in slum development in this urban agglomeration
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The role of oncogenic Cbl mutants in Kit signaling and myeloid transformation
No full textAcute myeloid leukemia (AML) is a hematopoietic cell disorder characterized by a block in differentiation and increased proliferation and survival of malignant blasts. Expansion of the malignant cell clone effects the normal production of blood cells and – if left untreated – leads to death. Receptor tyrosine kinases (RTKs) play an important role in the pathogenesis of AML, as they are either often mutated or overexpressed. In normal hematopoiesis, RTK signal termination is tightly controlled, and involves ubiquitination, internalization, endocytosis and degradation. Cbl proteins are E3 ligases and have been shown to ubiquitinate several activated RTKs, including Flt3 and Kit, targeting them for degradation. Recently, several Cbl mutations have been identified: Cbl-R420Q was identified in an AML patient and Cbl-70Z was identified in a mouse lymphoma model. In this thesis work, the role of these Cbl mutants in Kit signaling and in a mouse transplantation model was studied. Cbl mutants (Cbl-R420Q, Cbl-70Z) have the ability to transform the myeloid 32D cell line in cooperation with Kit WT. Cbl mutants along with Kit promoted interleukin-3 (IL3)-independent proliferation and enhanced the cell survival of 32D cells. In contrast, expression of the Cbl mutants alone did not confer IL3-independent growth. Stem cell factor (SCF, the Kit ligand) dependent growth was enhanced in the presence of Cbl mutants and Cbl mutants promoted colonogenic growth in the presence of Kit. Furthermore, Cbl mutants inhibited the ubiquitination of the activated Kit receptor. In addition, Cbl mutants inhibited the endocytosis of the activated Kit receptor. Retroviral expression of Cbl mutants in transplanted bone marrow induced a generalized mastocytosis, a myeloproliferative disease and, in rare care cases, myeloid leukemia. Splenomegaly was observed in the presence of Cbl mutants. Furthermore, mast cells with variable range of infiltration were noticed in all the vital organs (spleen, liver, bone marrow, lung, kidney, heart) of Cbl (mutant) transplanted mice. Almost all recipients of bone marrow cells transduced with Cbl mutants developed a lethal hematologic disorder with a mean latency of 341 days in the Cbl-R420Q group and 395 days in the Cbl-70Z group. This is the first published report on a hematological disease with Cbl mutants in a mouse model. Co-immunoprecipitation studies indicated that Cbl-70Z binds to Kit, even in the absence of Kit ligand. Cbl-R420Q also bound to Kit in the absence of SCF, albeit to a lesser extent. Association of Cbl mutants to Kit was enhanced in the presence of SCF. Signaling studies demonstrated the constitutive activation of Akt and Erk in the presence of Cbl mutants and Kit. In addition, Cbl mutants enhanced the SCF-dependent Kit, Akt and Erk activation. Cbl-70Z, in association with kinase-dead Kit (Kit-KD) or kinase-dead Flt3 (Flt3-KD), conferred IL3-independent growth and survival to the myeloid 32D cell line. Cbl-R420Q provided only a slight growth advantage in the presence of Kit-KD. As demonstrated by pharmacological inhibition studies, Akt activation was necessary for the transformation mediated by Cbl-70Z and Kit-KD / Flt3-KD. Cbl mutants enhanced the Src family kinases (SFKs) activity. The pharmacological inhibition of SFK activity inhibited the proliferation and colonogenic growth. Interaction was found between Cbl-70Z, SFKs and Kit-KD. The SFK member Fyn was identified to bind to Cbl. In addition, kinase activity of SFKs was necessary for binding to Cbl, since SFKs inhibition by PP-2 abolished the binding between the complex-binding partners. Dasatinib and PP-2, both SFK inhibitors, inhibited the Cbl and Akt phosphorylation indicating that Fyn acts upstream of Akt. Inhibition of Kit with imatinib reduced the proliferation of cells overexpressing Kit WT and Cbl-70Z much stronger compared with cells expressing Kit-KD and Cbl-70Z, but much less than the dual KIT/SFK inhibitor dasatinib. This indicated that Kit kinase activity was required but not essential. The data presented in this thesis work implies that both RTK and SFK inhibition may have to be targeted, in order to effectively prevent transformation. In summary, the present thesis work indicates an important role of Cbl, Kit and SFKs in myeloid transformation and deregulated signal transduction.Die akute myeloische Leukämie (AML) ist eine Erkrankung hämatopoetischer Zellen, die durch einen Differenzierungsblock und die unkontrollierte Bildung unreifer hämatopoetischer Zellen oder Blasten charakterisiert ist. Dabei kommt es zu einer starken Einschränkung der normalen Hämatopoese, was letztlich ohne Behandlung zum Tod des Patienten führt. Die Entstehung einer AML wird grundsätzlich als Entwicklung angesehen, die in mehreren Schritten vonstatten geht. Genetische Veränderungen, wie Mutationen, Translokationen, Amplifikationen und Deletionen sind an der Pathogenese der AML beteiligt. Diese genetischen Veränderungen können in zwei Gruppen eingeteilt werden: solche die zu einem Proliferations- oder Überlebensvorteil führen (Klasse I Mutationen) und andere, die einen Differenzierungsblock hervorrufen (Klasse II Mutationen). Eine einzelne Mutation dieser Art ist nicht in der Lage alleine einer AML auszulösen. Während Kit-Mutationen relativ selten sind, wird bei der Mehrzahl der AML-Patienten eine Überexpression des Kit Rezeptors gefunden. Der Kit-Rezeptor wird durch seinen Liganden „Stem Cell Factor“ (SCF) aktiviert. Die Aktivierung von Kit führt zur Rekrutierung von Signalmolekülen. Sog. „Gain-of-function“-Mutationen von Kit führen zu einer konstitutiven Aktivierung des Rezeptors. Cbl-Proteine degradieren bekanntermaßen aktivierte Rezeptortyrosinkinasen (RTKs) durch Ubiquitinierung. Die Untersuchung der Signaltransduktion von RTKs wie Kit oder Flt3 und deren Degradation, ist für die Entwicklung neuer therapeutischer Strategien zu von enormer Wichtigkeit. Gegenstand der vorliegenden Untersuchung ist der Einfluss von Cbl-Mutanten (Cbl-R420Q und Cbl-70Z) auf die Kit–vermittelte Signaltransduktion. Cbl-R420Z wurde bei einem AML-Patienten gefunden, während Cbl-70Z in Maus-Myelom-Studien identifiziert wurde. Diese Cbl Mutanten haben die E3-Ligase Aktivität, die eine wichtige Rolle beim Transfer der Ubiquitin Moleküle zum Zielprotein spielt, verloren. ..
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