117,332 research outputs found
Investigating transcription, replication and chromatin structure in determining common fragile site instability
No full textCommon fragile sites are a set of genomic locations with a propensity to form
lesions, breaks and gaps on mitotic chromosomes upon induction of replication
stress. While the exact reasons for their fragility are unknown, CFS display instability
in a cell-type specific manner, suggesting a substantial contribution from an
epigenetic component. CFSs also overlap with sites of increased breakage and
deletions in tumour cells, as well as evolutionary breakpoints, implying that their
features shape genome stability in vivo. Previously, factors such as delays in
replication timing, low origin density and transcription of long genes have been
implicated in instability at CFS locations but comprehensive molecular studies are
lacking. Chromatin structure, an important factor that fits the profile of cell-type
specific contributor, has also not been investigated yet.
Throughout their efforts to determine the factors that lead to the appearance of
CFS lesions, investigators have focused on a single component at a time, potentially
missing out complex interactions between cellular processes that could underlie
fragility. Additional difficulties come from the cell-type specificity of CFS breakage: it
indicates that only cell type-matched data would be informative, limiting the scope
for studies using publicly available data.
To perform a comprehensive study defining the role of different factors in
determining CFS fragility, I explored replication timing, transcriptional landscapes
and chromatin environment across a number of CFSs in two cell types exhibiting
differential CFS breakage. Initially, I characterised the patterns of CFS fragility in the
two cell types on both the cytogenetic and the molecular level. I then used a FISH-based
technique to investigate the process of mitotic compaction at active CFS sites
and found that the cytogenetically fragile core of these sites sits within larger
regions which display a tendency to mis-fold in mitosis. The aberrant compaction of
these regions could be observed on cytogenetically normal metaphase
chromosomes, suggesting that finer scale abnormalities in chromosome structure
underlie the cytogenetically visible breaks at fragile sites. I also investigated the
links between transcription of long genes and CFS fragility using two approaches: I
quantified levels of expression across all fragile sites using RNA-seq and modified
transcription at a single active CFS using the CRISPR genome engineering
methodology. My results indicate a complex interplay between transcription and
CFS fragility: no simple linear correlation can be observed, but an increase of
transcriptional levels at the active CFS led to a corresponding increase in fragility. To
investigate the influence of the cell type specific replication programme and
replication stress on CFS instability, I mapped replication timing genome-wide in
unperturbed cells and under conditions of replication stress in both cell types. I
found that replication stress induces bi-directional changes in replication timing
throughout the genome as well as at CFS regions. Surprisingly, the genomic regions
showing the most extreme replication timing alterations under replication stress do
not overlap with CFS, implying that CFS instability is not fully explained by
replication delays as previously suggested. Instead, I observed a range of
replication-stress induced timing changes across CFS regions: while some CFSs
appear under-replicated, others display switches to both earlier and later
replication as well as differential recruitment of both early and late origins, implying
that dis-regulation of replication timing and origin firing, rather than simply delays,
underlie the sensitivity to CFS regions to replication stress. Finally, I investigated
large-scale chromatin states at two active CFSs throughout S phase and into G2, the
cell cycle stages most relevant stage for CFS breakage. I found that changes in large-scale
chromatin architecture accompany the replication timing shifts triggered by
replication stress, raising the possibility that such alterations contribute to
instability.
In conclusion, I assessed the influence of multiple relevant factors on CFS fragility. I
found that bi-directional replication timing changes and alterations in interphase
chromatin structure are likely to play a role, converging to promote mitotic folding
problems which ultimately result in the well-described cytogenetic lesions on
metaphase chromosomes and genomic instability
An in vitro study on the sizes of pulp chambers and clinical crowns of molars
No full textAddress for correspondence:
Assoc. Prof. E. Boteva;
Faculty of Dentisty;
Medical University – Sofia;
3 Sv. G. Sofiiski;
1431 Sofia;
e-mail: [email protected] macromorphology of pulp chambers has been carefully studied
in the last few decades. But there is a serious lack of knowledge on the sizes
in different dimensions of the pulp chambers of molars. Aims of the present study
are jo measure the range and mean dimensions of the pulp chambers of upper
and lower molars; to detect the relation between the sizes of clinical crowns and
pulp chambers for better endocavity preparation. 286 upper and lower molars, 161
fi rst and second upper molars, 125 fi rst and second lower molars – matured, fully
mineralized and sound are used for the study. Measurements of the clinical crownthree
dimensions for each tooth in mm: mesio-distal, from the approximal marginal
ridge, bucco-lingual, from the top of buccal cusp to the top of the mesio-lingual
(palatal) cusp. The height of the crown is measured from the buccal side. Measurements
of the pulp chambers: 40 randomly selected upper and lower molars, 20 in
each group without severe root canal curvatures are measured under the following
technology: the pulp chambers are opened with horizontal cuts, 1 mm apically from
the equator with diamond blend. After polishing the ridges the fi nal size of the endocavity
is 2 mm bellow the equator. Both buccolingual dimensions are measured
as L1 and L2, and the mean as L with endodontic fi le and endoblock in mm. It can
be useful for the lecture courses BL sizes less than ½ of the cusp distance to be
avoided for endocavity preparation. A careful approach to this sizes of crowns and
chambers can lead to safe hard dental tissues during endocavity preparation and
especially careful approach to the approximal walls of the teeth. This fi ndings are important for the prevention of crown fractures, of posts and pins and of crowns and bridges in young age groups
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
Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?
No full textIn this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Letter from unknown writer to Jesse L. Boyce
No full textLetter to Jesse L. Boyce from unknown author (possibly Jack) about the investigation into the powder magazine located in the Grand Canyon. Some personal news is included in the letter such as the writer's marriage to the daughter of C.A. Taylor, former Supervisor of Cochise County
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
The sizes of pulp chambers of molars with severe root curvatures – in vitro comparative study
No full textAddress for correspondence:
Assoc. Prof. Dr. Ekaterina Boteva
Deptartment of Conservative Dentistry
Faculty of Dental Medicine;
1 Georgy Sofi isky str.;
Sofia, Bulgaria;
tel. +359888328327;
e-mail: [email protected] macromorphology of pulp chambers has been studied in the
last few decades, but there is a lack of knowledge on the sizes of the pulp chambers
of molars. The aim of the present study was to measure the size of the pulp
chambers of upper and lower molars with different root curvatures and to compare
them with the same dimensions in molars without root curvatures. Seventy-seven
upper and lower molars, matured, fully mineralized and sound were selected in the
following groups: two groups, including upper and lower teeth, respectively and
three groups, divided as follows: with straight roots up to 25-30º, with severe curvatures
up to 45º and with abnormalities 45º-90º from the axial axis. Three dimensions
of the crowns were measured for each tooth in mm: one mesio-distal and two
bucco-lingual dimensions, one of then being measured from the top of buccal cusp
to the top of the mesio-lingual (palatal) cusp. All teeth were submitted to X-rays and
were photographed after opening the pulp chambers. Measurements of the pulp
chambers were made after opening with horizontal cuts, made 1 mm apically from
the equator with a diamond blend. The two buccolingual dimensions were refered
to as L1 and L2, the mean value – as L and the mesio-distal – as MD, sizes were
measured in the widest part of the pulp chamber with an endodontic fi le and endoblock
in mm. A careful approach to these sizes of the pulp chambers of the molars
with severe curvatures can safe hard dental tissues during endocavity and pulp
chamber preparation .These fi ndings are important for the prevention of crown and
root fractures, and teeth loses and for lowering the use of posts and pins and the
use of crowns and bridges in young age groups
Sarah L. Blum Author Visit - Warrior Nurse: PTSD and Healing
No full textHear Sarah L. Blum, author of Women Under Fire: Abuse in the Military, discuss her newest book, Warrior Nurse: PTSD and Healing followed by a Q&A and book signing.
Sarah L. Blum is a decorated Vietnam veteran who served as an operating room nurse during the intense fighting of 1967. In recognition of her service, she was awarded the Army Commendation Medal.
Sponsored by CWU Veterans Center and CWU Libraries.https://digitalcommons.cwu.edu/libraryevents/1252/thumbnail.jp
Lillian L. Lambert, Author, Speaker, and Entrepreneur
No full textLillian L. Lambert, Author, Speaker, and Entrepreneu
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