This study examined the relationship between Notch signaling and lymphatic malformations using immunohistochemistry on tissue samples from lymphatic malformation and lymphangiomatosis patients. The results showed that lymphatic malformation endothelial cells have reduced expression of lymphatic markers like Podoplanin compared to normal tissue. Lymphatic malformation tissues also had increased expression of the stem cell marker CD133. Analysis of lymphangiomatosis tissues found expression of lymphatic markers in abnormal cell types and high levels of lymphatic malformation progenitor cells. Notch3 was expressed in CD133-positive progenitor cells but not in lymphatic endothelial cells, suggesting it functions in lymphatic malformation progenitor cells rather than endothelial cells
Whole genome sequencing of arabidopsis thalianaBhavya Sree
arabidopsis is the representative of plant kingdom or the 'model plant'.it is the first plant genome sequenced. the sequences lead to the overall understanding of the plant kingdom, better understanding of various genes,the important metabolic pathways, evolution etc
New insights into the human genome by ENCODE project Senthil Natesan
It’s been ten years since scientists sequenced the human genome. But what do all these letters?
Researchers could identify in its 3 billion letters many of the regions that code for proteins, but those make
up little more than 1% of the genome, contained in around 21,000 genes a few familiar objects in an otherwise stark and unrecognizable landscape. Many biologists suspected that the information responsible
for the wondrous complexity of humans lay somewhere in the ‘deserts’ between the genes (The ENCODE Project Consortium, 2012).
Interpreting the human genome sequence is one of the leading challenges of 21st century biology
(Collins et al., 2003). In 2003, the National Human Genome Research Institute (NHGRI) embarked on an
ambitious project the Encyclopedia of DNA Elements (ENCODE), aiming to delineate all of the functional elements encoded in the human genome sequence (The ENCODE Project Consortium 2004). To further
this goal, NHGRI organized the ENCODE Consortium, an international group of investigators with diverse
backgrounds and expertise in production and analysis of high-throughput functional genomic data. In a pilot project phase spanning 2003–2007, the Consortium applied and compared a variety of experimental and computational methods to annotate functional elements in a defined 1% of the human genome (The ENCODE Project Consortium, 2007)
Genome: The entire chromosomal genetic material of an organism.
Sequencing a genome: Determining the identity and order of nucleotides in the genetic material – usually DNA, sometimes RNA, of an organism.
Whole genome sequencing of arabidopsis thalianaBhavya Sree
arabidopsis is the representative of plant kingdom or the 'model plant'.it is the first plant genome sequenced. the sequences lead to the overall understanding of the plant kingdom, better understanding of various genes,the important metabolic pathways, evolution etc
New insights into the human genome by ENCODE project Senthil Natesan
It’s been ten years since scientists sequenced the human genome. But what do all these letters?
Researchers could identify in its 3 billion letters many of the regions that code for proteins, but those make
up little more than 1% of the genome, contained in around 21,000 genes a few familiar objects in an otherwise stark and unrecognizable landscape. Many biologists suspected that the information responsible
for the wondrous complexity of humans lay somewhere in the ‘deserts’ between the genes (The ENCODE Project Consortium, 2012).
Interpreting the human genome sequence is one of the leading challenges of 21st century biology
(Collins et al., 2003). In 2003, the National Human Genome Research Institute (NHGRI) embarked on an
ambitious project the Encyclopedia of DNA Elements (ENCODE), aiming to delineate all of the functional elements encoded in the human genome sequence (The ENCODE Project Consortium 2004). To further
this goal, NHGRI organized the ENCODE Consortium, an international group of investigators with diverse
backgrounds and expertise in production and analysis of high-throughput functional genomic data. In a pilot project phase spanning 2003–2007, the Consortium applied and compared a variety of experimental and computational methods to annotate functional elements in a defined 1% of the human genome (The ENCODE Project Consortium, 2007)
Genome: The entire chromosomal genetic material of an organism.
Sequencing a genome: Determining the identity and order of nucleotides in the genetic material – usually DNA, sometimes RNA, of an organism.
This is a compilation of the Yeast genome project from the different databases and sources.
By:
Nazish Nehal,
M. Tech (Biotechnology),
University School of Biotechnology (USBT),
Guru Gobind Singh Indraprastha University (GGSIPU),
New Delhi (INDIA)
We propose an efficient algorithmic framework for time domain circuit simulation using exponential integrators. This work addresses several critical issues exposed by previous matrix exponential based circuit simulation research, and makes it capable of simulating stiff nonlinear circuit system at a large scale. In this framework, the system’s nonlinearity is treated with exponential Rosenbrock-Euler formulation. The matrix exponential and vector product is computed using invert Krylov subspace method. Our proposed method has several distinguished advantages over conventional formulations (e.g., the well-known backward Euler with Newton-Raphson method). The matrix factorization is performed only for the conductance/resistance matrix G, without being performed for the combinations of the capacitance/inductance matrix C and matrix G, which are used in traditional implicit formulations. Furthermore, due to the explicit nature of our formulation, we do not need to repeat LU decompositions when adjusting the length of time steps for error controls. Our algorithm is better suited to solving tightly coupled post-layout circuits in the pursuit for full-chip simulation. Our experimental results validate the advantages of our framework.
This is a compilation of the Yeast genome project from the different databases and sources.
By:
Nazish Nehal,
M. Tech (Biotechnology),
University School of Biotechnology (USBT),
Guru Gobind Singh Indraprastha University (GGSIPU),
New Delhi (INDIA)
We propose an efficient algorithmic framework for time domain circuit simulation using exponential integrators. This work addresses several critical issues exposed by previous matrix exponential based circuit simulation research, and makes it capable of simulating stiff nonlinear circuit system at a large scale. In this framework, the system’s nonlinearity is treated with exponential Rosenbrock-Euler formulation. The matrix exponential and vector product is computed using invert Krylov subspace method. Our proposed method has several distinguished advantages over conventional formulations (e.g., the well-known backward Euler with Newton-Raphson method). The matrix factorization is performed only for the conductance/resistance matrix G, without being performed for the combinations of the capacitance/inductance matrix C and matrix G, which are used in traditional implicit formulations. Furthermore, due to the explicit nature of our formulation, we do not need to repeat LU decompositions when adjusting the length of time steps for error controls. Our algorithm is better suited to solving tightly coupled post-layout circuits in the pursuit for full-chip simulation. Our experimental results validate the advantages of our framework.
Histopathological Correlation of Lymph Nodes Imprintsiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Lesions/ Tumors/ Cysts doesn't follow the text books. Hence, every enthusiastic Pathologist should be updated with the current trends in the subject. Here is an attempt made from the most common text books of Oral pathology.
05.28.09(b): Development of the Urinary SystemOpen.Michigan
Slideshow is from the University of Michigan Medical
School's M1 Embryology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Embryology
The successful of pregnancy in humans and rodents occur between the interaction maternal and fetal
interface, specially involving the participation of uNK cells. This interaction involved neo angiogenesis,
placentation and presence of mediators like nitric oxide. During the pregnancy the administration of LPS
in the dams can results in necrosis, preterm birth, IUGR, miscarriage or neurological problem. Once the
uNK cells are activated, they can produce vasodilators, like NO. So, the main purpose of this study was
to evaluate if LPS cause alteration in the uNK cells in pregnant mice and if the same behaviour can be
detected by NO in the blood. Also we evaluated the effect of LPS to cause neurological injuries. To do that
we used pregnant mice on gd 10th and those was treated with LPS for different times. Uterine samples
were collected at 0.5,1,2 and 6hr after LPS treated and processed for paraffin embedding and tissue
homogenate. The samples designated for paraffin embedding was performed the Dolichos biflorus (DBA)
lectin cytochemistry and anti-iNOS immunocytochemistry. The samples designated to tissue homogenates
were processed for SDS-PAGE and Western-blot using anti-iNOS and evaluate of NO concentration. We
found after 2h LPS exposure the mice showed fever and low capacity to explore different environment.
At the same time, we found increase in the nitrate/nitrito ratio in a dose dependent manner in the uterus
after 2h LPS exposure.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
2. Background
• Notch genes are required for proper lymphatic development in mice,
zebrafish, and several other animals. [1,2]. It’s hypothesized there’s a
direct relationship between level of expression of Notch genes and the
riseoflymphaticmalformations.
• Notch signaling also plays a key role in regulation of cell fate decisions
andangiogenesis,andinmice,hasbeenshowntoregulatearterialand
venousspecificationsofmajorvessels,suchasthedorsalaorta[3,4,5].In
addition,Notchsignalingpathwayisusedbyendothelialcellsinorderto
organizecellularbehaviorsduringthesproutingstage[1,6].
• Many comprehensive studies of the Notch signaling pathway have
revealed that there’s a direct relationship between the Hey1 and Hey2
genes and embryonic development, which later greatly affects physical
development after the prenatal stage, meaning it also directly affects
thegrowthandbranchingofbloodandlymphvessels[7,8,9].
3. Background (continued)
• In terms of phenotypic characteristics, there are two distinct types of lymphatic
malformation- microcystic and macrocystic. The main difference betweenthe two
typesisthesizeandshapeofthemalformations.
• Lymphangiomatosis is a condition in which the body simultaneously has both
microcysticandmacrocysticlymphaticmalformations,causingittobecategorizedas
a systemic LM. In most cases, lymphangiomatosis tends to involve several organ
systems.
• Lymphatic malformations are comprised of: lymphatic malformation endothelial
cells (LMECs) and lymphatic malformation progenitor cells (LMPC’s) [10]. It was
previously found that Notch1 and Notch3 were overexpressed in LM tissues, with
Notch1beingoverexpressedintheLMECpopulationandNotch3intheLMPCs[11].
• Inaddition,ithasbeennotedthatisolatedlymphaticmalformationendothelialcells
tendtoexpresshighlevelsofHey1,whichsuggestshighNotchsignalactivation.
• Because lymphangiomasotis is a collection of both types of LMs, it would be an
educated guess to hypothesize that lymphangiomatosis tissue would display an
overexpression of the two Notch genes (Notch1 and Notch3) in whatever cell
populationtheytendtobeoverlyexpressedin.
6. Significance
• Approximately 1 in 3500 births are affected by lymphatic
malformations, and this research would be greatly beneficial to and
alleviate the sufferings of a substantial portion of the population.
• A permanent treatment to this ailment would be of great value,
not only economic but also scientific.
• Normally, one surgery to remove or uproot a malformation can cost
anywhere from $10,000 to $45,000, which is very expensive and
often unaffordable for a middle class family.
• The scientific value of this research project is that, if the exact
relationship between Notch and malformations is discovered, then
that will allow scientists to develop drugs that could effectively
suppress the expression of those genes. Because this is also a
component of cancer research, research in this particular field
would lead to advancements in both fields.
7. Materials and Methods
• Immunohistochemistry is a process by which a set of cells are incubated with
antibodiesinorderto“stain”them.
• Forfrozentissue,theslideswere“prefixed”inacetoneforsometime,andthen
washedinPBS(phosphatebuffersaline).
• After incubation with blocking solution was complete, the antibodies were
administered to the tissue. Every set of tissue used in this project was “double-
stained,”meaningeachsetwasstainedwithtwoantibodies.
• After the staining process was completed, the slides were coverslipped and
observed under a fluorescence microscope, and the images taken were
documented.
• For paraffinized tissue, they were first washed in xylene and different
concentrations of ethanol in order to deparrafinize and rehydrate them. Next,
antigenretrievalinducedinordertouncrosslinkedproteins.
• The steps following the initial steps are the same standard ones as the steps
followedforstainingfrozentissue..
9. Figure 2: Expression of lymphatic
endothelial cell marker and
lymphatic vessel marker on
lymphangiomatosis tissue. The
tissuethatwasstainedwasaparaffin
section from a lymphangiomatosis
patient,isolatedfromthejugularvein
regionintheneck,themesentery(gut
area),thelungs,andthethoracicduct
inthecenterofthebody.Thetissues
were stained using the antibodies
Podoplanin and LYVE1 to show
expression of lymphatic endothelial
cells and lymphatic vessels,
respectively. In addition, DAPI was
used to visualize the nuclei. In the
tissuescollectedfromallfourregions
(jugular/lymphatic,mesenteryvessel,
lung, and thoracic duct), there was
high Podoplanin expression in the
vessels and surrounding tissue.
LYVE1expressionwasmuchmore
muted, and overlapped with that of
Podoplanin. The mesentery vessel,
out of all four regions, showed the
least expression of both markers,
althoughsomedegreeofexpression
isevident.
10. Figure3:Expressionofendothelial
cellmarkerandNotch3markeron
lymphangiomatosis tissue. The
tissuethatwasstainedwasaparaffin
embedded section from
lymphangiomatosis patient, isolated
from the jugular vein region in the
neck, the mesentery (gut area), the
lungs, and the thoracic duct in the
centerofthebody.Thetissueswere
stained using the antibodies
Podoplanin and Notch3 to show
expression of lymphatic endothelial
cells and Notch3 cell markers,
respectively,andDAPIwasusedto
visualize the nuclei. In the tissues
collected from the four
aforementionedregions,Podoplanin
expression is very high. Notch3
expression, however, was much
lower in the same tissues, and its
level of expression is debatable.
Although there is still obvious
expression of Podoplanin in the
tissues from the lung, it is
significantly lower when compared
totheotherregions.
11. Figure4:Expressionofstemcell
marker and Notch 3 marker on
lymphangiomatosis tissue. The
tissue that was stained was a
paraffin embedded section from
lymphangiomatosis patient,,
isolated from the jugular vein
regionintheneck,themesentery
(gut area), the lungs, and the
thoracicduct inthecenterofthe
body. The tissues were stained
with the antibodies CD133 and
Notch3, to show expression of
stem cell markers and Notch3
markersinLMPCsonthetissue,
respectively; DAPI was used to
visualize the nuclei. There is
CD133 expression in tissues
fromthelung,jugular/lymphatic,
and mesentery vessel regions.
There is also Notch3 expression
in the tissues collected from the
aforementioned regions. In
contrast, there appears to be no
expression of either antibody in
the tissue from the thoracic duct
region. The tissue from the
mesentery vessel appears to
showaco-expressionofCD133
andNotch3.
12. Figure5:Expressionofendothelialcell
marker and notch activity on
lymphangiomatosis tissue. The tissue
that was stained was a paraffin
embedded section from
lymphangiomatosis patient,, isolated
fromthejugularveinregionintheneck,
the mesentery (gut area), the lungs, and
thethoracicductinthecenterofthebody.
The tissues were stained using the
antibodies Podoplanin and Hey2, to
show expression of endothelial cell
markers and notch activity in the tissue,
respectively, which in turn show Notch
activity in lymphatic endothelial cells.
DAPI was also used to visualize the
nuclei. There is expression of both
Podoplanin and Hey2 in all tissues;
however, there’s a greater level of
expression of Podoplanin and Hey2 in
the thoracic duct tissue. In the tissues
collected from the lung and jugular
lymphaticregions,there’saslightlylower
expressionofbothantibodies,andinthe
mesentery vessel tissue, there’s scarcely
anyexpressionofeitherantibody.
13. Discussion – Analysis of Results
• Inthelymphaticvesselsofnormaltissue,highPodoplaninexpressionwasobserved,while
its expression was greatly reduced in lymphatic malformation tissues, which suggests
lymphatic malformation endothelial cells (LMECs) usually lining lymphatic vessels are
greatlyaffectedbythelymphaticmalformation,tothepointofdegeneration
• CD133expressionwasreversed:itsexpressionwaslowinthenormaltissue,andhighin
the LM tissues. CD133 is a stem cell marker, so the absence of stem cells in the normal
tissueandtheirpresenceinLMtissuesuggeststhatthepresenceoftheseCD133positive
lymphatic malformation progenitor cells (LMPCs) is abnormal in lymphatic
malformations.
• Characterization of lymphangiomatosis tissue revealed that lymphatic
endothelial cell markers Podoplanin and LYVE1 were expressed in several cell
typeswithdifferentlymorphology,besidesthetypicallymphaticvessels,causing
the resulting vessels to appear grossly deformed. This staining pattern was
consistent with that for LMPCs observed in the LM tissues, suggesting LMPCs
arepresentinlargequantitiesinlymphangiomatosistissue.
• Notch3 was not co-expressed with high Podoplanin levels in the
lymphangiomatosistissuesamples,indicatingit’snothighlyexpressedinLMECs.
14. Discussion – Analysis of Results (continued)
• Notch3 was not co-expressed with high Podoplanin levels in the
lymphangiomatosistissuesamples,indicatingit’snothighlyexpressedinLMECs.
• AsshowninFig.4,Notch3wasalsoexpressedintheCD133positivecellsinthe
samples while it was greatly muted or absent in the tissue samples from the
same area (when the jugular/lymphatic and thoracic duct regions of Fig. 3 are
comparedtothesameregionsinFig.4),indicativeofitssuspectedexpressionin
the LMPC population. This data suggests that Notch3 may function in the
lymphaticmalformationprogenitorcellpopulation.
• Hey2 expression was observed in the same cells that expressed high levels of
CD133andNotch3,andbecauseHey2isadownstreameffectorofNotchsignal
activationandwasabsentincellsshowinghighlevelsofPodoplanin(whichare,
therefore,lymphaticmalformationendothelialcells),itsuggeststhattheNotch3
gene has direct correlations with the formation of a lymphatic malformation
consistingprimarilyofLMECs.
• The absence of Notch3 and Hey2 in the Podoplanin positive LMECs suggests
that these proteins and Notch signaling do not function simultaneously in the
cellsfoundinlymphangiomatosistissue.
17. References
• 1.ShawberC,Kitajewski,J.Notchfunctioninthevasculature:insightsfromzebrafish,mouseandman.
BioEssays.2004;26.3:225-234
• 2.Schweisguth,F.RegulationofNotchSignalingActivity.CurrentBiology.2004;14:129-138
• 3. Funahashi Y, Shawber C, Kitajweski J. Notch genes: orchestrating endothelial differentiation.
EndothelialBiomedicine.41:368-374
• 4.NiessenK,ZhangG,RidgwayJRetal.TheNotch1-Dll4signalingpathwayregulatesmousepostnatal
lymphaticdevelopment.Blood.2011;118(7):1989-1997
• 5. Zheng W, Tammela T, Yamamoto M et al. Notch restricts lymphatic vessel sprouting induced by
vascularendothelialgrowthfactor.Blood.2011;118(4):1154-1162
• 6. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in
development.Science.1999;284(5415):770-776
• 7.XueY,LindsellCE,NortonCRetal.EmbryoniclethalityandvasculardefectsinmicelackingtheNotch
ligandJagged1.HumMolGenet.1999;8(5);723-730
• 8.TienAC,RajanA,BellenHJ.ANotchUpdated.J.CellBiol.2009;184:621-629
• 9.OliverG,SrinivasanRS.Endothelialcellplasticity:howtobecomeandremainalymphaticendothelial
cell.Development.2010;137:363-372
• 10. Wu JK, Adepoju O, De Silva D et al. A switch in Notch gene expression parallels stem cell to
endothelialtransitionininfantilehemangioma.SpringerScience+BusinessMediaBV.2010;
• 11. Johnson NC, Dillard ME, Baluk P et al. Lymphatic endothelial cell identity is reversible and its
maintenancerequiresProx1activity.GenesDev.2008;22:3282-3291.
18. Acknowledgements
• I’d like to thank my mentor Carrie Shawber for
allowing my to work with her in the
Kitajewski/Shawber lab in the Columbia
University Medical Center, and for providing
me with all the necessary protocols and
materials, along with guidance and
mentorship.