8 research outputs found
Filologia e società nella carriera di un maestro greco fra Quattro e Cinquecento: Giorgio Ermonimo di Sparta
No full textThe Author reflects on the historical and social aspects of the migration of the Byzantine scholars to Italy and then beyond the Alps after the fall of Constanti- nople and Mistrà, focusing upon on the figure of the Spartan teacher, diplomat and scribe George Hermonymos. In the first part, the Author discusses some problematic aspects of Hermonymos’ biography, as well as some issues related to his manuscript production and his writing. In the second, the Author offers a critical list of all the manuscripts copied, owned and / or annotated by Giorgio Ermonimo known to date, as well as a first census of the printed editions with manuscript interventions by him and, in addition, some examples of his Latin writing
Rating e-mail personality at zero acquaintance
No full textElectronic media play an ever-increasing role in our daily communication. But howwell can personality traits be perceived through a short e-mail message? Workingindependently and under experimenter supervision, thirty judges each rated 18 short e-mail texts. These texts were produced by authors of known personality, who briefly described their recent activities, and were collected as part of a previously reported study which demonstrated linguistic characteristics of personality. As predicted by the perception literature, we nd that even with minimal textual cues there is relatively high agreement, for ratings of author Extraversion. However, agreement for Neuroticism ratings appears to be further reduced by the environment, especially between target and judges. In addition to reducing the cues available for personality rating, the study extends the previous work in two main ways: rst, it measures one further dimension of target personality|Psychoticism|rather than the separate factors Agreeableness and Conscientiousness (along with Openness); and secondly, it adopts additional, novel exemplar-based and subjective measures of personality perception
Accurate prediction of ecDNA in interphase cancer cells using deep neural networks
No full textOncogene amplification is a key driver of cancer pathogenesis and is often mediated by extrachromosomal DNA (ecDNA). EcDNA amplifications are associated with increased pathogenicity of cancer and poorer outcomes for patients. EcDNA can be detected accurately using fluorescence in situ hybridization (FISH) when cells are arrested in metaphase. However, the majority of cancer cells are non-mitotic and must be analyzed in interphase, where it is difficult to discern extrachromosomal amplifications from chromosomal amplifications. Thus, there is a need for methods that accurately predict oncogene amplification status from interphase cells. Here, we present interSeg, a deep learning-based tool to cytogenetically determine the amplification status as EC-amp, HSR-amp, or not amplified from interphase FISH images. We trained and validated interSeg on 652 images (40,446 nuclei). Tests on 215 cultured cell and tissue model images (9,733 nuclei) showed 89% and 97% accuracy at the nuclear and sample levels, respectively. The neuroblastoma patient tissue hold-out set (67 samples and 1,937 nuclei) also revealed 97% accuracy at the sample level in detecting the presence of focal amplification. In experimentally and computationally mixed images, interSeg accurately predicted the level of heterogeneity. The results showcase interSeg as an important method for analyzing oncogene amplification
Coordinated inheritance of extrachromosomal DNAs in cancer cells
No full textThe chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells. How multiple ecDNA species within a tumour cell are assorted and maintained across somatic cell generations is unclear. Here we show that cooperative ecDNA species are coordinately inherited through mitotic co-segregation. Imaging and single-cell analyses show that multiple ecDNAs encoding distinct oncogenes co-occur and are correlated in copy number in human cancer cells. ecDNA species are coordinately segregated asymmetrically during mitosis, resulting in daughter cells with simultaneous copy-number gains in multiple ecDNA species before any selection. Intermolecular proximity and active transcription at the start of mitosis facilitate the coordinated segregation of ecDNA species, and transcription inhibition reduces co-segregation. Computational modelling reveals the quantitative principles of ecDNA co-segregation and co-selection, predicting their observed distributions in cancer cells. Coordinated inheritance of ecDNAs enables co-amplification of specialized ecDNAs containing only enhancer elements and guides therapeutic strategies to jointly deplete cooperating ecDNA oncogenes. Coordinated inheritance of ecDNAs confers stability to oncogene cooperation and novel gene regulatory circuits, allowing winning combinations of epigenetic states to be transmitted across cell generations
Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH
No full textExtrachromosomal DNA (ecDNA) is a common mode of oncogene amplification but is challenging to analyze. Here, we adapt CRISPR-CATCH, in vitro CRISPR-Cas9 treatment and pulsed field gel electrophoresis of agarose-entrapped genomic DNA, previously developed for bacterial chromosome segments, to isolate megabase-sized human ecDNAs. We demonstrate strong enrichment of ecDNA molecules containing EGFR, FGFR2 and MYC from human cancer cells and NRAS ecDNA from human metastatic melanoma with acquired therapeutic resistance. Targeted enrichment of ecDNA versus chromosomal DNA enabled phasing of genetic variants, identified the presence of an EGFRvIII mutation exclusively on ecDNAs and supported an excision model of ecDNA genesis in a glioblastoma model. CRISPR-CATCH followed by nanopore sequencing enabled single-molecule ecDNA methylation profiling and revealed hypomethylation of the EGFR promoter on ecDNAs. We distinguished heterogeneous ecDNA species within the same sample by size and sequence with base-pair resolution and discovered functionally specialized ecDNAs that amplify select enhancers or oncogene-coding sequences
ecDNA hubs drive cooperative intermolecular oncogene expression
No full textExtrachromosomal DNA (ecDNA) is prevalent in human cancers and mediates high expression of oncogenes through gene amplification and altered gene regulation. Gene induction typically involves cis-regulatory elements that contact and activate genes on the same chromosome. Here we show that ecDNA hubs-clusters of around 10-100 ecDNAs within the nucleus-enable intermolecular enhancer-gene interactions to promote oncogene overexpression. ecDNAs that encode multiple distinct oncogenes form hubs in diverse cancer cell types and primary tumours. Each ecDNA is more likely to transcribe the oncogene when spatially clustered with additional ecDNAs. ecDNA hubs are tethered by the bromodomain and extraterminal domain (BET) protein BRD4 in a MYC-amplified colorectal cancer cell line. The BET inhibitor JQ1 disperses ecDNA hubs and preferentially inhibits ecDNA-derived-oncogene transcription. The BRD4-bound PVT1 promoter is ectopically fused to MYC and duplicated in ecDNA, receiving promiscuous enhancer input to drive potent expression of MYC. Furthermore, the PVT1 promoter on an exogenous episome suffices to mediate gene activation in trans by ecDNA hubs in a JQ1-sensitive manner. Systematic silencing of ecDNA enhancers by CRISPR interference reveals intermolecular enhancer-gene activation among multiple oncogene loci that are amplified on distinct ecDNAs. Thus, protein-tethered ecDNA hubs enable intermolecular transcriptional regulation and may serve as units of oncogene function and cooperative evolution and as potential targets for cancer therapy
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No full textPENINSULA RAPID
TRANSIT CO.
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DAILY PALO ALTO TOOtS. THURSDAY, MAY aa, 1917.
PACE THREE
GOVERNMENT GOT THIS "CHASER" FOR A DOLLAR
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FIRE
LOANS
W. P. HtDE
Room U. Mi-si National lUah
Halldt-ag, Palo Alio, CmL
GUIDE ARIGHT.
Every man la th* tartar ef mmr-
BaBtual rtd.it.an Ilka a lurair-4-w*
bed/. Hi h, ii h were, • baa
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th* eeeka If it d*M net uu.de It
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PALO ALTO-SAN JOSE
AUTO BUSES
Ome.l*l Dally Tim* Tebl*
Hilf hourly Service to S*n Jo**
•net Way Points
EFFECTIVE MAY 15. 1»17
L«*va Pale
Alto. Circle.
6 J*> A M
7:4*,
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10: 15
10 45
11:16
11 46
12 16 PM
13:45
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4:25
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"Saturdays mtj Sunday*
Fare—40e one way.
t'lp .-©•rid* COl-nmutStloi
Intermediate points pro 1
AI night look fO' gr-ee
bua
For further
A. 50R.
.nfon
t'On phone P
DAViS SCHAUB AUTO
SERVICE, INC.
WOMAN ALL RUN DOWN
Msde Strong and Weil by Vlnol
Waynesboro. Pa. "I was all run
down after a bard spell of bronchitis
so It was hard for me to keep about I
bad pains In my chest and took cold
easily A friend asked me to try Vlnol
1 did and ll built me up so I a*n strong
and welt and I am able to do my house
t-ork whlrh I had not done for three
month* before taking Vlnol '" - Mrs Y
It Horboujch. Waynesboro. Ta.
Vlnol creates an apepllte. aids dl
geatlon. tnakes pun- blood and creates
simngth Your money back If It falls
Kacle Drug (\> Palo Alto
FOR SALE
3 Large Bargains
llematllu) or« (-teeter an
ahin'le hungaloB < lo*e In a
modern In. i>rovemeni*
F>0*20tl Tl lot Hornet ave
line n.-ii Wi-h.ler at feel
la 1. lota .".OiJtH- rU. h near
Be* I I. I.i ti It 1Kb S. h.-ol cite
GEO. H. BENTLEY
."VIM 1 hut ..11 Hrpne*.
"Tale of Two Sleeves"
Shows Knight Motor
Willys-Overland Company Will
Show Interesting Film at
Varaity Next Week
Striking arene* ilea, rhptlve ol the
making of an autoniuhlle motor
neier btaTor* »ho*an on a motion l>Ir
lute atheen mill be it-r-es* here In s
Tale of Tao Sleeve*, ibe motion
picture awry of the knight sleeve
|»alve motor bi the Varslt, Theater
on ..edita-adai evening May 3ft
' Word of an addition (o the pl.liirc
reached Mr Allen of the Palo Alio
I Hardware tomi-am .e*(erda>
underaund tal,I Mr Allen.
i tbat In addition to further scene*
deaerlptlT* of the ileatgn and opera -
" *f lhe Knight motor (he Willys
|(>.erland i'omiian> ha* hud produced
a l**efi|re calculated tt. t-wtwUll*. In
...-e-.| •i.iurn Thl* picture form-, a
leaaon In automobile driving A <*r
. |s -h..an and aeated al the a heel 1*
[a girl who operalee the dutch |.e.la.
] "» It. h button an.I o'het aim |i|e
. me. h*nl*ni» ol Hi*, modern autoino
Th.. ami l» pael ahen aomen
b*-*i|la(e t(i drl.c a ga*ollne tar Thr
rmaiin fi.f ihla l> t hat the in anil ■
fa.turer- reallalng aotiien do not
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ietllle,t Ibe lw|M*r*llng tm*. l.aiilMt. of
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Marquee Featuring
"The Pinch Hitter"
C Gardner Sullivan Who Wrote
Hell's Hinge*." Is the
Author
i- Gardner Sullivan rhlel of ihe
rtuuoaa II Inee ai-enarlo atnlT. who
• rote Plain Jane The Wolf Wo
man Home Hell * Hinge*"
ami other atfren au**e*a*e* has re
■ «rded another h|l with The Pinch
Hitter in whlrh Chartc-* Kay atar*
I ik.< Plain Jan* H I* a atnrv of
lhe >*0l tt-*le campus '*'i- aurpasses
lhai play In the ahurnlsi.. • of lm
mm and rharai-ler development
Hnlll.an la a man of aide Dew*.
i-a i'i*r eiperlem-e having e-rrve.! on
leading 4all|e* tbrnuchetii th" «-oun-
tri He ws* horn In Stillwater
Minn nod waa e.liimted at the Inl
Protect Your Oak Trees
Against Defoliation
By Caterpillars
SPRAY EARLY
Absolute Satisfaction
Prompt Service
S. P. Mc CLENAMAN
AkHtiRlci l nkisi
UT AdallM'a Ave*aae
PHONK 9«fU
Palo Alto
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I-..-H ion on i I.r i egula r *ta(T Mr
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a.11 hot min .1l*i.la. tntlivldiialll v" of
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in*: Plain lane Home and "A
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an in Tlie Pin. h Hitter '
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-he Hartiuee Imlai und tomnrroa
Arroya Honda
Creamery Butter
Manufactured by B. D. Weeks,
La Hon,I.i. San Malr-n ( ininlv
2 lb square 80c
FULLER & CO.
The Leading Oroceri*
,»•.* .-a*
162 University Ave Phone 751-2
1
UNITED STATES POSTOFFICE. FALO ALTO
Schedule ol Mails South. E.K and North
MA.la. th M* r.i.lil... 'ti
New 6,000 House to
Be Built at Menlo Park
Train rtualng h*r*
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■ IK lo .1" ■!.> Til I
Memorial
Day
Excursions
Between all
Points In
California.
AIm> to Nevada
aad Oicfo-.
PouiU.
I a krl, oa .ale
May 29. 30. re
mm limit. May 3 I
I-ot lurthrt paibca-
!».. A*t AG£NTS
Southern
Pacific
Wntt tor (older un thr Ariat hr
Trsil of Ariron.
Printing
of Highest
Quality
THE highest quality ol printed
matter ia only obtainable through
the use of th* lateat equipment,
th* exerciac of arostic taste in com-
position and the careful *eie*t-tioo nf
th* product of th* paper mills It it
a habit witii ua to look after all tb*
caaential* of best printing.
Charles A llt.i.lv Will Huild a
Two-Story House for Mra
Violet Foster
' l a lie* v lh ad < »f Menlo Par*
MAIIafl T«l BACRAMKSTO. (Al..
The flr*t i*c Iraitm ahove ar* lae most d I reel to H*. rametiio and flan
ioaolDts
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The** mallp are due to arrlv* aV>*(on Mas* . three hours later tbaa
\r* York. N Y
riled
I I-
Times Publishing Co.
Palo Alto
..r lhe a or It Ihe |ir|re lieiOg 1 -' 4»
rhe home |a t „ lie eompleled w Ith
in niiieii days
DIPLOMATIC FORMS.
Tha "Pretec-wl" I* "the Cod* o' Intse-
-llJr. fo t**-«ll."
! In theee day* of offielal ootra autl
| repJle* Hi*, puhlle la lierominK familiar
I with the language of ttie dlpiuinath-
: Ooeumeut. and even tbuwe who never
i beard of the fatnt-iu or-.to.oi - hi. I.
i Ilea le tbe arehlve* of tl*e foreign ■'".■.■
I In Pari*. rau*t iiave n-.ti-.-l (he alojl
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lu tbe time or 1...-1'.* XIV. ia a t-.-l;
of reremoulal rule* to Ire ol.Berved In
• II written or persona) OtDclal Inter
je-jaira* tictweru the bea.la of different
' statea or tbelr lulnlsters It cue* Into
tbe tnlnuirat detail *■ to (he atyle* and
Htl* lo he given to arate*. their h**da
| and their puhlle totnUtera, and Indl
i .-ate* "the forma and eourtealea lo lie
| os-eer-verl In all International aria."
Tb* prol.«-.*, la. in fart, what M
i Pradrer-Fodere. a well known autborlt*
on the sut.>«*<-t. has dew-rlhed II. ' t h.
i-*r*le of International pollteneea," for
as time went on. all natloo* gr*duall-
oa**jan to adopt tbe *ame forms, until
tod*y th* cud* may he aaid (o h* prae
tlrallj nnlTersal In it* ajuilleatlo., li
-levntee ap*rl*l atlentl.ai (o such mat
ter* as tbe ending of * letter Thus
sa a i-eeetit writer bas --ototed .ait
when tbe British foreign minister eon
I elude* a letter to tbe British am!*****-*
| dor it **ra*hlaf*ton wttb th* words. I
■ am, with areal truth and r**a-**Kt. sir
I yotir rl i e.irle')' « moat ol-edlent. hut*.
] hi* *erTaii(." be la governed by pnre
! deal even In such s detail as gl* li..'
1 «lr" a line lo Itself rhrlatlaii 8<l*ii..
\I.*nlir*r
rra.n Closing hare
No 7:. 8 21 a m
No Tf.-- ■■ ft 21 a m
No 7f. k 21 i m.
No bt - t it p tn.
No •>-,_ HI p. ■
No 5 6 5t7p tn.
MAII,*. OOtXQ NORTH
Due (o arrlv* at Tim* of arrival
.Portland, Or* I Sl p n neit day
Seattle. Wash li 10 p m neit day
. , . Spokane.Wash . 6 r.O am second day
. .. .Portland. Or*. 7 20 a m second dar
Seattle, Waab . J 10pm -second day
Spokane.Wash HS po second dar
A Tr.r.a Freah.
••8lJ'.•■ a;i i ihr fair <-Bura*eer. I bj.
selling Btoek lu a ;,ea<-h or*liard '
"Are you a fair aample of the ot
chard output'/'* be liitjulred "If *->
think I'U Ui.aet - Kaiisas Uty Jour
Yosemite-'
In sheer cliffs and waterfalls
it stands supreme.
In scenic grandeur it is unsurpassed.
Remarkably low fares.
A A J i-A For ticket* on aai*
\ /1 nil <**Ujr r**ont 11ib1( -
Mr I ill I month * from dat* of
$on % ZmTm*
For tickets on sale
Satnr
rti limit
day* From dale of
Inetude* auto *ta-g* far* from B) Porta) ": hotels and camp*
Write for Illustrated YosemKe llook
let Agent* will gladly assist .vou In
arranging vour trip
Southern Pacific
Write/or folder on the Apache Trail of Arizon
Extrachromosomal DNA micronucleation constrains tumour fitness and improves patient survival
No full textExtrachromosomal DNA (ecDNA) contributes to cancer genome instability by enabling high-copy oncogene amplification, intratumoural heterogeneity and rapid genetic change. Micronuclei (MN) are frequently observed in chromosomally unstable cancers, yet their origins and relevance in ecDNA-driven tumours remain incompletely understood. Here, we investigate the relationship between ecDNA segregation errors and MN formation. We find that ecDNA frequently localizes to MN and represents a prominent source of MN content in ecDNA-positive cancer cells. Mitotic clustering of oncogene-bearing ecDNAs is associated with asymmetric inheritance and mis-segregation into MN. Transfer of oncogenes from ecDNA into MN is accompanied by reduced transcriptional output. Single-MN sequencing shows that individual MN are enriched for ecDNA to a degree that exceeds expectations from stochastic mis-segregation and that in MN oncogenes originating from multiple distinct ecDNAs coalesce. Using live-cell imaging, we observe that cells inheriting ecDNA-positive MN show limited proliferative capacity and an increased likelihood of cell death. In neuroblastoma patients with MYCN-amplified ecDNA, higher frequencies of ecDNA-positive MN at diagnosis are associated with improved event-free and overall survival. Together, these findings link ecDNA mis-segregation to MN formation and reduced cellular fitness, suggesting that ecDNA-positive MN may reflect a state of impaired oncogenic ecDNA function with potential relevance for clinical outcome
