Human papillomavirus (HPV)-induced cancers are expected to remain a major health problem worldwide for decades. The growth of HPV-positive cancer cells depends on the sustained expression of the ...viral E6 and E7 oncogenes which act in concert with still poorly defined cellular alterations. E6/E7 constitute attractive therapeutic targets since E6/E7 inhibition rapidly induces senescence in HPV-positive cancer cells. This cellular response is linked to the reconstitution of the antiproliferative p53 and pRb pathways, and to prosenescent mTOR signaling. Hypoxic HPV-positive cancer cells could be a major obstacle for treatment strategies targeting E6/E7 since they downregulate E6/E7 but evade senescence through hypoxia-induced mTOR impairment. Prospective E6/E7 inhibitors may therefore benefit from a combination with treatment strategies directed against hypoxic tumor cells.
Despite the availability of prophylactic vaccines which protect against infection with oncogenic human papillomavirus (HPV) types, HPV-linked carcinogenesis is expected to remain an important health problem for decades to come.
Targeting the viral E6/E7 oncogenes for functional inhibition should be an attractive therapeutic strategy to treat HPV-positive cancers with high specificity.
Active mTOR signaling is critical to enable HPV-positive cancer cells to efficiently induce senescence in response to E6/E7 inhibition. Hypoxic HPV-positive cancer cells downregulate E6/E7 and evade senescence due to hypoxia-linked impairment of mTOR, posing a potential problem for the therapeutic efficacy of prospective E6/E7 inhibitors.
Similar to chemotherapy and radiotherapy, therapeutic strategies aiming at E6/E7 inhibition could benefit from a combination with agents targeting hypoxic tumor cells.
A
bstract
The four-form field strength in F-theory compactifications on Calabi-Yau four-folds takes its value in the middle cohomology group
H
4
. The middle cohomology is decomposed into a vertical, ...a horizontal and a remaining component, all three of which are present in general. We argue that a flux along the remaining or vertical component may break some symmetry, while a purely horizontal flux does not influence the unbroken part of the gauge group or the net chirality of charged matter fields. This makes the decomposition crucial to the counting of flux vacua in the context of F-theory GUTs. We use mirror symmetry to derive a combinatorial formula for the dimensions of these components applicable to any toric Calabi-Yau hypersurface, and also make a partial attempt at providing a geometric characterization of the four-cycles Poincaré dual to the remaining component of
H
4
. It is also found in general elliptic Calabi-Yau fourfolds supporting SU(5) gauge symmetry that a remaining component can be present, for example, in a form crucial to the symmetry breaking SU(5) − → SU(3)
C
× SU(2)
L
× U(1)
Y
. The dimension of the horizontal component is used to derive an estimate of the statistical distribution of the number of generations and the rank of 7-brane gauge groups in the landscape of F-theory flux vacua.
The concept of free energy has its origins in 19th century thermodynamics, but has recently found its way into the behavioral and neural sciences, where it has been promoted for its wide ...applicability and has even been suggested as a fundamental principle of understanding intelligent behavior and brain function. We argue that there are essentially two different notions of free energy in current models of intelligent agency, that can both be considered as applications of Bayesian inference to the problem of action selection: one that appears when trading off accuracy and uncertainty based on a general maximum entropy principle, and one that formulates action selection in terms of minimizing an error measure that quantifies deviations of beliefs and policies from given reference models. The first approach provides a normative rule for action selection in the face of model uncertainty or when information processing capabilities are limited. The second approach directly aims to formulate the action selection problem as an inference problem in the context of Bayesian brain theories, also known as Active Inference in the literature. We elucidate the main ideas and discuss critical technical and conceptual issues revolving around these two notions of free energy that both claim to apply at all levels of decision-making, from the high-level deliberation of reasoning down to the low-level information processing of perception.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Four-pomeron vertex Braun, M. A.
The European physical journal. C, Particles and fields,
12/2021, Letnik:
81, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The four-pomeron vertex is studied in the perturbative QCD. Its dominating terms of the leading (zeroth and first) orders in the coupling constant and subdominant in the number of colors are ...constructed. The vertex consists of two terms, one with a derivative in rapidity
∂
y
and the other with the BFKL interaction between pomerons. The corresponding part of the action and equations of motion are found. The iterative solution of the latter is possible only for rapidities smaller than 2 and quite large coupling constant
α
s
, of the order or greater than unity, when the quadruple pomeron interaction is relatively small. Also iteration of the part with
∂
y
is unstable in the infrared region and compels to introduce an infrared cut. The variational approach with simple trying functions allows to find the minimum of the action at
α
s
of the order 0.2 and rapidities up to 25. Numerical estimates for O–O collisions show that actually the influence of the quadruple pomeron interaction turns out to be rather small.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the effective action approach the imaginary part of the triple pomeron amplitude is calculated. The found dependence on the longitudinal momentum transfer
e
-
is found to separate as a simple ...factor
1
/
|
e
-
|
. This result is used to calculate the high-mass diffraction on a hadron and double scattering cross-section off a composite target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The C-odd amplitude for the elastic
pp
and
p
p
¯
scattering due to the exchange of the QCD odderon proposed by J. Bartels, L.N. Lipatov and G.P. Vacca is calculated with the Fukugita–Kwiecinski ...proton impact factor. The found amplitude is very small and cannot be felt in the differential cross-sections at 2.76 and 1.96 TeV respectively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diffractive scattering on the deuteron Braun, M. A.
The European physical journal. C, Particles and fields,
05/2017, Letnik:
77, Številka:
5
Journal Article
Recenzirano
Odprti dostop
High-mass diffractive production of protons on the deuteron target is studied in perturbative QCD in the BFKL approach. A leading order rearrangement contribution and the standard triple pomeron (the ...impulse approximation) are studied. In the perturbative limit
α
s
→
0
the rearrangement contribution dominates. Numerical estimates at realistic values of
α
s
and energies strongly depend on assumptions made about the behavior of the pomeron attached to the proton due to unitarization. They indicate that irrespective of these assumptions in the realistic situation the rearrangement and triple pomeron contributions turn out to be of comparable magnitude due to the large dimensions of the deuteron.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To characterize the incidence of stress urinary incontinence (SUI) after radical prostatectomy (RP), its treatment, and impact on quality of life (QoL) and work status 1 year after RP.
Prostate ...cancer patients treated by RP (1998-2016) were selected from CaPSURE. SUI was defined as any pads per day (ppd) 1 year after RP. SUI procedures were tracked by CPT codes (sling and artificial sphincter). Patients reported work status (full-time, part-time, unpaid), UCLA PCa Index urinary function (UF) and bother (UB) and SF36 Index physical function (PF). Associations of incontinence with UF, UB and PF and work status changes were assessed (ANOVA). Lifetable estimates and Cox proportional hazards regression evaluated risk of undergoing SUI procedures.
664/2,989 (22%) men treated with RP reported SUI at 1 year. More men with SUI had ≥GG2, intermediate to high-risk disease and non-nerve sparing surgery (all p<0.01).
Cumulative incidence of SUI procedures was 1.4% at 10 years after RP. Age (HR 2.68 per 10 years, 95% CI 1.41-5.08) and number of ppd at 1 year (HR 3.20, 95% CI 2.27-4.50) were associated with undergoing SUI procedures.
UF declined at 1 year after RP, while UB and PF remained stable. UF, UB and PF were inversely associated with number of ppd (all p<0.01). Change in work status was not associated with incontinence or QoL scores.
Incontinence affected QoL without impacting work status, suggesting that men with SUI after RP may continue working and go under-treated despite impact on quality of life.
A
bstract
We study the duality between four-dimensional
N
= 2 compactifications of heterotic and type IIA string theories. Via adiabatic fibration of the duality in six dimensions, type IIA string ...theory compactified on a K3-fibred Calabi-Yau threefold has a potential heterotic dual compactification. This adiabatic picture fails whenever the K3 fibre degenerates into multiple components over points in the base of the fibration. Guided by monodromy, we identify such degenerate K3 fibres as solitons generalizing the NS5-brane in heterotic string theory. The theory of degenerations of K3 surfaces can then be used to find which solitons can be present on the heterotic side. Similar to small instanton transitions, these solitons escort singular transitions between different Calabi-Yau threefolds. Starting from well-known examples of heterotic-type IIA duality, such transitions can take us to type IIA compactifications with unknown heterotic duals.
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