Renal cancer ranks 10
in the mortality structure of the Russian Federation. The introduction of checkpoint inhibitors has changed the paradigm of treatment of patients with malignant neoplasms.
Data ...from clinical trials have shown good progression-free median and median overall survival. Each cancer center has been accumulating its own experience in treating patients with renal cell cancer by applying modern target drugs and immunotherapy.
In routine clinical practice, oncologists do not get the results that have been demonstrated in clinical trials when evaluating the effectiveness of the therapy.
In this single-center clinical study, we discuss the results of using nivolumab as mono-therapy and the combination of nivolumab with ipilimumab in metastatic renal parenchyma cancer patients.
We first advance a mathematical novelty that the three geometrically and topologically distinct objects mentioned in the title can be exactly obtained from the Jordan frame vacuum Brans I solution by ...a combination of coordinate transformations, trigonometric identities and complex Wick rotation. Next, we study their respective accretion properties using the Page–Thorne model which studies accretion properties exclusively for
r
≥
r
ms
(the minimally stable radius of particle orbits), while the radii of singularity/throat/horizon
r
<
r
ms
. Also, its Page–Thorne efficiency
ϵ
is found to increase with decreasing
r
ms
and also yields
ϵ
=
0.0572
for Schwarzschild black hole (SBH). But in the singular limit
r
→
r
s
(radius of singularity), we have
ϵ
→
1
giving rise to
100
%
efficiency in agreement with the efficiency of the naked singularity constructed in 10. We show that the differential accretion luminosity
d
L
∞
d
ln
r
of Buchdahl naked singularity (BNS) is always substantially larger than that of SBH, while Eddington luminosity at infinity
L
Edd
∞
for BNS could be arbitrarily large at
r
→
r
s
due to the scalar field
ϕ
that is defined in
(
r
s
,
∞
)
. It is concluded that BNS accretion profiles can still be higher than those of regular objects in the universe.
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Proteins perform their functions in solution but their structures are most frequently studied inside crystals. Here we probe how the crystal packing alters microsecond dynamics, using solid-state NMR ...measurements and multi-microsecond MD simulations of different crystal forms of ubiquitin. In particular, near-rotary-resonance relaxation dispersion (NERRD) experiments probe angular backbone motion, while Bloch-McConnell relaxation dispersion data report on fluctuations of the local electronic environment. These experiments and simulations reveal that the packing of the protein can significantly alter the thermodynamics and kinetics of local conformational exchange. Moreover, we report small-amplitude reorientational motion of protein molecules in the crystal lattice with an ~3-5° amplitude on a tens-of-microseconds time scale in one of the crystals, but not in others. An intriguing possibility arises that overall motion is to some extent coupled to local dynamics. Our study highlights the importance of considering the packing when analyzing dynamics of crystalline proteins.X-ray crystallography is the main method for protein structure determination. Here the authors combine solid-state NMR measurements and molecular dynamics simulations and show that crystal packing alters the thermodynamics and kinetics of local conformational exchange as well as overall rocking motion of protein molecules in the crystal lattice.
This paper concerns the issue of asymptotic acceptance of the true Hessian and the full step by the sequential quadratic programming algorithm for equality-constrained optimization problems. In order ...to enforce global convergence, the algorithm is equipped with a standard Armijo linesearch procedure for a nonsmooth exact penalty function. The specificity of considerations here is that the standard assumptions for local superlinear convergence of the method may be violated. The analysis focuses on the case when there exist critical Lagrange multipliers, and does not require regularity assumptions on the constraints or satisfaction of second-order sufficient optimality conditions. The results provide a basis for application of known acceleration techniques, such as extrapolation, and allow the formulation of algorithms that can outperform the standard SQP with BFGS approximations of the Hessian on problems with degenerate constraints. This claim is confirmed by some numerical experiments.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
It is well known that the Einstein-scalar system of general relativity can in principle yield non-unique exact spinning naked singularities, which lead to unique Kerr black hole when the scalar field ...is switched off. It is a challenging task to observationally distinguish these two types of objects. Since accretion process could be a viable diagnostic for this distinction, the purpose of the present work is to explore whether there could be features in the accretion profiles distinguishing the singularity from a Kerr black hole. Here we study the Novikov–Thorne thin accretion to a
new
spinning naked singularity with a scalar charge
σ
recently reported by Bogush and Gal’tsov (BG). Our study reveals that: (1) the conversion efficiency
ϵ
of the BG naked singularity is
independent
of
σ
and (2) the maxima of emissivity profiles for the BG singularity tend to shift towards the inner disk ISCO boundary
r
=
r
ms
and peak at a value significantly larger than those of a Kerr black hole with the increase of
a
,
σ
and relative shrinking of
-
g
. All these effects are
quantitatively
tabulated, which reveal, for instance, that the flux from the naked singularity could be as high as
10
5
times larger than that of a Kerr black hole. Since these distinguishing features are known to be shared also by other models of naked singularity, it is tempting to speculate that such behavior could be hallmark of naked singularities.
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It has been argued that the recently detected ring-down gravity waveforms could be indicative only of the presence of light rings in a horizonless object, such as a surgical Schwarzschild wormhole, ...with the frequencies differing drastically from those of the horizon quasinormal mode frequencies ωQNM at late times. While the possibility of such a horizonless alternative is novel by itself, we show by the example of the Ellis-Bronnikov wormhole that the differences in ωQNM in the eikonal limit (large l) need not be drastic. This result will be reached by exploiting the connection between ωQNM and the Bozza strong field lensing parameters. We shall also show that the lensing observables of the Ellis-Bronnikov wormhole can be very close to those of a black hole (say, SgrA* hosted by our galaxy) of the same mass. This situation indicates that the ring-down frequencies and lensing observables of the Ellis-Bronnikov wormhole can remarkably mimic those of a black hole. The constraint on wormhole parameter γ imposed by experimental accuracy is briefly discussed. We also provide independent arguments supporting the stability of the Ellis-Bronnikov wormhole proven recently.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
On the inverse hoop conjecture of Hod Nandi, K. K.; Izmailov, R. N.; Potapov, A. A. ...
The European physical journal. C, Particles and fields,
11/2021, Volume:
81, Issue:
11
Journal Article
Peer reviewed
Open access
Recently, Hod has shown that Thorne’s hoop conjecture (
C
(
R
)
4
π
M
(
r
≤
R
)
≤
1
⇒
horizon) is violated by stationary black holes and so he proposed a new inverse hoop conjecture characterizing ...such black holes (that is, horizon
⇒
H
=
π
A
C
eq
2
≤
1
). In this paper, it is exemplified that stationary
hairy
black holes, endowed with Lorentz symmetry violating Bumblebee vector field related to quantum gravity and dilaton field of string theory, also respect the inverse conjecture. It is shown that stationary hairy singularity, recently derived by Bogush and Galt’sov, does not respect the conjecture thereby protecting it. However, curiously, there are two horizonless stationary wormholes that can also respect the conjecture. Thus one may also state that throat
⇒
H
≤
1
, suggesting that the inverse conjecture may be a necessary but not sufficient proposition.
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Recently, a class of static spherically symmetric power law corrected Lorentz violating (LV) Schwarzschild black holes in the Kalb–Ramond model have been derived and studied in the specific range of ...LV parameters (
0
<
λ
≤
2
,
Υ
≥
0
) that correspond to energy condition preserving (
ρ
>
0
) source. On the other hand, there exist well known black holes that do not preserve the energy conditions. In this paper, we shall therefore relax energy conditions and numerically explore the horizon patterns of the enlarged class of LSMA black holes. Four generic types of LV corrected black holes emerge, which interestingly include the analogue of the
braneworld
black hole (
ρ
<
0
) lending to
Υ
a new interpretation of “tidal charge” known as an imprint from the 5
d
bulk in the Randall–Sundrum scenario. We shall then show that Thorne’s hoop conjecture,
H
≤
1
, where
H
is the Hod function, consistently holds for three types and their generalizations. However, intriguingly, it turns out that, for the remaining type (viz., Schwarzschild–de Sitter and its generalizations), the hoop conjecture does
not
hold. It is also shown that braneworld tidal charge black holes increases the LV correction to planetary perihelion advance in contrast to the decrease due to ordinary black holes thereby providing a qualitative distinction between them.
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The hoop conjecture, due to Thorne, is a fundamental aspect of black holes in classical general relativity. Recently, generalized classes of regular spherically symmetric static black holes with ...arbitrary exponents coupled to nonlinear electrodynamics have been constructed in the literature. The conjecture in those spacetimes could be violated if only the asymptotic mass
M
∞
is used. To avoid such violations, Hod earlier suggested the appropriate mass function and stated the conjecture in terms of what we call the Hod function. The conjecture can then be applied to any given static spacetime to test whether or not it represents black holes. It is shown here that the conjecture is protected in the above constructed class of generalized spacetimes thus supporting them as black holes. However, it is argued that there are factors, including violation of the conjecture, that militate against the proposed
new
class of solutions to be qualifying as black holes. Finally, we exemplify that the Hod mass
M
(
r
≤
R
)
in the conjecture is exactly the
matter
counterpart of the Misner–Sharp
geometrical
quasilocal mass
m
(
r
≤
R
)
of general relativity. Thus any conclusion based on Hod function is strictly a conclusion of general relativity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Here we report the results of the pilot project of exosomal miRNA expression levels in clear cell renal cell carcinoma (ccRCC) patients with different clinical response to ICIs (nivolumab) and ...treatment related toxicity. Immune-related adverse events (irAEs) are a major cause of immune checkpoint inhibitors cancellation and therapy failure. Modern studies demonstrate evidence that exosomes are of great importance in the formation of tumor resistance to ICIs drugs and therapy. We performed exosomal miRNA-146a expression analysis using qPCR on 86 ccRCC patients and revealed a statistically significant (p = 0.01) decreased expression level in ccRCC patients with CTCAE grade 3–4 (M±SEM 1.71 ± 0.13) compared to CTCAE grade 0–2 group (M±SEM 2.30 ± 0.24). The expression levels of miRNA-126, miRNA-218 and miRNA-410 did not show statistically significant differences in the comparison groups (p > 0.05). Association analysis of rs2910164 in the miRNA-146a gene demonstrated that CC genotype and C allele carriers had higher risk of developing severe irAEs (p = 0.03, OR = 6.12; p = 0.01, OR = 2.42, respectively) compare with GG and GC carriers. That is the first attempt to identify biomarkers of ICIs treatment efficacy for ccRCC in the Volga-Ural region based on exosomal miRNAs analysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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