C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding ...motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein-protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.
The soft X‐ray emissions from the Earth's magnetosheath and cusp regions are simulated under different solar wind conditions, based on the PPMLR‐MHD code. The X‐ray images observed by a hypothetical ...telescope are presented, and the basic responses of the magnetopause and cusp regions are discernable in these images. From certain viewing geometries, the magnetopause position in the equatorial plane, as well as the latitudinal scales and azimuthal extent of cusp can be directly extracted from the X‐ray images. With these reconstructed positions, the issues we are able to analyze include but are not limited to the compression of magnetopause and widening of the cusp after an enhancement of solar wind flux, as well as the erosion of the magnetopause and equatorward motion of cusp after the southward turning of the interplanetary magnetic field. Hence, the X‐ray imaging is an appropriate technique to study the large‐scale motion of magnetopause and cusps in response to solar wind variations.
Key Points
X‐ray images are estimated based on MHD simulations under different solar wind conditions
Responses of the magnetopause to solar wind changes are analyzed from X‐ray images
Responses of the cusp to solar wind variations are presented via X‐ray images
Background
In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab‐paclitaxel (GnP) have been publicly funded for first‐line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic ...pancreatic cancer (mPC) since April 2015. We examined the real‐world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC.
Methods
Patients receiving first‐line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population‐based databases. Overall survival (OS) was assessed using Kaplan‐Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models.
Results
For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70‐0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia‐related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia‐related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar.
Conclusion
In the real world, FFX had longer OS, less frequent all‐cause EDV and all‐cause hospitalization, but more febrile neutropenia‐related hospitalization compared to GnP.
In the real world, implementation of universal public funding of FOLFIRINOX for metastatic pancreatic cancer was associated with improved overall survival, less frequent all‐cause emergency department visits, less frequent all‐cause hospitalization, but increased febrile neutropenia‐related hospitalization compared to patients treated with gemcitabine + nab‐paclitaxel. Expanding funding to include unresectable locally advanced pancreatic cancer was associated with a similar trend in benefits, but with improved absolute survival.
To analyze the trends of human schistosomiasis prevalence in Hubei Province from 2004 to 2018, so as to provide the evidence for formulating the schistosomiasis elimination strategy in the province.
...All data pertaining to human schistosomiasis prevalence in Hubei Province were collected from 2004 to 2018, and the trends for changes in seroprevalence, egg-positive rate and prevalence of human
infection were analyzed using a Joinpoint regression model.
Both of the numbers of residents seropositive and egg-positive for
infections appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the prevalence of human
infections reduced from 6.85% in 2004 to 0 in 2018. Joinpoint regression analysis showed that the prevalence of human
infections appeared an overall tendency towards a reduction in Hubei Province from 2004 to 2018 average annual percent change (AAPC) = -24.1%,
< 0.01, and the trends for the reduction were both significant during the period from 2004 to 2006 annual percent change (AP
Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with ...single-agent gemcitabine in clinical trials.
To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit.
This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021.
First-line chemotherapy for advanced pancreatic cancer.
The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching.
From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio HR, 0.75 95% CI, 0.69-0.81). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 95% CI, 0.78-0.94).
This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.
Recently, a new kind of distributed element superconducting resonators with granular aluminum (grAl) has been developed for circuit quantum electrodynamics. Given that lumped element resonators ...possess certain advantages over the distributed element ones, in this paper, we use a relatively simple micro-nanotechnology, without the etching process, to fabricate the designed lumped element superconducting grAl resonators. They are deposited on silicon substrates by DC magnetron sputtering of pure Al in an atmosphere of Ar and O2. By cryogenic microwave transmission measurements, at a temperature of 50 mK, we find that, compared with a usual Al resonator of the same size, such a device shows significantly strong nonlinearity and thus higher kinetic inductance. The noise features, quality factors, and temperature-dependence of the resonant frequencies have been investigated experimentally. It is believed that the lumped element superconducting resonators with high kinetic inductance demonstrated here could also be applied to superconducting quantum computation and photon counting in the future.
Cryogenic detector and qubit readout systems often include radio-frequency low-pass filters (LPFs) at the input/output paths to protect the sensitive devices from stray radiation traveling down the ...coaxial lines. For this application, a popular solution is to use custom-made copper powder filters, which are LPFs with injection of copper powder-loaded epoxy. They are very effective in attenuating high frequency (THz and far infrared) radiation but often introduce a few dBs of undesired insertion loss at the readout band below 10 GHz. Here, we describe a LPF design concept based on low-
T
c
(
≈
700
mK) Ti/TiN superconducting artificial (lumped-element-loaded) transmission lines. We carefully design the unit inductance
L
u
and unit capacitance
C
u
to make the cut-off frequency
f
c
=
1
/
(
π
L
u
C
u
)
≈
30
GHz and the characteristic impedance
Z
0
=
L
u
/
C
u
≈
50
Ohm. Above the gap frequency (
≈
50
GHz), the transmission line behaves as a lossy line made of normal metal which naturally attenuates the high-frequency radiations. In addition, the cavity resonances and spurious pass-bands at high frequencies can be effectively suppressed by adding a layer of microwave absorber below the substrate and by introducing an aperiodic loading of unit structures. A detailed design and electromagnetic simulation using realistic material parameters are presented. Our LPF design offers the advantages of close-to-zero insertion loss below 10 GHz, precise and sharp frequency roll-off, and linear phase response. The LPF can be placed in a separate package with compact size and easily connected to other superconducting circuits.
•Triaxial shear tests are carried out to obtain the parameters of loose deposits.•The cracks are in agreement with the line of asymmetrical lateral stress.•Stress concentration occurs and leads to ...local cracking at the secondary lining.
Tunnels constructed in loose deposits with low strength and complex composition are usually subjected to asymmetrical stresses at the entrance and exit. The secondary tunnel lining is prone to excessive deformation, cracking, or even collapse, seriously affecting the safety of tunnel construction and operation. In this paper, a large shallow highway tunnel in loose deposits is used as an example to study the cracking mechanism of secondary lining. Triaxial consolidated-drained shear tests are carried out on large remolded specimens to obtain the mechanical parameters of the surrounding soil. Three-dimensional numerical modeling is conducted based on the field monitoring data to simulate the process of tunnel construction and to analyze the mechanical mechanism of cracking in the secondary lining. It is shown that even with the 30m advance pipe roof at the tunnel entrance, the apparent difference in stiffness between the retaining wall and the surrounding soil results in an obvious stress concentration at the spring of the secondary lining near the end of the retaining wall, due to the effect of highly asymmetrical stresses. In addition, loose deposits are very sensitive to construction disturbances. Large horizontal deformation towards the lower topography occurs during tunnel construction. With increasing overburden depth, the stress concentration at the spring level and the horizontal deformation in the secondary lining increases, which are the main reasons for cracking in the secondary lining. These findings can be useful for tunnel design and construction in the similar type of loose deposits.
We deposit thin titanium nitride (TiN) and TiN/Ti/TiN multilayer films on sapphire substrates and measure the reflectance and transmittance in the wavelength range from 400 to 2000 nm using a ...spectrophotometer. The optical constants (complex refractive indices), including the refractive index
n
and the extinction coefficient
k
, have been derived. With the extracted refractive indices, we propose an optical stack structure using low-loss amorphous Si (a-Si) anti-reflective coating and a backside aluminum (Al) reflecting mirror, which can in theory achieve 100% photon absorption at 1550 nm. The proposed optical design shows great promise in enhancing the optical efficiency of TiN-based microwave kinetic inductance photon-number-resolving detectors.
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