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Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers.

Background Most diabetes care occurs in primary care. Continuous glucose monitoring (CGM) is associated with clinical, behavioral, and psychosocial benefits. While CGM uptake in primary care is increasing, understanding models to support CGM use in diverse primary care practices is needed. The PREPARE 4 CGM study evaluated strategies to implement CGM in primary care. We compared characteristics among practices choosing a practice-led, self-paced CGM implementation strategy or referral to a virtual CGM implementation service that provided patients and their referring primary care practices CGM initiation and data interpretation support for at least six months. Methods Colorado PC practices interested in implementing CGM enrolled and chose to use the American Academy of Family Physicians Transformation in Practice Series (TIPS): CGM implementation modules or refer patients to a virtual CGM initiation and education service designed and staffed by a primary care multi-disciplinary team. In this multiple methods study, baseline practice characteristics were compared across study arms using chi-square and t-tests. Semi-structured interviews with practice members provided additional context to explain study arm selection. Results Of 76 practices enrolled, 46 chose self-paced implementation using TIPS modules, 16 of which (35%) had a diabetes care and education specialist (DCES) in the practice; of the 30 that chose the virtual CGM initiation service, none (0%) had a DCES, X 2 (1, N  = 62) = 11.046, p  <.001. Aside from having a DCES, no differences in 37 other practice characteristics were seen between groups. Conclusions Primary care practices were eager to implement CGM. All practices with a DCES chose to implement CGM on their own; of the practices without a DCES, implementation method selection was evenly split (half chose to implement on their own, half chose virCIS). DCESs may have potential as diabetes technology champions in primary care practices. Referral to the virtual CGM implementation service allowed access to a certified DCES and multidisciplinary team for practices without them. As many practices without a DCES also chose to implement CGM on their own, multiple models may be necessary to foster CGM implementation in primary care. Trial registration This project was reviewed and approved by the Colorado Multiple Institutional Review Board (COMIRB; Protocol 21-4269) and registered with ClinicalTrials.gov on March 23, 2022 (NCT05336214).

Hyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of CP asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this paper, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis uses the framework and systematic uncertainties derived from the ongoing T2K experiment. With a total exposure of 7.5 MW × 107 sec integrated proton beam power (corresponding to 1.56×1022 protons on target with a 30 GeV proton beam) to a 2.5-degree off-axis neutrino beam, it is expected that the leptonic CP phase δCP can be determined to better than 19 degrees for all possible values of δCP, and CP violation can be established with a statistical significance of more than 3σ (5σ) for 76% (58%) of the δCP parameter space. Using both νe appearance and νμ disappearance data, the expected 1σ uncertainty of sin2θ23 is 0.015(0.006) for sin2θ23=0.5(0.45).

We present results of a search for spin-independent dark matter-nucleon interactions in a 1 cm\\(^2\\) by 1 mm thick (0.233 gram) high-resolution silicon athermal phonon detector operated above ground. For interactions in the substrate, this detector achieves a r.m.s. baseline energy resolution of 361.5 \\(\\pm\\) 0.4 MeV/\\(c^2\\), the best for any athermal phonon detector to date. With an exposure of 0.233g \\(\\times\\) 12 hours, we place the most stringent constraints on dark matter masses between 44 and 87 MeV/\\(c^2\\), with the lowest unexplored cross section of 4 \\(\\times 10^{-32}\\) cm\\(^2\\) at 87 MeV/\\(c^2\\). We employ a conservative salting technique to reach the lowest dark matter mass ever probed via direct detection experiment. This constraint is enabled by two-channel rejection of low-energy backgrounds that are coupled to individual sensors.

SuperCDMS SNOLAB uses kilogram-scale germanium and silicon detectors to search for dark matter. Each detector has Transition Edge Sensors (TESs) patterned on the top and bottom faces of a large crystal substrate, with the TESs electrically grouped into six phonon readout channels per face. Noise correlations are expected among a detector's readout channels, in part because the channels and their readout electronics are located in close proximity to one another. Moreover, owing to the large size of the detectors, energy deposits can produce vastly different phonon propagation patterns depending on their location in the substrate, resulting in a strong position dependence in the readout-channel pulse shapes. Both of these effects can degrade the energy resolution and consequently diminish the dark matter search sensitivity of the experiment if not accounted for properly. We present a new algorithm for pulse reconstruction, mathematically formulated to take into account correlated noise and pulse shape variations. This new algorithm fits N readout channels with a superposition of M pulse templates simultaneously - hence termed the N\\(\\times\\)M filter. We describe a method to derive the pulse templates using principal component analysis (PCA) and to extract energy and position information using a gradient boosted decision tree (GBDT). We show that these new N\\(\\times\\)M and GBDT analysis tools can reduce the impact from correlated noise sources while improving the reconstructed energy resolution for simulated mono-energetic events by more than a factor of three and for the 71Ge K-shell electron-capture peak recoils measured in a previous version of SuperCDMS called CDMSlite to \\(<\\) 50 eV from the previously published value of \\(\\sim\\)100 eV. These results lay the groundwork for position reconstruction in SuperCDMS with the N\\(\\times\\)M outputs.

The current laws of physics do not explain the observed imbalance of matter and antimatter in the universe. Sakharov proposed that an explanation would require the violation of CP symmetry between matter and antimatter. The only CP violation observed so far is in the weak interactions of quarks, and it is too small to explain the matter-antimatter imbalance of the universe. It has been shown that CP violation in the lepton sector could generate the matter-antimatter disparity through the process called leptogenesis. The quantum mixing of neutrinos, the neutral leptons in the Standard Model, provides a potential source of CP violation through a complex phase dCP, which may have consequences for theoretical models of leptogenesis. This CP violation can be measured in muon neutrino to electron neutrino oscillations and the corresponding antineutrino oscillations, which are experimentally accessible with accelerator-produced beams as established by the T2K experiment. Until now, the value of dCP has not been significantly constrained by neutrino oscillation experiments. Here the T2K collaboration reports a measurement that favors large enhancement of the neutrino oscillation probability, excluding values of dCP which result in a large enhancement of the observed anti-neutrino oscillation probability at three standard deviations (3 sigma). The 3 sigma confidence level interval for dCP, which is cyclic and repeats every 2pi, is [-3.41,-0.03] for the so-called normal mass ordering, and [-2.54,-0.32] for the inverted mass ordering. Our results show an indication of CP violation in the lepton sector. Herein we establish methods for sensitive searches for matter-antimatter asymmetry in neutrino oscillations using accelerator-produced neutrino beams. Future measurements with larger data samples will determine whether the leptonic CP violation is larger than the quark sector CP violation.

The electron (anti-)neutrino component of the T2K neutrino beam constitutes the largest background in the measurement of electron (anti-)neutrino appearance at the far detector. The electron neutrino scattering is measured directly with the T2K off-axis near detector, ND280. The selection of the electron (anti-)neutrino events in the plastic scintillator target from both neutrino and anti-neutrino mode beams is discussed in this paper. The flux integrated single differential charged-current inclusive electron (anti-)neutrino cross-sections, \\(d\\sigma/dp\\) and \\(d\\sigma/d\\cos(\\theta)\\), and the total cross-sections in a limited phase-space in momentum and scattering angle (\\(p > 300\\) MeV/c and \\(\\theta \\leq 45^{\\circ}\\)) are measured using a binned maximum likelihood fit and compared to the neutrino Monte Carlo generator predictions, resulting in good agreement.

This article presents constraints on dark-matter-electron interactions obtained from the first underground data-taking campaign with multiple SuperCDMS HVeV detectors operated in the same housing. An exposure of 7.63 g-days is used to set upper limits on the dark-matter-electron scattering cross section for dark matter masses between 0.5 and 1000 MeV/\\(c^2\\), as well as upper limits on dark photon kinetic mixing and axion-like particle axioelectric coupling for masses between 1.2 and 23.3 eV/\\(c^2\\). Compared to an earlier HVeV search, sensitivity was improved as a result of an increased overburden of 225 meters of water equivalent, an anticoincidence event selection, and better pile-up rejection. In the case of dark-matter-electron scattering via a heavy mediator, an improvement by up to a factor of 25 in cross-section sensitivity was achieved.

This article presents constraints on dark-matter-electron interactions obtained from the first underground data-taking campaign with multiple SuperCDMS HVeV detectors operated in the same housing. An exposure of 7.63 g-days is used to set upper limits on the dark-matter-electron scattering cross section for dark matter masses between 0.5 and 1000 MeV/\\(c^2\\), as well as upper limits on dark photon kinetic mixing and axion-like particle axioelectric coupling for masses between 1.2 and 23.3 eV/\\(c^2\\). Compared to an earlier HVeV search, sensitivity was improved as a result of an increased overburden of 225 meters of water equivalent, an anticoincidence event selection, and better pile-up rejection. In the case of dark-matter-electron scattering via a heavy mediator, an improvement by up to a factor of 25 in cross-section sensitivity was achieved.

This paper reports the first simultaneous measurement of the double differential muon neutrino charged-current cross section on oxygen and carbon without pions in the final state as a function of the outgoing muon kinematics, made at the ND280 off-axis near detector of the T2K experiment. The ratio of the oxygen and carbon cross sections is also provided to help validate various models' ability to extrapolate between carbon and oxygen nuclear targets, as is required in T2K oscillation analyses. The data are taken using a neutrino beam with an energy spectrum peaked at 0.6 GeV. The extracted measurement is compared with the prediction from different Monte Carlo neutrino-nucleus interaction event generators, showing particular model separation for very forward-going muons. Overall, of the models tested, the result is best described using Local Fermi Gas descriptions of the nuclear ground state with RPA suppression.