Thymidine Kinase 1 (TK1) plays an important role in DNA precursor synthesis and serum TK1 activity has been used as a biomarker for prognosis and therapy monitoring of different malignancies. AroCell ...has developed a dual monoclonal antibody ELISA for determination of TK1 protein in clinical samples. The purpose of the study is to validate the ELISA analytically in relation to the gold standard,
3
H-deoxythymidine (dThd) phosphorylation assay for TK1 activity using sera from patients with different malignancies. The colorimetric TK 210 ELISA was validated analytically by assessment of precision, linearity, interfering substances, and stability. For the clinical validation, serum samples from patients with hematological malignancies (n = 100), breast cancer (n = 56), prostate cancer (n = 70) and blood donors (n = 159) were analyzed using TK 210 ELISA and TK1 activity by
3
H-deoxythymidine (dThd) phosphorylation assay. The sandwich TK 210 ELISA was highly specific for TK1 protein having a detection limit of 0.12 ng/mL, with a functional sensitivity of 0.25 ng/mL. Within-run CVs ranged from 5.5% to 10% and between-run CVs ranged from 5% to 15%. The ratio of observed to expected dilutional parallelism of 5 serum samples was in the range of 80–120%. Samples exhibited stability through four freeze/thaw cycles and 5 days at 4°C. Further, the ROC curve analysis showed that TK 210 ELISA and
3
H-dThd phosphorylation assay had similar sensitivity (62% vs 59%) in hematological malignancies. However, in the case of breast and prostate cancer sera, TK 210 ELISA had higher sensitivity (59% and 44%) compared to
3
H-dThd phosphorylation assay (47% and 25%) at a specificity of 98%. These data demonstrate that the dual monoclonal antibody based AroCell TK 210 ELISA is a robust, accurate and precise tool for measuring TK1 protein in different malignancies that can improve the clinical applications of TK1 as a biomarker in cancer management.
Context.
Parker Solar Probe’s first solar encounter has revealed the presence of sudden magnetic field deflections in the slow Alfvénic solar wind. These structures, which are often called ...switchbacks, are associated with proton velocity enhancements.
Aims.
We study their statistical properties with a special focus on their boundaries.
Methods.
Using data from SWEAP and FIELDS, we investigate particle and wavefield properties. The magnetic boundaries are analyzed with the minimum variance technique.
Results.
Switchbacks are found to be Alfvénic in 73% of cases and compressible in 27%. The correlations between magnetic field magnitude and density fluctuations reveal the existence of both positive and negative correlations, and the absence of perturbations in the magnetic field magnitude. Switchbacks do not lead to a magnetic shear in the ambient field. Their boundaries can be interpreted in terms of rotational or tangential discontinuities. The former are more frequent.
Conclusions.
Our findings provide constraints on the possible generation mechanisms of switchbacks, which have to be able to also account for structures that are not purely Alfvénic. One of the possible candidates, among others, manifesting the described characteristics is the firehose instability.
Thymidine Kinase 1 (TK1) plays an important role in DNA precursor synthesis and serum TK1 activity has been used as a biomarker for prognosis and therapy monitoring of different malignancies. AroCell ...has developed a dual monoclonal antibody ELISA for determination of TK1 protein in clinical samples. The purpose of the study is to validate the ELISA analytically in relation to the gold standard, 3H-deoxythymidine (dThd) phosphorylation assay for TK1 activity using sera from patients with different malignancies. The colorimetric TK 210 ELISA was validated analytically by assessment of precision, linearity, interfering substances, and stability. For the clinical validation, serum samples from patients with hematological malignancies (n = 100), breast cancer (n = 56), prostate cancer (n = 70) and blood donors (n = 159) were analyzed using TK 210 ELISA and TK1 activity by 3H-deoxythymidine (dThd) phosphorylation assay. The sandwich TK 210 ELISA was highly specific for TK1 protein having a detection limit of 0.12 ng/mL, with a functional sensitivity of 0.25 ng/mL. Within-run CVs ranged from 5.5% to 10% and between-run CVs ranged from 5% to 15%. The ratio of observed to expected dilutional parallelism of 5 serum samples was in the range of 80–120%. Samples exhibited stability through four freeze/thaw cycles and 5 days at 4°C. Further, the ROC curve analysis showed that TK 210 ELISA and 3H-dThd phosphorylation assay had similar sensitivity (62% vs 59%) in hematological malignancies. However, in the case of breast and prostate cancer sera, TK 210 ELISA had higher sensitivity (59% and 44%) compared to 3H-dThd phosphorylation assay (47% and 25%) at a specificity of 98%. These data demonstrate that the dual monoclonal antibody based AroCell TK 210 ELISA is a robust, accurate and precise tool for measuring TK1 protein in different malignancies that can improve the clinical applications of TK1 as a biomarker in cancer management.
Aims.
We studied the properties and occurrence of narrowband whistler waves and their interaction with strahl electrons observed between 0.17 and 0.26 au during the first encounter of Parker Solar ...Probe.
Methods.
We used Digital Fields Board band-pass filtered (BPF) data from FIELDS to detect the signatures of whistler waves. Additionally parameters derived from the particle distribution functions measured by the Solar Wind Electrons Alphas and Protons (SWEAP) instrument suite were used to investigate the plasma properties, and FIELDS suite measurements were used to investigate the electromagnetic (EM) fields properties corresponding to the observed whistler signatures.
Results.
We observe that the occurrence of whistler waves is low, nearly ~1.5% and less than 0.5% in the analyzed peak and average BPF data, respectively. Whistlers occur highly intermittently and 80% of the whistlers appear continuously for less than 3 s. The spacecraft frequencies of the analyzed waves are less than 0.2 electron cyclotron frequency (
f
ce
). The occurrence rate of whistler waves was found to be anticorrelated with the solar wind bulk velocity. The study of the duration of the whistler intervals revealed an anticorrelation between the duration and the solar wind velocity, as well as between the duration and the normalized amplitude of magnetic field variations. The pitch-angle widths (PAWs) of the field-aligned electron population referred to as the strahl are broader by at least 12 degrees during the presence of large amplitude narrowband whistler waves. This observation points toward an EM wave electron interaction, resulting in pitch-angle scattering. PAWs of strahl electrons corresponding to the short duration whistlers are higher compared to the long duration whistlers, indicating short duration whistlers scatter the strahl electrons better than the long duration ones. Parallel cuts through the strahl electron velocity distribution function (VDF) observed during the whistler intervals appear to depart from the Maxwellian shape typically found in the near-Sun strahl VDFs. The relative decrease in the parallel electron temperature and the increase in PAW for the electrons in the strahl energy range suggests that the interaction with whistler waves results in a transfer of electron momentum from the parallel to the perpendicular direction.
Abstract In this work we analyze plasma and magnetic field data provided by the Parker Solar Probe and Solar Orbiter missions to investigate the radial evolution of the heating of Alfvénic slow wind ...by imbalanced Alfvén-wave (AW) turbulent fluctuations from 0.06 to 1 au. in our analysis we focus on slow solar-wind intervals with highly imbalanced and incompressible turbulence (i.e., magnetic compressibility C B = δ B / B ≤ 0.25, plasma compressibility C n = δ n / n ≤ 0.25, and normalized cross helicity σ c ≥ 0.65). First, we estimate the AW turbulent dissipation rate from the wave energy equation and find that the radial profile trend is similar to the proton heating rate. Second, we find that the scaling of the empirical AW turbulent dissipation rate Q W obtained from the wave energy equation matches the scaling from the phenomenological AW turbulent dissipation rate Q CH09 (with Q CH09 ≃ 1.55 Q W ) derived by Chandran & Hollweg based on the model of reflection-driven turbulence. Our results suggest that, as in the fast solar wind, AW turbulence plays a major role in the ion heating that occurs in incompressible slow-wind streams.
Thymidine kinase 1 (TK1), involved in DNA precursor synthesis, is used as a serum biomarker in cancer diagnostics in both human and veterinary medicine. We investigated the utility of serum TK1 ...protein (TK1p) and TK1 activity (TK1a) determinations for prognosis and monitoring of canine hematological malignancies. The combination of TK1p or TK1a with canine C-reactive protein (CRP) determinations was also investigated.
Serum samples from 51 client-owned dogs with naive hematological malignancies and from 149 healthy subjects were included. Serum TK1p levels were determined using a prototype TK1-ELISA, TK1a using the 3H–dThd phosphorylation assay, and CRP using an immunoturbidimetric assay.
Mean TK1p in sera from dogs with tumors was significantly higher than from healthy dogs (mean ± SD = 3.9 ± 5.9 vs. 0.45 ± 0.15 ng/mL). Similarly, TK1a in hematological malignancies was significantly higher than in healthy dogs (mean ± SD = 15.1 ± 31.3 vs. 0.96 ± 0.33 pmol/min/mL). The receiver-operating characteristic indicated that a combination of TK1p or TK1a with CRP gave higher sensitivity than either biomarker alone for the prognosis of hematological malignancies. Median pretreatment TK1p and TK1a levels were significantly higher than in dogs in remission and correlated with clinical outcome. Kaplan-Meier curve analysis showed that naive dogs with high TK1p, TK1a, and CRP had significantly shorter survival.
This study present two new polyclonal antibodies used in an ELISA system to determine TK1p. The study also show that combining TK1p or TK1a with CRP gave higher sensitivity than either biomarker alone. Monitoring patients in the study while undergoing chemotherapy, suggests that the TK1 + CRP combination could be useful in a biomarker panel, possibly aiding the prognosis and therapy monitoring of hematological malignancies in dogs.
•Hematological malignancies are common in dogs.•Response to treatment (chemotherapy) is usually excellent but relapses are common and prognosis hard to predict.•Thymidine Kinase 1 (TK1) is an enzyme involved in cell proliferation and DNA-synthesis, upregulated in tumor disease.•A robust and sensitive TK1 ELISA was developed.•TK1 protein shows promise as a biomarker for canine hematological tumors to monitor response and early predict relapse.
In this study changes in thymidine kinase 1 (TK1) levels after 24 hours of Doxorubicin (Dox) exposure of CEM and MDA MB-231 cells were determined using the commercially available AroCell TK 210 ELISA ...test. In cell extracts, TK1 levels increased twofold with 1 µM Dox in both cell lines, while the TK1 levels in the culture media increased with 5 and 10 µM of Dox only in case of CEM cells. In conclusion, this study reveals that the TK 210 ELISA can measure changes in intra- and extracellular TK1 levels apparently related to the mechanism of cytotoxicity of anti-cancer agents.
Context. The nature and evolution of the solar wind magnetic field rotations is studied in data from the Parker Solar Probe. Aims. We investigated the magnetic field deflections in the inner ...heliosphere below 0.5 au in a distance- and scale-dependent manner to shed some light on the mechanism behind their evolution. Methods. We used the magnetic field data from the FIELDS instrument suite to study the evolution of the magnetic field vector increment and rotation distributions that contain switchbacks. Results. We find that the rotation distributions evolve in a scale-dependent fashion. They have the same shape at small scales regardless of the radial distance, in contrast to larger scales, where the shape evolves with distance. The increments are shown to evolve towards a log-normal shape with increasing radial distance, even though the log-normal fit works quite well at all distances, especially at small scales. The rotation distributions are shown to evolve towards a previously developed rotation model moving away from the Sun. Conclusions. Our results suggest a scenario in which the evolution of the rotation distributions is primarily the result of the expansion-driven growth of the fluctuations, which are reshaped into a log-normal distribution by the solar wind turbulence.
Aims.
We applied the quasi-thermal noise (QTN) method to Parker Solar Probe (PSP) observations to derive the total electron temperature (
T
e
). We combined a set of encounters to make up a 12-day ...period of observations around each perihelion from encounter one (E01) to ten (E10), with E08 not included. Here, the heliocentric distance varies from about 13 to 60 solar radii (
R
⊙
).
Methods.
The QTN technique is a reliable tool to yield accurate measurements of the electron parameters in the solar wind. We obtained
T
e
from the linear fit of the high-frequency part of the QTN spectra acquired by the RFS/FIELDS instrument. Then, we provided the mean radial electron temperature profile, and examined the electron temperature gradients for different solar wind populations (i.e. classified by the proton bulk speed,
V
p
, and the solar wind mass flux).
Results.
We find that the total electron temperature decreases with the distance as ∼
R
−0.66
, which is much slower than adiabatic. The extrapolated
T
e
based on PSP observations is consistent with the exospheric solar wind model prediction at ∼10
R
⊙
, Helios observations at ∼0.3 AU, and Wind observations at 1 AU. Also,
T
e
, extrapolated back to 10
R
⊙
, is almost the same as the Strahl electron temperature,
T
s
(measured by SPAN-E), which is considered to be closely related to or even almost equal to the coronal electron temperature. Furthermore, the radial
T
e
profiles in the slower solar wind (or flux tube with larger mass flux) are steeper than those in the faster solar wind (or flux tube with smaller mass flux). The more pronounced anticorrelation of
V
p
–
T
e
is observed when the solar wind is slower and located closer to the Sun.
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