The TOI-178 system consists of a nearby, late-K-dwarf with six transiting planets in the super-Earth to mini-Neptune regime, with radii ranging from sim 1.1 to 2.9 $R_ oplus $ and orbital periods ...between 1.9 and 20.7 days. All the planets, but the innermost one, form a chain of Laplace resonances. The fine-tuning and fragility of such orbital configurations ensure that no significant scattering or collision event has taken place since the formation and migration of the planets in the protoplanetary disc, thereby providing important anchors for planet formation models. We aim to improve the characterisation of the architecture of this key system and, in particular, the masses and radii of its planets. In addition, since this system is one of the few resonant chains that can be characterised by both photometry and radial velocities, we propose to use it as a test bench for the robustness of the planetary mass determination with each technique. We performed a global analysis of all the available photometry from CHEOPS, TESS and NGTS, and radial velocity from ESPRESSO, using a photo-dynamical modelling of the light curve. We also tried different sets of priors on the masses and eccentricity, as well as different stellar activity models, to study their effects on the masses estimated by transit-timing variations (TTVs) and radial velocities (RVs). We demonstrate how stellar activity prevents a robust mass estimation for the three outer planets using radial velocity data alone. We also show that our joint photo-dynamical and radial velocity analysis has resulted in a robust mass determination for planets $c$ to $g$, with precision of $ 12<!PCT!>$ for the mass of planet $c$, and better than $10<!PCT!>$ for planets $d$ to $g$. The new precisions on the radii range from $2$ to $3<!PCT!>$. The understanding of this synergy between photometric and radial velocity measurements will be valuable for the PLATO mission. We also show that TOI-178 is indeed currently locked in the resonant configuration, librating around an equilibrium of the chain.
Objectives. The incidence of cervical dysplasia and carcinoma is known to be increased in HIV-infected women. In addition, there is a positive correlation between HIV viral load (VL), CD4+ count, and ...opportunistic infections, as well as the incidence of various malignancies. This study compares HIV VL and CD4+ count with the presence of cervical dysplasia, as well as with the degree of severity of dysplasia.
Methods. A retrospective chart review of 350 HIV-infected women with polymerase chain reaction (PCR) quantitation of viral load was performed to identify 82 women with biopsy-proven cervical dysplasia and 25 women without any significant cervical pathology. The highest plasma VL within a year of the patients' cervical pathology and corresponding CD4+ count was selected and compared with cervical pathology. Univariate and multivariate statistical analysis using Student's t test and logistic regression analysis was used to analyze the significance of other risk factors such as age, race, smoking history, history of illicit drug use, and prior sexually transmitted disease as well as of viral load and CD4+ count.
Results. Of 82 cases of cervical dysplasia, 33 (40.24%) were mild (CIN I), 47 (57.32%) were either moderate or severe (CIN II–III) dysplasia, and 2 demonstrated invasive squamous cell carcinoma (2.44%). A significant statistical difference was found when comparing either HIV plasma VL or CD4+ T-cell counts with the presence of cervical dysplasia on biopsy (P < 0.005). However, only CD4+ count was identified as an independent risk factor for the presence of cervical dysplasia after multivariate analysis.
Conclusion. In our population, there is a significant correlation between VL and CD4+ count and the presence of cervical dysplasia. However, VL does not appear to be an independent risk factor for cervical dysplasia in this population of HIV-infected women.
Surface pressure (
π) versus specific molecular area (
A) isotherms of Langmuir monolayers of dimyristoylphosphatidylcholine (DMPC) lipid on pure water were studied in pristine form and in presence ...of three non-steroidal anti-inflammatory drugs, meloxicam (MX), piroxicam (PX) and tenoxicam (TX) in the subphase. Data were taken at three drug/lipid (D/L) ratios of 0.026, 0.05, and 0.1. Integration of drug to the lipid monolayer was measured by the increase in
A (Δ
A) of DMPC monolayer due to the presence of drugs. All three drugs could be integrated in the monolayer resulting in a positive value of Δ
A for D/L ratio of 0.026. Above this D/L value, there is an anomalous, monotonic decrease in Δ
A for MX and TX resulting, finally, in negative Δ
A values. For PX, however, decrease in Δ
A values at D/L of 0.05 is partially compensated at D/L of 0.1. We have tentatively explained these observations by invoking two competing forces in the overall drug–lipid interaction. One of these is an ‘in-plane’ force that tends to integrate the drug molecule to the plane formed by the lipid monolayer and the other is an ‘out-of-plane’ force that perturbs the drug and the lipid molecules such that the monolayer plane is no longer well defined.
To develop a model to predict transmission of HIV-1 from men to women.
HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to ...develop a probabilistic model.
Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois.
Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined.
Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma).
The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse.
This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.
Addition of an electrolyte such as NaCl to ionic micelles such as sodium dodecyl sulfate (SDS) alters the ionic atmosphere of the bulk solvent, thereby changing both the micellar properties and the ...interaction pattern of micelles with a molecule in the solvent. In this study, we show how added NaCl in the presence of SDS micelles modulates the surface charge of the micelles, which in turn fine-tunes the switchover equilibrium between anionic and global neutral forms of piroxicam. The presence of salt alters the CMC and aggregation number of SDS micelles. The binding of the global neutral form of piroxicam with SDS is found to be strongly modulated by the presence of counterion in the bulk solvent.
Display omitted The switchover equilibrium between anionic and neutral forms of piroxicam in presence of SDS micelles can be fine-tuned by the modulation of surface charge of micelles by the addition of NaCl.
Molecules, whose p
K
a values can be easily fine-tuned by their microenvironment, are expected to be profoundly affected by the heterogeneous environments of membranes. Membrane parameters can have a ...strong effect in choosing a particular structural form of a molecule for incorporation/interaction. A case study has been presented for piroxicam, a non-steroidal anti-inflammatory drug of oxicam group, whose targets are cyclooxygenases, which are membrane active proteins. The structural dynamism of piroxicam is reflected in the ease with which it can switchover or convert from one prototropic form to the other guided by its environment. In this work we have studied the effect of varying hydrophobic chain length and surface charges in fine-tuning the interaction of piroxicam with micelles. Interaction of piroxicam with three types of micelles with identical negatively charged head groups and varying tail lengths viz., sodium dodecyl sulfate (S12S), sodium decyl sulfate (S10S) and sodium octyl sulfate (S8S) shows that there is a shift in the apparent p
K
a in the direction that favors the switchover or conversion from the anionic form to the global neutral form. The binding constants of piroxicam with three micelles show a linear dependence on chain length. Interaction was also studied with micelles having oppositely charged head groups and different chain lengths viz., dodecyl
N,
N,
N-trimethyl ammonium bromide (DTAB) and cetyl
N,
N,
N-trimethyl ammonium bromide (CTAB). For micelles having identical chain lengths but oppositely charged head groups viz., S12S and DTAB, p
K
a shifts in two opposite directions compared to that in the absence of any surfactant. This is expected when electrostatic force is the only driving force. This case study demonstrates the effect of hydrophobic chain length and surface charges in fine-tuning the equilibrium between different structural forms of piroxicam. Our results also imply that for structurally dynamic drugs like piroxicam the nature of the biomembranes, characterized by different membrane parameters, should play a crucial role in choosing a particular structural form of the drug that will be finally presented to their targets.
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