Miracle-dz/UniFAR-FTUs huggingface dataset:
Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice

As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)–encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8+ T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials. Description Self-amplifying and non-replicating mRNA vaccines are immunogenic and control tumor burden in mice bearing HPV-associated tumors. Comparing mRNA vaccines head-to-head mRNA vaccines can be delivered through multiple platforms. Here, Ramos da Silva and colleagues compared three different mRNA platforms as a therapeutic vaccine for human papillomavirus–associated cancers. The three vaccines tested were an unmodified non-replicating mRNA vaccine, a nucleoside-modified non-replicating mRNA vaccine, and a self-amplifying mRNA vaccine. All three vaccines encoded the same antigen, a fusion protein of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D, so differences between the vaccines’ efficacy were due to the platform. The authors found that a single dose of self-amplifying or unmodified non-replicating mRNA vaccines, both encapsulated in lipid nanoparticles, led to robust control of tumor burden in two orthotopic murine models. Further, all three vaccines outperformed a protein vaccine and an electroporated DNA vaccine containing or encoding the same antigen. These results highlight the translational potential of mRNA cancer vaccines. —CM
An Ecological Review of Homicide Bereavement’s Risk Factors: Implications for Future Research

This literature review focused on homicide bereavement (HB) risk factors. A content analysis was conducted on 83 empirical papers published in English from January 2000 to December 2021 in peer-reviewed journals. Extracted HB risk factors were synthesized according to six main dimensions: individual level; situational homicide-related factors; and micro, meso, exo, and macro social levels. The review demonstrates that macro-level and situational homicide-related risk factors are in special need of further study. In addition, how HB risk factors interact with one another to influence HB also requires further study. Future research may benefit from examining whether and how individuals experiencing HB influence related factors at various social levels. Last, given that almost all reviewed studies were conducted in Western societies, the sociocultural and ethnic diversity in HB risk factors is in dire need of future study.
A comparative study between angiotensin receptor neprilysin inhibitor (thiorphan/irbesartan) with each of nitrate and carvedilol in a rat model of myocardial ischemic reperfusion injury

The combined angiotensin receptor neprilysin inhibitor is a promising cardioprotective pharmacological agent. This study investigated the beneficial effects of thiorphan (TH)/irbesartan (IRB), in myocardial ischemia–reperfusion (IR) injury, compared to each of nitroglycerin and carvedilol. Male Wistar rats were divided into five groups (10 rats/group): Sham, untreated I/R, TH/IRB + IR (0.1/10 mg/kg), nitroglycerin + IR (0.2 mg/kg), and carvedilol + IR (10 mg/kg). Mean arterial blood pressure, cardiac functions and arrhythmia incidence, duration and score were assessed. Cardiac levels of creatine kinase‐MB (CK‐MB), oxidative stress, endothelin‐1, ATP, Na+/K+ ATPase pump activity and mitochondria complexes activities were measured. Histopathological examination, Bcl/Bax immunohistochemistry studies and electron microscopy examination of left ventricle were performed. TH/IRB preserved the cardiac functions and mitochondrial complexes activities, mitigated cardiac damage, reduced oxidative stress and arrhythmia severity, improved the histopathological changes and decreased cardiac apoptosis. TH/IRB showed a comparable effect to each of nitroglycerin and carvedilol in alleviating the IR injury consequences. TH/IRB showed significant preservation of mitochondrial complexes activity I and II compared to nitroglycerin. TH/IRB significantly increased LVdP/dtmax and decreased oxidative stress, cardiac damage and endothelin‐1 along with increasing the ATP content, Na+/K+ ATPase pump activity and mitochondrial complexes activity when compared to carvedilol. TH/IRB showed a cardioprotective effect in reducing IR injury that is comparable to each of nitroglycerin and carvedilol that could be explained in part by its ability to preserve mitochondrial function, increase ATP, decrease oxidative stress as well as endothelin 1.
Monotonic change-point estimation of multivariate Poisson processes using a multi-attribute control chart and MLE

In this paper, a new multi-attribute control chart is initially proposed to monitor multi-attribute processes based on a transformation technique. Then, the maximum likelihood estimator of a multivariate Poisson process change point is derived for unknown changes that are assumed to belong to a family of monotonic changes. Using extensive simulation experiments, the performance of the proposed change-point estimator is compared to the ones derived for step changes and linear-trend disturbances, when the true change types are step change, linear trends and multiple-step changes. We show when the type of the change is not known a priori, the proposed estimator is an appropriate choice, since it accurately estimates the true time of the process changes, regardless of change type, shift magnitudes and process dimension.
A question of Stark

One of the programs of Stark’s conjectures is to nd as many connections as possible between the values that Artin L{functions or their derivatives take (especially at s =0 ) and arithmetic information associated to algebraic number elds. The most rened of Stark’s conjectures involves the values of rst derivatives of L{functions at s =0 :It was recognized early on that the conjecture should be extended to cover cases where the order of vanishing of the L{functions at s =0 is greater than one. In 1980, Stark posed a question along these lines that we will consider in detail here. In particular, we will study his question for relative quadratic extensions and prove that an armative answer to his question exists for all cases considered.
Stochastic and Perturbed Parameter Representations of Model Uncertainty in Convection Parameterization

AbstractIt is now acknowledged that representing model uncertainty in atmospheric simulators is essential for the production of reliable probabilistic forecasts, and a number of different techniques have been proposed for this purpose. This paper presents new perturbed parameter schemes for use in the European Centre for Medium-Range Weather Forecasts (ECMWF) convection scheme. Two types of scheme are developed and implemented. Both schemes represent the joint uncertainty in four of the parameters in the convection parameterization scheme, which was estimated using the Ensemble Prediction and Parameter Estimation System (EPPES). The first scheme developed is a fixed perturbed parameter scheme, where the values of uncertain parameters are varied between ensemble members, but held constant over the duration of the forecast. The second is a stochastically varying perturbed parameter scheme. The performance of these schemes was compared to the ECMWF operational stochastic scheme, stochastically perturbed para.
The Zakharov equation with separate mean flow and mean surface

Abstract Using the Hamiltonian approach of Krasitskii (J. Fluid Mech., vol. 272, 1994, pp. 1–20), we derive a variant of the Zakharov equation in which the wave-induced mean surface elevation and the surface potential of the wave-induced mean flow are represented as separate variables governed by separate evolution equations. The kernel function of this new variant is simpler, and in particular also well defined in the uniform-wave-train limit for waves on finite depth. This form of the Zakharov equation may be advantageous in some applications. One example is the derivation of nonlinear Schrödinger equations in the narrow-band limit, where the handling of the mean flow and mean surface is significantly simpler than when starting from the original Zakharov equation. In this paper we have used the alternative form of the Zakharov equation to derive a Hamiltonian nonlinear Schrödinger equation for directional waves on arbitrary depth, valid to one order higher in bandwidth than the Hamiltonian equation recently presented by Craig, Guyenne and Sulem (Wave Motion, vol. 47, 2010, pp. 552–563).
Hypoxic volatile metabolic markers in the MDA-MB-231 breast cancer cell line

Hypoxia in disease describes persistent low oxygen conditions, observed in a range of pathologies, including cancer. In the discovery of biomarkers in biological models, pathophysiological traits present a source of translatable metabolic products for the diagnosis of disease in humans. Part of the metabolome is represented by its volatile, gaseous fraction; the volatilome. Human volatile profiles, such as those found in breath, are able to diagnose disease, however accurate volatile biomarker discovery is required to target reliable biomarkers to develop new diagnostic tools. Using custom chambers to control oxygen levels and facilitate headspace sampling, the MDA-MB-231 breast cancer cell line was exposed to hypoxia (1% oxygen) for 24 hours. The maintenance of hypoxic conditions in the system was successfully validated over this time period. Targeting and non-targeting gas chromatography mass spectrometry approaches revealed four significantly altered volatile organic compounds when compared to control cells. Three compounds were actively consumed by cells: methyl chloride, acetone and n-Hexane. Cells under hypoxia also produced significant amounts of styrene. This work presents a novel methodology for identification of volatile metabolisms under controlled gas conditions with novel observations of volatile metabolisms by breast cancer cells.
Integrating metabolic scaling and coexistence theories

Metabolic scaling and coexistence theories have been pivotal in mathematizing both the energy expenditures and transformations across individuals and populations. Yet, it is unclear how the sustainability of biodiversity depends on metabolic scaling relationships. Here, we provide a tractable and scalable perspective to study how the possibilities for multispecies coexistence (i.e., feasibility) change as a function of the dependence of a population’s metabolism on body size. This integration predicts that, regardless of body size distribution among populations, there is a reciprocal relationship between the scaling exponents defining the dependence of competitive effects and expected carrying capacities on body size. In line with empirical observations, our integration predicts that expected carrying capacities lead to equilibrium biomasses that are independent from body size, and consequently, to equilibrium abundances that are inversely related to body size. We show that this even distribution of equilibrium biomasses increases the possibilities for multispecies coexistence under random environmental perturbations. Additionally, this integration establishes that the possibilities for multispecies coexistence is maximized when no species has an energetic competitive advantage. This integration opens new opportunities to increase our understanding of how metabolic scaling relationships at the individual and population levels shape processes at the community level.
Hyperbolic hypersurfaces in ℙⁿ of Fermat-Waring type

In this note we show that there are algebraic families of hyperbolic, Fermat- Waring type hypersurfaces in P n of degree 4(n − 1) 2 , for all dimensions n ≥ 2. Moreover, there are hyperbolic Fermat-Waring hypersurfaces in P n of degree 4n 2 − 2n + 1 possessing complete hyperbolic, hyperbolically embedded complements.
Individual differences in neural event segmentation of continuous experiences

Event segmentation is a spontaneous part of perception, important for processing continuous information and organizing it into memory. While neural and behavioral event segmentation show a degree of inter-subject consistency, meaningful individual variability exists atop these shared patterns. Here we characterized individual differences in the location of neural event boundaries across four short movies that evoked variable interpretations. Event boundary alignment across subjects followed a posterior-to-anterior gradient that was tightly correlated with the rate of segmentation: slower-segmenting regions that integrate information over longer time periods showed more individual variability in boundary locations. This relationship held irrespective of the stimulus, but the degree to which boundaries in particular regions were shared versus idiosyncratic depended on certain aspects of movie content. Furthermore, this variability was behaviorally significant in that similarity of neural boundary locations during movie-watching predicted similarity in how the movie was ultimately remembered and appraised. In particular, we identified a subset of regions in which neural boundary locations are both aligned with behavioral boundaries during encoding and predictive of stimulus interpretation, suggesting that event segmentation may be a mechanism by which narratives generate variable memories and appraisals of stimuli.
First Results of a CO Survey of the Large Magellanic Cloud with NANTEN; Giant Molecular Clouds as Formation Sites of Populous Clusters

A new survey of the LMC has been completed in 2.6 mm carbon monoxide emission with NANTEN. This survey has revealed 107 giant molecular clouds, the first complete sample of giant molecular clouds in a single galaxy at a linear resolution of ~ 40 pc. The cloud mass ranges from ~ 6x 10 4 to 2 x 10 6 M®, and the total molecular mass has been estimated to be 4-7 x 10 7 M® for a molecular column density of > 1.0 x 10 21 cm -2 , corresponding to 5-10% of the atomic mass. The molecular clouds exhibit a good spatial correlation with the youngest stellar clusters whose ages are < 10 Myr, demonstrating that cluster formation is on-going in these clouds. On the other hand, they show little correlation with older clusters or with supernova remnants, suggesting that the molecular clouds are being rapidly dissipated in several Myrs, probably due to the UV photons of massive stars in clusters.
IRREGULAR SATELLITES OF THE OUTER PLANETS: ORBITAL UNCERTAINTIES AND ASTROMETRIC RECOVERIES IN 2009–2011

More than 100 small satellites have been identified orbiting the giant planets in distant, inclined, eccentric orbits. Detailed study of these objects requires that their orbits be known well enough to permit routine observations both from the Earth and from spacecraft. Unfortunately, many of the satellites have very poorly known orbits due to a scarcity of astrometric measurements. We have developed a reliable method to estimate the future on-sky position uncertainties of the satellites and have verified that those uncertainties provide a correct measure of the true on-sky positional uncertainty. Based on the uncertainties, we identified a set of satellites that are effectively “lost” and another set that would be lost if additional observations were not obtained in the near future. We attempted recoveries of 26 of the latter group using the Hale 5 m and CFHT 3.6 m telescopes and found 23. This validated our method's predictions and led to significant improvements in our knowledge of the orbits of the recovered moons. There remains a handful of irregular moons which are recoverable and whose orbits will benefit from additional observations during the next decade, while 16 moons of Jupiter and Saturn are essentially lost and will require a re-survey to be located again.
Letrozole cotreatment improves the follicular output rate in high-body-mass-index women with polycystic ovary syndrome undergoing IVF treatment

Background Women who have polycystic ovary syndrome (PCOS) with high body mass index (BMI) typically have an attenuated ovarian response and decreased follicular size, which are linked to unfavourable clinical outcomes following in vitro fertilization (IVF) therapy. The follicular output rate (FORT), a qualitative indicator of follicular response, seems to be positively linked to the clinical outcomes of IVF. Progestin-primed ovarian stimulation (PPOS) has become an alternative to gonadotropin-releasing hormone (GnRH) analogues to inhibit the premature luteinizing hormone (LH) surge. As letrozole (LE) shows promise in enhancing ovarian response, we compared PPOS with and without LE for PCOS in high BMI women with a focus on the FORT and associated clinical and pregnancy outcomes. Methods For the recruited 1508 women, ten variables including AFC; age; basal sex hormone level; BMI; infertility type; period of infertility and number of previous IVF attempts were chosen in the propensity score matching (PSM) model to match 1374 women who taken the MPA+ hMG protocol with 134 women who received the MPA+ hMG+ LE treatment at a 1:1 ratio. FORT was selected as the primary outcome measure. The number of oocytes retrieved, viable embryos, hMG dosage, duration, oocyte maturity rate, fertilization rate, and implantation rate were established as secondary outcomes. Results FORT was substantially elevated in the MPA+hMG+LE group compared with the MPA+hMG group (61% [35%, 86%] vs. 40% [25%, 60%], P <.001). Interestingly, the LE cotreatment group had a considerably lower mature oocyte rate despite having a similar number of mature oocytes and embryos recovered. The average hMG dosages and durations in the study group were similar to those in the control group. The implantation rate in the study group was numerically higher but without statistic significant than that in the control groups (43.15% (107/248) vs. 38.59% (115/298), OR 1.008, 95% CI 0.901-1.127; P >. 05). Conclusion The effect of LE combined with PPOS on FORT is better than the effect of the standard PPOS treatment in women with PCOS and a high BMI, but there is no substantially beneficial impact on pregnancy outcomes or the cycle features of COS, including consumption of hMG.
Kerr magnetooptic study of slow to intermediate speed propagation phenomena in thin Ni-Fe films

Evidence of high-speed propagation phenomena has been previously cited as a possible mechanism for slow to intermediate speed switching. Quasi-static Kerr magnetooptical observation of propagation phenomena for applied fields and total switching times well into the region of "incoherent rotation" has resulted in a more complete and quantitative description of these effects. The ability of the quasi-static procedure to predict the results of uninterrupted dynamic flux reversal is demonstrated. In particular, for applied easy-axis field H s well above coercive field H c but below the anisotropy field H k , a pair of "zigzag walls" composed of connected domain tips extended in the hard direction is observed to switch approximately 100 percent of the film by longitudinal motion. For threshold fields near the theoretical astroid value, well-defined propagation fronts have been observed and their velocities carefully measured. Finally, the resulting velocity-field data are used to predict with good accuracy the results of experiments on uninterrupted reversal under a ramp field H_{s} = st for s up to 5 \times 10^{6} Oe/s.
Fatigue experimental study on full-scale large sectional model of orthotropic steel deck of urban rail bridge

The fatigue problem of orthotropic steel bridge decks of urban rail transit steel bridges has gradually become one of the hot research topics. And it is also a key problem that restricts the further development of rail transit steel bridges. In this paper, the orthotropic steel bridge deck structure of a long-span urban rail transit cable-stayed bridge is studied. Based on the segmental finite element model and full-scale model, the fatigue details of the joint weld between an orthotropic steel bridge deck and U-rib were studied theoretically and experimentally. The theoretical model of the segment is analyzed to obtain the hot spot stress characteristics. On this basis, the full-scale model fatigue test and the fatigue performance evaluation are completed based on the S-N curve. The results show that the fatigue performance of the bridge deck and U-rib joints of the orthotropic steel bridge deck structure model meets the design requirements and has a certain safety reserve. The joint fatigue details of the bridge deck, the U-rib joint weld, and the diaphragm plate are the sensitive areas that are most likely to occur fatigue failure first and need to be paid attention to in the later bridge maintenance and inspection.
Study of correlations between LOC/SOC transition, intrinsic toroidal rotation reversal and TEM/ITG bifurcation with different working gases in TCV

The effects of different working gases on the transition from linear ohmic confinement (LOC) regime to saturated ohmic confinement (SOC) regime and its relation to the intrinsic toroidal rotation reversal phenomenon were explored in the TCV tokamak. The energy confinement saturation was studied across D, H and He density ramps, and a range of ECRH injection power and through variations of ohmic plasma current. The occurrence of rotation reversal, concomitantly with the LOC–SOC transition, was observed only for certain cases, making us formally exclude a causal relation between the two phenomena. A strong correlation between the evolution of toroidal rotation profiles and electron density gradients was, however, observed, in agreement with previous works (Lebschy et al 2017 Nucl. Fusion 58 026013; Hornsby et al 2018 Nucl. Fusion 58 056008). Linear gyrokinetic simulations were performed to probe the turbulent regime of these discharges, showing a dominance of trapped electron mode (TEM) during the LOC phase and a mixture of TEM and ion temperature gradient (ITG) following the transition to SOC regime in D. Such a TEM/ITG bifurcation was less pronounced in H and He. MHD activity was monitored throughout the discharges and possible correlations between sawteeth instability activity, energy confinement time saturation and rotation reversal are highlighted.