Miracle-dz/UniFAR-FTUs huggingface dataset:
ORY‐1001, a KDM1A inhibitor, inhibits proliferation, and promotes apoptosis of triple negative breast cancer cells by inactivating androgen receptor

Breast cancer (BC), which is widely considered as the most common cancer in women around the world, evokes ~1.7 million new BC cases and 522,000 BC‐related deaths each year. Triple negative breast cancer (TNBC) is clinically confirmed as one of the most aggressive subtypes of BC. ORY‐1001, a clinically used lysine specific demethylase 1 (LSD1/KDM1A) inhibitor, was investigated herein to confirm its role in the progression of TNBC and reveal the potential mechanism. After treatment with ORY‐1001 in MDA‐MB‐231 and BT549 cells, the cell proliferation and apoptosis were respectively measured by CCK‐8 and TUNEL assays. The expression of proliferation‐ and apoptosis‐associated proteins was tested by means of western blot analysis. Then, R1881, an androgen receptor (AR) agonist, was used to evaluate whether the effects of ORY‐1001 on proliferation and apoptosis of TNBC cells was mediated by regulating AR. Results indicated that ORY‐1001 treatment restrained the proliferation while enhanced the apoptosis of BC cells, accompanied by the change of proliferation‐ and apoptosis‐related proteins expression. Furthermore, ORY‐1001 reduced the level of AR in BC cells. After the activation of AR by R1881, the decreased proliferation and enhanced apoptosis of BC cells triggered by ORY‐1001 intervention were partially abolished. In conclusion, this paper has presented the first evidence to suggest that ORY‐1001 inhibits proliferation and promotes apoptosis of TNBC cells by suppressing AR expression, which may constitute the theoretical basis for the clinical use of ORY‐1001 in the treatment of this disease.
Curved Approach in High Jump Induces Greater Jumping Height without Greater Joint Kinetic Exertions than Straight Approach

ABSTRACT Purpose The most height-specific jumping mode, the athletic high jump, is characterized as a running single-leg jump (RSLJ) from a curved approach. The main advantage of a curved approach is believed to be facilitation of bar clearance. However, the effect of a curved approach on center-of-mass (CoM) height generation has not been clarified. Here, we show that the curved RSLJ (C-RSLJ) is more suitable than the straight RSLJ (S-RSLJ) for CoM height generation. Methods We collected data using motion capture from 13 male high jumpers (personal best, 2.02–2.31 m) that performed C-RSLJ and S-RSLJ. We then compared the energy generation contributing to CoM height (Evert) in each approach. Results All participants attained greater CoM height in C-RSLJ than in S-RSLJ (difference, 0.055 ± 0.024 m). Three-dimensional joint kinematics and kinetics were similar between both approaches, except for the ankle plantar-flexion torque, which was smaller in C-RSLJ. The sum of positive work was comparable between the approaches, whereas the sum of negative work in C-RSLJ was significantly smaller than in S-RSLJ. The shank forward rotation induced a larger difference in Evert generation between C-RSLJ and S-RSLJ (0.80 ± 0.36 J·kg−1) than any other segment (≤0.36 J·kg−1). Conclusions Compared with a straight approach, a curved approach induces greater CoM height without increasing joint kinetic exertions during takeoff. The curved approach changes the initial condition of the takeoff and promotes the transformation of horizontal kinetic energy into Evert. This study provides novel practical perspectives for high jumpers and highlights the importance of segment biomechanics in human motor performance.
Face Recognition by Humans and Machines: Three Fundamental Advances from Deep Learning.

Deep learning models currently achieve human levels of performance on real-world face recognition tasks. We review scientific progress in understanding human face processing using computational approaches based on deep learning. This review is organized around three fundamental advances. First, deep networks trained for face identification generate a representation that retains structured information about the face (e.g., identity, demographics, appearance, social traits, expression) and the input image (e.g., viewpoint, illumination). This forces us to rethink the universe of possible solutions to the problem of inverse optics in vision. Second, deep learning models indicate that high-level visual representations of faces cannot be understood in terms of interpretable features. This has implications for understanding neural tuning and population coding in the high-level visual cortex. Third, learning in deep networks is a multistep process that forces theoretical consideration of diverse categories of learning that can overlap, accumulate over time, and interact. Diverse learning types are needed to model the development of human face processing skills, cross-race effects, and familiarity with individual faces. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Dual inhibition of FGFR4 and BCL-xL inhibits multi-resistant ovarian cancer with BCL2L1 gain

Aim: Overexpression of BCL2L1 (BCL-xL) was associated with platinum resistance in ovarian cancer (OvCa). However, role of copy number (CN) gain of BCL2L1 in OvCa remains elusive. Methods: In silico analyses of multiple public datasets were perform. Validation was carried out in our tissue microarray (TMA) of OvCa cases. In vitro and in vivo assays was performed to explore potential targeted compound against BCL2L1-gained OvCa. Results: BCL2L1 was gained in ~60% of OvCa. BCL2L1 was differentially expressed between healthy and cancerous ovarian cases. BCL2L1 gain was not prognostic either in overall or in progression-free survival but higher BCL2L1 expression was associated with worsened survival, indicating biological distinction between CN gain and overexpression of the gene. BCL2L1 gain was associated with multi-resistance to various drug with no significant sensitivity to any single agent. Only CRISPR-mediated BCL2L1 knockout, but not shRNA could be inhibitive. Combined genetic silencing of FGFR4/NCAM and BCL2L1 with shRNA induced potent inhibition of BCL2L1-gained OvCa with durable effect. Combined inhibition of FGFR/BCL-xL was required for inhibiting BCL2L1-gained OvCa in vitro and in vivo. Only dual inhibition of FGFR/BCL-xL without platinum was tolerable in vivo. Conclusion: Gain of BCL2L1 is associated with resistance to multiple anti-cancer agents in OvCa. Dual inhibition of FGFR4 and BCL-xL showed potent effect and tolerable toxicity, holding promise to further translation.
New Parameter of the Second Half of the P-Wave, P-Wave Duration, and Atrial Conduction Times Predict Atrial Fibrillation during Electrophysiological Studies

Objective: Several P-wave parameters reflect atrial conduction characteristics and have been used to predict atrial fibrillation (AF). The aim of this study was to determine the relationship between maximum P-wave duration (PMax) and new P-wave parameters, with atrial conduction times (CT), and to assess their predictive value of AF during electrophysiological studies (AF-EPS). Subjects and Methods: This was a cross-sectional study in 153 randomly selected patients aged 18–70 years, undergoing EPS. The patients were divided into 2 groups designated as no AF-EPS and AF-EPS, depending on whether AF occurred during EPS or not. Different P-wave parameters and atrial CT were compared for both study groups. Subsequently, the predictive value of the P-wave parameters and the atrial CT for AF-EPS was evaluated. Results: The values of CT, PMax, and maximum Ppeak-Pend interval (Pp-eMax) were significantly higher in patients with AF-EPS. Almost all P-wave parameters were correlated with the left CT. PMax, Pp-eMax, and CT were univariate and multivariate predictors of AF-EPS. The largest ROC area was presented by interatrial CT (0.852; p < 0.001; cutoff value: ≥82.5 ms; sensitivity: 91.1%; specificity: 81.1%). Pp-eMax showed greater sensitivity (79.5%) to discriminate AF-EPS than PMax (72.7%), but the latter had better specificity (60.4% vs. 41.5%). Conclusions: Left atrial CT were directly and significantly correlated with PMax and almost all the parameters of the second half of the P-wave. CT, PMax, and Pp-eMax (new parameter) were good predictors of AF-EPS, although CT did more robustly.
Association of heart rate with cardiovascular events and mortality in hypertensive and normotensive population: a nationwide prospective cohort study

Background Cardiovascular disease is the leading cause of death worldwide. We assessed the association of baseline heart rate with cardiovascular events and mortality in hypertensive and normotensive populations using a prospective urban and rural epidemiology cohort study in China. Methods A total of 29,554 individuals were involved in our analysis, distributed equally between groups of normotensive and hypertensive. The primary outcomes were myocardial infarction, stroke, major cardiovascular diseases, and cardiovascular mortality. Cox frailty models were utilized to estimate hazard ratios for cardiovascular outcomes, and restricted cubic splines were used to explore the shape of the association between baseline heart rate and cardiovascular mortality. Results During a total observational time of 230,813 person-years, 402 myocardial infarction events, 1,096 stroke events, 1,540 major cardiovascular events, and 356 cardiovascular deaths were documented. In adjusted analyses, normotensive subjects with baseline heart rate >82.5 beats per minute had a 3.30-fold greater risk of cardiovascular death and an increased 72% risk of myocardial infarction, compared with individuals whose baseline heart rate was 65.5–71 beats per minute. A similar trend was observed for cardiovascular mortality in the hypertensive population, but the association was attenuated. Multivariable-adjusted restricted cubic splines showed linear associations between baseline heart rate and cardiovascular mortality in two groups of people (all P<0.05 for linearity). Conclusions Elevated baseline heart rate is associated with an increased risk of cardiovascular mortality and myocardial infarction in the normotensive population. The association is attenuated for cardiovascular death in hypertensive patients.
Overview of virus and cancer relationships. Position paper

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of an overview of the relationship between viruses and cancer with a multidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.
System Justification or Social Dominance? A Multilevel Test of the Ideological Motivators of Perceived Discrimination

Although system-justifying beliefs often mitigate perceptions of discrimination, status-based asymmetries in the ideological motivators of perceived discrimination are unknown. Because the content and societal implications of discrimination claims are status-dependant, social dominance orientation (SDO) should motivate perceptions of (reverse) discrimination among members of high-status groups, whereas system justification should motivate the minimization of perceived discrimination among the disadvantaged. We tested these hypotheses using multilevel regressions among a nationwide random sample of New Zealand Europeans (n = 29,169) and ethnic minorities (n = 5,118). As hypothesized, group-based dominance correlated positively with perceived (reverse) discrimination among ethnic-majority group members, whereas system justification correlated negatively with perceived discrimination among the disadvantaged. Furthermore, the proportion of minorities within the region strengthened the victimizing effects of SDO-Dominance, but not SDO-Egalitarianism, among the advantaged. Together, these results reveal status-based asymmetries in the motives underlying perceptions of discrimination and identify a key contextual moderator of this association.
Explore the role of CR1 genetic variants in late-onset Alzheimer’s disease susceptibility

Supplemental Digital Content is available in the text. Background Complement component (3b/4b) receptor 1 (CR1) is an interesting candidate gene which has a close connection with Alzheimer’s disease, and its polymorphisms have been reported to link to the late-onset Alzheimer’s disease (LOAD) susceptibility. However, the findings of these related studies are inconsistent. Objective To explore the effect of CR1 genetic variants in LOAD susceptibility. MethodsWe searched relevant studies for the period up to 1 November 2020. And odds ratios (ORs) and their 95% confidence intervals (CIs) were utilized to assess the strength of the association. In addition, we carried out a case-control association study to assess their genetic association. Results Finally, a total of 30 articles with 30108 LOAD cases and 37895 controls were included. Significant allele frequency between LOAD patients and controls was observed in rs3818361 and rs6656401 (rs3818361, T vs. C: OR,1.18; 95% CI, 1.13–1.23; rs6656401, A vs. G: OR, 1.23; 95% CI, 1.10–1.36). Moreover, these results remain significant in subgroup of rs3818361 in Asia or America (OR,1.26; 95% CI,1.06–1.45; OR, 1.18; 95% CI, 1.13–1.24, respectively) and rs6656401 in Europe (OR = 1.26; 95% CI, 1.09–1.42). In addition, the two single nucleotide polymorphisms were proved to significantly increase LOAD risk in the overall population under the dominant model (OR = 1.12; 95% CI, 1.02–1.21; OR = 1.18, 95% CI, 1.15–1.22, respectively). Our case–control study showed that the distribution of rs6656401 genotype was significant (P = 0.000; OR, 6.889; 95% CI, 2.709–17.520), suggesting the A allele of rs6656401 is the risk allele. Conclusion These available data indicate that rs6656401 in CR1 is significant to increase LOAD risk.
The source scaling and seismic productivity of slow slip transients

Aseismic and seismic slip scaling indicate similar physics governing tremor and earthquake swarms during slow slip events. Slow slip events (SSEs) represent a slow faulting process leading to aseismic strain release often accompanied by seismic tremor or earthquake swarms. The larger SSEs last longer and are often associated with intense and energetic tremor activity, suggesting that aseismic slip controls tremor genesis. A similar pattern has been observed for SSEs that trigger earthquake swarms, although no comparative studies exist on the source parameters of SSEs and tremor or earthquake swarms. We analyze the source scaling of SSEs and associated tremor- or swarm-like seismicity through our newly compiled dataset. We find a correlation between the aseismic and seismic moment release indicating that the shallower SSEs produce larger seismic moment release than deeper SSEs. The scaling may arise from the heterogeneous frictional and rheological properties of faults prone to SSEs and is mainly controlled by temperature. Our results indicate that similar physical phenomena govern tremor and earthquake swarms during SSEs.
SMC Complexes Are Guarded by the SUMO Protease Ulp2 Against SUMO-Chain-Mediated Turnover

Structural maintenance of chromosomes (SMC) complexes, cohesin, condensin and Smc5/6, are essential for viability and participate in multiple processes, including sister chromatid cohesion, chromosome condensation, and DNA repair. Here we show that SUMO chains target all three SMC complexes and are antagonized by the SUMO protease Ulp2 to prevent their turnover. We uncover that the essential role of the cohesin-associated subunit Pds5 is to counteract SUMO chains jointly with Ulp2. Importantly, fusion of Ulp2 to kleisin Scc1 supports viability of PDS5 null cells and protects cohesin from proteasomal degradation mediated by the SUMO-targeted ubiquitin ligase Slx5/Slx8. The lethality of PDS5 deleted cells can also be bypassed by simultaneous loss of the PCNA unloader, Elg1, and the cohesin releaser, Wpl1, but only when Ulp2 is functional. Condensin and Smc5/6 complex are similarly guarded by Ulp2 against unscheduled SUMO-chain assembly, which we propose to time the availability of SMC complexes on chromatin.
Anticipatory Driving in Automated Vehicles: The Effects of Driving Experience and Distraction

Objective To understand the influence of driving experience and distraction on drivers’ anticipation of upcoming traffic events in automated vehicles. Background In nonautomated vehicles, experienced drivers spend more time looking at cues that indicate upcoming traffic events compared with novices, and distracted drivers spend less time looking at these cues compared with nondistracted drivers. Further, pre-event actions (i.e., proactive control actions prior to traffic events) are more prevalent among experienced drivers and nondistracted drivers. However, there is a research gap on the combined effects of experience and distraction on driver anticipation in automated vehicles. Methods A simulator experiment was conducted with 16 experienced and 16 novice drivers in a vehicle equipped with adaptive cruise control and lane-keeping assist systems (resulting in SAE Level 2 driving automation). Half of the participants in each experience group were provided with a self-paced primarily visual-manual secondary task. Results Drivers with the task spent less time looking at cues and were less likely to perform anticipatory driving behaviors (i.e., pre-event actions or preparation for pre-event actions such as hovering fingers over the automation disengage button). Experienced drivers exhibited more anticipatory driving behaviors, but their attention toward the cues was similar to novices for both task conditions. Conclusion In line with nonautomated vehicle research, in automated vehicles, secondary task engagement impedes anticipation while driving experience facilitates anticipation. Application Though Level 2 automation can relieve drivers of manually controlling the vehicle and allow engagement in distractions, visual-manual distraction engagement can impede anticipatory driving and should be restricted.
Possible Infanticidal Event of an Aye-Aye (Daubentonia madagascariensis) in Torotorofotsy, Madagascar

Infanticide occurs in an array of mammalian species, especially primates. Most infanticidal events occur in polygynous societies, though they sometimes happen in nongregarious populations. We witnessed a possible infanticidal event of a 3-month-old male aye-aye, a species that exhibits a dispersed multimale social system, in Torotorofotsy, Madagascar. Though firsthand killing of the infant was not observed, physical injuries to the infant, vocalizations of the adult female, and her subsequent chase of the adult male aye-aye strongly indicates infanticide. If true, this would be the first recorded incident of an infanticidal event in a noyau primate. The evidence for three different explanations of infanticide is evaluated.
Absorbtion et dissipation d'énergie dans un plasma hors équilibre

P. 9. Preface / Alix GicquelP. 11. Introduction : le reseau Plasmas froids et la Mission des Ressources et Competences Technologiques du CNRS / Gerard Lelievre, Francoise Massines et Elodie Girard I - Generation et dissipation d'energie P. 17. I-1. Absorbtion et dissipation d'energie dans un plasma hors equilibre / J.-P. Bœuf P. 49. I-2. Plasmas hors-equilibre a des pressions atmospheriques / K. Hassouni, F. Massines, J.-M. Pouvesle P. 109. I-3. Les plasmas thermiques / A. Gleizes II - Acces aux caracteristiques et aux especes du plasma P. 141. II-1. Le plasma d'arc dans le procede de projection thermique / J.-F. Couderc P. 159. II-2. Mesures de sondes electrostatiques en plasma basse pression / S. Bechu P. 225. II-3. Diagnostics laser et spectroscopie de masse dans les plasmas reactifs / J. Jolly P. 255. II-4. Saturation optique et autres pieges en spectroscopie laser / N. Sadeghi P. 275. II-5. Pieges en spectroscopie de masse / A. Granier P. 297. II-6. Source d'ionisation par micro pointes pour la spectroscopie de masse spatiale / F. Cipriani, J.-M. Illiano, J.-J. Berthelier III - Technologie des reacteurs a plasmas P. 323. III-1. Plasmas micro-onde basses pressions excites a la resonance cyclotronique electronique / Y. Arnal P. 353. III-2. Technologie des reacteur a plasma: Dimensionnement des reacteurs a Plasma micro-onde haute pression / F. Sylva, G. Hagelaar, K. Hassouni, A. Gicquel P. 367. III-3. Technologie des reacteurs a plasmas: Plasmas inductifs et capacitifs en basse pression / Ph. Lefaucheux P. 391. III-4. Les Plasmas thermique / C. Verdy, R. Boblot, H. Deng, P. Gougeon, C. Coddet
New triazolothiadiazole and triazolothiadiazine derivatives as kinesin Eg5 and HIV inhibitors: synthesis, QSAR and modeling studies

Abstract A new series of fused 1,2,4-triazoles, namely 6-aryl-3-(furan-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 3a–h and 4a–f as well as 6-aryl-3-(furan-2-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines 5a–h, were synthesized by the condensation of 4-amino-5-(furan-2-yl)-4H-1,2,4-triazole-3-thiol (2) with substituted aromatic acids and phenacyl bromides, respectively. The structures of the newly synthesized compounds were established using spectroscopic analysis, while that of 3e was confirmed independently by a single-crystal X-ray structure determination. The compounds were evaluated for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells using an MTT assay. In a docking study, 4b interacted with several amino acids in the reverse transcriptase (RT) binding site of HIV-1. Some new analogues were selected for evaluation of their Eg5 inhibitory activity using an in vitro malachite green ATPase assay. The QSAR of these new analogues was studied as well.
Computer simulations of the interaction of fullerene clusters with lipid membranes

Abstract Extensive coarse-grained simulations were performed to investigate the interactions of fullerene cluster with DMPC (dimyristoyl phosphatidyl choline) lipid membranes. The self-organised structures of pristine molecules in aqueous solutions are comparable with that in full-atomistic simulations. We find that the interaction between and membranes depends on the initial aggregation state of fullerene molecules. The insertion of aggregates with small size induced an increase of the bilayer thickness and membrane area. They disaggregate after entering the membrane interior, while larger ones can penetrate into the membrane as solid-like nanoparticles. Our simulations show that the lipids can be extracted from the outer monolayer of the membrane to accommodate the cluster during the insertion process. Particularly, multiple lipid and water molecules under the cluster can be transferred to the opposite side of the membrane, which can cause membrane asymmetry and osmotic pressure for small unilamellar vesicles. Our results suggest that mechanical damage may be a potential mechanism for membrane disruption and fullerene toxicity.