Miracle-dz/UniFAR-FTUs huggingface dataset:
Estrogen-induced Activation of Cdk4 and Cdk2 during G1-S Phase Progression Is Accompanied by Increased Cyclin D1 Expression and Decreased Cyclin-dependent Kinase Inhibitor Association with Cyclin E-Cdk2*

Estrogens induce cell proliferation in target tissues by stimulating progression through G1 phase of the cell cycle, but the underlying molecular targets remain undefined. To determine the role of the cyclin/cyclin-dependent kinase (CDK)/retinoblastoma protein (pRB) pathway in this response we treated MCF-7 breast cancer cells with the pure estrogen antagonist ICI 182780 to inhibit estrogen-induced gene expression and induce G1 phase arrest. Subsequent treatment with 17β-estradiol resulted in the synchronous entry of cells into S phase commencing at 12 h. The proportion of cells in S phase reached a maximum of 60% at 21–24 h. Cells subsequently completed mitosis and entered a second semisynchronous round of replication. Entry into S phase was preceded by increased activity of both Cdk4 and cyclin E-Cdk2 and hyperphosphorylation of pRB, all within the first 3–6 h of estradiol treatment. The increase in Cdk4 activity was accompanied by increases in cyclin D1 mRNA and protein, indicating that an initiating event in the activation of Cdk4 was increased cyclin D1 gene expression. In contrast, the levels of Cdk2 and the CDK inhibitors p21 (WAF1/CIP1/SDI1) and p27 (KIP1) in total cell lysates and in cyclin E immunoprecipitates were unaltered at these early time points. However, an inhibitory activity was present in antiestrogen-pretreated cell lysates toward recombinant cyclin E-Cdk2 and was relieved by estradiol treatment. This activity was attributable predominantly to p21. These apparently conflicting data were resolved by performing gel filtration chromatography, which revealed that only a minority of cyclin E-Cdk2 complexes were active following estradiol treatment. Active complexes eluted at a higher molecular weight than inactive complexes, were relatively deficient in both p21 and p27, and contained Cdk2 with increased threonine 160 phosphorylation, consistent with a mechanism of activation of cyclin E-Cdk2 involving both reduced CDK inhibitor association and CDK-activating kinase-mediated phosphorylation of Cdk2. These results provide an explanation for the early activation of both cyclin D1-Cdk4 and cyclin E-Cdk2 complexes that accompany G1-S phase progression in response to estradiol.
Public Integrity Auditing for Dynamic Data Sharing With Multiuser Modification

In past years, the rapid development of cloud storage services makes it easier than ever for cloud users to share data with each other. To ensure users' confidence of the integrity of their shared data on cloud, a number of techniques have been proposed for data integrity auditing with focuses on various practical features, e.g., the support of dynamic data, public integrity auditing, low communication/computational audit cost, and low storage overhead. However, most of these techniques consider that only the original data owner can modify the shared data, which limits these techniques to client read-only applications. Recently, a few attempts started considering more realistic scenarios by allowing multiple cloud users to modify data with integrity assurance. Nevertheless, these attempts are still far from practical due to the tremendous computational cost on cloud users, especially when high error detection probability is required by the system. In this paper, we propose a novel integrity auditing scheme for cloud data sharing services characterized by multiuser modification, public auditing, high error detection probability, efficient user revocation as well as practical computational/communication auditing performance. Our scheme can resist user impersonation attack, which is not considered in existing techniques that support multiuser modification. Batch auditing of multiple tasks is also efficiently supported in our scheme. Extensive experiments on Amazon EC2 cloud and different client devices (contemporary and mobile devices) show that our design allows the client to audit the integrity of a shared file with a constant computational cost of 340 ms on PC (4.6 s on mobile device) and a bounded communication cost of 77 kB for 99% error detection probability with data corruption rate of 1%.
Broadcast vs. Unicast Review Technology: Does It Matter?

Code review is the process of having other team members examine changes to a software system in order to evaluate their technical content and quality. Over the years, multiple tools have been proposed to help software developers conduct and manage code reviews. Some software organizations have been migrating from broadcast review technology to a more advanced unicast review approach such as Jira, but it is unclear if these unicast review technology leads to better code reviews. This paper empirically studies review data of five Apache projects that switched from broadcast based code review to unicast based, to understand the impact of review technology on review effectiveness and quality. Results suggest that broadcast based review is twice faster than review done with unicast based review technology. However, unicast's review quality seems to be better than that of the broadcast based. Our findings suggest that the medium (i.e., broadcast or unicast) technology used for code reviews can relate to the effectiveness and quality of reviews activities.
Hybrid Genetic Algorithms: A Review

Hybrid genetic algorithms have received significant interest in recent years and are being increasingly used to solve real-world problems. A genetic algorithm is able to incorporate other techniques within its framework to produce a hybrid that reaps the best from the combination. In this paper, different forms of integration between genetic algorithms and other search and optimization techniques are reviewed. This paper also aims to examine several issues that need to be taken into consideration when designing a hybrid genetic algorithm that uses another search method as a local search tool. These issues include the different approaches for employing local search information and various mechanisms for achieving a balance between a global genetic algorithm and a local search method. Index Terms—Genetic algorithms, evolutionary computation, hybrid genetic algorithms, genetic-local hybrid algorithms, memetic algorithms, Lamarckian search, Baldwinian search.
Enhancing the Antibiotic Antibacterial Effect by Sub Lethal Tellurite Concentrations: Tellurite and Cefotaxime Act Synergistically in Escherichia coli

The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or µM concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both Gram negative and Gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens.
Magnetic Resonance Perfusion Measurements for the Noninvasive Detection of Coronary Artery Disease

Background—With MRI, an index of myocardial perfusion reserve (MPRI) can be determined. We assessed the value of this technique for the noninvasive detection of coronary artery disease (CAD) in patients with suspected CAD. Methods and Results—Eighty-four patients referred for a primary diagnostic coronary angiography were examined with a 1.5 T MRI tomograph (Philips-ACS). For each heartbeat, 5 slices were acquired during the first pass of 0.025 mmol gadolinium-diethylenetriamine pentaacetic acid/kg body weight before and during adenosine vasodilation by using a turbo-gradient echo/echo-planar imaging-hybrid sequence. MPRI was determined from the alteration of the upslope of the myocardial signal intensity curves for 6 equiangular segments per slice. Receiver operating characteristics were performed for different criteria to differentiate ischemic and nonischemic segments. Prevalence of CAD was 51%. Best results were achieved when only the 3 inner slices were assessed and a threshold value of 1.1 was used for the second smallest value as a marker for significant CAD. This approach yielded a sensitivity of 88%, specificity of 90%, and accuracy of 89%. Conclusion—The determination of MPRI with MRI yields a high diagnostic accuracy in patients with suspected CAD.
Method of rotations for bilinear singular integrals

Suppose that Ω lies in the Hardy space H of the unit circle S in R. We use the Calderón–Zygmund method of rotations and the uniform boundedness of the bilinear Hilbert transforms to show that the bilinear singular operator with the rough kernel p.v. Ω(x/|x|)|x|−2 is bounded from L(R) × L(R) to L(R), for a large set of indices satisfying 1/p+ 1/q = 1/r. We also provide an example of a function Ω in L(S) with mean value zero to show that the singular integral operator given by convolution with p.v. Ω(x/|x|)|x|−2 is not bounded from L1(R)× L2(R) to L(R) for 1/2 < p < 1, 1 < p1, p2 <∞, 1/p1 + 1/p2 = 1/p, 1 ≤ q <∞, and 1/p + 1/q > 2.
The Toarcian Oceanic Anoxic Event in southwestern Gondwana: an example from the Andean Basin, northern Chile

Palaeoenvironmental and palaeoclimatic changes during the Toarcian Oceanic Anoxic Event (T-OAE) are reported from two successions deposited in the Andean Basin (Chile), based on a high-resolution biostratigraphic (calcareous nannofossils), sedimentological, mineralogical and geochemical analysis. A large negative carbon-isotope excursion was identified in a lower Toarcian storm-dominated marl–limestone alternation, underlining the global extent of the carbon-cycle perturbation and the occurrence of episodic high-energy conditions during the T-OAE. Low total organic carbon content and absence of redox-sensitive trace-element enrichment indicate that the dynamic depositional conditions did not favour the development of oxygen-depleted conditions and the preservation of organic matter. The decrease in kaolinite reflects a shift to more arid conditions, whereas the increase in the chemical index of alteration at the onset of the T-OAE is probably related to a change in the sediment source. Less hydrolytic activity probably promoted a decrease in nutrient input in the Andean Basin. Mercury anomalies support the link between the onset of the Karoo–Ferrar large igneous province activity, the carbon cycle perturbation and the generated environmental change. This paper presents one of the most complete T-OAE studies from the southern hemisphere, and reveals that regional conditions strongly modulated the expression of this global event in the Andean Basin. Supplementary material: the complete dataset, the coefficient of correlation (r) for major and trace elements, and the nannofossil assemblages are available at: https://doi.org/10.6084/m9.figshare. c.4133687
A Novel Flexible Room Temperature Ethanol Gas Sensor Based on SnO2 Doped Poly-Diallyldimethylammonium Chloride

A novel flexible room temperature ethanol gas sensor was fabricated and demonstrated in this paper. The polyimide (PI) substrate-based sensor was formed by depositing a mixture of SnO2 nanopowder and poly-diallyldimethylammonium chloride (PDDAC) on as-patterned interdigitated electrodes. PDDAC acted both as the binder, promoting the adhesion between SnO2 and the flexible PI substrate, and the dopant. We found that the response of SnO2-PDDAC sensor is significantly higher than that of SnO2 alone, indicating that the doping with PDDAC effectively improved the sensor performance. The SnO2-PDDAC sensor has a detection limit of 10 ppm at room temperature and shows good selectivity to ethanol, making it very suitable for monitoring drunken driving. The microstructures of the samples were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscope (TEM) and Fourier transform infrared spectra (FT-IR), and the sensing mechanism is also discussed in detail.
Functional Evolution of a cis-Regulatory Module

Lack of knowledge about how regulatory regions evolve in relation to their structure–function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module—the even-skipped stripe 2 enhancer—from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure–function, mechanisms of speciation and computational identification of regulatory modules.
Amplitude balanced PEF estimation

Inverse theory teaches us that the residual, or misfit functi on, should be weighted by the inverse covariance matrix of the noise. Because the covariance operator is often difficult to estimate, we can approximate it with a diagonal weight that can be more easily computed. This paper investigates the possible choices of weighting functions for the data residual when prediction-error filters are estimated. Examples with 2-D and 3-D field data prove that it is better to weight the residual than to weight the dat a before starting the inversion.
WSN4QoL: A WSN-Oriented Healthcare System Architecture

People worldwide are getting older and this fact has pushed the need for designing new, more pervasive, and possibly cost effective healthcare systems. In this field, distributed and networked embedded systems, such as wireless sensor networks (WSNs), are the most appealing technology to achieve continuous monitoring of aged people for their own safety, without affecting their daily activities. This paper proposes recent advancements in this field by introducing WSN4QoL, a Marie Curie project which involves academic and industrial partners from three EU countries. The project aims to propose new WSN-based technologies to meet the specific requirements of pervasive healthcare applications. In particular, in this paper, the system architecture is presented to cope with the challenges imposed by the specific application scenario. This includes a network coding (NC) mechanism and a distributed localization solution that have been implemented on WSN testbeds to achieve efficiency in the communications and to enable indoor people tracking. Preliminary results in a real environment show good system performance that meet our expectations.
Losing control of your languages: A case study

Bilingual speakers are usually quite good at restricting their lexicalization output to the desired language while preventing all sorts of language intrusions from the language not in use. However, brain damage can affect these abilities of language control, leading to striking and flagrant linguistic behaviours, such as pathological language mixing (pLM) and pathological switching (pLS). In this paper we report the performance of a Catalan–Spanish bilingual individual (R.R.T.) who, due to a neuroinflammatory disease and subcortical lesions, shows pLS. We tested R.R. T. in several tasks of language production and control, such as picture naming (objects and actions), word translation, blocked naming, and language switching task. R.R. T. was also tested in executive control (EC) tasks, such as task switching and a flanker task. We found several interesting results. First, cross-language intrusions were present much more frequently when R.R. T. was asked to speak in her first (and dominant) language (Catalan) than when she was asked to do so in the nondominant language (Spanish). Second, the results provide evidence suggesting that damage to certain subcortical structures may lead to problems in controlling the language output during verbalization in bilingual speakers. Third, we observed that R.R. T. seemed to show more difficulties in language control with verbs. Fourth, R.R. T. showed impaired performance compared to controls in both task switching and a flanker task. The results are discussed in relation to other findings of pLM and pLS in published single-case reports and in relation to EC deficits.
Glutathione and Catalase Provide Overlapping Defenses for Protection against Respiration-Generated Hydrogen Peroxide in Haemophilus influenzae

ABSTRACT Glutathione is an abundant and ubiquitous low-molecular-weight thiol that may play a role in many cellular processes, including protection against the deleterious effects of reactive oxygen species. We address here the role of glutathione in protection against hydrogen peroxide (H2O2) in Haemophilus influenzae and show that glutathione and catalase provide overlapping defense systems. H. influenzae is naturally glutathione deficient and imports glutathione from the growth medium. Mutant H. influenzae lacking catalase and cultured in glutathione-deficient minimal medium is completely devoid of H2O2 scavenging activity and, accordingly, substantial amounts of H2O2 accumulate in the growth medium. H. influenzae generates H2O2 at rates similar to those reported for Escherichia coli, but the toxicity of this harmful metabolite is averted by glutathione-based H2O2 removal, which appears to be the primary system for protection against H2O2 endogenously generated during aerobic respiration. When H2O2 concentrations exceed low micromolar levels, the hktE gene-encoded catalase becomes the predominant scavenger. The requirement for glutathione in protection against oxidative stress is analogous to that in higher and lower eukaryotes but is unlike the situation in other bacteria in which glutathione is dispensable for aerobic growth during both normal and oxidative stress conditions.
Association of kinase insert domain-containing receptor (KDR) gene polymorphism/ haplotypes with recurrent spontaneous abortion and genetic structure

Background: Recurrent spontaneous abortion is one of the diseases that can lead to physical, psychological, and, economical problems for both individuals and society. Recently a few numbers of genetic polymorphisms in kinase insert domain-containing receptor (KDR) gene are examined that can endanger the life of the fetus in pregnant women. Objective: The risk of KDR gene polymorphisms was investigated in Iranian women with idiopathic recurrent spontaneous abortion (RSA). Materials and Methods: A case controlled study was performed. One hundred idiopathic recurrent spontaneous abortion patients with at least two consecutive pregnancy losses before 20 weeks of gestational age with normal karyotypes were included in the study. Also, 100 healthy women with at least one natural pregnancy were studied as control group. Two functional SNPs located in KDR gene; rs1870377 (Q472H), and rs2305948 (V297I) as well as one tag SNP in the intron region (rs6838752) were genotyped by using PCR based restriction fragment length polymorphism (PCR-RFLP) technique. Haplotype frequency was determined for these three SNPs’ genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to study genetic variation. Results: Functional SNP (rs1870377) was highly linked to tag SNP (rs6838752) (D´ value=0. 214; χ2 = 16.44, p<0. 001). K means clustering showed that k = 8 as the best fit for the optimal number of genetic subgroups in our studied materials. This result was in agreement with Neighbor Joining cluster analysis. Conclusion: In our study, the allele and genotype frequencies were not associated with RSA between patient and control individuals. Inconsistent results in different populations with different allele frequencies among RSA patients and controls may be due to ethnic variation and used sample size.
Gene expression analysis of protein synthesis pathways in bovine mammary epithelial cells purified from milk during lactation and short-term restricted feeding.

The objective of the study was to investigate selected key regulatory pathways of milk protein biosynthesis in primary bovine mammary epithelial cells (MECs) of dairy cows during the first 155 days of lactation. In addition, cows were exposed to feed restriction for a short period (FR) during different stages of lactation (week 4 and 21 pp) to study adjustment processes of molecular protein biosynthesis to metabolic challenge. Morning milk samples from twenty-four Holstein-Friesian cows were collected throughout the experimental period (n = 10 per animal). MEC from raw milk were purified using an immunomagnetic separation technique and used for real-time quantitative PCR analyses. As was seen in transcript abundances of all major milk proteins, mRNA levels of E74-like factor 5 (ELF5), an enhancer of signal transducer and activator of transcription (STAT) action, concomitantly decreased towards mid-lactation. Expression of ELF5 as well as of all milk protein genes showed a similar increase during FR in early lactation. Occasional changes in expression could be seen in other Janus kinase (JAK)/STAT factors and in mammalian target of rapamycin (mTOR) pathway elements. Amino acid transfer and glucose transporter and the β-casein expression were also partially affected. In conclusion, our findings suggest a pivotal role of the transcription factor ELF5 in milk protein mRNA expression with complementary JAK/STAT and mTOR signalling for the regulation of protein biosynthesis in the bovine mammary gland.
Role of EG‐VEGF in human placentation: Physiological and pathological implications

Pre‐eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro‐ and anti‐invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR‐8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG‐VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG‐VEGF inhibits EVT migration, invasion and tube‐like organisation. EG‐VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)‐2 and MMP‐9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG‐VEGF‐induced inhibitory effects. Furthermore, we determined EG‐VEGF circulating levels in normal and PE patients. Our results showed that EG‐VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non‐pregnant levels. More important, EG‐VEGF levels were significantly elevated in PE patients compared with age‐matched controls. These findings identify EG‐VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down‐regulate placental expression of EG‐VEGF at the end of the first trimester of pregnancy might lead to PE.