Miracle-dz/UniFAR-FTUs huggingface dataset:
AKT/mTOR as Novel Targets of Polyphenol Piceatannol Possibly Contributing to Inhibition of Proliferation of Cultured Prostate Cancer Cells

The polyphenol piceatannol has shown inhibition against tyrosine and serine/threonine kinases. Whether piceatannol also exerts activity on the mammalian target of rapamycin (mTOR), a kinase involved in growth control of eukaryotic cells, is not known. In this study, we tested the effects of piceatannol on proliferation of androgen-dependent (AD) LNCaP and androgen-independent (AI) DU145 and PC-3 prostate cancer (CaP) cells. Suppression of AD and AI CaP cell growth by piceatannol was accompanied by cell cycle blockade in G1/S and S phases for LNCaP and PC-3 and induction of apoptosis in DU145 cells. Induction of apoptosis by piceatannol in DU145 cells was evident by reduced expression of poly(ADP-ribose) polymerase (PARP), cleavage of caspase 3 and apoptosis inducing factor AIF, and an increase in cytochrome c. The apoptotic changes occurred in concordance with DNA damage, supported by increased phosphorylated histone H2AX. Immunoblot analyses showed that exposure of different-stage CaP cells to piceatannol also resulted in cell-type-specific downregulation of mTOR and its upstream and downstream effector proteins, AKT and eIF-4E-BP1. We propose that the observed AKT and mTOR changes are new targets of piceatannol possibly contributing to its inhibitory activities on proliferation of CaP cells.
Viscoelastic Response of the Periodontal Ligament: An Experimental–Numerical Analysis

A viscoelastic constitutive model for the periodontal ligament (PDL) capable of accounting for large strains, anisotropy, and inelastic time-dependent effects was developed. Anisotropy characteristics are determined by the composite nature of the tissue and, in particular, by the distribution of collagen fibres. Time-dependent viscous phenomena are due to microstructural modifications during loading, such as fluid fluxes moving through the solid matrix and the internal rearrangement of fibers and constitutive adaptation. The viscoelastic model presented here was implemented in a general purpose finite element code. In vitro experimental tests were carried out on the PDL specimens of adult pigs to obtain stress-relaxation and cyclic stress-strain curves. The comparison of experimental and numerical results revealed good correspondence and confirmed the capability of the formulation assumed to properly interpret the viscoelastic behavior of the PDL.
Effective semantic pixel labelling with convolutional networks and Conditional Random Fields

Large amounts of available training data and increasing computing power have led to the recent success of deep convolutional neural networks (CNN) on a large number of applications. In this paper, we propose an effective semantic pixel labelling using CNN features, hand-crafted features and Conditional Random Fields (CRFs). Both CNN and hand-crafted features are applied to dense image patches to produce per-pixel class probabilities. The CRF infers a labelling that smooths regions while respecting the edges present in the imagery. The method is applied to the ISPRS 2D semantic labelling challenge dataset with competitive classification accuracy.
DNA Polymerase II (polB) Is Involved in a New DNA Repair Pathway for DNA Interstrand Cross-Links inEscherichia coli

ABSTRACT DNA-DNA interstrand cross-links are the cytotoxic lesions for many chemotherapeutic agents. A plasmid with a single nitrogen mustard (HN2) interstrand cross-link (inter-HN2-pTZSV28) was constructed and transformed into Escherichia coli, and its replication efficiency (RE = [number of transformants from inter-HN2-pTZSV28]/[number of transformants from control]) was determined to be ∼0.6. Previous work showed that RE was high because the cross-link was repaired by a pathway involving nucleotide excision repair (NER) but not recombination. (In fact, recombination was precluded because the cells do not receive lesion-free homologous DNA.) Herein, DNA polymerase II is shown to be in this new pathway, since the replication efficiency (RE) is higher in apolB+ (∼0.6) than in a ΔpolB(∼0.1) strain. Complementation with apolB+-containing plasmid restores RE to wild-type levels, which corroborates this conclusion. In separate experiments, E. coli was treated with HN2, and the relative sensitivity to killing was found to be as follows: wild type <polB < recA < polB recA ∼ uvrA. Because cells deficient in either recombination (recA) or DNA polymerase II (polB) are hypersensitive to nitrogen mustard killing,E. coli appears to have two pathways for cross-link repair: an NER/recombination pathway (which is possible when the cross-links are formed in cells where recombination can occur because there are multiple copies of the genome) and an NER/DNA polymerase II pathway. Furthermore, these results show that some cross-links are uniquely repaired by each pathway. This represents one of the first clearly defined pathway in which DNA polymerase II plays a role in E. coli. It remains to be determined why this new pathway prefers DNA polymerase II and why there are two pathways to repair cross-links.
Cockroach hypersensitivity in asthmatics in Lagos, Nigeria.

BACKGROUND Cockroach allergy occurs frequently in asthmatics in urban areas, where the level of cockroach infestation is usually high. The prevalence of cockroach allergy, as well as the effect of associated factors on cockroach sensitisation in Nigeria is largely unknown. OBJECTIVE To determine the prevalence of cockroach allergy in asthmatics in Lagos. DESIGN A prospective case-control study. SETTING Medical outpatient department of the Lagos University Teaching Hospital, Lagos, Nigeria. SUBJECTS Two hundred and two patients with confirmed bronchial asthma and one hundred non-asthmatic control subjects took part in the study. INTERVENTION The cockroach allergen was administered on all the subjects using skin prick technique. MAIN OUTCOME MEASURES The provocation of a skin reaction (wcal) fifteen minutes after administering the cockroach antigen. RESULTS Amongst the asthmatic patients 90 (44.6%) had positive skin tests to the cockroach allergen, compared to nine (9%) of the control subjects. There was a male preponderance of cockroach sensitivity amongst the asthmatic patients even though the difference between both sexes was not significant. Other highlights of the study included the fact that cockroach sensitivity was related to age, duration of asthma, nocturnal asthmatic attacks, frequency of attacks, and the levels of infestation. There was an insignificant relationship between cockroach sensitivity and the location of residences as well as the income status of the respondents. CONCLUSION There is the need for more studies on cockroach allergy in asthmatics in our environment.
The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases

We previously described IQGAP1 as a human protein related to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe. Here we report the identification of a liver-specific human protein that is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N-terminal calponin homology motif which functions as an F-actin binding domain in members of the spectrin, filamin, and fimbrin families. Both IQGAPs also harbor several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and four IQ motifs and have 25% sequence identity with almost the entire S. pombe sar1 RasGAP homolog. As predicted by the presence of IQ motifs, IQGAP2 binds calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the GTPase activity of Ras or its close relatives. Instead, IQGAP2 binds Cdc42 and Racl but not RhoA. This interaction involves the C-terminal half of IQGAP2 and appears to be independent of the nucleotide binding status of the GTPases. Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain, they could play roles in the Cdc42 and Rac1 controlled generation of specific actin structures.
Validation of a new live cell strain system: characterization of plasma membrane stress failure.

Motivated by our interest in lung deformation injury, we report on the validation of a new live cell strain system. We showed that the system maintains a cell culture environment equivalent to that provided by conventional incubators and that its strain ouput was uniform and reproducible. With this system, we defined cell deformation dose (i.e., membrane strain amplitude)-cell injury response relationships in alveolar epithelial cultures and studied the effects of temperature on them. Deformation injury occurred in the form of reversible, nonlethal plasma membrane stress failure events and was quantified as the fraction of cells with uptake and retention of fluorescein-labeled dextran (FITC-Dx). The undeformed control population showed virtually no FITC-Dx uptake at any temperature, which was also true for cells strained by 3%. However, when the membrane strain was increased to 18%, ~5% of cells experienced deformation injury at a temperature of 37 degrees C. Moreover, at that strain, a reduction in temperature to 4 degrees C resulted in a threefold increase in the number of cells with plasma membrane breaks (from 4.8 to 15.9%; P < 0.05). Cooling of cells to 4 degrees C also lowered the strain threshold at which deformation injury was first seen. That is, at a 9% substratum strain, cooling to 4 degrees C resulted in a 10-fold increase in the number of cells with FITC-Dx staining (0.7 vs. 7.5%, P < 0.05). At that temperature, A549 cells offered a 50% higher resistance to shape change (magnetic twisting cytometry measurements) than at 37 degrees C. We conclude that the strain-injury threshold of A549 cells is reduced at low temperatures, and we consider temperature effects on plasma-membrane fluidity, cytoskeletal stiffness, and lipid trafficking as responsible mechanisms.
Assessment of different treatment failure criteria in a cohort of relapsing–remitting multiple sclerosis patients treated with interferon β: Implications for clinical trials

Clinical trials with interferons in relapsing–remitting multiple sclerosis have shown a modest effect on disability using fixed definitions of treatment failure to measure disease progression. However, in the course of the disease, treatment failure may be influenced by interrater variability and frequent remissions. Thus, the purpose of this study was to assess the clinical usefulness of different treatment failure criteria in a cohort of relapsing–remitting multiple sclerosis patients treated with interferon β. We studied 252 patients with a follow‐up of more than 2 years. We used four different criteria of treatment failure with increasing stringency (1 Expanded Disability Status Scale [EDSS] point increase confirmed at 3 months, 1 EDSS point increase confirmed at 6 months, 1.5 EDSS points increase confirmed at 3 months, and 1.5 EDSS points increase confirmed at 6 months). We divided treatment failure into permanent treatment failure and transient treatment failure. We considered permanent treatment failure when treatment failure was confirmed on the last two scheduled visits and transient treatment failure when treatment failure was not confirmed on these visits at different time points (9, 12, 18, and 24 months). We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the different criteria of treatment failure to identify patients who achieved a high degree of disability after 4 years of follow‐up. Regardless of the stringency of treatment failure definitions, a variable proportion of patients with treatment failure had transient treatment failure depending on the criterion applied. Patients with transient treatment failure had a significantly lower EDSS at entry compared with those with permanent treatment failure or no treatment failure. The number of relapses in patients with transient treatment failure did not differ from that of patients with permanent treatment failure. The criterion of confirmed 1 EDSS point increase at 6 months showed the best sensitivity (76.5%), with satisfactory specificity (89%). Our study shows that a large proportion of patients treated with interferon experience transient treatment failure that may affect outcome interpretation in clinical trials. Using a more strict criterion, as extending time to confirmation of EDSS deterioration, and longer follow‐up may reduce this proportion of patients with transient treatment failure and improve the validity of the results attained in clinical trials.
Real-time planning for automated multi-view drone cinematography

We propose a method for automated aerial videography in dynamic and cluttered environments. An online receding horizon optimization formulation facilitates the planning process for novices and experts alike. The algorithm takes high-level plans as input, which we dub virtual rails, alongside interactively defined aesthetic framing objectives and jointly solves for 3D quadcopter motion plans and associated velocities. The method generates control inputs subject to constraints of a non-linear quadrotor model and dynamic constraints imposed by actors moving in an a priori unknown way. The output plans are physically feasible, for the horizon length, and we apply the resulting control inputs directly at each time-step, without requiring a separate trajectory tracking algorithm. The online nature of the method enables incorporation of feedback into the planning and control loop, makes the algorithm robust to disturbances. Furthermore, we extend the method to include coordination between multiple drones to enable dynamic multi-view shots, typical for action sequences and live TV coverage. The algorithm runs in real-time on standard hardware and computes motion plans for several drones in the order of milliseconds. Finally, we evaluate the approach qualitatively with a number of challenging shots, involving multiple drones and actors and qualitatively characterize the computational performance experimentally.
Smoothing Income Against Crop Flood Losses in Amazonia: Rain Forest or Rivers as a Safety Net?

This article examines the role of ex post labor supply in smoothing income in response to crop losses caused by large floods among riverine households in the Peruvian Amazon, where rich environmental endowments permit a variety of resource extractive activities and coping responses. The paper finds that households respond to crop losses primarily by intensifying fishing effort, not by relying on gathering of nontimber forest products, hunting, or asset liquidation. This ex post labor adjustment helps to smooth total income against small crop losses but less well against large crop losses. Both relatively nonpoor households with better fishing capital and poor young households with a physical labor advantage employ this natural insurance in rivers.
Plasma Nitrate and Incidence of Cardiovascular Disease and All‐Cause Mortality in the Community: The Framingham Offspring Study

Background Nitrate is a dietary component as well as an endogenously formed metabolite and source of the signaling molecule nitric oxide. Harmful as well as beneficial effects of nitrate have been advocated. Data regarding the prognostic relevance of plasma nitrate are limited. The aim of this study was to evaluate the prospective association of plasma nitrate with cardiovascular disease (CVD) and all‐cause mortality. Methods and Results We assayed plasma nitrate in 2855 Framingham Offspring Study participants (mean age 59 years, 54% women) by gas chromatography–mass spectrometry and evaluated its association with all‐cause mortality and incident CVD. On follow‐up (median 17.3 years), 775 participants died and 522 developed new‐onset CVD (of 2546 participants free of CVD at baseline). In multivariable models adjusting for standard risk factors, plasma nitrate was associated with an increased risk of death in participants (hazard ratio per unit increase in log‐nitrate 1.21; 95% confidence interval, 1.04–1.40 [P=0.015]). The strength of the association was attenuated by additional adjustment for estimated glomerular filtration rate (hazard ratio, 1.16; 95% confidence interval, 1.00–1.35 [P=0.057]). In contrast, no evidence was found for an association of plasma nitrate with incident CVD (multivariable‐adjusted hazard ratio per unit increase log‐nitrate 1.08; 95% confidence interval, 0.89–1.31 [P=0.42]). Conclusions In our prospective community‐based investigation, a higher plasma nitrate concentration was associated with all‐cause mortality but not with incident CVD. The association of nitrate with mortality may at least in part be attributable to its association with renal function.
Effect of X Irradiation on Secondary Palate Development in Mice

Abstract Hiranuma, H. , Jikko, A. , Maeda, T. , Abe, M. and Fuchihata, H. Effect of X Irradiation on Secondary Palate Development in Mice. The mechanisms whereby X irradiation induces palatal clefting were investigated in vivo and in an in vitro organ culture system. When pregnant mice at day 12.5 of gestation were exposed to a 4-Gy dose of whole-body X radiation, the incidence of palatal clefting in their offspring was 91%. The volume of the irradiated palatal shelves was too low for them to make contact with each other. On gestational day 13.5 after labeling, bromodeoxyuridine-positive cells were sparse and apoptotic cells were abundant in the irradiated shelves. To prevent secondary effects of irradiation from the injured maternal body, fetal palatal explants were immediately transferred to an organ culture system after X irradiation in utero. The incidence of palatal clefting was 24%, much lower than the incidence in vivo. The addition of 10–4 M of dexamethasone to the culture medium increased the incidence of palatal clefting to 56%. These findings indicated that X irradiation inhibited cell proliferation and induced apoptosis, resulting in small-volume palatal shelves that could not fuse with each other. The organ culture data also indicated that 4 Gy of irradiation appears to produce its effects both by a direct action on the fetus and indirectly by affecting the metabolism of the pregnant dam.
Insect outbreak shifts the direction of selection from fast to slow growth rates in the long-lived conifer Pinus ponderosa

Significance Understanding selection dynamics over time is fundamental for predicting evolutionary potential. This is critical in long-lived organisms, particularly trees, which are at increased risk of mortality because of climate change-related drought and associated stresses. For ponderosa pine, we show rare direct empirical evidence of strong context-dependent fluctuating selection on growth rates over time: fast growth was selected for before a mountain pine beetle outbreak but against after the outbreak, when a growth–survival trade-off emerged. Our results provide insight into the mechanisms contributing to the maintenance of genetic diversity in a long-lived organism, and show that strong and fluctuating selection can contribute to the evolutionary potential of trees under climate change. Long generation times limit species’ rapid evolution to changing environments. Trees provide critical global ecosystem services, but are under increasing risk of mortality because of climate change-mediated disturbances, such as insect outbreaks. The extent to which disturbance changes the dynamics and strength of selection is unknown, but has important implications on the evolutionary potential of tree populations. Using a 40-y-old Pinus ponderosa genetic experiment, we provide rare evidence of context-dependent fluctuating selection on growth rates over time in a long-lived species. Fast growth was selected at juvenile stages, whereas slow growth was selected at mature stages under strong herbivory caused by a mountain pine beetle (Dendroctonus ponderosae) outbreak. Such opposing forces led to no net evolutionary response over time, thus providing a mechanism for the maintenance of genetic diversity on growth rates. Greater survival to mountain pine beetle attack in slow-growing families reflected, in part, a host-based life-history trade-off. Contrary to expectations, genetic effects on tree survival were greatest at the peak of the outbreak and pointed to complex defense responses. Our results suggest that selection forces in tree populations may be more relevant than previously thought, and have implications for tree population responses to future environments and for tree breeding programs.
Power benefit study of monolithic 3D IC at the 7nm technology node

Monolithic 3D IC (M3D) is one potential technology to help with the challenges of continued circuit power and performance scaling. In this paper, for the first time, the power benefits of monolithic 3D IC (M3D) using a 7nm FinFET technology are investigated. The predictive 7nm Process Design Kit (PDK) and standard cell library for both high performance (HP) and low standby power (LSTP) device technologies are built based on NanGate 45nm PDK using accurate dimensional, material, and electrical parameters from publications and a commercial-grade tool flow. In addition, we implement full-chip M3D GDS layouts using both 7nm HP and LSTP cells and industry-standard physical design tools, and evaluate the resulting full-chip power, performance, and area metrics. Our study first shows that 7nm HP M3D designs outperform 7nm HP 2D designs by 16.8% in terms of iso-performance total power reduction. Moreover, 7nm LSTP M3D designs reduce the total power consumption by 14.3% compared to their 2D counterparts. This convincingly demonstrates the power benefits of M3D technologies in both high performance as well as low power future generation devices.
Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men.

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3',5'-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)