Miracle-dz/UniFAR-FTUs huggingface dataset:
CUTANEOUS WATER LOSS AND LIPIDS OF THE STRATUM CORNEUM IN DUSKY ANTBIRDS, A LOWLAND TROPICAL BIRD

Abstract ABSTRACT The stratum corneum, the outer layer of the epidermis, consists of flattened cells embedded in a matrix of lipids, primarily cholesterol, free fatty acids, ceramides, and cerebrosides. The stratum corneum forms a barrier to water vapor diffusion through the skin. In birds, the skin limits excessive water loss at thermoneutral temperatures, but also serves as a vehicle for thermoregulation during episodes of heat stress. We measured total evaporative water loss, cutaneous water loss, and lipids in the stratum corneum in Dusky Antbirds (Cercomacra tyrannina), the first such measurements ever made for birds living in tropical rain forests. We predicted that these birds would have high rates of cutaneous water loss because of their need to thermoregulate rather than to conserve water. We found that Dusky Antbirds lose twice as much water through their skin as birds from temperate environments. We also hypothesized that the proportion of cerebrosides in the stratum corneum would increase relative to that of ceramides if Dusky Antbirds use their skin as a thermoregulatory organ. However, we found that Dusky Antbirds did not show different proportions of ceramides and cerebrosides in the stratum corneum than other species of birds. We also found that Dusky Antbirds had low amounts of free fatty acids in their stratum corneum. Overall, our data support the idea that the interactions of the lipids in the stratum corneum may play an important role in determining rates of water vapor diffusion through the skin.
Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes

The mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression, however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG−/−) severely impairs glucose homeostasis leading to diabetes during late adulthood, especially in males associated with nonautoimmune insulinopenia and reversed alpha/beta cell ratio. Islet beta cell mass in PTTG−/− mice was already diminished before development of frank diabetes and only increased minimally during growth. BrdUrd incorporation of islet cells in PTTG-null mice was ≈65% lower (P < 0.005) than in the WT pancreas, whereas apoptosis rates were similar. PTTG−/− beta cells had pleiotropic nuclei, suggesting defects in cell division. The results indicated that securin is indispensable for normal pancreatic beta cell proliferation.
Juvenile Hormone Regulates Extreme Mandible Growth in Male Stag Beetles

The morphological diversity of insects is one of the most striking phenomena in biology. Evolutionary modifications to the relative sizes of body parts, including the evolution of traits with exaggerated proportions, are responsible for a vast range of body forms. Remarkable examples of an insect trait with exaggerated proportions are the mandibular weapons of stag beetles. Male stag beetles possess extremely enlarged mandibles which they use in combat with rival males over females. As with other sexually selected traits, stag beetle mandibles vary widely in size among males, and this variable growth results from differential larval nutrition. However, the mechanisms responsible for coupling nutrition with growth of stag beetle mandibles (or indeed any insect structure) remain largely unknown. Here, we demonstrate that during the development of male stag beetles (Cyclommatus metallifer), juvenile hormone (JH) titers are correlated with the extreme growth of an exaggerated weapon of sexual selection. We then investigate the putative role of JH in the development of the nutritionally-dependent, phenotypically plastic mandibles, by increasing hemolymph titers of JH with application of the JH analog fenoxycarb during larval and prepupal developmental periods. Increased JH signaling during the early prepupal period increased the proportional size of body parts, and this was especially pronounced in male mandibles, enhancing the exaggerated size of this trait. The direction of this response is consistent with the measured JH titers during this same period. Combined, our results support a role for JH in the nutrition-dependent regulation of extreme mandible growth in this species. In addition, they illuminate mechanisms underlying the evolution of trait proportion, the most salient feature of the evolutionary diversification of the insects.
Classification based on neuroimaging data by tensor boosting

Recent advances in medical imaging technologies generate a high volume of imaging data. Classification of cognitive outcome and disease status based on brain images is one of the most important tasks in neuroimaging studies. However it poses great challenge to the current classification methods due to the extremely high dimensionality and low signal to noise ratio in brain image data. In this article we propose a tensor boosting algorithm for classification based on neuroimaging data. The method is off-the-shelf, computationally simple and amenable to various modalities of neuroimaging data. The method is applied to an EEG data set from an alcoholism study and an MRI data set from an ADHD Global Competition and shows significantly improved classification performance.
International Journal of Child-Computer Interaction

The demand for developmentally appropriate tools and learning environments for early childhood computer science education is greater than ever. One of the most widely used introductory coding environments designed for children ages 5–7 is ScratchJr (Bers & Resnick, 2015; Flannery et al., 2013), which has over 40 million users worldwide. ScratchJr was designed as a ‘‘low floor, high ceiling’’ learning environment — meaning that it is accessible to novice users while also allowing more experienced users to grow their knowledge. In this paper, we evaluate how the ‘‘low floor, high ceiling’’ design of ScratchJr is received in practice through looking at the programming performance of users at different ages, timepoints, and experience levels. We find that the youngest, and most novice users were able to engage with the app to some extent with no instruction, but engagement was optimized with curricular support. Additionally, we found that the oldest, and most experienced users still had room for growth and discovery in the app. We conclude that the design decisions in ScratchJr such as iconography, block variation, and open-endedness of the environment creates a welcoming and engaging experience for a wide range of users, both children and adults. © 2023ElsevierB.V. Allrightsreserved.
Pharmacodynamic Effect of Switching Therapy in Patients With High On-Treatment Platelet Reactivity and Genotype Variation With High Clopidogrel Dose Versus Prasugrel: The RESET GENE Trial

Background—High on-treatment platelet reactivity (HTPR) is associated with adverse outcomes. We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs. Methods and Results—Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay, defining HTPR as area under the curve >450. Those with HTPR were randomized to prasugrel (10 mg/day) or high-dose clopidogrel (150 mg/day) for 2 weeks and then crossed-over to, respectively, clopidogrel and prasugrel, repeating the P2Y12 assay at the end of each cycle. Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients. The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel. Thirty-two patients were randomized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel. Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was (325.8 versus 478.5 area under the curve, P=0.028). No patient treated with prasugrel exhibited HTPR, whereas 9 (28.1%) receiving high-dose clopidogrel still had prevalence of HTPR (P=0.001). Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable. Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274), whereas it was significantly worse in the 14 (43.7%) carriers (HTPR in 43.7% versus 0, P=0.003). Conclusions—HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype. Conversely, high-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT01465828.
Wirelength-driven force-directed 3D FPGA placement

In this paper, a wirelength-driven force-directed three-dimension (3-D) Field Programmable Gate Arrays (FPGA) placement algorithm (3D-WFP) is presented. The algorithm is composed of three stages: Overlap permitted force-directed 2-D placement, legalization and 3-D layer partition. Different from traditional partition-based 3-D placers, we adjust the layer partition process after the 2-D global placement, which effectively provides the global interconnection and timing information for the next two sub-steps. To legalize the position of the logic block, a 3-D space filling curve is adopted. A low temperature simulated annealing (SA) is used to determine the blocks final layer. Only blocks with the same horizontal coordinate are permitted to interchange, the speed of the SA is very fast. Compared to recently publish 3-D FPGA placement work, this algorithm improves the half perimeter wire-length (HPWL) by 8.57%, almost at the same time cost and keeps the same timing performance.
Decisions to Treat or Not to Treat Pneumonia in Demented Psychogeriatric Nursing Home Patients: Evaluation of a Guideline

We evaluated a new guideline, in the form of a “checklist of considerations,” to support end-of-life decision making in the treatment of demented patients with pneumonia. Questionnaires were sent to nursing home physicians (NHPs) in The Netherlands at three times: before implementation of the checklist (concerning 91 individual patients), during use of the checklist (concerning another 107 individual patients), and after data collection (concerning the targeted patient category of demented nursing home patients with pneumonia as a whole). In the last questionnaire, one NHP from each nursing home (n = 55 NHPs) gave his or her general opinion about the checklist. We measured the usefulness of the checklist in supporting decision making and its frequency of actual use. The NHPs accepted the contents of the checklist for use in the targeted patient category. It was used in 46% of the incident cases of pneumonia. The checklist was considered more useful in supporting decision making for the targeted patient category (85% of the NHPs) than for the individual patient (47%). Possible explanations for this discrepancy in “usefulness” include the difference in the nature of the outcome measures and the fact that the checklist was used more frequently for the “easier cases. ” Information on individual patient level, patient category level, and nursing home and NHP characteristics is used to suggest checklist improvements.
Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a significant cause of cancer-related morbidity and mortality worldwide. Despite improvements in local therapies, including surgical resection, liver transplantation, and transarterial embolization, the prognosis remains poor for the majority of patients who develop recurrence or present with advanced disease. Systemic therapy with the tyrosine kinase inhibitor sorafenib represents a milestone in advanced HCC but provides a limited survival benefit. Ongoing efforts to study hepatocarcinogenesis have identified an important role for c-MET signaling in the promotion of tumor growth, angiogenesis, and metastasis. In this review, we summarize the preclinical data from human tissue, cell lines, and animal models that implicate c-MET in the pathogenesis of HCC. We also evaluate potential biomarkers that may estimate prognosis or predict response to c-MET inhibitors for more rational clinical trial design. Finally, we discuss the latest clinical trials of c-MET inhibitors in advanced HCC. Clin Cancer Res; 19(9); 2310–8. ©2013 AACR.
Role of human microsomal and human complementary DNA-expressed cytochromes P4501A2 and P4503A4 in the bioactivation of aflatoxin B1.

The metabolism of the carcinogenic mycotoxin aflatoxin B1 (AFB1) was examined in microsomes derived from human lymphoblastoid cell lines expressing transfected CYP1A2 or CYP3A4 complementary DNAs and in microsomes prepared from human liver donors (n = 4). Lymphoblast microsomes expressing only CYP1A2 activated AFB1 to AFB1-8,9-epoxide (AFB1-8,9-epoxide trapped as the glutathione, conjugate) at both 16 microM and 128 microM AFB1 concentrations, whereas activation of AFB1 to the epoxide in lymphoblast microsomes expressing only CYP3A4 was detected only at high substrate concentrations (128 microM AFB1). AFB1 epoxidation was strongly inhibited in CYP1A2 but not CYP3A4 lymphoblast microsomes pretreated with furafylline, a specific mechanism-based CYP1A2 inhibitor, whereas troleandomycin (TAO), a specific CYP3A inhibitor, strongly inhibited AFB1 epoxidation in CYP3A4 but not CYP1A2 microsomes. Formation of the hydroxylated metabolite aflatoxin M1 (AFM1) was observed only in the CYP1A2 microsomes whereas aflatoxin Q1 (AFQ1) production was observed exclusively in the CYP3A4 microsomes. Treatment of individual human liver microsomes (HLM) with TAO resulted in an average 20% inhibition of AFB1-8,9-epoxide formation at 16 microM AFB1, whereas incubation of HLM with furafylline at 16 microM AFB1 resulted in an average 72% inhibition of AFB1-8,9-epoxide formation at 16 microM AFB1. TAO was slightly more effective than furafylline in inhibiting AFB1 epoxidation at 128 microM AFB1 (46% inhibition by TAO, 32% inhibition by furafylline) in HLM. AFB1-8,9-epoxide formation was inhibited by 89% at low substrate concentration and 85% at high substrate concentrations when HLM were inhibited with a furafylline/TAO mixture. AFM1 formation was strongly inhibited by furafylline, whereas AFQ1 formation was strongly inhibited by TAO, in all HLM regardless of substrate concentration. Analysis of R-6- and R-10-hydroxywarfarin activities (respective markers of CYP1A2 and CYP3A4 activities) in the complementary DNA-expressed microsomes demonstrated that TAO was less effective than furafylline as a selective P450 isoenzyme inhibitor (60% inhibition of CYP3A4 by TAO as compared to 99% inhibition of CYP1A2 by furafylline). The rates of AFB1 epoxidation and AFQ1 formation in HLM were increased 7- and 18-fold, respectively, at high versus low substrate concentrations. These results are consistent with the hypothesis that CYP1A2 is the high-affinity P450 enzyme principally responsible for the bioactivation of AFB1 at low substrate concentrations associated with dietary exposure. CYP3A4 appears to have a relatively low affinity for AFB1 epoxidation and is primarily involved in AFB1 detoxification through AFQ1 formation in HLM. (ABSTRACT TRUNCATED AT 400 WORDS)
UvA-DARE (Digital Academic Repository) Verifiably Safe Exploration for End-to-End Reinforcement Learning

Deploying deep reinforcement learning in safety-critical settings requires developing algorithms that obey hard constraints during exploration. This paper contributes a first approach toward enforcing formal safety constraints on end-to-end policies with visual inputs. Our approach draws on recent advances in object detection and automated reasoning for hybrid dynamical systems. The approach is evaluated on a novel benchmark that emphasizes the challenge of safely exploring in the presence of hard constraints. Our benchmark draws from several proposed problem sets for safe learning and includes problems that emphasize challenges such as reward signals that are not aligned with safety constraints. On each of these benchmark problems, our algorithm completely avoids unsafe behavior while remaining competitive at optimizing for as much reward as is safe. We characterize safety constraints in terms of a refinement relation on Markov decision processes – rather than directly constraining the reinforcement learning algorithm so that it only takes safe actions, we instead refine the environment so that only safe actions are defined in the environment’s transition structure. This has pragmatic system design benefits and, more importantly, provides a clean conceptual setting in which we are able to prove important safety and efficiency properties. These allow us to transform the constrained optimization problem of acting safely in the original environment into an unconstrained optimization in a refined environment.
Multiple Routes to Oestrogen Antagonism

Several lines of evidence attest to the existence of alternative ligand binding sites on the oestrogen receptor (ER), including non-competitive inhibition by trilostane or tamoxifen. It is possible that the inhibitory action of conventional oestrogen agonists at high concentrations may indicate that they too interact at alternative ER sites, albeit at low affinity. To test this possibility an oestrogen reporter assay was used to compare the activity of different oestrogens and antagonists in breast cancer and prostate cell lines. All four cell lines tested contained different amounts of oestrogen receptor α (ERα), ERβ, progesterone receptor and coregulator mRNA. Though differences were observed in response to stimulation and inhibition, these correlated only with the presence or absence of ERα, and not with the other components. Thus stimulation of the reporter by oestradiol and oestrone was biphasic in the breast cancer cells, while prostate cells were unable to respond. Only T47D cells were stimulated by oestriol or diethylstilboestrol, however reporter activity of all the cell lines was repressed by 10μM diethylstilboestrol. Reporter activity of MCF-7 cells was inhibited by tamoxifen, raloxifene and ICI 182,780, but stimulated by trilostane, yet all these antioestrogens inhibited agonist-stimulated activity. Trilostane also inhibited the agonism seen in cells co-treated with E2 and tamoxifen. It is clear that several of the compounds tested may have either agonist or antagonist effects under different conditions and at different concentrations, acting through ERα alone. Though biphasic dose response curves, or hormesis, have been attributed to various mechanisms, we here provide evidence that alternative ligand binding sites may contribute to this phenomenon.
The Cluster-Scale AGN Outburst in Hydra A

Deep Chandra observations of the Hydra A Cluster reveal a feature in the X-ray surface brightness that surrounds the 330 MHz radio lobes of the AGN at the cluster center. Surface brightness profiles of this feature and its close association with the radio lobes argue strongly that it is a shock front driven by the expanding radio lobes. The Chandra image also reveals other new structure on smaller scales that is associated with the radio source, including a large cavity and filament. The shock front extends 200-300 kpc from the AGN at the cluster center, and its strength varies along the front, with Mach numbers in the range ~1.2-1.4. It is stronger where it is more distant from the cluster center, as expected for a shock driven by expanding radio lobes. Simple modeling gives an age for the shock front of ~1.4 × 108 yr and a total energy driving it of ~1061 ergs. The mean mechanical power driving the shock is comparable to quasar luminosities, well in excess of that needed to regulate the cooling core in Hydra A. This suggests that the feedback regulating cooling cores is inefficient, in that the bulk of the energy is deposited beyond the cooling core. In that case, a significant part of cluster "preheating" is a by-product of the regulation of cooling cores.
Defect clustering-aware spare-TSV allocation for 3D ICs

The manufacturing yield challenge of three-dimensional integrated circuit (3D ICs) is one of the key obstacles in the industry adoption of 3D integration based on through-silicon-vias (TSVs). The addition of spare TSVs to repair faulty functional TSVs is an effective method for yield and reliability enhancement, but this approach results in significant hardware cost and delay overhead. Most existing solutions are only suitable for a “dual-uniform” scenario in which both the placement and the defect probabilities of functional TSVs are assumed to be uniform. In this paper, we propose a design technique that is compatible with non-uniform TSV placement and it can repair faulty TSVs based on a realistic clustered defect-distribution model. The proposed solution is based on two consecutive stages, which utilize a greedy algorithm and an integer-linear-programming formulation, respectively. By considering the trade-off between chip yield, hardware cost, and delay overhead, the proposed technique provides higher yield and reliability under a clustered defect distribution, and with minimum hardware cost and delay overhead, compared to the previous work.
The behavior of subluminous X-ray transients near the Galactic center as observed using the X-ray telescope aboard Swift

In this paper we report on the spectral analysis of seven X-ray transients, which were found to be active during a monitoring campaign of the Galactic center carried out in 2006 and 2007 using the X-ray telescope aboard the Swift satellite. This campaign detected new outbursts of five known X-ray transients and discovered two new systems. Their 2-10 keV peak luminosities range from similar to 10(34) to 6 x 10(36) erg s(-1), which implies that all seven X-ray transients are subluminous compared to the bright X-ray transients that have peak luminosities of 10(37-39) erg s(-1). Two of the sources discussed in this paper are confirmed neutron star systems (AX J1745.6-2901 and GRS 1741-2853), while the five others have an unknown nature. We discuss the characteristics of the observed outbursts and the duty cycles of the various systems. Several of the detected transients seem to undergo enhanced X-ray activity with levels intermediate between quiescence and full outburst. We discuss the possibility that the subluminous appearance of the eclipsing X-ray burster AX J1745.6-2901 is due to line-of-sight effects. We detected two type-I X-ray bursts with a duration of 50-60 s from AX J1745.6-2901, which we discuss in view of the bursting behavior of low-luminosity X-ray transients. Assuming that we are dealing with accreting neutron stars and black holes, we estimate the time-average accretion rate, , of the transients, which is an important input parameter for binary evolution models that attempt to explain the nature of subluminous X-ray transients. Our estimates lie in the range of 3 x 10(-13) M-circle dot yr(-1) less than or similar to less than or similar to 1 x 10(-10) M-circle dot yr(-1), if the systems are neutron star X-ray binaries and between 4 x 10(-14) M-circle dot yr(-1) less than or similar to less than or similar to 2 x 10(-11) M-circle dot yr(-1) for a scenario where the accreting object is a black hole. Some of the systems have such low estimated mass-accretion rates that they possibly pose a challenge for binary evolution models.