Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia

Objective To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Methods and Design Insulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20–22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion. Results Intact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion. Conclusions Exposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets, highlighting adaptive capacities of possible importance in an islet transplantation setting. Results also indicate idiosyncrasies of β-cells that do not respire in response to a standard inclusion of malate in SUIT protocols.
The Explanatory Power of the General Theory of Crime: A Comparative Analysis of a General Population and Serious Offender Sample

Abstract The purpose of this study was to investigate—via direct comparison—the fundamental supposition that the general theory of crime should be valid for both criminal and analogous behavior in both an offender and a general population sample. The core constructs of the theory, namely the influence of parenting style on self-control and the relationship with different manifestations of deviance, were analyzed by comparing a sample of incarcerated sexual and violent offenders with a general population sample. The validity of the general theory could only be confirmed for the offender population.
Searches for periodic gravitational waves from unknown isolated sources and Scorpius X-1: Results from the second LIGO science run

We carry out two searches for periodic gravitational waves using the most sensitive few hours of data from the second LIGO science run. The first search is targeted at isolated, previously unknown neutron stars and covers the entire sky in the frequency band 160-728.8 Hz. The second search targets the accreting neutron star in the low-mass X-ray binary Scorpius X-1, covers the frequency bands 464-484 Hz and 604-624 Hz, and two binary orbit parameters. Both searches look for coincidences between the Livingston and Hanford 4-km interferometers. For isolated neutron stars our 95% confidence upper limits on the gravitational wave strain amplitude range from 6.6E-23 to 1E-21 across the frequency band; For Scorpius X-1 they range from 1.7E-22 to 1.3E-21 across the two 20-Hz frequency bands. The upper limits presented in this paper are the first broad-band wide parameter space upper limits on periodic gravitational waves using coherent search techniques. The methods developed here lay the foundations for upcoming hierarchical searches of more sensitive data which may detect astrophysical signals.
Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells

Abstract Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO2 and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6–8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn+ ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.
Making Sense of Software Development and Personality Types

It's common sense to state that the production of any software product involves a human element, at least to some extent. We all have different personality traits, and the way we perceive, plan, and execute any activity is influenced by these characteristics. Typically, software development is a product of teamwork, involving several people performing various tasks. The success and failure of software projects reveal the human factor as one of vital importance. Not everyone can excel at every task, thus better results are achieved if people with particular personality traits are assigned to different aspects of a project, especially the roles best suited to their ability. The authors mapped some opposing psychological traits, such as extroversion-introversion, sensing-intuition, thinking-feeling, and judging-perceiving, to the main stages of a software development life cycle. Consequently, they concluded that assigning a person with specific psychological characteristics to the stage of the software life cycle best suited for his or her traits increases the chances of a successful outcome for the project.
On the Validation of Lifestyle Traits: A Review and Illustration

How valid are lifestyle trait concepts and measures? A literature review shows little published evidence to suggest lifestyle trait researchers have rigorously tested the validity of their concepts and measures. An illustrative validation study demonstrates how trait validation efforts can improve. The validation study carefully scrutinizes three previously proposed lifestyle traits and provides only partial support for the validity of two of the three traits evaluated.
Bovine placentome development during early pregnancy

M. B. Aires, K. Y. Degaki, V. Dantzer and A. T. Yamada 1 Department of Morphology, Federal University of Sergipe, Sao Cristovao 49100-000, SE, Brazil 2 Laboratory of Development and Reproductive Biology, Institute of Biology, PO Box 6109, University of Campinas, Campinas 13083-970, SP, Brazil 3 Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Copenhagen University, Dyrlaegevej 16, 1870 Frederiksberg C, Copenhagen, Denmark
Open inflation without anthropic principle

We propose the mechanism of quantum creation of the open Universe in the observable range of values of $\Omega$. This mechanism is based on the no-boundary quantum state with the Hawking-Turok instanton in the model with nonminimally coupled inflaton field and does not use any anthropic considerations. Rather, the probability distribution peak with necessary parameters of the inflation stage is generated on this instanton due to quantum loop effects. In contrast with a similar mechanism for closed models, existing only for the tunneling quantum state of the Universe, open inflation originates from the no-boundary cosmological wavefunction.
Terrestrial Localization by Using Angle of Arrival Measurements in Wireless Sensor Network

Localisation in wireless sensor network is the process of determining the geographical location of the sensor nodes. Conventional localization is space oriented which uses GPS (Global Positioning System) signal to obtain the location information of the nodes. But the GPS signals fail to work in indoor environments, the reason for which it becomes mandatory to opt for terrestrial localisation. The proposed indoor-terrestrial localisation work aims at designing localisation service through WSN where sensor nodes are mobile and form cluster. As most of the wireless sensor applications, essentially requires reliable information of the physical location of the sensor nodes, the work aims to provide localisation using the Angle of arrival (AoA) for angular estimation. The use of triangulation method for the position calculation and the Root Minimum Mean Square Error analysis (RMMSE) of the actual position in contrast to the calculated position further assists the sensor nodes to achieve reliable location information.
Pheromone detection by mammalian vomeronasal neurons

The vomeronasal organ (VNO) of mammals plays an essential role in the perception of chemical stimuli of social nature including pheromone‐like signals but direct evidence for the transduction of pheromones by vomeronasal sensory neurons has been lacking. The recent development of electrophysiological and optical imaging methods using confocal microscopy has enabled researchers to systematically analyze sensory responses in large populations of mouse vomeronasal neurons. These experiments revealed that vomeronasal neurons are surprisingly sensitive and highly discriminative detectors of volatile, urinary metabolites that have pheromonal activity in recipient mice. Functional mapping studies of pheromone receptor activation have uncovered the basic principles of sensory processing by vomeronasal neurons and revealed striking differences in the neural mechanisms by which chemosensory information is detected by receptor neurons in the VNO and the main olfactory epithelium. These advances offer the opportunity to decipher the logic of mammalian pheromonal communication. Microsc. Res. Tech. 58:251–260, 2002. © 2002 Wiley‐Liss, Inc.
Carlos Chávez’s Polysemic Style:: Constructing the National, Seeking the Cosmopolitan

The critical discourse on Carlos Chavez’s music is full of contradictions regarding the presence within it of signifiers of the Mexican, the pre-Columbian, and the indigenous. Between 1918 and 1928 Chavez in fact developed, from stylistic preferences that appeared early in his compositions, a polysemic language that he could use equally well to address the very modern or the primitive, the pre-Columbian or the contemporary mestizo , in and only in those works in which he chose to do so. Chavez’s referents emerged in dialogue with the cultural and political contexts in which he worked, those of post-revolutionary Mexico and modern New York. But he was attracted above all to modernism and modernity, and was impacted by cosmopolitan forces at home and abroad. By the end of the decade he had earned a position within the modern musical field’s network of social relations, and had drawn the attention of agents of recognition such as Edgard Varese, Paul Rosenfeld, Aaron Copland, and Henry Cowell. These composers and critics added Chavez’s constructed difference to their much-sought collective difference as Americans within a European art. Chavez’s own use of explicit Mexican referents in some of his works shaped the early reception of his music as quintessentially American/Mexican, eventually influencing the way we understand it today.
T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses

Cell-mediated adaptive immunity is very important in tumor immune surveillance and tumor vaccination. However, the genetic program underlying an effective adaptive antitumor immunity is elusive. T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8+ T cells. However, whether they are important for T cell-mediated antitumor immunity is controversial. In this paper, we show that the combined germline deletion of T-bet and T cell-specific deletion of Eomes resulted in profound defects in adaptive antitumor immune responses. T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8+ T cell differentiation to Tc17 or Tc2 cells. Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells. Instead, T-bet and Eomes are crucial for tumor infiltration by CD8+ T cells. This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
Sensor Network with Multiple Mobile Access Points

We consider sensor networks with mobile access points where data at sensor nodes are collected by multiple mobile access points. Using throughput and energy efficiency as performance measures, we address the optimal coverage areas of and the cooperation among the mobile access points. We show that when the mobile access points do not cooperate in demodulation, disjoint coverage areas are optimal for throughput while completely overlapped coverage areas are optimal for energy efficiency. When the mobile access points decode their received packets jointly, the optimal configuration appears to have a phase transition. Specifically, in order to maximize throughput, the coverage areas of the mobile access points should be completely overlapped when SNR is smaller than a threshold and disjoint otherwise. Length: Regular Paper.
Chronic lymphocytic leukemia (CLL)—Then and now

The field of chronic lymphocytic leukemia (CLL) has witnessed considerable change since the time clinical staging was introduced in clinical practice in 1975. Over the years, the prognostication in CLL has expanded with the addition in late 90s of mutational status of variable region of immunoglobulin heavy chain (IGHV), and chromosomal analyses using fluorescent in situ hybridization (FISH). More recently, stereotypy of BCR (B cell receptor) and whole exome sequencing (WES) based discovery of specific mutations such as NOTCH1, TP53, SF3B1, XPO‐1, BIRC3, ATM, and RPS15 further refined the current prognostication system in CLL. In therapy, the field of CLL has seen major changes from oral chlorambucil and steroids prior to 1980s, to chemo‐immunotherapy (CIT) with fludarabine, cyclophosphamide, rituximab (FCR) to the orally administered targeted therapeutic agents inhibiting kinases in the B cell receptor (BCR) signaling pathway such as Ibrutinib (BTK inhibitor) and Idelalisib (p110 PI3Kδ inhibitor) and novel anti‐CD20 mAb's (monoclonal antibodies) such as obinutuzumab. This progress is continuing and other targeted therapeutics such as Bcl2 antagonists (Venetoclax or ABT‐199) and finally chimeric antigen receptor against T cells (CART) are in the process of being developed. This review is an attempt to summarize the major benchmarks in the prognostication and in the therapy of CLL. The topic allocated to us by Dr Ayalew Tefferi and Dr Carlo Brugnara is very appropriate to reminisce what our understanding of chronic lymphocytic leukemia (CLL) was in 1976 and how rapidly have the advances occurring in this field affected the patients with CLL. Am. J. Hematol. 91:330–340, 2016. © 2015 Wiley Periodicals, Inc.
Monitoring the Antitumor Response of Naive and Memory CD8 T Cells in RAG1−/− Mice by Positron-Emission Tomography1

Therapeutic antitumor immunity depends on a highly migratory CTL population capable of activation and trafficking between lymphoid and tumor-bearing microanatomic sites. We recently adapted positron-emission tomography gene expression imaging for noninvasive, longitudinal localization and quantitation of antitumor T lymphocyte migration in vivo. In this study, we apply this system to enumerate the temporal accumulation of naive vs memory T cells. Naive or memory OT-1 CD8+ T cells, retrovirally marked with the sr39TK gene, were adoptively transferred into RAG1−/− animals bearing EL-4 or EG.7 (an OVA-expressing subline), and repetitively imaged by microPET over several weeks. Memory cells demonstrated early accumulation and apparent proliferation, with large T cell numbers at the Ag-positive tumor as early as day 1 after T cell transfer. Naive T cells did not accumulate in the E.G7 tumor until day 8, and reached only 25% of the peak levels achieved by memory T cells. Both naive and memory cells eradicated the Ag-expressing tumor at a comparable density of intratumoral T cells (2–4 × 106/g). However, due to the slower rate of T cell expansion and continued tumor growth, naive cells required ∼10-fold higher Ag-specific precursor frequency to reach a tumoricidal cell density. As recently reported, memory but not naive T cells accumulated in local lymph nodes and lungs, where they persisted as a resident population after tumor eradication. Positron-emission tomography-based immunologic imaging is a noninvasive modality providing unique and meaningful information on the dynamics of the antitumor CTL response.
Health trends from an international sample of older adults with intellectual and developmental disabilities

Abstract Background: The aim of this study was to compare the health status data of 4449 adults with intellectual disabilities (ID) aged 40 years and older, from three international sites and identify cross-cultural trends in the prevalence of age-associated organ system morbidities. Study group: Data from samples of older adults with ID in Taiwan, Israel and New York State, United States, collected in three previous studies, were combined for analysis using multivariate logistic regression analyses. Methods: All data were collected using the Rochester Health Status Survey (RHSS), a survey instrument designed to collect data on demographics, morbidity, and health services usage of adults with ID through chart-review by a medical professional. Results: Irrespective of site, the likelihood of the presence of auditory problems, gastrointestinal, cardiovascular, infectious disease, eye, musculoskeletal, and respiratory conditions in people with ID increased with age and the likelihood of the presence of dermatological, endocrine, and psychiatric conditions did not increase with age. Conclusions: Prevalence of organ system diseases with increasing age in people with ID seems to be similar to expected patterns in reference population data for people without ID. The data suggest that it could be useful to increase vigilance, preventive measures, and appropriate screenings for people with ID, similar to efforts that have been incorporated in general practice guidelines. Such efforts may be useful in the delay of onset and/or reduction of the prevalence of some morbidities and secondary disability-related conditions in people with ID. Further studies are needed in these areas.
Solving mixed-integer nonlinear programmes using adaptively refined mixed-integer linear programmes

ABSTRACT We propose a method for solving mixed-integer nonlinear programmes (MINLPs) to global optimality by discretization of occurring nonlinearities. The main idea is based on using piecewise linear functions to construct mixed-integer linear programme (MIP) relaxations of the underlying MINLP. In order to find a global optimum of the given MINLP, we develop an iterative algorithm which solves MIP relaxations that are adaptively refined. We are able to give convergence results for a wide range of MINLPs requiring only continuous nonlinearities with bounded domains and an oracle computing maxima of the nonlinearities on their domain. Moreover, the practicalness of our approach is shown numerically by an application from the field of gas network optimization.
Viscoelastic properties of human cortical bone tissue depend on gender and elastic modulus

Bone exhibits rate‐dependent failure behavior, suggesting that viscoelasticity is a factor in the damage and fracture of bone. Microdamage initiates at scales below the macroscopic porosity in bone, and, as such, is affected by the intrinsic viscoelasticity of the bone tissue. The viscoelasticity of the bone tissue can be measured by nanoindentation and recording the creep behavior at constant load. The viscoelastic properties have been used to assess differences in tissue behavior with respect to fracture healing, aging, and mouse strains. In this study, we compared the viscoelastic behavior of human cortical bone between genders by using nanoindentation at a fixed load of 10 mN to measure the creep time constant. Bones from females had a significantly greater time constant, indicating slower creep and relaxation, than bones from males. The creep time constants decreased with increasing tissue modulus. The mineralization, collagen content, and collagen cross‐link density, which were bulk measurements, were analyzed to determine if the differences in viscoelastic behavior were explained by compositional differences in the bone. However, none of the parameters differed between genders, nor were they correlated to the viscoelastic time constant. As such, the difference must depend on other matrix proteins that we did not assess or differences in the microstructural organization. This is one of the only intrinsic bone material properties that has been found to differ between males and females, and it may be important for assessing differences in fracture risk, since crack propagation is generally sensitive to viscoelastic properties. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:693–699, 2012
Limb malformations of rat fetuses exposed to a distal inhibitor of cholesterol biosynthesis DOI 10.1194/jlr.M200082-JLR200

Triparanol, an inhibitor of desmosterol Δ24 reductase, produces a high rate of limb malformations in rat fetuses exposed at gestational day 10 (gd 10) to a single oral dose (150–200 mg/kg) given to the pregnant dam. AY9944, another efficient distal inhibitor of cholesterol biosynthesis that blocks dehydrocholesterol Δ7 reductase, produces a similar degree of cholesterol depletion but fewer malformations. Gas liquid chromatography–mass spectrometry (GC-MS) profiling of the sterols in the serum of the dams and in extracted embryos shows that in addition to desmosterol Δ24 reductase inhibition the conversion of Δ8 to Δ7 unsaturated sterols is also blocked by Triparanol. Therefore, the inhibitor induces the accumulation of desmosterol (Δ8 cholesten-3β-ol, 8-dehydrocholesterol) and zymosterol (Δ8, Δ24 cholestadien-3β-ol) in embryo tissues. The high concentration of the teratogenic drug assayed in the embryos at three successive gestational days (10–30 μg/g) is thought to cause the blockade in both Δ24 reductase and Δ8-Δ7 isomerase, which results in the particular profile of aberrant sterols. Comparison of the animal model with human syndromes, including limb osseous and skeleton perturbations, suggests a combination of desmosterol and Δ8 unsaturated sterols as being involved in the deleterious influence on limb bone formation.