Miracle-dz/UniFAR-FTUs huggingface dataset:
Human BAT Possesses Molecular Signatures That Resemble Beige/Brite Cells

Brown adipose tissue (BAT) dissipates chemical energy and generates heat to protect animals from cold and obesity. Rodents possess two types of UCP-1 positive brown adipocytes arising from distinct developmental lineages: “classical” brown adipocytes develop during the prenatal stage whereas “beige” or “brite” cells that reside in white adipose tissue (WAT) develop during the postnatal stage in response to chronic cold or PPARγ agonists. Beige cells’ inducible characteristics make them a promising therapeutic target for obesity treatment, however, the relevance of this cell type in humans remains unknown. In the present study, we determined the gene signatures that were unique to classical brown adipocytes and to beige cells induced by a specific PPARγ agonist rosiglitazone in mice. Subsequently we applied the transcriptional data to humans and examined the molecular signatures of human BAT isolated from multiple adipose depots. To our surprise, nearly all the human BAT abundantly expressed beige cell-selective genes, but the expression of classical brown fat-selective genes were nearly undetectable. Interestingly, expression of known brown fat-selective genes such as PRDM16 was strongly correlated with that of the newly identified beige cell-selective genes, but not with that of classical brown fat-selective genes. Furthermore, histological analyses showed that a new beige cell marker, CITED1, was selectively expressed in the UCP1-positive beige cells as well as in human BAT. These data indicate that human BAT may be primary composed of beige/brite cells.
Presynaptic calcium channels in rat cortical synaptosomes: fast- kinetics of phasic calcium influx, channel inactivation, and relationship to nitrendipine receptors

Fast-mixing and rapid-filtration techniques were used to analyze the kinetics of potassium-depolarization-dependent (delta K+ = 47.5 mM) influx of 45Ca into synaptosomes, in the time range from 50 msec to 5 sec. The results are consistent with the presence in synaptosomes of a homogeneous population of voltage-sensitive Ca channels. With 1 mM Cao in the medium, the delta K+-dependent Ca influx has a single- exponential time course with the half-life, t1/2 approximately 0.5–0.7 sec. Ca influx, measured between 0.1 and 10 mM Cao, shows half- saturation (KCa) at 1.5 mM Cao and has the limiting value (JCamax) of 5.9 nmol/sec/mg protein, or a current of approximately 0.06 pA/micron2 surface area. The estimated density of functional Ca channels is 0.6–6 micron-2. Voltage- and time-dependent inactivation of Ca channels was measured in synaptosomes predepolarized in 52.5 mM Ko+ with Ca omitted from the medium. Channel inactivation is a single-exponential process with a half-life of t1/2 approximately 2.3 sec. Channel recovery in 5 mM Ko+ media is likewise a single-exponential process with a half-life of t1/2 approximately 4.3 sec. The slower rate of voltage-dependent channel inactivation than of decay of Ca influx suggests that Ca entry into synaptosomes terminates by a mechanism that depends on Ca influx itself. Synaptosomes contain 200 fmol/mg protein, or approximately 6 micron-2 high-affinity (KD = 0.12 nM) 3H-nitrendipine binding sites; however, nitrendipine at concentrations greater than 10(4) X KD is without effect on the phasic influx of Ca measured at 215 msec with either 1.0 or 0.1 mM Cao. This suggests that Ca channels characterized in this study belong to a class of dihydropyridine-insensitive channels.
The macroscopic delamination of thin films from elastic substrates

The wrinkling and delamination of stiff thin films adhered to a polymer substrate have important applications in “flexible electronics. ” The resulting periodic structures, when used for circuitry, have remarkable mechanical properties because stretching or twisting of the substrate is mostly accommodated through bending of the film, which minimizes fatigue or fracture. To date, applications in this context have used substrate patterning to create an anisotropic substrate-film adhesion energy, thereby producing a controlled array of delamination “blisters. ” However, even in the absence of such patterning, blisters appear spontaneously, with a characteristic size. Here, we perform well-controlled experiments at macroscopic scales to study what sets the dimensions of these blisters in terms of the material properties and explain our results by using a combination of scaling and analytical methods. Besides pointing to a method for determining the interfacial toughness, our analysis suggests a number of design guidelines for the thin films used in flexible electronic applications. Crucially, we show that, to avoid the possibility that delamination may cause fatigue damage, the thin film thickness must be greater than a critical value, which we determine.
TLR activation enhances C5a-induced pro-inflammatory responses by negatively modulating the second C5a receptor, C5L2

TLR and complement activation ensures efficient clearance of infection. Previous studies documented synergism between TLRs and the receptor for the pro‐inflammatory complement peptide C5a (C5aR/CD88), and regulation of TLR‐induced pro‐inflammatory responses by C5aR, suggesting crosstalk between TLRs and C5aR. However, it is unclear whether and how TLRs modulate C5a‐induced pro‐inflammatory responses. We demonstrate a marked positive modulatory effect of TLR activation on cell sensitivity to C5a in vitro and ex vivo and identify an underlying mechanistic target. Pre‐exposure of PBMCs and whole blood to diverse TLR ligands or bacteria enhanced C5a‐induced pro‐inflammatory responses. This effect was not observed in TLR4 signalling‐deficient mice. TLR‐induced hypersensitivity to C5a did not result from C5aR upregulation or modulation of C5a‐induced Ca2+ mobilization. Rather, TLRs targeted another C5a receptor, C5L2 (acting as a negative modulator of C5aR), by reducing C5L2 activity. TLR‐induced hypersensitivity to C5a was mimicked by blocking C5L2 and was not observed in C5L2KO mice. Furthermore, TLR activation inhibited C5L2 expression upon C5a stimulation. These findings identify a novel pathway of crosstalk within the innate immune system that amplifies innate host defense at the TLR‐complement interface. Unravelling the mutually regulated activities of TLRs and complement may reveal new therapeutic avenues to control inflammation.
SERVICE CLIMATE EFFECfS ON CUSTOMER A".-rr."UDES: AN EXAMINA nON OF BOUNDARY CONDmONS

PCT No. PCT/JP96/03631 Sec. 371 Date Jun. 12, 1998 Sec. 102(e) Date Jun. 12, 1998 PCT Filed Dec. 12, 1996 PCT Pub. No. WO97/21426 PCT Pub. Date Jun. 19, 1997An aerosol preparation which when sprayed forms a sherbet-like solid, which comprises a concentrate containing a lower alcohol having 1 to 3 carbon atoms and a higher alcohol having at least 12 carbon atoms and a propellant containing a liquefied gas. Said aerosol preparation does not require any complicated emulsifying procedure for the production, can contain components labile in water and have a durable cooling effect, and therefore, it is quickly calmative on the pain caused by contusion, sprain, muscular fatigue, etc. and the itch caused by athlete's foot, insect bite, etc.
Dynamics of the SPRY domain–containing SOCS box protein 2: Flexibility of key functional loops

The SPRY domain was identified originally as a sequence repeat in the dual‐specificity kinase splA and ryanodine receptors and subsequently found in many other distinct proteins, including more than 70 encoded in the human genome. It is a subdomain of the B30.2/SPRY domain and is believed to function as a protein–protein interaction module. Three‐dimensional structures of several B30.2/SPRY domain–containing proteins have been reported recently: murine SSB‐2 in solution by NMR spectroscopy, a Drosophila SSB (GUSTAVUS), and human PRYSPRY protein by X‐ray crystallography. The three structures share a core of two antiparallel β‐sheets for the B30.2/SPRY domain but show differences located mainly at one end of the β‐sandwich. Analysis of SSB‐2 residues required for interactions with its intracellular ligands has provided insights into B30.2/SPRY binding specificity and identified loop residues critical for the function of this domain. We have investigated the backbone dynamics of SSB‐2 by means of Modelfree analysis of its backbone 15N relaxation parameters and carried out coarse‐grained dynamics simulation of B30.2/SPRY domain–containing proteins using normal mode analysis. Translational self‐diffusion coefficients of SSB‐2 measured using pulsed field gradient NMR were used to confirm the monomeric state of SSB‐2 in solution. These results, together with previously reported amide exchange data, highlight the underlying flexibility of the loop regions of B30.2/SPRY domain–containing proteins that have been shown to be important for protein–protein interactions. The underlying flexibility of certain regions of the B30.2/SPRY domain–containing proteins may also contribute to some apparent structural differences observed between GUSTAVUS or PRYSPRY and SSB‐2.
Downregulation of Transient Receptor Potential Melastatin 8 by Protein Kinase C-Mediated Dephosphorylation

Transient receptor potential melastatin 8 (TRPM8) and transient receptor potential vanilloid 1 (TRPV1) are ion channels that detect cold and hot sensations, respectively. Their activation depolarizes the peripheral nerve terminals resulting in action potentials that propagate to brain via the spinal cord. These receptors also play a significant role in synaptic transmission between dorsal root ganglion (DRG) and dorsal horn (DH) neurons. Here, we show that TRPM8 is functionally downregulated by activation of protein kinase C (PKC) resulting in inhibition of membrane currents and increases in intracellular Ca2+ compared with upregulation of TRPV1 in cloned and native receptors. Bradykinin significantly downregulates TRPM8 via activation of PKC in DRG neurons. Activation of TRPM8 or TRPV1 at first sensory synapse between DRG and DH neurons leads to a robust increase in frequency of spontaneous/miniature EPSCs. PKC activation blunts TRPM8- and facilitates TRPV1-mediated synaptic transmission. Significantly, downregulation is attributable to PKC-mediated dephosphorylation of TRPM8 that could be reversed by phosphatase inhibitors. These findings suggest that inflammatory thermal hyperalgesia mediated by TRPV1 may be further aggravated by downregulation of TRPM8, because the latter could mediate the much needed cool/soothing sensation.
Measuring Information Technology Payoff: A Meta - Analysis of Structural Variables in Firm - Level Empirical Research

Payoffs from information technology (IT) continue to generate interest and debate both among academicians and practitioners. The extant literature cites inadequate sample size, lack of process orientation, and analysis methods among the reasons some studies have shown mixed results in establishing a relationship between IT investment and firm performance.In this paper we examine the structural variables that affect IT payoff through a meta analysis of 66 firm-level empirical studies between 1990 and 2000. Employing logistic regression and discriminant analyses, we present statistical evidence of the characteristics that discriminate between IT payoff studies that observed a positive effect and those that did not. In addition, we conduct ordinary least squares (OLS) regression on a continuous measure of IT payoff to examine the influence of structural variables on the result of IT payoff studies.The results indicate that the sample size, data source (firm-level or secondary), and industry in which the study is conducted influence the likelihood of the study finding greater improvements on firm performance. The choice of the dependent variable(s) also appears to influence the outcome (although we did not find support for process-oriented measurement), the type of statistical analysis conducted, and whether the study adopted a cross-sectional or longitudinal design. Finally, we present implications of the findings and recommendations for future research.
Economic Emission Load Dispatch by Modified Shuffled Frog Leaping Algorithm

This paper presents a newly developed optimization approach involving a modified shuffled frog leaping algorithm (MSFLA) applied for the solution of the economic emission load dispatch (EELD) problem. The approach utilizes the local search strategies for searching global solution. MSFLA is developed on the same frame work of shuffled frog leaping algorithm (SFLA). In this proposed algorithm, a search-acceleration parameter is introduced. To obtain the best compromising solution a pareto– optimal decision making approach is applied to a standard IEEE 30-bus six generator test system. The results confirm the potential and effectiveness of the proposed algorithm compared to various methods performed. The quality and usefulness of the proposed algorithm are demonstrated through its application to a standard test system in comparison with the other existing techniques. The current proposal was found to be better than, or at least comparable to them considering the quality of the solutions obtained. The MSFLA algorithm appears to be a robust and reliable optimization algorithm for the solution of the power system problems.
A HERO'S LITTLE HORSE: DISCOVERY OF A DISSOLVING STAR CLUSTER IN PEGASUS

We report the discovery of an ultra-faint stellar system in the constellation of Pegasus. This concentration of stars was detected by applying our overdensity detection algorithm to the Sloan Digital Sky Survey Data Release 10 and confirmed with deeper photometry from the Dark Energy Camera (DECam) at the 4 m Blanco telescope. The best-fitting model isochrone indicates that this stellar system, Kim 1, features an old (12 Gyr) and metal-poor ([Fe/H] ∼ -1.7) stellar population at a heliocentric distance of 19.8 ± 0.9 kpc. We measure a half-light radius of 6.9 ± 0.6 pc using a Plummer profile. The small physical size and the extremely low luminosity are comparable to the faintest known star clusters Segue 3, Koposov 1 and 2, and Muñoz 1. However, Kim 1 exhibits a lower star concentration and is lacking a well-defined center. It also has an unusually high ellipticity and irregular outer isophotes, which suggests that we are seeing an intermediate mass star cluster being stripped by the Galactic tidal field. An extended search for evidence of an associated stellar stream within the 3 DECam field remains inconclusive. The finding of Kim 1 is consistent with current overdensity detection limits and supports the hypothesis that there are still a substantial number of extreme low-luminosity star clusters undetected in the wider Milky Way halo.
Immune history profoundly affects broadly protective B cell responses to influenza

The quality of the B cell response to influenza vaccination is dependent on the preexisting memory B cell repertoire. Stalking a flu vaccine A universal flu vaccine has been a Sisyphean trial—despite successful seasonal vaccines, the immune system has to start over with newly mutated influenza strains. Now, Andrews et al. look in depth at the B cell response to the pandemic 2009 H1N1 vaccine over time. They found that people with low titers of preexisting antibodies were more likely to generate a broadly reactive response that targets the more conserved hemagglutinin (HA) stalk region, whereas those with higher levels of preexisting antibodies responded by targeting the more variable HA head. The preexisting head antibodies were immunodominant and prevented clear access to the stalk. These data suggest that exposure history is critical in designing a universal flu vaccine. Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years. Analysis of monoclonal antibodies generated from vaccine-induced plasmablasts demonstrated that individuals with low preexisting serological titers to the vaccinating strain generated a broadly reactive, hemagglutinin (HA) stalk–biased response. Higher preexisting serum antibody levels correlated with a strain-specific HA head–dominated response. We demonstrate that this HA head immunodominance encompasses poor accessibility of the HA stalk epitopes. Further, we show polyreactivity of HA stalk–reactive antibodies that could cause counterselection of these cells. Thus, preexisting memory B cells against HA head epitopes predominate, inhibiting a broadly protective response against the HA stalk upon revaccination with similar strains. Consideration of influenza exposure history is critical for new vaccine strategies designed to elicit broadly neutralizing antibodies.
A frequency-based hypothesis for mechanically targeting and selectively attacking cancer cells

Experimental studies recently performed on single cancer and healthy cells have demonstrated that the former are about 70% softer than the latter, regardless of the cell lines and the measurement technique used for determining the mechanical properties. At least in principle, the difference in cell stiffness might thus be exploited to create mechanical-based targeting strategies for discriminating neoplastic transformations within human cell populations and for designing innovative complementary tools to cell-specific molecular tumour markers, leading to possible applications in the diagnosis and treatment of cancer diseases. With the aim of characterizing and gaining insight into the overall frequency response of single-cell systems to mechanical stimuli (typically low-intensity therapeutic ultrasound), a generalized viscoelastic paradigm, combining classical and spring-pot-based models, is introduced for modelling this problem by neglecting the cascade of mechanobiological events involving the cell nucleus, cytoskeleton, elastic membrane and cytosol. Theoretical results show that differences in stiffness, experimentally observed ex vivo and in vitro, allow healthy and cancer cells to be discriminated, by highlighting frequencies (from tens to hundreds of kilohertz) associated with resonance-like phenomena—prevailing on thermal fluctuations—that could be helpful in targeting and selectively attacking tumour cells.
Phylogeny of the Oniticellini and Onthophagini dung beetles (Scarabaeidae, Scarabaeinae) from morphological evidence

Abstract A phylogenetic study was conducted to hypothesize relationships of most of the genera of the Oniticellini and Onthophagini for the first time using morphological characters from a diverse array of external and internal sclerites. The monophyly and sister relationship of both tribes was found using Bayesian and parsimony analyses with heavily to moderately weighted data. An alternative hypothesis based on parsimony analyses of unweighted or slightly weighted data show a paraphyletic Oniticellini without the Onthophagini, although recognition of the subtribe Helictopleurina as a tribe would eliminate non-monophyly. Of the three Oniticellini subtribes, the Helictopleurina and Drepanocerina are monophyletic. There is no support for the monophyly of the Oniticellina or the Onthophagini subtribe Alloscelina, as currently defined. The genus Liatongus is paraphyletic, while strong support was found for monophyly of the Madagascan genus, Helictopleurus. The genus Onthophagus is never monophyletic in any analysis performed. Two new subtribes are also proposed: Liatongina subtr. n. including the genus Liatongus and Attavicina subtr. n. including the genera Attavicinus and Paroniticellus. Topological evidence shows that the ancestral oniticellines and onthophagines were all coprophagous with alternative food sources evolving relatively recently. Both myrmecophily and termitophily probably evolved only once in the onthophagines. The phylogenetic analysis supports an African origin for the two tribes, with a relatively early age for the split of the Madagascar helictopleurines from the remaining oniticellines via dispersal. Furthermore, the presence of the oniticellines in the New World is hypothesized to be due to two relatively old dispersal events via Beringia and two relatively recent trans-Atlantic invasions of the Caribbean.
Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory

476 NATURE | VOL 411 | 24 MAY 2001 | www.nature. com about the test grating (48 c.p.d.) on the frequency scale. The contrast of the 36 c.p.d. adapting grating was set to half of its threshold contrast, 3.5%. No measurable tilt after-effect was found under this condition (Fig. 2b). Similarly, in measurements of the elevation in contrast threshold produced by pre-exposure to a range of adapting grating contrasts, at three spatial frequencies spanning the resolution limit, we found that adapting gratings of frequency greater than the resolution limit were more effective than correspondingly subthreshold gratings of lower frequency (although subthreshold gratings in the high but resolvable frequency range were not entirely ineffective). Thus, the cortical requirement for conscious perception seems to depend on spatial frequency, and not only on contrast or signal strength represented at the cortical input. The idea that limits on visual resolution are partly imposed at the cortical level is supported by evidence that cortically projecting thalamic relay neurons in macaque often respond well to spatial frequencies far above the human resolution limit, in some cases exceeding 100 c.p.d. (ref. 15). If the projection from thalamus to cortex were as precise as the one from retina to thalamus, this would allow the visual system to form a representation of unresolvable patterns at the cortical site of pattern adaptation. The lower spatialfrequency limits for cortical after-effects (70 c.p.d.), as compared with thalamic neurons (100 c.p.d.), may re ̄ect imperfect precision in the projection from thalamus to cortex. In normal vision with incoherent light, diffraction markedly reduces the retinal image contrast for spatial frequencies near the resolution limit. Why should the cortex have orientation-selective mechanisms (or frequency-selective ones) that respond to high spatial frequencies that are normally only faintly represented in the retinal image? One answer derives from the view that neural mechanisms might compensate for optical blur: frequency components that have been optically attenuated might even require a reciprocal enhancement of neural sensitivity for their appropriate representation. But on our evidence, activation of orientation-selective units at the stage of cortical pattern adaptation is not suf®cient for perceptual awareness of the pattern orientation. The nature of the added requirement is not clear: one possibility is that information must be relayed from primary visual cortex to another region of the brain to be represented in conscious experience. M
Performance of an ultra-wideband communication system in the presence of narrowband BPSK- and QPSK-modulated OFDM interference

An analysis is derived for calculating the bit-error probability of an ultra-wideband (UWB) communication system operating with binary phase-shift keying and quaternary phase-shift keying narrowband interference in additive white Gaussian noise. The analytical expressions are valid when phase transitions of the interfering symbols can be ignored. The accuracy of the Gaussian approximation is assessed, and several modulation schemes proposed for UWB communication are evaluated in terms of capability of interference suppression