cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 117: Pharmacological targeting of activated PSC decreases resistance to gemcitabine and increases survival in murine PDA

Background: Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of cancer owing to its insensitivity to many chemotherapeutic drugs. Gemcitabine remains a cornerstone of PDA treatment despite suboptimal efficacy in clinics. One major mechanism by which PDA becomes resistant to gemcitabine is its conversion to inactive derivative, dFdU by upregulation of the enzyme, cytidine deaminase (Cda) in cancer cells. Activated pancreatic stellate cells (PSC) are the major source of IGF1 in the tumor microenvironment, which may be responsible for an increase in Cda expression in cancer cells. We previously reported a rationally designed protein, ProAgio that targets integrin αVβ3 at a novel site. Here we demonstrate that ProAgio specifically induces apoptosis of integrin αVβ3-expressing activated PSC and therefore circumvents gemcitabine resistance in murine PDA models. Objective: To test whether targeting activated PSC restores chemotherapeutic sensitivity in previously unresponsive PDA tumors in a murine model. Methods: To study the effect of ProAgio and gemcitabine combination in PDA, we used two murine PDA models: a) KP orthotopic mouse model where KPC cells were orthotopically injected into the pancreas and, b) LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model. Mice were treated with 20 doses of ProAgio (10mg/kg; i.p.) and 10 doses of gemcitabine twice weekly (50mg/kg; i.p.). IGF1 and Cda levels were analyzed by ELISA and immunohistochemistry. The intratumoral levels of the gemcitabine prodrug 2′,2′-difluorodeoxcytidine (dFdC) and the inactivated and activated metabolites (2′,2′-difluorodeoxyuridine (dFdU) and gemcitabine triphosphate (dFdCTP) respectively were determined by LCMS. Results: Our data in murine PDA models clearly demonstrate that pharmacological targeting of activated PSC by ProAgio can stabilize PDA, and when combined with gemcitabine significantly increased the survival benefit by 3-fold (p Citation Format: Ravi Chakra Turaga, Malvika Sharma, Falguni Mishra, Zhi-Ren Liu. Pharmacological targeting of activated PSC decreases resistance to gemcitabine and increases survival in murine PDA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 117.
Conclusion: Progress and Its Discontents

The final chapter looks at Yuval Harari’s 21 Lessons for the 21st Century to examine why liberal academic culture often rejects global progress and focuses on negative portrayals of the world. By using Freud’s fundamental concepts to analyze Harari’s work, I provide a model for psychoanalytic cultural criticism. The goal then of this work is to show that psychoanalysis is not only still relevant today, but in actuality, Freud’s theories and practices have never been more essential for understanding and changing ourselves and the world around us.
Allopregnanolone Reverses Bioenergetic Deficits in Female Triple Transgenic Alzheimer’s Mouse Model

Previously, we reported that the neurosteroid allopregnanolone (Allo) promoted neural stem cell regeneration, restored cognitive function, and reduced Alzheimer's Disease (AD) pathology in the triple transgenic Alzheimer's mouse model (3xTgAD). To investigate the underlying systems biology of Allo action in AD models in vivo, we assessed the regulation of Allo on the bioenergetic system of the brain. Outcomes of these analysis indicated that Allo significantly reversed deficits in mitochondrial respiration and biogenesis and key mitochondrial enzyme activity and reduced lipid peroxidation in the 3xTgAD mice in vivo. To explore the mechanisms by which Allo regulates the brain metabolism, we conducted targeted transcriptome analysis. These data further confirmed that Allo upregulated genes involved in glucose metabolism, mitochondrial bioenergetics, and signaling pathways while simultaneously downregulating genes involved in Alzheimer's pathology, fatty acid metabolism, and mitochondrial uncoupling and dynamics. Upstream regulatory pathway analysis predicted that Allo induced peroxisome proliferator-activated receptor gamma (PPARG) and coactivator 1-alpha (PPARGC1A) pathways while simultaneously inhibiting the presenilin 1 (PSEN 1), phosphatase and tensin homolog (PTEN), and tumor necrosis factor (TNF) pathways to reduce AD pathology. Collectively, these data indicate that Allo functions as a systems biology regulator of bioenergetics, cholesterol homeostasis, and β-amyloid reduction in the brain. These systems are critical to neurological health, thus providing a plausible mechanistic rationale for Allo as a therapeutic to promote neural cell function and reduce the burden of AD pathology.
Exploiting Time Asynchrony in Multi-User Transmit Beamforming

In this paper, we analyze the benefits of intentionally adding timing mismatch in the downlink transmit beamforming for wireless transmission. Transmit beamforming enables the so-called space-division multiple access (SDMA), where multiple spatially separated users are served simultaneously. The optimal beamforming vectors can be found to minimize the average transmit power under each user’s Quality-of-Service (QoS) constraint. We show that intentionally adding timing offsets between the transmitted signals can significantly reduce the average transmission power compared with the conventional optimal beamforming method while providing the same QoSs for users. The frequency-selectivity in communication channels provides the opportunity to exploit intelligent design for performance improvement. The frequency-selectivity is limited in environments with line-of-sight links or little scattering. In such environments, we propose the use of intentional time delays to induce frequency-selectivity that can be exploited. We provide three different methods exploiting the artificially induced frequency-selectivity which improve the performance with a computational complexity similar to that of the optimal synchronous beamforming. We derive the expressions for the achievable rates using the proposed methods and then provide efficient algorithms to solve the minimum power optimization. We show analytically and numerically that our proposed methods can provide the same QoS while serving more users, utilizing a fewer number of transmit antennas and using reduced power compared with the conventional beamforming methods.
Comparative Minimum Inhibitory Concentrations of Danofloxacin and Six Commonly Used Antibacterials Against Pasteurella and Haempophilus From Pneumonic Cattle

Fluoroquinolone antimicrobials exhibit inhibitory and bactericidal activity by blocking DNA gyrase (topoisomerase II), an essential bacterial enzyme.1 These compounds possess excellent antimicrobial activity against bacterial and mycoplasmal pathogens, however few in-vitro studies have been conducted to evaluate the activity of fluoroquinolone antimicrobials against respiratory pathogens of veterinary significance2,3,4 This report summarizes the results of an extensive survey to determine Minimum Inhibitory Concentrations (MIC) of danofloxacin*, a new fluoroquinolone antimicrobial, and six commonly used antibacterials against P. haemolytica, P. multocida, and H.somnus isolated from pneumonic cattle.
A predictive model for electrostatic energy harvesters with impact-based frequency up-conversion

This paper reports a predictive model for vibration-to-electrical energy harvesters (e-VEHs) based on an in-plane, gap-closing variable capacitor with frequency up-conversion triggered by the impact between the electrodes. Since the output power is proportional to the output frequency, rectifying low-frequency ambient vibrations (1-50 Hz) to high-frequency electrical signals (200-600 Hz) increases the power output. While such device has been previously reported experimentally, this is the first time to describe a model able to predict the experimental data. The model is based on lumped approximation. The central area supporting the mobile electrodes, or the shuttle mass, is represented by a point mass suspended by springs and has its own equation of motion. The motion of the electrodes attached to the shuttle is described by a set of two equations, each associated with a distinct dynamic mode. In these equations, the electrodes are represented by an equivalent mass and spring constant. The first equation describes the separate motion of mobile and fixed electrodes. In this mode, the electrodes experience damped free vibration due to the electrostatic and air damping between them. The second equation describes the combined motion when the two sets of electrodes move together. In this mode, the air damping forces between the collided electrodes are eliminated and the electrostatic force is kept constant. The motion equations are solved simultaneously with Kirchhoff's law to compute the voltage drop across a resistor in series with the variable capacitor and a DC bias voltage source. Predictions are shown to be consistent with the experimental results, and frequency up-conversion effects are observed with exponentially decaying voltage amplitude as seen in experiments. A parametric study is also carried out to identify main parameters that affect the up-conversion, laying the foundation for future design optimization to maximize the power output.
Reverse Dynamization Accelerates Bone-Healing in a Large-Animal Osteotomy Model.

BACKGROUND Reverse dynamization is a mechanical manipulation regimen designed to accelerate bone-healing and remodeling. It is based on the hypothesis that a fracture that is initially stabilized less rigidly allows micromotion to encourage initial cartilaginous callus formation. Once substantial callus has formed, the stabilization should then be converted to a rigid configuration to prevent the disruption of neovascularization. The aim of the present study was to investigate whether bone-healing can be accelerated using a regimen of reverse dynamization in a large-animal osteotomy model. METHODS Transverse 2-mm tibial osteotomies were created in 18 goats, stabilized using circular external fixation, and divided into groups of 6 goats each: static fixation (rigid fixation), dynamic fixation (continuous micromotion using dynamizers), and reverse dynamization (initial micromotion using dynamizers followed by rigid fixation at 3 weeks postoperatively). Healing was assessed with the use of radiographs, micro-computed tomography, and mechanical testing. RESULTS Radiographic evaluation showed earlier and more robust callus formation in the dynamic fixation and reverse dynamization groups compared with the static fixation group. After 8 weeks of treatment, the reverse dynamization group had reduced callus size, less bone volume, higher bone mineral density, and no evidence of radiolucent lines compared with the static fixation and dynamic fixation groups. This appearance is characteristic of advanced remodeling, returning closest to the values of intact bone. Moreover, the tibiae in the reverse dynamization group were significantly stronger in torsion compared with those in the static fixation and dynamic fixation groups. CONCLUSIONS These findings confirmed that tibial osteotomies under reverse dynamization healed faster, healed objectively better, and were considerably stronger, all suggesting an accelerated healing and remodeling process. CLINICAL RELEVANCE This study demonstrates that the concept of reverse dynamization challenges the current understanding regarding the optimal fixation stability necessary to maximize the regenerative capacity of bone-healing. When reverse dynamization is employed in the clinical setting, it may be able to improve the treatment of fractures by reducing the time to union and potentially lowering the risk of delayed union and nonunion.
Substance Flow Analysis of Mercury Intentionally Used in Products in the United States

Mercury-containing products release mercury (Hg) throughout their lifecycles, frequently in ways that are difficult to measure directly. Therefore, there are considerable uncertainties about the magnitude of mercury releases associated with products, about which products and which release pathways contribute the most to mercury releases, and about the likely impact on mercury releases of various possible interventions in the mercury content of products or in the management of mercury-containing wastes. This article presents an effort to use substance flow analysis to develop improved estimates of the environmental releases caused by mercury-containing products and to provide policy-makers with a better understanding of opportunities for reducing releases of mercury caused by products.
Hydrosilyation of CO2 using a silatrane hydride: structural characterization of a silyl formate compound

The silatrane hydride compound, [N(CH2CH2O)3]SiH, reacts with CO2 in the presence of the [tris(2-pyridylthio)methyl]zinc hydride complex, [Tptm]ZnH, to afford the silyl formate and methoxide deriva...
Predictive Ability of Directors’ and Officers’ Liability Insurance Coverage for Class Action Lawsuit Settlements

The primary conclusion from prior literature is that firm size, as a measure of firm resources and capacity to pay, is a key predictor of class action securities settlement amount, and the merits of the case are less important in settlement negotiations. The purpose of this study is to shed additional light on the settlement determination process: given defendant incentives to avoid paying out of pocket and plaintiff incentives to settle quickly with maximum settlement, does directors’ and officers’ (DO high D&O coverage has stronger explanatory power for settlements than low coverage, presumably due to the marginal benefits of plaintiff attorney effort at high levels of coverage to yield the big payoff. In sum, this paper contributes to the existing literature on predicting class action securities lawsuit settlements, which even though D&O coverage levels are unobservable to investors, impacts decision-making important to shareholders.
Jigsaw: A Slice-and-Dice Approach to Non-uniform FFT Acceleration for MRI Image Reconstruction

The Fast Fourier Transform (FFT) is a fundamental algorithm in signal processing; significant efforts have been made to improve its performance using software optimizations and specialized hardware accelerators. Computational imaging modalities, such as MRI, often rely on the Non-uniform Fast Fourier Transform (NuFFT), a variant of the FFT for processing data acquired from non-uniform sampling patterns. The most time-consuming step of the NuFFT algorithm is “gridding;” wherein non-uniform samples are interpolated to allow a uniform FFT to be computed over the data. Each non-uniform sample affects a window of non-contiguous memory locations, resulting in poor cache and memory bandwidth utilization. As a result, gridding can account for more than 99.6% of the NuFFT computation time, while the FFT requires less than 0.4%. We present Slice-and-Dice, a novel approach to the NuFFT’s gridding step that eliminates the presorting operations required by prior methods and maps more efficiently to hardware. Our GPU implementation achieves gridding speedups of over 250× and 16× vs prior state-of-the-art CPU and GPU implementations, respectively. We achieve further speedup and energy efficiency gains by implementing Slice-and-Dice in hardware with JIGSAW, a streaming hardware accelerator for non-uniform data gridding. JIGSAW uses stall-free fixed-point pipelines to process M non-uniform samples in approximately M cycles, irrespective of sampling pattern—yielding speedups of over 1500× the CPU baseline and 36× the state-of-the-art GPU implementation, consuming $\sim 200\mathrm{m}\mathrm{W}$ power and $\sim 12\mathrm{m}\mathrm{m}^{2}$ area in 16 nm technology. Slice-and-Dice GPU and JIGSAW ASIC implementations achieve unprecedented end-to-end NuFFT speedups of 8× and 36× compared to the state-of-the-art GPU implementation, respectively.
Ruffling is Essential for Staphylococcus aureus IsdG-catalyzed Degradation of Heme to Staphylobilin

Non-canonical heme oxygenases are enzymes that degrade heme to non-biliverdin products within bacterial heme iron acquisition pathways. These enzymes all contain a conserved second-sphere Trp residue that is essential for enzymatic turnover. Previous studies have revealed several important roles for the conserved second-sphere Trp in Staphylococcus aureus IsdG, S. aureus IsdI, and Mycobacterium tuberculosis MhuD. However, a general model for the geometric, electron-ic, and functional role of the second-sphere Trp had not been deduced prior to this work. Here, UV/Vis absorption (Abs) and circular dichroism (CD) spectroscopies were employed to show that the W67F variant of IsdG perturbs the heme substrate conformation without altering the protein secondary structure. In general, it can now be stated that a dynamic equilibrium between “planar” and “ruffled” substrate conformations exists within non-canonical heme oxygenases, and that the second-sphere Trp favors population of the “ruffled” substrate conformation. 1H nuclear magnetic resonance and magnetic CD spectroscopies were used to characterize the electronic structures of IsdG and IsdI variants with different substrate conformational distributions. These data revealed that the “ruffled” substrate conformation promotes partial porphyrin-to-iron electron transfer, which makes the meso carbons of the porphyrin ring susceptible to radical attack. Finally, UV/Vis Abs spectroscopy was utilized to quantify the enzymatic rates, and electrospray ionization mass spec-trometry was used to identify the product distributions, for variants of IsdG with altered substrate conformational distri-butions. In general, the rate of heme monooxygenation to meso-hydroxyheme by non-canonical heme oxygenasess de-pends upon the population of the “ruffled” substrate conformation. Also, the production of staphylobilin or mycobilin by these enzymes is correlated with the population of the “ruffled” substrate conformation, since variants that favor popula-tion of the “planar” substrate conformation yield significant amounts of biliverdin. These data can be understood within the framework of a concerted rearrangement mechanism for the monooxygenation of heme to meso-hydroxyheme by non-canonical heme oxygenases. However, the mechanisms of IsdG/IsdI and MhuD must diverge following this interme-diate in order to generate distinct staphylobilin and mycobilin products, respectively.
An Inclusive Structural Analysis on the Design of 1.2kV 4H-SiC Planar MOSFETs

A detailed structural analysis of 1.2 kV 4H-SiC MOSFETs with accumulation mode channel is reported in this paper. 1.2 kV SiC MOSFETs with a variety of cell designs were fabricated and compared with respect to the output and transfer characteristics, and blocking behaviors. All the design rules, such as channel length, JFET width, contact openings, gate-to-source overlap, and cell pitch were investigated to clearly provide the quantitative impact on the static performances. 2D-simulation was also conducted to support experimental results. As a result, it turned out that the channel length is the most determining factor for the specific on-resistance, resulting in 0.364 $\text{m}\Omega $ -cm2 increase per $0.1~ {\mu }\text{m}$ increase in the channel length. However, the channel potential is also largely dependent on the channel length such that the leakage current tends to increase with short channel design. The enhanced doping in the JFET region with a current spreading layer (CSL) is essential for achieving a narrower JFET width, which satisfies all static performances, as well as device reliability and ruggedness. Methods to further improve the trade-off characteristics using other design aspects are discussed in this paper.
MOTIVATIONS AND EXPECTATIONS FOR VIRTUAL GIFT-GIVING IN DOUYIN LIVE STREAMS

Mobile live streaming recently advanced as popular form of content creation for streamers on short-video apps like Douyin and TikTok to make money through virtual gifts from viewers. Virtual gifts are primarily used to reward streamers for their content or performance in a live stream, yet on Douyin social aspects seem to be more crucial for virtual gifting. We are looking at three types of live streams by young male hosts (= streamers) on Douyin to analyze the motivations of female viewers to watch and make virtual gifts to the hosts and to explore resulting power relations between hosts and viewers. We conducted 12 semi-structured interviews with female of all three live streams who sent virtual gifts to hosts. We find female viewers send virtual gifts, for example, because they wanted to make the host happy or to help them achieve an assigned virtual gifts task. We did not find aspects of power imbalances regarding the monetary or social value of virtual gifts. While interviewees do not expect anything from the hosts in return for their virtual gifts, they appreciate online gestures, like a host blowing a kiss. In contrast, we observed viewers send virtual gifts to help a host win a live stream competition which holds implicit expectations. Overall, we find female viewers of male-hosted Douyin live streams mainly use virtual gifts as a social means of appreciation and support for friendship in a parasocial online interaction.
The 21st Century Frontier of Particle Accelerator Technology

Modern day RF particle accelerators were born in 1940s and 50s following World War II, stimulated by W. Hansen's invention of the MARK I electron linear accelerator at Stanford utilizing RF resonant cavities and powered by the klystron that had recently been invented by the Varian brothers. In the ensuing 75 years accelerators have become an engine of scientific discovery leading to experimental verification of the Standard Model for particle physics; to xray free-electron lasers for ultra-fast chemical and materials science; and to applications such as radiation oncology, industrial processing, and national security. The tremendous development of accelerator technology over the last half-century has even capitalized on developments such as superconducting RF technology to enable very high average power operation. We now find ourselves at the point where the current technology can no longer deliver the desired performance required in the future at a cost that is acceptable and within the desired size and power constraints. Understanding the coupling of particle beams, electromagnetic fields, materials properties, and plasmas underpins the future of accelerator science and technology. Exciting R&D is underway in numerous areas that has the promise of greatly increasing the science reach of high-energy physics accelerators as well as enabling a broad range of applications for smaller and even compact accelerators in areas that include industrial processing, medical, security, and others. Advancements are occurring in the understanding of accelerator materials properties, advanced electrodynamic accelerating structure topology, operation in new frequency regimes up to millimeter-wave/THz, high efficiency RF power generation, and advanced manufacturing that could dramatically improve the cost/capability curve for these systems. Unconventional approaches are also being considered that utilize accelerators powered by lasers and high energy electron beams to generate intense accelerating fields in silicon microstructures and plasmas. These technology developments and novel approaches seek to achieve breakthroughs in accelerating gradient, cost, and efficiency leading to a new era of discovery science and applications.
In Vitro Culture of Bovine Fibroblasts using Select Serum-Free Media Supplemented with Chlorella vulgaris Extract

Standard cell culture practices require addition of animal-derived serum to culture media to achieve adequate cell growth. Typically, 5-10% by volume of fetal bovine serum (FBS) is used, which accounts for a vast majority of the cost of media while also imposing environmental and ethical concerns associated with the use of animal serum. Here we tested the efficacy of culturing cells by replacing serum in the media with algae extract and select additives. Using LC-MS, we compared molecular signatures of FBS to Chlorella algae extracts and identified NAD(H)/NADP(H) as common and relatively abundant features in their characteristic profiles. Bovine fibroblasts, cultured in serum-free media supplemented with C. vulgaris extract and just two growth factors plus insulin, showed significant growth with enhanced viability compared to control cells cultured without serum, albeit still lower than that of controls cultured with 10% FBS. Moreover, C. vulgaris extract enhanced cell viability beyond that of cells cultured with the two growth factors and insulin alone. These results suggest that key components in serum which are essential for cell growth may also be present in C. vulgaris extract, demonstrating that it may be used at least as a partial alternative to serum for cell culture applications.
Microscale creep and stress relaxation experiments with individual collagen fibrils

Abstract Nanoscale macromolecular biological structures exhibit time-dependent mechanical behavior, yet a quantitative understanding of their creep and stress relaxation behavior remains elusive, largely due to experimental challenges in attaining sufficient spatial and temporal resolution and control of stress or strain in conditions that guarantee their molecular integrity. To address this gap, an experimental methodology was developed to conduct creep and stress relaxation experiments with individual mammalian collagen fibrils. An image-based edge detection method, implemented with high magnification optical microscopy and combined with closed-loop proportional–integral–derivative (PID) control, was implemented and calibrated to apply constant force or stretch ratio to individual collagen fibrils via a Microelectromechanical Systems (MEMS) device. This experimental methodology allowed for real-time control of uniaxial tensile stress or strain with ~25 nm displacement accuracy. The overall experimental system was tuned to apply step inputs with rise times below 0.5 s, less than 5% overshoot, and steady-state error smaller than 1%. Three collagen fibrils with diameters in the range 101–121 nm were subjected to creep and stress relaxation tests in the range 4–20% engineering strain, under partially hydrated conditions. The collagen fibrils demonstrated non-linear viscoelastic behavior that was described well by the adaptive quasi-linear viscoelastic model. The results of this study demonstrated for the first time that mammalian collagen fibrils, the building blocks of connective tissues, exhibit nonlinear viscoelastic behavior in their partially hydrated state.
Of Charities and Clawbacks: The European Union Proposal on Successions and Wills as a Threat to Charitable Giving

The recent European Union proposal to bring about a more uniform body of law governing choice of law and related issues in international inheritance cases 2 is perhaps, a necessary response to the increasingly international nature of the EU’s (and the world’s) inhabitants and their assets. As written, though, it is rather heavily tilted toward the civil law values of continental Europe and threatens to collide jarringly with common law traditions, in particular the Anglo-American fondness for trusts and charitable giving. This article provides a look at these different traditions, and then examines the relevant inheritance law provisions of EU member states, the UK, and the US before looking at the proposal itself.
Development of the aging cell surface: Reduction of gap junction-mediated metabolic cooperation with progressive subcultivation of human embryo fibroblasts (IMR-90)

Abstract Gap junctions develop between IMR-90 fibroblasts in cultures which have been serially subcultivated until reduced proliferative rates are produced. However, distribution is sparse and the junctions exhibit relatively few component subunits. To investigate whether a concomitant reduction in the ability of senescent cells to maintain metabolic coupling occurs, autoradiography was used to determine the relative exchange of [ 3 H]uridine nucleotides between early and late passage cells. In addition, the rate of reappearance of gap junctions between dissociated cells of both sample groups was examined by freeze-fracturing and electron microscopy. Gap junctions form between young cells approx. 1 h after reassociation in culture. Structurally complete gap junctions are present within 2 h. In contrast, membranes of cells in senescent cultures do not exhibit particle arrays typical of forming junctions until one or more hours of incubation. Small but assembled junctions are observed after 4 or more hours of reassociation. Autoradiography reveals some 70% of young cells to be receiving label from young donors following a 4 h period of metabolic exchange, whereas only 30% of older cells receive label after comparable periods of incubation. Statistical analyses of reciprocal experiments using young donor/old recipients and old donor/young recipients suggest that recipient cells may have a slightly larger effect on the exchange reaction than donor cells. We conclude that contact-mediated metabolic cooperation is reduced with increased serial subcultivation of cells.
A data parallel algorithm for raytracing of heterogeneous databases

We describe a new data parallel algorithm for raytracing. Load balancing is achieved through the use of processor allocation, which continually remaps available resources. In this manner heterogeneous data bases are handled without the usual problems of low resource usage. The proposed approach adapts well to both extremes: a small number of rays and a large database; a large number of rays and a small database. The algorithm scales linearly|over a wide range|in the number of rays and available processors. We present an implementation on the Connection Machine CM2 system and provide timings.
Milk fat globule-epidermal growth factor-factor VIII downregulates interleukin-17 expression in sepsis by modulating STAT3 activation.

Background Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in inflammation. In sepsis, interleukin (IL)-17 acts as a proinflammatory cytokine to exaggerate systemic inflammation. We hypothesize that MFG-E8 downregulates IL-17 expression in sepsis. Methods Sepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) at a dosage of 20 μg/kg body weight or phosphate-buffered saline was concurrently injected. After 10 hours, blood and spleen samples were harvested for analysis. For in vitro studies, splenocytes isolated from healthy mice pretreated with rmMFG-E8 and splenocytes from MFG-E8 knockout (mfge8-/-) mice were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, followed by measurement of IL-17 expression with either quantitative PCR or enzyme-linked immunosorbent assay. Results At 10 hours after CLP, rmMFG-E8 inhibited the elevated levels of IL-17 protein in serum by 31%, compared with the vehicle. In the spleen, rmMFG-E8 reduced the upregulated IL-17 mRNA and protein levels by 81% and 51%, respectively. This correlated with a significant reduction in organ injury markers AST and ALT in sepsis after administration of rmMFG-E8. In vitro treatment of splenocytes isolated from healthy mice with rmMFG-E8 showed significant downregulation in PMA/ionomycin-induced IL-17 expression. In contrast, CD4 T-cells from mfge8-/- mice showed significant upregulation of IL-17 compared with wild-type mice. The phosphorylated level of signal transducer and activator of transcription 3 (STAT3) was downregulated in spleen tissue of septic mice treated with rmMFG-E8. Conversely, mfge8-/- mice showed increased phosphorylated STAT3 compared with wild-type mice after sepsis. Conclusion Our findings demonstrate MFG-E8–mediated downregulation of IL-17 expression, implicating its potential as a novel therapeutic agent against sepsis.
Simulating seismic wave propagation in 3D elastic media using staggered-grid finite differences

This article provides an overview of the application of the staggered-grid finite-difference technique to model wave propagation problems in 3D elastic media. In addition to presenting generalized, discrete representations of the differential equations of motion using the staggered-grid approach, we also provide detailed formulations that describe the incorporation of moment-tensor sources, the implementation of a stable and accurate representation of a planar free-surface boundary for 3D models, and the derivation and implementation of an approximate technique to model spatially variable anelastic attenuation within time-domain finite-difference computations. The comparison of results obtained using the staggered-grid technique with those obtained using a frequency-wavenumber algorithm shows excellent agreement between the two methods for a variety of models. In addition, this article also introduces a memory optimization procedure that allows large-scale 3D finite-difference problems to be computed on a conventional, single-processor desktop workstation. With this technique, model storage is accommodated using both external (hard-disk) and internal (core) memory. To reduce system overhead, a cascaded time update procedure is utilized to maximize the number of computations performed between I/O operations. This formulation greatly expands the applicability of the 3D finite-difference technique by providing an efficient and practical algorithm for implementation on commonly available workstation platforms.
A randomized algorithm for simultaneous identification of linear systems

The authors propose, for the first time in system theory, a robust version of the well-known system identification problem. The problem, which they call the simultaneous identification problem, arises in trying to identify the parameters of a time-varying system. In the past, an identifier for a time-varying system was constructed by an immediate generalization of the ideas pertaining to a time invariant system. Unless the time variation of the plant is assumed to be slow, such an identification scheme would result in poor performance. As an alternative, a probabilistic randomized algorithm is presented, and its convergence is investigated. >
Beyond Raised Fields: Exploring Farming Practices and Processes of Agricultural Change in the Ancient Lake Titicaca Basin of the Andes

In the Lake Titicaca Basin of the Andes, narratives of agricultural change have focused exclusively on a single innovation: raised fields. In this article, I examine macrobotanical remains and other archaeological datasets to elucidate a wider range of past farming practices that contributed to processes of agricultural change on the Taraco Peninsula, Bolivia, during the Formative Period (1500 B.C.E.–C.E. 500). This analysis reveals strong continuities in crop selection through time, with farmers gradually diversifying a basic set of cultigens—quinoa and tubers—but never abandoning them. Patterns in wild plant species indicate continuity in agropastoral land use up to the Late Formative Period (second century C.E.) when the unintended consequences of long-term tilling and camelid grazing transformed the botanical landscape into one that required a new set of practices to remove weeds and replenish nutrients to the soils. Examining how these practices and the farmers enacting them articulated with broader processes of demographic, environmental, and sociopolitical change reveals dynamic, multivariate courses of agricultural change even before the inclusion of raised fields.
Magmatic inclusions in rhyolites, contaminated basalts, and compositional zonation beneath the Coso volcanic field, California

Basaltic lava flows and high-silica rhyolite domes form the Pleistocene part of the Coso volcanic field in southeastern California. The distribution of vents maps the areal zonation inferred for the upper parts of the Coso magmatic system. Subalkalic basalts (<50% SiO2) were erupted well away from the rhyolite field at any given time. Compositional variation among these basalts can be ascribed to crystal fractionation. Erupted volumes of these basalts decrease with increasing differentiation. Mafic lavas containing up to 58% SiO2, erupted adjacent to the rhyolite field, formed by mixing of basaltic and silicic magma. Basaltic magma interacted with crustal rocks to form other SiO2-rich mafic lavas erupted near the Sierra Nevada fault zone. Several rhyolite domes in the Coso volcanic field contain sparse andesitic inclusions (55–61% SiO2). Pillow-like forms, intricate commingling and local diffusive mixing of andesite and rhyolite at contacts, concentric vesicle distribution, and crystal morphologies indicative of undercooling show that inclusions were incorporated in their rhyolitic hosts as blobs of magma. Inclusions were probably dispersed throughout small volumes of rhyolitic magma by convective (mechanical) mixing. Inclusion magma was formed by mixing (hybridization) at the interface between basaltic and rhyolitic magmas that coexisted in vertically zoned igneous systems. Relict phenocrysts and the bulk compositions of inclusions suggest that silicic endmembers were less differentiated than erupted high-silica rhyolite. Changes in inferred endmembers of magma mixtures with time suggest that the steepness of chemical gradients near the silicic/mafic interface in the zoned reservoir may have decreased as the system matured, although a high-silica rhyolitic cap persisted. The Coso example is an extreme case of large thermal and compositional contrast between inclusion and host magmas; lesser differences between intermediate composition magmas and inclusions lead to undercooling phenomena that suggest smaller ΔT. Vertical compositional zonation in magma chambers has been documented through study of products of voluminous pyroclastic eruptions. Magmatic inclusions in volcanic rocks provide evidence for compositional zonation and mixing processes in igneous systems when only lava is erupted.
Disruption of 5-hydroxytryptaminergic neuronal function blocks the action of morphine on tuberoinfundibular dopaminergic neurons.

Abstract Subcutaneous injections of morphine to male rats reduced dopamine(DA) turnover (α-methyltyrosine-induced decline of DA concentrations) in the median eminence, and increased DA turnover in the striatum. Selective destruction of central 5-hydroxytryptamine(5HT)-neurons with intracerebroventricular injections of 5,7-dihydroxytryptamine, or the administration of metergoline, a putative 5HT antagonist, blocked the inhibitory effects of morphine on DA turnover in the median eminence. In the same experiments disruption of 5HT neurotransmission processes caused a similar but less dramatic antagonism of the stimulatory actions of morphine on DA turnover in the striatum. Thus, 5HT neurons play a role in mediating the effects of morphine on tuberoinfundibular and possibly on nigrostriatal DA neurons.
Arms control in the information age

(1997). Arms control in the information age. Contemporary Security Policy: Vol. 18, ARMS CONTROL New Approoaches to Theory and Policy, pp. 25-50.
Effects of adsorption on mass transfer in immobilization matrices

Abstract The effect of adsorption on mass transfer within immobilization matrices was investigated using pentachlorophenol (PCP) with polyurethane foam and with alginate beads containing activated carbon. The adsorption of polyurethane foam increased the mass transfer rate by approximately 20 times. The mass transfer rate in beads was also increased by the adsorption on immobilized activated carbon. The effect of adsorption can be explained by the decrease of solute concentration in matrix pores and by surface diffusion. This process has been modeled using an effective diffusivity model for porous media.
Cumulative distribution functions associated with particle coarsening processes

Abstract Cumulative probability distributions have been derived for the diffusion-controlled coarsening of spherical precipitates, grain-boundary precipitates, and fibers in unidirectionally solidified eutectic alloys. The effect of the volume fraction of particles, φ, is included in the derivations. In all cases the cumulative distribution functions are expressed analytically for the limiting cases φ = 0 and φ = 1. It is shown that the cumulative distributions for interface-reaction-controlled and diffusion-controlled coarsening of spherical precipitates when φ = 1 are identical. Some of the advantages and implications of the calculations are discussed.
Disruption of Follicular Maturation and Delay of Ovulation after Administration of the Antiprogesterone RU486

To investigate the role of progesterone in the follicular phase, we examined the effects of RU486 in eight normal cycling women studied with daily and frequent blood sampling (every 10 min for 10 h) during three menstrual cycles (control-treatment-recovery). RU486 (3 mg/kg, orally) was administered for 3 consecutive days after ultrasound documentation of a dominant follicle. In six of the eight women, RU486 was given after emergence of the dominant follicle, while in two women, RU486 was initiated during the preovulatory period when estradiol levels had exceeded 917 pmol/L. In the six women given RU486 after emergence of the dominant follicle, RU486 significantly prolonged the follicular phase duration from 15.6 +/- 1.9 (+/- SD) to 28.6 +/- 9.3 days (P less than 0.01) and extended the treatment cycle length to 42.3 +/- 9.1 (+/- SD) days (P less than 0.01). During RU486 treatment, mean serum estradiol levels decreased from 385 +/- 43 to 228 +/- 28 pmol/L (P less than 0.01), while LH, FSH, ACTH, cortisol, and progesterone levels changed little. LH pulse frequency and amplitude on the last day of RU486 administration did not differ from control values. Collapse of the dominant follicle was evident on ultrasound after RU486 administration and was not accompanied by uterine bleeding. In the two women treated during the preovulatory period, the follicular phase was not prolonged, and RU486 failed to delay the onset of the LH surge. Our findings indicate that RU486 treatment during the follicular phase interrupts normal follicular development, resulting in a delay of ovulation and a reinitiation of follicular recruitment.
Some open problems on the solutions of the delay difference equationsx n+1=A/x n 2 +1/x n−k p

We discuss the dynamics of the positive solutions of the delay difference equation in the title for some special values of the parametersA, p, andk, and we pose a conjecture and two open problems.
Why do some people have more difficulty learning to use an information retrieval system than others

The population using information retrieval systems is becoming increasingly diverse. We find a wide range of skills in ability to use these systems; this diverse population must be accommodated by the next generation of systems. This paper reports on a study to identify variables related to information retrieval aptitude, based on results from earlier studies of searchers and programmers. A sample of undergraduate subjects from English, psychology, and engineering majors was given a series of psychometric tests and compared to known populations. We find that engineering majors exhibit academic background and personality characteristics most like those of skilled searchers and programmers, with contrasting patterns or no discernible patterns in English and psychology majors. The strength of most associations increases when restricted to subjects who have either stayed in one major or who have changed major only within one disciplinary area. About half the variance in choice of major can be explained by scores on the tests administered, and a comparable amount of variance in test scores can be explained by the academic background variables.
Wireless ultrasound pitch-catch sensor powered by microwave energy

This paper presents a compact, batteryless wireless ultrasound pitch-catch system that wirelessly transmits the excitation signals to the actuator installed on the structure, and acquires the ultrasound sensing signal from the wireless sensor. The principle of frequency conversion is used to transform the ultrasound signals to microwave signals so that it can be wirelessly transmitted without digitization. As such, the power hungry digital-to-analog data conversion at the wireless actuator is eliminated. The wireless sensor node is equipped with a low power amplifier, which can be powered continuously by a microwave energy harvester. In addition, compact microstrip patch antennas are implemented for wireless transmissions, which help to achieve a compact interrogation unit.
Skin in psychoanalysis

Skin in psychoanalysis, by Jorge Ulnik, translated by Valeria Muscio, London, Karnac, 2008, 284 pp., £22.50 (paperback), ISBN 987-1-85575-516-1 Louise is the girl with the perfect skinShe says turn...
Interocular Asymmetry of Foveal Thickness in Parkinson Disease

Purpose. To quantify interocular asymmetry (IA) of foveal thickness in Parkinson disease (PD) versus that of controls. Design. Prospective case-control series. Methods. In vivo assessment of foveal thickness of 46 eyes of 23 PD patients and 36 eyes of 18 control subjects was studied using spectral domain optical coherence tomography (SD-OCT). Inner versus outer layer retinal segmentation and macular volumes were quantified using the manufacturer's software, while foveal thickness was measured using the raw data from each eye in a grid covering a 6 by 6 mm area centered on the foveola in 0.25 mm steps. Thickness data were entered into MATLAB software. Results. Macular volumes differed significantly at the largest (Zone 3) diameter centered on the foveola (ETDRS protocol). By segmenting inner from outer layers, we found that the IA in PD is mostly due to changes on the slope of the foveal pit at the radial distances of 0.5 and 0.75 mm (1.5 mm and 1 mm diameter). Conclusions. About half of the PD patients had IA of the slope of the foveal pit. IA is a potentially useful marker of PD and is expected to be comparable across different SD-OCT equipment. Data of larger groups may be developed in future multicenter studies.
Musical Differences in Learning-Disabled and Normal-Achieving Readers, Aged Seven, Eight and Nine

In the United States, learning-disabled children have been mainstreamed into general music classes where group instruction predominates without adequate evaluation of possible learning strengths an...
A Rapid, Asymmetric Synthesis of the Decahydrofluorene Core of the Hirsutellones

A tandem ketene-trapping/Diels-Alder cyclization sequence was the pivotal transformation in an efficient, asymmetric synthesis of a decahydrofluorene tricyclic structure possessing eight stereogenic centers and key features of the hirsutellone class of antitubercular natural products. The hirsutellone-like beta-keto ester that was fashioned by this sequence (13 steps; 6% overall yield) demonstrated significant inhibitory activity against Mycobacterium tuberculosis. The mechanism of action of this antitubercular compound is not yet known.
Thermal Radiative Heat Transfer Between Closely Spaced Nanostructures

Thermal emission control with nanostructures has attracted considerable attention because of its potential applications in thermophotovoltaic (TPV) devices [1–3]. The optical-to-electrical conversion in a TPV system is driven by photons with energy higher than the electronic bandgap of the photovoltaic cell. A narrow-band emitter with emission spectrum slightly above the bandgap is ideal, which maximizes the conversion efficiency as well as minimizes the waste heat that deteriorates the performance of the cell. Specially designed nanostructures alters the band structure of photons in much the same way as the crystal lattice does on electrons inside semiconductors, thus changing the thermal emission spectrum. By employing nanostructure-enabled emission control, Lin, et al, projected an efficiency of 34% for TPV systems [2].Copyright © 2005 by ASME