cssi/SciSciGPT-SciSciNet huggingface dataset:
Hepatic insulin sensitivity is improved in high-fat diet-fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis.

Park2 is an E3 ubiquitin ligase known for its role in mitochondrial quality control via the mitophagy pathway. Park2 KO mice are protected from diet-induced obesity and hepatic insulin sensitivity is improved in high-fat diet (HFD)-fed Park2 KO mice even under body weight-matched conditions. In order to better understand the cellular mechanism by which Park2 KO mice are protected from diet-induced hepatic insulin resistance, we determined changes in multiple pathways commonly associated with the pathogenesis of insulin resistance, namely levels of bioactive lipid species, activation of the endoplasmic reticulum (ER) stress response and changes in cytokine levels and signaling. We report for the first time that whole-body insulin sensitivity is unchanged in regular chow (RC)-fed Park2 KO mice, and that liver diacylglycerol levels are reduced and very-long-chain ceramides are increased in Park2 KO mice fed HFD for 1 week. Hepatic transcriptional markers of the ER stress response were reduced and plasma tumor necrosis factor-α (TNFα), interleukin-6 and -10 (IL6, IL10) were significantly increased in HFD-fed Park2 KO mice; however, there were no detectable differences in hepatic inflammatory signaling pathways between groups. Interestingly, hepatic adenylate charge was reduced in HFD-fed Park2 KO liver and was associated increased activation of AMPK. These data suggest that negative energy balance that contributed to protection from obesity during chronic HFD manifested at the level of the hepatocyte during short-term HFD feeding and contributed to the improved hepatic insulin sensitivity.
Network administration with the Raspberry PI

INFS 361, Network Administration, is a junior-level networking class taken by MIS majors at the University of Tennessee at Martin. During the fall of 2013, a collection of assignments based upon the Raspberry Pi computers was used to enhance the hands-on portion of the class. These assignments focused upon the installation and configuration of networking software. In addition, most assignments incorporated a challenge: an extra credit opportunity involving further effort.
Characterization of silk-hyaluronic acid composite hydrogels towards vitreous humor substitutes.

Abstract Multiple ophthalmic pathologies, such as retinal detachment and diabetic retinopathy, require the removal and replacement of the vitreous humor. Clinical tamponades such as silicone oil and fluorinated gases are utilized but limited due to complications and toxicity. Therefore, there is a need for biocompatible, stable, vitreous humor substitutes. In this study, enzymatically crosslinked silk-hyaluronic acid (HA) hydrogels formed using horseradish peroxidase and H 2O2 were characterized for use as vitreous humor substitutes. The composite network structure was characterized with dynamic light scattering. In addition, the rheological, optical, and swelling properties of hydrogels with varying silk to HA ratios and crosslinking densities controlled via H 2O2 were determined over time. Hydrogels had refractive indexes of 1.336 and were clear with 75–91% light transmission. Hydrogel shear storage modulus ranged between ~6 and 240 Pa where increased H 2O2 increased the modulus. After 1 month of aging, there were no changes in modulus for hydrogels with lower silk ratios, while those with higher silk ratios exhibited a significant increase in modulus. Decreasing H2O2 concentration in the reactions led to increased hydrogel volume during swelling, with higher silk ratios returning to their original size after 15 days. Dynamic light scattering results show three diffusive modes, revealing the possible structures of the hydrogel composite and are consistent with the mechanical properties and swelling results. The normalized intraocular pressure of ex vivo porcine eyes after injecting hydrogels were comparable with those treated with silicone oil showing the potential clinical utility of the hydrogels as vitreous substitutes. The versatility of the silk-HA hydrogel system, the tunable swelling properties, and the stability of hydrogels with lower silk ratios show the benefit of utilizing silk-HA hydrogels as vitreous substitutes.
Dynamic Collaborative Visualization Ecosystem to Support the Analysis of Large-Scale Disparate Data

There is no one display device or software package that is ideally suited for interactively visualizing related nonspatial, 1D, 2D, 3D, and 4D datasets. This is a major drawback, as the benefits of interactive visualization and advanced display technologies cannot be brought to bear. The Dynamic Collaborative Visualization Ecosystem (DynaCoVE) framework addresses this limitation by unifying SciVis, InfoVis, and display technology tools. Pre-existing packages are wrapped as DynaCoVE clients. This entails tracking user interactions with their GUI’s and also automatically updating them in response to cues from the DynaCoVE server. The DynaCoVE server then acts as a message broker between many collaborating clients. A messaging protocol was defined based on ZeroMQ’s majordomo protocol to enable efficient communication between clients and the server. Thus, visualization software packages that were never intended to be used together can be linked to perform cross display visual analytics. The system is intended to be data and user centric while remaining software, algorithm and display agnostic. This is accomplished in part by providing a common metavisualization graph interface to setup cross-display visualizations. To date DynaCoVE clients for Looker, VisIt, and VTK have been tested together with traditional monitors, tiled displays, and an immersive CAVE-type system.
Large domain movements through lipid bilayer mediate substrate release and inhibition of glutamate transporters

Glutamate transporters are essential players in glutamatergic neurotransmission in the brain, where they maintain extracellular glutamate below cytotoxic levels and allow for rounds of transmission. The structural bases of their function are well established, particularly within a model archaeal homologue, sodium and aspartate symporter GltPh. However, the mechanism of gating on the cytoplasmic side remains ambiguous. We report Cryo-EM structures of GltPh reconstituted into nanodiscs, including those structurally constrained in the cytoplasm-facing state and either apo, bound to sodium ions only, substrate, or blockers. The structures show that both substrate translocation and release involve movements of the bulky transport domain through the lipid bilayer. They further reveal a novel mode of inhibitor binding and show how solutes release is coupled to protein conformational changes. Finally, we describe how domain movements are associated with the displacement of bound lipids and significant membrane deformations, highlighting the potential regulatory role of the bilayer.
Spinal and paraspinal inflammatory reactions after epidural steroid injection in a patient taking disease-modifying antirheumatic drugs

Background Disease-modifying anti-rheumatic drugs (DMARDs) are used in the management of rheumatoid arthritis (RA) and are classified as conventional DMARDs and biologic agents. A concern with DMARDs is the increased risk of infection after surgery. A practice advisory from the American Society of Anesthesiologists recommend alternatives to neuraxial injections in patients who are immunocompromized. We describe a patient who was on several DMARDs and developed inflammatory reactions in her bilateral paraspinal muscles and lumbar spine after an epidural steroid injection (ESI). Case presentation The patient was a 79-year-old woman; she was taking methotrexate, adalimumab and prednisone for her RA. She had a left L5-S1 paramedian ESI for her L5 radiculitis. After relief of her back and radicular pain for 5 weeks, she had an acute exacerbation of her back pain. MRI showed bilateral paraspinal fluid accumulations and enhancement in her ligamentum flavum. Cultures of the aspirated fluid and biopsy specimens were negative for fungal, aerobic and anaerobic organisms. A repeat MRI 2 months later showed diminution of the fluid collection but with a new fluid accumulation near the left L4-5 facet and left L4 pedicle. Repeat cultures and gram stain of the specimens taken from the pedicle and the paraspinal muscles were negative. The patient was followed by her rheumatologist and in the pain clinic until resolution of her symptoms. Conclusions Several society guidelines recommend the continuation of methotrexate but stoppage of the biologic DMARDS before surgery. The occurrence of an intense inflammatory reaction after an ESI in our patient calls for additional research on the subject and shared decision-making between the pain physician, patient and rheumatologist especially in patients on several DMARDs.
Navigating Stigma Trajectory and Mental Health Among Young Adults Living with Perinatal HIV in New York City.

Perceived HIV stigma and mental health are fluid across the lifespan for people living with perinatally-acquired HIV (PHIV). The process of navigating discredited identities over time in the context of other life demands potentially exerts a toll on the mental health of adolescents and young adults living with PHIV (AYAPHIV). Based on data from a longitudinal study in New York City examining mental health and health risk behaviors among 182 AYAPHIV, we examined if increased perceived HIV stigma predicted mental health, future orientation, HIV-disclosure, and healthcare transition over time (2003–2018). Findings from linear mixed-effects modeling indicated that older age predicted poorer mental health, less future orientation, more HIV-serostatus disclosure, and adult medical services utilization. Perceived stigma was the only significant predictor of mental health and mediated the association between age and mental health—highlighting the importance of addressing stigma across development for AYAPHIV while addressing systems that perpetuate them.
Quantum-limited metrology of terahertz fields with integrated transducers

The metrology of terahertz waves is a prerequisite for future applications in communications, sensing or spectroscopy. Electro-optic transduction, the technique by which a terahertz signal is mapped onto an optical or near-infrared signal, has emerged as one of the most sensitive metrology techniques that also provides sub-picosecond temporal resolution. As such, it has been employed to detect quantum terahertz fields for the first time. Recent advances in the miniaturization of these transducers target increased sensitivities, a small footprint and compatibility with large photonic architectures. In this talk, I will outline the basics of electric field metrology at the quantum limit and discuss how integrated photonics could open entirely new avenues in the area of spatially and temporally multiplexed terahertz detection.
Accuracy of a drilling with a custom 3D printed guide or free-hand technique in canine experimental sacroiliac luxations

OBJECTIVE To improve the accuracy of drilling during the repair of sacroiliac luxations (SILs) with a 3D-printed patient-specific drill guide (3D-GDT) compared to free-hand drilling technique (FHDT). STUDY DESIGN Blinded, randomized, prospective ex vivo study. SAMPLE POPULATION Sixteen canine cadavers (20-25 kg). METHODS Dorsal, bilateral SILs were created. Pelvic CT was performed pre- and post-drilling. The FHDT was drilled followed by 3D-GDT. CT and 3D measurements of craniocaudal and dorsoventral angles were compared between FHDT and 3D-GDT, as well as deviations of entry and exit points relative to optimal trajectory. RESULTS Mean craniocaudal and dorsoventral angles for both CT- and 3D-measured 3D-GDT (CT 4.2 ± 3.9° and 3.9 ± 3.2°, respectively; 3D 5.1 ± 5.1° and 2.8 ± 2.3°, respectively p = .0006) were lower compared to FHDT (CT 11.8 ± 4.0°, p < .0001 and 8.9 ± 6.1°, p = .01; 3D 12.4 ± 5.9°, p = .0006 and 5.3 ± 5.24°, p = .05). Entry dorsoventral and end craniocaudal, dorsoventral, and 3D linear deviations were reduced with 3D-GDT. Sacral corridor disruption was present in 20% (3/15) for FHDT compared with 0% for 3D-GDT. CT and 3D analyses were in strong agreement (r = 0.77). CONCLUSION Deviations of drill trajectories were minimized relative to optimal trajectories with 3D-GDT compared to FHDT in the dorsoventral and craniocaudal planes. CLINICAL SIGNIFICANCE The use of 3D-GDT improves accuracy of sacral drilling compared with FHDT in canine cadavers. These results justify further evaluation in a clinical, prospective study.
Primary Hyperparathyroidism: Diagnosis and Workup

The diagnosis of primary hyperparathyroidism (PHPT) is made by demonstrating simultaneous elevation of serum calcium and parathyroid hormone (PTH) levels in a patient who does not have hypocalciuria. Over the past decade, it has also been recognized that there is a normocalcemic variant of PHPT where the serum calcium level is normal, but usually at the upper end of the normal range, and the serum PTH is either elevated or inappropriately high. A normohormonal variant of PHPT is also now recognized, where hypercalcemia is accompanied by inappropriately high PTH that is still within the normal reference range. Elderly patients are the least likely to be referred for parathyroid surgery. As the US population ages, appropriate use of parathyroidectomy may play an important role in increasing health-care value by reducing costly negative health events of hyperparathyroidism such as fragility fracture and kidney stone formation. Most parathyroid surgeons believe that hyperparathyroidism is under-recognized, underreported, and undertreated.
Physics of Solids-Plastic Flow

T E papers published by von Karman in the fields of solid s tate physics and plastic flow represent a small fraction only of his scientific production. Each one of these papers, however, was an outstanding contribution which resulted in a bet ter understanding of very fundamental physical problems. Following a chronological order, von Karman ' s most impor tant contributions were on the plastic flow of brit t le materials under combined stresses, on the specific heat of solids, and on the propagation of plastic deformation in solids.
Ranolazine Increases Exercise Capacity in Heart Failure with Preserved Ejection Fraction (HFpEF)

Background: Intracellular calcium (Ca) overload of cardiomyocytes and increased myocardial tension have been identified as pathophysiologic mechanisms in HFpEF. Ranolazine (RAN), an inhibitor of the late sodium (Na) current, has the potential to improve cardiac function by reducing intracellular Na, thus decreasing the exchange of outward Na for inward Ca. Methods: We performed a randomized double-blind placebo-controlled study of RAN 1000 mg twice daily versus placebo (PB) for 6 weeks in HFpEF patients. Although a larger sample size was anticipated, only 10 patients were studied due to slow enrollment. The primary endpoint was change in exercise time (ET) on cardiopulmonary exercise testing, with change in peak oxygen consumption (VO2) as a pre-specified secondary endpoint. Results: Six subjects were randomized to RAN and 4 to PB. Percent change in ET was not significantly different (P50.24); however, peak VO2 did significantly improve with RAN (11.2[95%CI 2.8-19.7] vs. -15.1[95%CI -41.5-11.3]%, P50.009). Markers of increased left ventricular filling pressures and cardiac performance (peak heart rate and peak O2 pulse) did not change. Conclusions: Ranolazine significantly increased peak VO2 in subjects with HFpEF. There were no changes in markers of LV filling pressure or performance suggesting other mechanisms may underlie this change. These findings provide a basis for a larger study of RAN in HFpEF that includes measurements of the central and peripheral effects of this agent.
Lessons from theory revision applied to constructive induction

Two challenges of integrating theory knowledge and inductive learning are: 1) A representation language appropriate for a coarse theory may be inappropriate for an improved theory. While the original representation may concisely express the initial theory, a more accurate theory forced to use that same representation may be bulky, cumbersome, and difficult to reach. 2) A theory structure suitable for a coarse domain theory may be insufficient for a fine-tuned theory. Systems that produce only small, local changes to a theory have limited value for accomplishing complex structural alterations that may be required. An analysis of various theory revision systems and theory-guided learning systems reveals specific strengths and weaknesses in terms of these two challenges. Designed to capture the underlying qualities of each system, and to implement flexibility of representation and structure, a new system uses theory-guided constructive induction. Experiments in three domains show improvement over previous systems.
Lattice vector quantization for image coding

The authors investigate the application of several lattice vector quantizers, namely D/sub N/ for N >
Fine-grained sticky provenance architecture for office documents

Current business situations require improved confidentiality and integrity for office documents. However, existing content management systems for office documents lack required security properties such as the *-property, or have problems such as label creep. In this paper we propose a meta-data format called sticky provenance and a fine-grained information flow control architecture using the sticky provenance. The sticky provenance contains the change history and the labels of an office document in a secure form, and it ensures the verifiability of the change history of the documents in distributed environments. The Provenance Manager, which is a key module of the architecture, reduces the label creep problem of the information flow control models with the sticky provenance. In other words, the sticky provenance and the Provenance Manager can introduce a practical fine-grained information flow control capability to office applications so that we can ensure both the confidentiality and the verifiability of office documents.
Mechanism of killing by virus-induced cytotoxic T lymphocytes elicited in vivo.

The mechanism of lysis by in vivo-induced cytotoxic T lymphocytes (CTL) was examined with virus-specific CTL from mice infected with lymphocytic choriomeningitis virus (LCMV). LCMV-induced T cells were shown to have greater than 10 times the serine esterase activity of T cells from normal mice, and high levels of serine esterase were located in the LCMV-induced CD8+ cell population. Serine esterase was also induced in purified T-cell preparations isolated from mice infected with other viruses (mouse hepatitis, Pichinde, and vaccinia). In contrast, the interferon inducer poly(I.C) only marginally enhanced serine esterase in T cells. Serine esterase activity was released from the LCMV-induced T cells upon incubation with syngeneic but not allogeneic LCMV-infected target cells. Both cytotoxicity and the release of serine esterase were calcium dependent. Serine esterase released from disrupted LCMV-induced T cells was in the form of the fast-sedimenting particles, suggesting its inclusion in granules. Competitive substrates for serine esterase blocked killing by LCMV-specific CTL, but serine esterase-containing granules isolated from LCMV-induced CTL, in contrast to granules isolated from a rat natural killer cell tumor line, did not display detectable hemolytic activity. Fragmentation of target cell DNA was observed during the lytic process mediated by LCMV-specific CTL, and the release of the DNA label [125I]iododeoxyuridine from target cells and the accompanying fragmentation of DNA also were calcium dependent. These data support the hypothesis that the mechanism of killing by in vivo-induced T cells involves a calcium-dependent secretion of serine esterase-containing granules and a target cell death by a process involving nuclear degradation and DNA fragmentation.
Neuroimage evidence and the insanity defense.

The introduction of neuroscientific evidence in criminal trials has given rise to fears that neuroimagery presented by an expert witness might inordinately influence jurors' evaluations of the defendant. In this experiment, a diverse sample of 1,170 community members from throughout the U.S. evaluated a written mock trial in which psychological, neuropsychological, neuroscientific, and neuroimage-based expert evidence was presented in support of a not guilty by reason of insanity (NGRI) defense. No evidence of an independent influence of neuroimagery was found. Overall, neuroscience-based evidence was found to be more persuasive than psychological and anecdotal family history evidence. These effects were consistent across different insanity standards. Despite the non-influence of neuroimagery, however, jurors who were not provided with a neuroimage indicated that they believed neuroimagery would have been the most helpful kind of evidence in their evaluations of the defendant. Copyright © 2011 John Wiley & Sons, Ltd.
Reynolds Number Dependence of Energy Spectra in the Overlap Region of Isotropic Turbulence

A Near-Asymptotics analysis of the turbulence energy spectrum is presented that accounts for the effects of finite Reynolds number recently reported by Mydlarski and Warhaft [21]. From dimensional and physical considerations (following Kolmogorov and von Karman), proper scalings are defined for both low and high wavenumbers, but with functions describing the entire range of the spectrum. The scaling for low wavenumbers uses the kinetic energy and the integral scale, L, based on the integral of the correlation function. The fact that the two scaled profiles describe the entire spectrum for finite values of Reynolds number, but reduce to different profiles in the limit, is used to determine their functional forms in the “overlap” region that both retain in the limit. The spectra in the overlap follow a power law, E(k) =Ck −5/3 + μ, where μ and C are Reynolds number dependent. In the limit of infinite Reynolds number, μ → 0 and C → constant, so the Kolmogorov/Obukhov theory is recovered in the limit. Explicit expressions for μ and the other parameters are obtained, and these are compared to the Mydlarski/Warhaft data. To get a better estimate of the exponent from the experimental data, existing models for low and high wavenumbers are modified to account for the Reynolds number dependence. They are then used to build a spectral model covering all the range of wavenumbers at every Reynolds number. Experimental data from grid-generated turbulence are examined and found to be in good agreement with the theory and the model. Finally, from the theory and data, an explicit form for the Reynolds number dependence of φ = ɛL/u 3 is obtained.
Dietary self-monitoring and long-term success with weight management

Objective To examine the contributions of frequency, consistency, and comprehensiveness of dietary self-monitoring to long-term weight change.
Severe hemorrhage and maternal death associated with amniotic fluid embolism.

S UDI)EN maternal death shortly before, during, or after delivery is frequently preceded by shock. The predisposing factors to ohst,etrical shock may be numerous and not always detectable. One of t,he unkllowu factr)rs has been identified ant1 esperirnent:llly sul)stalltiat,etl 1)~ Steiner and Lushl,augh,l who first described amniotic fluid eml)olism. Since t.heir original c.omrnunic;~tiol~ almut 55 cases harr been reported in the work1 literature. In 1911 Steiiter ant1 Lushbaugh’ reported t,hree cases from t,he Chicago I ,ying-in Hospital. 1 lowever, during the past twelve years no maternal tlenth has been attrilnlte(l to this condition in this samt’ institution. Recently a patient who succuml~etl with nncont~~ollable l>ostpiLrt,uln hemoryhage was found to ha\Tc a massive atnniot~ic fluitl emholism.
Differences between gingivitis and periodontitis associated microbial flora in the beagle dog. Relationship of plaque parameters to histological parameters of periodontal disease

The predominant dental plaque flora was compared between two groups of adult beagle dogs, (1) ten with gingivitis and (2) ten with advanced periodontitis. Plaque from a maxillary third premolar was cultured under strict anaerobic conditions. Specimens comprising the marginal periodontal tissues were taken at the plaque sampling site and analyzed for some histological parameters of periodontal disease. The periodontitis dogs scored significantly higher for crevice depth, length of ulcerated crevice epithelium, area of inflamed connective tissue, and loss of attachment. Supragingival periodontitis plaque had significantly higher anaerobic to aerobic ratio, proportions and CFU of esculin negative streptococci, but lower proportions of Actinomyces viscosus. Subgingival periodontitis plaque had significantly higher anaerobic to aerobic ratio, microscopic counts of spirochetes, total viable CFU, proportions and CFU of esculin negative streptococci and Fusobacterium nucieatum, as well as CPU of Bacteroides asaccharolyticus, Gram negative bacilli and coccobacilli, but significantly lower proportions of A. viscosus and unspeciated actinomycetes. The total viable CFU, proportions and CFU of esculin negative streptococci correlated with all four histological parameters of periodontal disease. The CFU of B. asaccharolyticus, bacilli, and coccobacilli correlated with the length of ulcerated crevice epithelium and loss of attachment, but F. nucleatum only with the area of inflamed connective tissue and loss of attachment.
A Review of: “Handbook of Pharmaceutical Excipients, 5th edition”

The formulation, development, and manufacturing of drug-delivery systems relies heavily on the use of excipients to aid in processing, stability, and bioavailability. A detailed knowledge of variou...
Anonymous Networking under Memory Constraints

Chaum Mixes, a class of proxy servers or relays which use randomized reordering and batching of packets from multiple users to provide source anonymity, have been used extensively for anonymous remailing, browsing and peer-to-peer file sharing. In this work, an analytical framework is proposed to measure and optimize the anonymity provided by mixing strategies when the mixes have memory restrictions. Specifically, an information-theoretic metric of anonymity is proposed for buffer constrained mixes, and using Poisson traffic models, fundamental trade-offs between achievable anonymity and the buffer size are studied analytically. In particular, a buffer-constrained mixing strategy is proposed that is asymptotically optimal and obtains the best convergence rate amongst known mixing strategies. The strategy is generalized to a network of mixes, where the achievable anonymity is expressed as a function of the topology and the buffer constraints of individual mixes.
Effects of different ions on resting polarization and on the mass receptor potential of carotid body chemosensors.

The carotid body and its own nerve were removed from cats anesthetized with sodium pentobarbital and placed in an air gap system; the carotid body was bathed in modified Locke's solution equilibrated with 50% O2 in N2, pH 7.43 at 35°C. The sensory discharges, changes in “resting” receptor polarization and the mass receptor potential evoked by ACh or NaCN were recorded with nonpolarizable electrodes placed across the gap. Receptor potentials and sensory discharges evoked by ACh showed an appreciable increase in amplitude and frequency when the preparation was bathed in eserinized Locke. Eserine did not change appreciably the responses evoked by NaCN. Excessive depolarization elicited by either ACh or NaCN was accompanied by sensory discharge block. Removal of K+ ions from the bathing solution induced receptor hyperpolarization and an increase in the amplitude of the evoked receptor potentials. An increase of K+ concentration had the opposite effect. Reduction of Na+ or NaCl to one half, or total removal of this salt, induced an initial reduction and later disappearance of the sensory discharges, some receptor hyperpolarization and a reduction in the amplitude of the evoked receptor potentials. Reduction or removal of Ca++ produced receptor depolarization, a marked depression of the evoked receptor potentials, an increase in the frequency of the sensory discharges and a reduction in the amplitude of the nerve action potentials. High Ca++ or Mg++ had little or no effect on action potential amplitude or resting polarization, but decreased sensory discharge frequency and the evoked receptor potentials. Total or partial replacement of Ca++ with Mg++ induced complex effects: (1) receptor depolarization which occurred in low Ca++, was prevented by addition of Mg++ ions; (2) the amplitude of the evoked receptor potentials was depressed; (3) the nerve discharge frequency was reduced as it was in high Mg++ solutions; and (4) the amplitude of the nerve action potentials was reduced as it was in low Ca++ solutions. Temperature had a marked effect on the chemoreceptors since a t high temperatures the receptors were depolarized and the discharge frequency increased. The baseline discharge and responses evoked by ACh or NaCN were depressed at low temperatures. The results are discussed in terms of possible receptor mechanisms influenced by the different ions.
Catalytic Properties of RNase BN/RNase Z from Escherichia coli RNase BN IS BOTH AN EXO- AND ENDORIBONUCLEASE

Processing of the 3′ terminus of tRNA in many organisms is carried out by an endoribonuclease termed RNase Z or 3′-tRNase, which cleaves after the discriminator nucleotide to allow addition of the universal -CCA sequence. In some eubacteria, such as Escherichia coli, the -CCA sequence is encoded in all known tRNA genes. Nevertheless, an RNase Z homologue (RNase BN) is still present, even though its action is not needed for tRNA maturation. To help identify which RNA molecules might be potential substrates for RNase BN, we carried out a detailed examination of its specificity and catalytic potential using a variety of synthetic substrates. We show here that RNase BN is active on both double- and single-stranded RNA but that duplex RNA is preferred. The enzyme displays a profound base specificity, showing no activity on runs of C residues. RNase BN is strongly inhibited by the presence of a 3′-CCA sequence or a 3′-phosphoryl group. Digestion by RNase BN leads to 3-mers as the limit products, but the rate slows on molecules shorter than 10 nucleotides in length. Most interestingly, RNase BN acts as a distributive exoribonuclease on some substrates, releasing mononucleotides and a ladder of digestion products. However, RNase BN also cleaves endonucleolytically, releasing 3′ fragments as short as 4 nucleotides. Although the presence of a 3′-phosphoryl group abolishes exoribonuclease action, it has no effect on the endoribonucleolytic cleavages. These data suggest that RNase BN may differ from other members of the RNase Z family, and they provide important information to be considered in identifying a physiological role for this enzyme.
Polyadenylated RNA sequences from vaccinia virus-infected cells selectively inhibit translation in a cell-free system: structural properties and mechanism of inhibition.

Abstract The mechanism of vaccinia virus-induced selective inhibition of host cell protein synthesis was studied in a nonpermissive (Chinese hamster ovary, CHO) and in a permissive mouse cell line (L cells). Small polyadenylated RNAs obtained from uninfected and infected cells were fractionated into six size classes by polyacrylamide gel electrophoresis. The RNAs from the first two largest fractions (>500 nucleotides, nt) were translated into some low-molecular-weight polypeptides, whereas, the RNAs from the remaining fractions (400–500, 300–400, 200–300, and 100–200 nt) had no translational activity in reticulocyte lysates. When these nontranslating polyadenylated short sequences (POLADS) were added to the cell-free system together with HeLa cell mRNAs, translation was inhibited from 70%, by the 400- to 500-nt fraction, to about 20%, by the 100- to 200-nt fraction. The degree of inhibition of protein synthesis was clearly dependent on the size of POLADS. The translation of vaccinia virus mRNAs in the cell-free system was inhibited by about 25% with the 400- to 500-nt fraction, by 5% with the 300- to 400-nt fraction, while the smaller size POLADS had no inhibitory effect. The inhibition of HeLa cell and vaccinia virus mRNA translation by POLADS was reversed by the simultaneous addition of oligo(dT) to the cell-free system. POLADS were also obtained from uninfected cells, but they inhibited the translation of HeLa cell and vaccinia virus mRNAs to a much lesser extent. The removal of the poly(A) moiety from POLADS by treatment with ribonuclease H and oligo(dT) abolished their inhibitory effect on HeLa cell mRNA translation. The average length of the poly(A) tails of POLADS obtained from infected cells was longer than that of POLADS from normal cells. Inhibition of HeLa cell mRNA translation mediated by POLADS in the cell-free system was reversed (∼70%) by addition of crude initiation factors (ribosomal salt wash, RSW). Significantly, inhibition of translation by POLADS was reversed (>90%) by addition of purified poly(A) binding protein (PAB). Purified initiation factor 4A (elF-4A) also reversed this inhibition, but to a lesser extent than RSW and PAB. Our results show that the translation of vaccinia virus mRNAs is resistant to POLADS, suggesting that POLADS, by virtue of their long poly(A) tails, may sequester PAB and thus, play a role in selective inhibition.
Costs of harvesting, transportation and milling in the Brazilian Amazon: Estimation and policy implications

Abstract We estimate economic cost functions for timber harvesting, transportation and milling in the Brazilian Amazon using a 2003 sample of 527 firms in both new and older frontier locations. We find that labor wage, distance from the forest to the processing location, type of equipment, and the type of the frontier all factor significantly in the total and marginal cost of each activity, and that predicted processing costs are not significantly different on new frontiers implying a lack of technology adoption as industry expansion into the Amazon has occurred. We also show that capturing economies of scale in logging by increasing average annual logging volumes by 50% and reducing the number of firms to about 1400 could lead to an industry wide cost savings of approximately US$90 million per year. Similar economies of scale are also present in log transport but not in processing. Further, if improved logging techniques allow harvest for an additional 1 month per year, for example through better planning, the industry could reduce logging costs by almost US$30 million. This points towards generating forest policies and economic conditions that encourage firm size growth, as opposed to those policies encouraging massive entry of small, unregulated and inefficient firms, and the adoption of management practices that allow for additional time in the forest.
A cis-prolyl peptide bond isomerization dominates the folding of the alpha subunit of Trp synthase, a TIM barrel protein.

Abstract The cis/trans isomerization of prolyl peptide bonds has been suggested to dominate the folding of the alpha subunit of tryptophan synthase from Escherichia coli (αTS). To test the role of the unique cis isomer between Asp27 and Pro28, the folding properties of P28A, P28G and G3P28G, a three-glycine insertion mutant between Asp27 and Gly28, were investigated using urea as a denaturant. Circular dichroism analysis demonstrated that none of the mutations perturb the secondary structure significantly, although the aromatic side-chain packing is altered for P28A and P28G. All three mutant proteins inherited the three-state thermodynamic behavior observed in wild-type αTS, ensuring that the fundamental features of the energy surface are intact. Kinetic studies showed that neither alanine nor glycine substitutions at Pro28 results in the elimination of any slow-refolding phases. By contrast, the G3P28G mutant eliminates the fastest of the slow-refolding phases and one of the two unfolding phases. Double-jump experiments on G3P28G confirm the assignment of the missing refolding phase to the isomerization of the Asp27-Pro28 peptide bond. These results imply that the local stability conveyed by the tight, overlapping turns containing the cis peptide bond is sufficient to favor the cis isomer for several non-prolyl residues. The free energy required to drive the isomerization reaction is provided by the formation of the stable intermediate, demonstrating that the acquisition of structure and stability is required to induce subsequent rate-limiting steps in the folding of αTS.
Watching nanoparticle kinetics in liquid

Real-time monitoring of reaction kinetics involved in nanoparticle growth and transformation in liquid environments is crucial for understanding the complex chemical and physical events associated with nanophase evolution. Accordingly, in situ techniques that can “see through” liquids to probe nanomaterial variation are in high demand, as they will help us understand reaction mechanisms and design better synthetic strategies for building nanoparticles with precisely tailored properties. In this review, in situ transmission x-ray microscopy and time-resolved high-energy x-ray scattering techniques are discussed, highlight their capabilities in studying the dynamic processes of nanoparticles.
Natural occurrence of the nucleopolyhedrosis virus of the gypsy moth,Lymantria dispar [Lep.: Lymantriidae] in wild birds and mammals

Three species of birds and 5 species of mammals were captured in the wild from 2 plots in which mortality from naturally occurring nucleopolyhedrosis virus (NPV) among gypsy moth,Lymantria dispar (L.), larvae was 15% and 70%. Bioassays of intestinal contents showed that blue jays,Cyanocitta cristata (L.), towhees,Pipilo erythrophthalmus (L.), white-footed mice,Peromyscus leucopus (Rafinesque), redback voles,Clethrionomys gapperi (Vigers), raccoons,Procyon lotor (L.), and a chipmunk,Tamias striatus (L.), contained infectious (L.), and masked shrews,Sorex cinereus (Kerr), did not. Comparisons among mice and voles indicated that those collected from the plot in which the NPV mortality was greatest (70%) contained the most virus. We concluded that birds and mammals can passively transport infectious gypsy moth NPV in the wild.
Abnormal pattern electroretinograms in patients with senile dementia of the Alzheimer type.

Abstract Patients with senile dementia of the Alzheimer type frequently have difficulty performing visual tasks. These difficulties may be due, at least partially, to degenerative changes in both the primary visual pathway and the visual association areas. To determine whether retinal ganglion cell dysfunction contributes to visual loss in senile dementia of the Alzheimer type, we tested a group of patients with this disease (n = 13) using the pattern-reversal electroretinogram to both low (4.0 reversals per second) and high (16.0 reversals per second) temporal frequency checkerboard patterns (1.0 degree checks). Significant amplitude reductions were noted for the patients relative to age-matched control subjects (n = 30). In addition, the observed amplitude reductions were most pronounced for the high temporal frequency condition. Therefore, the results are consistent with retinal ganglion cell dysfunction and support the notion that optic nerve damage induced by senile dementia of the Alzheimer type preferentially affects the larger, faster-conducting retinal ganglion cells along with their retinocortical projections.
Immunoglobulin bearing lymphocytes and plasma cells in human periodontal disease

Gingival biopsies from areas characterized as clinically normal, mild gingivitis, or periodontitis were examined. Immunoglobulin (IgG, IgA, IgM, IgE and IgD) bearing cells at the sulcular and oral epithelium - lamina propria junctions as well as the central lamina propria areas were quantitated. Normal gingiva (P. I. = 0-0·2) contained few lymphocytes and plasma cells. Biopsies from areas of mild gingivitis (P. I. = 0·2-1) were infiltrated at the sulcular epithelium - lamina propria junction by lymphocytes lacking membrane associated immunoglobulins (94 %). Few plasma cells were evident. In contrast, tissue associated with periodontitis (P. I. = 4·0–8·0) contained significant numbers of immunoglobulin bearing lymphocytes (78 %, IgG; 9 %, IgM; and 4 % IgA) and plasma cells (67 %, IgG; 24 %, IgM; and 8 % IgA) distributed throughout all three major tissue areas. These findings indicated that the nature of cellular infiltrates differed in mild gingivitis and periodontitis. The presence of predominantly IgG and IgM containing cells in periodontitis had important implications for the contribution of nonspecific effector mechanisms to the destruction of periodontal tissue.
Horizontal Power, Vertical Weakness: Enhancing the “Circuit of Culture”

Imagined as a way to account for a broader conceptualization of meaning, the “circuit of culture” encourages scholars to consider the contribution of sometimes overlapping cultural processes, such as production, consumption, regulation, representation, and identity. In this article, the author considers the way the circuit prompts him to think “horizontally” in his research. But he argues that the circuit can be augmented and improved by the recognition of deeper, “vertical” dimensions of meaning. For instance, would it be possible to account for the researcher's own cultural processes in her/his reports? What about those of the audience members for these reports? The author presents an example of this approach with the interpretation of a Smokey Bear advertisement. He concludes that such efforts to pull together these elements will be rewarded with more powerful, nuanced statements of the process of meaning.
The paediatrician and the sexually abused child

. Sexual abuse is an aspect of cruelty to children which merits greater scientific attention. It has potential for damaging the mental health of the victim and intergenerational cycles of this behaviour pattern may develop. The paediatrician is in a position to detect children at risk and may be able to intervene. Three types of sexual abuse are described (i) single sexual attacks which may be accompanied by physical violence: (ii) sexual exploitation of children for financial gain, and (iii) longstanding sexual relationships, generally between girls and father figures; these are far the most common. Although it is hard to separate the effects of premature sexual experience from other adverse environmental influences. the child victim of longstanding sexual abuse emerges immature, with considerable confusion as to her role in the family, and with constricted personality development. Her primary motivation is attention seeking, and she adopts sexual activity with an adult as a means of survival in often deplorable conditions. The sensitivity of management following the assault being made public is an important factor in determining eventual adjustment.
Cyclosporine and the thymus: Influence of irradiation and age on thymic immunopathology and recovery

With the proper experimental conditions, previous studies have demonstrated that syngeneic and autologous radiation chimeras treated with cyclosporine (CsA) routinely develop a syndrome resembling graft-vs-host disease (GVHD) after CsA is discontinued. The thymus is clearly important in the pathogenesis. Thymectomy prior to CsA prevents the development of syngeneic GVHD and the process can be adoptively transferred via thymocytes. The thymus, however, must be within the field of irradiation and the animal must be young. Here we examine how irradiation and advanced age influence the thymic immunopathologic changes induced by CsA and influence the recovery post-CsA. Young LEW rats, with or without pre-CsA mediastinal irradiation, demonstrate a marked involution of the thymic medulla with associated loss of medullary epithelium, Hassall's corpuscles, class II antigen expression, and maturation of thymocytes. While the control group underwent rapid and complete regeneration of the medulla post-CsA, however, the medullary changes in the irradiated group were prolonged or permanent. Most of these animals had changes of chronic GVHD. Older LEW rats had a more prominent medulla prior to CsA. In contrast to younger rats, the medulla did not show significant involution with CsA. While the Hassall's corpuscles disappeared, the medullae still had fusiform epithelium, dendritic cells, and class II antigen expression. Phenotype stains demonstrated many mature-appearing CD4+/CD8- lymphocytes. In light of evidence indicating the importance of the medullary microenvironment to the maintenance of self tolerance, the medullary effects of CsA are most likely essential to the development of autoimmunity. Young rats rapidly lose the ability to maintain tolerance. While unirradiated rats rapidly reestablish the proper microenvironment following CsA, irradiated rats have a prolonged loss. Older rats may resist the development of autoimmunity by retaining the medullary microenvironment.
Behavior of 2.8- and 3.2-eV photoluminescence bands in Mg-doped GaN at different temperatures and excitation densities

The blue and ultraviolet photoluminescence bands in Mg-doped GaN have been investigated over a wide range of temperatures and excitation intensities. Redshifts of the bands were observed with increasing temperature. The bands underwent a blueshift with increased excitation density. The observed shifts of the 3.2 eV band are explained by a potential fluctuation model for a compensated semiconductor. In contrast, the shifts of the 2.8 eV band are essentially related to saturation of luminescence from distant donor-acceptor pairs responsible for this emission. Thermal quenching of the 2.8 eV luminescence band was observed at high temperatures with an activation energy of 0.3--0.4 eV. It is attributed to thermal release of trapped electrons from a deep donor state.
Quantum Catalysis of Magnetic Phase Transitions in a Quantum Simulator

We control quantum fluctuations to create the ground state magnetic phases of a classical Ising model with a tunable longitudinal magnetic field using a system of 6 to 10 atomic ion spins. Because of the long-range Ising interactions, the various ground state spin configurations are separated by multiple first-order phase transitions, which in our zero temperature system cannot be driven by thermal fluctuations. We instead use a transverse magnetic field as a quantum catalyst to observe the first steps of the complete fractal devil's staircase, which emerges in the thermodynamic limit and can be mapped to a large number of many-body and energy-optimization problems.
Friction and Wear of Refractory Compounds

The sliding characteristics of the borides, carbides, nitrides, and silicides and oxides of several metals were investigated in air at temperatures up to 2000 F. Tests were of the crossed-cylinder type and friction and wear effects measured under repetitive sliding conditions. Correlation of the friction and wear characteristics with known or predicted solid solubility was only fair. High hardness coupled with low fracture strength and excessive brittleness of these materials produced fracturing of asperities and abrasive wear before a true measure of the adhesion could be obtained. Oxidation products were found to provide some lubrication at elevated temperatures, particularly the formation of B2O3 on boron carbide. However, none was effective at room temperature. Contributed by the A.S.L.E. Technical Committee on Lubrication Fundamentals and presented at the Annual Meeting of the American Society of Lubrication Engineers held in Cincinnati, Ohio, April, 1960.