cssi/SciSciGPT-SciSciNet huggingface dataset:
Anthropogenic noise and the bioacoustics of terrestrial invertebrates

Anthropogenic noise is an important issue of environmental concern owing to its wide-ranging effects on the physiology, behavior and ecology of animals. To date, research has focused on the impacts of far-field airborne noise (i.e. pressure waves) on vertebrates, with few exceptions. However, invertebrates and the other acoustic modalities they rely on, primarily near-field airborne and substrate-borne sound (i.e. particle motion and vibrations, respectively) have received little attention. Here, we review the literature on the impacts of different types of anthropogenic noise (airborne far-field, airborne near-field, substrate-borne) on terrestrial invertebrates. Using literature on invertebrate bioacoustics, we propose a framework for understanding the potential impact of anthropogenic noise on invertebrates and outline predictions of possible constraints and adaptations for invertebrates in responding to anthropogenic noise. We argue that understanding the impacts of anthropogenic noise requires us to consider multiple modalities of sound and to cultivate a broader understanding of invertebrate bioacoustics.
NDARC NASA Design and Analysis of Rotorcraft

The NASA Design and Analysis of Rotorcraft (NDARC) software is an aircraft system analysis tool that supports both conceptual design efforts and technology impact assessments. The principal tasks are to design (or size) a rotorcraft to meet specified requirements, including vertical takeoff and landing (VTOL) operation, and then analyze the performance of the aircraft for a set of conditions. For broad and lasting utility, it is important that the code have the capability to model general rotorcraft configurations, and estimate the performance and weights of advanced rotor concepts. The architecture of the NDARC code accommodates configuration flexibility, a hierarchy of models, and ultimately multidisciplinary design, analysis, and optimization. Initially the software is implemented with low-fidelity models, typically appropriate for the conceptual design environment. An NDARC job consists of one or more cases, each case optionally performing design and analysis tasks. The design task involves sizing the rotorcraft to satisfy specified design conditions and missions. The analysis tasks can include off-design mission performance calculation, flight performance calculation for point operating conditions, and generation of subsystem or component performance maps. For analysis tasks, the aircraft description can come from the sizing task, from a previous case or a previous NDARC job, or be independently generated (typically the description of an existing aircraft). The aircraft consists of a set of components, including fuselage, rotors, wings, tails, and propulsion. For each component, attributes such as performance, drag, and weight can be calculated; and the aircraft attributes are obtained from the sum of the component attributes. Description and analysis of conventional rotorcraft configurations is facilitated, while retaining the capability to model novel and advanced concepts. Specific rotorcraft configurations considered are single-main-rotor and tail-rotor helicopter, tandem helicopter, coaxial helicopter, and tiltrotor. The architecture of the code accommodates addition of new or higher-fidelity attribute models for a component, as well as addition of new components.
Maturation of arteriovenous fistulas in patients with ventricular assist devices.

Objective:Postoperative renal dysfunction necessitating hemodialysis after implantation of ventricular assist devices presents a challenge with respect to establishment of hemodialysis access. Lack...
A step in the right direction: Lessons learned from the USMLE Step 1.

Every year, thousands of medical students in the United States and internationally take the USMLE Step 1 exam, just as their mentors did before them. Numerous commentators – physicians and students...
The Interplay between Retinal Pathways of Cholesterol Output and Its Effects on Mouse Retina.

In mammalian retina, cholesterol excess is mainly metabolized to oxysterols by cytochromes P450 27A1 (CYP27A1) and 46A1 (CYP46A1) or removed on lipoprotein particles containing apolipoprotein E (APOE). In contrast, esterification by sterol-O-acyltransferase 1 (SOAT) plays only a minor role in this process. Accordingly, retinal cholesterol levels are unchanged in Soat1−/− mice but are increased in Cyp27a1−/−Cyp46a1−/− and Apoe−/− mice. Herein, we characterized Cyp27a1−/−Cyp46a1−/−Soat1−/− and Cyp27a1−/−Cyp46a1−/−Apoe−/− mice. In the former, retinal cholesterol levels, anatomical gross structure, and vasculature were normal, yet the electroretinographic responses were impaired. Conversely, in Cyp27a1−/−Cyp46a1−/−Apoe−/− mice, retinal cholesterol levels were increased while anatomical structure and vasculature were unaffected with only male mice showing a decrease in electroretinographic responses. Sterol profiling, qRT-PCR, proteomics, and transmission electron microscopy mapped potential compensatory mechanisms in the Cyp27a1−/−Cyp46a1−/−Soat1−/− and Cyp27a1−/−Cyp46a1−/−Apoe−/− retina. These included decreased cholesterol biosynthesis along with enhanced formation of intra- and extracellular vesicles, possibly a reserve mechanism for lowering retinal cholesterol. In addition, there was altered abundance of proteins in Cyp27a1−/−Cyp46a1−/−Soat1−/− mice that can affect photoreceptor function, survival, and retinal energy homeostasis (glucose and fatty acid metabolism). Therefore, the levels of retinal cholesterol do not seem to predict retinal abnormalities, and it is rather the network of compensatory mechanisms that appears to determine retinal phenotype.
The Incredible Lightness of Water Vapor

AbstractThe molar mass of water vapor is much less than that of dry air. This makes a moist parcel lighter than a dry parcel of the same temperature and pressure. This effect is referred to as the ...
DXA after menopause.

To the Editor : I want to commend Drs. Tough DeSapri and Brook for their excellent summary on the use of the FRAX tool in assessing the need for dual-energy x-ray absorptiometry (DXA) in postmenopausal women.[1][1] A thought experiment that we engage in with our fellows is to take the FRAX tool and
Development of Cu2+-Based Distance Methods and Force Field Parameters for the Determination of PNA Conformations and Dynamics by EPR and MD Simulations.

Peptide nucleic acids (PNA) are a promising group of synthetic analogues of DNA and RNA that offer several distinct advantages over the naturally-occurring nucleic acids for applications such as bi...
Application-Oriented Marine Isomerases in Biocatalysis.

The class EC 5.xx, a group of enzymes that interconvert optical, geometric, or positional isomers are interesting biocatalysts for the synthesis of pharmaceuticals and pharmaceutical intermediates. This class, named “isomerases,” can transform cheap biomolecules into expensive isomers with suitable stereochemistry useful in synthetic medicinal chemistry, and interesting cases of production of l-ribose, d-psicose, lactulose, and d-phenylalanine are known. However, in two published reports about potential biocatalysts of marine origin, isomerases are hardly mentioned. Therefore, it is of interest to deepen the knowledge of these biocatalysts from the marine environment with this specialized in-depth analysis conducted using a literature search without time limit constraints. In this review, the focus is dedicated mainly to example applications in biocatalysis that are not numerous confirming the general view previously reported. However, from this overall literature analysis, curiosity-driven scientific interest for marine isomerases seems to have been long-standing. However, the major fields in which application examples are framed are placed at the cutting edge of current biotechnological development. Since these enzymes can offer properties of industrial interest, this will act as a promoter for future studies of marine-originating isomerases in applied biocatalysis.
Lipid nanoparticle formulation of niclosamide (nano NCM) effectively inhibits SARS-CoV-2 replication in vitro .

As exemplified by the COVID-19 pandemic, highly infective respiratory viruses can spread rapidly in the population because of lack of effective approaches to control viral replication and spread. Niclosamide (NCM) is an old anthelminthic drug (World Health Organization essential medicine list) with pleiotropic pharmacological activities. Several recent publications demonstrated that NCM has broad antiviral activities and potently inhibits viral replication, including replication of SARS-CoV-2, SARS-CoV, and dengue viruses. Unfortunately, NCM is almost completely insoluble in water, which limits its clinical use. We developed a cost-effective lipid nanoparticle formulation of NCM (nano NCM) using only FDA-approved excipient and demonstrated potency against SARS-CoV-2 infection in cells (Vero E6 and ACE2-expressing lung epithelium cells).
RE: Effect of Nasopharyngeal Carcinoma-Derived Exosomes on Human Regulatory T Cells

Ca2+ signals are critical for T-cell function, and Ca2+ influx is an early event in T-cell activation. TEX, ubiquitously present in the tumor microenvironment and plasma, carry a cargo of suppressive and stimulatory molecules. TEX bind to the surface of immune cells, suppressing functions of some T cells while up-regulating functions of others. To determine whether binding of TEX or exosomes produced by normal cells (EXO) to primary T cells results in delivery of signals regulating activation, human PBMC or different freshlyisolated T-cell subsets were co-incubated with PKH-26 labeled exosomes isolated from normal or HNSCC plasma specimens and from supernatants of HNSCC cell lines as described by us (Muller et al., J. Immunol. Methods, 2014). CD4+ T cell, CD8+ T cell and CD4 + CD39+ Treg were isolated from normal PBMC using AutoMACS. Binding of PKH-26-labeled TEX or EXO by T cells, NK cells or monocytes was evaluated following co-incubation for 24–96 h using an AMNIS image cytometer. The strength of Ca2+ influx induced by TEX or EXO in various T cells was measured by confocal microscopy after staining the T cells with a Fura-2 or Fluo-4 dye. AMNIS flow data showed that binding of TEX and EXO to T cells was time and dose-dependent, but exosomes were not internalized even after prolonged [96 h] co-incubation. Ca2+ influx was time dependent and was observed only after co-incubation of T cells with TEX but not (or only minimally) with EXO. Among T cells, CD4 + CD39+ Treg were preferentially targeted by TEX, showing the strongest Ca2+ influx within 30 min. In AMNIS, TEX binding to Treg gave a significantly stronger signal than that measured with CD4+ or CD8+ T cells. This strong, sustained Ca2+ influx induced in Treg by TEX is consistent with our previous functional data demonstrating selective TEX-mediated Treg activation and proliferation. The data also emphasizes the fact that activation of Treg functions by TEX is regulated through signals delivered to the Treg surface and does not require exosome up-take or their internalization by the target cells.
Various Preparations of Elemental Boron

Elemental boron has been prepared by the hydrogen reduction of boron bromide on hot wires and by other methods. Crystals up to 0.1 mm in length were grown on a tantalum wire at 1500°C. Boron diffusion into the wire at this temperature was serious. B4C crystals up to 1 mm in diameter were grown on a graphite disk heated to 2000°C. Infrared transmission, resistivity, and hardness tests were made on the samples.
Interactive and Dynamic Graphics for Data Analysis: A Case Study On Quasar Data

This paper describes the use of interactive and dynamic statistical graphics for a classification task of separating quasars from non-squasars, using measurements on red and blue plates, radio and optical values. Multivariate plotting techniques used are the scatterplot matrix, parallel coordinate plot and tours, an extension of 3D rotation to arbitrary dimensional rotation.
Improving hidden Markov models with a similarity histogram for typing pattern biometrics

A highly feasible user-authentication biometric is to examine and identify the typing patterns exhibited among people in order to authenticate the users whenever during a user session. We interpret keystroke data as four-dimensional timing vectors, and clusters of keystroke vectors can thus form the static basis for analysis. Associated with the key transition is also a more dynamic probability distribution that can be used to form a Markov chain. For a special keystroke, there is ideally one cluster of vectors that resembles it; but since the actual observed cluster are usually formed from various different keys, only a set of probabilities to what a given key really is assured. This can be transcribed as a hidden state being observed in a hidden Markov model (HMM). In our previous research, we implemented a user-authentication process with a HMM that learned the special typing patterns from individuals, and then identified them. During the training stage, the timing information of each keystroke within a word was first gathered from each user as repeated words were typed. Then the key-transition and observation probability matrices for each user were built from the gathered typing data. Afterward, the model was tested with typing data from words that each user had entered separately to match their profiles. We chose to examine the typing patterns of users' login names since they would be the most frequently typed individual words. We found the HMM approach to be very suitable for our process due to the stochastic nature of typing patterns, and because it reveals pattern distributions and predicts possible keystroke sequences. However, an issue regarding the accuracy of observation being translated by the probability matrices was noted in the first-order non-ergodic HMM that was applied. Extended from our previous work, we propose a method to improve the process with a histogram of the similarity measured between the actual observation and the cluster centroid that it resembles. Such a histogram can be easily applied to higher-order models as the key factor when setting matching thresholds. The experimental results are thus improved due to the adaptive histogram in the process.
Performance enhancement in deep-submicron poly-SiGe-gated CMOS devices

Poly-SiGe- and poly-Si-gated N/PMOS devices with physical channel lengths down to 0.1 /spl mu/m and gate oxide thicknesses down to 25 /spl Aring/ were fabricated. Device performance and reliability were characterized. The poly SiGe-gated NMOS and PMOS devices provide superior current drive due to less gate-depletion effect and higher inversion hole mobility in poly-SiGe-gated devices. In addition, gate oxide integrity in poly-SiGe-gated MOSFET is as good as poly-Si-gated device. Poly-SiGe-gated PMOSFET has better reliability than poly-Si-gated PMOSFET due to reduction of boron penetration.
Orientation dependence of the magnetic field distributions in large single crystals of YBa2Cu3O7

Abstract We have analyzed transverse field μ SR data taken for fields parallel to, 45 ∘ from, and 90 ∘ from the c -axis of large crystals of YBa 2 Cu 3 O 7 . For each orientation, the applied field was about 10 mT and in a μ SR apparatus at TRIUMF. The crystals had significant green phase inclusions which pinned the vortices from very near the transition temperature of about 92 K. Four different fitting functions were applied. The last fitting function used an anisotropic field distribution developed by Daemen et al. which should be appropriate for our low-field case and gives greater freedom to the function. With this function we were able to obtain fits for all angles using a reasonable penetration depth in the ab plane ( λ ab = 0.14 μ m ) and a reasonable mass asymmetry, Γ = 30 .
Formation of γ‐Keto Esters From β‐Keto Esters: Methyl 5,5‐Dimethyl‐4‐Oxohexanoate

Methyl 5,5-dimethyl-4-oxohexanoate R Methyl 4,4-dimethyl-3-oxopentanoate P Methyl 5,5-dimethyl-4-oxohexanoate Keywords: diethylzinc, pyrophoric; esters, of substituted monobasic acids, keto esters; ketones, monoketones, keto esters; alkylation, C-alkylation
Summer Annual and Winter Annual Weed Control in Field Soil and Soilless Media with Gallery (lsoxaben)

Abstract Field and container experiments were conducted to evaluate Gallery (isoxaben) efficacy on several common nursery and landscape weeds. Gallery was applied at rates from 0.14 to 1.1 kg ai/ha...
The developmental expression in rat of proteases furin, PC1, PC2, and carboxypeptidase E: implications for early maturation of proteolytic processing capacity

The genes encoding mammalian subtilisin-like endoproteases furin, PC1, and PC2 have been isolated and are implicated in endoproteolytic cleavage of precursor molecules, which is a key step in posttranslational maturation of proproteins and neuropeptide precursors. Following endoproteolytic cleavage, the carboxyl-terminal basic amino acid residues are removed by carboxypeptidase E (CPE). We have examined the expression of these genes during rat development by in situ hybridization and compared their expression patterns to those of potential substrates. In the primitive streak stage of embryogenesis (e7) furin is expressed in both endoderm and mesoderm. This overall expression pattern is maintained until e10, when a distinctly higher level of furin expression is observed in the heart and liver primordia. In mid- and late gestational stages furin is broadly expressed in the peripheral tissues, and, therefore, may contribute to the proteolytic processing of numerous fetal proproteins, such as the precursors for natriuretic factors in heart and IGF-II throughout the embryo. In contrast, the expressions of PC1 and PC2 are initiated much later (e13) and are mainly confined to the developing nervous system, but with distinct spatial distributions. At midgestational ages, PC1 mRNA is mainly expressed in the hypothalamus and peripheral ganglia, while PC2 is expressed not only in these tissues but also in the thalamus, midbrain, pons, medulla oblongata, cortical plate, and spinal cord. Besides neuropeptide precursor processing in the nervous system, PC1 and PC2 may also be involved in the proteolytic processing in additional regions as evidenced by the finding that both PC1 and PC2 mRNAs are expressed in the embryonic pituitary and pancreas. CPE mRNA is expressed in both neural tissues and some non-neural tissues. In the developing nervous system, the expression of CPE encompasses all the regions where PC1 and PC2 are expressed and in fact includes most brain regions as neurogenesis proceeds. CPE mRNA is also expressed in some peripheral tissues, such as the embryonic heart and cartilage primordia, and in some cases its expression overlaps with furin expression. Thus, CPE may functionally collaborate during development with the subtilisin family of endoproteases in the completion of proteolytic processing of neuropeptide precursors in the nervous system and proproteins in the peripheral tissues. In the pituitary, the endoproteolytic processing of polyfunctional precursor proopiomelanocortin (POMC) occurs in a developmentally regulated manner. We have shown that while PC2 mRNA is predominantly expressed in the intermediate lobe in the adult, we observed an increased expression of PC2 mRNA in developing rat anterior lobe, peaking at early postnatal stages.(ABSTRACT TRUNCATED AT 400 WORDS)
Frost grain size metamorphism: Implications for remote sensing of planetary surfaces

The effective grain size of a material on a planetary surface affects the strength of absorption features observed in the reflectance of a particulate surface. In the case of a planetary surface containing volatile ices, the absorption characteristics can change in connection with processes leading to a change in the grain size of the material. The present investigation is concerned with an evaluation regarding the occurrence of such processes and the implications for remote sensing applications. It is found that quantitative modeling of the kinetics of grain growth and destruction by thermal and nonthermal processes can provide a means to reconcile apparent optical paths in the volatile portions of planetary surfaces with the physical history of those surfaces. Attention is also given to conditions in the case of the Pluto/Triton system, Uranus and Saturnian satellites, and the Galilean system.
Hydrogenation of α-Methylstyrene in a Piston-Oscillating Monolith Reactor

The hydrogenation of α-methylstyrene (AMS) to cumene was investigated in a novel piston-oscillating monolith reactor (POMR). Low-frequency (0−17.5 Hz) and -amplitude (2.5 mm) mechanical oscillations were applied to the three-phase system at 46 °C and 0.44 MPa of H2. For comparison purposes, the reaction was also carried out in a stirred tank at identical temperatures and pressures and at similar power input per volume. Results show activity improvements of up to 84% for 17.5 Hz, 2.5 mm piston oscillations over low-frequency gas flow pulsing conditions, and significantly greater improvements when compared to trickle beds or conventional monolith reactors. The POMR also gives as good or better selectivity toward cumene than a stirred tank at identical conditions. While the effects of catalyst pretreatment and its impact on the Pd crystallite size also have an important role in determining the catalyst activity and long-term stability in AMS hydrogenation, these results suggest that the impact of low-frequen...
NASA Program of Airborne Optical Observations

NASA's Ames Research Center currently operates a Convair 990 four-engine jet transport as a National Facility for airborne scientific research (astronomy, aurora, airglow, meteorology, earth resources). This aircraft can carry about twelve experiments to 12 km for several hours. A second aircraft, a twin-engine Lear Jet, has been used on a limited basis for airborne science and can carry one experiment to 15 km for 1 h. Mobility and altitude are the principal advantages over ground sites, while large payload and personnel carrying capabilities, combined with ease of operations and relatively low cost, are the main advantages compared to balloons, rockets, or satellites. Typical airborne instrumentation and scientific results are presented.
Wortmannin reduces insulin signaling and death in seizure-prone Pcmt1-/- mice.

L-isoaspartyl (D-aspartyl) O-methyltransferase deficient mice (Pcmt1−/−) accumulate isomerized aspartyl residues in intracellular proteins until their death due to seizures at approximately 45 days. Previous studies have shown that these mice have constitutively activated insulin signaling in their brains, and that these brains are 20–30% larger than those from age-matched wild-type animals. To determine whether insulin pathway activation and brain enlargement is responsible for the fatal seizures, we administered wortmannin, an inhibitor of the phosphoinositide 3-kinase that catalyzes an early step in the insulin pathway. Oral wortmannin reduced the average brain size in the Pcmt1−/− animals to within 6% of the wild-type DMSO administered controls, and nearly doubled the lifespan of Pcmt1−/− at 60% survival of the original population. Immunoblotting revealed significant decreases in phosphorylation of Akt, PDK1, and mTOR in Pcmt1−/− mice and Akt and PDK1 in wild-type animals upon treatment with wortmannin. These data suggest activation of the insulin pathway and its resulting brain enlargement contributes to the early death of Pcmt1−/− mice, but is not solely responsible for the early death observed in these animals.
Bleu Ribbon Chocolates: How Can Small Businesses Adapt to a Changing Environment?

Bleu Ribbon Chocolates is a small regional manufacturer of high-quality chocolate that sells its products via trade accounts, corporate-owned stores, and online/mail. Historically, the company has ...
Hemocyte classification and differential counts in the dungeness crab, Cancer magister

Abstract The primary purposes of this research were to describe and classify the circulating hemocytes of Cancer magister and devise a method for making differential hemocyte counts for crustaceans. C. magister hemocytes were classified using two simple criteria: the presence or absence of cytoplasmic granules and staining characteristics of the granules, if present. Hyalinocytes (HC) were devoid of granules, intermediate granulocytes (IG) contained basophilic granules or a mixture of basophilic and acidophilic granules, and eosinophilic granulocytes (EG) contained large, acidophilic granules. Hemocyte renewal and a hypothetical maturation sequence of C. magister hemocytes are described and discussed. Differential counts revealed that granulocytes were more abundant than hyalinocytes. For 22 crabs, the mean percentage (and range) of each hemocyte class was: IG, 65.97 (57.50–73.80); EG, 17.76 (4.70–26.47); and HC, 16.25 (3.40–34.67). After additional data are collected and analyzed, the routine use of differential counts may prove to be a valuable method for monitoring the status and health of C. magister and perhaps other crustaceans as well.
A Method of Growing Oriented Sections of Certain Optical Crystals

A new method is described for growing extended crystal sections normal to a threefold axis from melts of sodium nitrate, and of certain alkali halides such as potassium bromide and potassium iodide. Such sections result when crystallization in the melt is started at a mica cleavage surface and is allowed to proceed in a direction normal thereto, the mica acting as an insoluble, infusible seed for the new crystal growth. The mica cleavage surface adsorbs from the melt a hexagonal net of alkali ions whose side is 5.17A, and this plane net constitutes the first layer of the new crystal growth.
Aflatoxicol M1, A New Metabolite of Aflatoxicol

1. Using dog liver microsomal preparations, we have isolated and identified a new metabolite of aflatoxicol, aflatoxicol M1; this metabolic transformation is analogous to the conversion of aflatoxin B1 to aflatoxin M1. 2. Aflatoxicol M1 can also be produced from aflatoxin M1 by a reductase present in rabbit liver cytosol, a reaction analogous to the reduction of aflatoxin B1 to aflatoxicol. 3. In addition, aflatoxicol M1 can be oxidized to aflatoxin M1 by a carbon monoxide-insensitive dehydrogenase activity associated with human liver microsomes, a reaction analogous to the production of aflatoxin B1 from aflatoxicol by this fraction. 4. Ultra-violet, fluorescence, and mass spectral characteristics of aflatoxicol M1 are described. 5. The significance of this new aflatoxin metabolite and the possibility that it may be biologically active are discussed.
Exploring zipping and assembly as a protein folding principle.

It has been proposed that proteins fold by a process called Zipping and Assembly (ZA277;985-994 that folding rates correlate with contact order, (b) neither too few nor too many nucleation sites per chain, and (c) assembly steps that do not occur too early in the folding process. We find that the efficiency increases with chain length, although our range of chain lengths is limited. We believe these insights may be useful for developing faster protein conformational search algorithms.
Discontinuity of 26 s rRNA in Acanthamoeba castellani.

A low molecular weight RNA has been identified as a constituent of the large rRNA (26 s rRNA) in the free-living amoeba, Acanthamoeba castellani, by using treatments designed to disrupt complementary base pairing (e.g. brief heating, dimethylsulfoxide, low salt or low pH, etc.). The molecular size of the low molecular weight RNA, estimated from its mobility on polyacrylamide gels, is 4.3 × 104 daltons. Additionally, exposure of 26 s rRNA to the above treatments led to the observation that the remainder of the molecule is discontinuous and composed of two sharply defined RNA species with mobilities on polyacrylamide gels corresponding to molecular weights of 0.88 × 106 and 0.60 × 106 daltons. The larger rRNA derived from the dissociation of the 26 s rRNA (i.e. 0.88 × 106 daltons) is identical in size to the rRNA characteristic of the small ribosomal subunit. The demonstration of low molecular weight RNA in the large rRNA of a single-celled eukaryote supports the suggestion that low molecular weight RNA may represent a distinct evolutionary difference between prokaryotes and eukaryotes. Moreover, the discontinuity of the remainder of the 26 s rRNA in A. castellani indicates that further modification of the large rRNA may have occurred during evolution of eukaryotic organisms.
Microarray Analysis of Host Cell Gene Transcription in Response to Varicella-Zoster Virus Infection of Human T Cells and Fibroblasts In Vitro and SCIDhu Skin Xenografts In Vivo

During primary infection, varicella-zoster virus (VZV) is spread via lymphocytes to skin, where it induces a rash and establishes latency in sensory ganglia. A live, attenuated varicella vaccine (vOka) was generated by using the VZV Oka strain (pOka), but the molecular basis for vOka attenuation remains unknown. Little is known concerning the effects of wild-type or attenuated VZV on cellular gene regulation in the host cells that are critical for pathogenesis. In this study, transcriptional profiles of primary human T cells and fibroblasts infected with VZV in cell culture were determined by using 40,000-spot human cDNA microarrays. Cellular gene transcription in human skin xenografts in SCID mice that were infected with VZV in vivo was also evaluated. The profiles of cellular gene transcripts that were induced or inhibited in infected human foreskin fibroblasts (HFFs), T cells, and skin in response to pOka and vOka infection were similar. However, significant alterations in cellular gene regulation were observed among the three differentiated human cell types that were examined, suggesting specific differences in the biological consequences of VZV infection related to the target cell. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time reverse transcription-PCR analysis of VZV-infected cells. Interestingly, the transcription of caspase 8 was found to be decreased in infected T cells but not in HFFs or skin, which may signify a tissue-specific antiapoptosis mechanism. The use of microarrays to demonstrate differences in effects on host cell genes in primary, biologically relevant cell types provides background information for experiments to link these various response phenotypes with mechanisms of VZV pathogenesis that are important for the natural course of human infection.
Glyceroneogenesis in rat and guinea pig adipose tissue during the fed and fasted states

While both pyruvate and lactate are good substrates for glyceride-glycerol synthesis in isolated adipocytes from fed rats and guinea pigs, neither alanine nor serine appear to support glyceroneogenesis. Fasting increases the proportion of radioactive pyruvate or lactate incorporated into glyceride-glycerol and reciprocally decreases the proportion incorporated into fatty acids. However, the total incorporation of radioactivity into triacylglycerol is considerably lower in isolated adipocytes from fasted than from fed animals. Addition of glucose to the incubation medium promotes the incorporation of radioactive lactate into both fatty acids and glyceride-glycerol by adipocytes from fasted as well as fed animals. The concentration of alpha-glycerolphosphate is considerably higher in adipose tissue of fed than fasted animals. In general, these results support the presence of a glyceroneogenic pathway in rat and guinea pig adipose tissue. However, it would appear that the physiologic significance of this pathway is less important in the fasted than the fed state, where it may play some role in the esterification of intracellular fatty acids.
Involvement of 5-methylcytosine in sunlight-induced mutagenesis.

Abstract In human skin cancers, more than 30 % of all mutations in the p53 gene are transitions at dipyrimidines within the sequence context CpG, i.e. 5′-TCG and 5′-CCG, found at several mutational hotspots. Since CpGs are methylated along the p53 gene, these mutations may be derived from solar UV-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. In Xorder to define the contribution of 5-methylcytosine to sunlight-induced mutations, we have used mouse fibroblasts containing the CpG-methylated lacI transgene as a mutational target. We sequenced 182 UVC (254 nm UV)-induced mutations and 170 mutations induced by a solar UV simulator, along with 75 mutations in untreated cells. Only a few of the mutations in untreated cells were transitions at dipyrimidines, but more than 95 % of the UVC and solar irradiation-induced mutations were targeted to dipyrimidine sites, the majority being transitions. After UVC irradiation, 6 % of the base substitutions were at dipyrimidines containing 5-methylcytosine and only 2.2 % of all mutations were transitions within this sequence context. However, 24 % of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of them were transitions. Two sunlight-induced mutational hotspots at methylated CpGs correlated with sequences that form the highest levels of cyclobutane pyrimidine dimers after irradiation with sunlight but not with UVC. The data indicate that dipyrimidines that contain 5-methylcytosine are preferential targets for sunlight-induced mutagenesis in cultured mammalian cells, thus explaining the large proportion of p53 mutations at such sites in skin tumors in vivo.
An indwelling cannula system for the primate eye.

Abstract An indwelling cannula system was designed as an instrument for chronic drug infusion into the vitreous cavity and tested in the cynomolgus monkey eye with repeated injections or continuous infusion using a pumping device. The cannula was passed through the pars plana and its tip situated in the vitreous cavity close to the macular area. Clinical observations up to 18 months did not reveal any adverse effects due to implantation. Histopathological observations from 1 week to 18 months after surgery revealed tissue proliferation around the cannula was minimal and localized only at the wound site, where proliferative tissue originated from the episclera and ciliary epithelium. Retina and choroid at the posterior pole showed normal morphology. Light microscopic autoradiograms demonstrated the function of this system. Injections of tritiated leucine through the cannula resulted in narrow bands of radioactive labelling of the photoreceptor outer segments corresponding to each injection. In contrast, chronic delivery using the pumping device resulted in a diffuse and wide band of labelling. These results strongly suggest that this system did not adversely affect the eye and that repeated intravitreal injections or chronic drug delivery into the vitreous are feasible using this system. Furthermore, autoradiographic results suggest that the drugs infused into the vitreous cavity spread readily into the retina.
Developments in and prospects for external debt position and burden of developing countries: The case of Korea

Abstract The delay of strong economic recovery by industrialized nations, slowed world export growth, and higher interest rates have worsened the financial situation of a number of developing countries which have relied on external borrowings to sustain current account deficits and protect economic development. Recently, well-publicized concerns over the ability to these countries to repay their considerable debt burden have been raised. To shed light on these concerns, the paper focuses on Korea—one of the heavier debt-holding countries. It describes the process through which Korea has acquired its external debt over the past decade, assesses the trends in its debt burden, and presents prospects for the period 1982–1986. Using the Korean experience, the paper shows that the most common indicators used for evaluating foreign debt burden, such as the long-term service ratio, need to be supplemented by other measurements. In a world economy characterized by short-term debts with variable interest rates, the paper suggests that an important tool in analyzing the external debt burden should be the short-term debt burden.
Generalized Bullous Eruption after Routine Vaccination in a Child with Diffuse Cutaneous Mastocytosis

Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School Division of Allergy, Immunology and Pulmonology, MassGeneral Hospital for Children, Harvard Medical School Department of Dermatology, Massachusetts General Hospital, Harvard Medical School Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School Conflicts of interest: M.C.C. has received consultancy fees from Merck and Sanofi and has received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication August 16, 2012; accepted for publication August 28, 2012. Available online November 6, 2012. Cite this article as: Bankova LG, Walter JE, Iyengar SR, Lorenzo ME, Hornick JL, Castells MC. Generalized bullous eruption after foutine vaccination in a child with diffuse cutaneous mastocytosis. J Allergy Clin Immunol: In Practice 2013;1:94-6. http://dx.doi.org/10.1016/j.jaip.2012.08.008. Corresponding author: Mariana C. Castells, MD, PhD, One Jimmy Fund Way, Smith Building, Rm 626 D, Boston, MA 02115. E-mail: mcastells@partners.org. J Allergy Clin Immunol: In Practice 2013;1:94-6. 2213-2198/$36.0
Threonine Requirement and Threonine Imbalance in Broiler Chickens

Three experiments were conducted to determine the effect of excess dietary protein on threonine requirement of broiler chicks to 14 d of age (Experiments 1 and 2) and to determine the threonine requirement from 16 to 28 d of age (Experiment 3). Two dietary protein levels were used in Experiments 1 and 2:20% CP in a threonine-limiting basal diet containing wheat, peanut meal, and selected amino acids and 25% CP in the same basal diet supplemented with a mixture of amino acids lacking threonine. A threonine-limiting 25% CP diet based on corn, soybean meal, and amino acids was also included in Experiment 2. The threonine requirement of chicks from 16 to 28 d of age was determined using a single CP level (20%) in Experiment 3. Threonine requirements were estimated by broken line regression analysis of weight gain and feed efficiency. Threonine requirements based on weight gain were 7.7 and 6.7 g/kg of diet in Experiments 1 and 2, respectively, for chicks receiving the 20% CP diets. The requirements increased to 8.6 and 8.2 g/kg, respectively, for chicks fed the 25% CP diets based on wheat, peanut meal, and amino acids. The requirement for maximum weight gain of chicks fed 25% CP based on corn, soybean meal, and amino acids was 7.7 g/kg of diet. However, chicks ate more of this diet, and on an intake basis, the requirement of the chicks fed the 25% CP diets based on wheat and peanut meal or corn and soybean meal did not differ. Requirements based on feed efficiency were equal to, or less than, those based on weight gain in Experiments 1 and 2. Body moisture and fat contents were affected by dietary CP level (P < .01), ingredient composition (P < .01), and threonine content (P < .05). Estimates of threonine requirements based on regression analysis of plasma threonine concentrations were higher than those based on weight gain or feed efficiency. The threonine requirements of chicks fed a 20% CP diet from 16 to 28 d of age were 6.3 and 6.9 g/kg of diet based on weight gain and feed efficiency, respectively.
Epidemiological Standardization of a Test for Susceptibility to Mumps

An enzyme-linked immunosorbent assay (ELISA) for antibody to mumps virus is described. It is standardized with sera from putatively susceptible and immune populations. The ranges for 49 susceptible and 19 immune children were an optical density of -0.020 to 0.028 and 0.133 to 0.640, respectively. When compared with the microneutralization assay for evaluating vaccine responses, the ELISA appeared to be more sensitive while retaining its specificity. The failure rate after mumps vaccination in 301 children was 1.7% (5 of 301) by the ELISA and 12% (36 of 301) or 7.6% (23 of 301) by the microneutralization assay, depending on whether a high (30-100 50% tissue culture infectious dose [TCID50]) or low (10-20 TCID50) dose of virus was used.
Wood-derived copper–graphite composites produced via additive-assisted electrodeposition

An additive-assisted copper electroplating technique designed for infiltrating high-aspect-ratio pores was adapted to work with three-dimensional wood-derived graphitic scaffolds with aspect ratios ranging from 15 to 300. The poor wettability of the carbon/copper system necessitates the development of alternative infiltration techniques to produce composite structures from highly porous precursors such as wood-derived graphite. By incorporating electrolyte additives, copper infiltration was demonstrated into red oak-derived graphite scaffolds, producing a composite with a biologically-derived microstructure. Copper infiltration was studied as a function of electrolyte chemistry and deposition time in two dimensions using electron microscopy techniques and in three dimensions using X-ray computed tomography.
Paul Ehrlich: pathfinder in cell biology. 1. Chronicle of his life and accomplishments in immunology, cancer research, and chemotherapy.

The paper reviews the life of Paul Ehrlich and his biomedical accomplishments in immunology, cancer research, and chemotherapy. Ehrlich achieved renown as an organic chemist, histologist, hematologist, immunologist, and pharmacologist. He disliked the formality of school but managed to excel in Latin and mathematics. His role model was an older cousin, Carl Welgert, who became a lifelong friend. Ehrlich studied medicine at Breslau, Strasbourg, Freiburg, and Leipzig, coming under the influence of Wilhelm Waldeyer, Julius Cohnheim, Rudolf Heidenhein, and Ferdinand Cohn. As a medical student, Ehrlich was captivated by structural organic chemistry and dyes. When he was 23, his first paper was published on selective staining. His doctoral thesis, “Contribution to the Theory and Practice of Histological Staining” contained most of the germinal ideas that would guide his future career. Most of his early work was centered in Berlin at Charite Hospital, where he did pioneering studies on blood and intravital stain...
Pro-inflammatory Cytokines and Environmental Stress Cause p38 Mitogen-activated Protein Kinase Activation by Dual Phosphorylation on Tyrosine and Threonine (∗)

Protein kinases activated by dual phosphorylation on Tyr and Thr (MAP kinases) can be grouped into two major classes: ERK and JNK. The ERK group regulates multiple targets in response to growth factors via a Ras-dependent mechanism. In contrast, JNK activates the transcription factor c-Jun in response to pro-inflammatory cytokines and exposure of cells to several forms of environmental stress. Recently, a novel mammalian protein kinase (p38) that shares sequence similarity with mitogen-activated protein (MAP) kinases was identified. Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182. Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. Together, these data establish that p38 is a member of the mammalian MAP kinase group.
A brief history of scanning

Incessant scanning of hosts by attackers looking for vulnerable servers has become a fact of Internet life. In this paper we present an initial study of the scanning activity observed at one site over the past 12.5 years. We study the onset of scanning in the late 1990s and its evolution in terms of characteristics such as the number of scanners, targets and probing patterns. While our study is preliminary in many ways, it provides the first longitudinal examination of a now ubiquitous Internet phenomenon.
In vivo threonine phosphorylation of immunoglobulin binding protein (BiP) maps to its protein binding domain

Immunoglobin binding protein (BiP) molecules exist as both monomers and oligomers and phosphorylated BiP is restricted to the oligomeric pool. Modified BiP is not bound to proteins such as immunoglobulin heavy chain and consequently, may constitute an inactive form. Unlike earlier analysis of mammalian BiP isolated by two-dimensional gel electrophoresis, results here demonstrated that immunoprecipitated BiP displayed predominantly threonine phosphorylation with only a trace of detectable phosphoserine. Like other Hsp70 family members, BiP is comprised of three domains: an amino terminal domain which binds nucleotide, an 18 kilodalton domain which binds peptide, and a carboxyl terminal variable domain of unknown function. Cyanogen bromide cleavage and enzymatic digestion experiments mapped threonine phosphorylation to a site within a 47 amino acid sequence of the peptide binding domain which contains seven threonine residues. Partial proteinase K digestion in the presence of ATP independently verified that the in vivo phosphorylation site of mammalian (BiP) is located within the peptide binding domain. Furthermore, phosphorylation did not impede BiPs ATP-induced conformational change. Thus, the peptide binding domain of BiP is phosphorylated on threonine residue(s) mapping to not more than two tryptic fragments within the peptide binding domain. This location on the molecule could explain why phosphorylated BiP is not detected bound to proteins in vivo.
Recent advances in the design and discovery of small-molecule therapeutics targeting HER2/neu

The human epidermal growth factor receptor (HER) family is a highly explored and promising anticancer drug target. At present, several investigational agents targeted to the HER family of receptors are in various stages of development. Five drugs are already in the clinic for the treatment of cancers that overexpress HER family receptors. Two FDA-approved small-molecule drugs, gefitinib and erlotinib, inhibit HER1 tyrosine kinase activity. Two mAbs, cetuximab and panitumumab, target the extracellular domain of HER1, and another, trastuzumab, targets the extracellular domain of HER2. HER2 is a prominent member of the HER family of receptor tyrosine kinases and serves as a preferred dimerization partner for other HER family members. This paper reviews recently patented small-molecule inhibitors of HER2 receptor kinase activity, and inhibitors of HER2 expression and shedding. Apart from the well-explored quinazoline class of compounds (e.g., lapatinib), arylazole, benzodithiazole, pyrrolopyridazine, pyrrolot...
Object-oriented DEVS

We present an approach called object behavior specification that combines principles of systems theory with those of object orientation. The approach adds a middle layer between the set-theoretic formalism of DEVS (discrete event system specification) and its implementation in C++ and JAVA. Historically, the implementation came first and the object behavior specification was abstracted from it. However, once established, the approach may enable enhanced reuse of DEVS implementation designs. We also show the applicability of the approach to improved formalization of animation and dynamic structure implementations.
Expression and sequence of outer surface protein C among North American isolates of Borrelia burgdorferi

The expression of outer surface protein C (OspC) was determined for North American Borrelia burgdorferi isolates HB19, DN127c19-2, 25015 and both low and high culture passage B31. A monoclonal antibody detected the presence of OspC protein in only two isolates, while polyclonal antiserum identified this protein in all five isolates. The ospC gene was cloned and sequenced for isolates HB19, DN127c19-2 and 25015, and compared with the published ospC sequences of other Lyme disease spirochetes. Bothe the nucleotide and amino acid sequences were found to vary as much among isolates from the same geographic area as between isolates of different species.