cssi/SciSciGPT-SciSciNet huggingface dataset:
Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.

Background & aim Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that is responsible for a growing fraction of cirrhosis and liver cancer cases worldwide. Changes in the gut microbiome have been implicated in NASH pathogenesis, but the lack of suitable murine models has been a barrier to progress. We have therefore characterized the microbiome in a well-validated murine NASH model to establish its value in modeling human disease. Methods The composition of intestinal microbiota was monitored in mice on a 12- or 24-week NASH protocol consisting of high fat, high sugar Western Diet (WD) plus once weekly i.p injection of low-dose CCl4. Additional mice were subjected to WD-only or CCl4-only conditions to assess the independent effect of these variables on the microbiome. Results There was substantial remodeling of the intestinal microbiome in NASH mice, characterized by declines in both species diversity and bacterial abundance. Based on changes to beta diversity, microbiota from NASH mice clustered separately from controls in principal coordinate analyses. A comparison between WD-only and CCl4-only controls with the NASH model identified WD as the primary driver of early changes to the microbiome, resulting in loss of diversity within the 1st week. A NASH signature emerged progressively at weeks 6 and 12, including, most notably, a reproducible bloom of the Firmicute order Erysipelotrichales. Conclusions We have established a valuable model to study the role of gut microbes in NASH, enabling us to identify a new NASH gut microbiome signature.
Emerging applications of microfluidic techniques for in vitro toxicity studies of atmospheric particulate matter

Exposure to atmospheric particulate matter (PM) is a leading global health risk. Despite extensive studies, it remains unclear as to what components or characteristics of PM best account for its to...
The effects of rosiglitazone therapy in early stage breast cancer

430 Peroxisome proliferator-activated receptor gamma (PPARγ) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids as well as synthetic drugs such as the thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARγ is associated with antiproliferative and differentiating effects on human breast cancer cells in vitro and in vivo. To test the hypothesis that PPARγ ligand therapy might inhibit tumor growth and progression in human breast cancer, we conducted a Phase I clinical trial of short-term (2 to 6 weeks) treatment with the thiazolidinedione rosiglitazone in women with early stage breast cancer. Administered between the time of diagnostic biopsy and definitive surgery, rosiglitazone (8 mg/day) was well-tolerated by the 38 study subjects, without serious adverse events. Treatment with rosiglitazone resulted in increased serum adiponectin (p
Intracranial ectopic pituitary adenoma. Case report.

✓ The authors report a unique case of ectopic intracranial pituitary adenoma, associated clinically with generalized seizures and aggressive behavior. The lesion presumably arose from cells in the pars tuberalis and did not involve the sella turcica.
Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock (INM6P.406)

Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and specifically defends against bacterial pathogens that invade the cytosol. During endotoxemia, however, excessive caspase-11 activation causes shock. We report that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected, providing a mechanism of evasion for cytosol-invasive Francisella. Priming the caspase-11 pathway in vivo resulted in extreme sensitivity to subsequent LPS challenge in both wild type and Tlr4-deficient mice, whereas caspase 11-deficient mice were relatively resistant. Together, our data reveal a new pathway for detecting cytoplasmic LPS.
Interpretation of concentration‐discharge patterns in acid‐neutralizing capacity during storm flow in three small, forested catchments in Shenandoah National Park, Virginia

[1] Episodic concentration-discharge (c-Q) plots are a popular tool for interpreting the hydrochemical response of small, forested catchments. Application of the method involves assuming an underlying conceptual model of runoff processes and comparing observed c-Q looping patterns with those predicted by the model. We analyzed and interpreted c-Q plots of acid-neutralizing capacity (ANC) for 133 storms collected over a 7-year period from three catchments in Shenandoah National Park, Virginia. Because of their underlying lithologies the catchments represent a gradient in both hydrologic and geochemical behavior, ranging from a flashy, acidic, poorly buffered catchment to a moderate, neutral, well-buffered catchment. The relative frequency of observed anticlockwise c-Q loops in each catchment decreased along this gradient. Discriminant function analysis indicated that prestorm base flow ANC was an important predictor of loop rotation direction; however, the strength of the predictive relationship decreased along the same gradient. The trends were consistent with several equally plausible three-component mixing models. Uncertainty regarding end-member timing and relative volume and possible time variation in end-member concentrations were key factors precluding identification of a unique model. The inconclusive results obtained on this large data set suggest that identification of underlying runoff mechanisms on the basis of a small number of c-Q plots without additional supporting evidence is likely to be misleading.
Aligning justice system processing with developmental science

An essay is presented about the proposals to reform the legal systems in the U.S. to make them consistent with social knowledge on mature judgment and treatment efficacy of juvenile offenders. It highlights the strengths and weaknesses of the proposed justice policy options, which include the establishment of special courts and correctional facilities for offenders 18 to 24 years old. The author also suggests considerations for fairer and more effective criminal rehabilitation. KEYWORDS: Juvenile justice; Juvenile delinquency
Preparation and Characterization of Simple Dihalomethylidene Platinum Dihalide Complexes in Reactions of Laser-Ablated Pt Atoms with Tetrahalomethanes

Platinum atoms react with tetrachlorofluoromethanes upon laser-ablation and with ultraviolet irradiation to form dihalomethylidene platinum dihalide complexes, CX2═PtX2. These new molecules are identified from carbon-13 and chlorine isotopic shifts, displacements in functional group frequencies as chlorine is replaced with fluorine, and comparison to frequencies calculated by density functional theory. The Pt—C bond lengths calculated here, 1.810 to 1.816 A, are shorter than analogous bond lengths measured earlier for Pt(II) carbene complexes (1.943−1.950 A). The computed effective Pt−C bond orders range from 1.41 to 1.70 as chlorine is replaced by fluorine since the more electronegative halogen appears to concentrate the Pt 5d orbitals and make them bond better with carbon. These platinum methylidene complexes thus have a substantial amount of double bond character from dπ−pπ bonding.
Cerebrospinal fluid shunt placement in the pediatric population: a model of hospitalization cost.

Object There have been no large-scale analyses on cost drivers in CSF shunt surgery for the treatment of pediatric hydrocephalus. The objective of this study was to develop a cost model for hospitalization costs in pediatric CSF shunt surgery and to examine risk factors for increased costs. Methods Data were extracted from the Kids' Inpatient Database (KID) of the Healthcare Cost and Utilization Project. Children with initial CSF shunt placement in the 2009 KID were examined. Patient charge was converted to cost using a cost-to-charge ratio. The factors associated with costs of CSF shunt hospitalizations were examined, including patient demographics, hospital characteristics, and clinical data. The natural log transformation of cost per inpatient day (CoPID) was analyzed. Three multivariate linear regression models were used to characterize the cost. Variance inflation factor was used to identify multicollinearity for each model. Results A total of 2519 patients met the inclusion criteria and were include...
Promoter specificity of a sporulation-induced form of RNA polymerase from Bacillus subtilis.

The program of gene expression that underlies endospore formation by Bacillus subtilis may be controlled in part by a sporulation-induced form of RNA polymerase, Eσ29. The nucleotide sequences of four promoters, which are known to be recognized by Eσ29, are highly conserved at two regions, 10 bp and 35 bp upstream from the start point of transcription. We have used oligonucleotide-directed mutagenesis to construct several base substitutions in the ctc promoter from B. subtilis to test the role of the highly conserved sequences in utilization of the promoter by Eσ29. In vitro transcription analysis demonstrated that the conserved nucleotides at positions −15, −14 and −12 affect the utilization of the promoter by Eσ29. These and previous results support a model in which Eσ29 recognizes its cognate promoters by interacting with nucleotides near the −10 and −35 regions. We also examined the effects of these base substitutions on utilization of the promoter by two other forms of RNA polymerase from B. subtilis, Eσ37 and Eσ29.
Angiogenin antagonists prevent tumor growth in vivo.

Abstract A noncytotoxic neutralizing monoclonal antibody (mAb), 26-2F, to human angiogenin (Ang), a potent inducer of neovascularization, has been reported to prevent or delay the establishment of HT-29 human tumor xenografts in athymic mice. In the present study the tumor model was modified to increase sensitivity to Ang antagonists to facilitate further investigations and comparisons of their capacity to inhibit tumor growth. An increase in the percentage of tumor-free mice from 10-25% to 65% is observed in this modified model after treatment with mAb 26-2F. An additional neutralizing mAb, 36u, that interacts with a different epitope on Ang similarly prevents the appearance of tumors, both alone and in combination with mAb 26-2F. In those tumors that develop in mice treated with these agents, the number of vascular elements is reduced. Actin, an Ang antagonist that unlike the mAbs binds both human and mouse Ang, also prevents the establishment of tumors while exhibiting no toxic effects at daily doses > 50 times the molar amount of circulating mouse Ang. Ang antagonists also inhibit the appearance of tumors derived from two other Ang-secreting human tumor cell lines--i.e., A549 lung adenocarcinoma and HT-1080 fibrosarcoma. These results demonstrate that inhibition of the action of Ang is an effective therapeutic approach for the treatment of malignant disease.
Some characteristics of the guinea pig electrocardiogram.

Abstract The time-relations of the electrocardiograms of normal, male guinea pigs are given. The data are in agreement with previous work with the exception of a longer P wave. In the relationship of Q-T duration to heart rate, using the equation Q-T = K·√R−R, K was found to equal 7.94 ± 0.81. There was no evidence of correlation between heart rate and body weight in these animals.
A user's perspective on augmentative communication

During a series of in-depth interviews, an augmentative communication user reflected on the effectiveness of the devices designed for her during her school career. Data secured through 104 hours of interviews were analyzed for emerging themes. These themes indicated several tendencies: giving a disproportionate amount of emphasis to “device usage” over “speech usage,” overlooking major limitations in certain augmentative devices, and allowing professionals to dominate the decision-making process. Implications of these findings are addressed in the “Discussion” section.
961. Angiopoietin-1 Enhances the Effect of Paclitaxel on Breast Cancer Cell Killing in a Mouse Model

Top of pageAbstract Angiogenesis has an important role in tumor growth and metastasis. Various factors, such as VEGFs and angiopoietins, have been implicated in the regulation of vessel formation. Angiopoietins regulate angiogenesis by activating or blocking the activation of Tie2, a surface receptor tyrosine kinase generally restricted to endothelial cells. Angiopoietin-1 (Ang1) promotes endothelial cell survival, helps to maintain vascular integrity and is thus involved in vessel maturation. Conversely, Ang2 acts as an antagonist of the Ang1/ Tie2 interaction. Solid tumors require blood vessels for growth, although tumor neovascularization is structurally and functionally abnormal with leaky and tortuous vessels. These abnormalities contribute to impaired blood supply and interstitial hypertension, which interferes with the delivery of therapeutics to the tumor. Since Ang1 stabilizes blood vessels and inhibits vascular permeability, we hypothesized that normalization of tumor vasculature by Ang1 could improve drug delivery and thereby enhance cancer cell killing. The impact of Ang1 delivered by a non-replicating adenoviral vector (AdAng1) on the anti-tumor effect of paclitaxel was studied in a 4T1 murine breast cancer model. The expression and secretion of Ang1 from 4T1 cells infected by AdAng1 in vitro was first confirmed by immunostaining and immunoblotting. AdAng1 did not affect the growth of 4T1 cells in vitro, as the growth rates of 4T1 cells infected with AdAng1 or control AdCon virus were similar. Paclitaxel did inhibit the growth of 4T1 cells in vitro, but the growth inhibition was similar in control virus and AdAng1 treated cultures. For the in vivo model, 4T1 cells were first treated with either AdAng1, AdCon or PBS, and then injected into the flank of syngeneic BALB/c mice. Paclitaxel was administered by i.p. injection twice a week, starting at day 7. The combination of AdAng1 administration together with Paclitaxel reduced tumor growth compared to Paclitaxel alone, AdAng1 alone or control virus plus Paclitaxel. In summary, this study indicates that Ang1 can enhance the effect of chemotherapy in a breast cancer model. These effects are likely to be related to Ang1-mediated vessel normalization and thereby improved drug delivery to the tumor cells.
Relationship between Jones and Mueller matrices for random media

The effect of a linear random medium on the state of polarization of the transmitted light is investigated, and the connection between the Stokes vector formalism and the coherence or polarization matrix formalism is discussed. It is shown that an ensemble of Jones matrices corresponds to the Mueller matrix in general.
Four senses of 'meaning' in the history of ideas: Quentin skinner's theory of historical interpretation

At least four different senses of 'meaning' need to be kept separate when describing the proper way to do the history of ideas. The first sense, communicative meaning, relies on the communicative intentions of the author and is very close to H. P. Grice's 'nonnatural meaning'. The second sense, meaning as significance or importance, is close to Grice's "natural meaning," but I focus on a type that depends on human interests; in this sense, meaning as significance is always relative to a person or group and changes as the events or the interests of the person or group change. I show that Quentin Skinner in his classic article, "Meaning and Understanding in the History of Ideas," confuses these senses. While historians of ideas often focus on identifying communicative meaning, what historians care most about is the significance or importance that something had for people in the past or in the present.
Development of detectability limits for on-orbit inspection of space shuttle wing leading edge

At the conclusion of the Columbia Accident Investigation, one of the recommendations of the Columbia Accident Investigation Board (CAIB) was that NASA develop and implement an inspection plan for the Reinforced Carbon-Carbon (RCC) system components. To address these issues, a group of scientists and engineers at NASA Langley Research Center proposed the use of an IR camera to inspect the RCC. Any crack in an RCC panel changes the thermal resistance of the material in the direction perpendicular to the crack. The change in thermal resistance can be made visible by introducing a heat flow across the crack and using an IR camera to image the resulting surface temperature distribution. The temperature difference across the crack depends on the change in the thermal resistance, the length of the crack, the local thermal gradient, and the rate of radiation exchange with the environment. The current paper describes how the authors derived the minimum thermal gradient detectability limits for a through crack in an RCC panel. This paper will also show, through the use of a transient, 3-dimensional, finite element model, that these minimum gradients naturally exist on-orbit. The results from the finite element model showed that there exists sufficient thermal gradient to detect a crack on 96% of the RCC leading edge.
An analytic representation of the six‐dimensional potential energy surface of hydrogen fluoride dimer

We present a semiglobal potential energy surface for HF dimer that should be especially realistic in the vicinity of the two equivalent hydrogen‐bonded‐complex geometries and the transition state separating them. It is based on fits to 106 correlated calculations and 378 SCF calculations of the energy of the planar complex plus a separate fit to the empirical out‐of‐plane bending potential of Barton and Howard at a sequence of geometries along the minimum energy path for the degenerate rearrangement connecting the two minima.
Self-Regulated Insulin Delivery-Artificial Pancreas

AbstractA chemical mediated artificial pancreas has been designed that will deliver glycosylated insulin (G-Ins) in response to glucose concentrations. This system is based on the competitive binding between G-Ins and glucose to a saccharide binding substrate, Concanavalin A (Con-A). Con-A has was evaluated as a soluble monomeric protein, enclosed within microcapsules, formed into microspheres, and synthesized as a soluble high molecular weight oligomer. These forms were designed to maintain the binding characteristics of Con-A and G-Ins and to prevent leakage or permeation of Con-A across the device membrane.
Enhancement of Light Extraction in GaInN Light-Emitting Diodes with Graded-Index Indium Tin Oxide Layer

Enhancement of light extraction in a GaInN light-emitting diode employing a graded-refractive index ITO anti-reflection coating deposited by oblique-angle electron-beam evaporation is presented.
The red face: Flushing disorders

Abstract Flushing is a transient reddening of the face and frequently other areas, including the neck, upper chest, pinnae, and epigastric area. 1 Flushing is the visible sign of a generalized increase in cutaneous blood flow 2 despite the limited distribution of the erythema. Because therapy is individualized according to the specific factors causing the flushing, the first step in the management of a patient with a flushing disorder is a specific diagnosis.
The effect of substrates and inhibitors of cytochrome P-450 on the NADPH inhibition of the ATP-dependent, hepatic, microsomal calcium pump.

In hepatic microsomes one or more isozymes of cytochrome P-450 inhibits the ATP-dependent Ca2+ pump. This inhibition is reversible by GSH and appears to be due to a direct oxidation of the pump proteins by the oxygenated cytochrome. To determine which isozyme mediates this inhibiton, we have examined the effect of various substrates and inhibitors on the NADPH inhibition of Ca2+ uptake. We find that aminopyrine, benzphetamine and SKF-525A reverse this inhibition while a number of other substrates do not. This pattern suggests that a previously unreported isozyme of cytochrome P-450 mediates the Ca2+ pump inhibition.
Reciprocal regulation of Rag expression in thymocytes by the zinc-finger proteins, Zfp608 and Zfp609

Recombination-activating gene 1 (Rag1) and Rag2 enzymes are required for T cell receptor assembly and thymocyte development. The mechanisms underlying the transcriptional activation and repression of Rag1 and Rag2 are incompletely understood. The zinc-finger protein, Zfp608, represses Rag1 and Rag2 expression when expressed in thymocytes blocking T-cell maturation. Here we show that the related zinc-finger protein, Zfp609, is necessary for Rag1 and Rag2 expression in developing thymocytes. Zfp608 represses Rag1 and Rag2 expression indirectly by repressing the expression of Zfp609. Thus, the balance of Zfp608 and Zfp609 plays a critical role in regulating Rag1 and Rag2 expression, which may manifest itself not only during development of immature thymocytes into mature T cells but also in generation of the T-cell arm of the adaptive immune system, which does not fully develop until after birth.
Quantitative Analysis of Acid Mucopolysaccharides in the Normal and Kanamycin Intoxicated Cochlea

Quantitative analysis of acid mucopoly-saccharides in the kanamyciri intoxicated guinea pig cochlea was performed using the modified turbidi-metric method based on the formation of insoluble complexes between acid mucopolysaccharides and cetyltrimethylammonium bromide, in combination with enzymic analysis. A decreased quantity of acid mucopolysaccharides in the ha vascularis and the spiral ligament was observed in comparison with the normal. The factors involved in the decrease of acid mucopolysaccharides and its effect on the inner ear function were discussed.
The Decision-Making Process in Language Program Placement: Test and Nontest Factors Interacting in Context

The use of tests has been targeted as a critical point in validity, which suggests that contexts for test use warrant closer investigation. This article describes a study of decision making during test use in the context of a university intensive English language program. Over a period of 2½ years, data were collected by audio-recording placement sessions in which the program director and an instructor made decisions based on a three-part placement exam, TOEFL scores, course grades, instructor evaluations, and other information. Analysis of the sessions revealed four major areas impacting test use and the decision-making process: (a) test performance and score factors, (b) student factors, (c) test user factors, and (d) program factors (i.e., number and size of levels, curriculum, textbooks). These four areas represent factors in the placement process that are clearly about tests (test performance and score) and factors that have less relation to tests or scores such as test users and programmatic factors...
Biochemical characterization of an electrogenic vacuolar proton pump in purified chicken osteoclast plasma membrane vesicles

A well-characterized chicken osteoclast plasma membrane vesicle preparation manifested Mg2(+)-dependent ATP hydrolyzing activity of 0.213 mumol inorganic phosphate released per mg protein per minute (n = 7). The Mg2+ dependence showed a high-affinity component with a KMg of 1.293 microM and Vmax of 0.063 mumol Pi per mg protein per minute, and a low-affinity component with a KMg of 297.6 microM and a Vmax of 0.232 mumol Pi per mg protein per minute. The Mg2(+)-ATPase activity was inhibited by N,N'-dicyclohexylcarbodiimide (DCCD, 0.2 mM, 50.7%), N-ethylmaleimide (0.5 mM, 34.6%), nolinium bromide (1 mM, 29.9%), 4,4'-diisothiocyano-2,2'-stilbene sulfonic acid (DIDS, 1 mM, 45.1%), and p-chloromercuribenzoic acid (PCMB, 0.1 mM, 33.8%). Sodium orthovanadate (Na3 VO4) at 1 microM had no effect but caused 29.5% inhibition at 1 mM. Na+ could substitute for K+ without loss of activity, NO3- caused 19.5% inhibition when substituted for Cl-, and acetate replacement of Cl- resulted in 36.4% stimulation of Mg2(+)-ATPase. ATP, GTP, ITP, CTP, and ADP were all hydrolyzed effectively. DCCD (0.2 mM), NEM (0.5 mM), nolinium bromide (1 mM), and DIDS (50 microM) almost completely abolished proton transport as measured spectrofluorometrically by acridine orange quenching. Na3 VO4 (1 mM) had no effect, and duramycin (80 micrograms/ml) inhibited transport 52.7%. K+ replacement of Na+ caused a 79.2% increase in initial proton transport rate. NO3- and acetate substitution of Cl- resulted in a 46.1 and 55.7% decrease in transport, respectively. ATP supports transport far more effectively than the other nucleotides tested. ADP was ineffective. Experiments using the potassium ionophore, valinomycin, indicated that the proton pump functions electrogenically, with Cl- most likely cotransported by an anion transporter. The proton pump also seems to have at least one anion-sensitive site, elucidated by experiments in the presence of NO3- and Cl-.
82 CEREBRAL NITRIC OXIDE SYNTHETASE ACTIVITY FOLLOWING HYPOXIA IN NEWBORN PIGLETS

Recent studies in animal models suggest, that nitric oxide (NO), produced by nitric oxide synthetase (NOS) during conversion of L-arginine into L-citrulline, is a source of free radicals following hypoxia. The present study tested the hypothesis that NOS was altered in cortical tissue after one hour of cerebral hypoxia. Newborn piglets (6 hypoxia, 6 normoxia) were anesthetized and ventilated; hypoxia was induced by lowering the FiO2 to 0.05-0.07 in the hypoxia group, and was maintained for one hour. Cerebral cortical tissue obtained from each piglet was homogenized and dialyzed for 6 hours to remove endogenous arginine. The activity of NOS was assessed using the conversion of 3H-L-arginine into 3H-L-citrulline in the presence of calcium and NADPH, followed by counting the amount of 3H-L-citrulline formed after removal of 3H-L-arginine by ion-exchange. Due to NOS activity NO and 3H-L-citrulline are formed on an equimolar basis. Results showed, that NOS activity was present in both groups: normoxia: 265±85, hypoxia: 230±165 fmol NO/mg protein/min. Differences between the hypoxia and normoxia groups were not significant. The results indicate that cerebral NOS in newborn piglets is resistant to hypoxia. The present in vitro data do not preclude, that NOS activity is increased in vivo during hypoxia by a cellular influx of calcium, thereby possibly contributing to the formation of free radicals and membrane lipid peroxidation following hypoxia. Funded by NIH #HD-20337, USA and Ter Meulen Fund, the Netherlands.
Massenspektroskopie und ihre Anwendung auf strukturelle und stereochemische Probleme, LXXVII. Einfluß behinderter Rotation sowie anderer energetischer Faktoren auf die McLafferty‐Umlagerung von Ketonen

Folgende Faktoren beeinflussen den Ablauf zweier konkurrierender McLafferty-Umlagerungen (Ubertragung eines γ-standigen Wasserstoffatoms bei der β-Spaltung von Carbonylverbindungen): 1. Natur des abgespaltenen Olefins, 2. Art des ubertragenen Wasserstoffatoms (prim., sek., usw.), 3. behinderte Rotation.
Auditory nerve neurophonic recorded from the round window of the Mongolian gerbil

In the Mongolian gerbil, round window (RW) recordings of averaged responses to phase-locked acoustic stimuli which are not alternated in polarity can include both the cochlear mirophonic (CM) and auditory nerve neurophonic (ANN). The ANN can dominate the recordings when the RW electrode is referenced to some portion of the body that allows the two electrodes to straddle the auditory nerve. Concentric bipolar RW electrodes are biased in favor of the CM. When there is a substantial ANN component in the RW response, as the sinusoidal stimulus intensity increases there is a non-monotonic increase of amplitude and a pronounced change of phase of the response. When the phase-locked stimuli are alternated in polarity in order to cancel the CM, a residual response is often observed. This residual response has twice the frequency of the stimulus and is decreased in amplitude by forward masking. It also shows a pattern of amplitude decrement following the stimulus onset, resembling adaptation of the firing rate of cochlear nerve axons. Tetrodotoxin (TTX) eliminates the non-monotonic RW amplitude input-output (I/O) function, reduces the phase changes of the response as the stimulus intensity is increased, eliminates the residual non-canceled response to alternated stimuli, and the time-limited amplitude decrements which resemble adaptation. Following application of TTX, the RW response of the gerbil to stimuli with non-alternated polarity much more closely resembles the CM responses of other animals. It is concluded that the gerbil's residual response following cancellation of the CM is the ANN, and that the RW of the gerbil is a convenient site for recording measures of phase-locked cochlear axonal activity.
Carotene and Novel Apocarotenoid Concentrations in Orange-fleshed Cucumis melo Melons: Determinations of β-Carotene Bioaccessibility and Bioavailability

Muskmelons, both cantaloupe (Cucumis melo Reticulatus Group) and orange-fleshed honeydew (C. melo Inodorus Group), a cross between orange-fleshed cantaloupe and green-fleshed honeydew, are excellent sources of β-carotene. Although β-carotene from melon is an important dietary antioxidant and precursor of vitamin A, its bioaccessibility/bioavailability is unknown. We compared β-carotene concentrations from previously frozen orange-fleshed honeydew and cantaloupe melons grown under the same glasshouse conditions, and from freshly harvested field-grown, orange-fleshed honeydew melon to determine β-carotene bioaccessibility/bioavailability, concentrations of novel β-apocarotenals, and chromoplast structure of orange-fleshed honeydew melon. β-Carotene and β-apocarotenal concentrations were determined by HPLC and/or HPLC-MS, β-carotene bioaccessibility/bioavailability was determined by in vitro digestion and Caco-2 cell uptake, and chromoplast structure was determined by electron microscopy. The average β-carotene concentrations (μg/g dry weight) for the orange-fleshed honeydew and cantaloupe were 242.8 and 176.3 respectively. The average dry weights per gram of wet weight of orange-fleshed honeydew and cantaloupe were 0.094 g and 0.071 g, respectively. The bioaccessibility of field-grown orange-fleshed honeydew melons was determined to be 3.2 ± 0.3%, bioavailability in Caco-2 cells was about 11%, and chromoplast structure from orange-fleshed honeydew melons was globular (as opposed to crystalline) in nature. We detected β-apo-8'-, β-apo-10', β-apo-12'-, and β-apo-14'-carotenals and β-apo-13-carotenone in orange-fleshed melons (at a level of 1-2% of total β-carotene). Orange-fleshed honeydew melon fruit had higher amounts of β-carotene than cantaloupe. The bioaccessibility/bioavailability of β-carotene from orange-fleshed melons was comparable to that from carrot (Daucus carota).
Imaging and manipulation of high-density lipoproteins

The atomic force microscope (AFM) has been used to image a variety of biological systems, but has rarely been applied to soluble protein-lipid complexes. One of the primary physiological protein-lipid complexes is the high-density lipoproteins (HDL), responsible for the transport of cholesterol from the peripheral tissues and other lipoproteins to the liver. We have used the AFM to directly image discoidal reconstituted HDL (rHDL) particles for the first time. The height of these particles is consistent with a phospholipid bilayer structure, but careful high resolution measurements of particle diameters has indicated that they fuse when adsorbed to mica. Furthermore, it has been demonstrated that the AFM can be used to initiate this bilayer fusion in a controlled manner, allowing the fabrication of stabilized, nanometer scale, phospholipid bilayer "domains."
Physicochemical characterization of carbohydrate-solvent interactions by near-infrared spectroscopy

Abstract Near-infrared (n.i.r.) spectroscopy of carbohydrates in solvents of different proton-acceptor strengths shows splittings in the first-overtone, OH absorptions that are characteristic of a double minimum in the hydrogen-bond, potential-energy curve. On the basis of their specific, n.i.r. absorption maxima in methyl sulfoxide, N,N -dimethylformamide, and 19:1 HCONMe 2 -water, α- D -glucose, β- D -glucose, and glycogen can be differentiated from each other. These carbohydrates also exhibit previously undefined absorption maxima that are assigned as nonsolvent, hydrogen-bonded OH groups, and the intensity of these bands decreases as the hydrogen-bonding strength of the solvent (Me 2 SO☆19:1 HCONMe 2 -water☆HCONMe 2 ) increases. A n.i.r. method for determination of the thermodynamic parameters of hydrogen bonding for cyclohexanol, α- D -glucose, and glycogen in hydrogen-bonding solvents has been designed on the basis of nonsolvent and solvent hydrogen-bonded species at various temperatures.
Gitterparameter und thermische Ausdehnungskoeffizienten des CdO zwischen 40 und 1300°K. Fehlbau des Oxids

Der Einflus des Cd-Uberschusses im CdO auf den Gitterparameter a, auf die Farbe und die Dichte des Oxids wurde untersucht. Acht Praparate, nach verschiedenen Methoden dargestellt, dienten zur Bestimmung von a. Oxide, die keinen merklichen Cd-Uberschus besasen, hatten alle fast dasselbe a25 = 4,6951 ± 0,0002 A. Die Farbe der Praparate anderte sich von rotlich braun bis schwarz; jedoch bei hoher mikroskopischer Vergroserung, in durchfallendem Licht, erschienen sie alle rot. Diese und andere Tatsachen fuhrten zum Schlus, das das bei hoheren Temperaturen geloste Cd sich gewissermasen beim Abkuhlen aus dem Oxid ausscheidet. Die Anderung des Gitterparameters infolge Loslichkeit mus deshalb von der Expansivitat abgezogen werden; eine lineare Beziehung zwischen at und t (im Bereich von 300 bis 1000°K) wurde erhalten (α = 1,15 · 10−5 Grad−1). Unter 300° verminderte sich α und wurde gleich Null bei 40°K. Die Dichte des an Luft erhitzten CdO war groser (99,67% der Rontgendichte von 8,2375 gcm−1 bei 25°) als die des Cd-haltigen Oxids, was auf das Vorhandensein von Leerstellen in groseren Mengen in letzterem hinweist. The influence of excess Cd in CdO on the lattice parameter, color and density was explored. Eight samples were prepared by various methods and the lattice parameter determined. The oxides, showing no excess of Cd (as tested with KMnO4) had all nearly the same a25 = 4,6951 ± 0,0002 A. The color of the samples varied from reddish brown to black; however, in transmitted light at high microscopic magnification, all of them appeared red. These and other facts led to the conclusion that Cd, if dissolved at elevated temperatures in CdO, segregates to a certain degree upon cooling. Hence, the lattice parameter increase due to solubility of Cd in CdO, had to be subtracted from the total to obtain the pure thermal expansivity: a straight line for a versus t between 300 and 1000°K resulted, α = 1,15 · 10−5 deg−1 was obtained. α started to decrease below 300° and became zero at 40°K. The density of the CdO heated in air was larger (99,67% of the theoretical 8.2375 gcm−3 at 25°C) than that of the excess Cd containing oxide, indicating the presence of vacancies in larger amounts in the latter preparation.
Top Management Team Size, CEO Dominance, and firm Performance: The Moderating Roles of Environmental Turbulence and Discretion

Adopting an information-processing perspective and drawing on work in social psychology, this study examined the effects of top management team size and chief executive officer (CEO) dominance on firm performance in different environments. Data from 47 organizations revealed that firms with large teams performed better and firms with dominant CEOs performed worse in a turbulent environment than in a stable one. In addition, the association between team size and CEO dominance, and firm performance, is significant in an environment that allows top managers high discretion in making strategic choices but is not significant in a low-discretion environment.
Self-reported frailty is associated with low calcaneal bone mineral density in a multiracial population of community-dwelling elderly.

Introduction Low bone mineral density (BMD) is associated with frailty assessed using performance-based measures. However, the latter can be cumbersome and difficult to standardize. We examined whether an easily obtained self-reported frailty measure also predicted low BMD.
Improvement in Chronic Muscle Fasciculations With Dietary Change: A Suspected Case of Gluten Neuropathy

Objective The purpose of this case report is to describe a patient with chronic, multisite muscle fasciculations who presented to a chiropractic teaching clinic and was treated with dietary modifications.
TWO CONSEQUENCES OF HOMOSEXUAL COURTSHIP PERFORMED BY DROSOPHILA MELANOGASTER AND DROSOPHILA AFFINIS MALES.

Analyse du comportement de cour de D. a. pour determiner si des modifications du comportement de cour dependantes de l'experience apparaissent apres que des mâles matures aient courtises de jeunes mâles conspecifiques. De plus, les interactions des especes croisees de D. m. et D. a. sont etudiees pour savoir si le comportement de cour homosexuel est modifiee par l'experience des individus.
High symptom burden prior to radiation therapy for head and neck cancer: A patient-reported outcomes study

Background As a first step toward developing effective strategies to control symptoms associated with head and neck cancer (HNC) and its treatment, we sought to describe the pattern of symptoms experienced before radiation therapy. Methods Subjects completed the MD Anderson Symptom Inventory–Head and Neck Module before beginning radiation therapy. Results In all, 270 patients participated. Symptom severity and interference varied between treatment-naive patients and those with prior treatment. Cluster analyses revealed that 33% of patients had high symptom burden. Symptoms most often rated moderate-to-severe were fatigue, sleep disturbance, distress, pain, and problems chewing and swallowing. Poorer performance status, higher T classification, and receipt of previous treatment correlated with higher symptom burden. Conclusions A substantial proportion of patients were experiencing high symptom burden. Because few interventions currently exist for several of the most problematic symptoms, research in symptom reduction that targets the pattern of symptoms described here is greatly needed. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1490–1498, 2013
Active query selection for learning rankers

Methods that reduce the amount of labeled data needed for training have focused more on selecting which documents to label than on which queries should be labeled. One exception to this (Long et al. 2010) uses expected loss optimization (ELO) to estimate which queries should be selected but is limited to rankers that predict absolute graded relevance. In this work, we demonstrate how to easily adapt ELO to work with any ranker and show that estimating expected loss in DCG is more robust than NDCG even when the final performance measure is NDCG.
Earthworm and soil microarthropod responses to oily waste application

Abstract The land treatment of an industrial oily waste was investigated to determine the effect of its application on earthworm and soil microarthropod populations. Oily waste was applied and rototilled into field plots at seven application rates that ranged from 0.17 to 9.5 kg m −2 total oil and grease, or from 0.09 to 5.25% oil and grease in the zone of incorporation. Control plots consisted of those with no waste application or rototilling, and those with rototilling only. Microarthropod population density, followed over 2 yr, showed an immediate negative effect of rototilling; clear negative effects of oily waste application occurred regardless of application rate. In all cases, recovery from rototilling was faster than recovery from waste application. It was recovery time, rather than initial effects, which varied with application rate; heavier applications required longer periods of recovery. Earthworms were able to recover much faster from rototilling than from the oily waste applications. Earthworm biomass had not completely recovered from the highest waste application rate 3 yr after application.
The Surface of Nanoparticle Silicon as Studied by Solid-State NMR.

The surface structure and adjacent interior of commercially available silicon nanopowder (np-Si) was studied using multinuclear, solid-state NMR spectroscopy. The results are consistent with an overall picture in which the bulk of the np-Si interior consists of highly ordered ("crystalline") silicon atoms, each bound tetrahedrally to four other silicon atoms. From a combination of ¹H, 29Si and ²H magic-angle-spinning (MAS) NMR results and quantum mechanical 29Si chemical shift calculations, silicon atoms on the surface of "as-received" np-Si were found to exist in a variety of chemical structures, with apparent populations in the order (a) (Si-O-)₃Si-H > (b) (Si-O-)₃SiOH > (c) (HO-)nSi(Si)m(-OSi)4-m-n ≈ (d) (Si-O-)₂Si(H)OH > (e) (Si-O-)₂Si(-OH)₂ > (f) (Si-O-)₄Si, where Si stands for a surface silicon atom and Si represents another silicon atom that is attached to Si by either a Si-Si bond or a Si-O-Si linkage. The relative populations of each of these structures can be modified by chemical treatment, including with O₂ gas at elevated temperature. A deliberately oxidized sample displays an increased population of (Si-O-)₃Si-H, as well as (Si-O-)₃SiOH sites. Considerable heterogeneity of some surface structures was observed. A combination of ¹H and ²H MAS experiments provide evidence for a substantial population of silanol (Si-OH) moieties, some of which are not readily H-exchangeable, along with the dominant Si-H sites, on the surface of "as-received" np-Si; the silanol moieties are enhanced by deliberate oxidation. An extension of the DEPTH background suppression method is also demonstrated that permits measurement of the T₂ relaxation parameter simultaneously with background suppression.
Fine Structure and Activity of Discrete RAG-HMG Complexes on V(D)J Recombination Signals

Two lymphoid cell-specific proteins, RAG-1 and RAG-2, initiate V(D)J recombination by introducing DNA breaks at recombination signal sequences (RSSs). Although the RAG proteins themselves bind and cleave DNA substrates containing either a 12-RSS or a 23-RSS, DNA-bending proteins HMG-1 and HMG-2 are known to promote these processes, particularly with 23-RSS substrates. Using in-gel cleavage assays and DNA footprinting techniques, I analyzed the catalytic activity and protein-DNA contacts in discrete 12-RSS and 23-RSS complexes containing the RAG proteins and either HMG-1 or HMG-2. I found that both the cleavage activity and the pattern of protein-DNA contacts in RAG-HMG complexes assembled on 12-RSS substrates closely resembled those obtained from analogous 12-RSS complexes lacking HMG protein. In contrast, 23-RSS complexes containing both RAG proteins and either HMG-1 or HMG-2 exhibited enhanced cleavage activity and displayed an altered distribution of cleavage products compared to 23-RSS complexes containing only RAG-1 and RAG-2. Moreover, HMG-dependent heptamer contacts in 23-RSS complexes were observed. The protein-DNA contacts in RAG-RSS-HMG complexes assembled on 12-RSS or 23-RSS substrates were strikingly similar at comparable positions, suggesting that the RAG proteins mediate HMG-dependent heptamer contacts in 23-RSS complexes. Results of ethylation interference experiments suggest that the HMG protein is positioned 5' of the nonamer in 23-RSS complexes, interacting largely with the side of the duplex opposite the one contacting the RAG proteins. Thus, HMG protein plays the dual role of bringing critical elements of the 23-RSS heptamer into the same phase as the 12-RSS to promote RAG binding and assisting in the catalysis of 23-RSS cleavage.
Rod-cone interaction in the dark-adapted fovea.

The foveal cone threshold was significantly lower after 45 min of dark adaptation than it was near the start of the cone plateau of the dark-adaptation curve. A concentric rod background subsequently raised the threshold by an amount correlated with the difference between the cone plateau and the dark-adapted thresholds. Paradoxically, the rod background also lowered the cone threshold by an amount that differed from subject to subject. This sensitizing effect was identifiable by its relatively small variability across sessions. These results show that adaptation of parafoveal rods by either real light or dark light can change foveal cone thresholds.
Off the beaten track: the molecular structure of long-term memory: three novel hypotheses—electrical, chemical and anatomical (allosteric)

This opinion paper reviews three hypotheses relating to the possible molecular events involved in the formation of long-term memories that go beyond the classical theory, which is confined to strengthening Hebbian synapses. The aim of this paper is not to write detailed critiques of these three hypotheses but to present, for the first time in one location, their essential components to engage the interest of the reader in these new ventures.
Transcriptional Regulation of the Mouse Presenilin-1 Gene

The presenilin-1 (PS-1) gene encodes at least three separate mRNA transcripts from its 12 exons, which are spread over 50 kilobase pairs of mouse DNA. The first transcript begins with exon 1A, whereas the other transcripts begin with exon 1B. Different portions of exon 1B are spliced to give long and short mRNAs. The expression of all of these transcripts depends on a single promoter located just upstream of exon 1A. Although this region lacks a TATA box and a number of common initiator sequences, it does contain a CAAT box, a heat-shock responsive element, a polyomavirus enhancer activator-3 site, an Ets 1–3 site, and multiple-Sp1 and multiple-Ap2 binding sites, which are typically found in eukaryotic promoters. We have combined a reporter gene with various portions of this putative PS-1 promoter and measured firefly luciferase activity relative to an internal renilla luciferase standard. We identified a 25-base pair fragment spanning the 5′-transcription start site of exon 1A as containing the core of the promoter activity. The sequences downstream of this region had undetectable promoter activity, suggesting that this core element is the gene's only promoter, and it controls expression of all three transcripts. Although human PS-1 mRNA expression is clearly different from the mouse PS-1 mRNA pattern, the human and mouse core promoters do share limited homology.
Does succinylcholine maximize intubating conditions better than rocuronium for rapid sequence intubation

Succinylcholine is superior to rocuronium for creating excellent intubating conditions and should be the first-line paralytic agent used for rapid sequence intubations.
Telehealth: Seven Strategies To Successfully Implement Disruptive Technology And Transform Health Care

“Telehealth” refers to the use of electronic services to support a broad range of remote services, such as patient care, education, and monitoring. Telehealth must be integrated into traditional ambulatory and hospital-based practices if it is to achieve its full potential, including addressing the six domains of care quality defined by the Institute of Medicine: safe, effective, patient-centered, timely, efficient, and equitable. Telehealth is a disruptive technology that appears to threaten traditional health care delivery but has the potential to reform and transform the industry by reducing costs and increasing quality and patient satisfaction. This article outlines seven strategies critical to successful telehealth implementation: understanding patients’ and providers’ expectations, untethering telehealth from traditional revenue expectations, deconstructing the traditional health care encounter, being open to discovery, being mindful of the importance of space, redesigning care to improve value in h...