cssi/SciSciGPT-SciSciNet huggingface dataset:
Oxidative Degradation of Testosterone by Adaptive Enzymes

THE study of steroid synthesis by micro-organisms and certain oxidations and reductions of reactive groups at positions 3 and 17 of the steroid skeleton have been previously reported1. Turfitt2 has studied more extensive degradations of cholesterol by bacteria and has isolated products in which the side-chain has been removed and ring A opened. We should like to report the application of adaptive bacterial enzymes to the study of the oxidative degradation of steroid hormones.
Synthesis and Microstructure of Highly Oriented Lead Titanate Thin Films Prepared by a Sol-Gel Method

Thin films of PbTiO3 were deposited on fused silica, resistor-grade alumina, and single-crystal (100) MgO by a sol–gel processing method. Whereas the films deposited on silica and alumina substrates were randomly oriented and polycrystalline, highly {100} oriented PbTiO3 films were grown on the MgO single crystals. The perovskite-type structure was observed with films deposited on the single-crystal MgO and annealed at temperatures as low as 470°C, whereas a pyrochlore-type strcuture was observed with films on fused silica and alumina processed in a similar manner. All films heat-treated at temperatures in excess of 570°C showed significant formation of a second PbTi3O7 phase. The films were characterized by electron microscopy and glancing-incidence-angle X-ray diffraction.
Frequency domain adaptive filters using higher-order statistics with application to adaptive time delay estimation

Novel block-adaptive frequency domain filters based upon higher-order statistics are proposed for estimation of the parameters of a class of errors-in-variables models. The class includes moving average models as well as autoregressive models. The input to the system is restricted to be non-Gaussian with either non-vanishing bispectrum or non-vanishing trispectrum. The noise processes contaminating the input and the output measurements are assumed to be Gaussian if the input bispectrum vanishes, whereas they are allowed to be non-Gaussian with vanishing bispectra if the input has non-vanishing bispectrum. An integrated polyspectrum (bispectrum or trispectrum) of a random process is defined and exploited for adaptive parameter estimation. The integrated polyspectrum is computed as a cross-spectrum leading to substantial computational savings. Consistency of the proposed approaches is proved for the stationary case under certain mild sufficient conditions. The proposed approaches are applied to the problem of adaptive differential time delay estimation for non-Gaussian signals under spatially correlated Gaussian noise environment. Simulation results are presented to illustrate the proposed approaches.
Grammatical and literary structures

The structualist approaches that Roland Barthes and Claude Levi-Strauss employ to interpret literature contrast significantly with the analysis that transformational generative grammarians use to discover the deep structures of language. Although both groups search for "structures" and both apply "transformations" to their respective structures, they seem to be searching for two different things (Keesing, 1974). Literary structuralists attempt to uncover the implicit conceptual relationships that writers unconsciously assume. These are often myths or folktales discovered by comparing and contrasting the elements in the stories of various authors. Structuralists have borrowed the analytic techniques of structural anthropologists like Levi Strauss, who in turn adopted the techniques of descriptive linguists who sought to represent phonology by investigating minimal pairs of sound. Grammarians, on the other hand, discern deep structures in language by reconstructing the recursive rules (i.e., phrase structure rules) that produce a deep structure of abstractions that can be converted into the surface language by application of a set of nonrecursive transformational rules. Unlike literary structuralists, however, grammarians are less interested in the form of the deep structures discovered than they are in the process (application of rules) by which those same deep structures are formed. Literary critics, however, tend to view the conceptual structures of literature as exhibiting an ontological reality of their own. Observers of these two modes of analysis have already noted a number of differences between the two (Keesing, 1974; Culler, 1975). We explore here the relationship between grammatical deep structures and the conceptual patterns of literary structualism by outlining a general theory of interpreting literature.
Performance of mutual funds before and after closing to new investors

Abstract This study examines the decision to close mutual funds to new investors due to the growth of the funds' assets. The evidence indicates that funds perform better three years prior to closing to new investors than they do afterwards. Furthermore, the evidence indicates that the closed funds outperform the control portfolios of funds with similar investment objectives and asset size during the one- and three-year periods prior to closing. However, there is no significant difference in the performance of closed funds and their matched control portfolios during the one- and three-year periods after closing. Although the primary reason given for closing the funds is the desire to maintain performance in the face of growing assets, the strategy does not appear successful in accomplishing this objective.
Microchannel wall coatings for protein separations by capillary and chip electrophoresis.

The necessity for microchannel wall coatings in capillary and chip-based electrophoretic analysis of biomolecules is well understood. The regulation or elimination of EOF and the prevention of analyte adsorption is essential for the rapid, efficient separation of proteins and DNA within microchannels. Microchannel wall coatings and other wall modifications are especially critical for protein separations, both in fused-silica capillaries, and in glass or polymeric microfluidic devices. In this review, we present a discussion of recent advances in microchannel wall coatings of three major classes – covalently linked polymeric coatings, physically adsorbed polymeric coatings, and small molecule additives. We also briefly review modifications useful for polymeric microfluidic devices. Within each category of wall coatings, we discuss those used to eliminate EOF, to tune EOF, to prevent analyte adsorption, or to perform multiple functions. The knowledgeable application of the most promising recent developments in this area will allow for the separation of complex protein mixtures and for the development of novel microchannel wall modifications.
Nuclear transport of myelin basic protein

The multiple myelin basic protein (MBP) isoforms expressed by myelinating cells are now known to have different expression patterns. The relative abundance of the isoforms containing exon II is greater early in myelinogenesis, whereas in compact myelin the isoforms lacking this exon are more abundant. Further, the individual MBPs exhibit different intracellular localizations, indicating that the isoforms may not be functionally equivalent in myelinating cells. The major MBPs (14 kD and 18.5 kD) have strong affinity for membranes, while on the other hand, the less abundant isoforms (17 kD and 21.5 kD) localize to the nucleus of young oligodendrocytes, suggesting a regulatory role in the myelination program. The same intracellular distribution patterns have been observed when the MBPs are expressed in Hela cells and in shiverer oligodendrocytes. Thus, the intracellular fate of these proteins seems to be generally directed through alternative expression of exon II. Furthermore, the extent of MBPexII entry into the nucleus was found to be directly related to the growth state of host cells. In this paper, we demonstrate that nuclear proteins constitutively expressed by Hela cells also exhibit an apparently growth-related nucleo-cytoplasmic distribution revealing that MBPexII exhibits the same behavior as bona fide nuclear proteins. Also, to further characterize MBP nuclear transport, we explored various parameters of the translocation of MBP into the nucleus using an in vitro system. This experimental paradigm permits the uncoupling of synthesis and translocation events; thus, the transport of MBP into cell nuclei can be studied as a function of time. We also evaluated how changes in temperature as well as energy depletion affect the in vitro nuclear transport of MBP. J. Neurosci. Res. 50:258–264, 1997. © 1997 Wiley-Liss, Inc.
The biochemical and behavioral effects of phospholipase A2 and morphine microinjections in the periaqueductal gray of the rat

In order to characterize the in vivo action of phospholipase A/sub 2/ (PLA/sub 2/) on opiate receptors and opiate-induced behaviors, the effects of injections of PLA/sub 2/ into the periaqueductal gray region (PAG) of the rat were assessed on free fatty acid (FFA) release, opiate-binding levels, and morphine-induced behaviors. Rats received bilateral PAG injections of 2 ..mu..g of PLA/sub 2/ while anesthetized. One hour later, regions around the cannulae tracts in PLA/sub 2/-treated rats contained over 2.5 times more FFA than saline-injected controls, and /sup 3/H-dihydromorphine binding was reduced on average more than 70%. In another series of experiments, conscious rats were given 2 ..mu..g of PLA/sub 2/ prior to 10 ..mu..g of morphine through cannulae chronically implanted into the PAG. PLA/sub 2/ did not significantly attenuate morphine-induced analgesia as measured by the tail-flick test to radiant heat, but did prevent the explosive motor behavior observed following morphine injections alone. PLA/sub 2/ by itself did not induce analgesia, but did cause explosive motor behavior 2 hr after the injections. Neither lysophosphatidylcholine nor trypsin resulted in motor seizures following PAG injections. It was concluded that the behavioral effects of PLA/sub 2/ result from the unique properties of the enzyme, rather thanmore » generalized membrane damage, and that the opioid sites and mechanisms that mediate analgesia are different from those associated with explosive motor behavior. 36 references, 2 figures, 2 tables.« less
State of the knowledge for electromagnetic absorbed dose in man and animals

The paper gives the EM absorbed dose for man and animals at various frequencies for the plane wave irradiation condition for different orientations of the body relative to incident fields. Also included are the results for the whole-body absorption for conditions of electrical contact with ground and in the presence of reflecting surfaces of high conductivity and multiple animals. The data are given for the ditribution of power deposition in man models for the resonance conditions of highest whole-body electromagnetic absorption. The highlights of the results obtained with proportionately scaled saline- and biological-phantom-filled models of man have been confirmed by experiments with small laboratory animals, from 25-g mice to 2250-g rabbits.
Study of the Chemical and Physical Influences upon in Vitro Peptide-Mediated Silica Formation

Herein, we report on the ability to create complex 2-D and 3-D silica networks in vitro via polycationic peptide-mediated biosilicification under experimentally altered chemical and physical influences. These structures differ from the sphere-like silica network of particles obtained in vitro under static conditions. Under chemical influences, overall morphologies were observed to shift from a characteristic network of sphere-like silica particles to a sheetlike structure in the presence of -OH groups from additives and to sharp-edged, platelike structures in the presence of larger polycationic peptide matrixes. Under physical influences, using externally applied force fields, overall silica morphologies were observed to transition from sphere-like to fiberlike and dendrite-like structures. These findings could lead to the future development of bio-inspired complex 2-D and 3-D silica micro- and nano-devices.
Effect of intermittent washout periods on progressive lesioning of the nigrostriatal pathway with 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Abstract We have previously reported that a progressively increased dose of MPTP over the course of 4 weeks induces the gradual impairment of the nigrostriatal dopamine (DA) pathway and several behaviors [ Goldberg et al. (in press) Neuroscience]. To our knowledge, this is the first report of specific behavioral deficits correlated with discrete thresholds of DA loss in this pathway. In that study, MPTP was administered 5 d/wk, with behavioral and tissue analysis being carried out 3 days following the final injection at each dose. However, in order to better represent long-term progressive neurodegeneration the present study introduced a washout period of 10 days between each increased dose of MPTP. This implementation also controlled for any transient de-activation of tyrosine hydroxylase (TH), the enzyme that catalyzes synthesis of DA, caused by MPTP-induced oxidative stress which has been suggested following acute administration of the toxin [Smeyne and Jackson-Lewis (2005) Brian Res Mol Brain Res 134:57–66]. Additionally, by the end of the previous study, there was an ultimate decrease of 62% in the mean number of TH-labeled neurons/section in the substantia nigra pars compacta (SNpc) and a 74% decrease in caudate putamen (CPu) TH optical density with continuous MPTP. In the present study, we find that the washout periods lead to a final 79% decrease in the mean number of TH-labeled SNpc neurons/section, and a similar 74% decrease in CPu TH following the 32 mg/kg MPTP dose. Additionally, a dose-dependent decrease was observed in the mean number of SNpc TH-ir neurons/section in the current study which was not seen in the continuous MPTP protocol. These results suggest that a washout period following each increased MPTP dose allows for observation of continued cell death that might occur during the week following MPTP administration, and for therapeutic interventions to be applied at any of several stages during progressive neurodegeneration.
Tympanometry in rhesus monkeys: effects of aging and caloric restriction.

Caloric restriction is the only known method of increasing lifespan in laboratory animals. The present study was conducted as part of a larger investigation into the effect of caloric restriction on longevity of rhesus monkeys as a model for human aging. This study focused on the effects of caloric restriction and aging on measures of middle-ear function measured with tympanometry. Peak compensated static acoustic admittance (peak Ytm) tended to be reduced with aging. For tympanometric width (TW), the effect of age was significant with TW increasing with age. Males had a trend of narrower TW than females. A significant age by sex interaction indicated that TW for males stays relatively constant, whereas TW for females increases with age. The equivalent ear canal volume (Vea) was significantly larger in male monkeys than in female monkeys, and marginally larger for the control monkeys than for the caloric restricted monkeys. These results parallel many findings in middle-ear function in aging humans. Longi...
Boiling of liquids in a compact plate-fin heat exchanger

Abstract Prior to this study, no logical design method has existed for boiling heat transfer in compact, plate-fin, heat exchangers. This paper shows that a single-fin analysis can be used to predict the performance. Confirming tests were made with boiling Freon-113 and isopropanol heated by condensing steam, using a commercial compact heat exchanger having an 8·25 × 8·25 × 7·87 cm core which contained 11200 fins on the boiling side and 23 660 fins on the condensing side. The flow passages were 3·78 × 1·46 mm on the boiling side and 2·39 × 1·43 mm on the condensing side.
Instability-Driven SiGe Island Growth

Three-dimensional islanding is generally assumed to proceed through nucleation and growth. Here we present studies showing the growth of ${\mathrm{Si}}_{1\ensuremath{-}x}{\mathrm{Ge}}_{x}$ islands $(0.2lxl0.6)$ without nucleation. Rather, a strain-driven growth instability induces a network of elevated cells, where the angle of elevation self-limits when ${105}$ facets form pyramidal islands. These strain-modulated surfaces may serve as a template for the spatially controlled growth of quantum dot ensembles.
Skeletal analysis and mortuary practice in an Early Roman chamber tomb at Kenchreai, Greece

Recent exploration of the site of Kenchreai, the eastern port of Corinth in southern Greece, has focussed on a cemetery of subterranean chamber tombs dating chiefly to the Early Roman period (middle-late 1st to 3rd centuries AD). The copious but fragmentary human bones and teeth found in Tomb 10 have been disturbed since burial by natural processes, including bedrock erosion and the infiltration of moisture, roots and basic sediment, and by destructive looters. Nonetheless, the remains furnish considerable information about the mortuary practices of wealthy residents. Analysis of the remains in their archaeological and taphonomic contexts reveals that Tomb 10 contained at least 23 individuals, 15 inhumed in loculi and 8 cremated and placed in niches, sometimes in urns. The identification of males, females and subadults among the burned and unburned bones and teeth suggests that spouses, parents and children probably from several generations of the same lineage or household were buried here. The nature of the cremated fragments reflects a laborious process during which mourners burned bodies on substantial pyres at extremely high temperatures for a long time. Then they carefully extracted a representative sample of small fragments from throughout the reduced skeleton for burial at the tomb. This study contributes to a better understanding of mortuary practices in the Roman East, particularly the Greek world, where the chamber tomb was a common sepulchral type. Copyright © 2009 John Wiley & Sons, Ltd.
Mechanical Properties of Acrylic Pressure Sensitive Adhesives and Their Relationships to Industry Standard Testing

Abstract Dynamic mechanical and tensile stress-strain properties were measured for four sets of acrylic pressure sensitive adhesives, and were compared to industry standard “applications” peel and shear properties. Correlations were established showing that more than half of the range of performance shown by commercial PSA's is controlled by the bulk mechanical properties of the adhesive polymer. A few exceptions stand out clearly. Also, room temperature performance properties were found to correlate better with DMA at higher temperatures than with room temperature DMA. The contribution of tensile properties to peel strength and failure mode is discussed. The results can be used to relate PSA performance to well-known concepts in other areas of materials science, e.g. fracture toughness, rubber elasticity, and rheology, and to key variables in the adhesive formulation or selection process.
A new function for old drugs.

Antagonists of L-type Ca2+ channels (LTCC), such as amlodipine and verapamil, have been widely used for many years as anti-hypertensive and anti-anginal drugs. Anti-inflammatory activity has also been noted for these LTCC inhibitors1,2 and has been ascribed to their effects on NO production.1 Here, we briefly feature our recent study which assigns a previously unappreciated activity to these old drugs, a function which may account or at least contribute significantly to their anti-inflammatory activities.3 The function of the LTCC blockers is to suppress the participation of plasminogen in inflammatory cell recruitment.
Mixed mode fracture toughness and low cycle fatigue behavior in an HSLA-80 steel

Many structural components experience a combination of loads such as tension, torsion and shear. There has been an increasing number of studies of fracture toughness under loading conditions other than pure Mode I and under mixed mode loading conditions. In several high toughness materials (which fail by a microvoid nucleation and growth mechanism) the addition of a Mode III component to a Mode I-loaded sample leads to: (1) lower values of J{sub tc}, the overall critical value of J for stable crack growth and/or (2) lower values of dJ/da, beyond J{sub tc}. For example, with the introduction of a progressively increasing Mode III component, the values of J{sub tc} for a rotor steel dropped from 190 kJ/m{sup 2} in pure Mode I to a minimum of 98 kJ/m{sup 2} before increasing again. For a steel similar to that studied here, a significant drop in J{sub tc} did not occur with the introduction of mixed modality, but the dJ/da value was observed to exhibit a drop. The studies indicate that pure Mode I by itself is not a conservative design criterion for such tough materials. In this paper, the authors report the results of mixed mode fracture toughness testing on amore » modified ASTM A710 grade steel, designated HSLA-80, with applications in ship hulls. Preliminary results of low cycle fatigue crack growth behavior are also presented.« less
Time-Resolved Events on the Reaction Pathway of Transcript Initiation by a Single-Subunit RNA Polymerase: Raman Crystallographic Evidence

The nucleotidyl transfer reaction leading to formation of the first phosphodiester bond has been followed in real time by Raman microscopy, as it proceeds in single crystals of the N4 phage virion ...
The relationship between momentary response probabilities and momentary reinforcement effects

Premack’s probability hypothesis provides a simple empirical rule for predicting reinforcement effects, but has always been applied to response probabilities estimated by averaging over entire sessions. If the rule is robust, it should also predict momentary (e.g., within-sessions) changes in reinforcement from parallel momentary probability changes. It seems to do so. Six rats received noncontingent water (base), then leverpressed for water (contingency), each for 15 sessions. All sessions were divided into six subsessions. Average leverpressing for individual rats was a simple monotonie, usually linear, function of the probability of drinking—estimated from that subsession ’s counterpart during base. Similar results were obtained from a second study even though different instrumental and contingent events were used. With some generality, then, it is possible to apply the probability hypothesis to momentary reinforcement effects.
Studies on the mechanism of resistance of selected murine tumors to L-alanosine.

Abstract Sublines of P388 and L1210 leukemia were rendered resistant to l -alanosine [ l -2-amino-3-( N -hydroxy- N -nitrosamino) propionic acid] and designated P388/LAL and L1210/LAL. Assessments were made of certain biochemical and pharmacological determinants of the sensitivity or resistance to l -alanosine of these sensitive and resistant lines. It was observed that the antibiotic strongly inhibited adenylosuccinate synthetase and DNA synthesis only in the parent or sensitive lines; moreover, after a therapeutic dose of the drug, the concentration of l -alanosyl-AICOR ( l -alanosyl-5-amino-4-imidazole carboxylic acid ribonucleotide), the putative active anabolite of l -alanosine, was dramatically higher in these parent lines as compared with the resistant variants. Enzymologic studies established that, in P388/LAL, the specific activity of the enzyme SAICAR synthetase (5- amino -4- imidazole - N -succinocarboxamide ribonucleotide synthetase), which is believed to conjugate l -alanosine with the nascent purine AICOR (5-amino-4-imidazole carboxylic acid ribonucleotide), was depressed significantly; the same was not true for L1210/LAL. In both resistant lines, however, the enzymes of purine salvage were present at levels about 200 per cent higher than those measured in the native strains. These studies establish that resistance to l -alanosine is very likely pluricausal, but that the ability of susceptible cells to synthesize or retain l -alanosyl-AICOR is an element important to the process.
Perspectives of Parents Whose Children Have Dual Sensory Impairments

Although educators and other professionals acknowledge the importance of involving parents in their childrens' education, few researchers have investigated parental perceptions of educational and related services. This qualitative study identified four major themes during interviews with 28 families whose children have dual sensory impairments. These concerns clustered around parental perceptions of a “good life” for their children, as well as their experiences with fear, frustration, and change. Implications from the analysis may assist teachers, related service professionals, and administrators working with families to understand more fully parental perspectives.
Status of 3+N Sterile Neutrino Fits

Abstract Tension among recent short baseline neutrino experiments has pointed toward the possible need for one or more additional mass splittings in the existing neutrino oscillation framework. This would require the addition of at least one sterile (non-interacting) neutrino to the current model. This work summarizes fits to world data of models which include one, two, and three sterile neutrinos in the ∼ 1 eV 2 range and provides motivation for future short baseline searches.
Migraine Headache: Immunosuppressant Therapy.

There is very little literature on the use of immunosuppressant drugs in migraine treatment. Immunosuppressive agents are rarely, if ever, used as regular abortive drugs for episodic migraine attacks, and are never used as migraine preventives, because of the risk of side effects that come along with prolonged usage. Immunosuppressant drugs have been used in the emergency room as treatment for severe migraine attacks (intravenous corticosteroids), in the treatment of sustained or status migraine (oral or intravenous corticosteroids), in the treatment of drug-overuse headache (oral or intravenous corticosteroids), and in the treatment of immunosuppressant-induced headache in organ transplant recipients. Corticosteroids are commonly used as therapy for status migraine. Short courses of rapidly tapering doses of oral corticosteroids (prednisone or dexamethasone) can alleviate status migraine. Intravenous corticosteroids (methylprednisolone) in a single dose (emergency room or outpatient infusion unit) or as several days of repetitive dosing (in-hospital strategy) can be used to break long-lasting migraine attacks. A new use for corticosteroids in migraine therapy is to treat drug-overuse headache. Patients with drug-overuse or “rebound⫔eadache will only improve once their symptomatic medications have been discontinued. Stopping “rebounding medications” in the short-term can lead to withdrawal symptoms and a worsening of headache. In the long-term, it will lead to headache improvement. There are both outpatient and inpatient treatment strategies to detoxify patients off of misused medications. Corticosteroids have been used in the management of headache during the detoxification process as both outpatient treatments using short courses of oral corticosteroids or as repetitive intravenous therapy in an inpatient setting. Headache is a well-recognized but poorly reported side effect of organ transplantation. The approach to headache evaluation and management in the transplant setting is unique. Physicians must investigate all possible causes of headache from benign side effects of medications to precursors of potentially catastrophic neurologic abnormalities. One needs to think in terms of pharmacologic versus nonpharmacologic causes of headache. Immunosuppressive agents commonly known to cause headache include cyclosporine, tacrolimus (FK506), and muromonab CD3 (OKT3).
Update on paraneoplastic syndromes.

Purpose of reviewThis review discusses the varied clinical spectrum of neurologic paraneoplastic disorders, describes recent advances in our understanding of autoimmunity in these disorders, and outlines a practical clinical approach to patient management.Recent findingsParaneoplastic disorders may
Geopressure Detection Using Neural Classification of Seismic Attributes In Base Jilh Dolomite In Central Uthmaniyah, Saudi Arabia

Summary Use of neural network clustering techniques can illuminate seismic attributes indicative of geopressure in gas filled carbonate reservoirs. Here we adopt a two-step clustering technique. Initially, an unsupervised vector quantization (UVQ) analysis was used to identify the acoustic impedance along with its Fourier transform as potential attributes indicative of geopressure. Next, a supervised or learning vector quantization (SVQ) was applied to the selected attributes to generate a map consisting of 2 distinct target classes, one reflecting a zone of geopressure, and the other a normal formation-pressure zone. Results indicated the concentration of geopressure in low acoustic impedance zones. In addition, a UVQ analysis was performed on the porosity estimated from the acoustic impedance; detailed results revealed that areas of higher porosities were confined in the geopressured zones.
Preference for opening lines: Comparing ratings by men and women

Opening lines were conceptualized as a method for expanding one's marketplace for dating and marriage partners. In Study 1, university students and employees rated opening lines used by men for meeting women. Respondents (n=600) in one survey rated opening lines for general situations. Respondents (n=431) in a second survey rated opening lines for specific situations, including bars, restaurants, supermarkets, laundromats, and beaches. In Study 2, university students and employees (n=831) rated opening lines used by women for meeting men in general situations. Factor analyses identified three categories of opening lines: cute-flippant, innocuous, and direct. Overall, respondents agreed that cute-flippant opening lines were the least desirable and that innocuous and direct opening lines were the most desirable. Within this general consensus, there was a consistent tendency for women to dislike cute-flippant opening lines more than men and to prefer innocuous opening lines more than men. These differences were related to sex role socialization. Discussion focused on reasons people persist in using cute-flippant opening lines and on an attributional analysis of responses to opening lines.
Metallothionein-induced suppression of cytotoxic T lymphocyte function : An important immunoregulatory control

Exposure to environmental toxicants can alter a variety of cellular functions that are critical to immune function. Cellular responses to these changes include increased synthesis of a number of stress proteins, some of which have been shown to have immunomodulatory capacity. One of these stress proteins, metallothionein (MT) is a low molecular weight, cysteine-rich protein that can be induced by exposure to environmental stressors as well as many inflammatory and tumorigenic agents. As a consequence, high levels of MT have been found at sites of inflammation and in certain types of neoplastic cells. In light of the suppressive effects that MT has been found to have on T-dependent humoral immunity, we investigated the potential role that MT might play in cell-mediated immune functions that could contribute to antitumor immunity. We found that MT can cause dramatic decreases in murine cytotoxic T lymphocyte (CTL) activity against allogeneic target cells. MT also reduces the proliferative response of CTLL-2 cells to cytokines, and decreases the level of major histocompatibility complex (MHC) Class I and CD8 molecules detectable on the surface of lymphocytes, while having no significant effect on the level of CD4. These findings suggest that the immunosuppressive effects of MT may at least in part reflect interference with cell-cell interactions that are ordinarily critical to cell-mediated immunity. Despite this suppressive effect on CTL functioning, MT was found to augment mixed lymphocyte reactions (MLRs) in concert with increased interleukin-2 receptor (IL-2R) expression. This MT-augmented proliferation was observed in both allogeneic and syngeneic MLR. Taken together, these results indicate that MT may increase the number of immature T cells, but decrease their differentiation to the effector CTL stage. These effects of extracellular MT on T-cell function may contribute to the immunosuppression of cell-mediated immunity that has been ascribed to inducers of MT synthesis. In addition, they may point to the manipulation of MT levels as a means of reducing the undesirable immunomodulatory effects of these agents.
Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm resolution.

Abstract Background: The voltage-gated potassium channel Shaker from Drosophila consists of a tetramer of identical subunits, each containing six transmembrane segments. The atomic structure of a bacterial homolog, the potassium channel KcsA, is much smaller than Shaker. It does not have a voltage sensor and other important domains like the N-terminal tetramerization (T1) domain. The structure of these additional elements has to be studied in the more complex voltage-gated channels. Results: We determined the three-dimensional structure of the entire Shaker channel at 2.5 nm resolution using electron microscopy. The four-fold symmetric structure shows a large and a small domain linked by thin 2 nm long connectors. To interpret the structure, we used the crystal structures of the isolated T1 domain and the KcsA channel. A unique density assignment was made based on the symmetry and dimensions of the crystal structures and domains, identifying the smaller domain as the cytoplasmic mass of Shaker containing T1 and the larger domain as embedded in the membrane. Conclusions: The two-domain architecture of the Shaker channel is consistent with the recently proposed "hanging gondola" model for the T1 domain, putting the T1 domain at a distance from the membrane domain but attached to it by thin connectors. The space between the two domains is sufficient to permit cytoplasmic access of ions and the N-terminal inactivation domain to the pore region. A hanging gondola architecture has also been observed in the nicotinic acetylcholine receptor and the KcsA structure, suggesting that it is a common element of ion channels.
Head-centered orientation strategies in animate vision

The authors consider orienting, that is, establishing and maintaining a spatial relation between a motorized pair of cameras (the eye-head system) and a static or a moving object tracked over time. Motivated by physiological evidence, they propose a simple set of vision-based strategies aimed to perform head, eye, and body movements in a complex environment. Fixation is shown to be an essential feature in visual servoing, and is used to decouple control on head rotational degrees of freedom, making possible a metric-less approach to the orientation problem. An implementation of these strategies, using a binocular camera system mounted on a PUMA 700 robotic system, demontrated the effectiveness of the approach. >
Computing with arrays of coupled oscillators: an application to preattentive texture discrimination

Recent experimental findings (Gray et al. 1989; Eckhorn et al. 1988) seem to indicate that rapid oscillations and phase-lockings of different populations of cortical neurons play an important role in neural computations. In particular, global stimulus properties could be reflected in the correlated firing of spatially distant cells. Here we describe how simple coupled oscillator networks can be used to model the data and to investigate whether useful tasks can be performed by oscillator architectures. A specific demonstration is given for the problem of preattentive texture discrimination. Texture images are convolved with different sets of Gabor filters feeding into several corresponding arrays of coupled oscillators. After a brief transient, the dynamic evolution in the arrays leads to a separation of the textures by a phase labeling mechanism. The importance of noise and of long range connections is briefly discussed.
The Histone-Like Protein Hlp Is Essential for Growth of Streptococcus pyogenes: Comparison of Genetic Approaches To Study Essential Genes

Selection of possible targets for vaccine and drug development requires an understanding of the physiology of bacterial pathogens, for which the ability to manipulate expression of essential genes is critical. For Streptococcus pyogenes (the group A streptococcus [GAS]), an important human pathogen, the lack of genetic tools for such studies has seriously hampered research. To address this problem, we characterized variants of the inducible Ptet cassette, in both sense and antisense contexts, as tools to regulate transcription from GAS genes. We found that although the three-operator Ptet construct [Ptet(O)3] had low uninduced expression, its induction level was low, while the two-operator construct [Ptet(O)2] was inducible to a high level but showed significant constitutive expression. Use of Ptet(O)3 in the chromosome allowed us to demonstrate previously that RNases J1 and J2 are required for growth of GAS. Here we report that the uninduced level from the chromosomally inserted Ptet(O)2 construct was too high for us to observe differential growth. For the highly expressed histone-like protein (Hlp) of GAS, neither chromosomal insertion of Ptet(O)2 or Ptet(O)3 nor their use on a high-copy-number plasmid to produce antisense RNA specific to hlp resulted in adequate differential expression. However, by replacing the ribosome binding site of hlp with an engineered riboswitch to control translation of Hlp, we demonstrated for the first time that this protein is essential for GAS growth.
The role of transforming growth factor β in glaucoma and the therapeutic implications

Glaucoma is a progressive optic neuropathy frequently associated with elevated intraocular pressure, ocular vascular changes and extracellular matrix remodelling at the optic nerve head and in the trabecular meshwork. The pathogenesis is multifactorial and complex, but many recent studies have suggested that transforming growth factor-β (TGF-β) plays a major role in the process. Significantly elevated levels of TGF-β have been identified in the anterior chamber of glaucomatous eyes. TGF-β has also been shown to directly cause increased intraocular pressure. It is believed that this occurs through complex interaction with the trabecular meshwork, leading to decreased aqueous humour outflow. These processes occur through specific interactions with various proteins and signalling molecules also present in ocular tissues. By understanding the role that TGF-β plays in the pathogenesis of glaucoma, alternative therapeutic agents can be developed, which target these pathways and improve and assist in the management of disease. This review will cover previous investigative studies and discuss the current understanding of TGF-β's role in glaucoma and how it may serve as a potential therapeutic target.
The impact of fading on decentralized detection in power constrained wireless sensor networks

We study a binary decentralized detection problem in which a set of sensor nodes provides partial information about the state of nature to a fusion center. Sensor nodes have access to conditionally independent observations, given the state of nature, and they transmit their data over separate wireless channels. The communication link between each node and the fusion center is subject to fading, with certain nodes possibly having much better connections than others. Upon reception of the information, the fusion center attempts to accurately reconstruct the state of nature. Large deviation theory is employed to obtain design guidelines for wireless sensor networks with a large number of nodes. The normalized Chernoff information is shown to be an appropriate performance metric to compare prospective sensor nodes. For the specific example of binary sensor nodes sending data over Rayleigh fading channels, the performance loss due to fading is found to be small.
Ultrasound and thrombolysis

Thrombolytic therapy and mechanical interventions are frequently used in the treatment of both arterial and venous thrombotic disease. Limitations to these approaches include failure to achieve reperfusion and complications including bleeding and vessel wall damage. Increasing evidence indicates that the use of ultrasound offers potential therapeutic advantages. This review considers two distinct approaches which include the use of high intensity ultrasound to mechanically fragment clots and also the use of low intensity ultrasound to augment enzymatic fibrinolysis. High intensity ultrasound can be delivered via catheter or transcutaneously to disrupt clots in vitro or in animal models into small fragments. Initial clinical studies demonstrate potential clinical value in peripheral and coronary arterial thrombosis and occluded saphenous vein bypass grafts treated with the catheter approach. Studies in vitro indicate that low intensity ultrasound accelerates enzymatic thrombolysis through non-thermal mechanisms involving improvement in drug transport. The effect is larger at low frequencies, which also offer better tissue penetration and less heating. The ability to accelerate thrombolysis has been confirmed in animal models demonstrating markedly increased reperfusion and minimal toxicity. The use of ultrasound to mechanically disrupt occlusive thrombi or to accelerate enzymatic thrombolysis offers a new approach to treating occlusive thrombotic disease.
Precision grating for measuring microscope lens distortions

Microscopy is used in most technology processes where two-dimensional distributions, that are digital images of the shape and appearance of integrated circuit (IC) features, reveal important information. Optical microscopy and diffraction gratings can be used to measure the placement of IC features with a precision of less than 1 nm (1σ ) with a new technique of separately viewing multiple levels. However, the microscope’s optical and video camera distortion may cause significant errors in the IC feature measurement under some circumstances. In this paper, the optical and video camera distortions of an optical microscope used in IC feature measurement were studied by analyzing digital images of a precision grating. MATLAB programs were used to extract the value of intensity of each pixel in the grating image. By matching a position dependent, phase-varied ideal sinusoidal wave to the processed grating digital image, the phase of the best-fit sine wave was observed to vary by the equivalent of many nanometers at different locations within the digital image of the grating. This variation was similar, but significantly different, for different microscope objectives. It is believed to arise from optical distortion within the microscope, and possibly also from distortion within the camera. Impact of optic chromatic aberration and microscope stability on the measurement of IC features was also studied. The method described here is inexpensive and easy to implement since it does not require any sophisticated equipment or controlled environment. This technique provides an attractive option for small companies, university labs and instrument manufacturers.
The commercialization of the transistor radio in Japan: the functioning of an innovation community

In the 1950s, Japanese electronics firms moved from a technological level that seemed far behind their US and European rivals to dominate the first commercial markets for semiconductors. The processes by which this happened have been little studied and are not well understood. Aside from the apparent mystery of how the Japanese advanced so quickly with the technology are such related issues of importance to policymakers and managers as: did government contribute to or detract from the Japanese success? How did the major Japanese electron-tube producers, unlike their US counterparts and dominant firms in numerous other industries undergoing a major shift in technology, successfully make the transition to the new technology? This paper explores the history of the commercialization of the transistor radio, Japan's first successful semiconductor product. The history is organized into a theoretical framework to help permit systematic comparison and analysis.
Learning concept graphs from text with stick-breaking priors

We present a generative probabilistic model for learning general graph structures, which we term concept graphs, from text. Concept graphs provide a visual summary of the thematic content of a collection of documents—a task that is difficult to accomplish using only keyword search. The proposed model can learn different types of concept graph structures and is capable of utilizing partial prior knowledge about graph structure as well as labeled documents. We describe a generative model that is based on a stick-breaking process for graphs, and a Markov Chain Monte Carlo inference procedure. Experiments on simulated data show that the model can recover known graph structure when learning in both unsupervised and semi-supervised modes. We also show that the proposed model is competitive in terms of empirical log likelihood with existing structure-based topic models (hPAM and hLDA) on real-world text data sets. Finally, we illustrate the application of the model to the problem of updating Wikipedia category graphs.
Reply to Andriy Vasylchenko's Review of Formal Ontology and Conceptual Realism

Adriy Vasylchenko makes the interesting observation that our references are frequently emotionally charged. A comprehensive theory of reference, Vasylchenko suggests, should include an account of this phenomenon. We agree. Indeed, as we will see, the theory of reference in conceptual realism can be used to explain an important feature of our emotional states when we read a novel, or watch a play, a movie, or even when viewing a painting. This feature, which in aesthetics is called psychical distance, is connected in part with the difference between active and deactivated reference in conceptual realism. We will take up that issue at the end this reply. There is, however, an important misunderstanding in Vasylchenko’s review of how the notion of existential presupposition applies—or, as he claims, fails to apply—to fictional objects and more generally to the abstract intensional objects of conceptual realism. We will discuss this latter issue first, and then turn to the issue of our emotional states and psychical distance when reading fiction or watching a play or a film, and perhaps even when having an aesthetic experience in general.
DEP-Domain-Mediated Regulation of GPCR Signaling Responses

G protein-coupled receptors (GPCRs) mediate cellular responses to a variety of stimuli, but how specific responses are regulated has been elusive, as the types of GPCRs vastly outnumber the classes of G protein heterotrimers available to initiate downstream signaling. In our analysis of signaling proteins containing DEP domains (∼90 residue sequence motifs first recognized in fly Dishevelled, worm EGL-10, and mammalian Pleckstrin), we find that DEP domains are responsible for specific recognition of GPCRs. We examined the yeast regulator of G protein signaling (RGS) protein Sst2 and demonstrate that the DEP domains in Sst2 mediate binding to its cognate GPCR (Ste2). DEP-domain-mediated tethering promotes downregulation by placing the RGS protein in proximity to its substrate (receptor-activated Gα subunit). Sst2 docks to the Ste2 cytosolic tail, but only its unphosphorylated state, allowing for release and recycling of this regulator upon receptor desensitization and internalization. DEP-domain-mediated targeting of effectors and regulators to specific GPCRs provides a means to dictate the nature, duration, and specificity of the response.