cssi/SciSciGPT-SciSciNet huggingface dataset:
Bacterial resistances to inorganic mercury salts and organomercurials.

Abstract Environmental and clinical isolates of mercury-resistant (resistant to inorganic mercury salts and organomercurials) bacteria have genes for the enzymes mercuric ion reductase and organomercurial lyase. These genes are often plasmid-encoded, although chromosomally encoded resistance determinants have been occasionally identified. Organomercurial lyase cleaves the CHg bond and releases Hg(II) in addition to the appropriate organic compound. Mercuric reductase reduces Hg(II) to Hg(O), which is nontoxic and volatilizes from the medium. Mercuric reductase is a FAD-containing oxidoreductase and requires NAD(P)H and thiol for in vitro activity. The crystal structure of mercuric ion reductase has been partially solved. The primary sequence and the three-dimensional structure of the mercuric reductase are significantly homologous to those of other flavin-containing oxidoreductases, e.g., glutathione reductase and lipoamide dehydrogenase. The active site sequences are the most conserved region among these flavin-containing enzymes. Genes encoding other functions have been identified on all mercury ion resistance determinants studied thus far. All mercury resistance genes are clustered into an operon. Hg(II) is transported into the cell by the products of one to three genes encoded on the resistance determinants. The expression of the operon is regulated and is inducible by Hg(II). In some systems, the operon is inducible by both Hg(II) and some organomercurials. In gram-negative bacteria, two regulatory genes ( merR and merD ) were identified. The ( merR ) regulatory gene is transcribed divergently from the other genes in gram-negative bacteria. The product of merR represses operon expression in the absence of the inducers and activates transcription in the presence of the inducers. The product of merD coregulates (modulates) the expression of the operon. Both merR and merD gene products bind to the same operator DNA. The primary sequence of the promoter for the polycistronic mer operon is not ideal for efficient transcription by the RNA polymerase. The −10 and −35 sequences are separated by 19 (gram-negative systems) or 20 (gram-positive systems) nucleotides, 2 or 3 nucleotides longer than the 17-nucleotide optimum distance for binding and efficient transcription by the Escherichia coli σ 70 -containing RNA polymerase. The binding site of MerR is not altered by the presence of Hg(II) (inducer). Experimental data suggest that the MerR-Hg(II) complex alters the local structure of the promoter region, facilitating initiation of transcription of the mer operon by the RNA polymerase. In gram-positive bacteria MerR also positively regulates expression of the mer operon in the presence of Hg(II).
Seasonal occurrence and dominance of Centropages congeners in the Middle Atlantic Bight, USA

The copepod fauna of Middle Atlantic Bight waters regularly includes four species of Centropages: C. typicus, C. hamatus, C. velificatus, and C. bradyi. Seasonal collections of copepods with coarse-meshed (0.5 mm) bongo and neuston nets were often dominated by one of these congeners. A fifth species, C. violaceus, occurs very rarely, presumably as an expatriate from the Gulf Stream. C. typicus was the dominant large copepod in most seasons, especially at midshelf, but was largely replaced by Calanus finmarchicus after a severely cold winter (1977). The other Centropages species were less abundant and widespread: C. hamatus dominated inshore collections during winter and spring of 1977; C. bradyi was restricted mostly to outer shelf stations and was never abundant; C. velificatus appeared more frequently in the southern Bight, where it dominated a few inner shelf neuston collections in summer and fall.
AUTOMATED MAMMALIAN CELL BIOASSAYS FOR EVALUATING POTENTIAL THERAPEUTIC IMMUNOMODULATOR ANALOGS

Abstract Some mammalian cell lines in culture respond to exogenously added immunomodulators by induction of specific cell surface antigens or secretion of protein products. These proteins can be detected by immunoassay. The sample preparation and cell dosing steps of such cell based bioassays have been automated using a robotic liquid handling system housed in a containment chamber. These automated bioassays have been in nearly continuous use for over a year. Excellent cell viability has been maintained, and no contamination has been observed with either adherent or suspension target cell cultures. The cell response to addition of exogenous cytokine was identical when measured by either the automated or the manual assay. Data from triplicate samples evaluated on the same microtiter plate showed
Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 172.8 cells in culture

Abstract 5,5-diphenylhydantoin (Phenytoin, PHT), a widely used anticonvulsant, is also a vitamin K antagonist and disrupts bone metabolism, leading to osteomalacia. The vitamin K-dependently synthesized protein, osteocalcin, has been implicated as a key regulatory protein in bone resorption. The purpose of the present study was to determine whether PHT had an effect on osteocalcin secretion. Cells were grown to confluence in Ham's F-12 nutrient mixture, and treated with 1,25 (OH) 2 vitamin D 3 (2.6 μM to 2.6 pM) or PHT (5–100 μg/mL) for either 24 or 48 h of pretreatment. The media were then discarded, replaced with fresh media and test reagents, and quantitated for osteocalcin by radioimmunoassay at 0, 4, and 8 h secretion time points. Results were statistically analyzed by the Student's two-tailed t test. Controls showed a nearly linear secretion rate of osteocalcin, reaching 8–9 ng/10 6 cells by 8 h. Vitamin D 3 (2.6 nM) maximally stimulated secretion nearly two-fold after 24 or 48 h of pretreatment in comparison to controls. PHT alone (25–100 μg/mL) exerted an inhibitory effect, which appeared dose-dependent and was most evident at 4 and 8 h. PHT (50 μg/mL) had a significant effect, in the presence of a range of vitamin D 3 concentrations (2.6 μM to 2.6 pM), after 48 h of pretreatment. A maximal PHT dose of 100 μg/mL had no effect on either the viability or the numbers of cultured cells. These data indicate that PHT affects osteocalcin secretion from osteoblastic rat osteosarcoma (ROS 17 2.8 ) cells.
α-Defensin expression during myelopoiesis: identification of cis and trans elements that regulate expression of NP-3 in rat promyelocytes

Alpha-defensins are antimicrobial peptides that contribute to innate-immune functions of neutrophils and intestinal Paneth cells. Transcription of alpha-defensin genes occurs early in neutrophilic myelopoeisis. To examine the mechanisms that regulate alpha-defensin gene expression, we analyzed transcription of rat neutrophil alpha-defensin NP-3 in D4 cells, a subclone of the promyelocytic cell line IPC-81. Northern blot analysis showed that D4 cells express fivefold higher levels of alpha-defensin mRNA than the parental cell line in a manner relatively independent of passage number. Increased levels of steady-state mRNA in D4 cells correlated with markedly elevated peptide levels detected by immunocytochemical staining. To identify the cis-acting DNA elements involved in tissue-specific expression, D4 cells were transfected with luciferase reporter constructs containing NP-3 gene 5'-flanking sequences. Analyses of transfected D4 cells demonstrated that the proximal 87 base pair (bp) sequence contained cis-acting DNA elements necessary for optimal promoter activity. Mutational analyses within the 87-bp region suggested the involvement of the CAAT box and a putative polyoma enhancer-binding protein 2/core-binding factor (PEBP2/CBF) site in defensin gene transcription. Transient transfection analyses using tandem repeats of oligonucleotides containing these sequences demonstrated that proximity of the CAAT box and PEBP2/CBF site was important for defensin promoter activity. Electrophoretic mobility shift assays indicated that PEBP2/CBF or a PEBP2/CBF-related protein was involved in a specific protein-DNA interaction occurring within a DNA fragment containing the CAAT and PEBP2/CBF sequences. These data identify functional trans- and cis-elements that regulate rat defensin gene expression in high defensin-expressing promyelocytic cells.
TNFα-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish s-adenosylhomocysteine hydrolase

Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor S-adenosylmethionine (SAM). Elevated SAH in dtp larvae was associated with mitochondrial defects and increased expression of tnfa and pparg, an ortholog of the mammalian lipogenic gene. Antisense knockdown of tnfa rescued hepatic steatosis and liver degeneration in dtp larvae, whereas the overexpression of tnfa and the hepatic phenotype were unchanged in dtp larvae reared under germ-free conditions. These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFalpha. Although heterozygous dtp larvae had no discernible phenotype, hepatic steatosis was present in heterozygous adult dtp fish and in wild-type adult fish treated with an Ahcy inhibitor. These data argue that AHCY polymorphisms and AHCY inhibitors, which have shown promise in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection. Supporting this idea, hepatic injury and steatosis have been noted in patients with recently discovered AHCY mutations.
Optimization of the production of full‐length rCD4 in baculovirus‐infected Sf9 cells

The baculovirus-insect cell system is reliable in expressing a variety of recombinant proteins. A recombinant baculovirus encoding the full length human CD4 has been used to infect Spodoptera frugiperda 9 cells in 6-L-airlift fermentors. The procedured described in this report permitted a 6.5-fold enhancement of rCD4 expression as compared to standard procedures previously published. The increase of rCD4 expression on the cell surface was achieved by using the following steps: (1) Optimal seeding density of 0.8 x 10(6) cells/mL used to multiply cells at a maximum exponential growth of 4.5 x 10(6); (2) high multiplicity of infection (MOI) of 580 PFU/cell; (3) addition of medium at time of infection. In addition to full-length rCD4, a "short" rCD4 with largely deleted cytoplasmic sequence (last 31 C-terminal amino acids) was also efficiently expressed.
The Evolution of Emotions in Humans: A Darwinian–Durkheimian Analysis

Alexandra Maryanski's cladistic analysis of the last common ancestor to humans and apes reveals biological propensities in hominoids for autonomy, individualism, and weak-tie formation. The evolution of emotional capacities in humans, and the neuroanatomical bases for these capacities, are viewed as representing one of the many compensatory mechanisms for overcoming the low sociality contained in humans’ape ancestry. Speculation on the selection forces involved in hominids’growing capacity to use complex arrays of emotions for (a) mobilizing energy, (b) attuning, (c) sanctioning, (d) moral coding, (e) exchanging and (f) decision-making is conducted with an eye towards redirecting micro-level theorizing in sociology.
“Involvement” in cognitive-behavioral therapy with children: Process and its relationship to outcome

The rates of specific therapist and client verbal behaviors were examined within the context of behavioral, cognitive-behavioral, and attention-control interventions with children exhibiting classroom behavior problems. The 27 third- through sixth-grade children were referred by their teachers for participation in a treatment outcome study (Kendall & Braswell, 1982). All subjects were exposed to identical training materials and were seen for 12 50-minute sessions conducted over 7 weeks. All sessions were audiotaped. Seven-minute samples from the beginning, middle, and end of sessions 1, 2, 3, 10, 11, and 12 were scored according to a 13-category coding system. Correlations between these process categories and independent measures of treatment outcome suggested that child and therapist behaviors indicating active, positive “involvement” with the therapy tasks were associated with improvement and maintenance of therapy gains as assessed by teacher ratings of classroom behavior, while there were few significant relationships between the processes categories and the task performance and self-report measures of outcome and maintenance. In addition, in-session behavior was, for the most part, consistent with therapy labels. The importance of involvement in treatment, as a key factor in the quality of treatment, is discussed.
Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation.

Oligodendrocyte differentiation is accompanied by dramatic changes in gene expression as well as cell cycle arrest. To determine whether cell cycle arrest is sufficient to induce the changes in cell phenotype associated with differentiation, we inhibited oligodendrocyte precursor proliferation in vitro by overexpressing p27, a cyclin kinase inhibitor, using a recombinant adenovirus. Ectopic expression of p27 efficiently inhibited oligodendrocyte precursor cell division, even in the presence of exogenous mitogens, by blocking the activity of the cyclin-dependent kinase, cdk2. Although the cells had stopped dividing, they did not express galactocerebroside (GalC) or myelin basic protein (MBP), changes associated with oligodendrocyte differentiation, suggesting that they had not differentiated. After removal of exogenous mitogens, however, adenovirus-expressing oligodendrocyte precursors differentiated with a temporal profile similar to that of control, uninfected oligodendrocytes, as indicated by expression of GalC and MBP. We conclude that cell cycle arrest is not sufficient to induce differentiation of dividing oligodendrocyte precursors, and that modulation of additional, as yet unknown, signaling pathways is required for this to occur. J. Cell. Biochem. 76:270–279, 1999. © 1999 Wiley-Liss, Inc.
Initial results of land-reflected GPS bistatic radar measurements in SMEX02

Abstract To investigate scattering of Global Positioning System (GPS) signals from terrain and the potential for remotely sensing soil moisture with the L-band GPS bistatic radar concept, a prototype GPS bistatic radar participated in airborne measurements during the Soil Moisture Experiment 2002 (SMEX02). A 12-channel GPS navigation receiver, modified to perform bistatic radar measurements, was mounted on the NCAR C-130 aircraft to make co-located measurements with other instruments. Narrow pulse returns and comparison of the reflected GPS signal-to-noise ratio (SNR) measurements to digital imagery and cover maps indicated that the scattering was most likely quasi-specular, originating from a small footprint on the order of the first Fresnel zone (∼30 m). Temporal changes were observed in the measured signals and were expected to be proportional to varying soil moisture content. To investigate this effect, the bistatic signal measurements were interpolated to a spatial grid to produce daily maps of relative change of surface soil moisture over the study region. The maps of the study region showed a transition from dry surface soil moisture conditions to wet conditions following precipitation events occurring in the middle of the study period. Additionally, the maps showed the scattered power increased in areas with localized rainfall relative to areas without precipitation. Comparing the GPS-reflected SNR measurements with L-band brightness temperatures measured coincidently by the PALS radiometer showed good agreement in the trend measured by the two sensors. The scattered signal measurements were also compared with in situ soil moisture measurements and found to follow the general soil moisture trend as a function of time. These initial results from the first controlled experiment of GPS bistatic radar for soil moisture remote sensing indicate that the technique is sensitive to temporal and spatial variations in soil moisture.
Activity-Dependent Regulation of Inhibition via GAD67

Persistent alterations in network activity trigger compensatory changes in excitation and inhibition that restore neuronal firing rate to an optimal range. One example of such synaptic homeostasis is the downregulation of inhibitory transmission by chronic inactivity, in part through the reduction of vesicular transmitter content. The enzyme glutamic acid decarboxylase 67 (GAD67) is critical for GABA synthesis, but its involvement in homeostatic plasticity is unclear. We explored the role of GAD67 in activity-dependent synaptic plasticity using a mouse line (Gad1(-/-)) in which GAD67 expression is disrupted by genomic insertion of the green fluorescent protein (GFP). Homozygous deletion of Gad1 significantly reduced miniature inhibitory postsynaptic current (mIPSC) amplitudes and GABA levels in cultured hippocampal neurons. The fractional block of mIPSC amplitude by a low affinity, competitive GABA(A) receptor antagonist was higher in GAD67-lacking neurons, suggesting that GABA concentration in the synaptic cleft is lower in knockout animals. Chronic suppression of activity by the application of tetrodotoxin (TTX) reduced mIPSC amplitudes and the levels of GAD67 and GABA. Moreover, TTX reduced GFP levels in interneurons, suggesting that GAD67 gene expression is a key regulatory target of activity. These in vitro experiments were corroborated by in vivo studies in which olfactory deprivation reduced mIPSC amplitudes and GFP levels in glomerular neurons in the olfactory bulb. Importantly, TTX-induced downregulation of mIPSC was attenuated in Gad1(-/-) neurons. Altogether, these findings indicate that activity-driven expression of GAD67 critically controls GABA synthesis and, thus, vesicular filling of the transmitter.
An investigation into the potential use of serum Hsp70 as a novel tumour biomarker for Hsp90 inhibitors.

Hsp90 inhibitors are under investigation in multiple human clinical trials for the treatment of cancers, including myeloma, breast cancer, prostate, lung, melanoma, gastrointestinal stromal tumour and acute myeloid leukaemia. The pharmacodynamic activity of Hsp90 inhibitors in the clinic is currently assessed by Hsp70 induction in peripheral blood mononuclear cells using Western blot analysis, a method that is laborious, semiquantitative and difficult to implement in the clinic. Since Hsp70 was reported to be secreted by tumour cells and elevated in sera of cancer patients, serum Hsp70 has been evaluated as a potentially more robust, easily and reproducibly measured biomarker of Hsp90 inhibition as an alternative to cytosolic Hsp70. A highly sensitive and specific electrochemiluminescent ELISA was developed to measure serum Hsp70 and employed to evaluate Hsp70 levels in both ex vivo and xenograft samples. In ex vivo studies, maximal secretion of Hsp70 by tumour cells was observed between 48 and 72 h after...
Random oligonucleotide mutagenesis: application to a large protein coding sequence of a major histocompatibility complex class I gene, H-2DP

We have used random oligonucleotide mutagenesis (or saturation mutagenesis) to create a library of point mutations in the alpha 1 protein domain of a Major Histocompatibility Complex (MHC) molecule. This protein domain is critical for T cell and B cell recognition. We altered the MHC class I H-2DP gene sequence such that synthetic mutant alpha 1 exons (270 bp of coding sequence), which contain mutations identified by sequence analysis, can replace the wild type alpha 1 exon. The synthetic exons were constructed from twelve overlapping oligonucleotides which contained an average of 1.3 random point mutations per intact exon. DNA sequence analysis of mutant alpha 1 exons has shown a point mutant distribution that fits a Poisson distribution, and thus emphasizes the utility of this mutagenesis technique to "scan" a large protein sequence for important mutations. We report our use of saturation mutagenesis to scan an entire exon of the H-2DP gene, a cassette strategy to replace the wild type alpha 1 exon with individual mutant alpha 1 exons, and analysis of mutant molecules expressed on the surface of transfected mouse L cells.
Child Behavior Checklist Findings Further Support Comorbidity between ADHD and Major Depression in a Referred Sample

ABSTRACT Objective To examine the convergence of categorical and empirical diagnostic systems to evaluate whether psychiatric comorbidity of juvenile major depression with attention-deficit hyperactivity disorder (ADHD) is due to assessment bias. Method Using total predictive value and the odds ratio, the authors evaluated the convergence of Child Behavior Checklist (CBCL) scales with structured interview-derived diagnoses in 94 children with major depression, 97 with ADHD, and 115 normal control children with neither diagnosis. Results The CBCL Anxious/Depressed scale discriminated depressed from nondepressed children irrespective of comorbidity with ADHD, and the Attention Problems scale discriminated ADHD from non-ADHD children irrespective of comorbidity with major depression. Children with major depression comorbid with ADHD had CBCL correlates of both syndromes. Conclusions Since the CBCL is an empirically derived taxonomic system, the correspondence between the content-congruent CBCL scales and DSM-III-R categorical diagnoses of major depression and of ADHD indicates that previously reported findings of high overlap between these two disorders using structured diagnostic interview methodology and trained raters were not due to rater biases.
Distinct populations of microtubules: Tyrosinated and nontyrosinated alpha tubulin are distributed differently in vivo

A unique post-translational modification of tubulin has previously been described in which a tyrosine residue is reversibly added to the C terminus of the alpha-tubulin subunit. We have prepared peptide antibodies that specifically react (shown by competitive immunoassay and Western blots) with the tyrosinated (Tyr) and nontyrosinated (Glu) forms of alpha-tubulin. Immunofluorescence with these antibodies demonstrated that the distributions of Tyr and Glu tubulin in fixed cells were markedly different. Tyr tubulin was found throughout the interphase network of microtubules and in the metaphase spindle, whereas Glu tubulin was present in a limited subset of interphase microtubules and was absent from the astral fibers of the metaphase spindle. Double immunofluorescence showed that Glu and Tyr microtubules comprised distinct subsets of the total cellular microtubules. These results suggest that tyrosination is involved in the establishment of separate populations of microtubules that may functionally distinct.
Three-cluster resonating-group method in the coupled-channel formalism

Abstract Coupled-channel equations are derived by starting from an analytical formulation of a three-cluster resonating-group method. These equations are applied to the seven-nucleon system by including the 3 H + α, n + 6 Li, and n + 6 Li ∗ cluster configurations.
Role of Endometriosis in Cancer and Tumor Development

Endometriosis, like cancer, is characterized by cell invasion and unrestrained growth. Furthermore, endometriosis and cancer are similar in other aspects, such as the development of new blood vessels and a decrease in the number of cells undergoing apoptosis. In spite of these similarities, endometriosis is not considered a malignant disorder. The possibility that endometriosis could, however, transform and become cancer has been debated in the literature since 1925. Mutations in the genes that encode for metabolic and detoxification enzymes, such as GALT and GSTM, have been implicated in the pathogenesis of endometriosis and in the progression to carcinoma of the ovary. PTEN, a tumor suppressor commonly mutated (50%) in endometrial carcinoma, is found mutated in endometrioid carcinoma of the ovary, but not in other forms of ovarian cancer. A recent study has shown that somatic mutations in the PTEN gene were identified in 20% of endometrioid carcinomas and 20.6% of solitary endometrial cysts, suggesting that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma. In addition to cancerous transformation at the site of endometriosis, there is recent evidence to indicate that having endometriosis itself may increase a woman's risk of developing non-Hodgkin's lymphoma, malignant melanoma, and breast cancer.
Effects of chronic delta 9-tetrahydrocannabinol administration on schedule-controlled behavior of pigeons: cross-tolerance to pentobarbital and barbital.

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from Δ9-tetrahyrocannabinol (Δ9-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received Δ9-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to Δ9-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic Δ9-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic Δ9-THC administration did not differ significantly. Tolerance to Δ9-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from Δ9-THC to a barbiturate that normally undergoes little metabolism.
Issue Fluidity and Agenda Setting on the Warren Court

While justices have considerable discretion in the picking and choosing between cases in the creation of their agenda, how much discretion do they exercise in the picking and choosing between the issues that were presented by the parties, or even in developing new issues? Given the Warren Court's reputation for articulating broad rules that went beyond the particular circumstances of an individual case, especially in the area of civil rights and liberties, we would expect that this issue fluidity, particulary the expansion of issues, occurred with some frequency during this era. With an analysis of a random sample of 200 cases from the Warren Court, I found that the justices developed new issues in about one-fourth of all cases, while they suppressed issues that had been fully briefed and argued in over half of all cases. In addition, surprisingly, the Warren Court tended to suppress issues in civil rights and civil liberties cases, rather than expand them.
Percutaneous biliary drainage.

Percutaneous biliary drainage was one of the first nonvascular interventional radiology procedures to be widely used, and it continues to be performed today despite advances in endoscopic drainage. Currently, the procedure is usually reserved as a second-line therapy when endoscopic drainage is not feasible (e.g., due to prior biliary enteric anastomosis) or when endoscopic drainage fails.
Explaining the Political and Personal Consequences of Protest

The authors examine the consequences of social movement participation for late 1960s and early 1970s activists, most of whom participated in the antiwar, student, and civil rights protests. After providing an explanatory framework for understanding how social movement participation might have continuing influence across a number of social realms, they test whether run-of-the-mill participation in the antiwar and student protests of the late 1960s had an impact. Using data from the Youth-Parent Socialization Panel Study, they show how demonstrators differed from nonactivists in two time periods : shortly after their movement experiences in 1973; and when they were in their mid-thirties in 1982. Controlling for the factors that predict becoming a protester, they explore the influence of activism on : (1) politics; (2) status attainment; (3) religion; and (4) family. They find that controlling for factors that predict protest participation, these typical activists are significantly different from their nonactivist counterparts. Specifically, former protesters hold more liberal political orientations and are more aligned with liberal parties and actions; select occupations in the new class; are more educated; hold less traditional religious orientations and are less attached to religious organizations; marry later; and are less likely to have children
Protein-kinase-A-dependent activator in transcription factor CREB reveals new role for CREM repressors.

HORMONALLY induced increases in cyclic AMP levels induce phosphorylation of the transcription factor CREB at a serine residue at position 133 by protein kinase A (ref. 1), enhancing its ability to activate transcription without affecting its intracellular location or DNA-binding activity. This effect is dependent on a 60-amino-acid region of CREB that contains Serl33 and is termed the kinase-inducible domain (KID)2, which also occurs in the CREB-related CREM-α and -β proteins, although these are transcriptional repressers3. Here we show that the KID domain confers a cAMP-inducible increase on the activity of the Q2 activation domain from CREB and the acidic activation domains from the yeast proteins GAL4 and GCN4. Remarkably, it retains this ability even when attached to a separate polypeptide bound to an adjacent site in the promoter. KID may therefore be the first of a new class of conditional activators that work through other promoter-bound factors to stimulate gene expression in response to hormonal stimuli.
SmartFall: an automatic fall detection system based on subsequence matching for the SmartCane

Fall-induced injury has become a leading cause of death for the elderly. Many elderly people rely on canes as an assistive device to overcome problems such as balance disorder and leg weakness, which are believed to have led to many incidents of falling. In this paper, we present the design and the implementation of SmartFall, an automatic fall detection system for the SmartCane system we have developed previously. SmartFall employs subsequence matching, which differs fundamentally from most existing fall detection systems based on multi-stage thresholding. The SmartFall system achieves a near perfect fall detection rate for the four types of fall conducted in the experiments. After augmenting the algorithm with an assessment on the peak impact force, we have successfully reduced the false-positive rate of the system to close to zero for all six non-falling activities performed in the experiment.
Alpha-adrenergic inhibition of sympathetic neurotransmitter release mediated by modulation of N-type calcium-channel gating.

IN sympathetic neurons, catecholamines interact with prejunctional α-adrenergic receptors to reduce delivery of transmitter to postjunctional target organs1-4. This autoinhibitory feedback is a general phenomenon seen in diverse neurons containing a variety of transmitters2-4. The underlying mechanisms of α-adrenergic inhibition are not clear, although decreases in cyclic AMP and cAMP-mediated phosphorylation have been implicated1-4 (compare ref. 5). We have studied depolarization-induced catecholamine release and calcium-channel currents in frog sympathetic neurons. Here we show that α-adrenergic inhibition of transmitter release can be explained by inhibition of Ca2+-channel currents and not by modulation of intracellular proteins. Noradrenaline strongly reduces the activity of N-type Ca2+ channels, the dominant calcium entry pathway triggering sympathetic transmitter release6, whereas L-type Ca2+ channels are not significantly inhibited. The down-modulation of N-type channels involves changes in rapid gating kinetics but not in unitary flux. This is the first detailed description of inhibition of a high-voltage activated neuronal Ca2+ channel at the single-channel level. The coupling between α-adrenergic receptors and N-type channels involves a G protein, but not a readily diffusible cytoplasmic messenger or protein kinase C, and may be well suited for rapid and spatially localized feedback-control of transmitter release.
Effects of cyclopiazonic acid and aflatoxin singly and in combination on selected clinical, pathological and immunological responses of guinea pigs

Cyclopiazonic acid (CPA) and aflatoxin are known sometimes to coexist in nature but little is known of possible biological interaction in mammals that consume mixtures of these two mycotoxins. Guinea pigs were dosed orally with CPA (2.2 mg/kg) or aflatoxin (0.045 mg B1/kg) singly or in combination. Effects of toxin consumption were determined on clinical health, body weight gain, pathological change, and several immunologically related parameters including delayed cutaneous hypersensitivity, antibody response, complement hemolytic titer, intracutaneous mitogen (PHA) and in vitro lymphocyte blastogenesis. In contrast to an earlier study by others, significant synergy between these two toxins was demonstrated in reduced rate of body weight gain, lethality and histologic changes (vacuolization) in hepatocytes. Reductions in complement titer, intradermal PHA, delayed cutaneous hypersensitivity response and in vitro lymphocyte blastogenesis were related to aflatoxin activity. No effects on antibody formation to Brucella abortus were observed with either toxin or the combination of toxins. Cyclopiazonic acid appeared to restore the suppressive effects of aflatoxin in delayed cutaneous hypersensitivity response and in vitro lymphocyte blastogenesis.
Peptide sequencing using a patchwork approach and surface-induced dissociation in sector-TOF and dual quadrupole mass spectrometers.

Surface-induced ion activation in combination with a database search strategy based on the Patchwork concept is applied to the determination of peptide sequences. Surface-induced dissociation (SID) is performed in a tandem quadrupole mass spectrometer and in a hybrid sector/time-of-flight mass spectrometer in order to evaluate the importance of accurate mass analysis of the SID fragment ions for peptide identification. The modified Patchwork approach is based on piecing together the peptide blocks in a bidirectional way, simultaneously using low-mass fragments originating from the C-terminus and N-terminus of the molecule, and relying on the measurement of the peptide’s molecular weight with moderate mass accuracy. The results from this analysis are used as search filters in MASCOT’s (http://www.matrixscience.com) Sequence Query search engine, with the simultaneous addition of the full MS/MS peak list. SID is performed with collision targets coated with pure and mixed composition self-assembled monolayers produced by fluorocarbon and hydrocarbon alkanethiolate solutions of varying chemical composition. The resulting MS/MS spectra produced on pure and mixed hydrocarbon SAMs are submitted to the modified version of Patchwork sequencing. It is found that hydrocarbon surfaces improve the relative abundance of larger fragments. Under the moderate mass accuracy conditions (±0.3 u) offered by our linear-TOF-SID instrument, it is found that increasing the abundance of larger fragments dramatically improves the sequencing scores.
Significance of atypical category in voided urine specimens prepared by liquid-based technology: Experience of a single institution.

Introduction The goal of this study was to evaluate the clinical significance of atypical cytology in voided urine samples. We also studied any differences in outcome that may exist between the patients being surveyed versus high risk for urothelial carcinoma (UC). Materials and methods This was a retrospective study of all voided urine specimens with “atypical” cytology over a 10-year period. The patients were categorized into those with and without a prior diagnosis of UC as the “surveillance” and “de novo” (DG) groups. Follow-up was obtained. Clinical impact and outcomes of the 2 groups were compared. Results In this study, 5.7% of voided urine specimens were atypical. Mean age of patients in years, male/female ratio, and time to diagnosis in days was 59 versus 71, 23:15 versus 22:1, and 95 versus 43 in the DG and surveillance group, respectively. Rate of progression to UC was similar in both groups. High-grade UC was significantly higher in the DG. Conclusions Approximately 20% of patients in the DG were subsequently diagnosed with UC. The common causes for the atypical diagnosis that did not progress to UC were stones and benign prostatic hyperplasia. In the absence of an etiology for the atypia, further investigations are warranted.
A Methodology for the Experimental Evaluation of Seismic Pounding at Seat-Type Abutments of Horizontally Curved Bridges

Seat-type supports are normally used at bridge ends to accommodate thermal expansion and eliminate the high stresses that would otherwise be present in the superstructure when the ends are rigidly held. However, during large seismic events, there is high possibility that the joint gap between the end of the bridge and abutment backwall would close and high acceleration impact would result. It is expected that this abutment backwall pounding would significantly affect the bridge response. Yet, limited experimental research has been conducted to investigate the extent, how, and what components are affected by such effect. As a part of a Federal Highway Administration funded project, a two-fifths scale curved bridge model was constructed at University of Nevada, Reno Large Scale Structures Laboratory for shake table testing. One of the six configurations of the bridge model was designed to experimentally study the seismic performance of seat-type abutments, abutment backwall pounding, and its effect on bridge response. An abutment setup was designed to facilitate the investigation of the abutment impact accounting for the nonlinearity of the backfill soil. A compression-only device with permanent deformation was developed to represent the soil passive resistance. This paper describes the experimental setup developed to evaluate the seismic performance of seat-type abutments and characterize the interaction between the bridge superstructure, abutment backwalls, and nonlinear soil backfill.
Physicochemical and immunological characterization of the type E botulinum neurotoxin binding protein purified from Clostridium botulinum.

Type E botulinum neurotoxin is produced byClostridium botulinum along with a neurotoxin binding protein which helps protect the neurotoxin from adversepH, temperature, and proteolytic conditions. The neurotoxin binding protein has been purified as a 118-kDa protein. Secondary structure content of the neurotoxin binding protein as revealed by far-UV circular dichroism spectroscopy was 19% α-helix, 50%β-sheets, 28% random coils, and 3%β-turns. This compared to 22% α-helix, 44%β-sheets, 34% random coils, and noβ-turns of the type E botulinum neurotoxin. The complex of the two proteins revealed 25%α-helix, 45%β-sheets, 27% random coils, and 3%β-turns, suggesting a significant alteration at least in theα-helical folding of the two proteins upon their interaction. Tyrosine topography is altered considerably (28%) when the neurotoxin and its binding protein are separated, indicating strong interaction between the two proteins. Gel filtration results suggested that type E neurotoxin binding protein clearly complexes with type E neurotoxin. The interaction is favored at lowpH as indicated by an initial binding rate of 8.4 min−1 atpH 5.7 compared to 4.0 min−1 atpH 7.5 as determined using a fiber optic-based biosensor. The neurotoxin and its binding protein apparently are of equivalent antigenicity, as both reacted equally on enzyme-linked immunosorbent assay to polyclonal antibodies raised against the toxoid of their complex.
The ratio of maximum percent tumour accumulations of the pretargeting agent and the radiolabelled effector is independent of tumour size

Our previous studies have indicated that the optimal dosage ratio of pretargeting antibody to effector is proportional to their maximum percent tumour accumulations (MPTAs). This study quantitatively describes how both MPTAs and their ratio change with tumour size, to simplify pretargeting optimisation when tumour size varies. The CC49 antibody dosages below saturation of the tumour antigen level were first examined for the LS174T tumour mouse model. Then the MPTAs of the antibody in mice bearing tumours of different sizes were determined, always at antibody dosages below antigen saturation. Historical data from this laboratory were used to collect the MPTAs of the (99m)Tc-cMORF effector for different tumour sizes, always at effector dosages below that required to saturate the MORF in tumour. The MPTAs versus tumour sizes for both the antibody and the effector were fitted non-linearly. The best fit of the antibody MPTA (Y(antibody)) with tumour size (x) in grams was Y(antibody)=19.00 x(-0.65) while that for the effector was Y(effector)=4.51x(-0.66). Thus, even though the MPTAs of both vary with tumour size, the ratio (Y(antibody)/Y(effector)) is a constant at 4.21. In conclusion, the MPTA ratio of the antibody to the effector was found to be constant with tumour size, an observation that will simplify pretargeting optimisation because remeasurement of the optimum dosage ratio for different tumour sizes can be avoided. Theoretical considerations also suggest that this relationship may be universal for alternative antibody/effector pairs and for different target models, but this must be experimentally confirmed.
Nomenclature and knowledge-culture, or, we don’t call semen ‘penile mucous’

Science reflects cultural practices and also occurs within them, and this ‘knowledge-culture’ is constituted by the public imaginary (general understandings and perceptions of phenomena) and the ‘scientific imaginary’ (the ability to envision scientific questions, methods, meanings and material possibilities for studying phenomena). In this feminist science laboratory case study, I argue that nomenclature contributes to epistemologies of ignorance, delimiting knowledge-culture and the scientific imaginary about vaginal fluid, which has implications for understandings of women’s bodies as well as sexual health potentials. Abject terms for vaginal fluid (vaginal mucous; vaginal discharge) preclude its existence in the scientific imaginary except as passive signs of dis-ease. I argue for a gendered abjectness of vaginal fluid’s names by situating it next to fluids that are tied to other mucosal surfaces, thus showing that even when gender is not involved in the name, gendered knowledge-culture can still affe...
Binary frontal polymerization: A new method to produce simultaneous interpenetrating polymer networks (SINs)

We report a new method for the preparation of a simultaneous interpenetrating polymer network (SIN) using a thermal propagating front of two independent and noninterfering polymerization mechanisms. The system consists of the free radical crosslinking of triethylene glycol dimethacrylate (TGDMA) and the amine/BCl3 · amine curing of diglycidyl ether of bisphenol A (DGEBA). The front velocity dependence on the percentage of each monomer shows a minimum at 45% TGDMA. Temperature profile measurements indicate that a single reaction front propagates. A colored opaque material is produced, but SEM and TEM analysis were inconclusive whether phase separation occurred. Samples as large as 5 cm in diameter were prepared with this method. We conclude that this method should be especially suited for preparing large samples of IPNs in which significant phase separation occurs. © 1997 John Wiley & Sons, Inc.
1207 THE INSULIN RECEPTOR (IR) IS INTERNALIZED IN THE FETAL BRAIN CELLS

We studied 125I-insulin total and non-specific binding(IB) and 3H-deoxyglucose uptake (Gu) by 30d isolated fetal rabbit-brain cells (viability of >93%;n=8), to define the significance of the IR in the fetal brain. IB and Gu by brain cells were also assessed in the presence of 10mM phenylarsine oxide (PA) (n=4; prevents IR internalization) and 10μM chloroquin (CQ) (n=5; a lysosomotropic agent), to study the internalization and intracellular degradation of the IR (extracellular degradation was constant throughout the study). Peak specific IB per 6.4×105 cells was achieved by 1-3 min (2.74±0.18%, X+SEM), declining by 20 mln (0.48±0.15;p<0.001). A decrease in the peak binding was observed with PA (0.40±0.08;p<0.001), whereas CQ resulted in a peak IB of 1.32±0.19, with no decline in IB at 20 min (2.11±0.49;p<0.01). 1×10−6M insulin increased the Gu from 0.03±0.002 to 0.05±003nM/6.4×105 cells (p<0.01). PA inhibited Gu and the insulin induced increase in Gu by the brain cells, while CQ inhibited the insulin induced increase in Gu alone (0.02±0.0007;p<0.01). Summary: 1)In the presence of PA, IB is decreased 2)CQ delayed the decline in peak IB secondary to its lysosomotropic effects and decreased intracellular IR degradation 2)Insulin augmented Gu by fetal brain cells 4)Inhibition of IR internalization by PA or lysosomotropic effects by CQ interfered with the insulin induced Gu by the brain cells. We conclude that the insulin induced Gu by fetal brain cells is associated with internalization of the IR.
Combined stimulation of the glycine and polyamine sites of the NMDA receptor attenuates NMDA blockade-induced learning deficits of rats in a 14-unit T-maze

The present study examined the effects of multi-site activation of the glycine and polyamine sites of the NMDA receptor on memory formation in rats learning a 14-unit T-maze task. The competitive NMDA receptor antagonist, (±)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP, 9 mg/kg), was used to impair learning. The objectives were two-fold: (1) to investigate the effects of independent stimulation of the strychnine-insensitive glycine site or the polyamine site; (2) to investigate the effects of simultaneous activation of these two sites. Male, Fischer-344 rats were pretrained to a criterion of 13 out of 15 shock avoidances in a straight runway, and 24 h later were trained in a 14-unit T-maze that also required shock avoidance. Prior to maze training, rats received intraperitoneal (IP) injections of saline, saline plus CPP, CPP plus the glycine agonist, D-cycloserine (DCS, 30 or 40 mg/kg), CPP plus the polyamine agonist, spermine (SPM, 2.5 or 5 mg/kg), or CPP plus a combination of DCS (7.5 mg/kg) and SPM (0.625 mg/kg). Individual administration of either DCS or SPM attenuated the CPP-induced maze learning impairment in a dose-dependent manner. However, the combined treatment with both DCS and SPM completely reversed the learning deficit at doses five-fold less than either drug given alone. These findings provide additional evidence that the glycine and polyamine modulatory sites of the NMDA receptor are involved in memory formation. Furthermore, the potent synergistic effect resulting from combined activation of the glycine and polyamine sites would suggest a stronger interaction between these two sites than previously considered, and might provide new therapeutic approaches for enhancing glutamatergic function.
Valuation of New Products in Attribute Space

We contribute to the literature on new product valuation by presenting a model of new product introduction based on the distance metric (DM) approach of Pinkse, Slade, and Brett (2002) . Models based on the DM approach are capable of dealing with highly differentiated food categories that are often responsible for the lion’s share of new product activity. Furthermore, since new products are typically characterized by differences in observable attributes, the DM approach is appropriate in that it directly accounts for such differences. Our findings reveal that consumers benefit from new products even when the number of alternatives is already high. Copyright 2007, Oxford University Press.