cssi/SciSciGPT-SciSciNet huggingface dataset:
Artificial intelligence (AI)-assisted exome reanalysis greatly aids in the identification of new positive cases and reduces analysis time in a clinical diagnostic laboratory

Abstract Purpose Artificial intelligence (AI) and variant prioritization tools for genomic variant analysis are being rapidly developed for use in clinical diagnostic testing. However, their clinical utility and reliability are currently limited. Therefore, we performed a validation of a commercial AI tool (Moon) and a comprehensive reanalysis of previously collected clinical exome sequencing cases using an open-source variant prioritization tool (Exomiser) and the now-validated AI tool to test their feasibility in clinical diagnostics. Methods A validation study of Moon was performed with 29 positive cases determined by previous manual analysis. After validation, reanalysis was performed on 80 previously manually analyzed nondiagnostic exome cases using Moon. Finally, a comparison between Moon and Exomiser was completed regarding their ability to identify previously completed positive cases and to identify new positive cases. Results Moon correctly selected the causal variant(s) in 97% of manually analyzed positive cases and identified 7 new positive cases. Exomiser correctly identified the causal gene in 85% of positive cases and agreed with Moon by ranking the new gene in its top 10 list 43% of the time. Conclusion The use of AI in diagnostic laboratories greatly enhances exome sequencing analysis by reducing analysis time and increasing the diagnostic rate.
The Surgical Scheduling Problem: Current Research and Future Opportunities

This paper reviews the general problem of surgical scheduling. We organize the literature based on the time frame or planning horizon of the schedule into six categories: capacity planning, process reengineering/redesign, the surgical services portfolio, procedure duration estimation, schedule construction, and schedule execution, monitoring, and control. We survey past work and suggest topics for potential future research in each of those areas.
Electrochemistry of transition metal complexes encapsulated into zeolites

Summary The electrochemistry of transition metal complexes (Co(salen) and [Fe(bpy) 3 ] 2+ ) encapsulated into zeolites was studied using zeolite-modified electrodes (ZME). Grinding time, binding material, carbon source, electrolyte, solvent, scan rate, and the charge of the encapsulated complex all affect the cyclic and differential pulse voltammetry of these ZMEs.
In Vitro and In Vivo Nonimaging Tests

The radioimmunoassay (RIA) method was first developed by S.A. Berson and R.S. Yalow in the late 1950s for the determination of insulin in human serum. Currently, the method is employed extensively to determine numerous hormones, enzymes, antigens, and drugs in minute quantities (10-9-10-12 M) in human plasma in order to assess various disease conditions. The general term for this method in both immune and nonimmune systems is the competitive binding assay (CBA).
Equilibrium Dialysis and Cell Binding Studies on Bandeiraea simplicifoka Lectin

Abstract Equilibrium dialysis studies on the binding of the blood group B-specific Bandeiraea simplicifolia lectin to methyl α-D-galactopyranoside demonstrated the existence of one carbohydrate binding site per subunit for the tetrameric protein, with an intrinsic association constant of 8.6 × 104 M−1 at 2° and 3.3 × 104 M−1at 20°. These values correspond to a free energy of binding, δG0′ (pH 7.2), of −6.21 kcal/mol and −6.06 kcal/mol at 2° and 20°, respectively. The sites appeared homogeneous and noninteracting. B. simplicifolia lectin receptor sites per human B erythrocyte varied from 0.72 × 105 to 1.34 × 105 with an apparent association constant of 1.1 x 10′ Mm′ to 2.9 x 10′ M−1. The binding characteristics ofB. simplicifolia lectin are compared to other purified lectins.
Nettwerk: Digital Marketing in the Music Industry

How is music marketed in the digital era? Nettwerk Music Group built on its foundation as a social, grassroots marketer of music and artists, and emerged as a leader in the Internet-enabled social media environment. For most of the past decade Nettwerk CEO Terry McBride let fans consume music on their own terms. He encouraged file-sharing, the remixing of his artists' songs and videos, and an environment in which "the audience is the record company." In the digital marketplace compact discs mattered much less, said McBride. "Digital assets" were the currency, in the form of ad, television, movie, and videogame song placement, ringtones, mixes, and community-created content. But new artist-label contracts were needed if digital assets were going to flow freely. Moving away from the infrastructure of the music business also meant having to do without the financial, logistical, and promotional power of the major labels. To provide an alternative to the muscle of the major labels, the company is launching a venture capital project called "Polyphonic."
American Hazardscapes: Regionalization of Hazards and Disasters

Susan L. Cutter, ed. Washington, DC: Joseph Henry Press, 2001. xi and 211 pp., maps, diags., photos., refs., apps., and index. $47.95 cloth (ISBN 0-309-07443-6). American Hazardscapes: Regionalizat...
Linear Time Constant-Working Space Algorithm for Computing the Genus of a Digital Object

In recent years the design of space-efficient algorithms that work within a limited amount of memory is becoming a hot topic of research. This is particularly crucial for intelligent peripherals used in image analysis and processing, such as digital cameras, scanners, or printers, that are equipped with considerably lower memory than the usual computers. In the present paper we propose a constant-working space algorithm for determining the genus of a binary digital object. More precisely, given an m ×n binary array representing the image, we show how one can count the number of holes of the array with an optimal number of O (mn ) integer arithmetic operations and optimal O (1) working space. Our consideration covers the two basic possibilities for object and hole types determined by the adjacency relation adopted for the object and for the background. The algorithm is particularly based on certain combinatorial relation between some characteristics of a digital picture.
Aminopeptidase activity in marine chroococcoid cyanobacteria.

Synechococci are important primary producers in the ocean and can also utilize some components of the dissolved organic matter (DOM). The readily utilizable DOM in seawater is mainly polymeric (e.g., protein, polysaccharide) or phosphorylated and requires hydrolysis prior to uptake. We examined whether synechococci express ectoenzymes to hydrolyze DOM components and considered the possible significance of ectohydrolases for Synechococcus ecology and organic matter cycling in the sea. Five strains of non-nitrogen-fixing synechococci in axenic cultures were tested for enzyme activities with fluorogenic substrates. All strains show ectocellular aminopeptidase activity, but other enzymes were undetectable. The aminopeptidase level was in the range determined for five marine heterotrophic bacterial isolates tested for comparison. Aminopeptidase was not secreted into the medium; the majority (74%; tested in WH 7803) was cell surface bound, and a small fraction was periplasmic. The periplasmic activity was not released by cold osmotic shock of WH 7803. Phenylmethylsulfonyl fluoride and EDTA, inhibitors of serine and metalloproteases, strongly or completely inhibited WH 7803 aminopeptidase. The enzyme seemed constitutive; per-cell activity did not change during incubations in unenriched seawater, bovine serum albumin, or nitrate-replete mineral medium. In natural planktonic assemblages in the Southern California Bight, aminopeptidase activity was correlated with Synechococcus abundance as well as the abundance of other bacteria. Ectocellular aminopeptidase may be common in marine synechococci and play roles in their nitrogen nutrition, particularly in low-nitrate and low-light environments. Since synechococci are much less abundant than heterotrophic bacteria in seawater, the impact of Synechococcus aminopeptidase on proteolysis in the sea is likely to be episodic and restricted to specialized microenvironments.
A rapid kindling paradigm used to examine hippocampal neuroplasticity

The authors report the development of a stimulation paradigm designed to induce the kindled state in a significantly shorter time frame than the traditional kindling model of epilepsy. This paradigm was used to examine kindling in prenatally protein malnourished adult rats. Electrical stimulations of 5-s duration were applied to the perforant pathway every 5 min for 1 h over 5 days. Behavioral manifestations of seizure were scored on a five-point scale. The rapid kindling paradigm described provides a means of examining the development of kindled seizures in a significantly shorter period of time, but with comparable behavioral and electrophysiological outcome, than the traditional kindling paradigm. >
Referential Ambiguity in the Narrative Productions of African American Adults.

Purpose The purpose of this study was to examine the production of referential ambiguities in two contrasting narrative conditions among age-defined groups of healthy African American women. Method...
Ergodic Theory and Area Preserving Mappings

Much work has been done recently in numerical (computer) studies of area preserving mappings of the plane. Often the orbit of a single point seems to fill a region in the plane having positive area. Such a region is called an “ergodic zone”. In this paper we give an exposition of some mathematical techniques which can be used to show that under suitable hypotheses, the closure of an orbit of a single point has positive Lebesque measure. We then apply these techniques to show that a family of mappings called linked twist maps are ergodic.
Experimental stress fractures of the tibia. Biological and mechanical aetiology in rabbits

We have shown that stress fractures can be induced in the tibial diaphysis of an animal model by the repeated application of non-traumatic impulsive loads. The right hind limbs of 31 rabbits were loaded for three to nine weeks and changes in the bone were monitored by radiography and bone scintigraphy. The presence of stress fractures was confirmed histologically in some cases. Most animals sustained a stress fracture within six weeks and there was a positive correspondence between scintigraphic change and radiological evidence. Microscopic damage was evident at the sites of positive bone scans. The progression, location, and time of onset of stress fractures in this animal model were similar to those in clinical reports, making the model a useful one for the study of the aetiology of stress fractures.
Schur product techniques for commuting multivariable weighted shifts

Abstract In this paper we study the hyponormality and subnormality of 2-variable weighted shifts using the Schur product techniques in matrices. As applications, we generalize the result in [R. Curto, J. Yoon, Jointly hyponormal pairs of subnormal operators need not be jointly subnormal, Trans. Amer. Math. Soc. 358 (2006) 5135–5159, Theorem 5.2] and give a non-trivial, large class satisfying the Curto–Muhly–Xia conjecture [R. Curto, P. Muhly, J. Xia, Hyponormal pairs of commuting operators, Oper. Theory Adv. Appl. 35 (1988) 1–22] for 2-variable weighted shifts. Further, we give a complete characterization of hyponormality and subnormality in the class of flat, contractive, 2-variable weighted shifts T ≡ ( T 1 , T 2 ) with the condition that the norm of the 0th horizontal 1-variable weighted shift of T is a given constant.
Interplanetary Lyman-beta emissions

Derivation of the intensity of the diffuse hydrogen Lyman-beta glow at 1025 A which is due to resonance scattering of the solar H I 1025 A line by interstellar and interplanetary hydrogen. Two sources of neutral hydrogen are considered: the local interstellar medium interacting with the solar system, and the dust deionization of the H(+) component of the solar wind. It is shown that if the dust geometrical factor is less than or equal to five quintillionths per cm, observations of backscattered Lyman-beta radiation will provide a unique determination of the density and temperature of the local interstellar medium.
Gamma Glutamyl Peptidase: A Novel Enzyme From Hairless Mouse Epidermis

Abstract Recent literature has suggested that pyroglutamate (PCA) formation in stratum corneum occurs by spontaneous cyclization of glutamine residues derived from filaggrin breakdown. This paper describes an enzymatic alternative. Epidermal homogenates from hairless mice were found to catalyze the formation of PCA from both glutamine and glutamic acid at pH 6.2. Enzyme activity responsible for the first step in this reaction, γ-glutamyl peptide formation, was partially purified using ammonium sulfate precipitation followed by ion exchange, gel filtration, and hydroxylapatite chromatography. Enzyme preparations free of γ-glutamyl cyclotransferase activity (which forms PCA from certain γ-glutamyl peptides) catalyzed formation of γ-glutamyl-glutamine from glutamine and γ-glutamyl-glutamate from glutamic acid. Enzyme preparations catalyzed hydrolysis of a variety of γ-glutamyl peptides but did not split non-γ-glutamyl peptides or the transpeptidase substrate γ-glutamyl-ρ-nitroanilide. Ammonium sulfate fractions containing both γ-glutamyl peptidase and γ-glutamyl cyclotransferase activity catalyzed linear formation of PCA from glutamic acid for periods of up to 19 h. Using γ-glutamyl-leucine as a substrate, γ-glutamyl peptidase activity was found to be much higher in crude extracts from epidermis than in preparations from liver, kidney, spleen, intestine, lung, brain, or heart. This activity has not, to our knowledge, been previously described in mammalian tissues.
WDM-based local lightwave networks. II. Multihop systems

For pt.I see ibid., vol.6, no.3, p.12-27, 1992. A survey of wavelength-division-multiplexing (WDM)-based local lightwave networks is presented. The general characteristics of multihop systems are discussed, and various multihop approaches are reviewed. The construction of optimal structures based on minimizing the maximum link flow and optimizations based on minimization of the mean network packet delay are also reviewed. Regular topologies that have been studied as candidates for multihop lightwave networks, including the perfect shuffle, the de Bruijn graph, the toroid, and the hypercube, are discussed. Near-optimal node placement algorithms and shared-channel multihop systems are also discussed. >
Antibody to a cryptic, solid phase ClQ antigen in membranoproliferative nephritis

IgG containing material detected in membranoproliferative nephritis (MPGN) serum with a solid phase (sp) Clq ELISA has been presumed to be immune complexes. However, in serum from 13 MPGN patients containing large amounts of spClq-binding material, sucrose density ultracentrifugation and sieve chromatography showed spClq-binding protein to sediment at 7S or cofractionate with IgG. One serum (stored for 12 years) contained, in addition, spClq-binding material sedimenting at more than 19S. Isolated MPGN IgG was shown to bind to spClq. SpClq-binding material could be totally removed from MPGN serum by absorption with BSA-anti-BSA immune precipitates, and by acid elution of the precipitates IgG binding to spClq could be recovered. F(ab')2, isolated from pepsin digested MPGN IgG, continued to bind spClq. Binding of MPGN IgG or F(ab')2 to spClq was not inhibited by 2 M NaCl. Incubation of MPGN serum with 125I Clq followed by sucrose density ultracentrifugation resulted in a peak of radioactivity at 11S, the sedimentation rate of Clq, giving evidence that material binding fluid phase Clq is not present. SpClq-binding IgG was detected in 54% of 68 MPGN patients. These results indicate that the 7S spClq-binding IgG represents antibody to a cryptic antigen revealed only when Clq fixes to a solid surface.
Design and modeling of liquid metal based devices with tunable THz transmission

Novel design of tunable THz plasmonic devices based on liquid metals is presented in this paper. The designed devices will be able to dynamically control and change the spectrum responses of THz signals. An equivalent circuit model has also been developed to describe the operating principle of the proposed THz devices. Good agreement has been achieved between the theoretical models and the numerical results.
A laboratory experiment testing the antecedents of leader cognitions

A laboratory experiment was conducted to test relationships between leadership style, feedback on subordinate performance within the context of either the vision or goals of the organization, and leader cognitions representing a modified version of Wofford and Goodwin's (1994) cognitive processing model of leadership. The results indicated that: (1) positive feedback leads to the access of transformational cognitions, whereas negative feedback leads to the access of transactional cognitions; (2) negative feedback about subordinate performance causes transformational leaders to access transactional cognitions in response to subordinates; (3) the relationship between transformational leadership behavior and transformational cognitions is strengthened when feedback received about subordinates is vision-related compared to feedback that is goal-related; and (4) the relationship between transactional leadership behavior and transactional cognitions is strengthened when feedback received is goal-related compared to feedback that is vision-related. Limitations and future research directions are discussed. Copyright © 2000 John Wiley & Sons, Ltd.
Oxidizer−Fuel Interactions in Aqueous Combustion Synthesis. 1. Iron(III) Nitrate−Model Fuels

Aqueous (solution) combustion synthesis of iron oxide is investigated using iron(III) nitrate nonahydrate and three model fuels, each containing one specific functional group. The investigated ligands, in order of experimentally determined reactivity, are −NH2 > −OH > −COOH, where only the amino group triggers a vigorous combustion reaction. On the basis of the experimental findings, a reaction mechanism for iron oxide synthesis is proposed. During the first step, nitric acid is released during thermal decomposition of iron(III) nitrate. Subsequently, two reactions occur: nitric acid reacts with the amino group in a fast exothermic redox reaction, and it also decomposes thermally to release oxygen. The latter may react with carbon available in the fuel and thus increase the overall process exothermicity.
INACTIVITY OF TERBINAFINE IN A RAT MODEL OF PULMONARY ASPERGILLOSIS

In a model of bronchopulmonary aspergillosis terbinafine did not improve survival of experimental animals in doses up to 80 mg/kg/day despite adequate lung concentrations. Pretreatment and aerosolization of the compound were also ineffective. Terbinafine was markedly less active in vitro when serum was used instead of Yeast-Nitrogen-Glucose-broth. It is concluded that a lack of bioavailability in the presence of serum may explain the lack of activity of terbinafine in experimental aspergillosis.
What next for botulism vaccine development

Botulism is a severe neuroparalytic disease caused by the toxins produced from several Clostridium species. Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inducing a blockade at voluntary motor and autonomic cholinergic junctions that, if not treated, can be fatal. Vaccination to elicit protective circulating antibodies that bind, neutralize and clear toxins before they can be internalized and affect cholinergic neurons remains the most effective form of protection against BoNT. A pentavalent BoNT toxoid vaccine administered in the USA under an Investigational New Drug protocol to at-risk workers was discontinued by the CDC in 2011 due to diminished potency and reactogenic effects. Subsequent research efforts have primarily focused on recombinant protein antigens. This review focuses on the development of a recombinant bivalent vaccine (rBV A/B) composed of purified recombinant BoNT/A and BoNT/B receptor-binding domain proteins, as well as presenting a summary of progress and issues associated with alternative vaccines currently being developed against botulism.
Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter

Prolactin (PRL) modulates proliferation in the mammary gland and other tissues, in part through inducing transcription of cyclin D1, a key regulator of G(1) phase cell cycle progression. We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter. However, full promoter activity requires additional regions, and in this paper we explored PRL-induced activity at sites other than GAS1. We defined a second PRL-responsive region spanning -254 to -180 that contains a second GAS site (GAS2) and an Oct-1 binding site. Although mutational analysis indicated independence from GAS2, proximal promoter activity remained Stat5-dependent, suggesting alternative mechanisms. EMSA showed that Oct-1 binds the -254 to -180 region and that PRL decreased Oct-1 binding, leading to increased PRL-responsiveness of the proximal cyclin D1 promoter in multiple cell lines. This suggests a role for Oct-1 in PRL-dependent control of cyclin D1 transcription.
Spatial Linear Regression from Census Microdata: Combining Microdata and Small Area Data

Census microdata have become an extremely valuable source of information in social sciences research. These data, however, must have very coarse geographic resolution in order to protect respondent anonymity. Thus the geographic scale of these microdata sources is drastically different from the scale of many spatial processes—particularly neighborhood-scale processes. It is suggested that this difference in geographic scales creates a problem of conclusion validity for regression models which use anonymized microdata: measures of statistical significance are biased in these models. A correction to this problem in which small area data and population-density maps are used to estimate the effects of spatial dependence is presented. Monte Carlo evidence is presented which demonstrates that the conclusion-validity problem may be severe in practice. Further, this evidence shows that the suggested correction with small area data restores conclusion validity to statistical tests.
Aminoacidemias: effects on maze performance and cerebral serotonin.

The feeding of high dietary supplements of L- phenylalanine (7 percent) and L- leucine (7 percent) to weanling rats is associated with poor performance in a multiple-T, water-escape maze. Supplements high in L- tryptophan (5 percent), on the other hand, result in maze performance which is superior to that of controls. Adding 5 percent tryptophan to the high-phenylalanine diet reverses the behavioral deficit. The quality of maze performance correlated with the cerebral content of serotonin.
Death and the Mother from Dickens to Freud: Victorian Fiction and the Anxiety of Origins

Preface 1. The lady vanishes 2. Psychoanalytic cannibalism 3. Broken mirror, broken words: Bleak House 4. Wilkie Collins and the secret of the mother's plot 5. Denial, displacement, Deronda 6. Calling Dr. Darwin 7. Virginia Woolf's 'Victorian novel' Notes Index.
The relationship between dominance and spawning inHerotilapia multispinosa (Pisces: Cichlidae)

The outcomes of fights between all possible pairs of same-sexed individuals were used to infer the within-sex dominance rank of six male and six femaleHerotilapia multispinosa. The resulting dominance hierarchies were compared with the order in which all 12 fish spawned when placed together in a large aquarium. Two replications of dominance rank assessment and spawning order were carried out. The spawning order of females was highly correlated with their dominance rank in both replications. Males spawned in a similar order in both replications but did not form a stable dominance hierarchy as inferred from the outcomes of fights. It is suggested that this finding may be due to the importance of site attachment in the agonistic behavior of maleH. multispinosa.
Identification of Novel Classes of Protein Kinase Inhibitors Using Combinatorial Peptide Chemistry Based on Functional Genomics Knowledge

A discovery approach based on an intramolecular inhibitory mechanism was applied to a prototype calmodulin (CaM)-regulated protein kinase in order to demonstrate a proof-of-principle for the development of selective inhibitors. The overall approach used functional genomics analysis of myosin light chain kinase (MLCK) to identify short autoinhibitory sequences that lack CaM recognition activity, followed by recursive combinatorial peptide library production and comparative activity screens. Peptide 18 (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2), one of several selective inhibitors discovered, has an IC50 = 50 nM for MLCK, inhibits CaM kinase II only at 4000-fold higher concentrations, and does not inhibit cyclic AMP-dependent protein kinase. Analogues of peptide 18 containing conformationally constrained cis-4-aminocyclohexanecarboxylic acid retained affinity and selectivity. The inhibitors add to the armamentarium available for the deconvolution of complex signal transduction pathways and their relationship to homeostasis and disease, and the approach is potentially applicable to enzymes in which the catalytic and regulatory domains are found within the same open reading frame of a cDNA.
The potential for photodynamic therapy in the treatment of localized infections.

Summary At the present time photodynamic therapy (PDT) is receiving considerable interest for its potential as an antimicrobial therapy. This treatment may be a valuable tool in achieving a rapid reduction of the microbial burden perhaps even in the management of localized infections that are resistant to standard antibiotic regimens. A variety of photosensitizers from different groups including porphyrins, chlorophyll derivatives, phthalocyanines and azines have been effective in the photokilling of many Gram-positive and Gram-negative bacterial pathogens in addition to parasites, fungi, and viruses. Much of the suggested antimicrobial uses of this therapy are based on results from in vitro studies. Only a limited number of animal models of infection or clinical studies have been employed to assess the effectiveness of PDT. These studies have reported moderate successes that have not quite achieved the expectations projected from the in vitro results. In order to fully validate the potential of PDT as an antimicrobial therapy considerably more effort is required in the area of appropriate experimental models to better understand the mechanisms of photodynamic destruction of bacteria.
The clinical significance of absence of end-diastolic velocities of the umbilical artery detected in the severely preterm fetus

Objective: To determine whether there is a gestational age cutoff at the time of diagnosis of AEDV of the umbilical artery Doppler waveform that is associated with nearly zero perinatal survival. Methods: Over an 8-year period we identified and compared the outcomes of pregnancies in which AEDV of the umbilical artery Doppler waveform was detected between 19–24 and 25–28 weeks of gestation. All fetuses had normal structure and karyotypes. Small for gestational age (SGA) was defined as less than the 10th percentile for gestational age based on Brenner’s curve. Values are reported in median (range). Results: There were no survivors among the 27 cases identified at 19–24 weeks of gestation: 5 terminations for severe-SGA fetus (birth weight 336 [130–430] grams), 3 terminations for severe preeclampsia and SGA fetus, 12 fetal deaths, 7 neonatal deaths, and 10 cases (46%) of pregnancy-induced hypertension/preeclampsia (PIH/PE). All 8 cases detected at 25–28 weeks of gestation resulted in neonatal survival at discharge (P <0.0001), and there were 2 cases (25%) of PIH/PE (P = 0.54). Conclusion: In this study, AEDV of the umbilical artery Doppler waveform identified at less than 25 weeks of gestation is associated with a 100% perinatal mortality rate and a high rate of PIH/PE. This information should be incorporated into the counseling and management of women in this clinical setting.
Gender differences in rating stressful events, depression, and depressive cognition

Assessed gender differences in the ratings of stressful events, depression, and cognitive distortion. Responses of 70 males and 70 females (N = 140) to the Life Stress Questionnaire, the Beck Depression Inventory, and the Automatic Thought Questionnaire were studied. Statistical analyses revealed significant differences between sexes on all dependent measures. Men reported experiencing more stressful life change. However, women rated the impact of stressors more severely. Women had higher depression ratings, and men exhibited greater distortions in cognitive content. It is proposed that cognitive distortion may insulate men from depressive moods. Research on coping mechanisms used by men and women in dealing with similar stressful life events may be helpful in clarifying the relationship among gender, stress, and depression.
Post-transcriptional regulation of miRNA biogenesis and functions

MicroRNAs (miRNAs) are a highly conserved class of small (18–24 nucleotides) non-coding RNAs that regulate a broad spectrum of biological processes. Aberrations or corruptions of miRNA functions may lead to deregulated cell proliferation, tumorigenesis, and ultimately, cancer. Increasing evidences suggested that a large fraction of miRNAs is regulated at the posttranscriptional stage, which impacts on the level and function of miRNAs during cell development and human diseases. Recently, several distinct mechanisms are emerging to regulate the biogenesis, stability and function of miRNAs at post-transcriptional level, such as specific binding to terminal loops of miRNA precursors (primiRNAs or pre-miRNAs) by RNA-binding proteins and 3′-terminal modifications by particular enzymes. Signaling cascades and post-translational modifications of the core components of RNA machinery also take part in the posttranscriptional regulation of miRNAs.
Subtle discrimination in the rental housing market: Evidence from e-mail correspondence with landlords

Abstract We find that landlords practice subtle discrimination in the rental housing market through the use of language associated with describing and viewing a unit, inviting further correspondence, making a formal greeting, and using polite language when replying to e-mail inquiries from a white name more often than to an African American name, they also send longer e-mails and respond quicker to white names.
The Modern Treatment of Coronary Thrombosis with Myocardial Infarction

Coronary thrombosis with myocardial infarction is an extremely serious disease to the individual and to the nation. It kills at least 200,000 persons a year and cripples unknown numbers. The modern treatment is herein outlined. Established therapy is reviewed and evaluated. The use and technics for the control of anticoagulant therapy are discussed.
Structural Diversity in the Reaction of Mono- and Disubstituted Pyrazoles with Titanium Tetrachloride. Importance of Hydrogen Bonding and Trends in cis/trans Geometry of Binary Adducts with Unidentate Ligands.

Treatment of titanium tetrachloride with 3,5-di-tert-butylpyrazole affords the complexes [3,5-(C(CH3)3)2C3H3N2]2[TiCl6] and (3,5-(C(CH3)3)2C3HN2)2TiCl2 in 37 and 42% yields, respectively. An analogous reaction with 3,5-dimethylpyrazole, 3-methylpyrazole, 4-bromopyrazole, and 4-iodopyrazole leads to the formation of corresponding TiCl4L2 binary adducts in 30−86% yields. Crystal structures of [3,5-(C(CH3)3)2C3H3N2]2[TiCl6], (3,5-(C(CH3)3)2C3HN2)2TiCl2, TiCl4(3,5-(CH3)2C3H2N2)2, and TiCl4(4-IC3H3N2)2 were determined. [3,5-(C(CH3)3)2C3H3N2]2[TiCl6] crystallizes in the space group C2/c with a = 18.892(4) A, b = 7.1200(10) A, c = 24.461(6) A, β = 103.78(2)°, and Z = 4. (3,5-(C(CH3)3)2C3HN2)2TiCl2 crystallizes in the space group P21/n with a = 12.283(10) A, b = 17.891(8) A, c = 12.580(6) A, β = 90.96(4)°, and Z = 4. TiCl4(3,5-(CH3)2C3H2N2)2 crystallizes in the space group C2/c with a = 12.087(2) A, b = 12.922(3) A, c = 10.403(2) A, β = 92.08(2)°, and Z = 4. TiCl4(4-IC3H3N2)2 crystallizes in the space group C2/c ...
THE REDOX STATE OF THE 2FE-2S CLUSTERS IN SOXR PROTEIN REGULATES ITS ACTIVITY AS A TRANSCRIPTION FACTOR

SoxR protein is a redox-responsive transcription factor that governs a regulon of oxidative stress and antibiotic resistance genes in Escherichia coli. Purified SoxR contains oxidized [2Fe-2S] clusters and stimulates in vitro transcription of its target gene soxS up to 100-fold. SoxR transcriptional activity, but not DNA binding, is completely dependent on the [2Fe-2S] clusters; apo-SoxR prepared in vitro binds the soxS promoter with unchanged affinity but does not have transcription activity. Thus, modulation of the SoxR [2Fe-2S] clusters was proposed to control the protein's function in transcription. Here, we provide evidence that SoxR with reduced [2Fe-2S] clusters is inactive. Redox titration of purified SoxR revealed a midpoint potential of −285 ± 10 mV (pH 7.6). In vitro transcription assays showed that SoxR was inactivated when the [2Fe-2S] cluster was reduced (−380 mV), and full activity was restored upon reoxidation (+100 mV). The results suggest that one-electron oxidation and reduction of the [2Fe-2S] cluster regulate SoxR transcriptional activity.
Studies of cellular flames in hydrogenoxygennitrogen mixtures

Abstract For downwardly propagating flames in pyrex tubes at atmospheric pressure and intial temperature of 295°K, measurements were made of the nitrogen dilution required for quenching as a function of the hydrogenoxygen ratio, as well as of flame temperatures, flame speeds, temperature gradients behind the flame, unburnt hydrogen, and cell sizes. Theory including relative diffusion of reactants was compared with measured cell sizes. Agreement of measured extinctions was obtained using theory based on importance of conductive heat loss rates in comparison with overall rates of chemical heat release.
Apparent interaction between the Xga blood group system and the sex ratio: a note of explanation.

PROF. J. H. Bennett has called to our attention a possible source of confusion in our recent letter1. We left implicit the assumption that the expected sex-ratios in the two classes, ‘Before and including the first female’, and ‘After the first female’, were equal, and we failed to make clear that the numbers of children in our Table 1 included those from all-male sibships. If such sibships had been omitted, the sex ratio (male: female) would indeed have been expected to be higher in the first class than in the second, but when they are included, as was done, the expected ratios are equal. Other explanations of our observation, such as selective family limitation, do not account for its limitation to the single Xg—Xga mating type where the postulated ‘incompatibility’ could occur.
Hepatic steatosis is prevalent in stillborns delivered to women with diabetes mellitus.

ABSTRACTObjective:Maternal diabetes is a risk factor for pregnancy complications, including stillbirth and macrosomia. Evolving data suggest that diabetes during pregnancy also has long-term consequences for offspring, putting them at risk for obesity and the metabolic syndrome in childhood. Because
Finite difference analysis of torsional vibrations of pretwisted, rotating, cantilever beams with effects of warping

Theoretical natural frequencies of the first three modes of torsional vibration of pretwisted, rotating cantilever beams are determined for various thickness and aspect ratios. Conclusions concerning individual and collective effects of warping, pretwist, tension-torsion coupling and tennis racket effect (twist-rotational coupling) terms on the natural frequencies are drawn from numerical results obtained by using a finite difference procedure with first order central differences. The relative importance of structural warping, inertial warping, pretwist, tension-torsion and twist-rotational coupling terms is discussed for various rotational speeds. The accuracy of results obtained by using the finite difference approach is verified by a comparison with the exact solution for specialized simple cases of the equation of motion used in this paper.
Early phase laser induced plasma diagnostics and mass removal during single-pulse laser ablation of silicon

The electron number density and temperature during the early phase (<300 ns) of laser-induced plasmas from silicon using a 266-nm, 3-ns Nd:YAG laser were deduced via spectroscopic methods. These parameters were measured as a function of delay time vs. irradiance in the range of 2–80 GW/cm2, and compared with crater volume measurements. A dramatic change in plasma characteristics (electron number density, temperature, and degree of ionization) as well as a sharp increase of mass removal was observed when the irradiance was increased beyond a threshold of 20 GW/cm2. Possible mechanisms such as inverse bremsstrahlung and self-regulation were used to describe these data in the low irradiance region. Laser self-focusing and critical temperature are discussed to explain the dramatic changes after the irradiance reaches the threshold.
The Supreme Court and the Pledge of Allegiance: A Hollow Victory.

In Elk Grove Unified School District v Newdow (Elk Grove),1 the Supreme Court, in an 8–0 judgment,2 with three concurrences, upheld the words ‘under God’ in the Pledge of Allegiance. In light of the uproar caused by Elk Grove, this article is divided into three parts. After reviewing the history of the Pledge the second section examines the litigation involving the pledge, including Elk Grove in this regard. The article concludes with brief reflections on the meaning of Elk Grove.
AACAP 2001 Research Forum: Challenges and Recommendations Regarding Recruitment and Retention of Participants in Research Investigations

ABSTRACT Objective Clinical research depends on the participation of representative samples. At the 2001 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Workgroup on Research conducted a research forum with the purpose of improving recruitment and retention of children and adolescents in research protocols. Method An interdisciplinary group of participants focused on (1) consumers and families, (2) communities, (3) professionals and health care delivery systems, (4) regulatory bodies, and (5) alternative research designs. Obstacles and challenges were identified and solutions were discussed. Results Key recommendations include the following: Investigators must become involved with community stakeholders and more explicitly communicate with families about research procedures, risks, and benefits; budgets should include explicit items for case management and referrals to families who do not meet entry criteria; the culture of clinical settings must incorporate research conducted by clinicians; regulatory bodies must streamline and coordinate protocols and procedures; designs emphasizing flexible treatment strategies and adaptive treatments should be encouraged; and health care systems should consider changing incentives for research participation, including the radical notion that reimbursement be made in terms of improvement rather than service units. Conclusions An integrated approach is recommended, requiring direct involvement of investigators in communities where research is to be conducted.
Statistical Methods for Profiling Providers of Medical Care: Issues and Applications

Abstract Recent public debate on costs and effectiveness of health care in the United States has generated a growing emphasis on “profiling” of medical care providers. The process of profiling involves comparing resource use and quality of care among medical providers to a community or a normative standard. This is valuable for targeting quality improvement strategies. For example, hospital profiles may be used to determine whether institutions deviate in important ways in the process of care they deliver. In this article we propose a class of performance indices to profile providers. These indices are based on posterior tail probabilities of relevant model parameters that indicate the degree of poor performance by a provider. We apply our performance indices to profile hospitals on the basis of 30-day mortality rates for a cohort of elderly heart attack patients. The analysis used data from 96 acute care hospitals located in one state and accounted for patient and hospital characteristics using a hierarc...
Identification and expression of a novel type I procollagen C-proteinase enhancer protein gene from the glaucoma candidate region on 3q21-q24.

A novel human Type I procollagen C-proteinase enhancer protein-like gene, PCOLCE2, was identified by sequencing an EST in the primary open-angle glaucoma (POAG) region on 3q21. The total cDNA encoded a 415-amino-acid protein that has 43% identity to the Type I procollagen C-proteinase enhancer protein (PCOLCE1). PCOLCE2 contains two CUB domains, which are thought to be involved in protein-protein interactions, and an NTR module. PCOLCE2 message is expressed in the trabecular meshwork, lungs, heart, brain, liver, skeletal muscle, kidney, pancreas, and placenta as a 2-kb message. PCOLCE2, a 52-kDa protein, is expressed in the trabecular meshwork. A novel gene, PCOLCE2, has been identified and characterized. Based upon its homology with collagen-binding proteins, its expression in the trabecular meshwork, and its chromosome location, PCOLCE2 is a candidate gene for GLC1C. However, no coding sequence mutations were detected in PCOLCE2 in a POAG patient from the GLC1C family.
New Method to Quantify Angiogenesis in vivo Using Multi-photon Imaging

Efforts to understand the basic mechanisms of angiogenesis, that is, the formation of new blood vessels from existing vasculature, have been limited by the methods that are currently used to measure vessel growth. Although in vivo assays provide the best environment in which to track angiogenesis, inherent difficulties in obtaining reproducible data limit the power of this approach. Limitations include: environmental variations between experimental animals, induction of inflammatory responses by surgical methods, and labor-intensive blood vessel quantification procedures. A better assay would measure vessel growth in one animal at multiple time points and would focus on minimization of artifacts induced by experimental manipulation.
In Search of Peter Weir

Abstract As part of the preparation for a book on Australian director Peter Weir, the author visited Weir's home in Sydney for interviews about his life, career, and work.
The multiplicity of Hawaiian sovereignty claims and the struggle for meaningful autonomy

There are multiple Hawaiian political claims and entitlements. Is independence appropriate for Hawai'i? Is it appropriate for Hawaiians? These two questions are not one and the same. In the movemen...
Design, synthesis and biological studies of survivin dimerization modulators that prolong mitotic cycle.

Abstract Survivin, a member of the inhibitor of apoptosis protein (IAP) family proteins, has essential roles in cell division and inhibition of apoptosis. Several clinical studies in cancer patients have shown that the elevated levels of survivin correlate with aggressiveness of the disease and resistance to radiation and chemotherapeutic treatments. Survivin is an integral component of chromosomal passenger complex (CPC) where it binds to borealin and INCENP through its dimerization interface. Thus, disruption of functional survivin along its dimer interface with a small molecule is hypothesized to inhibit the proliferation of cancer cells and sensitize them to therapeutic agents and radiation. Recently, a small molecule (Abbott8) was reported to bind at the dimerization interface of survivin. Further development of this compound was accomplished by computational modeling of the molecular interactions along the dimerization interface, which has led to the design of promising survivin dimerization modulators. Two of the most potent survivin modulators, LLP3 and LLP9 at concentrations between 50 and 100 nM, caused delay in mitotic progression and major mitotic defects in proliferating human umbilical vein endothelial cells (HUVEC) and prostate cancer cells (PC3).
Dissipative contributions of internal multiplicative noise: II. Spin systems☆

Abstract We analyze the relaxation of a spin interacting with a heat bath of other spins, in an external magnetic field, starting from a fully dynamical (Hamiltonian) description. We derive a generalized Langevin equation for the spin system in which the initial conditions of the bath spins act as fluctuations. The generalized Langevin equation has multiplicative fluctuations and nonlinear dissipation (relaxation) contributions which obey a fluctuation-dissipation theorem. As a natural consequence, our spin system relaxes to a canonical distribution. We also examine the moment equations for the spin in the Langevin limit. Because of the nonlinear dissipative contributions, the moment equations form a nonlinear linked hierarchy which under certain conditions reduces to the linear Bloch equations. Our theory yields expressions for the longitudinal and transverse relaxation times in terms of the microscopic parameters of the system, the external magnetic field and the temperature.
Jun, Fos, MyoD1, and myogenin proteins are increased in skeletal muscle fiber nuclei after denervation.

After denervation, mRNA levels of the jun and fos protooncogenes and of the muscular differentiation factors myoD1 and myogenin are increased. Here, immunohistochemistry was used (a) to show that this increase in mRNA is followed by an increase in the transcription factor proteins, and (b) to determine which cell populations in skeletal muscle express these factors after denervation. Rat diaphragms were denervated and analyzed after periods of 90 min-8 days. An increase in Fos and Jun as well as MyoD1 and Myogenin immunoreactivity was found after 2–2.5 days of denervation. Fos, MyoD1, and Myogenin immunoreactivity was mostly confined to muscle cell nuclei, whereas Jun antibodies stained muscle cell and some interstitial cell nuclei. A selective expression of any of the four transcription factors in muscle cell nuclei closely associated with motor endplates could not be detected in either denervated or innervated muscle at any time point examined, indicating that synaptic and extrasynaptic muscle cell nuclei are activated simultaneously after denervation. These results suggest that a genetic program which includes protooncogenes and myogenic differentiation factors is activated in skeletal muscle after denervation.
Morphology-dependent resonances of spherical droplets with numerous microscopic inclusions

We use the recently extended superposition T-matrix method to study the behavior of a sharp Lorenz-Mie resonance upon filling a spherical micrometer-sized droplet with tens and hundreds of randomly positioned microscopic inclusions. We show that as the number of inclusions increases, the extinction cross-section peak and the sharp asymmetry-parameter minimum become suppressed, widen, and move toward smaller droplet size parameters, while ratios of diagonal elements of the scattering matrix exhibit sharp angular features indicative of a distinctly nonspherical particle. Our results highlight the limitedness of the concept of an effective refractive index of an inhomogeneous spherical particle.