cssi/SciSciGPT-SciSciNet huggingface dataset:
Avances en tecnología de la anticoncepción

It is completely unnecessary to emphasize the need for contraception in a world in which every year eighty million individuals are added. In just 25 years the world population will double its current size. In many parts of the world food shortages and other natural resources it is already becoming evident, in others, the consequences of the growth rates of the population feel mainly in the deterioration of the environment. Everywhere in the world the pressures of ever-growing populations and more young people are able to create social and political disorder and violence.
Ruling out Hopf bifurcations in biochemical reaction networks

We describe a new graphical approach to the question of whether dynamical systems modeling networks of interacting elements admit Hopf bifurcations. The techniques make use of the spectral properties of additive compound matrices: in particular, we show that a condition on the cycles of a labelled digraph (called the DSR[2] graph) rules out the possibility of nonreal eigenvalues of the Jacobian matrix passing through the imaginary axis.
Electric braking performance analysis of PMSM for electric vehicle applications

This paper analyzed the performances of plug braking and regenerative braking of Permanent Magnet Synchronous Motor (PMSM), which is often used as the driving motor of electric vehicles. The electric braking principles are briefly explained at first. The performance analysis focuses on maximum braking torque, braking torque ripple and the feedback power of braking energy. The two main control methods for PMSM, six step commutation control and field oriented control (FOC), have been analyzed. A simulation system has also been developed in this paper and the analysis is supported by the results of simulation and preliminary experiments.
Mechanism of the von Braun amide degradations with carbonyl bromide or phosphorus pentabromide

Abstract The isolation of the α-bromobenziminium hexafluoroantimonate 6, the first intermediate in the amide degradation with carbonyl bromide, was previously announced. Present studies reveal that using either COBr2 or PBr5, the very first intermediate is the iminium tribromide (7). Reaction of the crystalline tribromide with cyclohexane gave the monobromide 8 nearly quantitatively and in crystalline form. Heating of the cyclic iminium monobromide 8 to 120° generates in high yield the α,ω-dihalogenoalkane (type 13) and benzonitrile, while heating to 100° in bromobenzene allows isolation of the ω-bromoalkyl benzimidoyl bromide (9 or 10). An independent synthesis of this and other imidoyl bromides is elaborated. the equilibrium of imidoyl bromides with N-alkyl nitrilium (11) can be shifted toward the nitrilium salt by dissolving in liquid sulfur dioxide or reacting with methyl fluorosulfate. All these steps have been monitored by NMR. The ω-bromoalkyl imidoyl bromide at 120° undergoes fragmentation via the nitrilium ion to an α,ω-dibromoalkane and benzonitrile. In addition to gaining mechanistic information (1) we achieved isolation of crystalline n-alkylene-α-bromoiminium bromides, and their smooth thermal decomposition, which makes the von Pechmann-von Braun type of degradation competitive to the Hofmann methylation; (2) new procedure was found for preparing ammonium tribromides and iododibromides using carbonyl bromide; (3) a number of the heterofore unknown imidoyl bromides have been prepared and characterized, and their thermolysis and mass spectra studied.
Information Technology Systems Deliver Competitiveness for ABC Parcel Services

ABC Parcel Services is a leader in package delivery via ground and air shipping. It has provided services internationally as well as in all the 50 United States for almost 100 years. At the beginning of 2001, the CEO and the management of the company were faced with an unusual fiercely competitive market and rapidly changing customer requirements. The automation implemented thus far did not justify premium prices from the customers anymore. Customers were able to receive the same services that ABC was able to provide using this automation, at competitive prices from other providers in the market. It was obvious to the management that a value added service had to be provided to keep the edge over the competition. Looking at the changing business landscape, one area that was identified as critical was a customer centric approach using automation. The results from the implementation of such a system were expected to be tremendous for the organization to counter the competitive pressure of rival organizations and maintain market leadership.
Geosmin Biosynthesis. Streptomyces coelicolor Germacradienol/Germacrene D Synthase Converts Farnesyl Diphosphate to Geosmin

Geosmin is responsible for the characteristic odor of moist soil. Incubation of recombinant germacradienol synthase, encoded by the SCO6073 (SC9B1.20) gene of the Gram-positive soil bacterium Streptomyces coelicolor, with farnesyl diphosphate (2, FPP) in the presence of Mg2+ gave a mixture of (4S,7R)-germacra-1(10)E,5E-diene-11-ol (3) (74%), (-)-(7S)-germacrene D (4) (10%), geosmin (1) (13%), and a hydrocarbon, tentatively assigned the structure of octalin 5 (3%). Individual incubations of recombinant germacradienol synthase with [1,1-2H2]FPP (2a), (1R)-[1-2H]-FPP (2b), and (1S)-[1-2H]-FPP (2c), as well as with FPP (2) in D2O, and GC-MS analysis of the resulting deuterated products supported a mechanism of geosmin formation involving proton-initiated cyclization and retro-Prins fragmentation of the initially formed germacradienol to give intermediate 5, followed by protonation of 5, 1,2-hydride shift, and capture of water.
The mechanism of phenytoin crystal growth

Abstract Phenytoin crystal growth kinetics have been measured as a function of pH, supersaturation and temperature in phosphate buffer. Incorporation of growth units into the crystal lattice was not influenced by diffusion from the bulk to the solid surface. Thus, the rate limiting step for phenytoin growth is surface integration. Phenytoin crystal growth is via a screw-dislocation mechanism; this mechanism explains the observed dependence of growth rate on supersaturation and the increase in growth rate with pH.
Future employment among homeless single mothers: the effects of full-time work experience and depressive symptomatology.

SUMMARY This study examines the relationship between work and depressive symptomatology for extremely destitute single mothers–mothers who have experiencedan episode of homelessness. Using longitudinal data collected from 294 respondents who became homeless in 1992 and were followed for approximately two years, we find that a history of full-time work is the best predictor of whether a woman will find full-time employment in the aftermath of an episode of homelessness. Even an extensive history of part-time or informal work was not predictive of finding employment after leaving a homeless shelter. A woman's level of depressive symptomatology at the onset of homelessness predicted her strategy in dealing with the shelter bureaucracy. Women with full-time work histories who experienced high levels of depressive moods at the onset of a shelter episode were likely to leave the shelter quickly. Those with lower levels of depressive symptomatology stayed and were more likely than others to complete an education...
Drag coefficient and terminal velocity of spherical and nonspherical particles

Explicit equations are developed for the drag coefficient and for the terminal velocity of falling spherical and nonspherical particles. The goodness of fit of these equations to the reported experimental data is evaluated and is compared with that of other recently proposed equations. Accurate design charts for CD and ut are prepared and displayed for all particle sphericities.
Influence of alloying on the superconducting transition temperature of La3In

Abstract The effects of heat treatment and stoichiometry on the superconducting transition temperature Tc of La3In were studied. The mechanical properties indicate that La3In is surprisingly ductile for an intermetallic compound. The effects on Tc of alloying by substituting Ca, Se, Y, Yb, Lu and Th for La, and Mg, AI, Mn, Zn, Ga, Ge, Cd, Sn, Tl, Pb and Bi for In were investigated. Additions of interstitial non-metallic elements (H, B, C, N, O and Si) were also studied. Almost all impurity elements lower Tc. For La substitutions dTc/dn was found to be proportional to the square of the difference in the radii (rR − rLa) but the change in the electron concentration had little if any effect on Tc. For In substitutions the size of the impurity atom had only a minor influence on dTc/dn, while an increase in the electron concentration accelerated the depression of Tc. Solid solubility limits were also deduced when sufficient data were available.
Cytogenetic and molecular diagnosis of chromosome 5 deletions in myelodysplasia

Deletions of chromosome 5, del(5q), are frequently observed in myelodysplasia (MDS). We evaluated molecular detection of loss of heterozygosity (LOH) as a diagnostic method to detect del(5q) in a series of 60 MDS cases at a single institution. LOH was compared to cytogenetics on the same clinical specimen, resolving ambiguous cases by fluorescent in situ hybridization (FISH) and additional LOH. There was poor concordance between molecular and cytogenetic results, but most discrepancies could be resolved by FISH and additional LOH. Molecular analysis was of low sensitivity because most cases contained a relatively high proportion of cells without del(5q), but it was accurate, while cytogenetics overestimated the proportion of cells with del(5q) and failed to detect some cases with complex rearrangements. Minor clones were detected both by FISH and LOH. Overall, we found an incidence of 23% (14 of 60 cases) for del(5q) in MDS. The results also suggest that there is a high degree of genetic heterogeneity in the cellular population of MDS. Although del(5q) is common in MDS, it may not be present in all cells, leading to diagnostic challenges.
A theory of isobaric spin analogue resonances

Abstract A theory of isobaric spin analogue resonances is formulated using Feshbach's unified theory of nuclear reactions. The analysis is applicable to both elastic and inelastic scattering of protons from analogue resonances; explicit formulae are given for the elastic and inelastic amplitudes. The mixing of analogue states with “normal” states is also considered in detail and formulae for the transition amplitudes including mixing are given.
Recognizing the D-loop of transfer RNAs

Mechanisms that maintain fidelity and repair mistakes are ubiquitous throughout the protein biosynthesis pathway (1). The aminoacyl tRNAs serve as critical turning points in translation, because they link the nucleic acid genetic code with the amino acid building blocks of proteins. Misacylation of tRNAs can have devastating results, affecting the very survivability of an organism. Accuracy in tRNA aminoacylation therefore is paramount to the fidelity of the genetic code. Aminoacyl tRNAs are generated typically through action of the diverse family of aminoacyl-tRNA synthetases (AARSs). One of the hallmarks of these enzymes is the exquisite specificity with which each selects and aminoacylates only its cognate tRNA(s) with only its cognate amino acid (2–5). Herculean efforts spanning nearly 25 years have produced crystal structures for 19 of the 20 AARSs (alanyl-tRNA synthetase is the last holdout). Many of these structures provide detailed molecular insight into the nature of tRNA recognition and discrimination by either providing a structure of the enzyme in complex with its cognate tRNA or suggesting a model that can be tested biochemically. Thus, a clear picture is beginning to emerge, delineating some of the common and not-so-common themes used by the AARSs to discriminate cognate from noncognate tRNAs. [There are several reviews available that describe tRNA recognition by AARSs in detail (4–7).]
ACR Appropriateness Criteria(®) on suspected physical abuse-child.

The appropriate imaging for pediatric patients being evaluated for suspected physical abuse depends on the age of the child, the presence of neurologic signs and symptoms, evidence of thoracic or abdominopelvic injuries, and whether the injuries are discrepant with the clinical history. The clinical presentations reviewed consider these factors and provide evidence-based consensus recommendations by the ACR Appropriateness Criteria ® Expert Panel on Pediatric Imaging.
Using freshwater resources to rehabilitate refugees and build transboundary cooperation

After the conflict between India and Pakistan upon their independence in 1947, India sought to use the Indus River to rehabilitate millions of refugees, reconstruct the economy, and facilitate post-conflict peacebuilding in Punjab. But this drew on the only freshwater available to Pakistan. The World Bank's mediation averted further conflict through the Indus Waters Treaty and the construction of hydrological infrastructure in order to subsidize post-conflict peacebuilding. The treaty established a commission and conflict-resolution mechanisms to manage disputes of the development of the Indus. Pakistan is using these mechanisms to address the current Kishanganga Project dispute with India.
Evaluation of the effectiveness factor for a multiple species biofilm

An existing dynamic biofilm multiple species computer simulation (Wanner & Gujer, 1986) is used to model both heterotrophic carbon‐oxidizing and autotrophic nitrogen‐oxidizing bacterial populations within an accumulating biofilm, a system characteristic of the biological nitrification treatment of domestic waste‐waters. Such simulation predicts spatial distributions of N‐number of microbial species metabolizing a possible M‐number of substrates in an expanding (or contracting) biofilm as a function of time. Here the effects of substrate mass transfer limitations and bacterial species distributions on the overall biofilm effectiveness factor, a heterogeneous reaction‐based concept commonly used to interpret the effects of mass transfer on immobilized biological processes, are assessed.
Raman and Infrared Spectroscopy of Cyanide-Inhibited CO Dehydrogenase/Acetyl-CoA Synthase from Clostridium thermoaceticum: Evidence for Bimetallic Enzymatic CO Oxidation

Clostridium thermoaceticum and other autotrophic anaerobic bacteria contain a bifunctional enzyme, carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS), that catalyzes two reactions of CO at two separate Ni−FeS clusters. Oxidation of CO to CO2 is catalyzed by Cluster C, while incorporation of CO into acetyl-CoA occurs at Cluster A. In this study, resonance Raman [RR] and infrared [IR] spectroscopy are applied to the adduct of Cluster C with cyanide, a selective inhibitor of CO oxidation. The RR spectra reveal that CN- binds simultaneously to Fe and Ni, because bands whose 13C and 15N shifts identify them as cyanide−metal stretching and bending modes are sensitive to incorporation of both 54Fe and 64Ni into the enzyme. The IR spectrum reveals a low frequency, 2037 cm-1, for the C−N stretch, indicative of FeII binding via the C end. Vibrational modeling of the frequencies and isotope shifts indicates a bent Fe−CN−Ni bridging geometry, with a ∼140° C−N−Ni angle. This geometry of the inhibitory adduct...
A versatile next generation nucleon decay & neutrino detector

Abstract We present a concept for an underwater third generation nucleon decay and neutrino detector, with remarkable versatility and reduced costs.
Γ-Hydroxybutyric Acid-Induced Cognitive Deficits in the Female Adolescent Rat

gamma-hydroxybutyric acid (GHB), a "club drug," is abused for its euphoric, sedative, and anabolic effects. GHB use and abuse is most prevalent among adolescents and young adults. Most GHB users report amnesia. In the present study, we tested the hypothesis that GHB treatment in female adolescent rats causes deficits in spatial learning and memory. Adolescent female rats were treated daily with GHB (100 mg/kg) for 5 consecutive days. Control rats received isovolumetric saline. Experimental and control rats were tested in the hidden platform task (reference memory) of the Morris water maze. GHB-treated adolescent female rats had significantly longer latencies than saline-treated controls, and in the probe trial drug-treated rats spent less time in the quadrant where the platform was present prior to its removal than did control adolescent rats. Together, these data indicate that GHB exposure in adolescent female rats has a negative impact on spatial learning and memory.
Beaded filaments and long-spacing fibrils: Relation to type VI collagen

"Beaded filaments" have been found in fibroblast cultures prepared from chicken embryo leg tendons and cornea and from the dermis of human skin. With negative staining, they appear as single, unbranched, flexible strands approximately 3 nm in width and up to at least 2 microns in length. Pairs of "beads" are distributed on the filament at regular intervals of 110 nm. The beaded filaments appear to be resistant to the action of trypsin and bacterial collagenase. The filaments also occur in bundles with beads laterally aligned to form long-spacing-type fibrils, which appear to be identical with many fibrous-long-spacing-type fibrils described, but not identified, by others in a variety of normal and pathological tissues. The long-spacing fibrils are numerous at several sites of active collagen fibrillogenesis. Comparison of the beaded filament structure with molecular models for various collagens described in the literature suggests that they are a filamentous form of type VI collagen.
Multiple sightings of large groups of Arnoux's beaked whales (Berardius arnouxii) in the Gerlache Strait, Antarctica

On 5 May 2009, during the Multi-Scale and Interdisciplinary Study of Humpbacks And Prey (MISHAP09) cruise, a large group of socially active Arnoux’s beaked whales (Berardius arnouxii) was sighted in the southern-central region of the Gerlache Strait near the entrance of the Schollaert Channel between Brabant and Cuverville Islands, Antarctica (64◦33.9′S, 62◦37.1′W) (Fig. 1). Later, on 7 June 2009 in a similar location (64◦37.5′S, 62◦51.8′W), another sighting was made of a large group of Arnoux’s beaked whales. These represent two of the few confirmed sightings of this species in the nearshore waters around the Antarctic Peninsula, one of the only documentations of surface social activity, and the largest number of animals ever reported in a single group. At 1230 local time on 5 May, a large group of animals (approximately 60) was sighted 3 km from the ARSV LM Gould. The water depth around the whales was between 700 and 800 m. The first sighting cue was a series of short, bushy blows. As the ship approached, the animals became visible at the surface and were identified based on coloration, size, and shape of their head and melon, and rostrum shape. After the initial sighting, a second separate subgroup of animals (approximately 15) was sighted in the same area. Both groups of animals were traveling consistently to the southwest, deeper into the Gerlache Strait. Animals were seen surfacing quickly in close proximity to one another (<2 m), and often in physical contact with each other. During the course of the sighting we observed tail slapping by several individuals and three breaches. Photographs were obtained from an inflatable boat at a distance of approximately 100 m (Fig. 2). Several of the whales were visibly scarred with single or two parallel
Background radiation in the Albuquerque, New Mexico, U.S.A., area

Background radiation levels in the Albuquerque, New Mexico, area are elevated when compared to much of the United States. Soil K, U, and Th are somewhat elevated compared to average values in this country and generate roughly 60 mrem per year to the average resident. Cosmic ray contribution, due to the mean elevation of 5,200 ft above sea level, is 80 mrem/yr—well over the average for the United States. Thirty percent of the homes in Albuquerque contain indoor radon levels over the EPA action level of 4 pCi/l compared to 10–12 percent of homes for the entire United States. Indoor radon contributes about 100–300 mrem/yr. Food, beverages, and x-ray doses are assumed at an average-equivalent for the United States and locally yield 96 mrem/yr. Total contributions from other minor sources (color TV, coal, weapons fallout, etc.) are under 10 mrem/yr. Thus total background radiation received by Albuquerque residents is about 330–530 mrem/yr, well in excess of the rest of the United States. The spread in mrem values is due to variations in the contribution from indoor radon.
How Many Balance Functions Does it Take to Determine a Utility Function

Call b your balance function at wealth W if you are indifferent between W and a 50–50 lottery with outcomes x and b(x). Given one b, u is arbitrary on one side of W but then determined on the other. Given two b‘s, u is arbitrary between the two W′ s but then determined elsewhere. Additional properties of u restrict the b’s but do not ordinarily make u unique. Contradictions can occur. Given three b′ s, an algorithm is developed using minimal domains of definition that determines the relative utility of the W’s. If it is irrational, then the set S generated by applying all combinations of b’s to W′ s is dense and u is determined. If finitely many b’s are rationally related, then S is discrete, a further algorithm determines it, the values of u on S are equally spaced, and u is arbitrary between any two adjacent points of S but then determined elsewhere. Infinitely many balance functions determine u unless they are rationally related in a uniform way.
β-Aspartylglycine in urine and enzymic hydrolyzates of proteins

Abstract Dietary gelatin significantly elevated the urinary excretion of β-aspartylglycine in humans. The peptide was also found in enzymic digests of collagen prepared by the sequential action of collagenase, Pronase, and the combination of prolidase and leucinaminopeptidase. Nonenzymic conversion of normally occurring α-aspartylglycine to the β-peptide may explain the presence of the peptide in digests of lysozyme and to some extent the high levels in collagen. However, the greater amounts found in polymerized fibrin compared with fibrinogen indicate an enzymic formation of the peptide bond during polymerization. In agreement with the theory that β-aspartylglycine bonds link polypeptide chains of certain proteins was the finding of more β-aspartylglycine in the highly cross-linked Achilles tendon collagen than in skin collagen.
Voice-activated retrieval of mammography reference images.

We undertook this project to integrate context sensitive computer-based educational and decision making aids into the film interpretation and reporting process, and to determine the clinical utility of this method as a guide for further system development. An image database of 347 digital mammography images was assembled and image features were coded. An interface was developed to a computerized speech recognition radiology reporting system which was modified to translate reported findings into database search terms. These observations were used to formulate database search strategies which not only retrieved similar cases from the image database, but also other cases that were related to the index case in different ways. The search results were organized into image sets intended to address common questions that arise during image interpretation. An evaluation of the clinical utility of this method was performed as a guide for further system development. We found that voice dictation of prototypical mammographic cases resulted in automatic retrieval of reference images. The retrieved images were organized into sets matching findings, diagnostic hypotheses, diagnosis, spectrum of findings or diagnoses, closest match to dictated case, or user specified parameters. Two mammographers graded the clinical utility of each form of system output. We concluded that case specific and problem specific image sets may be automatically generated from spoken case dictation. A potentially large number of retrieved images may be divided into subsets which anticipate common clinical problems. This automatic method of context sensitive image retrieval may provide a “continuous’; form of education integrated into routine case interpretation.
Effects of excess dietary cholesterol on adrenal cholesterol accumulation and steroidogenesis

Rats maintained on diets containing 3% cholesterol for 10 weeks show marked increase in adrenal cholesterol content. The greatest part of the increase is in the cholesterol ester fraction (329%), although free cholesterol is also elevated (140%). Morphologically, a marked increase in the lipid droplet content of the cells is observed. The microsomal fraction was enriched in cholesterol with parallel increases in microsomal ACAT activity in both normal and supplemented groups. Neutral cytosolic cholesterol esterase is unaffected by the diet. No significant increase in cholesterol occurred in the mitochondrial fraction. However, cholesterol binding to cytochrome P450 was affected by the diet under certain conditions. Cholesterol supplementation elevates adrenal corticosteroid levels (43%). Mild stress results in greater increases in adrenal corticosteroids after dietary supplementation. Aminoglutethimide produces inhibition of the stress induced increase in adrenal corticosteroids. This inhibition is less pronounced in cholesterol supplemented animals than in normal animals. The lack of similar effects on plasma corticosteroid levels suggests that enhanced metabolism and clearance of the plasma corticosteroids may be taking place.
The behavior of subinterface cracks with crack-face contact

Abstract Plane strain problems for a crack parallel to an interface between dissimilar materials, with a crack-face contact zone near one of the crack tips, are studied. These subinterface crack problems are formulated as nonlinear systems of Cauchy-type singular integral equations which are solved numerically. The physically pathological feature of interpenetration of the crack faces is eliminated in the solutions by accounting for contact of the crack faces. The solutions predict that for a subinterface crack in a combined normal and shear stress field, the crack may extend even when the normal stress is compressive. The behavior of a subinterface crack depends on both Dundurs parameters α and β rather than only on β for an interface crack. The behavior of the cracks can be determined from the interaction of the singularities at the crack tips caused by the normal and shear stress fields.
Larviposition by nasopharyngeal bot fly parasites of Columbian black-tailed deer: a correction

Abstract. Previous reports of Cephenemyia jellisoni Townsend (Diptera: Oestridae) larvipositing onto the lips/lower muzzle of deer, with larvae invading via the mouth, are shown to be erroneous. Additional studies with deer models baited with CO2, 1-octen-3-ol and Deer Trail Scent, and muzzle and nostrils treated with insect adhesive, revealed that only C. apicata Bennett & Sabrosky larviposited onto the lips/lower muzzle; C. jellisoni, by contrast, larviposited into the nostrils. Larval depositions were associated with females of both species observed attacking models. Females of both species also were found stuck on adhesive-treated, baited models not attended by observers. During several seasons of exposure, such models received 89 C. jellisoni larvipositions into the nostrils and 87 C. apicata larvipositions onto the lips/lower muzzle. In laboratory experiments nearly all larvae of both species remained stuck in adhesive within 1 mm or less of where they were deposited.
Reductive Dimerization of the Cyclohexadienyl Complex [Mn(CO)3(η5-C6H7)] through a Radical Pathway

Slow naphthalenide reduction of [Mn(η 5 C 6 H 7 )(CO) 3 ] (1) generates the transient anionic radical [Mn(η 5 -C 6 H 7 )(CO) 3 ] . - (4 . - ), which adds as a nucleophile to 1 to form, after further reduction, [Mn(CO) 3 {η 4 -C 6 H 7 -CO-Mn(η 5 -C 6 H 7 )(CO) 2 }] 2 - , while fast reduction of 1 at low temperature gives [{Mn(CO) 3 } 2 (μ 2 -η 4 :η 4 -C 6 H 7 -C 6 H 7 )] 2 - , a dimer of 4 . - . Both reactions suggest that formation of transient 4 . - allows access to new reaction manifolds in which the cyclohexadienyl ligand of the classic complex 1 has been activated to further reactions.
The art and science of data curation

Purpose – For the past decade, as universities have increased their research commitments, the production of large data sets has become prevalent. Up to this point, the storage and curation of these data sets has been somewhat ad hoc and voluntary. Given recent mandatory stipulations coming from government funding sources regarding the handling of data sets, it is imperative that libraries step into this gap and provision data management services for their institutions. This column aims to explore two primary areas in which libraries can provision services for their parent institutions regarding data management. Design/methodology/approach – The column is exploratory in nature. Practical implications – As academic libraries take the lead in data management services, there are many positive implications for their parent institutions. Organizing and preserving important data sets could have a significant impact on the worldwide research community. Originality/value – All academic libraries, no matter their s...
A New Class of Multimerization Selective Inhibitors of HIV-1 Integrase

The quinoline-based allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are promising candidates for clinically useful antiviral agents. Studies using these compounds have highlighted the role of IN in both early and late stages of virus replication. However, dissecting the exact mechanism of action of the quinoline-based ALLINIs has been complicated by the multifunctional nature of these inhibitors because they both inhibit IN binding with its cofactor LEDGF/p75 and promote aberrant IN multimerization with similar potencies in vitro. Here we report design of small molecules that allowed us to probe the role of HIV-1 IN multimerization independently from IN-LEDGF/p75 interactions in infected cells. We altered the rigid quinoline moiety in ALLINIs and designed pyridine-based molecules with a rotatable single bond to allow these compounds to bridge between interacting IN subunits optimally and promote oligomerization. The most potent pyridine-based inhibitor, KF116, potently (EC50 of 0.024 µM) blocked HIV-1 replication by inducing aberrant IN multimerization in virus particles, whereas it was not effective when added to target cells. Furthermore, KF116 inhibited the HIV-1 IN variant with the A128T substitution, which confers resistance to the majority of quinoline-based ALLINIs. A genome-wide HIV-1 integration site analysis demonstrated that addition of KF116 to target or producer cells did not affect LEDGF/p75-dependent HIV-1 integration in host chromosomes, indicating that this compound is not detectably inhibiting IN-LEDGF/p75 binding. These findings delineate the significance of correctly ordered IN structure for HIV-1 particle morphogenesis and demonstrate feasibility of exploiting IN multimerization as a therapeutic target. Furthermore, pyridine-based compounds present a novel class of multimerization selective IN inhibitors as investigational probes for HIV-1 molecular biology.
Complex permittivity and clay mineralogy of grain-size fractions in a wet silt soil

We determined the complex permittivity and clay mineralogy of grain-size fractions in a wet silt soil. We used one clay-size fraction and three silt-size fractions, measured permittivity with low error from 25 MHz to 2–4 GHz with time-domain spectroscopy, and estimated mineral weight percentages using X-ray diffraction (XRD). The volumetric water contents were near 30%, and the temperature was 25°C . For the whole soil, standard fractionation procedures yielded 2.4% clay-size particles by weight, but XRD showed that the phyllosilicate clay minerals kaolinite, illite, and smectite made up 17% and were significantly present in all fractions. Above approximately 500MHz , all real parts were similar. Below approximately 500 MHz , the real and imaginary permittivities increased with decreasing grain size as frequency decreased, and the imaginary parts became dominated by direct-current conduction. Similarly, below approximately 500 MHz , the measured permittivity of montmorillonite, a common smectite, dominate...
Technology Component: A Modified Systems Approach to Creative Thought

The role of technology in the creative process is changing drastically, given the technological advancements of recent years. Although the role of technology is acknowledged in the systems approach to creativity, the model needs modifications to account for the increased importance of technology in the creative process. This article outlines the effects of technology on the individual, society, and the domain, and argues that the original model be revised to include a new component called the technology component. The proposed changes to the system are illustrated and the implications of a modified systems approach to the creative process are discussed.
Direct calorimetry of marine invertebrates entering anoxic states

Metabolic rates of 10 species of invertebrates were determined as they depleted the dissolved oxygen in a small volume of water, and entered anoxic states. The animals included eight marine forms (four mollusks, two brachiopods, a crustacean, and a polychaete), a brackish-water crab, and a freshwater oligochaete. Rates of heat production (QH) were calculated from measurements of temperature change in a heat-retention calorimeter. Rates of oxygen consumption (QO) were calculated from concurrent decreases in oxygen concentration (CO) determined by polarographic oxygen sensor. When the water was fully saturated with oxygen, QH and QO of all species were equal, and most rates were 1–7 J/hr-gm wet weight. A swimming crustacean and the oligochaete had rates five times higher, possibly due to high activity. QO decreased with CO in all species. However, the relation was species specific, most animals showing overreaction to declining CO. In Callinectes only partial regulation of QO was observed at CO above 55% saturation. In all species, QH decreased more slowly than QO over most of the CO range, and decreased rapidly at some critically low CO. The relation between metabolic rate and oxygen saturation was summarized in the fraction (KO) of the fully aerobic rate found when CO was at exactly onehalf saturation, analogous to a Michaelis constant, but not implying a particular mechanism. The KO for QO averaged 0.70, and the KO for QH in 8 species averaged 0.22. In two bivalves QH was often above the initial fully aerobic level at intermediate CO.
Uniform Magnetic Fields and Equilibrium Flame Temperatures

The impact of a constant uniform magnetic field on equilibrium flame temperature under constant volume conditions was examined. The equilibrium combustion compositions were found using an expression for Helmholtz free energy that included a magnetic-field contribution. Changes in the Helmholtz free energy for a mixture of paramagnetic and diamagnetic ideal gases were minimized using the method of Lagrange multipliers. The magnetic susceptibility for the paramagnetic gases was calculated using the Curie law. Equilibrium flame temperatures were obtained from the first law of thermodynamics for a closed adiabatic system with no work interactions. A model reaction of methane in air was used to quantitatively examine changes in the equilibrium flame temperature and product mole fractions as a function of volume and magnetic induction. Equilibrium flame temperature and product mole fractions were plotted as a function of magnetic-field strength and volume for all product species. The results indicate that with the increase in magnetic-field strength, the equilibrium flame temperature increases for all volumes considered.
Prediction of recipes for cotton cationisation and reactive dyeing to shade match conventionally dyed cotton

Cationisation allows cotton to be dyed with anionic dyestuffs (including anionic pigment dispersions) without the need for salt, and with decreased usage of dye, water, and energy. Appropriate cationisation levels play a part in dyeing properties such as fabric levelness, in fastness properties such as lightfastness, and in the overall cost of the cationisation treatment. The objective of this work is to assess whether it is possible simultaneously to predict a dye recipe and cationisation treatment level for cotton to yield a colourless or nearly colourless dyebath at the completion of the dyeing to match the shade of conventional fibre reactive dyeing of cotton. It has been shown that it is possible to model a cold pad batch cationisation process, relate the colour yield data and cationisation level for individual dyes, and finally predict a dyeing recipe and the required corresponding cationisation treatment to match the shade of conventional fibre reactive dyeing of cotton. The predicted dye recipe and cationisation amount yield colourless or nearly colourless dyebaths at the conclusion of the dyeing process.
Microcephaly – no small deal

Anatomic shortening of the fetal frontal lobe seems to precede microcephaly. Brain size determines the size of the calvarium. The report by Pilu and colleagues provides a physiological basis for recent anatomical observations made regarding microcephaly. Biometry of the frontal lobe of the fetal brain may be a valuable tool for the identification of the fetus at risk for microcephaly. A thorough investigation of the subtle brain anatomy of the developing fetus is necessary in suspicious cases. Prenatal studies have suggested that abnormalities of neurocranial architecture occur in approximately two-thirds of cases. Steinlin and colleagues found a much higher incidence in children (90%) affected by microcephaly. Either the progressive nature of the condition or the improved sensitivity of childhood magnetic resonance imaging (used in their study) over prenatal ultrasonography for the detection of subtle brain abnormalities may account for this difference. However, high-resolution ultrasonographic instruments should allow for the detection of many accompanying neuroanatomic abnormalities, possibly before the markedly small calvarium is seen. Finally, Pilu and colleagues have shown that the underlying conditions that may predispose to brain atrophy may be recognizable with Doppler ultrasonography.
Use of a μ-antisense oligodeoxynucleotide as a μ opioid receptor noncompetitive antagonist in vivo

We examined whether μ-antisense (AS) oligodeoxynucleotide (oligo) treatment can be used in a manner similar to the μ-selective irreversible antagonist β-funaltrexamine (β-FNA) for in vivo pharmacology. Rats were injected intracerebroventricularly (icv) with a μ-AS or a missense (MS) oligo on days 1, 3, 5, 7, and 9 and were tested for the antinociceptive effect of sc injection of morphine on days 2, 4, 6, 8, and 10 in the cold water tail-flick (CWT) test. In another set of experiments, rats were also tested for the antinociceptive action of morphine twenty-four hours after icv injection of β-FNA. Both β-FNA and μ-AS produced rightward shifts in the dose-effect curves of morphine. In addition, pretreatment with 2.5 μg or more of β-FNA or the μ-AS oligo for 5–9 days (but not for 1–3 days) reduced the maximal analgesic effect of morphine. The approximate fraction of functional receptor remaining for morphine was determined with the method of Furchgott to be 49.5% following 2.5 μg of β-FNA; that after 5 days of the μ-AS oligo treatment was 50.8%. The results suggest that the μ-AS oligo can be used in the same manner as highly selective, irreversible μ opioid receptor ligands. Thus, properly designed AS oligos against receptors are of particular benefit when irreversible antagonists are not available. AS oligos represent a new class of selective and powerful pharmacological antagonists.
The role of the brain in metamorphosis of the olfactory epithelium in the frog, Xenopus laevis.

Abstract Retrograde signaling from the brain to the olfactory sensory epithelium is important for neuronal survival, but the importance of the olfactory bulb in retrograde signaling during the naturally-induced, neuronal plasticity occurring during metamorphosis is unclear. The olfactory system of the African clawed frog (Xenopus laevis) undergoes dramatic rearrangements during metamorphosis, making this an ideal system in which to examine interactions between the brain and the olfactory sensory epithelium. The main olfactory epithelium of larvae, located in the principal cavity (PC), changes at metamorphosis in function, receptor neuron morphology, biochemistry, and axon termination sites. A new, “middle”, cavity forms during metamorphosis that assumes all the characteristics of the larval PC. Using a combination of bulbectomy and olfactory transplantation, we investigated changes in expression of a marker protein (E7) and in apical ultrastructure in olfactory receptor neurons either (1) connected to the olfactory bulb, (2) connected to non-olfactory brain regions, or (3) with no apparent central nervous system (CNS) connections. We find that neurons in the middle cavity (MC) lacking connections with the CNS appear mature but neurons in the PC do not. Supporting cells in the PC undergo the changes normally observed during metamorphosis. Neurons connected to non-olfactory brain regions, either after bulbectomy or transplantation, appeared normal with regard to the changes normally expected after metamorphosis. These results suggest that influence from the brain is necessary for metamorphic changes in the X. laevis olfactory epithelium, but that these signals are not confined to the olfactory bulb; non-olfactory brain regions can also support these metamorphic changes.
CBFβ enhances de novo protein biosynthesis of its binding partners HIV-1 Vif and RUNX1 and potentiates the Vif-induced degradation of APOBEC3G

ABSTRACT Vif is a lentiviral accessory protein that regulates viral infectivity in part by inducing proteasomal degradation of APOBEC3G (A3G). Recently, CBFβ was found to facilitate Vif-dependent degradation of A3G. However, the exact role of CBFβ remains unclear. Several studies noted reduced Vif expression in CBFβ knockdown cells while others saw no significant impact of CBFβ on Vif stability. Here, we confirmed that CBFβ increases Vif steady-state levels. CBFβ affected expression of neither viral Gag nor Vpu protein, indicating that CBFβ regulates Vif expression posttranscriptionally. Kinetic studies revealed effects of CBFβ on both metabolic stability and the rate of Vif biosynthesis. These effects were dependent on the ability of CBFβ to interact with Vif. Importantly, at comparable Vif levels, CBFβ further enhanced A3G degradation, suggesting that CBFβ facilitates A3G degradation by increasing the levels of Vif and by independently augmenting the ability of Vif to target A3G for degradation. CBFβ also increased expression of RUNX1 by enhancing RUNX1 biosynthesis. Unlike Vif, however, CBFβ had no detectable effect on RUNX1 metabolic stability. We propose that CBFβ acts as a chaperone to stabilize Vif during and after synthesis and to facilitate interaction of Vif with cellular cofactors required for the efficient degradation of A3G. IMPORTANCE In this study, we show that CBFβ has a profound effect on the expression of the HIV-1 infectivity factor Vif and the cellular transcription factor RUNX1, two proteins that physically interact with CBFβ. Kinetic studies revealed that CBFβ increases the rate of Vif and RUNX1 biosynthesis at the level of translation. Mutants of Vif unable to physically interact with CBFβ were nonresponsive to CBFβ. Our data suggest that CBFβ exerts a chaperone-like activity (i) to minimize the production of defective ribosomal products (DRiPs) by binding to nascent protein to prevent premature termination and (ii) to stabilize mature protein conformation to ensure proper function of Vif and RUNX1. Thus, we identified a novel mechanism of protein regulation that affects both viral and cellular factors and thus has broad implications beyond the immediate HIV field.
Effects Of Molecular Structure on Ion Disintegration Patterns In Ionization of O 2 and N 2 by Short Laser Pulses

We demonstrate that the structure of the outermost orbitals of oxygen and nitrogen can be observed in the angular distribution of coincident ion pairs generated by the double ionization of these molecules by 8 fs laser pulses. We do this by establishing that these ions emerge from well defined excited electronic states of O2+2 and N2+2 respectively and that they are produced dominantly through a process which involves electron rescattering. The angular distributions of the ions from the two targets are very different, reflecting the different structures of the outermost orbitals of the two molecules.
Trends in Egg Production, Egg Weight, and Hatchability on Low-Protein and Normal Diets

Abstract TRENDS in egg production and egg weight during the first year of production have been studied by many investigators, but data relating to the trend in hatchability appear to be somewhat scanty. This paper presents data on the average hatchability of eggs, during each month of the first year of production, from pullets receiving low-protein and normal diets, together with data on average egg production and egg weight for the same birds which have been included for purposes of comparison with the hatchability data. The data herein reported were obtained as part of a study of the effects of some nutritional factors on hatchability, conducted by the staffs of the nutrition and physiology laboratories at the U. S. Animal Husbandry Experiment Farm, Beltsville, Maryland. The observations were made over a period of three years, a different group of pullets being used each year. The experimental work was usually begun during . . .
Humerus fractures in llamas and alpacas: seven cases (1998-2004).

Objective— To describe treatment and outcome of humerus fractures in llamas and alpacas. Study Design— Retrospective study. Animals— Llamas (n=4) and alpacas (3) with humerus fracture. Methods— Medical records (January 1, 1998–August 1, 2004) were reviewed for small camelids with a humeral fracture. Retrieved data were signalment, history, physical examination and radiographic findings, surgical and medical treatment, and outcome. Results— Humeral fracture occurred in 7 of 38 (18%) camelids admitted with fractures. Affected animals were aged from 1 month to 3 years old. Fracture configuration included long-oblique (n=4), short-oblique (2), and Salter-Harris Type II fracture of the proximal physis (1). One adult llama was managed by stall confinement and surgical repair was attempted in the other camelids: fixation by screws inserted in lag fashion (n=3), intramedullary pinning and fixation by screws inserted in lag fashion (1), rush pinning (1), and bone plating (1). A Velpeau sling was used for additional support in 3 animals. All fractures healed but temporary radial nerve paresis occurred in 3 animals. Limb shortening and permanent lameness occurred in the llama managed conservatively. Conclusions— Humerus fractures in small camelids are amenable to surgical repair which may offer better long-term outcome than medical treatment alone. Clinical Relevance— Surgical treatment of humerus fractures should have a good prognosis in llamas and alpacas. In select cases, minimally invasive techniques, such as rush pinning or fixation by screws inserted in lag fashion are sufficient for fracture healing.