cssi/SciSciGPT-SciSciNet huggingface dataset:
New fluorescence-based high-throughput screening assay for small molecule inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2).

Abstract Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (TOP2) mediated DNA damages and causes resistance to TOP2-targeted cancer therapy. Inhibiting TDP2 could sensitize cancer cells toward TOP2 inhibitors. However, potent TDP2 inhibitors with favorable physicochemical properties are not yet reported. Therefore, there is a need to search for novel molecular scaffolds capable of inhibiting TDP2. We report herein a new simple, robust, homogenous mix-and-read fluorescence biochemical assay based using humanized zebrafish TDP2 (14M_zTDP2), which provides biochemical and molecular structure basis for TDP2 inhibitor discovery. The assay was validated by screening a preselected library of 1600 compounds (Z′ ≥ 0.72) in a 384-well format, and by running in parallel gel-based assays with fluorescent DNA substrates. This library was curated via virtual high throughput screening (vHTS) of 460,000 compounds from Chembridge Library, using the crystal structure of the novel surrogate protein 14M_zTDP2. From this primary screening, we selected the best 32 compounds (2% of the library) to further assess their TDP2 inhibition potential, leading to the IC50 determination of 10 compounds. Based on the dose-response curve profile, pan-assay interference compounds (PAINS) structure identification, physicochemical properties and efficiency parameters, two hit compounds, 11a and 19a, were tested using a novel secondary fluorescence gel-based assay. Preliminary structure-activity relationship (SAR) studies identified guanidine derivative 12a as an improved hit with a 6.4-fold increase in potency over the original HTS hit 11a. This study highlights the importance of the development of combination approaches (biochemistry, crystallography and high throughput screening) for the discovery of TDP2 inhibitors.
A map estimation algorithm for Bayesian polynomial regression on riemannian manifolds

In this paper, we present a Bayesian formulation of polynomial regression on a Riemannian manifold. Previous methods for fitting a curve to manifold-valued data have been formulated as geometric, least-squares estimation problems. We show that least-squares estimation on manifolds, much like the familiar Euclidean case, suffers from overfitting when using higher-order polynomials. Our Bayesian model mitigates this overfitting by placing a prior on the polynomial coefficients that shrinks their magnitude, analogous to Bayesian Euclidean regression with a Gaussian prior on the coefficients. We develop an algorithm for computing maximum a posteriori estimates of polynomial coefficients and the noise variance. Experiments on synthetically generated sphere data and a real shape regression problem demonstrate the advantages of our approach.
Collaborative Virtual Laboratory Environments with Hardware in the Loop

Over the last decade, the research community has expanded substantial efforts aiming at designing, agreeing on, and rolling out technical standards and powerful universal development tools that allow the rapid and cost-effective integration of specific experimental devices into standardized remote laboratory platforms. In this chapter, a virtual laboratory system with experimental hardware in the loop is described.
Reoperative Dupuytren Contracture

Dupuytren disease (DD) is a challenging clinical problem even with primary surgical cases. However, in the face of recurrence, the surgeon is frequently left with a more challenging and complex problem. Soft tissues may be more adherent because of scar formation, and the anatomy may be distorted making identification of structures such as the nerves and vessels more problematic. Furthermore, the flexor pulley system can be damaged while trying to remove some of these recurrent cords and adherent scar risking potential bow-stringing of the flexor tendons. This chapter outlines some of the options for reoperation on recurrent DD. This type of surgery takes not only skill, but extreme patience on the part of the surgeon as the dissection can be quite tedious. Fortunately, patients are usually grateful for the improvement in function that is obtained.
Biotin–Protein Bond: Instability and Structural Modification to Provide Stability for In Vivo Applications

Biotinylation of proteins is a powerful tool for investigating biological phenomenon, both in vitro and in vivo. Biotinylating reagents that form covalent bonds with several types of amino acid residues are commercially available. However, most, if not all, of these commercially available biotinylating agents produce biotin-protein bonds that are susceptible to cleavage in human plasma. Here, we describe the use of immunoglobulin G as a model protein for evaluation of biotin-protein bond stability and for the investigation of the mechanism of biotin release. We also describe the synthesis of a biotin-protein bond that is stable in human plasma and a method for evaluation of that stability.
Microaggressions and Diurnal Cortisol: Examining Within-Person Associations Among African-American and Latino Young Adults.

Abstract Purpose We examined the relations between African-American and Latino young adults’ microaggressions and subsequent changes in weekly diurnal cortisol parameters (i.e., cortisol awakening responses, overall cortisol output (AUC), and diurnal slopes). Methods Young adults (N = 53, Mage = 20years, SD = .90; 72% female) participated in a 4-week diary study in which they reported their weekly experiences of microaggressions and completed 2 days ofsaliva samples each week. Saliva samples were obtained at waking, 30-minutes after waking, and bedtime on each sampling day (six samples each week; 24 samples total). In line with an idiographic approach to stress, young adults’ increases and decreases in microaggressions (relative to their own average) were linked to changes in cortisol parameters the following week. Results Increases in microaggressions predicted greater AUC the subsequent week, controlling for gender, race, parental education, prior week's AUC, and weekly behavioral controls. Follow-up analyses of specific types of microaggressions indicated that experiences centered around criminality and second-class citizenship also related to increases in young adults’ cortisol awakening responses the subsequent week. Microaggressions were unrelated to changes in diurnal slopes. Conclusions Microaggressions were linked to subsequent changes in diurnal cortisol among African-American and Latino young adults. Given the rigorous within-person design, findings point to the importance and impact of subtle forms of discrimination on young adults’ hypothalamic-pituitary-adrenal axis activity, which is theorized to underlie health and well-being.
Alpine Skiing Injuries.

Context:Alpine skiing is a popular sport worldwide but has significant risk for injury. The epidemiology of skiing-related injuries has been described, which has led to the identification of risk f...
Cohabitation and Contraceptive Use in the United States: A Focus on Race and Ethnicity

While cohabitation has been increasing and a growing context to have and raise children, there has been little attention to one of the key determinants of fertility and effective contraceptive use. Drawing data from the 2013–2015 National Survey of Family Growth (N = 2285), we provide a contemporary portrait of contraceptive use among cohabiting American women. Specifically, we were guided by two main goals. First, we compared cohabiting and married women’s contraceptive use patterns and the variation by race and ethnicity. Second, we focused solely on cohabiting unions; and examined the racial and ethnic variation among cohabiting women. We found that cohabiting women are more likely to use effective methods of contraception than married women. Nonetheless, our findings point to the fact that white cohabiting women are driving the higher patterns of contraceptive use among cohabiting women. Indeed, a further examination of the variation among women in cohabiting relationships shows that black cohabitors are less likely to use effective contraception in cohabiting relationships, compared to whites. Our findings contribute to understanding the reproductive behaviors among a growing set of couples, cohabitors.
Programmable plasmonic phase modulation of free-space wavefronts at gigahertz rates

Space-variant control of optical wavefronts is important for many applications in photonics, such as the generation of structured light beams, and is achieved with spatial light modulators. Commercial devices, at present, are based on liquid-crystal and digital micromirror technologies and are typically limited to kilohertz switching speeds. To realize significantly higher operating speeds, new technologies and approaches are necessary. Here we demonstrate two-dimensional control of free-space optical fields at a wavelength of 1,550 nm at a 1 GHz modulation speed using a programmable plasmonic phase modulator based on near-field interactions between surface plasmons and materials with an electrooptic response. High χ(2) and χ(3) dielectric thin films of either aluminium nitride or silicon-rich silicon nitride are used as an active modulation layer in a surface plasmon resonance configuration to realize programmable space-variant control of optical wavefronts in a 4 × 4 pixel array at high speed. A 4 × 4 pixel spatial light modulation scheme based on plasmonics offers high-speed spatial light modulation at the telecommunications wavelength of 1,550 nm.
A Transformation-Proximal Bundle Algorithm for Solving Multistage Adaptive Robust Optimization Problems

This paper proposes a novel transformation-proximal bundle algorithmic framework to solve multistage adaptive robust optimization (ARO) problems. Different from existing solution methods, the proposed algorithmic framework partitions recourse decisions into state decisions and local decisions. It applies affine decision rule only to state decision variables and allows local decision variables to be fully adjustable. In this way, the original multistage ARO problem is proved to be transformed into a two-stage ARO problem. The proximal bundle algorithm with the Moreau- Yosida regularization is further developed for the exact solution of the resulting two-stage ARO problem. The transformation-proximal bundle algorithmic framework could generate less conservative solutions compared with the decision rule based approach, while enjoying a high computational efficiency. An application on multiperiod inventory control problem under demand uncertainty is presented to demonstrate the effectiveness and superiority of the proposed algorithm.
Optimal Guidance Algorithms for Parking Search with Reservations

To alleviate the congestion caused by searching for parking, internet- or smartphone-based parking reservation systems have been deployed in major cities. We develop algorithms to provide optimal guidance to individual drivers on where to search for or reserve parking and how to navigate the traffic while searching for parking, a problem which has yet to be addressed in the literature. Drivers holding a reservation pay a holding cost per unit time until they park, so it is often suboptimal to reserve parking before departing. We formulate a Markov decision process to decide both where to attempt to reserve parking and which route to take. The optimal parking space to reserve changes as the driver travels through the network. Results on the downtown Austin network show that reserving parking affects route choice and reduces cruising for parking compared to not reserving parking. Our model and solution algorithm could be integrated with GPS navigation systems to provide guidance to individual drivers on optimal navigation and use of parking reservation systems.
The Magic of Mathematics

bring a "magic trick" to school. It is usually one of those situations where the spectator is required to deal cards into various piles for an interminable length of time; or think of the year of his or her birth, multiply that number by the number of days in the year, divide by the Social Security number, and so on, ad infinitum. However, that process does not stop others from asking at the denouement, "How did you do that?" Are you beginning to see the connection? Many of those tricks that students enjoy so much, those deceptions they want so much to unravel, are math ematical in nature. We are pleased to say that our appreciation for tricks of this type is a shared joy. When Catherine Mulligan, a mathematics instructor at Miami Uni versity in Ohio, taught a course in mathematics to middle school students, she discovered that card tricks were their favorite activity. After she demon strated a card trick, her students asked the magic question, "How did you do that?" Mulligan was then able to segue into a mathematics lesson (Mul ligan 1989). So, apropos to the topic at hand, let us look into a card trick.
Uprooting and liberation: problematics of Central and Eastern European exile in Škvorecký’s The engineer of human souls and Hoffman’s Lost in translation

To be thrust into exile is necessarily to develop a complex and profoundly problematic relationship to the past, and arguably nowhere is this more tangible than in the exile literature of Central and Eastern Europe. This paper analyses Josef Skvorecký’s The engineer of human souls (1984) and Eva Hoffman’s Lost in translation (1989) in an exploration of the literary representation of twentieth-century Central and Eastern-European exile to North America. Drawing on the philosophies of Brodsky, Milosz, Suvin and Said, I focus on the plurality of vision afforded by exile, the relationship between exile and (semi)-autobiographical writing, differing opinions towards the host land and native homeland, and issues of “rootedness” and “double-centredness” in the exiled individual, in order to examine the problematic relationship between past and present, uprooting and liberation, in Polish and Czech exile literature.
Plywood wood based composites using crystalline/amorphous PLA polymer adhesives

Abstract Tailored crystalline and amorphous powdered polylactic acid (PLA) bio-renewable green polymers were studied for their use as adhesive for the joining of 2 and 3-ply veneers to produce and test plywood panels for strength, substrate failure and water soak resistance properties per ANSI/HPVA standards. For 3-ply construction Douglas Fir (DF) was used for the core whereas, Southern Pine (SP) veneer was used for the faces per sponsor specifications. It was found that heat or ionizing radiation tailored crystalline and amorphous type PLA-based adhesive resin formulations can both offer adequate strength as measured by the attained shear stress [ranging through ~3.4 MPa (500 psi)], and degree of substrate failure (50–90%) for a range of adhesive loadings ranging from 85 g/m2 to 300 g/m2. Highest shear strength values approaching 500 psi were obtained with emulsion spray based application using amorphous PLA in the 125–250 μm range. For 2-ply samples prepared with either crystalline or amorphous PLA adhesive, both offered satisfactory strength and soak resistance. Successful dry shear strength and 3-cycle soak water resistance under standard conditions were possible to achieve with amorphous PLA formulation for both 2-ply and 3-ply plywood samples. 3-ply tests with panels using crystalline form PLA adhesive formulation did not meet 3-cycle resistance metrics even with 300 g/m2 adhesive loading; although, 1-cycle soak resistance was possible. The superior performance of the amorphous formulation is deemed to arise out of improved wetting and substrate penetration due to its x10 higher melt index and x3 lower relative viscosity as compared with the crystalline form polymer adhesive. Plywood samples prepared with PLA formulations (as yet without cross-linking or strength tailoring), did not survive boiling water testing metrics as would be required of Type I (exterior grade) plywood. However, the research results indicate that ANSI/HVPA metrics for Type II (interior grade) plywood are attainable using the as-formulated amorphous form PLA based adhesive and the associated application methods described in the paper.
Chapter 6 – Guided Waves

This chapter will deal with an important class of waves that have widespread applications in SHM – the class of guided waves . Guided waves are especially important for SHM because they can travel large distances in structures with only little energy loss. Thus, they enable the SHM of large areas from a single location. The chapter starts with Rayleigh waves, a.k.a. surface acoustic waves (SAW), which travel close to a free surface with very little penetration in the depth of the solid. For this reason, Rayleigh waves are also known as surface-guided waves. The chapter continues with shear-horizontal (SH) waves in plates. The particle motion of SH waves is polarized parallel to the plate surface and perpendicular to the direction of wave propagation. The SH waves are multimodal and dispersive (with the exception of the very fundamental mode, SH0, which is nondispersive). Next, the chapter discusses Lamb waves in plates, which are dispersive and multimodal. For relatively small values of the frequency–thickness product fdfd, only the basic symmetric and antisymmetric Lamb wave modes (S0 and A0) exist. As the fdfd product approaches zero, the S0 and A0 modes degenerate in the basic axial and flexural plate modes discussed in Chapter 5. At the other extreme, as fd→∞fd→∞, the S0 and A0 Lamb wave modes degenerate into Rayleigh waves confined to the plate surface. Lamb waves are studied in both rectangular and circular coordinates. The chapter ends with a brief review of guided waves in tubes and cylindrical shells in which dispersive longitudinal (axial), flexural, and torsional multi-mode guided waves can simultaneously exist.
Cardiac Resynchronization Therapy Selection in a Patient with Non Left Bundle Branch Block

A patient with heart failure with reduced ejection fraction and a wide QRS complex is evaluated for cardiac resynchronization therapy.
Reported Use of Non-Steroidal Anti-Inflammatory Drugs in Food Animal Practice

A cross-sectional study was designed to determine 1) the extent to which nonsteroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of food animals, 2) demographic and practice factors that may influence their use, and 3) if withdrawal times for milk and slaughter are recommended.
Synapse regulation by transplanted astrocytes: a tissue culture study.

Publisher Summary The cerebellar Purkinje cell somata, dendrites, and proximal axonal segments are ensheathed by processes of specialized protoplasmic astrocytes, the Golgi epithelial cells, and the Fananas cells. This chapter presents a discussion on the tissue culture study of synapse regulation by transplanted astrocytes. It is of interest that optic nerve astrocytes are able to ensheath Purkinje cells in the same manner as Golgi epithelial cells, and reduction of excessive numbers of synapses around Purkinje cell somata is associated with astroglial ensheathment. The chapter suggests that astrocytes play a role in synapse regulation, including (1) regulation of the synaptic density around certain neurons, and (2) induction of dendritic growth cones. These functions can be added to the long list of properties already ascribed to astrocytes. Apparently, an understanding of the various functions of these cells is essential to an appreciation of the host-graft interactions that may occur during central nervous system transplantation.
Formation of a template committed complex on the promoter of a gene for the U6 small nuclear RNA from the human requires multiple sequence elements, including the distal region.

Vertebrate U6 small nuclear RNA (snRNA) loci exemplify a novel class of polymerase III-transcribed genes that lack an intragenic control region (ICR). Instead important transcriptional control elements are located in the 5‘-flanking region and resemble those found in promoters and enhancers of polymerase II-transcribed genes. These include a proximal sequence element (PSE), a TATA element, and a distal region containing, at least, an octamer motif. We have used Sarkosyl to characterize steps in U6 promoter transcription in vitro in an unfractionated S100 extract and find very similar properties to those of the adenovirus VA1 gene that contains an ICR. Preformed preinitiation complexes are stable to 0.015% Sarkosyl and can undergo multiple rounds of initiation upon addition of nucleoside triphosphates. A higher concentration (0.075%) prevents reinitiation. In addition, we have investigated the formation of transcription complexes on this promoter in a S100 extract using a template competition assay. No stable complexes are detected with plasmid templates that contain clustered point mutations in the PSE nor with DNAs lacking the U6 5‘-flanking region. A plasmid template containing mutations in the TATA element is partially deficient in competitive ability. Furthermore, the distal region upstream of position–148 is necessary for efficient stable complex formation. Within this region, the consensus octamer motif is one component needed to form complexes that withstand competition by a wild-type U6 promoter. The human U2 gene enhancer ligated to the U6 proximal region supports formation of a complex that competes at an intermediate level.
Mouse Mammary Tumor Virus-Directed Gene Expression in Transgenic Mice

Transgenic mice have proven to be useful for the study of many different biological phenomenon, such as gene regulation, oncogenesis, and immunological function. The expression of novel gene products in transgenic mice, such as the major histocompatibility antigens, has allowed investigators to more easily study the role of these antigens in tissue transplantation and rejection, in organ development and tumorigenesis. A useful vector for use in such studies would be one that is capable of directing expression of a variety of gene products to specific cell types in different tissues. We have been studying the tissue-specific expression of the mouse mammary tumor virus (MMTV), with the goal of developing such vectors.
Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. II. High affinity uptake sites for dopamine

Weaver (gene symbol wv) is an autosomal recessive mutation in the mouse that causes the death of neurons in the cerebellum and of dopamine- containing neurons in the mid-brain. In the accompanying paper and in previous reports, the selective nature of the deficit produced by the gene in the dopamine-containing systems has been described after analysis of the patterns of the residual innervation in the striatum and the patterns of cell death in the midbrain. In the present report, we describe deficits in the terminals of the mesostriatal system occurring prior to a detectable dopamine deficiency in the striatum and prior to the onset of cell death in the mesencephalic dopamine- containing neurons during development. We have also found deficits in the remaining terminals of the adult weaver's striatum after the weaver pattern of innervation has been permanently established. Axonal terminals in the caudoputamen are impaired in weaver mice at postnatal day 7, before the onset of dopamine depletion in the caudoputamen and cell death in the midbrain. The impairment was revealed by a markedly deficient high-affinity uptake for 3H-dopamine by synaptosomes prepared from the caudoputamen. Throughout the remainder of development and in adulthood, the extent of the deficit in 3H-dopamine uptake was always greater than that for dopamine content. No striatal region was completely spared the effects of the gene. In the nucleus accumbens of the weavers, where dopamine content is normal, 3H-dopamine uptake was reduced by 35% in the synaptosomal preparations. In the olfactory tubercle, dopamine levels were reduced by 44% but 3H-dopamine uptake was reduced by 60%.(ABSTRACT TRUNCATED AT 250 WORDS)
A compilation of location, size, and geomorphological parameters of volcanoes of the Michoacan-Guanajuato volcanic field, central Mexico.

Se han catalogado mas de mil centros volcanicos en el campo volcanico Michoacan-Guanajuato, el cual esta situado en la parte media del Cinturon Volcanico Mexicano. Los volcanes catalogados incluyen: 901 conos cineriticos o cupulas de lava, 43 domos, 22 maars o cercos anulares de tobas, 13 volcanes de tipo escudo con conos en las cimas y 61 flujos de lava no asociados a conos. Estos volcanes se distribuyen entre los 200 km y 430 km medidos desde la Fosa Americana Mediana. No se observa alineamiento preferencial, sin embargo, la concentracion maxima estimada se encuentra a los 250 km. Entre los indicadores morfologicos catalogicos catalogados para determinar la edad de los conos cineriticos, la densidad de las zanjas y la clasificacion geomorfologica de los flujos de lava resultaron sensibles dentro del limite de determinacion de edad mediante 14 C. Finalmente, se clasificaron 78 volcanes como morfologicamente jovenes, de edad de 40,000 anos o menos y un volumen de 31 km 3 , cifras que indican una tasa estimada en el volumen de erupcion de 0.8 km 3 /1 000 anos pare todo el campo volcanico en su conjunto.
Some consequences of inhibition in vitro of uridine diphosphate glucose synthesis in soluble extracts of rat liver

Abstract It has been shown that when exogenous UDP-glucose is added to a rat-liver supernatant system which converted [ 14 C]orotic acid to UDP-glucose via the polyphosphate uridine nucleotides, autoinhibition of the synthesis of this coenzyme occurred. This phenomenon has been shown to be due to a mass-action effect. As a consequence, the UTP pool in the inhibited system is maintained at a high level, and accordingly, the synthesis of cytidine nucleotides, and the labeling of the s-RNA of the preparation were increased.
A priority assignment model for standards and conditions in a long term care survey.

Abstract Presently a survey document is used in New York State to enforce Federal and State regulatory standards for long term care facilities (skilled nursing facilities and health related facilities). This document is used to establish Medicare and Medicaid certification for these facilities. This study describes the creation of a new survey process—a first stage consisting of a screening survey followed, if necessary, by an intensive survey. A priority assignment model which utilizes the judgements of experts from the New York State Office of Health Systems Management (OHSM) has been developed. This model is employed to develop ranks, priority weights and classifications for the various standards and the Federal conditions which the standards comprise (as well as equivalent State regulations). Saaty's Analytical Hierarchy Process is used to obtain the ranks and priority weights. The consistency of the experts' judgements is measured using Kendall's coefficient of agreement. An optimal split algorithm is used to subdivide the standards and conditions according to impact (high, moderate or low) on patient care, health and safety. The results are to be used as a management tool in developing decision rules for defining the scope of the intensive survey on the basis of screening survey results.
PREDICTING THE THERMAL PERFORMANCE FOR THE MULTI-OBJECTIVE VEHICLE UNDERHOOD PACKING OPTIMIZATION PROBLEM

The ever increasing demands towards improvement in vehicle performance and passenger comfort have led the automotive manufacturers to further enhance the design in the early stages of the vehicle development process. Though, these design changes enhance the overall vehicle performance to an extent, the placement of these components under the car hood also plays a vital role in increasing the vehicle performance. In the past, a study on the automobile underhood packaging or layout problem was conducted and a multi-objective optimization routine with three objectives namely, minimizing center of gravity height, maximizing vehicle components accessibility and maximizing survivability (for army vehicles) has been setup to determine the optimal locations of the underhood components. The previous study did not consider thermal performance as an objective. This study asserts the necessity of including thermal performance as an objective and makes an assessment of the several available thermal analyses that are performed on the automotive underhood to evaluate the thermal objective. A Neural Network approximation of the CFD analysis conducted over the automotive underhood is presented in this paper. The results obtained from the Neural Network are compared with the CFD results, showing good agreement. The Neural Network model is included in the multi-objective optimization routine and new layout results are obtained. A non-deterministic evolutionary multi-objective algorithm (AMGA-2) is used to perform the optimization process.Copyright © 2012 by ASME
Fusarium solani association with branch and trunk cankers on citrus weakened by cold weather in Florida

Injury or inoculation of apparently healthy citrus trunk bark and wood with Fusarium solani immediately prior to and after the December 1983 freeze resulted in cankers similar to natural branch and trunk cankers which formed on trees following the freeze. Fusarium solani was consistently isolated from active lesions of natural and induced cankered bark. Phytophora spp. were not isolated from cankered tissue. Earliest cankers appeared as a water-soaked area under the bark around the point of inoculation, later F. solani sporodochia formed on the bark surface. Older cankers became dry and cracked but produced no gum. Canker size ranged from 10–90 cm vertical diameter in spring 1984 inoculations but were only several cm diameter following late summer inoculations. Active cankers developed again after inoculation following the January 1985 freeze. Similar cankers were produced on ‘Hamlin’ sweet orange stems inoculated with F. solani.
DNA Accessibility in Nucleosomes

The cell nucleus is a highly dynamic reaction center for many DNA-based cellular processes, as well as an effective compaction center for DNA storage. The basic packing unit of chromatin is the nucleosome. Even this lowest level of genomic compaction presents a strong barrier to many DNA-binding cellular factors. In a coordinated and regulated fashion, DNA associated with nucleosomes must be made transiently accessible to permit many essential processes. Nucleosome stability and structure thus are intimately involved in the regulation of genetic information storage and retrieval. Single molecule mechanical studies are ideally suited to probe these processes and have become powerful complementary tools to traditional biochemical and molecular biological approaches. I will discuss our progress in mechanical studies of nucleosome stability and structure, as well as how DNA in nucleosomes may be accessed by motor proteins.
Titan at the edge: 2. A global simulation of Titan exiting and reentering Saturn's magnetosphere at 13:16 Saturn local time

[1] We use a multifluid/multiscale model of Titan inside Saturn's magnetosphere to examine how Titan's induced magnetosphere and ion tail are affected when Titan crosses Saturn's magnetopause at 13:16 Saturn local time (SLT). During the simulation Titan crosses Saturn's magnetopause twice, exiting and reentering Saturn's magnetosphere. The magnetic field in Saturn's magnetosheath is predominately northward. Once inside Saturn's magnetosheath, Titan's connection to Saturn's magnetosphere is removed by slow ionospheric convection. Evidence for reconnection at Titan is not seen. Inside the magnetosheath the plasma flow is not perpendicular to the magnetic field, and magnetic field lines do not strongly drape around Titan. Titan's ionosphere is extended in the magnetosheath because Titan's ionospheric plasma is not stripped away by convecting magnetic field at high altitudes. After Titan crosses back into Saturn's magnetosphere, the magnetospheric plasma and field removes Titan's extended ionosphere, and Titan's induced magnetosphere returns to a “typical” configuration. The simulation is used to determine the time scale of Titan's connection to Saturn's magnetic field lines or magnetosheath magnetic field lines after a magnetopause crossing. In the magnetosheath, slow (∼3 km/s) ionospheric convection removes Titan's connection to Saturn's magnetosphere in ∼1.8 h. After Titan crosses back into Saturn's rapidly rotating magnetosphere, Titan's connection to magnetosheath magnetic field lines is removed through ionospheric convection in ∼50 min. The results of the simulation are also compared to data from Cassini's T32 flyby.
Electronic structure of superconducting and non-superconducting compounds in the Pb2Sr2Y1−yCayCu3−xAgxO8 Family

Abstract Synchrotron-radiation photoemission spectroscopy has been used to search for differences in the electronic structure of superconducting and non-superconducting members of this novel family of compounds. We find no evidence of a Fermi edge for non-superconducting compounds, which is present for superconducting compounds. This result confirms that the absence of a Fermi edge in the early 1-2-3 photoemission spectra is an extrinsic effect. Studies of the resonating copper satellite did not produce evidence of Cu 1+ states.
The Use of Adhesives and Sealants in Electronics

This paper surveys the wide variety of resin compounds available to meet the demands of modern electronics. It describes the properties and characteristics relevant to choosing a compound for a required performance and reliability and presents some guides for selection and use. Experimental data supports the discussion and comparison of resin properties.
In a spin: the mysterious dancing epidemic of 1518

In 1518, one of the strangest epidemics in recorded history struck the city of Strasbourg. Hundreds of people were seized by an irresistible urge to dance, hop and leap into the air. In houses, halls and public spaces, as fear paralyzed the city and the members of the elite despaired, the dancing continued with mindless intensity. Seldom pausing to eat, drink or rest, many of them danced for days or even weeks. And before long, the chronicles agree, dozens were dying from exhaustion. What was it that could have impelled as many as 400 people to dance, in some cases to death?
Classification tree methods for development of decision rules for botulism and cyanide poisoning.

Introduction Identification of predictors of potential mass poisonings may increase the speed and accuracy with which patients are recognized, potentially reducing the number ultimately exposed and the degree to which they are affected. This analysis used a decision-tree method to sort such potential predictors.
Profit maximizing communities and the theory of local public expenditure

Abstract This paper examines profit maximization as a normative criterion for communities in a large metropolitan area. We develop a Tiebout-like model of residential location, define the “profits” of a community, and show that profit maximization leads to the efficient provision of public services and optimal community size. Communities do not in general act as profit maximizers, however, because individual property owners may not all share in a community's profits. Two institutional reforms are therefore suggested that would alter the distribution of profits in a way that makes the self-interested actions of property owners consonant with community profit maximization.
Good intentions: risk factors for unintended pregnancies in the US cohort of a microbicide trial.

Abstract Background The study was conducted to assess socio-behavioral and biological factors associated with unplanned pregnancy in the US cohort of a microbicide trial. Study Design We conducted a mixed-method, nested case-control study of risk factors for pregnancy within the US cohort of the microbicide trial HPTN 035. We developed an instrument to assess attitudes and beliefs about fertility control/contraceptive utilization among 122 women. Cases were HPTN 035 participants who became pregnant while enrolled, matched by time on study 1:4 with controls. Univariable and multivariable analysis were performed with pregnancy as the outcome of interest. Results Contraceptive method change during the trial was associated with unplanned pregnancy (OR=1.76). Participant desire/partners' desire for future children (OR=4.95) and young age (OR=0.88 annually above age 19 years) were independently associated with unintended pregnancy. Conclusion Within a trial that enrolls heterosexually active women, there may be ways to identify those at highest risk of becoming pregnant a priori.
Membrane Oligomerization and Cleavage Activates the Caspase-8 (FLICE/MACHα1) Death Signal

Many forms of apoptosis, including that caused by the death receptor CD95/Fas/APO-1, depend on the activation of caspases, which are proteases that cleave specific intracellular proteins to cause orderly cellular disintegration. The requirements for activating these crucial enzymatic mediators of death are not well understood. Using molecular chimeras with either CD8 or Tac, we find that oligomerization at the cell membrane powerfully induces caspase-8 autoactivation and apoptosis. Death induction was abrogated by the z-VAD-fmk, z-IETD-fmk, or p35 enzyme inhibitors or by a mutation in the active site cysteine but was surprisingly unaffected by death inhibitor Bcl-2. Amino acid substitutions that prevent the proteolytic separation of the caspase from its membrane-associated domain completely blocked apoptosis. Thus, oligomerization at the membrane is sufficient for caspase-8 autoactivation, but apoptosis could involve a death signal conveyed by the proteolytic release of the enzyme into the cytoplasm.
On the inhibition of chymotrypsin by ovomucoid.

Abstract A study has been made of the inhibition of chymotrypsin by ovomucoid. Marked inhibition is obtained only at high ovomucoid to chymotrypsin ratios. Electrophoretic and ultracentrifugal experiments show that this inhibition is accompanied by complex formation between the two proteins.
Structure of twin boundaries in La2 − xBaxCuO4

Abstract The structure of the twin boundary in the low-temperature-orthorhombic (LTO) phase of La2 − xBaxCuO4 is studied using a Landau-type free-energy model which reproduces the x − T phase diagram. We find that the twin boundaries that have the lowest free energy are those with low-temperature-tetragonal (LTT) structure in the center of the domain walls. Near the LTT-to-LTO phase-transition temperature, both the width as well as the density of the twin boundaries increase with decreasing temperature.
MHD simulations of accretion disks and jets: strengths and limitations

Observations are providing increasingly detailed quantitative information about the accretion flows that power such high energy systems as X-ray binaries and Active Galactic Nuclei. These observations have been modeled in some detail by a variety of accretion scenarios, but such models rely on unavoidable assumptions such as regular flow geometry and a simple, parameterized stress. Global numerical simulations offer a way to investigate the basic physical dynamics of accretion flows without these assumptions. We are now carrying out fully three-dimensional general relativistic magnetohydrodynamic simulations of time-dependent inflows into Kerr black holes. The results from recent global simulations of black hole accretion disks will be reviewed, and some implications of those results for observations will be discussed.
Functional integrity of isolated rat hepatocytes prepared by whole liver vs biopsy perfusion

Isolated rat hepatocytes prepared by a newly developed, versatile biopsy perfusion method (HB cells) were compared with hepatocytes prepared by conventional whole liver perfusion (HP cells), immediately after isolation and after 6 h in suspension culture. Thirteen parameters were used to assess the functional integrity of these cells. Both methods produced high yields of metabolically active hepatocytes that were virtually indistinguishable from each other. After 6 h, the average viability of both cell isolates declined ∼ 10%, mixed function oxidase activities were decreased ∼25% at most, and GSH levels were actually increased; other parameters were not significantly changed. The data indicate that HB-cell isolates are at least as viable and metabolically active as HP cells, and, because the biopsy perfusion method can be applied to liver samples from any species, it facilitates comparative studies.
Asymptotics of Estimating Equations under Natural Conditions

In a variety of statistical problems one needs to solve an equation in order to get an estimator. We consider the large sample properties of such estimators generated from samples that are not necessarily identically distributed. Very general assumptions that lead to the existence, strong consistency, and asymptotic normality of the estimators are given. A number of results that are useful in verifying the general assumptions are given and an example illustrates their use. General applications to maximum likelihood, iteratively reweighted least squares, and robust estimation are discussed briefly.
New infrared objects associated with OH masers

Results of a search for IR radiation at 10 microns from a sample of OH maser sources are reported. An IR source is discovered near each of six OH masers which emit mainly at 1612 MHz in two distinct velocity ranges. It is shown that all the sources have varied with time, that two sources have exhibited significant variations in color temperature, and that the energy distributions of the six objects over the spectral range from 2 to 20 microns fall into two categories. Absorption in the 2.3-micron band of CO is detected in two sources, and four are found to display substantial silicate absorption features. The energy distributions of the sources indicate that pumping by 35-micron photons is feasible, but 2.8-micron pumping is very unlikely; the distributions are best explained as emission from very thick dust shells at temperatures of about 500 K. The data are taken as supporting the hypothesis that every double-peaked OH maser emitting principally at 1612 MHz is associated with an IR object. The nature of the objects inside the dust shells and their evolutionary state are briefly discussed.
Non-hormonal stimulators and inhibitors of plant growth and development.

Summary 1. Plants contain growth regulators that are non-hormonal in nature. These regulators change in concentration during ontogeny and when applied exogenously, can either stimulate or depress growth. While the bulk of either the phenolic or terpenoid regulators are localized within the vacuole, they can also be found within other cellular compartments where they may act upon metabolic pathways, modifying either cell multiplication or elongation. 2. Non-hormonal growth regulators may affect the synthesis and/or destruction of phytohormones, mainly indole-3-acetic acid (IAA). These regulators behave non-specifically, modifying the actions of auxins, gibberellins and cytokinins upon growth. 3. A variety of both uncertainties and unresolved contradictions exist that have prevented a thorough elucidation of the mechanisms of actions of both phenolic and terpenoid regulators. These uncertainties and unresolved contradictions include lack of data regarding compartmentalization of many of the inhibitors. This raises the question of whether their intracellular concentrations become elevated sufficiently to affect metabolic pathways in vivo. Exogenously applied regulators of non-hormonal nature usually interfere with growth only at high concentrations. Therefore, the possibility cannot be excluded that under these conditions, reactions occur within the cell that are absent in vivo. 4. The specific properties of natural non-hormonal regulators are similar in certain respects to phytohormones. For example, both of them may be biogenetically bound within metabolic centres: shikimate (phenolics, indoles, alkaloids), bi-benzi (coumarins) or acetate-mevalonate (terpenoids, fluorens, sesquiterpenes, cytokinins). In addition, both non-hormonal regulators and phytohormones exhibit biological activity in growth bioassays. 5. Non-hormonal regulators may possess a number of useful purposes, e.g. test substances such as fusicoccin permit the investigation of the mode of action of phytohormones, specific inhibitors blocking special forms of growth and protectors of phytohormone activity in culture.
Facilitated Interaction between the Pyruvate Dehydrogenase Kinase Isoform 2 and the Dihydrolipoyl Acetyltransferase

Abstract The dihydrolipoyl acetyltransferase (E2) has an enormous impact on pyruvate dehydrogenase kinase (PDK) phosphorylation of the pyruvate dehydrogenase (E1) component by acting as a mobile binding framework and in facilitating and mediating regulation of PDK activity. Analytical ultracentrifugation (AUC) studies established that the soluble PDK2 isoform is a stable dimer. The interaction of PDK2 with the lipoyl domains of E2 (L1, L2) and the E3-binding protein (L3) were characterized by AUC. PDK2 interacted very weakly with L2 (Kd ≃ 175 μm for 2 L2/PDK2) but much tighter with dimeric glutathione S-transferase (GST)-L2 (Kd ≃ 3 μm), supporting the importance of bifunctional binding. Reduction of lipoyl groups resulted in ∼8-fold tighter binding of PDK2 to GST-L2red, which was ∼300-fold tighter than binding of 2 L2red and also much tighter than binding by GST-L1red and GST-L3red. The E2 60-mer bound ∼18 PDK2 dimers with a Kd similar to GST-L2. E2·E1 bound more PDK2 (∼27.6) than E2 with ∼2-fold tighter affinity. Lipoate reduction fostered somewhat tighter binding at more sites by E2 and severalfold tighter binding at the majority of sites on E2·E1. ATP and ADP decreased the affinity of PDK2 for E2 by 3–5-fold and adenosine 5′-(β,γ-imino)triphosphate or phosphorylation of E1 similarly reduced PDK2 binding to E2·E1. Reversible bifunctional binding to L2 with the mandatory singly held transition fits the proposed “hand-over-hand” movement of a kinase dimer to access E1 without dissociating from the complex. The gain in binding interactions upon lipoate reduction likely aids reduction-engendered stimulation of PDK2 activity; loosening of binding as a result of adenine nucleotides and phosphorylation may instigate movement of lipoyl domain-held kinase to a new E1 substrate.
Characterization of a chick embryonic erythrocyte antigen using immunochemical electron microscopy.

Abstract We have characterized an embryonic antigen on the surface of chick erythrocytes using immunochemical electron microscopy. An indirect surface labeling technique (hemocyanin conjugated to goat antirabbit IgG and specific antisera prepared in rabbits) revealed that the antigenic sites, at hatching, nearly saturate the surface of erythrocytes with hemocyanin markers. The number of antigenic sites gradually decreases with age, and the antigen can no longer be detected at 7 months. Further, the antigen has been detected on the very earliest primitive erythrocytes which form in the extra-embryonic mesenchyme before circulation begins. The embryonic antigen appears to be firmly associated with the erythrocyte surface and cannot be removed by extensive washing either with phosphate-buffered saline or with EDTA. Labeling unfixed cells at 37 °C produces clustering of the surface markers, suggesting that the antigen is associated with a membrane component which is fairly free to move in the plane of the membrane. In addition, the erythrocytes from newly hatched chicks were found to agglutinate more readily with several different lectins, particularly Concanavalin A (ConA), than did the erythrocytes from adults. Three times more ConA is bound to chick erythrocytes than to adult erythrocytes, as estimated by electron microscopy. Although this difference in lectin binding suggests that the ConA-binding sites might be related to the embryonic antigen, the sugars known to block lectin-induced hemagglutination had no blocking effect on antiserum-induced agglutination or on antibody binding, as visualized by the electron microscope technique. Also, ConA binding was not inhibited by treatment of the chick erythrocytes with the specific antiserum.