cssi/SciSciGPT-SciSciNet huggingface dataset:
Proteasome regulation of ERBB2 chaperone association, intracellular trafficking and overexpressed membrane receptor levels

3761 To better understand ERBB2 receptor mechanisms subject to therapeutic modulation, we investigated the proteasome dependence of ERBB2 receptor chaperone formation, trafficking, perinuclear accumulation and intracellular degradation using two ERBB2 amplified and overexpressing human breast cancer cell lines, SKBR3 and BT474. Following culture treatment with a 20S proteasome-inhibiting dose of PS341/bortezomib (5-25 nM), these cancer cells demonstrate growth inhibition (SRB assay) and apoptosis induction (p85 PARP formation) along with marked loss of phospho-ERBB2 and total ERBB2 protein levels by 48-72 h. Within the first 24 h of proteasome inhibition, treated cells show an early shift in the association of 185 kDa ERBB2 protein with molecular chaperones, from one that stabilizes (Hsp90) to one that targets the receptor for degradation (Hsp70). Altered chaperone binding occurs in conjunction with ERBB2 protein ubiquitination and before significant loss in receptor content; and both the altered chaperone binding and receptor ubiquitination are associated with relocalization of immunoreactive ERBB2 from the cell surface to a perinuclear compartment that co-localizes with an immunoreactive lysosomal protein, LAMP1. The bortezomib induced perinuclear relocalization of ERBB2 can be prevented by co-treatment of these cells with the protein synthesis inhibitor cycloheximide. As well, co-treatment with a non-toxic dose of the lysosomal processing inhibitor, chloroquine, prevents bortezomib induced ERBB2 decay in these ERBB2-positive cells. In summary, early effects following proteasome inhibition appear to include altered chaperone binding and the perinuclear sequestration of ubiquitinated ERBB2 that is newly synthesized or endocytosed, followed by lysosomal degradation of receptor protein and loss of the critical receptor signals needed for proliferation and survival of these ERBB2-positive cancer cells. Apart from shedding light on the increased cytotoxic sensitivity of ERBB2-positive cancer cells to proteasome inhibitors like bortezomib, these findings suggest that the proteasome system plays a critical role in maintaining intracellular trafficking, chaperone recruitment, and appropriate cell surface localization of ERBB2 receptors, at least in epithelial cells transformed by ERBB2 amplification and overexpression.
Lifetime Socioeconomic Position and Functional Decline in Older Mexican Americans: Results from the Sacramento Area Latino Study on Aging

Functional impairment and disability in old age are major health problems that are not well studied in Mexican Americans who are likely to be immigrants and to live in poverty the majority of their lives. Moreover, nativity and socioeconomic position (SEP) over the life course interact and influence late life health status and disability. The Sacramento Area Latino Study on Aging (SALSA) study is a cohort of 1789 older Mexican Americans that was actively followed from 1998 to 2008. Activities of daily living and instrumental activities of daily living (ADL and IADL) were measured annually during this period. Health conditions were measured annually as well. Functional disabilities increased most rapidly in US born women compared to immigrant women and men. Those participants whose SEP trajectory remained high throughout life experienced the lowest increase in ADL or IADL impairment compared to those who were always low. Exposure to the US environment may adversely affect women more than men and US born more than Mexican-born.
Fuzzy Fractional Approximations by Fuzzy Normalized Bell and Squashing Type Neural Networks

This chapter deals with the determination of the fuzzy fractional rate of convergence to the unit to some fuzzy neural network operators, namely, the fuzzy normalized bell and “squashing” type operators.
Empirical and model-based reasoning in expert systems

Many expert systems are now being written which rely on highly-compiled, empirical knowledge for their reasoning power. Model-based reasoning has significant theoretical advantages. I constructed two expert systems for the same domain, one using large-grained compiled knowledge, the second using model-based reasoning. The use of model-based reasoning resulted in improved knowledge accessibility and flexibility, and expanded problem-solving ability.
Truth is marching on: the Lasershow Spectacular at the Stone Mountain Park Confederate Memorial and the changing narratives of history.

The overarching goal of this paper is to examine the changing historical narratives of the Stone Mountain Park Confederate Memorial as seen through the Lasershow Spectacular, and how this performance speaks to broader issues of race, identity, geography, and memory. The implications of this discourse are especially significant for the identity construction of marginalized collectives. I begin with a brief theoretical explanation of history and cultural memory as socially constructed, including the significance of who gets to create it, its relationship with identity, and the connection between history and cultural memory and popular/consumer culture. Next, I discuss the current state of heritage tourism and how it relates to issues of racial (in)justice. Finally, I turn to Stone Mountain and the Lasershow Spectacular as a case study to examine the social construction of history and cultural memory at a tourist attraction, specifically discussing how the African-American experience is addressed (or not add...
Numerical methods in engineering with Python

Numerical Methods in Engineering with Python, 2nd Edition is a text for engineering students and a reference for practicing engineers, especially those who wish to explore Python. This new edition features 18 additional exercises and the addition of rational function interpolation. Brent's method of root finding was replaced by Ridder's method, and the Fletcher-Reeves method of optimization was dropped in favor of the downhill simplex method. Each numerical method is explained in detail, and its shortcomings are pointed out. The examples that follow individual topics fall into two categories: hand computations that illustrate the inner workings of the method and small programs that show how the computer code is utilized in solving a problem. This second edition also includes more robust computer code with each method, which is available on the book Web site. This code is made simple and easy to understand by avoiding complex bookkeeping schemes, while maintaining the essential features of the method.
Probabilistic plan management

Abstract : The general problem of planning for uncertain domains remains a difficult challenge. Research that focuses on constructing plans by reasoning with explicit models of uncertainty has produced some promising mechanisms for coping with specific types of domain uncertainties; however, these approaches generally have difficulty scaling. Research in robust planning has alternatively emphasized the use of deterministic planning techniques, with the goal of constructing a flexible plan (or set of plans) that can absorb deviations during execution. Such approaches are scalable, but either result in overly conservative plans, or ignore the potential leverage that can be provided by explicit uncertainty models. The main contribution of this work is a composite approach to planning that couples the strengths of both the above approaches while minimizing their weaknesses. Our approach, called Probabilistic Plan Management (PPM), takes advantage of the known uncertainty model while avoiding the overhead of non-deterministic planning. PPM takes as its starting point a deterministic plan that is built with deterministic modeling assumptions. PPM begins by layering an uncertainty analysis on top of the plan. The analysis calculates the overall expected outcome of execution and can be used to identify expected weak areas of the schedule.
Genetic characterization of Pseudomonas syringae pv. syringae strains from stone fruits in California.

Strains of Pseudomonas syringae pv. syringae were isolated from healthy and diseased stone fruit tissues sampled from 43 orchard sites in California in 1995 and 1996. These strains, together with P. syringae strains from other hosts and pathovars, were tested for pathogenicity and the presence of the syrB and syrC genes and were genetically characterized by using enterobacterial repetitive intergenic consensus (ERIC) primers and PCR. All 89 strains of P. syringae pv. syringae tested were moderately to highly pathogenic on Lovell peach seedlings regardless of the host of origin, while strains of other pathovars exhibited low or no pathogenicity. The 19 strains of P. syringae pv. syringae examined by restriction fragment length polymorphism analysis contained the syrB and syrC genes, whereas no hybridization occurred with 4 strains of other P. syringae pathovars. The P. syringae pv. syringae strains from stone fruit, except for a strain from New Zealand, generated ERIC genomic fingerprints which shared four fragments of similar mobility. Of the P. syringae pv. syringae strains tested from other hosts, only strains from rose, kiwi, and pear generated genomic fingerprints that had the same four fragments as the stone fruit strains. Analysis of the ERIC fingerprints from P. syringae pv. syringae strains showed that the strains isolated from stone fruits formed a distinct cluster separate from most of the strains isolated from other hosts. These results provide evidence of host specialization within the diverse pathovar P. syringae pv. syringae.
Preparation of Highly Immunogenic Ribosomal Fractions of Mycobacterium tuberculosis by Use of Sodium Dodecyl Sulfate

Youmans, Anne S. (Northwestern University Medical School, Chicago, Ill.), and Guy P. Youmans. Preparation of highly immunogenic ribosomal fractions of Mycobacterium tuberculosis by use of sodium dodecyl sulfate. J. Bacteriol. 91:2139-2145. 1966.-Ribosomal fractions of Mycobacterium tuberculosis, strain H37Ra, were prepared by treatment of the intracellular particulate fraction with 0.25 or 0.5% sodium dodecylsulfate (SDS) followed by centrifugation at 144,700 x g for 3 hr. This procedure has greatly simplified the preparation of ribosomal fractions and has given fractions composed of approximately 50% ribonucleic acid (RNA) and 15 to 20% protein. When incorporated into Freund's incomplete adjuvant and injected intraperitoneally into CF-1 mice, the SDS ribosomal fractions were more immunogenic than the particulate fractions from which they were prepared. They were as much as 100 times more immunogenic than ribosomal fractions prepared by differential centrifugation, 1 mug (dry weight) per mouse being sufficient for the induction of some immunity. However, none of these ribosomal preparations, in comparable doses, was as immunogenic as the living cells from which they were prepared. It was also shown that the addition of 10(-4)m MgCl(2) to the final diluent increased immunogenic activity, whereas larger concentrations (10(-3)m) reduced immunogenic activity. Preparation of the ribosomal fraction from ruptured cells in one continuous process during the course of 1 day increased the activity. Two-week-old H37Ra cells contained more RNA and were more immunogenic than the older cultures which have been used in the past.
Nicht nur zur Neujahrszeit

Aufschreie. Stohnen. „Boll erschoss das System — Einheit verloren — das Fundament!“ Der Notarzt kniete uber dem unter Schock stehenden Firmenpatriarchen, der am Boden innerhalb seines schwarzen Seidenanzuges vollig zusammengesunken war. Viele Menschen, teils in weisen Kitteln, teils in dunklen Anzugen oder Kostumen, rannten wie kopflos (der Kopf des Ganzen lag ja am Boden) in dem zentralen Firmenraum hin und her, ohne Plan, was zu tun ware. Sie rangen die Hande und starrten vorwiegend in die eine Ecke des Raumes, wo sich Weiskittel um den Zentralcomputer bemuhten. Aus einem nervenden Lautsprecher, der oben im Kronleuchter eingebaut war, tonte unablassig wiederholend die Ansage einer Frauenstimme, die einschmeichelnd klang, sanft, so wie wir uns Engelsstimmen vorstellen: „Input, bitte. Geben Sie mir noch bessere Zahlen. Bitte Input!“
A survey of the topological properties of symplectomorphism groups

The special structures that arise in symplectic topology (particularly Gromov--Witten invariants and quantum homology) place as yet rather poorly understood restrictions on the topological properties of symplectomorphism groups. This article surveys some recent work by Abreu, Lalonde, McDuff, Polterovich and Seidel, concentrating particularly on the homotopy properties of the action of the group of Hamiltonian symplectomorphisms on the underlying manifold M. It sketches the proof that the evaluation map \pi_1(Ham(M))\to \pi_1(M) given by {\phi_t}\mapsto {\phi_t(x_0)} is trivial, as well as explaining similar vanishing results for the action of the homology of Ham(M) on the homology of M. Applications to Hamiltonian stability are discussed.
Complicating the role of p53 in aging.

Recently, we described a p53 mutant mouse model (p53+/m mouse model) that presented a paradox, in which tumor free survival was coupled to reduced lifespan instead of extended lifespan (Tyner et al., 2002). The p53+/m mice expressed a truncated p53 transcript attached to a leader sequence and showed a moderate increase in p53 activity. Based on this data we hypothesized that enhanced levels of p53 caused the early aging and cancer resistance phenotypes. This hypothesis was attractive as it indirectly implied a ‘fine tuning’ mechanism of tumor suppressor gene expression to maintain homeostasis at the organismal level (Campisi, 2002; Kirkwood, 2002). Our results also lent support to the evolutionary theory of antagonistic pleiotropy that predicts the deleterious effects of tumor-suppressor genes later in life (Williams, 1957). These observations notwithstanding, the p53+/m mouse model presented a caveat, in which tumor free survival was coupled to reduced lifespan instead of extended lifespan. Studies in model organisms have shown that enhanced resistance to oxidative stress correlates with increased longevity (Johnson et al., 2002; Murakami et al., 2003). The tumor suppressor functions of p53 overwhelmingly categorize it as a longevity assurance gene and suggest a synergistic effect on lifespan via tumor free survival of the organism. We show that there are 24 genes deleted in the p53+/m mouse model, complicating the role of p53 in aging and raising the possibility that the phenotypes while resembling ‘premature aging-like’ symptoms, may not be related to the physiological changes seen during normal aging processes.
Eyewitness identification for prudent police

Purpose – Both anecdotal and empirical evidence indicates that even well-intentioned eyewitnesses can make inaccurate identifications resulting in erroneous prosecutions and wrongful convictions. The risk of erroneous identification increases when witnesses are asked to identify people belonging to other races. The purpose of this paper is to evaluate the policies which enhance the likelihood of obtaining accurate identifications from eyewitnesses. Legal implications especially relevant to police administrators in the USA including constitutional considerations and risks of civil liability are integrated with the empirical record and used to make policy recommendations likely to decrease legal and public relations entanglements for police. Design/methodology/approach – This paper integrates an empirical literature review with legal research and analysis in order to advocate for prudent policy reforms. Findings – Both the empirical record and current US law indicate that police administrators would be well-advised to require serial, double-blind identification procedures where witnesses are routinely warned about the perpetrator’s potential absence and required to give immediate certainty statements. Officers should be prohibited from using the same suspect with the same witness more than once and should be provided with training on the inherent dangers of inaccuracy associated with cross-racial identifications. Originality/value – While a significant amount of material concerning eyewitness identification exists, most of the existing work does not integrate legal realities, especially those concerning civil liability, within the framework of the eyewitness identification literature. Nor does past work contextualize the need for reform with the emerging racially charged atmosphere in which US police must currently work.
Do Data Breach Disclosure Laws Reduce Identity Theft? (Updated)

In the United States, identity theft resulted in corporate and consumer losses of $56 billion dollars in 2005, with up to 35 percent of known identity thefts caused by corporate data breaches. Many states have responded by adopting “data breach disclosure laws” that require firms to notify consumers if their personal information has been lost or stolen. While the laws are expected to reduce identity theft, their effect has yet to be empirically measured. We use panel data from the U.S. Federal Trade Commission to estimate the impact of data breach disclosure laws on identity theft from 2002 to 2009. We find that adoption of data breach disclosure laws reduce identity theft caused by data breaches by 6.1 percent, on average.
Simultaneous inversion of surface-wave phase velocity and attenuation: Rayleigh and Love waves over continental and oceanic paths

A formalism for the simultaneous inversion of surface-wave phase velocity and attenuation, previously developed for Love waves, is extended in this paper to Rayleigh waves. The simultaneous inversion technique permits the specification of the intrinsic dispersion-attenuation relation that arises from linearity and causality, and takes full account of the dependence of surface-wave phase velocity and Q −1 on the real and imaginary parts of an anelastic earth structure. The formalism, including resolution analysis and extremal inversion, is applied to combined Love- and Rayleigh-wave data sets for a tectonically active and a stable continental path and to Rayleigh-wave data for a stable oceanic path. The depth to the low Q zone is 60 ± 20 km for the central Pacific, 80 ± 20 km for western North America, and 130 ± 30 km for east-central North America. Q −1 within the low- Q , low-velocity zone, however, is greater beneath western North America than beneath the central Pacific; the low- Q zone beneath east-central North America need not be a low-velocity zone at frequencies above 1 Hz. The surface-wave data cannot distinguish among several possible intrinsic dispersion-attenuation relations for the upper mantle.
On the accuracy of block implicit and operator-splitting algorithms in confined flame propagation problems

The propagation of a one-dimensional, confined, laminar flame is studied by means of two operator-splitting methods, four linear block implicit schemes and the standard implicit and Crank-Nicolson techniques. It is shown that the implicit method underestimates the flame speed and pressure because of first-order temporal truncation errors. Second-order accurate, in both space and time, methods yield nearly the same flame location and pressure as the operator-splitting techniques and the Crank-Nicolson scheme. Block linear methods which are first-order accurate in time and second-order accurate in space show temperature oscillations in the burned gas region near the flame front. These methods are found to be unstable when a delta formulation is used and the flame approaches the combustor wall. The instabilities are attributed to the large magnitude of the source terms and the rate of change of these terms with respect to time. A reduction in the time step brings the results of first-order accurate block met...
Sequence of the 5′ end of the sendai virus genome and its variable representation in complementary form at the 3′ ends of copy-back defective interfering RNA species: Identification of the L gene terminus

Direct sequencing showed that the 5' termini of several defective interfering RNA species, both fusion and copy-back types, were homologous to the 5' terminus of the Sendai virus genome. Size analyses of spontaneously formed terminal duplexes (stems) of three copy-back defective interfering RNA species revealed variable extents of terminal complementarity, ranging from about 155 to 210 nucleotides. Direct sequencing of the 3' terminus of one of these copy-back RNA species demonstrated its complementarity to the 5'-terminal sequence of the virus genome. This copy-back sequence contained, in complementary form, the 5' terminus of the L gene, comprising the same sequence, 3'-AUUCUUUUU-5', that was previously identified at the 5' ends of the five other major Sendai virus genes.
The Cyclic 3',5'-Adenosine Monophosphate Receptor Protein and Regulation of Cyclic 3',5'-Adenosine Monophosphate Synthesis in Escherichia coli

Rates of synthesis of cyclic 3′,5′-adenosine monophosphate (cAMP) were measured in cultures of Escherichia coli aerating without a carbon source. This technique provides a representative measure of adenylate cyclase activity in the absence of inhibition caused by transport of the carbon source. Adenylate cyclase activity was found to vary more than 20-fold depending on the carbon source that had been available during growth. Synthesis of cAMP in cells aerating in the absence of the carbon source was highest when cells had been grown with glucose or fructose which inhibit adenylate cyclase activity severely. Synthesis of cAMP was much lower when cells had been grown with glycerol or succinate which cause only minimal inhibition of the activity. The variation in cAMP synthesis due to different carbon sources requires a functional cAMP receptor protein (CRP). Crp- mutants synthesize cAMP at comparable rates regardless of the carbon source that afforded growth. A novel mutant of E. coli having a CRP no longer dependent on cAMP has been isolated and characterized. Adenylate cyclase activity in this mutant no longer responds normally to variations in the carbon source.
A comparative analysis of the validity of several approaches to the scoring of the behavior of the preterm infant

Abstract A group of very low birthweight preterm infants (mean weight = 1193.6 g; mean gestational age = 31.1 weeks) were examined with the PREMIE. The PREMIE is a modification of the scoring system of the full term Brazelton Neonatal Behavioral Assessment (BNBAS) examination for use with preterm infants. Infants were assessed during the acute phase of cardio-respiratory illness (mean age = 7 days) and during the recovery phase (mean age = 22 days). Many modifications in procedure were required. Several analyses were performed to assess the redundancy and the comparative validity of the scoring systems of the PREMIE, the BNBAS, and the BNBAS + (the BNBAS plus a set of five additional preterm items). Results indicated that the three scoring systems were highly redundant, that they were equally related to physiologic and clinical variables, and that they were similar in their sensitivity to behavioral change and stability. Overall the results offered little in the way of differentiating among these three scoring systems with this group of infants, raising doubts about the need to use the PREMIE or other scoring systems like it for many research purposes.
White Cell Transfusions Born Again

(1993). White Cell Transfusions Born Again. Leukemia & Lymphoma: Vol. 11, No. sup2, pp. 161-165.
Linear rank tests for censored survival data

We describe a class of rank test procedures for the two-sample problem with right censored survival data. The class of tests is directly generalized from the linear rank tests by assigning each observation a rank according to its corresponding Wilcoxon scores. It allows a flexible choice of score functions, in particular, those powerful against scale differences between the two survival distributions. Monte Carlo simulations have shown that some members of this class have great power in detecting crossing-curve alternatives (alternatives where underlying survival curves cross over). The class also contains tests essentially equivalent to the Gehan-Wilcoxon and the logrank tests.
Gathering a sex history from a physically disabled adult

Sexuality is a health issue and should be integrated into clinical settings that focus on the rehabilitation needs of people with disabilities. It is as critical as any other activity of daily living and should be given an equal priority by the health care team. Finally, it is important for health professionals to have a good understanding of their own sexual issues if they are to be effective with their patients. Based on these assumptions, this article provides an overview and definition of basic sexual questions and concerns for people with disabilities. It provides an overview of the interview process with appropriate questions for both men and women as well as their partners.
The Quenching of Mercury Resonance Radiation by Hydrogen, Carbon Monoxide and Nitrogen

An investigation was made of the dependence upon the temperature of the quenching of mercury resonance radiation by hydrogen, carbon monoxide and nitrogen. The quenching by hydrogen was effectively independent of the temperature from 473\ifmmode^\circ\else\textdegree\fi{}K to 973\ifmmode^\circ\else\textdegree\fi{}K, but that by carbon monoxide and by nitrogen decreased with increasing temperature. This decrease was somewhat more marked in nitrogen than in carbon monoxide. These results show that the metastable $2^{3}P_{0}$ state of the mercury atom is involved in the quenching by carbon monoxide and by nitrogen, but not appreciably in the quenching by hydrogen. The quenching by hydrogen may be accounted for by a reaction involving the dissociation of the hydrogen molecule by collision with a $2^{3}P_{1}$ mercury atom, followed in a certain small fraction of the cases by the probable excitation by collision with a second $2^{3}P_{1}$ atom of the mercury hydride molecule so produced. The effective cross sections for energy transfer in the first process at the different temperatures are given. The quenching by carbon monoxide and by nitrogen may be accounted for by the transition $2^{3}P_{1}\ensuremath{\rightarrow}2^{3}P_{0}$ of the mercury atoms at gas collisions, by the return of some of the $2^{3}P_{0}$ atoms to the $2^{3}P_{1}$ state at subsequent gas collisions, and by the reduction of the remainder of them by several distinct processes to the $1^{1}S_{0}$ state. The effective cross sections for the different processes are given.
Pulmonary manifestations of acquired immunodeficiency syndrome.

T HE ACQUIRED immunodeficiency syndrome (AIDS) epidemic continues to spread worldwide more than a decade after the first case was recognized in 1981. In the United States, over 1 million individuals are infected with the human immunodeficiency virus (HIV), and there are 40 to 60,000 new cases of infection diagnosed each year. 1,2 No vaccine or cure for AIDS has yet been developed nor have efforts at prevention stemmed the tide of new cases. Along with its relentless spread, the AIDS epidemic continues to change and evolve over time. The phrase "living with HIV" is but one indication of how dramatically the face of AIDS has changed in the last 5 years. 2 Individuals infected with HIV are now living much longer than previously anticipated. Almost 51% of HIV-positive patients in one San Francisco cohort are still alive after 11 years of follow-up.2 The use of zidovudine (AZT) and other antiviral treatments have slowed the progression of HIV disease in many individuals, and prophylactic treatments for infections such aspneumocystis carinii pneumonia (PCP), tuberculosis (TB), and pneumococcal pneumonia also have contributed to better prognosis. 2 As treatments and prophylaxis have changed, so have the manifestations of AIDS. Once
Multicultural Counseling and Qualitative Research: Shared Worldview and Skills

In this article, similarities are identified between multicultural counseling competencies and the basic assumptions and methodology of qualitative research. Having an understanding of one's own biases, assumptions, and worldviews possessing knowledge and understanding of the culturally different client's (participant's) worldview; and using appropriate strategies and skills are characteristics that are shared by multicultural counseling and qualitative research. These characteristics are addressed under aspects of qualitative research, namely, selection of the research question; researcher as instrument; relationship between researcher and participants; and data collection, analysis, and validity.
Signalling by middlemen

Abstract Two variations on signalling models which arise in markets with middlemen are presented. First, if middlemen are risk-neutral, then pooling always occurs in (Nash) equilibrium. Second, if middlemen are risk-averse, then pooling reactive equilibria may exist. The analysis offers insights into the absence of contracts designed to separate agents in many middlemen relationships.
Developmental Pathology, Dopamine, and Stress: A Model for the Age of Onset of Schizophrenia Symptoms

It is unknown why the onset of schizophrenia is typically during late adolescence or early adulthood. The fact that numerous brain maturational processes normally occur during this age period has led researchers to postulate how such processes may be related to the onset of symptoms. To help elucidate the question of age of onset, we selectively review schizophrenia-associated abnormalities of dopamine and related systems, including glutamate and hypothalamic-pituitary-adrenal systems; relevant models of pathophysiology; and the systems' developmental aspects. Based on current findings and conceptualizations, a model is then proposed in which, during adolescence, interactive pathological and normal adolescence-associated processes trigger a positive feedback system that results in a rapid increase in pathology that is proposed to underlie the development of active psychotic symptoms during late adolescence or early adulthood.
Are Alternatives the Next Bubble

Institutional investors have been steadily increasing their allocation to alternative assets in recent years. The alternative world currently comprises of about $3 trillion in assets and spans a wide variety of asset classes and strategies such as real estate, private equity, commodities and hedge funds. Many investors now view alternative assets as an effective solution to the mediocre performance of traditional assets. Is this shift into alternatives just creating another bubble? This article investigates whether the recent performance of alternative assets will continue to persist in the future. The analysis uses three signals to detect a bubble: excess returns, expensive valuation, and speculative activity. The results show that among commodities, energy demonstrates most evidence of being a bubble whereas non-energy commodities show less evidence. The results also show that hedge funds and private equity do not demonstrate much evidence of being a bubble.
Interannual forcing mechanisms of California Current transports II: Mesoscale eddies

Abstract Mesoscale eddies exert dominant control of cross-shelf exchanges, yet the forcing dynamics underlying their interannual and decadal variability remain uncertain. Using an ensemble of high-resolution ocean model hindcasts of the central and eastern North Pacific from 1950 to 2010 we diagnose the forcing mechanisms of low-frequency eddy variability in the California Current System (CCS). We quantify eddy activity by developing eddy counts based on closed contours of the Okubo-Weiss parameter and find that the spatial and temporal features of model-derived counts largely reproduce the short AVISO observational record. Comparison of model ensemble members allows us to separate the intrinsic and deterministic fractions of eddy variability in the northern CCS (34.5–50°N) and in the southern CCS (28.5–34.5°N). In the North, a large fraction of low-frequency eddy variability (30% anticyclones, 20% cyclones) is deterministic and shared with satellite observations. We develop a diagnostic model based on indices of the large-scale barotropic and baroclinic states of the CCS which recovers this deterministic variance. This model also strongly correlates with local atmospheric forcing. In contrast to the North, Southern CCS eddy counts exhibit very little deterministic variance, and eddy formation closely resembles a red-noise process. This new understanding of the external forcings of eddy variability allows us to better estimate how climate variability and change impact mesoscale transports in the California Current. The skill of our diagnostic model and its close association with local wind stress curl indicate that local atmospheric forcing is the dominant driver of eddy activity on interannual and decadal time scales north of pt. conception (~33°N).
Reasonable Consumer or Ignorant Consumer? How The FTC Decides

This article examines the alternatives which have been avail able to the Federal Trade Commission in deciding what members of the consuming public it is committed to protecting. The choice has been between the "reasonable man standard," under which it protects only those who act reasonably in the market place and not those who act foolishly, and the "ignorant man standard," under which it protects all consumers without regard for the reasonableness or foolishness of their behavior. A third possibility is a standard lying between these two, under which the Commission protects consumers acting foolishly provided such actions are committed not by stray individuals but by sub stantial segments of the population.
Hapten‐specific responses to the phenyltrimethylamino hapten. II. Regulation of delayed‐type hypersensitivity by genetically restricted, anti‐idiotypic suppressor T cells induced by the monovalent antigen L‐tyrosine‐p‐azo‐phenyltrimethylammonium

Inoculation of A/J mice with the synthetic monovalent antigen, L-tyrosine-p azophenyltrimethylammonium [tyr(TMA)] results in the formation of idiotype-specific suppressor T cells (Ts) which exclusively shut down clones of B cells that bear a dominant cross-reactive idiotype (CRI) associated with anti-TMA antibodies (J. Exp. Med. 1980.251: 528). It was of interest to find out whether this same population would also suppress T cell-mediated immunity specific for the TMA ligand. Accordingly, the tyr(TMA)-induced Ts population was tested for its ability to modulate delayed-type hypersensitivity (DTH) reactions specific for TMA. A/J mice were primed with tyr(TMA) in adjuvant and 6-7 weeks later spleen cells were tested for suppressor activity. Transfer of the tyr(TMA) immune population 24 h prior to priming, or at any other time point before challenge, resulted in a significant suppression of the response. This suppression, both induction phase as well as effector phase, is mediated by T cells since treatment of the splenic population with anti-Thy-1 plus complement before transfer eliminates the suppressor activity. The suppressor activity is antigen-specific, since 5 x 107 spleen cells which markedly suppress TMA DTH have no effect on contact sensitivity to dinitrofluorobenzene. Binding experiments in petri dishes coated with CRI-bearing anti-TMA antibodies indicate that the majority of the Ts cells have specificity for the CRI and not for the antigen (TMA). Studies using serological reagents specific for different cell surface antigens indicate that the idiotype-specific Ts bear the I-J subregion-encoded surface antigen(s) as well as the Lyt-2+ phenotype. Transfer experiments utilizing appropriate strains of mice demonstrated that the Ts were both H-2- and Igh-V-restricted. Finally, a cell-free preparation obtained by sonicating the tyr(TMA)-primed population inhibited the TMA DTH reaction in the A/J (H-2a, Igh-1e) but not in the idiotype-positive A.SW (H-2s, Igh-1e), allotype-congenic strain C57.Ige nor in the idiotype-negative C57BL/6J partner. The role of the tyr(TMA)-primed, idiotype-specific Ts population in regulating TMA-related responses via the idiotypic network is discussed.
P. L. PROPER KNOT EQUIVALENCE CLASSES ARE GENERATED BY LOCALLY FLAT ISOTOPIES

A p. 1. proper knot is a proper p. 1. embedding of the real line into a p. 1. open 3-manifold. Two p. 1. proper knots are said to be equivalent if there is a p. 1. proper isotopy (possibly non-ambient) connecting them. A priori such an isotopy need not be locally flat: for example a local knot in the range could be shrunk to a point within a 3-cell. In this paper we show that, in essence, this is the only type of non-locally flat phenomena. We show that such a local knot can always be "combed to infinity". Thus if two p. 1. proper knots are connected by a p. 1. proper isotopy then the connecting isotopy can be modified to be a locally flat p. 1. proper isotopy. Hence, in proper knot theory, the smooth category and the p. 1. category are similar.
Neural Activation During Response Competition

Abstract The flanker task, introduced by Eriksen and Eriksen lEriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of a target letter in a nonsearch task. Perception & Psychophysics, 16, 143–149r, provides a means to selectively manipulate the presence or absence of response competition while keeping other task demands constant. We measured brain activity using functional magnetic resonance imaging (fMRI) during performance of the flanker task. In accordance with previous behavioral studies, trials in which the flanking stimuli indicated a different response than the central stimulus were performed significantly more slowly than trials in which all the stimuli indicated the same response. This reaction time effect was accompanied by increases in activity in four regions: the right ventrolateral prefrontal cortex, the supplementary motor area, the left superior parietal lobe, and the left anterior parietal cortex. The increases were not due to changes in stimulus complexity or the need to overcome previously learned associations between stimuli and responses. Correspondences between this study and other experiments manipulating response interference suggest that the frontal foci may be related to response inhibition processes whereas the posterior foci may be related to the activation of representations of the inappropriate responses.
In-vitro investigation of oxazol and urea analogues of morphinan at opioid receptors

A series of 2-amino-oxazole (7 and 8) analogs and 2-one-oxazole analogs (9 and 10) were synthesized from cyclorphan (1) or butorphan (2) and evaluated in-vitro by their binding affinity at mu, delta, and kappa opioid receptors and compared with their 2-aminothiozole analogs 5 and 6. Ligands 7-10 showed decreased affinities at kappa and mu receptors. Urea analogs (11-14) were also prepared from 2-aminocyclorphan (3) or 2-aminobutorphan (4) and evaluated in-vitro by their binding affinity at mu, delta, and kappa opioid receptors. The urea derived opioids retained their affinities at mu receptors while showing increased affinities at delta receptors and decreased affinities at kappa receptors. Functional activities of these compounds were measured in the [35S]GTPgammaS binding assay, illustrating that all of these ligands were kappa agonists. At the mu receptor, compounds 11 and 12 were mu agonist/antagonists.
Electrical diagnositics of quantum cascade lasers

The analysis of I-V and I-L curves in mid-IR quantum cascade lasers operating at room temperature is performed. When the ohmic component of the device resistance in the I-V curve is subtracted, the current I can be approximated by the exponential function, I = I s exp(eV j /e) where I s is the saturation current, Vj is the n-n junction voltage, and e is an energy parameter related to the tunneling mechanism which enables filling of upper states and emptying of lower states of the laser transition. Values of eare found to be in 0.68-1.45 eV range, and when divided by the number of stages in the cascade, the tunneling parameter of each stage is determined. The threshold related “kink” of differential I-V curves is shown. The effect of voltage saturation above the laser threshold is observed. Thus, the possibility of determination of the threshold using electrical measurements in quantum cascade lasers has been demonstrated.
Important Role of Translational Science in Rare Disease Innovation, Discovery, and Drug Development

Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease’s natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.
Responses of immunoglobulin-secreting cells in the skin of pigs during Sarcoptes scabiei infestation

Abstract Investigations using immunofluorescence and immunoperoxidase techniques revealed a gradual, but marked, increase in the numbers of immunoglobulin-secreting cells in the skin of pigs during the development of lesions of sarcoptic mange. This was followed by a marked decrease as the lesions regressed. The rise and fall in numbers of these immunoglobulin-secreting cells were observed in both newborn and older animals as they developed signs of cutaneous disease. IgG-secreting cells were the major immunoglobulin-containing cells, followed by IgM- and then IgA-containing cells in the skin of newborn animals. In older pigs, IgM-secreting cells were most prevalent, followed by IgG- and IgA-secreting cells. In multiple infestations, immunoglobulin-secreting cells in the dermis showed very little increase in numbers following the second infestation. Third, fourth and fifth infestations produced little or no increase.
Processing of Yttria powders derived from hydroxide precursors

Abstract Roles of calcination and sintering schedules on the final sintered density and microstructure of Y2O3 compacts were studied. Optimum calcination procedure appeared to be at 1000°C and for one hour in air atmosphere. Final sintered density of 95% theoretical was achieved around 1450° and nearly pore free (>99% theoretical) pellets were obtained at 1650°C for one hour sintering in vacuum. High heating/cooling rates when coupled with high sintering temperature caused discontinuous grain growth and large internal cracks.
MOSFET technology for low-voltage/low-power applications

Certain limits influence MOSFET technology in low-voltage applications. When we reduce the power supply voltage in modern short-channel devices, both active power dissipation and hot carrier reliability improve more than Linearly. However, strong off-state power consumption requirements and increasing numbers of FETs in each integrated circuit, combined with the physical limit to the subthreshold slope, force designers to choose between high performance and high density. >
Effect of initial composition distribution on the phase transformation behavior in the Fe-Cr-Ni system

A finite-difference implicit numerical model was used to study the diffusion-controlled {alpha}{minus}{gamma} (ferrite-to-austenite) solid-state phase transformation in the Fe-Cr-Ni system. The influence of a nonuniform initial composition distribution was examined in order to assess the impact that nonuniform solute profiles resulting from solidification may have on subsequent transformation behavior in weldments and castings. A significant impact on the transformation kinetics and transformation path was found in some cases. Factors that affect the degree of influence are discussed.
Sinusitis and asthma: associated airway diseases.

Sinusitis and asthma often coexist in patients. In fact, these airways disorders are similar histologically, with tissue eosinophils, increased glandular tissue, and edema. Medical or surgical therapy for sinusitis often greatly improves asthma, suggesting that sinusitis may exacerbate asthma. Possible mechanisms by which asthma could be worsened by sinus disease include neural reflex pathways and interference with the important nasal functions of heating, humidification, and filtration. Health professionals treating asthmatic patients should consider sinusitis as a possible underlying cause, in addition to other triggers (eg, allergic rhinitis and gastroesophageal reflux disease).
ICCAD-2014 CAD contest in incremental timing-driven placement and benchmark suite: Special session paper: CAD contest

Circuit performance is greatly affected by the quality and optimization metrics of placement algorithms. At modern technology nodes, improving routability and reducing total wirelength are no longer sufficient to close timing, as nets may require specialized attention to reduce negative slack. To this end, incremental timing-driven placement (TDP) seeks to address these imposed timing constraints by leveraging timing information during optimization while respecting relative density and displacement thresholds with respect to the original placement. The goal of the ICCAD-2014 Contest is to encourage research in incremental TDP by providing (i) a flexible timing-oriented place­ment framework, including a publicly-available academic timer, (ii) a set of benchmarks and the associated cell library with timing information and (iii) an evaluation metric that objectively defines the quality of newly-developed algorithms.
Psychometric properties of the Communication Confidence Rating Scale for Aphasia (CCRSA): Phase 2

Background: The construct of communication confidence was introduced by participants and family members during qualitative post-treatment interviews as part of a research study using a computer programme to deliver language therapy. However, there was no standardised method of evaluating communication confidence. Therefore the Communication Confidence Rating Scale for Aphasia (CCRSA) was developed, asking persons to self-rate communication confidence. Aims: This study reports data from the second phase of the project in which the CCRSA was revised to include 10 items. This revised 10-item self-rating scale of communication confidence (CCRSA) was evaluated psychometrically. Methods & Procedures: The revised 10-item questionnaire was administered 94 times to 47 participants with aphasia from a variety of settings. Psychometric properties of the 10-item CCRSA were investigated using rating scale (Rasch) analysis. Outcomes & Results: Person reliability of the 10-item CCRSA was .81. The four-category rating sc...
Double-Fold C-H Oxygenation of Arenes Using PyrDipSi: a General and Efficient Traceless/Modifiable Silicon-Tethered Directing Group

The efficient Pd-catalyzed double-fold C-H oxygenation of arenes into resorcinols using newly developed 2-pyrimidyldiisopropylsilyl (PyrDipSi) directing group is described. Its employment allows for a sequential introduction of OAc and OPiv groups in a one-pot manner to produce orthogonally protected resorcinol derivatives. PyrDipSi group is superior over the previously developed 2-pyridyldiisopropylsilyl (PyDipSi) group, as it is efficient for monooxygenation of ortho-substituted arenes. Notably, PyrDipSi group can be easily installed into arene molecule and can be easily removed or modified after the oxygenation reaction.