cssi/SciSciGPT-SciSciNet huggingface dataset:
Chapter 1 – Drug Discovery and Development: An Overview of Modern Methods and Principles

The identification of novel therapeutics is a long and complex process that involves a wide range of scientific disciplines and techniques. This process can be divided into two distinct phases. The discovery phase includes target selection as well as the identification of potential lead compounds using high throughput screening and/or in silico screening methods. Lead optimization eventually produces a clinical candidate. The second phase, also referred to as the development phase, is focused on determining the clinical utility of a candidate compound in patients. Clinical trials designed to determine the safety and efficacy of candidate compounds provide data to support regulatory approval. This chapter provides an overview of the process as a means of introducing the major topics covered in the remainder of the text.
When Was the Last Time You Were Restrained by a Prince? Conservatism and the Development of Maritime Law

This chapter examines how some concepts and contractual terms used by maritime law tend to lag far behind what is actually going on in maritime practice. The stubborn persistence of the 1946 version of the New York Produce Exchange time charter form, provides just one example among many. Sometimes—often—international instruments of maritime law have been created with wholly admirable precision to meet modern commercial needs, but have moved far ahead of maritime practice, proving incapable of moving national laws or commercial usage along with them. Sometimes, familiar and widely-used legal terms continue to deal with issues that have long ceased to be of relevance in maritime practice. In short, the idea that maritime law moves smoothly in lockstep with the needs of maritime commerce is an illusion. Very often, maritime law either moves on its own, or it does not move at all. The examples in this chapter are widely disparate in character, but they have one thing in common: they are examples of maritime law at distant odds from maritime practice.
Charge-Driven Phase Separation of RNA and Proteins without Disorder

ABSTRACT Phase separation of globular RNA and positively charged proteins is reported from a combination of coarse-grained simulations parametrized based on atomistic simulations, theory informed by the coarse-grained simulations, and experimental validation via confocal microscopy and FRET spectroscopy. Phase separation is found to depend on concentration, size, and charge of the proteins, requiring a minimum protein size, minimum protein charge, and minimum protein concentration before condensates can form. The general principle for phase separation is based on electrostatic complementarity rather than invoking polymer character as in most previous studies. Simulation results furthermore suggest that such phase separation may occur in heterogenous cellular environment, not just between tRNA and cellular proteins but also between ribosomes and proteins where there may be competition for positively charged proteins. STATEMENT OF SIGNIFICANCE Liquid-liquid phase separation has been recognized as a key mechanism for forming membrane-less organelles in cells. Commonly discussed mechanisms invoke a role of disordered peptides and specific multi-valent interactions. We report here phase separation of RNA and proteins based on a more universal principle of charge complementarity that does not require disorder or specific interactions. The findings are supported by coarse-grained simulations, theory, and experimental validation via microscopy and FRET spectroscopy. The implications of this work are that condensate formation may be an even more universal phenomenon in biological systems than thought to date.
4.9 – Autonomic Nervous System

Publisher Summary This chapter describes the autonomic nervous system (ANS). The ANS is divided into three divisions that include the sympathetic, parasympathetic, and enteric. The sympathetic division regulates the use of metabolic resources and coordinating the emergency response of the body to potentially life-threatening situations. The parasympathetic division usually presides over the restoration of metabolic reserves and the elimination of wastes. The sympathetic nervous system consists of nuclei in the brain stem that connects to preganglionic neurons in the interomedial gray in the spinal cord. The preganglionic fibers exiting the cord through the ventral root reach the paravertebral ganglia over the white rami communicans. The paravertebral ganglia form a sympathetic chain on each side of the cord. Preganglionic fibers synapse with neurons in the paravertebral ganglion at the same level of the cord, ascend the chain to make synapses above, descend the chain to make synapses below, or travel through the ganglion to prevertebral ganglia. The receptors at the preganglionic parasympathetic synapse are nicotinic and those at the postganglionic synapse are muscarinic. The pupillary light reflex involves special retinal cells that sense light but do not contribute to image formation. It is found that these intrinsically photosensitive retinal ganglion cells use a different chromophore—melanopsin—to detect light.
Follow, select and assemble method FSAM for VE and re assembly.

ABSTRACT We modified the methods by Ballard et al. [1]. They sought to study eye-hand coordination strategies and created both a real world and a virtual model copying task consisting of three different areas: model, source, and workspace. Participants followed a pickup and place exercise and used a mouse to control stimuli presented on a computer monitor in the virtual task. We also considered the method presented by Hayhoe et al. [2] and Aivar et al. [3] who designed a similar model copying task in a 3D virtual environment. Stimuli were displayed in a head mounted display and participants held a motion sensor to select and move virtual objects in 3D space. Moreover, Aivar et al. [3] also included extra assembly pieces and a variation in the position of the assembly pieces located in the resource area. • It proposes an assembly task designed at a 1:1 scale for two environments, real and virtual environments. • It introduces a reading sequence for the model that is being replicated and it also introduces distractor assembly blocks with similar colors and shapes as the required assembly blocks, and a change in the location for all assembly blocks in the resource area. • It modifies the interaction for the VR environment by using hand gestures to select, move and position virtual assembly blocks. This was possible by incorporating a LEAP® motion controller which although it does not provide haptic feedback, it provides a virtual representation of the participant's hand. Our VE also includes visual and auditory feedback to guide depth perception and virtual control. The software used for this research study is available at: http://virtualete.com/research/fsam.php
Maternal, paternal, and other caregivers' stimulation in low- and- middle-income countries

Background and objectives Globally, studies have shown associations between maternal stimulation and early child development. Yet, little is known about the prevalence of paternal and other caregivers' stimulation practices, particularly in low- and- middle-income countries (LMICs). Methods Data from the Multiple Indicators Cluster Survey (MICS) and the Demographic and Health Survey (DHS) were combined across 62 LMICs (2010-2018). The sample included 205,150 mothers of children aged 3 and 4 years. High levels of stimulation were defined as caregiver engagement in at least 4 out of 6 possible activities with the child. The proportion of mothers, fathers, and other caregivers providing high levels of stimulation was calculated by country, region, and for the whole sample. Socioeconomic disparities within and between countries were estimated. Results On average, 39.8% (95% CI 37.4 to 42.2) of mothers, 11.9% (95% CI 10.1 to 13.8) of fathers, and 20.7% (95% CI 18.4 to 23.0) of other adult caregivers provided high levels of stimulation. Stimulation varied by region, country income group, and Human Development Index (HDI), with higher levels of maternal and paternal-but not other caregivers'-stimulation in high-income and high-HDI countries. Within countries, stimulation levels were, on average, lower in the poorest relative to the richest households, and some but not all countries exhibited differences by child sex (i.e., boys vs. girls) or area (i.e., urban vs. rural). Conclusions Results suggest a need for intervention efforts that focus on increasing caregiver stimulation in LMICs, particularly for fathers and in low-income contexts.
China’s ‘Silk Road’ Public Diplomacy in Central Asia: Rethinking the ‘Network’ Approach to the Study of Public Diplomacy and Its Instrumentalism

This chapter shows how the Chinese government’s foreign policy agenda offers opportunities and benefits to public and cultural actors in Central Asia through the ‘Silk Road’ initiative. It begins by contextualizing the ‘Silk Road’ public diplomacy strategy in terms of the general debates on soft power and the public diplomacy of the People’s Republic of China (PRC). It analyzes the conceptual framework for studying people-to-people exchange and the involvement of local actors and notes that the Chinese state and its policies are mostly studied as imposed, top-down, and thus inauthentic initiatives. The chapter then uses the ‘network approach’ to public diplomacy (Hocking 2005) as well as debates on the instrumentalism of cultural policy (Nisbett 2013) to introduce a new perspective into the debate. The approach is illustrated using examples of dynamics within the academic and cultural networks in the major cities of Almaty (in Kazakhstan) and Tashkent (in Uzbekistan). In the conclusion, the chapter suggests adopting insights from transnationalism to study public diplomacy and, specifically, explores how the scope of the study of the ‘new public diplomacy’ might be theoretically broadened in the future. The chapter argues that public diplomacy not only needs a ‘new’ name or perception, but also needs to step outside of critical or applied approaches and to change units of reference and analysis that are not dependent only on ‘China’ (or the nation-state) and the idea of monocentric distribution of power, interests, and resources.
TENSILE PROPERTIES OF CHEMICALLY GROUTED SAND.

Although the tensile properties (strength, stiffness, failure strain, and mode of failure) of grouted soils are important in many soil-structure interaction problems, little effort has been directed toward identifying and quantifying the mechanisms responsible for the manifested behavior. In this study chemically grouted sand is considered as a two-phase particulate composite, and the tensile properties are examined at both the particulate and the composite levels. Both the adhesive and cohesive properties of the grout are seen to influence the behavior of grouted sand, and an experimental program was conducted to quantify particular relationships for each. These data, together with the porosity of the sand, are employed to formulate two strength models for predicting the tensile behavior of a grouted sand from a knowledge of the properties of the constituents. Comparisons are made between the tensile and compressive properties of grout and grouted sand, and the development of cracks within the specimen is offered as an explanation for the observed nonlinearity in the stress-strain response when either grouted sand or pure grout cured for more than about 2 weeks is tested in compression.
Change Is the Only Constant: Beginning Teacher Perceptions of Implementing the Common Core State Standards

This study explored the relationship between implementing the CCSS and beginning teacher attrition. This study is important for three related reasons: a) mandated reform has been linked to professional vulnerability (Day et al., 2005), b) vulnerability has been linked to diminished self-efficacy (Lasky, 2005), and c) diminished self-efficacy has been linked to teacher attrition ( Skaalvik & Skaalvik, 2007) . Semi-structured interviews with 3 elementary beginning teachers were analyzed to uncover key themes. Our participants said the change experienced was overwhelming. Findings may help policy-makers and teacher-leaders understand beginning teachers' experiences implementing reform in order to diminish rampant beginning teacher attrition.
Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System

ABSTRACT Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients. In vivo , the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection. IMPORTANCE Mumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV.
Liver transplantation in the management of fulminant hepatic failure

Abstract Liver transplantation is now performed for the treatment of fulminant hepatic failure, but the selection of patients for this procedure has been incompletely described. We used worsening hepatic encephalopathy, clinical evidence of brain edema, and prolongation of the prothrombin time after 24–48 h of intensive medical treatment as key factors influencing the decision to recommend liver transplantation. Thirty-seven patients (29 adult, 8 pediatric) were admitted with fulminant hepatic failure. Ten improved with medical treatment, so liver transplantation was not recommended. Twentyseven deteriorated despite medical treatment. Eight of these, 7 with grade 4 hepatic encephalopathy and persistent coagulopathy, did not receive transplantation because of contraindications (n = 5), failure to find a donor (n = 1), or refusal of therapy (n = 2). None of these survived. Sixteen of the other 19 patients developed grade 4 hepatic encephalopathy, 5 had brain edema, and all had persistent coagulopathy, so liver transplantation was performed. One year actuarial survival was 58%. This retrospective analysis confirms that survival exceeding 50% can be obtained with liver transplantation in patients with fulminant hepatic failure. Additional studies of prognostic markers are needed to define the role of liver transplantation in the management of this disease.
Professional development processes that promote teacher change: the case of a video-based program focused on leveraging students’ mathematical errors

This study examined processes at the core of teacher professional development (PD) experiences that might positively impact teacher learning and more specifically teacher change. Four processes were considered in the context of a PD program focused on student mathematical errors: analysis of students’ mathematical misconceptions as a lever for changing practice; review and discussion of images of existing and innovative teaching practices; video-enhanced reflection and detailing of new practices; and cycles of examination/implementation and feedback/revision. Participants were four US elementary school teachers, whose engagement in the PD program was studied through video observations and interviews. Findings revealed several positive shifts in teachers’ interests and classroom practices. Challenges involved teacher content knowledge and counteracting cultural beliefs and practices on the role of errors in learning. The conclusions discuss implications for PD scale-up.
100G technology development for optical transport networks

Technology development leading to 100G deployment today is reviewed. The benefits of 100G technologies to optical transport network are summarized. Technologies for future transport channel designs with a channel speed beyond 100G are speculated.
Maternal Dietary Protein Deficiency Decreases Nitric Oxide Synthase and Ornithine Decarboxylase Activities in Placenta and Endometrium of Pigs During Early Gestation

Little is known about the mechanism responsible for retarded placental and fetal growth induced by maternal dietary protein malnutrition. On the basis of the recent finding that nitric oxide (NO) and polyamines (products of L-arginine) play an important role in embryonic and placental development, the present study was designed to determine whether protein deficiency decreases placental and endometrial activities of NO synthase (NOS) and ornithine decarboxylase (ODC) (the first and key regulatory enzyme in polyamine synthesis). Primiparous gilts selected genetically for low or high plasma total cholesterol concentrations (low line and high line, respectively) were mated and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5% crude protein. At d 40 or 60 of gestation, they were hysterectomized, and placenta and endometrium were obtained for incubations, NOS and ODC assays, and measurements of free amino acids and polyamines. Maternal dietary protein restriction decreased arginine and ornithine concentrations, constitutive and inducible NOS activities and NO production, as well as ODC activity and polyamine concentrations in placenta and endometrium of both lines of gilts. Placental NO synthase activity and NO generation were lower in high line gilts than in low line gilts. ODC activities and polyamine concentrations in placenta and endometrium were decreased at d 60 compared with d 40 of gestation. These changes in placental and endometrial synthesis of NO and polyamines during early gestation may be a mechanism responsible for reduced placental and fetal growth in protein-deficient gilts and for altered conceptus development in high line gilts.
Jackup Rig Weight Algorithm

Weight is an important design factor and a primary feature in determining the physical characteristics of a rig. In the marine construction industry, lightship displacements are widely reported, but in jackup construction, designers protect information on the weight of the vessel because weights are an indicator of the design and strength of a rig’s legs which is an important distinguishing feature among designs. Methods for predicting ship weight based on physical attributes have been used for decades, but given the structural differences between jackups and ships, these techniques do not adequately predict rig weight. In this chapter we present an empirically derived lightship displacement function useful for first-order estimates.
Rates and Predictors of Invalid Baseline Test Performance in High School and Collegiate Athletes for 3 Computerized Neurocognitive Tests ANAM, Axon Sports, and ImPACT

Background:Preseason baseline testing using computerized neurocognitive tests (CNTs) is increasingly performed on athletes. Adequate effort is critical to establish valid estimates of ability, but many users do not evaluate performance validity, and the conditions that affect validity are not well understood across the available CNTs.Purpose:To examine the rates and predictors of invalid baseline performance for 3 popular CNTs: Automated Neuropsychological Assessment Metrics (ANAM), Axon Sports, and Immediate Post-Concussion and Cognitive Testing (ImPACT).Study Design:Controlled laboratory study.Methods:High school and collegiate athletes (N = 2063) completed 2 of 3 CNTs each during preseason evaluations. All possible pairings were present across the sample, and the order of administration was randomized. Examiners provided 1-on-1, scripted pretest instructions, emphasizing the importance of good effort. Profile validity was determined by the manufacturers’ standard criteria.Results:The overall percentage...
POLYMORPHIC SITES AND THE MECHANISM OF EVOLUTION IN HUMAN MITOCHONDRIAL DNA

Twelve restriction enzymes were used to screen for the presence or absence of cleavage sites at 441 locations in the mitochondrial DNA of 112 humans from four continents. Cleavage maps were constructed by comparison of DNA fragment sizes with those expected from the published sequence for one human mtDNA. One hundred and sixty-three of the sites were polymorphic, i.e., present in some individuals but absent from others, 278 sites being invariant. These polymorphisms probably result from single base substitutions and occur in all functional regions of the genome.—In 77 cases, it was possible to specify the exact nature and location (within a restriction site) of the mutation responsible for the absence of a restriction site in a known human mtDNA sequence and its presence in another human mtDNA. Fifty-two of these 77 gain mutations occur in genes coding for proteins, 34 being silent and 18 causing amino acid replacements; moreover, nine of the replacements are radical.—Notable also is the anomalous ratio of transitions to transversions required to account for these 77 restriction site differences between the known human mtDNA sequences and other human mtDNAs. This ratio is lower for most groups of restriction sites than has been reported from sequence comparisons of limited parts of the mtDNA genome in closely related mammals, perhaps indicating a special functional role or sensitivity to mutagenesis for palindromic regions containing high levels of guanine and cytosine.—From the genomic distribution of the 163 polymorphic sites, it is inferred that the level of point mutational variability in tRNA and rRNA genes is nearly as high as in protein-coding genes but lower than in noncoding mtDNA. Thus, the functional constraints operating on components of the protein-synthetic apparatus may be lower for mitochondria than for other systems. Furthermore, the mitochondrial genes for tRNAs that recognize four codons are more variable than those recognizing only two codons.—Among the more variable of the human mitochondrial genes coding for proteins is that for subunit 2 of cytochrome oxidase; this polypeptide appears to have been evolving about five times faster in primates than in other mammals. Cytochrome c, a nuclearly encoded protein that interacts directly with the oxidase 2 subunit in electron transport, has also evolved faster in primates than in rodents or ungulates. This example, along with that for the mitochondrial rRNA genes and the nuclear genes coding for mitochondrial ribosomal proteins, provides evidence for coevolution between specific nuclear and mitochondrial genes.
An Alternative Tropical Cyclone Intensity Forecast Verification Technique

Abstract The National Hurricane Center (NHC) does not verify official or model forecasts if those forecasts call for a tropical cyclone to dissipate or if the real tropical cyclone dissipates. A new technique in which these forecasts are included in a contingency table with all other forecasts is presented. Skill scores and probabilities are calculated. Forecast verifications with the currently used technique have shown a slight improvement in intensity forecasts. The new technique, taking into account all forecasts, suggests that the probability of a forecast having a large (>30 kt) error is decreasing, and the likelihood of the error being less than about 10 kt is increasing in time, at all forecast lead times except 12 h when the forecasts are already quite good.
Size Invariance of Polyelectrolyte Dendrimers

To quantify the swelling response of polyelectrolyte dendrimers in aqueous solutions as affected by changes in solution conditions, we have studied eighth generation, G8, poly(amidoamine) (PAMAM) d...
Finite element formulation of exact non‐reflecting boundary conditions for the time‐dependent wave equation

A modi ed version of an exact Non-re ecting Boundary Condition (NRBC) rst derived by Grote and Keller is implemented in a nite element formulation for the scalar wave equation. The NRBC annihilate the rst N wave harmonics on a spherical truncation boundary, and may be viewed as an extension of the secondorder local boundary condition derived by Bayliss and Turkel. Two alternative nite element formulations are given. In the rst, the boundary operator is implemented directly as a ‘natural’ boundary condition in the weak form of the initial–boundary value problem. In the second, the operator is implemented indirectly by introducing auxiliary variables on the truncation boundary. Several versions of implicit and explicit timeintegration schemes are presented for solution of the nite element semidiscrete equations concurrently with the rst-order di erential equations associated with the NRBC and an auxiliary variable. Numerical studies are performed to assess the accuracy and convergence properties of the NRBC when implemented in the nite element method. The results demonstrate that the nite element formulation of the (modi ed) NRBC is remarkably robust, and highly accurate. Copyright ? 1999 John Wiley & Sons, Ltd.
Examining the link between prevalence of severe early childhood caries and self-reported oral health and quality of life outcomes

(60.6 vs. 49.6%), multiples (6.1 vs. 2.1%), prematurely born (67.7 vs. 11.7%), weighed less than 2500 grams (71.2 vs. 12.0%), were born in a breech position (26.1 vs. 3.5%), and were delivered by caesarean section (26.5 vs. 18.7%). Their mothers were more often younger than 20 years and 35 years and older [OR1⁄41.8], more often had a Maroon, Creole or Indigenous ethnicity [OR’s respectively 1.3, 2.1, 2.5], and were less often Hindustani [OR1⁄40.8] or Javanese [OR1⁄40.3]. Low birth weight, premature birth and a breech position were independently associated with a 6.6, 4.9 and 3.8 times increased risk of neonatal death, respectively. In addition, most babies (74%) died in the early neonatal period and within 24 hours after birth (34%), due to respiratory insufficiency as a result of infant respiratory distress syndrome (IRDS), which accounted for 53% of deaths, followed by sepsis/infection (24%) and congenital malformations (19%). Interpretation: Neonatal mortality in Suriname is high compared with more developed countries (5&) but is comparable with other countries in the Caribbean region (19&). Early neonatal death accounts for a large proportion of neonatal mortality in the multi-ethnic society of Suriname. Two-thirds of these infants are born prematurely and the timing of death is often in the first 24 hours after birth. More than half of the newborns died as a result of respiratory insufficiency. It is imperative that further measures are taken to reduce neonatal mortality. The initiation of a national neonatal intensive care unit would be a major step forward to achieve this goal. Funding: Ministry of Health Suriname and TNO Netherlands Organization for Applied Scientific Research. Abstract #: 01SEDH037
A Cell for X-Ray Examination of Compounds Requiring a Special Atmosphere

Several techniques have been previously described for the x-ray examination of compounds that cannot be exposed to the atmosphere. However, most of these devises are unsuitable for a geiger type x-ray diffraction spectrometer, and their usefulness is limited to equipment utilizing cameras. A very convenient and inexpensive sealed sample holder, which is described in this paper, is based upon the large specimen area available in a focusing camera and geiger type spectrometer, and which can be successfully employed to either prevent sample exposure to the atmosphere or provide a special atmosphere to the sample for chemical studies.
Dark solitary waves in optical fibers.

It is argued that the form of dark solitary wave solution [∼tanh p(z − υgt)] previously predicted is highly questionable because the radial dependence of the field was not properly treated. In this Letter a previously developed method for exactly treating the radial dependence of the field is extended to dark-pulse wave solutions, and a new class of solutions is presented that exists in the anomalous dispersion region of the fiber. The average intensity for these solutions exhibits a double hump, in contrast to the single hump associated with the bright-pulse wave.
Oversulfated dermatan sulfate extracted from Hurler spleen.

Abstract Oversulfated dermatan sulfate has been found in an aqueous extract of Hurler spleen. It is possible that the deficiency of the protein moiety of the glycosaminoglycan complexes in this disease may allow oversulfation of the carbohydrate polymer, thus contributing to its deposition in various organs.
Teaching the imitation and spontaneous use of descriptive gestures in young children with autism using a naturalistic behavioral intervention.

Children with autism exhibit deficits in the imitation and spontaneous use of descriptive gestures. Reciprocal Imitation Training (RIT), a naturalistic imitation intervention, has ben shown to increase object imitation skills in young children with autism. A single-subject, multiple-baseline design acroess five young children with autism was used to determine whether RIT could be adapted to target the imitation of descriptive gestures. All participants increased their imitation of gestures in the treatment setting and on a structured imitation assessment. Gains generalized to a novel therapist, setting, and materials and maintained at a 1-month follow-up. Three participants also increased their spontaneous use of descriptive gestures. These results provide support for the effectiveness of a naturalistic intervention for teaching gesture imitation.
“Hooked on” Prescription-Type Opiates Prior to Using Heroin: Results from a Survey of Syringe Exchange Clients

The availability and diversion of prescription-type opioids increased dramatically in the first decade of the twenty-first century. One possible consequence of increased prescription opioid use and accessibility is the associated rise in opioid dependence, potentially resulting in heroin addiction. This study aimed to determine how common initial dependence on prescription-type opioids is among heroin injectors; associations with demographic and drug-using characteristics were also examined. Interview data were collected at syringe exchanges in King County, Washington in 2009. Among the respondents who had used heroin in the prior four months, 39% reported being "hooked on" prescription-type opioids first. Regression analysis indicated that younger age, sedative use and no recent crack use were independently associated with self-report of being hooked on prescription-type opioids prior to using heroin. These data quantify the phenomenon of being hooked on prescription-type opioids prior to initiating heroin use. Further research is needed to characterize the epidemiology, etiology and trajectory of prescription-type opioid and heroin use in the context of continuing widespread availability of prescription-type opioids.
Trauma to the ankylotic spine: imaging spectrum of vertebral and soft tissue injuries

The objectives of the study were to review the clinical entities that can cause ankylosis of the spine and to illustrate the spectrum of traumatic injury patterns. Ankylosing spondylitis, diffuse idiopathic systemic hyperostosis, degenerative spondyloarthropathy, and spinal canal stenosis can render the spine susceptible to trivial trauma. Multidetector computed tomography and magnetic resonance imaging can accurately diagnose vertebral and soft tissue traumatic injury patterns in this patient population.
Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation.

Abstract The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H2O2) and its biologic significance are unclear. We found that the addition of increasing concentrations of H2O2 progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivatuion of XO by H2O2 was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H2O2 was accompanied by prodcction of hydroxyl radical (·OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H2O2 to deflavo XO dit not produce ·OH. Inactivation of XO by H2O2 was decreased by simultaneous addition of the ·OH scavenger, DMSO. However, inactivation of XO by H2O2 and formation of ·OH were not decreased following addition of the metal chelator, DETAPAC, and/or the O2 scavenger, superoxide dismutase. The results suggest that inactivation of XO by H2O2 occurs by production of ·OH following direct reduction of H2O2 by XO at the flavian site.
Ultrafast folding of a computationally designed Trp-cage mutant: Trp2-cage.

Miniproteins provide useful model systems for understanding the principles of protein folding and design. These proteins also serve as useful test cases for theories of protein folding, and their small size and ultrafast folding kinetics put them in a regime of size and time scales that is now becoming accessible to molecular dynamics simulations. Previous estimates have suggested the “speed limit” for folding is on the order of 1 μs. Here a computationally designed mutant of the 20-residue Trp-cage miniprotein, Trp2-cage, is presented. The Trp2-cage has greater stability than the parent and folds on the ultrafast time scale of 1 μs at room temperature, as determined from infrared temperature-jump experiments.
CONCUR: A language for continuous, concurrent processes

Hendrix's robot modeling system presented a simulation method in which time is represented as a continuous phenomenon. This paper introduces the language CONCUR, which realizes Hendrix's concept through an extension of the LISP environment. CONCUR uses generalized procedures (scenarios) operating in a data-driven mode to implement Hendrix's events. The heart of CONCUR is a generalized pattern-matcher which permits operators within the patterns to bind variables and modify the match process. We include several detailed examples in addition to an implementation of the pattern matcher.
Congruences on ω n -Bisimple Semigroups

Let S be a bisimple semigroup and let E s denote its set of idempotents. We may partially order E s in the following manner: if e , f ∈ E s , e ≧ f if and only if ef = fe = e . We then say that E s is under or assumes its natural order. Let I 0 denote the non-negative integers and let n denote a natural number. If E s , under its natural order, isomorphic to ( I 0 ) n under the reverse of the usual lexicographic order, we call S an ω n -bisimple semigroup. (See [9] for an explanation of notation.) We determined the structure of ω n -bisimple semigroups completely mod groups in [9]. The ω n -bisimple semigroups, the I -bisimple semigroups [8], and the ω n I -bisimple semigroups [9] are classes of simple semigroups except completely simple semigroups whose structure has been determined mod groups.
Impact of Manufacturing System Configuration on Performance

Manufacturing systems can be designed in many configurations. Different configurations have profound impact on the performance of the system in terms of reliability and productivity, product quality, capacity scalability, and cost. This paper analyzes these performance measures for different system configurations assuming known machine level reliability and process capability.
A Fresh Look at Discordant Redshift Galaxies in Compact Groups

We reexamine the statistics of discordant redshift galaxies in compact groups. We find that 43 out of 100 groups in the Hickson catalog contain at least one discordant redshift galaxy. We show that, despite the prevailing impression, all previous attempts have failed to explain this large number of discordant redshift galaxies. The order of magnitude excess survives all of our attempts to refine the sample.
Albedo Feedback, the Meridional Structure of the Effective Heat Diffusivity, and Climatic Sensitivity: Results from Dynamic and Diffusive Models

Abstract The sensitivity of a two-level primitive equation atmospheric model to solar constant perturbations is examined in the presence of surface albedo feedback. The model is simplified to the point that a large number of numerical experiments can be performed and statistically steady states defined with relative case. Exceptionally sensitive equilibrium states are found that are unrelated to the large and small ice-cap instabilities obtained in the simplest diffusive energy balance models. Similar results are produced in a two-level diffusive model closely patterned after the dynamic model, and in a more highly idealized one-level model, by choosing a diffusivity with pronounced meridional structure resembling that of the effective diffusivity of the dynamic model. Sensitive states occur in the diffusive models when the albedo gradient enters the region equatorward of 60° in which the effective heat diffusivity of the atmosphere increases with increasing latitude.
A case study of internal wave-wave interaction patterns shown in the satellite images in the Mid-Atlantic Bight

Many internal wave-wave interaction patterns have been observed both in satellite radar and optical images, however, very few studies have been made on characteristics of interaction patterns such as phase shifts and the amplitude change in the interaction center. In this paper, two clear oblique interaction patterns are respectively observed in a RADARSAT-1 synthetic aperture radar (SAR) image and a SPOT-2 optical image in the Mid-Atlantic Bight. A two-soliton solution based on the Kadomtsev-Petviashvili equation is used to simulate the two patterns. We find that one pattern fits the interaction with negative phase shift resulting in an amplitude increase in the interaction center; the other fits with positive phase shift resulting in an amplitude decrease in the interaction center.
Models for Hardware-Software System Operational-Performance Evaluation

Stochastic models for hardware-software systems are developed and used to study their performance as a function of hardware-software failure and maintenance rates. Expressions are derived for the distribution of time to a specified number of software errors, system occupancy probabilities, system reliability, availability, and average availability. The behavior of these measures is investigated via numerical examples.
Fuzzy classification with an artificial chemical process

In this work, a new algorithm to extract a compact set of if/then rules from data for classification problems is presented. The premise is extracted directly using LARES as a learning tool, which is a new global optimization procedure based on a new recently introduced paradigm called artificial chemical process. The conclusion part is determined using soft computing techniques. In the learning phase, the objective function minimizes the number of misclassified patterns from training data and reduces the conflicts between the rules to generate the pattern partition. The proposed method has many potential applications in industrial processes. Several examples are presented, including fault detection and operation of reactions with unstable regimes.
Grammar: the barest essentials.

It is useful to consider the concept of grammar as primary and that of language as derived.
"Why wasn't Lorentz Einstein?" An Examination of the Scientific Method of H. A. Lorentz

People do not realize how great was the influence of Lorentz on the development of modern physics. We cannot imagine how it would have gone had not Lorentz made so many greut contributions. The physicist of the present generation regards the point of view achieved by Lorentz as the only possible one; at the time, however, it was a surprising and audacious step, without which the later development would not have been possible.
Laryngeal muscle activity during stuttering

Laryngeal muscle activity during fluent and stuttered utterances was investigated via electromyography. Analysis revealed that stuttering was accompanied by high levels of laryngeal muscle activity and disruption of normal reciprocity between abductor and adductor muscle groups. Results are interpreted as demonstrating the existence of a laryngeal component in stuttering and showing a strong correlation between abnormal laryngeal muscle activity and moments of stuttering.
Nonsurgical Recovery of Uterine Embryos in the Baboon

A nonsurgical technique is described for the recovery of baboon eggs using an Isaacs endometrial cell sampler modified for continuous medium flow. After gentle insertion of the catheter through the undilated cervix, 10 ml of warm medium is injected at the rate of 1 to 2 mI/mm and collected into a 15 ml tube. Thirty.seven eggs have been recovered from 80 flushes (46%) on 33 baboons. The recovery rate has increased with additional experience; 23 eggs have been obtained from the last 40 flushes (57.5%) compared with 14 from the first 40 (35%). Eggs have been recovered from five successive flushes in one animal, and 18 eggs have been recovered from 24 flushes (75%) on four animals. Successful recoveries were performed 0 to 6 days after sex skin detumescence, indicating that the unfertilized baboon egg does not degenerate immediately after entering the uterus. Twenty-one eggs have been recovered from flushes during 44 mated cycles (48%) on 21 animals, and of these 14 (67%) were fertilized. Developmental stages of recovered embryos ranged from 4-cell to expanding blastocyst.
Effect of hemicholinium no. 3 on amphibian nerve.

Abstract The effect of hemicholinium No. 3 (HC-3) on the amplitude of action potentials recorded from partially stripped frog sciatic nerves has been studied. Stimulation and recordings were carried out in nerve chambers to which various concentrations of HC-3 could be added (10 −3 –10 −5 m ). The stimulating pulse was a square wave, supermaximal for all fibers and delivered to the nerve at various frequencies (0,10,30 cycle/sec). When compared to a control Ringer's solution, HC-3 was found to markedly depress the amplitude of the action potential with the effect being both concentration and frequency dependent. Choline, when added in varying concentrations (10 −3 –10 −5 m ) to the HC-3 solution, reduced the effect of HC-3 in a manner suggestive of competitive interactions. Choline at ten times the HC-3 concentration maintained the response of the nerve within control limits. Based on the concept that HC-3 interferes with cholinergic transmission, these data could be interpreted as indicating the involvement of acetylcholine in nerve conduction. If, however, as the current hypothesis suggests, HC-3 exerts its effect by competing with the transport of choline, one cannot exclude the possibility that cations other than choline are similarly affected.
Singular initial data and uniform global bounds for the hyper-viscous Navier–Stokes equation with periodic boundary conditions

Abstract In the hyper-viscous Navier–Stokes equations of incompressible flow, the operator A=−Δ is replaced by Aα,a,b≡aAα+bA for real numbers α,a,b with α⩾1 and b⩾0. We treat here the case a>0 and equip A (and hence Aα,a,b) with periodic boundary conditions over a rectangular solid Ω⊂R n . For initial data in L p (Ω) with α⩾n/(2p)+1/2 we establish local existence and uniqueness of strong solutions, generalizing a result of Giga/Miyakawa for α=1 and b=0. Specializing to the case p=2, which holds a particular physical relevance in terms of the total energy of the system, it is somewhat interesting to note that the condition α⩾n/4+1/2 is sufficient also to establish global existence of these unique regular solutions and uniform higher-order bounds. For the borderline case α=n/4+1/2 we generalize standard existing (for n=3) “folklore” results and use energy techniques and Gronwall's inequality to obtain first a time-dependent Hα-bound, and then convert to a time-independent global exponential Hα-bound. This is to be expected, given that uniform bounds already exist for n=2,α=1 ([6, pp. 78–79]), and the folklore bounds already suggest that the α⩾n/4+1/2 cases for n⩾3 should behave as well as the n=2 case. What is slightly less expected is that the n⩾3 cases are easier to prove and give better bounds, e.g. the uniform bound for n⩾3 depends on the square of the data in the exponential rather than the fourth power for n=2. More significantly, for α>n/4+1/2 we use our own entirely semigroup techniques to obtain uniform global bounds which bootstrap directly from the uniform L2-estimate and are algebraic in terms of the uniform L2-bounds on the initial and forcing data. The integer powers on the square of the data increase without bound as α↓n/4+1/2, thus “anticipating” the exponential bound in the borderline case α=n/4+1/2. We prove our results for the case a=1 and b=0; the general case with a>0 and b⩾0 can be recovered by using norm-equivalence. We note that the hyperviscous Navier–Stokes equations have both physical and numerical application.
Effects of Kelthane and temperature on the respiration of Crangon franciscorum

Abstract 1. The effects of temperature and the chlorinated hydrocarbon pesticide Kelthane on the respiration of the adult estuarine shrimp Crangon franciscorum , Stimpson were determined. 2. C. franciscorum respiration was determined after 48 hr of acclimation and 96 hr of exposure to six Kelthane concentrations (843, 475, 208, 130, 89 and 0 μg/l) at each of three temperatures (16.0°C, 19.0°C and 23.8°C). 3. C. franciscorum is a partial metabolic regulator over the temperature range tested. 4. All Kelthane exposure levels depressed oxygen consumption below control rates.
Blood and tissue concentrations of Bisantrene measured by a simple fluorometric assay

We have developed a simple sensitive fluorometric assay for the measurement of total Bisantrene in plasma, red blood cells, and tissues to facilitate preclinical and clinical pharmacologic assessment of this active anticancer agent. The assay was used to measure the plasma disappearance and tissue concentrations of Bisantrene in the rabbit. Results are comparable to those reported with HPLC assays and with measurement of radioactivity in combusted tissue following IV administration of radiolabeled Bisantrene. We demonstrated that when a plasma concentration of approximately 50 μg/ml is not exceeded, Bisantrene remains in solution at that concentration. If Bisantrene is introduced into plasma at a concentration exceeding 50 μg/ml, precipitation of the drug is initiated and continues until the plasma concentration is no greater than 15 μg/ml. This finding supports our previous recommendation that in clinical trials Bisantrene should be administered at low concentrations over prolonged periods of time to maximize the bioavailability of the drug by minimizing precipitation of the drug in plasma.