cssi/SciSciGPT-SciSciNet huggingface dataset:
Monoclonal antibody therapeutics: Leading companies to maximise sales and market share

A close look at the biology and pharmacology of monoclonal antibodies reveals both their continuing promise as therapeutic agents to address unmet medical needs, as well as a number of challenges to the future discovery and development of this unique class of biologics. A remarkably consistent experience of reliable clinical efficacy and safety ensures that Biotech and Pharma have strong incentives to accelerate the antibody drug discovery process. Their attractive commercial potential invites consideration of potential challenges to the future expansion of the monoclonal antibody drug market. Four challenges arise from scientific and technical aspects of the antibody drug format: drug target limitations, biodistribution limitations, species specificity issues, and limitations to the route of administration and four challenges are based in the commercial and clinical use of antibody drugs: cost of goods, product differentiation within the antibody market, competition from small molecule drugs, and price sensitivity of clinical acceptance. Despite these challenges and recent setbacks, such as the withdrawal and subsequent relaunch of Tysabri and the TGN1412 Phase I disaster, the prevailing opinion is that monoclonal antibodies will continue to be safe and effective medicines that are worthy of commercialisation.
A poisson-gamma model for two-stage cluster sampling data

We propose a model for count data from two-stage cluster sampling, where observations within each cluster are subjected simultaneously to internal influences and external factors at the cluster level. This model can be seen as a two-stage hierarchical model with local and global predictors. This parameter-driven model causes the counts within a cluster to share a common latent factor and to be correlated. Maximum likelihood (ml) estimation based on an EM algorithm for the model is discussed. Simulation study is carried out to assess the benefit of using ml estimates compared to a standard Poisson regression analysis that ignores the within cluster correlation.
A Predominant Role of Acyl-CoA:monoacylglycerol Acyltransferase-2 in Dietary Fat Absorption Implicated by Tissue Distribution, Subcellular Localization, and Up-regulation by High Fat Diet

Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at high levels in human liver, the lower gastrointestinal tract, and the mouse kidney, but the physiological significance of such expression has not yet been studied. Using an affinity-purified antibody, the present study investigated the expression of murine MGAT2 protein along the intestinal tract, determined its subcellular localization, and studied its regulation by diet and in db/db mouse. Results demonstrate a high level of MGAT2 expression in the small intestine in a proximal-to-distal gradient that correlated well with both MGAT enzyme activity and fat absorption pattern. In contrast, MGAT2 protein was not detectable in other sections of the digestive tract, including stomach, cecum, colon, and rectum, or other mouse tissues such as kidney, liver, and adipocytes. Immunohistological studies provided direct evidence that the enzyme is expressed not only in the villi, but also in the crypt regions of the small intestine, which suggests that MGAT2 expression occurs prior to the maturation of enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2-transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by diabetes in the db/db mouse, however, the total intestinal MGAT activity was significantly enhanced. Finally, an up-regulation of both MGAT2 protein expression and MGAT activity was observed in mice fed a high fat diet, implicating a role of MGAT2 in diet-induced obesity. Taken together, our data suggest a predominant role of MGAT2 in dietary fat absorption.
Acute Leukemia Characterized by Trisomy 8 in Down's Syndrome

Summary Of the myeloproliferative disorders which develop in Down's syndrome, acute leukemia associated with trisomy 8 has distinct characteristics. It is non-lymphoblastic in type and has a preleukemic phase in which thrombocytopenia is a prominent feature. One case occurring in a 20 mth-old girl is reported and 3 other similar cases reviewed. Acquired trisomy 8 in Down's syndrome is linked to leukemogenesis and confers non-lymphoblastic differentiation
A Simple Model of Particle Coalescence and Breakup

Abstract A simple model of the evolution of particle size distributions by coalescence and spontaneous and binary disintegrations is formulated. Spontaneous disintegration involves single particles, while coalescence and binary disintegrations involve pairs of particles. Analytical solutions for the mean mass of the distribution and the equilibrium size distribution are obtained for the case of constant collection kernel and disintegration parameters. At equilibrium, the forms of the size distributions are identical under the action of coalescence and either or both disintegration processes; the particle concentration is proportional to the total mass concentration (M) and the mean mass of the distribution is independent of M when only coalescence and binary disintegrations are operative. At small values of M, the effects of spontaneous disintegrations dominate over those of binary disintegrations while the reverse is the case at large values of M. Some of the findings of the present simple model are in q...
A bound for global solutions of semilinear heat equations

We show that global positive solutions of the initial-boundary value problem foru t =Δu+u p are bounded, provided thatp>1 is subcritical. Our bound depends only on sup norm of the initial data and is useful to classify initial data by the asymptotic behavior of the solutions as time tend to infinity.
Hepatitis C viral infection in patients with chronic kidney disease.

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Teaching police ethics: An experiential model

Attempts have been made in recent years to decrease police misconduct and improve police performance in areas of ethical decision-making. One attempt has been to provide ethics instruction to police officers at training academies and in-service training sessions. Experiential case studies have been used to help students apply theoretical concepts to practical situations. An evaluation of the experiential teaching model for police ethics was made in a quasiexperimental research design with two groups of police officers. The results supported the experiential approach for teaching police ethics. Police officers were found to better differentiate between ethical and unethical conduct in both an idealistic and realistic manner.
Physicians' Experiences with Patients Who Transgress Boundaries

BACKGROUND: Boundary violations have been discussed in the literature, but most studies report on physician transgressions of boundaries or sexual transgressions by patients. We studied the incidence of all types of boundary transgressions by patients and physicians’ responses to these transgressions.
God at the bedside

Not long ago, in the oncology clinic where I work, my patient Anna Angelo asked me to pray to God. At the time, prayer was far from the forefront of my mind. Anna (her name has been changed to maintain confidentiality) is a 71-year-old woman from Boston's North End with long-standing cardiac and hepatobiliary disease. Six years ago, breast cancer developed. The tumor was incurable from the time of diagnosis, since it had already spread to bone. The cancer cells tested positive for estrogen and progesterone receptors, and Anna was treated with a series of hormonal agents, which, over the . . .
THE EARLY PHASE OF THYROID HORMONE FORMATION: STUDIES IN TISSUE SLICES1

Sheep thyroid slices were incubated for various periods of time in buffered solutions containing I131. The nature and the distribution of labeled components were determined. The slices accumulated up to 70% of flask I m during 1 hour, but a large fraction of this iodide was not bound to protein as PBI131. Slices were homogenized and PBI131 content of the separated nuclear, mitochondrial, microsomal, and supernatant fractions of the homogenate was determined. No definite evidence of transfer of particulate PBI131 to the soluble fraction of the coll was obtained, although this phenomenon was suggested by some experiments. Labeled MIT and DIT were present in thyroglobulin within 2 minutes after start of incubation, but thyroxine and triiodothyronine were not identified. In most experiments DIT/MIT ratio increased gradually during incubation. The only soluble labeled protein identified was thyroglobulin.
Municipal wastewater contamination in the Southern California Bight. Part II. Cytosolic distribution of contaminants and biochemical effects in fish livers

Abstract The objective of this study was to examine the cytosolic distribution of metals and oxygenated organic metabolites (MTBs), and biochemical effects, in livers of fish collected from both highly contaminated and less contaminated southern California coastal sites. Cytosolic extracts were separated by Sephadex G-75 column chromatography into high molecular weight (> 20 000 daltons) enzyme-containing (ENZ) pools, medium molecular weight (3000–20000 daltons) metallothionein- or metallothionein-like-containing (MT) pools, and low molecular weight ( Concentrations of Cd, Cu and Zn were frequently lower in cytosolic pools of longspine combfish, yellowchin sculpin, and California tonguefish from highly contaminated Palos Verdes (PV) relative to those from less contaminated Santa Monica Bay (SMB) despite much higher concentrations of these metals in sediments at PV. Patterns of cytosolic metal distribution differed more between metals than between species or sampling locations. Most Cd, Cu and Zn occurred in the MT pools of these three species, with the exception of Zn in California tonguefish which occurred predominately in the ENZ pool. In all three species, ENZ-Cu showed positive slopes when regressed against total cytosolic Cu, while ENZ-Cd showed no significant slopes when regressed against total cytosolic Cd. Patterns for Zn were the least consistent among species, with higher ENZ-Zn slopes occurring in fish livers with lower cytosolic Zn concentrations. The largest portion of DDT and PCB oxygenated MTBs occurred in GSH pools of scorpionfish livers from PV or less contaminated Cortes Bank (CB). Concentrations of MTBs in ENZ- and MT-pools of CB scorpionfish livers showed positive slopes when regressed against total cytosolic- and GSH-MTBs. Positive slopes for regressions of ENZ-Cu, -Zn and -MTBs against total cytosolic concentrations are consistent with the model of an equilibrium-dependent exchange of these among cytosolic pools. The lower metal concentrations, higher glutathione concentrations, and higher catalase activities found in fish from PV relative to those from SMB are in accordance with effects known to result from exposure to organic contaminants.
The neuroplastic phenomenon: a physiologic link between chronic pain and learning

Recent advances in the understanding of how the mind works is the result of painstaking research which has isolated tiny regions of the spinal cord and brain, and singular chemical pathways or responses to sole neurotransmitters. The true nature of the central nervous system has eluded investigators because of its fully integrated, constantly changing structure and a symphony of chemical mediators. Each sensation, thought, feeling, movement and social interaction changes the structure and function of the brain. The mere presence of another living organism can have profound effects on the mind and body through imperceptible olfactory stimuli. Neuroplasticity is a general term referring to the ability of neurons to alter their structure and function in response to internal and external stimuli. Although differences occur with aging, this is a lifelong process. Physical and chemical neuroplastic changes occur with learning, memory and chronic pain. Evidence presented supports the notion that chronic pain is a maladaptive learned phenomenon. Further evidence supports that if severe pain is allowed to persist for more than 24 hours, the neuroplastic changes associated with the development of incurable chronic pain syndromes begin to take place. Even after chronic pain is well established, new thought and behavior patterns can be learned, allowing sufferers to restore more adaptive physiologic, cognitive and behavioral patterns.
INTERDEPENDENCE OF RULE-LEARNING AND ATTRIBUTE-LEARNING

Two experiments investigated the relationship between rule-learning and attribute-learning in concept identification. Exp. I yielded evidence that the two processes are interdependent. Thus different rules were apparently learned when different attributes were necessary to the solution. The number of defining attributes Ss used in a conjunction depended on whether size or position was a necessary attribute. This outcome was interpreted as a function of attribute-interaction. Incidental evidence indirectly supported the interpretation by clearly demonstrating a form of attribute-interaction. The findings of Exp. II clarified the preceding results. Ss did not use all the attributes about which they had information in forming rules. Exp. I may thus also have demonstrated the interdependence of rule-utilization and attribute-utilization.
The 26Mg(p, n)26Al reaction and the energy dependence of the spin-isospin effective interaction☆

Abstract Cross section for the 26 Mg(p, n) 26 Al reaction leading to the isobaric analog state and to low-lying 1 + , T = 0 states have been measured at bombarding energies of 24.6, 35.0 and 45.0 MeV. Several different approaches have been used to obtain values of the spin-flip ( V στ ) and no spin-flip ( V τ ) parts of the effective interactions. The ratio V στ / V τ increases with increasing energy between 25 and 45 MeV. Extracted values of V στ are somewhat larger than those obtained from lighter nuclei.
Motile Systems: Tubulin-based motility races ahead

Abstract Recent structural studies raise the possibility that our first atomic models for how motor proteins work may come from tubulin-based motility, and not the actin–myosin system of muscle.
Simulation and observation of ice formation (freeze-over) in a lake

The date on which a lake freezes over has significance for the safety of winter lake recreation, for winterkill of fish and for the water quality of ice-covered lakes. This paper describes the development and application of a new algorithm to predict the date of ice formation on a lake. It uses a full heat budget equation to estimate surface cooling, quantifies the effect of forced convective (wind) mixing and includes the latent heat removed by ice formation. The algorithm has a fine spatial resolution near the water surface where temperature gradients before freeze-over are the greatest. Detailed field measurements of water temperatures and local weather data leading to freeze-over of Ryan Lake, Minnesota, are reported and used to verify the algorithm development. Inverse temperature stratification occurs in the near-surface water several hours before ice formation. The new algorithm is combined with a year-round temperature model and tested against observations in Ryan Lake and eight other Minnesota lakes for multiple (9-36) years. The difference between the simulated and observed permanent ice formation dates is less than 6 days for all lakes studied.
Disulfide bonds are required for Serratia marcescens nuclease activity

The role of the two disulfide bonds found in the Serratia marcescens nuclease were tested by site directed mutagenesis and were found essential for nuclease activity, although slight residual activity remained. The requirement for disulfide bond formation may play a role in preventing the lethal action of nuclease while in the bacterial cytoplasm.
Folate-dependent enzymes in cultured Chinese hamster ovary cells: impaired mitochondrial serine hydroxymethyltransferase activity in two additional glycine--auxotroph complementation classes.

Abstract Two glycine-requiring Chinese hamster ovary (CHO) auxotrophs (GLYB and AUXB2) representative of the Gly − mutant classes B and C are shown to have defects in folate metabolism. These defects result in 10-fold lower rates of whole cell l -[U- 14 C]serine-to-[ 14 C]glycine conversion relative to the parental CHO lines (2 vs 20 nmol/h/10 6 cells). This restriction in serine hydroxymethyltransferase (SHMT) activity is localized in the mitochondria. Intact mitochondria from GLYB and AUXB2 convert labeled serine to glycine at 1–4% the rate and with only 1–3% of the total capacity of parental CHO mitochondria. Yet, GLYB and AUXB2 contain parental cell amounts of cytosolic and mitochondrial SHMT, the latter displaying normal substrate K m values. The whole cell and mitochondrial impairments in glycine formation are corrected in GLYB (but not AUXB2) by a prior growth with 100 μ m dl -folinate. They are also partially restored in spontaneous or chemically induced Gly + revertants of GLYB and AUXB2. Subcellular fractionation experiments suggest that a low content (one-fifth parental) of mitochondrial folylpolyglutamates contributes to the auxotrophy of GLYB. Solubilized mitochondrial SHMT from both Gly − auxotrophs cleaves the alternate substrates allothreonine and β-phenylserine at parental CHO rates, without tetrahydrofolate. Consequently, both GLYB and AUXB2 exhibit normal growth rates in the presence of folate plus 1 m m dl -allothreonine (without glycine). These studies demonstrate that mitochondrial SHMT is potentially functional in the Gly − mutant classes B (GLYB) and C (AUXB2). The impaired SHMT activity in vivo and in isolated mitochondria may result from a deficiency in mitochondrial recycling of 5,10-methylenetetrahydrofolate back to tetrahydrofolate. The multiple glycine + adenosine + thymidine auxotroph CHO AUXB1 closely mimics GLYB and AUXB2 with respect to whole cell and mitochondrial glycine synthesis, but the primary cause is different. It is due to a lack of folylpolyglutamate synthetase activity.
Reverse Micelles as a Tool to Probe the Synergy Between Confinement and Osmolytes with Respect to Protein Hydration Properties

There is a rapidly growing awareness not only that dynamics are essential for protein function but that functionally important protein motions are tightly coupled to hydration shell dynamics. The dynamics of hydration waters are in turn a function of both confinement conditions and the presence of surrounding cosolutes/osmolytes. Mimicking the combination of confinement and osmolyte levels for proteins in the in vivo cell environment is challenging. Here we present results obtained through the use of reverse micelles as a unique medium chosen to represent this crowded environment of proteins. The effects on the hydration properties of proteins encapsulated within reverse micelles are presented, and compared with confinement within Sol-gels. The addition of biologically relevant osmolytes to the reverse micelles and Sol-gels is used to expose potential synergy between confinement and osmolyte with respect to impact on hydration.
Modern 5-year survival of resectable esophageal adenocarcinoma: single institution experience with 263 patients.

Background Surgery, as the mainstay of treatment for localized esophageal cancer, is currently being challenged by the assumed high risk of esophagectomy and the poor longterm survival after resection. Epidemiologic and clinical changes over the past decade indicate that these assumptions should be reevaluated. The aim of this study was to assess the modern outcomes of esophagectomy for adenocarcinoma. Study design We studied 263 consecutive patients (215 men, 48 women), who had esophagectomy for adenocarcinoma from 1992 to 2002. Ninety-seven (37%) were stage I, 63 (24%) were stage II, 93 (35%) were stage III, and 10 (4%) were stage IV. Forty-five percent (119 of 263) had curative en bloc resection, 52% (138 of 263) had node involvement, and 18% (48) received neoadjuvant therapy. Results Seventeen percent (44 of 263) of the patients were identified in a Barrett's surveillance program. The frequency of T1N0 adenocarcinoma increased over the study period (p=0.024). The overall 5-year survival was 46.5%, and for the last 5 years of the study was 50.4%. The overall 5-year survival for stage I was 81%; for stage II, 51%; for stage III, 14%; and for stage IV, 0%. Complications occurred in 61% and there were 12 perioperative deaths (4.5%). Cox proportional hazard analysis identified tumor stage and type of resection as independent predictors of survival. Conclusions Nearly half of patients undergoing esophagectomy for adenocarcinoma survive ≥5 years. Improvements in survival are associated with increased detection of early stage disease, and a liberal use of en bloc resection. Nonsurgical treatments should be compared with these contemporary outcomes measures.
PHYSICAL CHANGES AND MUTAGENESIS.

Ultraviolet irradiation of DNA in vitro and in vivo results in the formation of a known structural change — the dimerization of adjacent thymines in the same polynucleotide chain. Many lines of evidence indicate that thymine dimers are responsible for a major part of the lethal, and perhaps mutagenic, effects of ultraviolet irradiation. For example: dimers are split by short-wavelength ultraviolet and by enzymic action in the presence of visible light; and the decrease in the number of dimers is well correlated with the observed increase in biological activity of DNA or increase in colony-forming ability of ultraviolet-irradiated cells. The obvious result of dimer formation is the blockage of DNA synthesis. Studies on an in vitro polymerase system indicate that, in the slow polymerization around thymine dimers, bases other than A are incorporated and that the polymerase product is not complementary to the primer. In cells of Escherichia coli, on the other hand, the major way of coping with the dimers is to remove them from the bacterial DNA in the form of small oligonucleotides. Such an error-correcting mechanism would be expected to work for all changes that affect the hydrogen bonding of normal DNA. Mistakes, in a repair mechanism, that are associated with the replacement of structurally incorrect regions in DNA by normal bases will be discussed as possible causes of mutagenesis.
Sounds from an animal colony entrain a circadian rhythm in the cat, Felis catus L.

Abstract Actograms of domestic cats were obtained in two settings, in a large animal colony where there were many cats and people, and in isolation in sound‐attenuating rooms. For the four cats that were studied in individual isolation, freeruns were obtained in constant dark, and then recordings of sounds from the animal colony were presented once a day at the same time for eight hours. Entrainment by the colony sounds was demonstrated in three of the four cats. The cats in the main colony exhibited a nocturnal pattern of entrainment to the LD cycles. The humans, present during the L phase, induced a prominent band of activity on the actogram. Because both LD cycles and laboratory routines have separate and independent capabilities of entraining the circadian system, Zeitgebers for the cat may be typically complex and diverse so that all temporal aspects of the environment are exploited.
Mandibular fractures in short-finned pilot whales, Globicephala macrorhynchus

This study's objective was to investigate mandibular fractures in 50 short-finned pilot whales, Globicephala macrorhynchus, from two mass strandings. Based on current theories that this species is sexually dimorphic and polygynous, hypotheses were: (1) males should suffer more frequent or more substantial mandibular fractures than should females, and (2) fracture occurrence should increase with male reproductive maturity and potential correlates of maturity, such as age and length. Fractures were described and correlated with physical characteristics to infer possible explanations for injuries. Mandibular fractures were surprisingly common in males and females, being found in more than half of the animals examined (27/50, or 54% overall; 17/36 or 47% of females and 10/14 or 71 % of males). Length was the only correlate of fracture presence; the proportion of animals showing evidence of fracture increased with length. These results offer some support to initial hypotheses, but there must be another set of consequences that contribute to mandibular fractures in females. A combination of intra- and interspecific interactions and life history characteristics may be responsible for fractures. Further research from a larger sample of this and other cetacean species are suggested to help elucidate both the causes and implications of mandibular fractures.
Independence of fushi tarazu expression with respect to cellular density in Drosophila embryos

Regularly spaced repeated morphological structures are a common developmental theme among higher eukaryotes. In Drosophila, this is evident in the repeated segments of the larval and the adult cuticle. It has been demonstrated through cell transplantation1 and more recently through molecular techniques2 that these repeated segmental units are established as early as nuclear cycle 14 in the blastoderm embryo. A number of genes have been shown to express their transcripts2, and in two instances their protein products3,4, in a spatially restricted manner at this early stage. Immunofluorescence probes against the protein product of one such gene, fushi tarazu (ftz), reveal that it is distributed in seven evenly spaced stripes across the cellularized cycle-14 blastoderm embryo3. The mechanisms that determine such spatial patterns of gene expression are of fundamental importance for the development of multicellular organisms, but in no case are they well understood. Here we examine the ftz pattern on blastoderm embryos derived from maternal-haploid 1182 (mh 1182)5,6 and daughterless-abo-like (dal)7 females which possess cell densities and sizes both above and below the wild-type levels. The number, spacing and width of the ftz protein positive bands are not altered in these abnormal embryos relative to the wild-type pattern, suggesting that the mechanism by which distance is measured with respect to the ftz protein is independent of cell size and density.
Evaluation of Fracture Toughness (JIC) Using Single Specimen Fracture Test Augmented by Finite Element Analysis

Fracture toughness is evaluated using the combination of results from a single compact tension fracture test and computationally developed key-curves. The key-curves - a family of load-deflection curves for the test specimen with different length cracks - were developed using the tensile flow properties of the material. By overlaying the experimental test results on these curves the crack length and crack growth during the test can be deduced. The value of J for each crack length is then evaluated from the experimental load-deflection data. The J versus crack extension curve is plotted and J/sub IC/ evaluated. The method is applied to the evaluation of the toughness of depleted uranium and is shown to substantially reduce the scatter often observed in the J versus ..delta..a data.
Observation of mode coupling in bitapered air-core photonic bandgap fibers

Abstract We report the fabrication and characterization of the first bitapers in air-core photonic bandgap fibers. Like conventional fiber bitapers, these devices are found to exhibit quasi-sinusoidally modulated transmission spectra, the signature of resonant coupling to a dominant cladding mode. However, unlike in conventional tapers of comparable length, the modulation period is very short (0.5–3.3 nm), which suggests that coupling takes place to a very high order cladding mode. Such coupling is observed even in comparatively weak bitapers (diameter reduction as low as ∼2%), indicating that air-core fibers are highly sensitive to tapering. The loss of weak tapers is observed to be small (
Injection of eluites in solvents stronger than the mobile phase in reversed-phase liquid chromatography

Abstract A study was made of the distortion and multiplication of peaks that occur when an eluite is injected dissolved in a solvent that is significantly stron
Schottky barrier formation at ErAs/GaAs interfaces: a case of Fermi level pinning by surface states

Schottky barrier heights and electronic structure are calculated for two model ErAs/GaAs (001) interfaces, using the linear muffin-tin orbital method, showing a clear pinning of the Fermi level by GaAs surface states. Implications for other ErAs/GaAs interfaces are discussed.
Hurricane-borne African Locusts (Schistocerca gregaria) on the Windward Islands

The research applies a geographic perspective to the interface of biotic, atmospheric and socio-economic factors. Wind as a factor in biotic distributions helps explain the existence and quality of life on many isolated islands. In the late summer of 1988, there were reports of African desert Locust (Schistocerca gregaria) invasion of the Windward Islands. The event was historically unprecedented, and agricultural experts in the eastern Caribbean were alarmed. A tentative hypothesis was that Hurricane Joan provided the transport mechanism. An alternative hypothesis is suggested here. The discussion helps explain why transatlantic African Desert Locust migrations are so unusual. Analysis is based on primary and secondary data sources that include synoptic weather maps, formal and informal scientific reports, written correspondence with agricultural experts in the impact area, and newspaper coverage of the invasion.
Association learning for emotional harbinger cues: When do previous emotional associations impair and when do they facilitate subsequent learning of new associations?

Neutral cues that predict emotional events (emotional harbingers) acquire emotional properties and attract attention. Given the importance of emotional harbingers for future survival, it is desirable to flexibly learn new facts about emotional harbingers when needed. However, recent research revealed that it is harder to learn new associations for emotional harbingers than cues that predict non-emotional events (neutral harbingers). In the current study, we addressed whether this impaired association learning for emotional harbingers is altered by one’s awareness of the contingencies between cues and emotional outcomes. Across three studies, we found that one’s awareness of the contingencies determines subsequent association learning of emotional harbingers. Emotional harbingers produced worse association learning than neutral harbingers when people were not aware of the contingencies between cues and emotional outcomes, but produced better association learning when people were aware of the contingencies. These results suggest that emotional harbingers do not always suffer from impaired association learning and can show facilitated learning depending on one’s contingency awareness.
Atomic displacement due to the electrostatic potential energy of very highly charged ions at solid surfaces

Unambiguous evidence of a new radiation effect is presented based upon the occurrence of single ion defects which are created through the interaction of the Coulombic potential of slow highly charged ions (e.g., Xe44+ and U70+) and the surface region of solid insulating surfaces (i.e. mica). In the cases studied, the kinetic energy of the ions is some 300 to 500 keV (~2.2 keVu), while the energy associated with the electrostatic potential of the incident ions approaches 200 keV. Defect production in mica has been investigated as a function of incident ion charge, using an atomic force microscope. The volume of “blister-like” defects has been found to be proportional to the incident ion charge. These cases are compared to those of slow singly charged (Xe+) and fast (MeV) Xe17+ ions. Similar defects have been found for Xe44+ ions incident on other insulators such as Lexan and silica glass.
DOMINANT KINGS AND FORGOTTEN QUEENS

Islands of History. By M. Sahlins. Chicago: University of Chicago Press, 1985. Pp. xix + 180. Price: US$22.50. Kingship and Sacrifice: Ritual and Society in Ancient Hawaii. By V. Valeri. Chicago: University of Chicago Press, 1985. Pp. xvii + 446.
Impaired Bone Formation in Pdia3 Deficient Mice

1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3) mediates 1α,25(OH)2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/− heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/− mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/− mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/− mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/− heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH)2D3’s actions in regulating skeletal development.
What's new in colon and rectal surgery.

What's New in Surgery evolves from the contributions of leaders in each of the fields of surgery. In every instance the author has been designated by the appropriate Council from the American College of Surgeons'Advisory Councils for the Surgical Specialties. This feature is now presented in issues of the Journal throughout the year.
Chemical synthesis and biological activity of a novel fluorescent etoposide derivative

Abstract The antineoplastic activity of etoposide resides in its ability to poison the nuclear enzyme DNA topoisomerase II (topo II). The factors that control the cellular entry and subcellular distribution of etoposide remain poorly understood. Therefore, we have synthesized a novel fluorescence-labeled etoposide (Bodipyetoposide) by coupling 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionylethylenediamine (Bodipy) to 4′-benzyloxycarbonyl-4′-demethylepipodophyllotoxin β- d -glucopyranoside, a precursor of etoposide. Bodipy-etoposide retained the ability to stabilize topo II-DNA covalent complexes in isolated nuclei, although it was significantly less potent and efficacious than etoposide. The growth inhibitory activity of Bodipy-etoposide was also approximately 200-fold less than that of etoposide in human leukemia K562 and DU-145 prostatic carcinoma cells. Nonetheless, etoposide-resistant K/VP.5 and K/VP.5-1 leukemia cells were cross-resistant to Bodipy-etoposide compared with parental K562 cells. Analysis by flow cytometry revealed a concentration-dependent Bodipy-etoposide cell association with no significant difference in drug association in the etoposide-resistant cell lines relative to the parental K562 cells. Using confocal laser scanning microscopy, we found significant cytoplasmic perinuclear localization of Bodipy-etoposide. Thus, Bodipy-etoposide displays promise as a tool to probe the factors controlling entry and subcellular distribution of etoposide-like compounds in live cells.
A theory for scattering by density fluctuations based on three-wave interaction

The theory of scattering by charged particle fluctuations of a plasma is developed for the case of zero magnetic field. The source current is derived on the basis of: (1) a three wave interaction between the incident and scattered electromagnetic waves and one electrostatic plasma wave (either Langmuir or ion acoustic), and (2) a synchronous interaction between the same two electromagnetic waves and the discrete components of the charged particle fluctuations. Previous work is generalized by no longer making the assumption that the frequency of the electromagnetic waves in large compared to the plasma frequency. The general result is then applied to incoherent scatter, and to scatter by strongly driven plasma waves. An expansion is carried out for each of those cases to determine the lower order corrections to the usual high frequency scattering formulas.
Nested Modeling of Hazards in the National Airspace System

Highly complex and coupled nature of the National Airspace System makes it challenging to understand the safety implications of changes to its operations. A comprehensive assessment of the hazards associated with the introduction of new technologies must involve modeling of interactions among aircraft behavior, supporting infrastructure, and the operational procedures. The traditional approach to risk assessment does not focus on the relative timing of relevant events. The likelihoods of those events are computed externally, usually by means of physics-based simulations, which, while increasingly realistic in capturing physical phenomena, are limited to describing only few relevant interactions to keep the overall complexity tractable. This paper discusses an intermediate layer of analysis with enough fidelity to capture time-dependent coupling among relevant entities of the system that is compact enough to track a large number of those relevant entities simultaneously. To this end, Stochastic Petri nets ...
Examining the characteristics and beliefs of hydroxyurea users and nonusers among adults with sickle cell disease

The attitudes of patients with sickle cell disease (SCD) toward the use of hydroxyurea (HU) therapy may contribute to the underutilization of HU in the United States, yet our understanding of these attitudes is limited. We examined the attitudes and beliefs of 94 adult SCD patients, comparing those who never used HU (n 5 37), formerly used HU (n 5 23), and were currently using HU (n 5 34). Seventy percent of current HU users reported some level of improvement from the drug ("average" or "very much") and 80% reported little or no trouble from side effects. Fifty-seven percent of former users reported taking HU for less than 6 months, with "doctor"s recommendation," or "not liking the way it made me feel" given as the most commonly reported reasons for stopping HU. Fifty percent of the never users reported receiving no information about HU from any source, and 85% of the never users thought that they would receive no improvement if they were to take HU. A deeper understanding of patient perspectives toward HU utilization is required as part of multipronged efforts to combat its underutilization in the treatment of SCD.
Cognitive Processing Therapy for Acute Stress Disorder Resulting from an Anti-Gay Assault.

This case study describes Cognitive Processing Therapy (CPT) with a 30-year-old gay man with symptoms of acute stress disorder (ASD) following a recent homophobic assault. Treatment addressed assault-related posttraumatic stress disorder symptoms and depressive symptoms. Also addressed were low self-esteem, helplessness, and high degrees of internalized homophobia. Client symptomatology was tracked using the PTSD Symptom Scale and the Beck Depression Inventory over the course of 12 sessions and for a 3-month posttermination session. Symptoms were significantly reduced by the end of the 12-week therapy and were maintained at 3-month follow-up. This case highlights the utility of this therapy in targeting both ASD symptoms and internalized homophobia relating to experiencing a hate crime-related assault. The authors elaborate on theoretical and applied issues in adapting a structured cognitive-behavioral intervention to the treatment of ASD symptoms associated with experiencing a hate crime.
Efficient extraction of xylan from delignified corn stover using dimethyl sulfoxide

Xylan can be extracted from biomass using either alkali (KOH or NaOH) or dimethyl sulfoxide (DMSO); however, DMSO extraction is the only method that produces a water-soluble xylan. In this study, DMSO extraction of corn stover was studied at different temperatures with the objective of finding a faster, more efficient extraction method. The temperature and time of extraction were compared followed by a basic structural analysis to ensure that no significant structural changes occurred under different temperatures. The resulting data showed that heating to 70 °C during extraction can give a yield comparable to room temperature extraction while reducing the extraction time by ~90 %. This method of heating was shown to be the most efficient method currently available and was shown to retain the important structural characteristics of xylan extracted with DMSO at room temperature.
Stratospheric Ozone Depletion and its Relationship to Skin Cancer

Several articles have appeared in the literature regarding the impact of stratospheric ozone depletion on the prevalence of skin cancer due to increasing ultraviolet radiation. While it has been shown that UVB radiation is related to carcinogenesis of both melanoma and non-melanoma skin cancer, it has not definitively been shown that stratospheric ozone depletion is translating into increased penetrating ultraviolet radiation. Estimates of increasing skin cancer in the future are dependent on calculations of UVB increases drawn from data on ozone depletion. The present article describes the history of stratospheric ozone depletion, how it may affect UVB penetration and skin cancer rates, and what is currently being done to prevent man's further detrimental effects on our atmosphere.
Effect of hunger on the drinking behaviour of rodents adapted for mesic and xeric environments

Abstract Observations of drinking behaviour were taken on six rodent species during fasting. Four of these species were wild-caught and had not previously been examined for food deprivation polydipsia (FDP). These data support an hypothesis that a negative correlation exists between water availability in the natural habitat and the occurrence of FDP. Namely, xerophilous species exhibit an absolute polydipsia during food deprivation while mesically adapted species evidence depressed water consumption. Urine analyses during food deprivation indicated substantial decreases in electrolyte and osmotic pressure concentrations in all species. The drinking patterns of the three desert species investigated are discussed with reference to the availability of green vegetation in the natural habitat; however, there is presently no explanation for the observed polydipsia.
Hemoglobin drops within minutes of injuries and predicts need for an intervention to stop hemorrhage.

Background:Hemoglobin (Hgb) levels obtained shortly after injury may not detect occult bleeding in trauma patients because of the time needed for plasma levels to equilibrate, or may be confounded by crystalloid-related hemodilution. We hypothesized that Hgb levels measured within minutes of arrival
New sulfur derivatives of 2,3-dichloropyrrolo(1,2-a) benzimidazol-1-one. Demonstration of regioselective thiolate addition and X-ray diffraction structures of 2-chloro-3-methylthiopyrrolo(1,2-a)benzimidazol-1-one and 2,3-di(benzylthio)pyrrolo(1,2-a)benzimidazol-1-one

The reaction of thiols with the heterocyclic compound 2,3-dichloropyrrolo[1,2-a] benzimidazol-1-one (1) has been investigated as a route to new redox-active, bidentate sulfur ligands. Treatment of 1 with either methylthiol or benzylthiol in the presence of pyridine affords monosulfide compounds 2-chloro-3-methylthiopyrrolo[1,2-a] benzimidazol-1-one (2) and 2-chloro-3-benzylthiopyrrolo[1,2-a]benzimidazol-1-one (3) and the disulfide derivatives 2,3-di(methylthio)pyrrolo[1,2-a]benzimidazol-1-one (4) and 2,3-di(benzylthio)pyrrolo[1,2-a]benzimidazol-1-one (5). The substitution of the first chlorine group in 2,3-dichloropyrrolo[1,2-a]benzimidazol-1-one (1) occurs regioselectively at C-3 to produce 2-chloro-3-methylthiopyrrolo[1,2-a]benzimidazol-1-one (2) and 2-chloro-3-benzylthiopyrrolo[1,2-a]benzimidazol-1-one (3), followed by replacement of the remaining chlorine group to furnish the disulfide compounds 4 and 5. The new thiols have been isolated by column chromatography and characterized in solution by spectroscopic methods. The molecular structures of 2-chloro-3-methylthiopyrrolo[1,2-a]benzimidazol-1-one and 2,3-di(benzylthio)pyrrolo[1,2-a]benzimidazol-1-one have been determined by X-ray crystallography. Compound 2 crystallizes as two independent molecules in the monoclinic space group P21/c, a = 13.221(2) A, b = 18.478(2) A, c = 8.948(1) A, β = 100.088(3)°, V = 2152.3(5) A3, Z = 8, and dcalc = 1.547 Mg/m3; R = 0.0354, Rw = 0.0739 for 2820 reflections with I > 2σ(I). Compound 5 crystallizes in the triclinic space group P-1, a = 5.180(1) A, b = 11.494(2) A, c = 17.243(3) A, α = 86.024(3)°, β = 88.606(4)°, γ = 81.235(3)°, V = 1012.1(4) A3, Z = 2, and dcalc = 1.360 Mg/m3; R = 0.0354, Rw = 0.0692 for 2655 reflections with I > 2σ(I). The redox properties of the disulfide compounds 4 and 5 have been explored by cyclic voltammetry, where a one-electron reduction at ca. −1.10 V has been observed for each compound. The site of electron accession in has been established by carrying out molecular orbital calculations at the extended Huuckel level on the model compound 2,3-di(thio)pyrrolo[1,2-a]benzimidazol-1-one.
Multiple-collision analysis of characteristic X-rays from low-energy Ar2+ travelling in solid targets

Abstract The density of atoms in a solid target fosters a multiple-collision mechanism that leads to the production of an equilibrium fraction of L-shell vacancies in an incident heavy ion. It is then possiblein a subsequent ion-atom collision in the solid for an L-vacancy to be transferred to the K-shell of a target atom via rotational coupling of the 2p π −2p σ molecular orbitals formed in the ion-atom quasimolecule. The vacancy-transfer cross section and the equilibrium fraction and lifetime of the vacancies can be found by using an appropriate multiple-collision analysis of the characteristic target and projectile X-rays. Results will be presented for 160–380 keV Ar 2+ incident of targets of Mg, Al, and Si.
Ethnicity in child maltreatment research: a content analysis.

The present study represents a content analysis of 1,133 articles published between 1977 and 1998 in Child Abuse and Neglect, Child Maltreatment, and Journal of Child Sexual Abuse was performed. Although there were indications of increased attention to ethnicity in child maltreatment research published between 1977 and 1998, the improvements were modest. Of the 1,133 articles examined, 6.7% focused on ethnicity. The percentage of studies that provided information on the ethnic composition of samples increased across time; however, only half of the studies published in the most recent years examined (1995-1998) reported information on the ethnicity of the participants. Although the percentage of articles that used ethnicity in analyses or as a control variable increased across time, three quarters of the articles published in the most recent years examined (1995-1998) did not include ethnicity in their analyses or design. Language: en