cssi/SciSciGPT-SciSciNet huggingface dataset:
Well-Defined Mannosylated Polymer for Peptide Vaccine Delivery with Enhanced Antitumor Immunity.

Peptide-based cancer vaccines offer production and safety advantages but have had limited clinical success due to their intrinsic instability, rapid clearance, and low cellular uptake. Nanoparticle-based delivery vehicles can improve the in vivo stability and cellular uptake of peptide antigens. Here, a well-defined, self-assembling mannosylated polymer is developed for anti-cancer peptide antigen delivery. The amphiphilic polymer is prepared by RAFT polymerization, and the peptide antigens are conjugated to the pH-sensitive hydrophobic block through the reversible disulfide linkage for selective release after cell entry. The polymer-peptide conjugates self-assemble into sub-100 nm micelles at physiological pH and dissociate at endosomal pH. The mannosylated micellar corona increases the accumulation of vaccine cargoes in the draining inguinal lymph nodes and facilitates nanoparticle uptake by professional antigen presenting cells. In vivo studies demonstrate that the mannosylated micelle formulation improved dendritic cell activation and enhanced antigen-specific T cell responses, resulting in higher antitumor immunity in tumor-bearing mice compared to free peptide antigen. The mannosylated polymer is therefore a simple and promising platform for the delivery of peptide cancer vaccines. This article is protected by copyright. All rights reserved.
Atos: A Task-Parallel GPU Dynamic Scheduling Framework for Dynamic Irregular Computations.

We present Atos, a task-parallel GPU dynamic scheduling framework that is especially suited to dynamic irregular applications. Compared to the dominant Bulk Synchronous Parallel (BSP) frameworks, Atos exposes additional concurrency by supporting task-parallel formulations of applications with relaxed dependencies, achieving higher GPU utilization, which is particularly significant for problems with concurrency bottlenecks. Atos also offers implicit task-parallel load balancing in addition to data-parallel load balancing, providing users the flexibility to balance between them to achieve optimal performance. Finally, Atos allows users to adapt to different use cases by controlling the kernel strategy and task-parallel granularity. We demonstrate that each of these controls is important in practice. We evaluate and analyze the performance of Atos vs. BSP on three applications: breadth-first search, PageRank, and graph coloring. Atos implementations achieve geomean speedups of 3.44x, 2.1x, and 2.77x and peak speedups of 12.8x, 3.2x, and 9.08x across three case studies, compared to a state-of-the-art BSP GPU implementation. Beyond simply quantifying the speedup, we extensively analyze the reasons behind each speedup. This deeper understanding allows us to derive general guidelines for how to select the optimal Atos configuration for different applications. Finally, our analysis provides insights for future dynamic scheduling framework designs.
Reduced object-based perception in the near-hand space

Previous studies have shown that hand proximity changes visual perception (Abrams et al. in Cognition 107(3):1035-1047, 2008). The present study examined the effects of hand proximity on object-based perception. In three experiments, participants viewed stimuli that were either near to or far from their hands. The target stimulus appeared, after a cue, in one of two rectangular objects: either at the location that had been previously cued, at the uncued end of the cued object, or in the uncued object. We found a significantly reduced same-object benefit in reaction time for stimuli near the hands in one experiment. Interestingly, we observed a same-object cost in sensitivity for stimuli near the hands in another experiment. The results reveal that object-based perception is disrupted in the near-hand space. This is consistent with previous findings revealing altered visual processing near the hands.
Connectionist approaches to inexact reasoning and learning systems for executive and decision support: conceptual design

Abstract Connectionist approaches to the representation and reasoning about problems addressed by executive and decision support systems are described. It is shown that analog object structures coupled with learning produce mechanisms for managerial problem diagnoses. These mechanisms are neural models with multiple-layer structures that support continuous input/output. Because a connectionist architecture is assumed, the prototype system is called the Connectionist Inexact Reasoning System or CIROS. Although uncharacteristic of neural architectures, an explanation capability is developed within CIROS and described herein. The primary contribution of CIROS is that it provides principles for design of inexact reasoning systems for managerial problem diagnosis.
Programming in an object-oriented environment

Part 1 Object-Oriented Concepts: Basic Concepts. The Object-Oriented Model of Computation. Class Hierarchy. Encapsulation. An Example Program. Object-Oriented Programming Languages. Part 2 Object-Oriented Environment: The Object-Oriented Advantage. Elements of Object-Oriented Systems. Data Structures and Algorithms. Object-oriented User Interfaces. Object-Oriented Databases. Object-Oriented Design. Conclusion. Appendexes: Summary of Terms. Listing: The hello World Exchange. Listing: The Course Scheduling Example. Listing: A Generic Collection Class.
Dangers of arterial catheters in critically ill neonates (I)

To the Editor.— We read with interest the recent article in Pediatrics.1 The authors present a case of aortic thrombosis associated with umbilical catheterization in a newborn delivered to a cocaine-addicted mother. We agree with the authors that the presence of an arterial catheter is the most likely cause of the arterial thrombosis, whereas cocaine may have had an additional vasoconstrictive effect. It would be interesting to know whether any placental infarct had been noted at the time of delivery.
Comparison of the Kois Dento-Facial Analyzer System with an earbow for mounting a maxillary cast

Abstract Statement of problem The Kois Dento-Facial Analyzer System (KDFA) is used by clinicians to mount maxillary casts and evaluate and treat patients. Limited information is available for understanding whether the KDFA should be considered as an alternative to an earbow. Purpose The purpose of this study was to evaluate maxillary casts mounted using the KDFA with casts mounted using Panadent's Pana-Mount Facebow (PMF). Both articulation methods were compared against a lateral cephalometric radiograph. Material and methods Fifteen dried human skulls were used. Lateral cephalometric radiographs and 2 maxillary impressions were made of each skull. One cast from each skull was mounted on an articulator by means of the KDFA and the other by using the PMF. A standardized photograph of each articulation was made, and the distance from the articular center to the incisal edge position and the occlusal plane angle were measured. The distance from condylar center to the incisal edge and the occlusal plane angle were measured from cephalometric radiographs. Finally, the 3-dimensional position of each articulation was determined with a Panadent CPI-III. A randomized complete block design analysis of variance (RCBD) and post hoc tests (Tukey-Kramer HSD) (α=.05) were used to evaluate the occlusal plane angle and axis-central incisor distance. A paired 2-sample t test for means (α=.05) was used to compare the X, Y, and Z distance at the right and left condyle. Results The KDFA and PMF mounted the maxillary cast in a position that was not statistically different from the skull when comparing the occlusal plane angle ( P =.165). Both the KDFA and the PMF located the maxillary central incisor edge position in a significantly different position compared with the skull ( P =.001) but were not significantly different from each other. The 3-dimensional location of the maxillary casts varied at the condyles by approximately 9 to 10.3 mm. Conclusion The KDFA mounted the maxillary cast in a position that was not statistically different from the PMF when comparing the incisal edge position and the occlusal plane angle. Both the KDFA and the PMF located the maxillary incisal edge position in a significantly different position compared with the anatomic position on dried human skulls.
Why don't smart teens have sex? A behavioral genetic approach

Academic achievement and cognitive ability have been shown to predict later age at first sexual intercourse. Using a sample of 536 same-sex twin pairs who were followed longitudinally from adolescence to early adulthood, this study tested whether relations between intelligence, academic achievement, and age at first sex were due to unmeasured genetic and environmental differences between families. Twins who differed in their intelligence or their academic achievement did not differ in their age at first sex. Rather, the association between intelligence and age at first sex could be attributed entirely to unmeasured environmental differences between families, whereas the association between academic achievement and age at first sex could be attributed entirely to genetic factors.
The hypothetical chemical and spectroscopic activity of Germane in the atmosphere of Jupiter

Abstract It is suggested that in a reducing environment such as the Jovian atmosphere, GeH 4 may be spectroscopically active. Absorption features might be detectable in the 4.7μ window in the Jovian upper atmosphere.
The transformation of laryngeal keratosis into invasive carcinoma.

Abstract Although 93.0% to 97.0% of all laryngeal carcinomas are diagnosed on the first biopsy, 3.0% to 6.7% of them occur in patients who have what is initially diagnosed as “laryngeal keratosis”. To study this phenomenon, we examined data from 1,019 patients with laryngeal keratosis seen between 1962 and 1981. Eleven patients with keratosis and initially undetected cancer at different laryngeal sites were excluded, as were 87 outside referrals for whom no records were available beyond the histologic report. The remaining 921 patients were classified on the basis of the initial histologic findings into groups comprising 604 patients with keratosis without atypia (group 1), 204 patients with mild atypia (group 2), 23 patients with moderate atypia (group 3), and 90 patients with severe atypia (group 4). All 921 were follwoed for from 5 to 25 years. Invasive carcinoma of the larynx developed in 18 patients from group 1 (3.0%), 15 from group 2 (7.4%), four from group 3 (17.4%), and 25 from group 4 (27.8%). Fifty-seven patients (91.9%) developed invasive carcinoma after less than 10 years but only five (8.1%) did so after 10 years or more.
C2 imagery of the inner coma of comet IRAS-Araki-Alcock

May 10, 1983 observations of the comet IRAS-Araki-Alcock are analyzed to determine the spatial molecular abundance of C2 in the inner coma, via the Delta-v = +1 Swan band sequence near 4690 A. The observations indicate a deficiency of C2 emission across a projected diameter of about 2000 km that is centered on the peak of continuum emission. Comet imagery indicates a sunward-pointing coma that suggests an outburst of subsurface volatile ices through a nonvolatile surface crust, as predicted for periodic comets. These results are discussed in the framework of instrumental and observational constraints.
Flotation machine design: impeller—stator interaction

Abstract The separate contributions of impellers and stators to suction are studied by means of interaction models. From these, suction can be predicted when interchangeable components are used in any combination, and in either direction of impeller rotation. Methods are devised by which numerical values of the impeller and stator terms can be simply assigned. The resulting model provides good agreement with experiment. The influence of variability in component geometry is reflected in the model parameters. Possible applications of the model are suggested.
Holographic synthetic aperture interferometry

A microwave or acoustic form of holographic interferometry is described in which synthetic aperture procedures are used.
Interlamellar Adsorption of Carbon Dioxide by Smectites

The adsorption of CO2 at low temperature (~ -70°C) on thin films of homoionic smectites was studied by X-ray diffraction and by i.r. absorption. An increase in the d001 spacings of these clay films upon adsorption of CO2 was observed. In addition, a dichroic effect was readily discernible by comparing the i.r. spectra at two different orientations of the smectite films; i.e. with the film normal and tilted 35° with respect to the i.r. beam. The CO2 stretching vibration at 2350 cm-1 was used for the i.r. study. These observations conclusively show that CO2 intercalates the smectite structure rather than being adsorbed only in pores between clay tactoids—the limiting process proposed by other investigators.
A rapid and robust alternative to Rachford–Rice in flash calculations

Abstract Rachford–Rice iterations are widely used in equation-of-state (EOS) flash calculations to determine phase equilibrium compositions from constant equilibrium ratios ( K -values). The method, however, can be slow to converge or may not converge at all for cases where at least one overall composition is zero or negative. Having a robust method for flash calculations in these special cases is important in calculating the minimum miscibility pressure (MMP) using method of characteristics (MOC). This paper presents a simple, fast, and robust alternative to Rachford–Rice and similar methods in flash calculations, whether overall compositions are positive, zero, or negative. The new objective function has two fewer asymptotes compared to Rachford–Rice and is based on solving for one of the equilibrium phase mole fractions, typically the lightest component. Results with the new objective function demonstrate that rapid convergence using Newton–Raphson (NR) iterations is assured because the correct solution is determined within a small range (window). In that window, no poles exist no matter the overall composition and the objective function is often nearly linear. Improved linearity of the objective function contributes to increased convergence speed even near critical points.
John Locke, Carolina, and the Two Treatises of Government:

Recent scholarship on John Locke’s Two Treatises of Government has drawn particular attention to the colonial antecedents and applications of the theory of appropriation in chapter V of theSecond Treatise. This attention has coincided with a more general interest among political theorists in the historical and theoretical relationship between liberalism and colonialism. This essay reviews the surviving evidence for Locke’s knowledge of the Carolina colony and argues that it was both more extensive and more enduring than previous commentators have suggested. In particular, the essay provides evidence that Locke was engaged in revising the Fundamental Constitutions of Carolina at just the moment in the summer of 1682 when he was most likely to have composed chapter V of theSecond Treatise and hence that there was an immediate and identifiable colonial context that contributed to his distinctive theory of property.
Control of Experimental Cecal Coccidiosis with Sulfaquinoxaline-Antibiotic Combinations

Abstract IN WORK on the control of cecal coccidiosis (Eimeria tenella) of chickens by feeding a standard diet medicated with sulfamethazine, it was determined that beneficial results could be obtained by fortifying the medicated feed with aureomycin (Gardiner, 1957, 1958). The amounts of antibiotic utilized were 100 and 200 grams per ton of feed. The addition of aureomycin to the medicated ration apparently had the effect of neutralizing the toxicity of the sulfamethazine when fed at the recommended level, and at the same time made possible the use of smaller amounts of the drug without reducing its effectiveness. White-Stevens et al. (1955) reported that sulfaquinoxaline, as well as sulfamethazine, is compatible with aureomycin. When employed as a preventive of coccidiosis, this drug usually is fed continously a t levels between 0.0125 and 0.0150%. However, the preventive level will not always protect a flock when the birds are kept in an environment …
The utility of presenting slides of a phobic stimulus in the context of a behavioral avoidance procedure

The study reported involves a comparison between in vivo and slide presentations of a phobic object. Female college students (N=82) who reported fear of rats were tested using a behavioral avoidance procedure. Subjects were divided into three groups. Subjects in an in vivo condition were instructed to bring a live rat increasingly closer by pressing a button on the test apparatus. Subjects in two slide conditions followed a similar procedure with a button press bringing the slide of a rat in clearer view. Behavioral, self-ratings, and psychophysiological measures were obtained. Subjects were classified as no-touch (NT) or touch (T) on the basis of a contact test which took place at the end of the experiment. The in vivo condition, as expected, produced in the NT subjects a reliably greater fear reaction when compared to T subjects and to the slide conditions. However, one of the slide conditions was also found to reliably discriminate behaviorally between NT and T subjects. This latter finding suggests the potential usage of slide material to discriminate at a clinical level other feared stimuli for which an in vivo phobic stimulus would be difficult or impossible to present. Other findings with implications for assessment of phobic behavior are reported.
Prevalence and significance of intrahepatic hepatitis delta virus antigen expression in HBeAg-negative patients with chronic type-B hepatitis in Taiwan.

A consecutive series of 97 HBeAg-negative patients with chronic type-B hepatitis, who were not drug addicts or hemophiliacs, were examined for the prevalence of intrahepatic expression of hepatitis delta virus (HDV) antigen (HDAg) by direct immunofluorescence. The clinical and histological features were compared between those with and without intrahepatic HDAg expression. Intrahepatic HDAg expression was detected in 15 (15.5%) of the 97 patients. All of the 15 were males between 18 and 71 years of age. Each had elevated SGPT levels, with 46.8% being greater than 10 times normal and 73.4% greater than five times normal. Histological study revealed chronic lobular hepatitis in nine and chronic active hepatitis in six, including two with cirrhosis. Compared to the 82 patients without intrahepatic HDAg expression, no difference in the age (34.1±14.3 vs 36.7±10.8) and sex (15∶0 vs 72∶10) distribution was evident, but greater biochemical and histological activity was present in HDV-positive patients.
Infantile Hemangiomas Masquerading as Other Periocular Disorders

Periocular tumors are common in infancy. The most common periocular tumors are capillary hemangiomas, which are present in 1-2% of newborns and develop in 10%–12% of children by the age of 1 year old. Deep capillary hemangiomas may be more challenging to diagnose than superficial capillary hemangiomas and can be confused with other orbital lesions. Deep orbital hemangiomas can mimic teratoma, lymphangioma, rhabdomyosarcoma, metastatic neuroblastoma, and granulocytic sarcoma. In this paper, we describe 2 pediatric cases where previously diagnosed dermoid cyst and dacrocystocele were found to be capillary hemangiomas upon biopsy. Approaches to distinguish capillary hemangiomas from other periocular tumors are further discussed. To our knowledge, this is the first case report of periocular hemangiomas imitating a dermoid cyst and a dacrocystocele. These cases emphasize the importance of including infantile hemangiomas in the differential diagnosis of subcutaneous periocular abnormalities.
Fine tuning of rational B-spline motions

This paper presents two algorithms for ne-tuning rational spatial motions suitable for Computer Aided Design. The rational motions are represented by rational B-spline curves in a projective dual three-space known as the Image Space of Spatial Kinematics. The problem of ne-tuning of rational motions is studied as that of ne-tuning the corresponding rational curves in the Image Space called the image curves. The path-smoothing algorithm automatically detects and smoothes out the third order geometric discontinuities in the path of a cubic rational Bspline image curve. The speed-smoothing algorithm uses a quintic rational spline image curve to obtain a second-order geometric approximation of the path of a cubic rational B-spline image curve while allowing specication of the speed and the rate of change of speed at the key points to obtain a near constant kinetic energy parametrization. The notion of kinetic energy is used in the paper as a natural way of combining the rotational and translational speed of a spatial motion. The results have applications in trajectory generation in robotics, planing of camera movement, spatial navigation in visualization and virtual reality systems, as well as mechanical system simulation.
A note on a matrix criterion for unique colorability of a signed graph

A signed graph,S, is colorable if its point set can be partitioned into subsets such that all positive lines join points of the same subset and all negative lines join points of different subsets.S is uniquely colorable if there is only one such partition. Developed in this note is a new matrix, called thetype matrix ofS, which provides a classification of the way pairs of points are joined inS. Such a classification yields a criterion for colorability and unique colorability.
Regiospecific Chlorination of (S)-β-Tyrosyl-S-Carrier Protein Catalyzed by SgcC3 in the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027

C-1027 is a potent antitumor antibiotic composed of an apo-protein and a reactive enediyne chromophore. The chromophore consists of four different chemical subunits including an (S)-3-chloro-4,5-dihydroxy-β-phenylalanine moiety, the biosynthesis of which from l-α-tyrosine is catalyzed by six proteins, SgcC, SgcC1, SgcC2, SgcC3, SgcC4, and SgcC5. Biochemical characterization of SgcC3 unveiled the following: (i) SgcC3 is a flavin adenine dinucleotide (FAD)-dependent halogenase; (ii) SgcC3 acts only on the SgcC2 peptidyl carrier protein-tethered substrates; (iii) SgcC3-catalyzed halogenation requires O2 and reduced FAD and either the C-1027 pathway-specific flavin reductase SgcE6 or E. coli flavin reductase (Fre) can support the SgcC3 activity; (iv) SgcC3 also efficiently catalyzes bromination but not fluorination or iodination; (v) SgcC3 can utilize both (S)- and (R)-β-tyrosyl-S-SgcC2 but not 3-hydroxy-β-tyrosyl-S-SgcC2 as a substrate. These results establish that SgcC3 catalyzes the third enzymatic transf...
Tech to the Future: Problems with Balance, Troubles with Therapy

The ability to balance is a prerequisite to sitting, standing, and walking and requires complicated physiological coordination. The disruption of any components of the equilibrioceptive, proprioceptive, or visual systems can significantly handicap balance, such as in some cases of cerebral palsy, spina bifida, arthrogryposis, cystic fibrosis, and many other diseases and injuries. Unfortunately, in patients with damaged brain function the disorder at the root of the problem cannot typically be treated but, with physical therapy and braces or other aids, the balance handicap may be overcome.
Statistical analysis of synthesis of Co-MCM-41 catalysts for production of aligned single walled carbon nanotubes (SWNT)

The need for a multivariable designed experimental approach to the synthesis of Co-MCM-41 is described. The designed experiment was implemented with a total of 28 experiments that produced a quantitative model. This model allows the synthesis of Co-MCM-41 with varying pore size but constant composition and a good degree of structural order.
An investigation of magnetic linear dichroism contributions to Mg Kα X-ray photoemission studies of iron

Abstract We present an investigation of magnetic linear dichroism in angle-resolved photoemission distributions (MLDAD) from Fe(011) using unpolarized Mg Kα radiation. The experimental geometry is identical to that previously used in recent spin-resolved X-ray photoelectron spectroscopy (SRXPS) studies of ferromagnets. For this geometry, the results indicate a small but observable MLDAD for the Fe 2 p 3 2 and 2 p 1 2 peaks. No definitive MLDAD is observed for the Fe 3p level, the Fe valence band, or Auger transitions originating from a 2 p 3 2 hole. For all spectral features, MLDAD spectral variations are very small in comparison to the intrinsic (exchange-induced) spin polarization of the Fe photoemission spectra.
Design of novel melanocortin receptor ligands: Multiple receptors, complex pharmacology, the challenge

The major pharmacophore for the melanocortin 1, 3, 4 and 5 receptors is the sequence -His-Phe-Arg-Trp-. There is a need for potent, biologically stable, receptor selective ligands, both agonists and antagonists, for these receptors. In this report we briefly examine the structural and biophysical approaches we have taken to develop selective agonist and antagonist ligands that can cross (or not) the blood brain barrier. Remaining questions and unmet needs are also discussed.
The wealth effects of targeted share repurchases

This paper examines the wealth impact of share repurchases that restrict participation to a particular sub-set of a firm’s stockholders. Repurchases at a premium from insiders and small shareholders increase the wealth of non-participating stockholders and are therefore consistent with the shareholders’ interest hypothesis. However, privately negotiated repurchases of single blocks from stockholders unaffiliated with the firm reduce the wealth of non-participating stockholders. In contrast to the evidence for general repurchases, no positive wealth effect offsets the significant repurchase premium paid to the selling stockholder. Indeed, the wealth loss to non-participating stockholders is significantly greater than the premium paid. This evidence is inconsistent with the shareholders’ interest hypothesis and supports the hypothesis that managers in their self-interest use single block repurchases to eliminate threats to their control over the firm’s resources.
Guiding Sensitization Searches Using Problem Reduction Graphs

In an earlier paper [10] the generation of problem reduction graphs from a search goal definition and a design language description of circuit behavior was presented. The objective of forming such a graph was to provide heuristic guidance for state space searches. Most state space searches use both heuristic cost weighting on the nodes and heuristic input vector generation. In this paper an approach is provided for computing the heuristic cost function based on its contribution to the search objective and the frequency with which that node has been reached in past searches. This is done by weighting the nodes of the problem reduction graph associated with the state search problem based on the frequency with which those problem reduction graph nodes have been reached in past searches. From this weighting follows an heuristic cost function which can be used to quickly compute node weights during the actual state space search. Input vectors are also suggested by the problem reduction graph. Because digital circuits so often partition naturally into control and data sections, the input vectors which can be applied at a given control state are taken from the problem reduction graph and so grouped. Four case studies demonstrate the usefulness of the method, while also showing that neither heuristic weighting nor input selection alone is adequate to provide general purpose state space search guidance.
Political apologia: The ritual of self‐defense

The need for presidential candidates to defend their character was especially strong in the 1976 campaign, partly because “trust” was a major issue in the campaign and partly because the media, reacting to their failures through most of the Nixon administration, were more aggressive. The persistent probes of the media also brought about a change in defense strategies.
Visual perception of the relative phasing of human limb movements.

Studies of bimanual coordination have found that only two stable relative phases (0° and 180°) are produced when a participant rhythmically moves two joints in different limbs at the same frequency. Increasing the frequency of oscillation causes an increase in relative phase variability in both of these phase modes. However, relative phasing at 180° is more variable than relative phasing at 0°, and when the frequency of oscillation reaches a critical frequency, a transition to 0° occurs. These results have been replicated when 2 people have coordinated their respective limb movements using vision. This inspired us to investigate the visual perception of relative phase. In Experiment 1, recordings of human interlimb oscillations exhibiting different frequencies, mean relative phases, and different amounts of phase variability were used to generate computer displays of spheres oscillating either side to side in a frontoparallel plane or in depth. Participants judged the stability of relative phase. Judgments covaried with phase variability only when the mean phase was 0° or 180°. Otherwise, judgments covaried with mean relative phase, even after extensive instruction and demonstration. In Experiment 2, mean relative phase and phase variability were manipulated independently via simulations, and participants were trained to perceive phase variability in testing sessions in which mean phase was held constant. The results of Experiment 1 were replicated. The HKB model was fitted to mean judgment standard deviations.
Plexiform neurofibroma in type 1 neurofibromatosis.

A 13-year-old African-American girl was admitted to the hospital for surgery. She was diagnosed with Type I neurofibromatosis at the age of 1 year after she was noted to have multiple cafe au lait spots. Her past medical history included a history of neurofibroma in the base of the brain, treated with radiation therapy and ventriculoperitoneal shunt, as well as a recent diagnosis of bilateral optic gliomas, treated with chemotherapy. Family history was negative for neurofibromatosis.
Genetic alteration of normal aging processes is responsible for extended longevity in Drosophila

The first step in a genetic analysis of aging is to identify and characterize the genetic mutants and their controls that will be used. Such mutants or strains are initially identified by their effect on the life span. Yet many genetic interventions are known to have some effect on the life span without necessarily affecting the aging process. It is therefore necessary to prove that one is actually dealing with an aging mutant before one draws strong inferences from the data. Casarett's rules provide an operational test for doing so, relying as they do on the comparison of aging bio-markers in the experimental and reference strains. We show that our previously described genetically based long-lived NDC-L strain and its normal-lived NDC-R control strain differ only in the chronological age of expression of two behavioral and three physiological functional age biomarkers. They do not differ in the sequence or the physiological age of expression of these biomarkers. These two strains comply with the Casarett rules and thereby comprise a valid tool with which to conduct a comparative genetic analysis of aging. The implications of the available data are discussed, including the possibility that aging in these strains of Drosophila melanogaster may be the result of a multiphasic developmental process.
Viewpoint: death of the knowledge worker

One of the many concerns in the information area in the early 1980s was how the implementation of technology would change the way we work. In the 1990s the feeling is will we work! This paper examines the current dilemma that technology has presented to the knowledge worker. The players in this scenario are the knowledge workers, unions, both public and private, and outsourcing. It is said that to try to restrict the flow of work in the name of saving jobs in the USA is futile. The author believes that perhaps this is an area that requires further study. In this discussion the author concludes that the fate of the knowledge worker is not in the hands of Divine Providence, but in the political arena.
Who Do I Look Like? Diversity in Self, Family, and Others

ABSTRACT In this introductory, hands-on, multicultural genetics lesson for elementary students, the author describes an activity used to engage learners in understanding diversity in self, family, and others. Students make connections between traits within their family and learn a few basic concepts about inheritance. At the end of the lesson, the author provides extension activities for interdisciplinary connections.
Retrograde flow rate is increased in growth cones from myosin IIB knockout mice

Growth cones of myosin-IIB-knockout mice have reduced outgrowth rates and traction force. There is a close relationship between traction force, retrograde flow and forward advance of growth cones. All three activities appear to be at least partially myosin dependent. Therefore, we have now tested for differences in retrograde flow rates between growth cones from myosin-IIB-knockout mice and their normal littermates. By placing nerve-growth-factor-coated silica beads on the surface of growth cones with laser tweezers, or by tracking GFP-myosin IIA spots, we found that the retrograde flow rate was increased more than two fold in the knockout growth cones compared with the wild type. These data suggest that both myosin IIA and IIB normally contribute to retrograde flow and the properties of the flow are strongly influenced by myosin IIB because of its location and abundance. However, in the absence of myosin IIB, myosin IIA takes over this function. The change in retrograde flow rate may reflect the difference in functional properties of these two myosins. Knockout growth cones also exhibited reduced stability of lamellipodia, possibly as a partial consequence of this increased retrograde flow rate. In addition, microtubules penetrated a shorter distance into filopodia, which suggests that the increase in flow rate may adversely affect the microtubule-dependent maturation of filopodia. Taken together these data support the idea that the forward advance of the growth cone is myosin II dependent and involves multiple myosin II isoforms.
Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells.

The efficacy of cisplatin in cancer chemotherapy is limited by the development of resistance. Although the molecular mechanisms involved in chemoresistance are poorly understood, cellular response to cisplatin is known to involve activation of MAPK and other signal transduction pathways. An understanding of early signal transduction events in the response to cisplatin could be valuable for improving the efficacy of cancer therapy. We compared cisplatin-induced activation of three MAPKs, JNK, p38, and ERK, in a cisplatin-sensitive human ovarian carcinoma cell line (2008) and its resistant subclone (2008C13). The JNK and p38 pathways were activated differentially in response to cisplatin, with the cisplatin-sensitive cells showing prolonged activation (8–12 h) and the cisplatin-resistant cells showing only transient activation (1–3 h) of JNK and p38. In the sensitive cells, inhibition of cisplatin-induced JNK and p38 activation blocked cisplatin-induced apoptosis; persistent activation of JNK resulted in hyperphosphorylation of the c-Jun transcription factor, which in turn stimulated the transcription of an immediate downstream target, the death inducer Fas ligand (FasL). Sequestration of FasL by incubation with a neutralizing anti-FasL antibody inhibited cisplatin-induced apoptosis. In contrast, chemoresistance in 2008C13 cells was associated with failure to up-regulate FasL. Moreover, in these cells, selective stimulation of the JNK/p38 MAPK pathways by adenovirus-mediated delivery of recombinant MKK7 or MKK3 led to sensitization to apoptosis through reactivating FasL expression. Thus, the JNK > c-Jun > FasL > Fas pathway plays an important role in mediating cisplatin-induced apoptosis in ovarian cancer cells, and the duration of JNK activation is critical in determining whether cells survive or undergo apoptosis.
Distance and velocity in Kepler's astronomy

Summary We will examine Kepler's use of a relation between velocity and distance from a centre of circular motion. This relation plays an essential role, through a derivation in chapter 40 of the Astronomia Nova, in the presentation of the Area Law of planetary motion. Kepler transcends ancient and contemporary applications of the distance-velocity relation by connecting it with his metaphysical commitment to the causal role of the Sun. His second main innovation is to replace the astronomical models of his predecessors with an account that derives trajectories from physical principles. In this paper we restrict our attention primarily to the first 40 chapters of Kepler's Astronomia Nova. Hence, we do not discuss Kepler's discovery of elliptical planetary orbits.
Phenomenological Treatment of the ϱ Trajectory

A phenomenological method is applied to the $\ensuremath{\rho}$ trajectory. It is argued that once the intercept is known, the method is expected to give reliable information about the trajectory in the region of interest for highenergy scattering. Solutions for different values of the intercept ranging from 0.3 to 0.8 are given. From certain general requirements the higher intercepts seem to be favored.
Dative stabilization of carbocations

Abstract Carbocations are well known intermediates in organic chemistry. While many carbocations are not stable enough to exist themselves, they may be stabilized by several factors, including resonance with nearby electron donors. Reactions that proceed via mechanisms involving carbocations include the Baeyer–Villiger reaction and the Criegee rearrangement. In both cases, the carbocation is stabilized through resonance by an oxygen atom. The role that oxygen plays in stabilizing carbocations was studied theoretically. The structures of several carbocations, based on the t-butyl ion, with varying numbers of oxygen atoms were optimized using second order Moller–Plesset perturbation theory methods. Relationships were found between the number of oxygen atoms and the amount of delocalization, as well as the charge of the formally positive carbon atom and the number of oxygen atoms bonded to it. Another study was performed on a set of larger cations. Evidence was found relating to the presence of dative bonds, the strength of which were found to be dependent on a number of factors.
Functional MRI of Human Brain during Breath Holding by BOLD and FAIR Techniques

BOLD (blood oxygenation level-dependent) and FAIR (flow-sensitive alternating inversion recovery) imaging techniques were used to investigate the oxygenation and hemodynamic responses of human brain during repeated challenges of breath holding and prolonged single breath holding. The effects of different breathing techniques on BOLD and FAIR image contrasts were carefully examined. With a periodic breath-holding paradigm of 30 s, global changes in gray matter were observable both in T*2-weighted and FAIR images. T*2-weighted images showed 1–4% relative signal intensity increases, while FAIR images demonstrated relative cerebral blood flow (CBF) increase up to 30–70%. The activated pixels depicted in FAIR images were about three times less than those seen in T*2-weighted images. With prolonged breath holding, it was observed that signal intensities in T*2-weighted and FAIR images were dependent on the breathing techniques used. Breath holding after expiration gave rise to immediate signal intensity increases in T*2-weighted and FAIR images, whereas breath holding performed after deep inspiration signals showed a biphasic change both in flow and T*2-weighted. T*2-weighted and FAIR signals showed a transient decrease before rising above the baseline level.
Is the primary complement lesion insufficient for lysis? Failure of cells damaged under osmotic protection to lyse in EDTA or at low temperature after removal of osmotic protection.

Abstract The extent of damage to cell membranes induced by specific antibody and complement under various conditions was monitored by leakage from the cells of isotopically labeled molecules of three sizes. The results have revealed that cells which have sustained complement-mediated membrane damage (indicated by loss of electrolytes) do not, in the absence of osmotic protection, proceed to undergo rapid colloid osmotic lysis, provided that (1) the primary complement-mediated damage was sustained in osmotically protective medium, (2) the damage was of limited extent, and (3) complement activity is stopped (by EDTA or low temperature) prior to removal of osmotic protection so that additional new damage is not done after the removal of osmotic protection. This was found both for mouse ascites tumor cells and erythrocytes. Moreover, the results suggest striking differences in the effect of low temperature on the lytic process in nucleated cells as compared with erythrocytes. In addition to the above-mentioned effects, low temperature can apparently prevent leakage of molecules as small as amino acids from damaged nucleated cells (but not from erythrocytes) in the absence of ostomic protection, no matter how extensive the previous (prelytic) complement-mediated damage, and irrespective of whether the cells were osmotically protected while the damage was administered. These findings have two, perhaps unrelated implications. First, low temperature has a striking ability to restrict further loss of intracellular constituents from damaged nucleated cells (but not from erythrocytes). Second, the results with nucleated cells and erythrocytes raise the possibility that the primary complement-induced lytic lesion either reseals spontaneously or is capable of being repaired.
Protein Domains that Interact with Receptor Tyrosine Kinases: Structural Aspects

This Teaching Resource provides lecture notes and slides for a class covering insights gained from structural analysis of the regulation of receptor tyrosine kinases and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with an overview of the many protein domains thus far implicated in cell signaling and then describes in detail the phosphotyrosine-binding domain (PTB). The application of structural information to rational drug design by targeting protein interaction domains is also covered.
What we really know about our abilities and our knowledge

Recently, it has become popular to state that “people hold overly favorable views of their abilities in many social and intellectual domains” [Kruger, J., & Dunning, D. (1999). Unskilled and unaware of it: how difficulties in recognising one's own incompetence lead to inflated self-assessments. Journal of Personality & Social Psychology, 77(6), (1999) 1121]. Research that supports this point tells only half of the story—in a manner documented by Cronbach’s [Cronbach, L. J. (1957). The two disciplines of scientific psychology. American Psychologist, 12, (1957) 671] classic article on the “two disciplines of scientific psychology.” That is, the recent research has only documented the experimental side of the scientific divide (which focuses on means and ignores individual differences). The current paper shows that research from the other side of the scientific divide, namely the correlational approach (which focuses on individual differences), provides a very different perspective for people’s views of their own intellectual abilities and knowledge. Previous research is reviewed, and an empirical study of 228 adults between 21 and 62 years of age is described where self-report assessments of abilities and knowledge are compared with objective measures. Correlations of self-rating and objective-score pairings show both substantial convergent and discriminant validity, indicating that individuals have both generally accurate and differentiated views of their relative standing on abilities and knowledge.
A comparison and analysis of three technics of taking roentgenograms of the temporomandibular joint

Three commonly used technics of filming the temporomandibular joint were evaluated for (1) roentgenographic distortion, (2) correct anatomic relationships, (3) roentgenographic detail, and (4) roentgenographic color and appearance. Each technic has its limitations, no technic is best in all respects, and that technic which most clearly demonstrates the desired information should be selected.
Gemin proteins are required for efficient assembly of Sm-class ribonucleoproteins

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of spinal motor neurons. The gene encoding the survival of motor neurons (SMN) protein is mutated in >95% of SMA cases. SMN is the central component of a large oligomeric complex, including Gemins2–7, that is necessary and sufficient for the in vivo assembly of Sm proteins onto the small nuclear (sn)RNAs that mediate pre-mRNA splicing. After cytoplasmic assembly of the Sm core, both SMN and splicing snRNPs are imported into the nucleus, accumulating in Cajal bodies for additional snRNA maturation steps before targeting to splicing factor compartments known as “speckles.” In this study, we analyzed the function of individual SMN complex members by RNA interference (RNAi). RNAi-mediated knockdown of SMN, Gemin2, Gemin3, and Gemin4 each disrupted Sm core assembly, whereas knockdown of Gemin5 and Snurportin1 had no effect. Assembly activity was rescued by expression of a GFP-SMN construct that is refractive to RNAi but not by similar constructs that contain SMA patient-derived mutations. Our results also demonstrate that Cajal body homeostasis requires SMN and ongoing snRNP biogenesis. Perturbation of SMN function results in disassembly of Cajal bodies and relocalization of the marker protein, coilin, to nucleoli. Moreover, in SMN-deficient cells, newly synthesized SmB proteins fail to associate with U2 snRNA or accumulate in Cajal bodies. Collectively, our results identify a previously uncharacterized function for Gemin3 and Gemin4 in Sm core assembly and correlate the activity of this pathway with SMA.
Pathology of hepatitis C

The basic morphological patterns of acute or chronic viral hepatitides are very similar, irrespective of the causative hepatitis viruses A, B, C, D or E. In addition, however, acute and chronic hepatitis C shows characteristic, although not pathognomonic histological changes. These consist of lymphoid aggregates in portal tracts, sometimes with germinal centers, damage of bile duct epithelium, and micro- or macrovesicular steatosis of hepatocytes. A combination of two of these three characteristic alterations is seen in over half of the patients with chronic hepatitis C and is helpful in the histological diagnosis of the disease.
Computational science and the future of computing research

Computer science is at heart an applied field. In the current US economic and political climate, where projects not applicable to "strategic" research are less likely to be funded, computational science and engineering applications will become a driving force behind all aspects of computing research. The paper discusses this shift towards the funding of strategic research.