cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall-cell lung cancer

BACKGROUND: Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naive patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standard, front-line, platinum-based doublets have not been extensively explored. We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naive patients with advanced, nonsquamous NSCLC. METHODS: Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Secondary endpoints included safety, response rates, and overall survival. RESULTS: The median number of chemotherapy and maintenance bevacizumab cycles/patient was 6 and 2, respectively. Grades 3-5 adverse events included febrile granulocytopenia (10%), infections (13%), bleeding (13%), thrombotic events (13%), hypertension (5%), bowel perforation (5%), and proteinuria (3%). Median progression-free survival was 7.9 months and median overall survival was 16.5 months. Partial responses were observed in 21 patients (53%), and stable disease ≥6 weeks occurred in another 17 patients (43%), for a disease control rate of 95%. CONCLUSIONS: Carboplatin, docetaxel, and bevacizumab were feasible and effective for front-line treatment of advanced, nonsquamous NSCLC. These data provide further evidence that bevacizumab may be used in combination with multiple standard, platinum-based doublets in this setting. Cancer 2010. © 2010 American Cancer Society.
Primate obstetrics: The biology of birth

A review of recent studies of cephalo-pelvic relationships in primates at birth reveal that body size is the primary determinant of cranial dimensions at term. Variation in intraordinal size relationships are used to predict the course of labor, and nonintrusive observational studies are required to test these predictions.
Observation of 〈001〉 dislocations and a mechanism for transgranular fracture on {001} in FeAl

Abstract Transmission electron microscopy of iron-rich, B2-structure, FeAl alloys which had been compressed at room temperature revealed the presence of 〈001〉 dislocations, in addition to APB-coupled 〈111〉 dislocations which are normally observed at room temperature. It appears that the 〈001〉 dislocations form through the interaction of the 〈111〉 dislocations. This reaction to produce 〈001〉 dislocations is outlined and shown to be energetically favorable. The production of these 〈001〉 dislocations on {100} planes is suggested to be a cause of transgranular cleavage on {100} in B2 alloys deforming by 〈100〉 slip.
Excitation of a Coaxial Line Through a Transverse Slot

A rocket with removed access plate is simulated by a section of coaxial transmission line with a transverse elliptical slot cut in its sheath. The internal circuit consists of two arbitrary impedances in series with the inner conductor at its ends. The object is to find the currents in these impedances when the cylinder is illuminated from the outside by an electromagneticfield that enters the aperture and excites the internal circuit. The problem is solved by application of the reciprocal theorem. The current in a dipole antenna is determined when this is inthe far field maintained by the slotted coaxial line when driven by a generator in series with one of the load impedances. The field in the aperture is replaced by equivalent electric and magnetic dipoles. The reciprocal theorem gives the current in the load impedance when the distantdipole is driven. A numerical example is given.
Zinc-stimulated Endocytosis Controls Activity of the Mouse ZIP1 and ZIP3 Zinc Uptake Transporters

The mouse mZip1 and mZip3 zinc transporters have been implicated in zinc acquisition by the cells of many tissues. This hypothesis raised the question of whether activity of these proteins is regulated to maintain zinc homeostasis. Neither mZIP1 nor mZIP3 mRNA levels are highly regulated by zinc status. Therefore, we investigated whether zinc controls the activity of these proteins post-translationally by altering their subcellular distribution. When expressed in transfected cells grown in zinc-replete medium, both mZip1 and mZip3 were largely present in intracellular organelles. However, these proteins were found to rapidly transit between the plasma membrane and intracellular compartments in zinc-replete cells. Zinc deficiency increased plasma membrane levels of mZip1 and mZip3 by decreasing their rates of endocytosis. Greater zinc deficiency was required to alter mZip3 distribution than was needed to affect mZip1. Increased surface levels correlated with increased zinc uptake activity. Taken together, these results suggest that post-translational control of mZip1 and mZip3 localization plays a role in zinc homeostasis. Moreover, our results indicate that zinc-responsive endocytosis is a conserved mechanism controlling activity of many mammalian zinc uptake transporters.
Abstract A29: Mdm2 E3 ubiquitin ligase function is dispensable for the degradation of Mdm2 itself

Mdm2 has long been considered the major negative regulator of both p53 stability and activity. The RING finger domain of Mdm2 confers its E3 ubiquitin ligase activity, and through this function Mdm2 controls p53 stability, additionally, auto-ubiquitination of Mdm2 is believed to be the primary mechanism of Mdm2 degradation. In vitro, mutation or truncation of the RING domain in Mdm2 resulted in loss of ubiquitin ligase activity towards both Mdm2 and its substrate p53. In contrast, recent knock-in mouse models indicate that under physiological conditions the Mdm2 RING-mediated E3 ubiquitin ligase function is dispensable for Mdm2 degradation. To investigate the in vivo significance of Mdm2 auto-ubiquitination, we compared two Mdm2 knock-in mouse strains each harboring a single amino acid substitution in RING domain (C462A) or C-terminus (Y487A). Both knock-in mutants disrupt Mdm2 E3 ligase activity for p53. We observed that (1) mutant Mdm2 protein (C462A or Y487A) fails to degrade p53 protein. (2) Wild type and mutant Mdm2 are degraded similarly. Despite efficient disruption of p53 degradation, half-life assays demonstrated that neither of the Mdm2 mutants affected the rate of degradation of Mdm2 itself indicating not only that Mdm2 auto-ubiquitination is not the primary mechanism for Mdm2 degradation in vivo, but also that an additional mechanism is in action to regulate Mdm2. (3) Inhibition of proteasomal degradation by MG-132 resulted in similar levels of accumulation of both wild type and mutant Mdm2s suggesting Mdm2 degradation is mediated via the proteasome. In vivo ubiquitination assay reconfirmed that Mdm2 RING domain mutation does not affect degradation and accumulation of Mdm2 itself, further implicating the possibility of an outside E3 ligase activity. In conclusion, auto-ubiquitination of Mdm2 is not necessary for Mdm2 degradation in vivo. The identification of E3 ubiquitin ligases with specificity for Mdm2 is an important next step to gain mechanistic insight into the regulation of Mdm2 regulation, and with that, p53. Citation Format: Tae-Hyung Kim, Yanping Zhang. Mdm2 E3 ubiquitin ligase function is dispensable for the degradation of Mdm2 itself. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A29.
Galactic substructure and dark-matter annihilation in the Milky Way halo

We study the effects of substructure on the rate of dark-matter annihilation in the Galactic halo. We use an analytic model for substructure that can extend numerical simulation results to scales too small to be resolved by the simulations. We first calibrate the analytic model to numerical simulations, and then determine the annihilation boost factor, for standard weakly interacting massive particle (WIMP) models as well as those with Sommerfeld (or other) enhancements, as a function of galactocentric radius in the Milky Way. We provide an estimate of the dependence of the gamma-ray intensity of WIMP annihilation as a function of angular distance from the Galactic center. This methodology, coupled with future numerical simulation results can be a powerful tool that can be used to constrain WIMP properties using Fermi all-sky data.
Understanding the rules of the road: proteomic approaches to interrogate the blood brain barrier.

The blood brain barrier (BBB) is often regarded as a passive barrier that protects brain parenchyma from toxic substances, circulating leukocytes, while allowing the passage of selected molecules. Recently, a combination of molecular profiling techniques have characterized the constituents of the BBB based on in vitro models using isolated endothelial cells and ex vivo models analyzing isolated blood vessels. Characterization of gene expression profiles that are specific to the endothelium of brain blood vessels, and the identification of proteins, cells and multi-cellular structure that comprise the BBB have led to a emerging consensus that the BBB is not, in and of itself, a simple barrier of specialized endothelial cells. Instead, regulation of transcytosis, permeability and drug translocation into the central nervous system is now viewed as a collection of neurovascular units that, together, give the BBB its unique biological properties. We will review recent technology advancing the understanding of the molecular basis of the BBB with a focus on proteomic approaches.
On the rotatory strength of d-d transitions of copper(II)-bis-α-amino acid complexes

Abstract The optical activity of the (2:1) copper(II)-bis-α-(L-aliphatic) amino acid complexes in the visible and the ultraviolet regions has been examined with reference to the symmetry rule for the origin of optical activity. It is concluded that the negative ellipticities above 210 nm, reflecting contributions from the n-π* and possibly the charge-transfer bands, and the negative dichroic band in the visible region, reflections of the d-d transitions, are consistent with the δ-conformation of the complexes. The rotatory strengths of the d-d transitions, as seen in the ellipticities at the negative extrema for the series of aliphatic complexes, exhibit a linear relationship with the inductive electron-withdrawing power of the vicinal groups, the latter being represented by the Taft constant and/or the dipole moment of the side chains. The complexes of aliphatic amino acids containing branching at the α-carbon atom exhibit ellipticities which are significantly larger than those predicted by the above linear relationship, whereas those containing branching at the β-carbon atom conform to the relationship. The higher activities of the complexes with branching at the α-carbon atom hvae been ascribed to the additive conformational selectivity resulting from rotational hindrance. The optical activity of the d-d transitions in bis-α-amino acid complexes, in general, is governed by the electronic characteristics of the vicinal groups.
Agent-Specific Responses in the Cingulate Cortex During Economic Exchanges

Interactions with other responsive agents lie at the core of all social exchange. During a social exchange with a partner, one fundamental variable that must be computed correctly is who gets credit for a shared outcome; this assignment is crucial for deciding on an optimal level of cooperation that avoids simple exploitation. We carried out an iterated, two-person economic exchange and made simultaneous hemodynamic measurements from each player's brain. These joint measurements revealed agent-specific responses in the social domain ("me" and "not me") arranged in a systematic spatial pattern along the cingulate cortex. This systematic response pattern did not depend on metrical aspects of the exchange, and it disappeared completely in the absence of a responding partner.
What can automaton theory tell us about the brain

Abstract The potential contribution of the theory of cellular automata to understanding of the brain is considered.
A strain of nuclear-polyhedrosis virus causing extensive cellular hypertrophy☆

Abstract A newly discovered strain of a nuclear-polyhedrosis virus causes extensive hypertrophy to the tracheal cells of the armyworm, Pseudaletia unipuncta. This extreme hypertrophy, the absence of infection in the fat cells, and the long period of lethal infection clearly differentiate it from the typical strain of a nuclear-polyhedrosis virus which has been described previously. It also differs from the typical strain in causing the following cytopathological changes: an increase in the number and an alteration in the appearance of the mitochondria in the infected cell, the development of innumerable folds in the cell and nuclear membranes, and the formation of electron-transparent areas in the cytoplasm. At an early stage of infection when the cellular hypertrophy is marked, there is at first no virus rods. The rods appear later, and the polyhedra still later. The polyhedra and virus rods of the new strain resemble those of the typical strain. Its infectivity is also enhanced by a granulosis virus in a synergistic association as in the case of the typical strain. When armyworm larvae are fed equal concentrations of the new and the typical strains, very few of them, if any, develop the signs and symptoms of the new strain. The larval specimens, from which the new strain was obtained, had been collected in a field in Hawaii during 1958 and 1960, and showed the typical signs and symptoms of nuclear polyhedrosis at the time of collection. Accordingly, the larval specimens may have been infected originally by two strains of a nuclear-polyhedrosis virus. Three larvae collected in alfalfa fields at Davis, California, also exhibited signs and symptoms of the new strain.
Understanding predisposition to schizophrenia: toward intervention and prevention.

Objective:Early intervention to prevent schizophrenia is one of the most important goals of schizophrenia research. However, the field is not yet ready to initiate trials to prevent prodromal or ps...
Exploiting human actions and object context for recognition tasks

Our goal is to exploit human motion and object context to perform action recognition and object classification. Towards this end, we introduce a framework for recognizing actions and objects by measuring image-, object- and action-based information from video. Hidden Markov models are combined with object context to classify hand actions, which are aggregated by a Bayesian classifier to summarize activities. We also use Bayesian methods to differentiate the class of unknown objects by evaluating detected actions along with low-level, extracted object features. Our approach is appropriate for locating and classifying objects under a variety of conditions including full occlusion. We show experiments where both familiar and previously unseen objects are recognized using action and context information.
A Second-Order Translation, Rotation and Scale Invariant Neural Network

A second-order architecture is presented here for translation, rotation and scale invariant processing of 2-D images mapped to n input units. This new architecture has a complexity of O(n) weights as opposed to the O(n3) weights usually required for a third-order, rotation invariant architecture. The reduction in complexity is due to the use of discrete frequency information. Simulations show favorable comparisons to other neural network architectures.
Mycotic Aneurysm of the Thoracic Aorta Due to Aspergillus terreus: Case Report and Review

Mycotic aneurysms of the aorta caused by fungi are uncommon. We describe an unusual case of aortic aneurysm infection caused by Aspergillus terreus, which most likely spread from an adjacent pulmonary focus. Successful treatment included partial pneumonectomy, resection of the aneurysm with graft repair, and prolonged sequential administration of amphotericin B and itraconazole. A review of the published experience with aortic aneurysms caused by Aspergillus species is also presented. When invasive aspergillosis is suspected in proximity to areas with major vascular structures in immunocompromised patients, further investigation to rule out vascular invasion may be warranted. If the diagnosis is confirmed, aggressive and prompt treatment with antifungal agents combined with surgical debridement is essential to improve outcome.
Resolving within- and between-population variation in feeding ecology with a biomechanical model

Studies of phenotypic plasticity have emphasized the effect of the environment on the phenotype, but plasticity can also be used as a tool to study the functional significance of key traits. By inducing variation in phenotypes and testing quantitative models that predict performance based on biological mechanisms, we can develop functionally general models of performance. Pumpkinseed sunfish from lakes with high snail availability have large levator posterior muscles (which are used to crush snail shells), whereas fish from lakes with few snails have relatively small muscles. Here we: (1) quantify differences in the feeding ability of an ontogenetic series of pumpkinseed from two populations; and (2) evaluate whether a biomechanical model can resolve the observed ontogenetic and between-population variation in feeding ecology. Mass, but not length, of the levator posterior muscle in fish from Three Lakes (a lake rich in snails) was greater than for comparably sized fish from Wintergreen Lake (a lake with few snails). Handling times were shorter, crushing strengths were 71% greater, and foraging rate (snail tissue mass consumed per time) and the fraction of thick-shelled snails in the diet were approximately 100% greater for fish from Three Lakes compared to comparably sized fish from Wintergreen. These between-lake differences were not significant after adjusting for variation in pharyngeal morphology, suggesting that the biomechanical model of snail crushing resolved observed ontogenetic and population-level variation in the feeding ecology of pumpkinseed.
Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins.

Background Biological organisms and their components are better conceived within categories based on similarity rather than on identity. Biologists routinely operate with similarity-based concepts such as "model organism" and "motif." There has been little exploration of the characteristics of the similarity-based categories that exist in biology. This study uses the case of the discovery and classification of zinc finger proteins to explore how biological categories based in similarity are represented.
Significance of Textural Variations, Baltimore Canyon Trough Area

ABSTRACT Estimates of the within-station variance show which of 31 variables can be used as effective indicators of textural differences within the Baltimore Canyon Trough area, a potentially-leasable area of the Atlantic continental shelf. The variables that are most diagnostic of differences between stations are the percentages of gravel and total sand, percentages of coarse, medium, and fine sand, median and mean phi sizes, skewness, and kurtosis. Some of the -phi-size fractions within the sand range cannot define areal trends effectively. The textural variability within the Baltimore Canyon Trough area reflects the reworked and sorted sediments that cover this part of the shelf and differs from that of the more gradational sediments on the W shington state continental shelf. The magnitude of the within-station variance is not only important geologically, but it has environmental and legal ramifications for any study that characterizes shelf areas with economic potential.
Is ‘hand preference’ coded in the hominin skeleton? An in-vivo study of bilateral morphological variation

Abstract The presumed link between bilateral asymmetry and lateralized habitual activity in extinct hominins is the basis upon which inferences of ‘hand preference’ often derive. While this presumption is reasonable, in-vivo comparisons of skeletal asymmetries and self-reported handedness are rare, and as a result the accuracy of these inferences is questionable. To assess this relationship in living humans, reported ‘handedness’ was compared against peripheral quantitative computed tomography (pQCT) derived bilateral measurements of humeral, ulnar, and tibial midshaft cortical area (CA) and torsional rigidity (J). Significant bilateral differences were found in the humerus for all groups, and in the ulna for the cricketer and field hockey sub-samples. Additionally, cricketers’ non-dominant tibiae were more robust than their dominant tibiae. An assessment of ‘Dominance Asymmetry’ revealed that measures of CA and J were higher in the dominant humeri in ∼90% of participants; in the ulna this was true in ∼75% of cases, and in the tibia CA and J were higher in the dominant limb less than 50% of the time. Comparisons of (self)‘Reported’ hand preference against ‘Predicted’ hand preference (based on the calculation of % Directional Asymmetry) revealed a low level of error for predictions based on both humeral (∼4–5% error) and ulnar (6–11% error) asymmetry. Error was decreased with the exclusion of individuals displaying less than 2.5–5% asymmetry. Contrarily, predictions based on tibial analyses had a much higher level of ‘error’ (∼45%). Overall, the results support currently accepted approaches for inferring ‘hand preference’ from measures of upper limb geometric asymmetry in the hominin skeleton.
Mechanotransduction and hyperpolarization-activated currents contribute to spontaneous activity in mouse vestibular ganglion neurons.

The hyperpolarization-activated, cyclic nucleotide–sensitive current, Ih, is present in vestibular hair cells and vestibular ganglion neurons, and is required for normal balance function. We sought to identify the molecular correlates and functional relevance of Ih in vestibular ganglion neurons. Ih is carried by channels consisting of homo- or heteromeric assemblies of four protein subunits from the Hcn gene family. The relative expression of Hcn1–4 mRNA was examined using a quantitative reverse transcription PCR (RT-PCR) screen. Hcn2 was the most highly expressed subunit in vestibular neuron cell bodies. Immunolocalization of HCN2 revealed robust expression in cell bodies of all vestibular ganglion neurons. To characterize Ih in vestibular neuron cell bodies and at hair cell–afferent synapses, we developed an intact, ex vivo preparation. We found robust physiological expression of Ih in 89% of cell bodies and 100% of calyx terminals. Ih was significantly larger in calyx terminals than in cell bodies; however, other biophysical characteristics were similar. Ih was absent in calyces lacking Hcn1 and Hcn2, but small Ih was still present in cell bodies, which suggests expression of an additional subunit, perhaps Hcn4. To determine the contributions of hair cell mechanotransduction and Ih to the firing patterns of calyx terminals, we recorded action potentials in current-clamp mode. Mechanotransduction currents were modulated by hair bundle defection and application of calcium chelators to disrupt tip links. Ih activity was modulated using ZD7288 and cAMP. We found that both hair cell transduction and Ih contribute to the rate and regularity of spontaneous action potentials in the vestibular afferent neurons. We propose that modulation of Ih in vestibular ganglion neurons may provide a mechanism for modulation of spontaneous activity in the vestibular periphery.
Protein kinase C-β, fibronectin, α5β1-integrin, and tumor necrosis factor-α are required for phorbol diester–induced apoptosis in human myeloid leukemia cells

The human myeloid HL-60 cell line and its cell variant HL-525 were used to study signaling events leading to apoptosis induction by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC) enzymes. Unlike parental cells, HL-525 cells are PKC-beta deficient and resistant to PMA-induced apoptosis. These cells regain susceptibility to apoptosis induction after transfection with a PKC-beta expression vector. By using this vector and specific neutralizing monoclonal antibodies (mAbs), it was established that PMA-induced apoptosis also called for an interaction between cell-surface alpha(5)beta(1)-integrin and its deposited ligand fibronectin (FN), which is downstream of PKC-beta activation. Experiments with mAbs, the PKC-beta vector, and exogenous FN revealed that the next step entailed an interaction between secreted tumor necrosis factor-alpha and its type I receptor. By using a sphingomyelinase inhibitor, it was concluded that the subsequent step involved ceramide production. Moreover, a permeable ceramide was effective in inducing apoptosis in both HL-60 and HL-525 cells, and this induction was caspase-1 and/or -4 dependent because an inhibitor of these caspases abrogated the induced apoptosis. Based on these and related differentiation studies, we conclude that the above signaling events, the early ones in particular, are shared with PMA-induced macrophage differentiation in the HL-60 cells. It is likely that once these cells acquire their macrophage phenotype and perform their tasks, they become superfluous and are eliminated from the body by a self-triggered apoptotic process that involves our proposed signaling scheme.
Ventricular septal aneurysm after atrioventricular septal repair with pericardium

A 2-month-old infant underwent a two-patch repair of a type C atrioventricular septal defect using autologous pericardium. Several months later a large, symptomatic aneurysm of the ventricular septal patch developed, requiring resection. The use of untreated autologous pericardium for large, congenital ventricular septal defects is unpredictable and should be avoided.
How patients with type 2 diabetes mellitus respond to motivational interviewing.

Abstract Aim To determine how patients with type 2 DM feel about a motivational interviewing (MI) intervention designed to promote positive behavior change. Method Qualitative study using focus groups conducted by the same facilitator. Setting Family or general internal medicine practice clinics affiliated with an academic medical center and a community general hospital. One site consisted of primarily low income Hispanic patients. Participants Four focus groups consisting of nineteen adult patients with type 2 diabetes mellitus solicited from a large NIH-funded randomized controlled trial on MI and diabetes. Results Across and within group analysis was performed on transcripts of the taped interviews. Patient perceptions of standard care were largely negative, with several individuals describing paternalistic and demeaning attitudes. Five themes related to MI emerged: Nonjudgmental Accountability, Being Heard and Responded to as a Person, Encouragement and Empowerment, Collaborative Action Planning and Goal Setting, and Coaching rather than Critiquing. Conclusions Some patients with type 2 diabetes are receptive to motivational interviewing which is a provider approach that is more patient-centered and empowering than traditional care.
'Model' or 'tool'? New definitions for translational research.

The term ‘model’ often describes non-human biological systems that are used to obtain a better understanding of human disorders. According to the most stringent definition, an animal ‘model’ would display exactly the same phenotype as seen in the relevant human disorder; however, this precise correspondence is often not present. In this Editorial, I propose the alternative, broader term ‘tool’ to describe a biological system that does not obviously (or precisely) recapitulate a human disorder, but that nonetheless provides useful insight into the etiology or treatment of that disorder. Applying the term ‘tool’ to biological systems used in disease-related studies will help to identify those systems that can most effectively address mechanisms underlying human disease. Conversely, differentiating ‘models’ from ‘tools’ will help to define more clearly the limitations of biological systems used in preclinical analyses.
Behavior of PCM/PM/BI-phase receivers in non-ideal channels

The performance of the residual carrier communication system that employs PCM/PM modulation technique with imperfect Bi-phase (or Bi-/spl phi/) data format and band-limited channels are investigated in this paper. Imperfect data stream consists of data imbalance and data asymmetry. Separate effects of data asymmetry, unbalanced data stream and InterSymbol Interference (ISI) caused by band-limited channel on performances of PCM/PMI/Bi-phase receivers are investigated. Only the effects of imperfect carrier tracking induced by an imperfect data stream are considered. The Symbol Error Rate (SER) performance degradation due to the presence of imperfect data stream is evaluated and compared with the results obtained by computer simulation. Furthermore, the SER performance is analyzed in the presence of band-limited channel. The effect of the ISI created by a band-limited channel on the system performance is evaluated and compared with the computer simulation results for an ideal low-pass filter. >
Classification in DLMS utilizing a KL-ONE representation language

Ford Motor Company's Direct Labor Management System (DLMS) is the knowledge-based subsystem of complex multiphase manufacturing process planning system. DLMS is a deployed production system that is used daily by Ford Body and Assembly Division personnel in the performance of their duties. The knowledge used to drive the assembly planning system is stored in a knowledge base that is based on the KL-ONE knowledge representation system. This paper discusses the use of KL-ONE in an application-oriented environment and gives a "report from the field" of KL-ONE in production use. Advantages and disadvantages of using KL-ONE to represent a dynamic, large-scale conceptual framework for process planning is discussed. >
An accurate method for voxelizing polygon meshes

The process of generating discrete surfaces in a volumetric representation, termed voxelization, is confronted with topological considerations as well as accuracy and efficiency requirements. The authors introduce a new method for voxelizing planar objects which, unlike existing methods, provides topological conformity through geometric measures. They extend their approach to provide, for the first time, an accurate and coherent method for voxelizing polygon meshes. This method eliminates common voxelization artifacts at edges and vertices. They prove the method's topological attributes and report performance of their implementation. Finally, they demonstrate that this approach forms a basis for a new set of voxelization algorithms by voxelizing an example cubic object.
Youth and homicide: An investigation of the age factor in criminal homicide

With the perception that juvenile violent crime is increasing, criminal justice policy toward juvenile crimes of violence has increasingly mirrored policy toward adult violent crime. Neither the justification for this policy change nor the literature on the topic indicates whether juvenile violent crime is, in fact, different from adult violent crime. We use data from all homicides in Baltimore from 1974 through 1984 to examine this question. The analysis shows that juvenile involvement in homicide, as measured by the absolute number of juvenile homicides, the proportion of juveniles involved in homicide, and the juvenile homicide rate, did not increase during this period. Further, the analysis shows that juvenile homicides differ significantly from adult homicides on a number of dimensions. Three different analytical techniques confirm the particular significance of multiple-offender homicides and concurrent felony homicides in the juvenile homicide pattern.
Two-stage tests for studying monotherapy and combination therapy in two-by-two factorial trials.

Two-stage testing involves a preliminary test of a nuisance parameter prior to testing main hypothesis. In a two-by-two factorial trial, the treatment interaction is the nuisance to the inference about the efficacy of one of the treatments given alone. In comparing a combination therapy to both of its component therapies, the nuisance parameter is the difference in the component effects. When the preliminary test is an integral part of inference about the main parameter, the actual level of significance for the two-stage test procedure can be much higher than the desired nominal level. If one places no restriction on the value of the nuisance parameter, then any two-stage test with its significance level properly controlled has undesirable properties. This applies to comparative studies of combination agents relative to the component agents. When the interaction with an ineffective treatment is null, two-stage testing may have some power advantage for assessing monotherapy efficacy.
Cardiovascular genetics—redefining the role of the clinical geneticist

Abstract In an effort to find a solution for the problem of providing comprehensive genetic services in the current managed care environment, The Golisano Children's Hospital at Strong, University of Rochester Medical Center decided to test a new role for the clinical geneticist. A board certified clinical geneticist/dysmorphologist was hired to build a new cardiovascular genetics program within the division of pediatric cardiology. This is a novel approach since most divisions of pediatric cardiology do not have a specifically designated geneticist as a member of their division. As one of seven cardiovascular genetics clinics in the United States (nine world wide) the Cardiovascular Genetics Program at The Children's Heart Center provides genetic services to a targeted, complex group of patients. In the first 9 months, the overall utilization (number of patient slots available/number of patients seen) of the clinic is 81% with a show rate of 85%. The program provides consultative services to pediatric cardiology as well as pediatric and adult medicine within the hospital and the community. The pediatric cardiovascular surgery service is regionalized including patients from Syracuse, Rochester and Buffalo, New York areas. The Cardiovascular Genetics Program offers initial, second opinion and follow-up evaluations to this entire upstate New York region. As a consultative service the Program supplies the PCP and/or surgeon with a comprehensive management plan in addition to the diagnostic evaluation. The PCP/surgeon executes the plan with support from the genetics staff as needed. It is the comprehensive nature of the management plan provided to the caregivers that improves quality of care and thus, outcome, even when a definitive diagnosis has not been established.
Nonisothermal healing and interlaminar bond strength evolution during thermoplastic matrix composites processing

Thermoplastic-matrix composite products are fabricated by applying heat and pressure to contacting thermoplastic surfaces, and consolidating the interface. The combined processes of interfacial contact area increase, referred to as intimate contact, and polymer Interdiffusion (healing) across the interfacial areas in contact are responsible for the development of interlaminar bond strength in the composite products. In this paper, a model for the healing process under nonisothermal conditions is presented starting from a fundamental formulation of the reptation of polymer chains. The healing model is coupled with an intimate contact model based on a fractal representation of the asperity structures on thermoplastic tow surfaces, to provide a comprehensive description of the interfacial bond strength evolution during nonisothermal processing. Nondimensional analysis is used to identify the ranges of a parameter, introduced as the fusion bonding number, which correspond to the interfacial bonding process being healing-limited, intimate-contact-limited, or equally dominated by both mechanisms.
Sociobiology and the Wayward Critic

The article begins by underscoring the widely noted "sociological crisis" and the message from the history of science that the crisis may be susceptible to resolution through an application of a general law pertaining to a neighboring science (sociobiology in our case). From here, the article proceeds to pinpoint the basic argument of Professor Crippen's article (this issue) and then critically examines the two articles that critically accompany it. We find some errors of interpretation in Professor Maryanski's article, but on the whole it is a constructive critique of Crippen's essay and a related invitation to a biologically informed evolutionary sociology. By contrast, Professor Freese's intenninable article fails to confront Crippen's argument and in the process offers a tortuous, tendentious itinerary of politically correct interpretations of scientific inquiry in general and sociobiological science in particular. For those keen to the intellectual culture that motivated eighteenth- and nineteenth- century students of "natural history," sociology is as much an immanent repercussion of the Copemican Revolution as are geology, quantum mechanics, chemistry, evolutionary biology, and any of the other scientific disciplines that in recent times have enlightened the inquisitive and unprepossessed mind. The degree to which sociologists are prepared to establish credentials worthy of this context is a different matter. Indeed, some sociologists, mistaking the nature of science, assert
PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2

Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 μM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 μM, 24 h) increased the MCT1 promoter activity (−871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-ζ isoform. 5′-deletion studies demonstrated that the MCT1 core promoter region (−229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.
The Torsional Dislocation Loop and Mode III Cylindrical Crack

The elastic fields of a torsional dislocation loop in a homogeneous material are first derived. The solution is based on torsional symmetry. The stress and displacement solutions are then extended to the case of a torsional loop in a bi-material. A main utility of basic dislocation solutions is in fracture mechanics. In particular, circular loop solutions can be used in the modeling of both cylindrical and penny-shaped cracks. In the present study we use them to model a Mode III cylindrical crack via the application of a “distributed-dislocation technique”. Stress intensity factors at the crack tips are presented. The influences of crack radius and material pair on the stress intensity factor of interfacial cracks are investigated.
Necrotizing fasciitis due to penicillin-resistant Streptococcus pneumoniae: case report and review of the literature.

Necrotizing fasciitis (NF) is a life-threatening infection involving rapid necrosis of subcutaneous and fascial tissues. Streptococcus pneumoniae (SPN) soft tissue infection is exceedingly uncommon, reported primarily in patients with immunosuppression or other underlying conditions. We report a case of NF and septic shock in a healthy 32-year-old man, whose only predisposing factor was antecedent blunt trauma. Pathological examination and culture of the extensive tissue debridement were positive only for SPN. The serotype 9V isolate was penicillin (PCN)-resistant (MIC=2.0), and closely-related by pulse field gel electrophoresis and multilocus fingerprinting to clone France 9V-3, an important genetic reservoir for increasing PCN-resistance worldwide. This unique case has implications for our pathogenic under-standing and empiric management of NF.
Continuing to Conduct Research in Nursing Homes Despite Controversial Findings: Reflections by a Research Scientist:

To illustrate the potential controversial nature of the research findings, the author first presents data from an ongoing study on the care of terminally ill nursing home residents, then responds to the question: "How can you go into nursing homes, find out all that you do, publish your findings, and continue to gain access to nursing homes?" Strategies used over the past 20 years to gain this access and to develop and maintain harmonious relationships during and after the data collection process are presented. The author emphasizes the importance of conducting research in settings that may generate controversial findings. Furthermore, she states that these findings should be presented to advocates and policy makers who are in a position to bring about changes that will improve the quality of care.
Insecticide resistance and cross-resistance in the house fly (Diptera: Muscidae).

A house fly strain, ALHF, was collected from a poultry farm in Alabama after a control failure with permethrin, and further selected in the laboratory with permethrin for five generations. The level of resistance to permethrin in ALHF was increased rapidly from an initial 260-fold to 1,800-fold after selection. Incomplete suppression of permethrin resistance by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF) reveals that P450 monooxygenase- and hydrolase-mediated detoxication, and one or more additional mechanisms are involved in resistance to permethrin. The ALHF strain showed a great ability to develop resistance or cross-resistance to different insecticides within and outside the pyrethroid group including some relatively new insecticides. Resistance to beta-cypermethrin, cypermethrin, deltamethrin, and propoxur (2,400–4,200-, 10,000-, and >290-fold, respectively, compared with a susceptible strain, aabys) in ALHF house flies was partially or mostly suppressed by PBO and DEF, indicating that P450 monooxygenases and hydrolases are involved in resistance to these insecticides. Partial reduction in resistance with PBO and DEF implies that multiresistance mechanisms are responsible for resistance. Fifteen- and more than fourfold resistance and cross-resistance to chlorpyrifos and imidacloprid, respectively, were not effected by PBO or DEF, indicating that P450 monooxygenases and hydrolases are not involved in resistance to these two insecticides. Forty-nine-fold cross-resistance to fipronil was mostly suppressed by PBO and DEF, revealing that monooxygenases are a major mechanism of cross-resistance to fipronil. Multiresistance mechanisms in the ALHF house fly strain, however, do not confer cross-resistance to spinosad, a novel insecticide derived from the bacterium Saccharopolyspora spinosa. Thus, we propose that spinosad be used as a potential insecticide against house fly pests, especially resistant flies.
Science Networks by Field: Who Seeks Advice and Support from Women?

Supporting and advancing women's science careers continues to be of interest to researchers, scientists, science funders and universities. Similarly, collaboration strategies and social networks are important to understanding the advancement of scientific careers. This research aims to marry these two lines of research, women in science and collaboration and network strategies, to investigate and compare the ways in which men and women scientists seek advice and support from women in their networks. Specifically, we use a sample of women and men in electrical engineering, computer science, physics, chemistry, earth and atmospheric sciences, and biology to assess (1) the extent to which female and male scientists seek advice from women colleagues and (2) the extent to which female and male scientists receive support from women in their networks. The results point to important differences in women's and men's advice and support networks across fields of science.
Ventriculostomies without dressings: Low infection rates but room for quality improvement

ObjectiveVentriculostomies are common procedures for patients with severe neurologic insults including trauma, aneurysmal rupture, tumor, infection or following an operation. Infection secondary to a ventriculostomy, meningitis or ventriculitis, carries a high morbidity and mortality. Insertion practices and maintenance of these interventions was evaluated.MethodsA retrospective review was completed of patients receiving ventriculostomies at a single institution from October 2007 through September 2013. Basic patient demographics, methods of insertion and presence of infection were collected and analyzed.ResultsThe mean of age of patients receiving ventriculostomies was 49 years of age and the most common indications for insertion were trauma, infection and nontraumatic intracranial hemorrhage (aneurysmal subarachnoid hemorrhage (SAH), hemorrhagic stroke, arteriovenous malformation (AVM)). External ventricular drains (EVDs) were inserted after minimal hair removal at the time of procedure, tunneling follo...
Abbreviating the Wealth Index to Measure Equity in Health Programs More Easily

Efforts to simplify the construction of the DHS wealth index are encouraged (while recognizing it is constructed differently in each country) but attempts to assess equity in health programs should bear in mind that it is not sufficient to calculate the wealth index just for the participants in the program. The quintile distributions can vary dramatically within sub-populations. Assessments of equity require knowledge of the distribution of potential participants as well as actual participants.
Distinguishing the subjective and the objective aspects of self-concept clarity

Since its introduction, self-concept clarity has been viewed as a construct related to the structure and organization of a person's self-concept. We argue, however, that self-concept clarity may best be understood as a combination of subjective, metacognitive beliefs about the self-concept and objective structure and organization. We consider the unique influences of both objective and subjective clarity and offer some suggestions and novel hypotheses for investigating this proposed distinction.