cssi/SciSciGPT-SciSciNet huggingface dataset:
Copresentation of Antigen and Ligands of Siglec-G Induces B Cell Tolerance Independent of CD22

Differentiation of self from nonself is indispensable for maintaining B cell tolerance in peripheral tissues. CD22 and Siglec-G (sialic acid–binding Ig-like lectin G) are two inhibitory coreceptors of the BCR that are implicated in maintenance of tolerance to self Ags. Enforced ligation of CD22 and the BCR by a nanoparticle displaying both Ag and CD22 ligands induces a tolerogenic circuit resulting in apoptosis of the Ag-reactive B cell. Whether Siglec-G also has this property has not been investigated in large part owing to the lack of a selective Siglec-G ligand. In this article, we report the development of a selective high-affinity ligand for Siglec-G and its application as a chemical tool to investigate the tolerogenic potential of Siglec-G. We find that liposomal nanoparticles decorated with Ag and Siglec-G ligand inhibit BCR signaling in both B1 and B2 B cells compared with liposomes displaying Ag alone. Not only is inhibition of B cell activation observed by ligating the BCR with Siglec-G, but robust tolerance toward T-independent and T-dependent Ags is also induced in mice. The ability of Siglec-G to inhibit B cell activation equally in both B1 and B2 subsets is consistent with our observation that Siglec-G is expressed at a relatively constant level throughout numerous B cell subsets. These results suggest that Siglec-G may contribute to maintenance of B cell tolerance toward self Ags in various B cell compartments.
Abnormalities of the Corpus Callosum in Children Prenatally Exposed to Alcohol

For 20 years, it has been known that fetal alcohol syndrome (FAS) is associated with abnormal brain development. Early autopsy studies point to the corpus callosum as one area affected by heavy alcohol exposure. Little is known, however, about the integrity of the brain in alcohol-exposed children who survive the perinatal period. This study was designed to assess the corpus callosum in living children exposed to high doses of alcohol prenatally. Thirteen children with histories of significant prenatal alcohol exposure and 12 normal control children were evaluated using magnetic resonance imaging. Using the midsagittal section, images were measured for the area of the corpus callosum using a computer-assisted measurement technique. In addition to the overall area, five equiangular regions were determined for each corpus callosum. Of the 13 alcohol-exposed children assessed, two had agenesis of the corpus callosum. The remaining alcohol-exposed children had significantly smaller overall callosal areas, as well as smaller regional areas of four of the five callosal regions, when compared with the normal control children. Importantly, when corrected for brain size, three of the five callosal regions were still smaller in the alcohol-exposed children, although overall area of the corpus callosum was no longer significantly different. These results suggest that prenatal exposure to high levels of alcohol is associated with abnormalities of the corpus callosum. They verify callosal agenesis in children with FAS, which previously had only been noted in autopsy reports.(ABSTRACT TRUNCATED AT 250 WORDS)
A Century of Sea Urchin Development

SYNOPSIS. In the last quarter of the nineteenth century several investigators including Richard and Oskar Hertwig, Theodor Boveri, Hans Driesch, Curt Herbst, T. H. Morgan and others turned their attention to sea urchin eggs and early embryos. This favorable combination of outstanding investigators and the sea urchin embryo as an experimental organism contributed to a fundamental understanding of the cell, fertilization and heredity. The advantages of the sea urchin continued to be recognized as experimental embryologists used these embryos to develop the concepts of gradients, regulative development and inductive interactions. Then, as developmental biology arose from chemical embryology, the sea urchin embryo once again emerged as an ideal experimental animal, pivotal in the understanding of the molecular and developmental biology of eukaryotic organisms.
The Inaugural Frank Ellis Lecture — Iatrogenic Cancer: The Impact of Intensity-modulated Radiotherapy

Abstract It is an honour and personal pleasure to give the inaugural Frank Ellis Lecture to celebrate his 100th birthday, and to acknowledge his enormous contributions to radiation oncology. Intensity-modulated radiotherapy (IMRT) allows dose to be concentrated in the tumour volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers because more fields are used which involves a bigger volume of normal tissue exposed to lower doses. It has been estimated that IMRT may double the incidence of solid cancers in long-term survivors. This may be acceptable in older patients if balanced by an improvement in local tumour control and redced toxicity. On the other hand, the incidence of second cancers is higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children. First, they are more sensitive to radiation-induced cancer than adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, there is the question of genetic susceptibility, as many childhood cancers involve a germline mutation. The levels of leakage radiation in current Linacs can be reduced, but the cost would be substantial. An alternative strategy is to replace X-rays with protons. This is an advantage only if the proton machine uses a pencil scanning beam, as passive modulation of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT.
Cigarette Smoking and Perceived Health in School Dropouts: A Comparison of Mexican American and Non-Hispanic White Adolescents

Objective: To examine the relations between educational attainment and health (cigarette smoking and perceived health) in Hispanic adolescents. Method: Participants included 3,360 Mexican American and non-Hispanic white adolescents ranging in age from 12 to 21 years. The sample included school dropouts, academically at-risk students, and control students. Results: School dropouts were 6.46 times more likely and academically at-risk students were 2.80 times more likely to smoke heavily than were control students. In addition, school dropouts reported poorer health than did their peers. Results suggest that the relation between educational attainment and perceived health is mediated by cigarette smoking. Conclusions: Increased awareness of educational attainment as a significant risk factor for smoking in Hispanic adolescents will enable smoking cessation services to be targeted more effectively.
Effect of Substrate Surface Structure and Deposition Conditions on the Microstructure of Tin Dioxide Thin Films Synthesized by Femtosecond Pulsed Laser Deposition

Tin oxide films were deposited on sapphire and silicon substrates using reactive femtosecond pulsed laser deposition at temperatures ranging from room temperature to 700°C. The effect of electrical discharge and background oxygen pressure on the thin film microstructure was studied. The microstructure of the films was characterized by transmission electron microscopy and x-ray diffraction. SnO2 films fabricated consist of different textures in microstructures that depend on the deposition conditions and substrate surface structures. For instance, films deposited on the (101¯2) sapphire (R-cut) are amorphous if deposited at room temperature, whereas films deposited at 700°C were epitaxial, single crystalline. Discharge and oxygen pressure had a strong effect on the ion/neutral ratio of the ablated plasma plume of SnO2.
Genetic depletion indicates a late role for U5 snRNP during in vitro spliceosome assembly.

The pre-mRNA splicing pathway is highly conserved from yeast (S. cerevisiae) to mammals. Of the four snRNPs involved in splicing three (U1, U2 and U4/U6) have been shown to be essential for in vitro splicing. To examine the remaining snRNP, we utilized our previously described genetic procedures (Seraphin and Rosbash, 1989) to prepare yeast extracts depleted of U5 snRNP. The results show that U5 snRNP is necessary for both steps of pre- mRNA splicing and for proper spliceosome assembly, i.e., addition of the U4/U5/U6 triple snRNP. The prior steps of U1 and U2 snRNP addition occur normally in the absence of U5 snRNP.
Photodynamic therapy: unapproved uses, dosages, or indications.

Photodynamic therapy (PDT) represents a promising treatment modality for a variety of malignant tumors and selected benign diseases. PDT is a bimodal procedure, involving the topical or systemic administration of a photosensitizing chemical and selective illumination of the target lesion with visible light. The combination of photosensitizer and light results in localized photodamage and subsequent cell death. The most distinguishing feature of PDT is its ability to discriminate between diseased and healthy tissues. In photodynamic diagnosis (PDD), the fluorescence of photosensitizing compounds is utilized as a diagnostic tool to delineate and detect neoplastic lesions. Worldwide clinical studies using various photosensitizers and light sources have shown that many cutaneous precancers and cancers respond completely or partially to PDT. The research on PDT in dermatology culminated in the recent approval of topical PDT with the porphyrin precursor -aminolevulinic acid for the treatment of actinic keratoses. Current clinical studies are evaluating the efficacy of PDT for the management of skin cancers as well as selected nonmalignant skin disorders. This article provides a comprehensive overview of unapproved uses of PDT in dermatology.
Synaptic transmission: Noisy synapses and noisy neurons

The finding that the synapses relaying sensory input to the cortex may have different properties than intracortical synapses has implications not only for sensory processing, but for the role of noise in neural computation as well.
Senior residents' perceived need of and preferences for "smart home" sensor technologies.

Objectives: The goal of meeting the desire of older adults to remain independent in their home setting while controlling healthcare costs has led to the conceptualization of “smart homes.” A smart home is a residence equipped with technology that enhances safety of residents and monitors their health conditions. The study aim is to assess older adults’ perceptions of specific smart home technologies (i.e., a bed sensor, gait monitor, stove sensor, motion sensor, and video sensor). Methods: The study setting is TigerPlace, a retirement community designed according to the Aging in Place model. Focus group sessions with fourteen residents were conducted to assess perceived advantages and concerns associated with specific applications, and preferences for recipients of sensor-generated information pertaining to residents’ activity levels, sleep patterns and potential emergencies. Sessions were audio-taped; tapes were transcribed, and a content analysis was performed. Results: A total of fourteen older adults over the age of 65 participated in three focus group sessions Most applications were perceived as useful, and participants would agree to their installation in their own home. Preference for specific sensors related to sensors’ appearance and residents’ own level of frailty and perceived need. Specific concerns about privacy were raised. Conclusions: The findings indicate an overall positive attitude toward sensor technologies for nonobtrusive monitoring. Researchers and practitioners are called upon to address ethical and technical challenges in this emerging domain.
Hydrographic Surveying from Personal Watercraft

A hydrographic surveying system has been designed and tested to acquire nearshore beach profile data. Traditional vessel-mounted echosounder surveying instrumentation was placed in watertight containers and configured for a personal watercraft for measurements of subaqueous nearshore beach profiles. The system is able to withstand the harsh environment of the nearshore and acquire beach profile information across the surf zone. This paper describes the system and results of a comparison in Myrtle Beach, S.C., between surveys collected over a 3-day period by the personal watercraft system and by a similar system mounted aboard a traditional coastal survey vessel. The bathymetric measurements for the personal watercraft-mounted echosounder surveying system display mean repetitive differences of 6 cm.
Current Trends in Education: How Single-subject Research Can Help Middle and High School Educators Keep Up with the Zeitgeist

Abstract Trends in educational research, teaching practices, and teacher responsibilities change over time. There is currently a movement away from relying on summative assessment and large-group research to assessing individual students on a formative basis. This push is partially legal, and the 2004 Individuals with Disabilities Education Improvement Act (IDEIA) is encouraging adoption of Response to Intervention (RtI) at all levels of education. One research methodology that is particularly poised to meet the call by IDEIA is single-subject research designs, which have recently been endorsed by the What Works Clearinghouse. This article provides an overview of common single-subject designs, discusses the underlying logic of these designs, identifies many advantages this methodology provides to the classroom, and describes the dimension of behavior that may be measured and graphed for visual analysis. Understanding single-subject research designs and their use at the middle and secondary level is one of...
Survival, complications, and analysis of risk factors after renal transplantation in cats.

Objective— To report survival, complications, and analyze risk factors for survival after renal transplantation (RTr) and cyclosporine-A based immunosuppression in cats. Study Design— Historical cohort. Animals— Cats (n=60). Methods— Data were obtained from medical records of cats that had RTr. Influence of various perioperative factors on survival and complications was evaluated. Occurrence of postoperative hypertension (HT), seizures, infection, acute allograft rejection (AR), congestive heart failure (CHF), and delayed graft function (DGF) was evaluated. Results— Survival to discharge after RTr was 77.5%. Estimated median overall survival time was 613 days; 6 month and 3 year overall survival proportions were 65% and 40%, respectively. Age, weight, and blood pressure influenced overall survival. Increased preoperative creatinine concentration, blood urea nitrogen, postoperative creatinine concentration, left ventricular wall thickness, and reduced creatinine reduction ratio influenced survival until discharge. HT was identified in 9/30 (30%) cats; however, no risk factors were identified, nor was HT related to seizures. AR was identified in 8/62 (13%) grafts. Infection, predominantly bacterial, developed in 22/60 (37%) cats. CHF occurred in 7/60 (12%) cats before discharge. Cats experiencing CHF were younger, had an increased incidence of heart murmurs, and poor initial graft function. DGF was identified in 5 cats and seizures in 2 cats. Conclusions— RTr affords cats with CRF long survival times. Older cats and cats with severe azotemia, HT, and cardiovascular disease may have increased mortality after RTr. Complications after RTr were common. Clinical Relevance— Clinicians should be aware of these risk factors when recommending feline RTr.
Critical behavior of charge-density waves below threshold: Numerical and scaling analysis.

The critical behavior of pinned charge-density waves (CDW's) is studied as the threshold for sliding is approached. Using the Fukuyama-Lee-Rice Hamiltonian with relaxational dynamics, the polarization and linear response are calculated numerically. Analytic bounds on the subthreshold motion are used to develop fast numerical algorithms for evolving the CDW configuration. Two approaches to threshold, reversible and irreversible, are studied, which differ in the details of the critical behavior. On the irreversible approach to threshold, the response due to avalanches triggered by local instabilities dominates the polarizability, which diverges in one and two dimensions
A Brief History of Great Discoveries in Pharmacology: In Celebration of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics

When the American Society of Pharmacology and Experimental Therapeutics (ASPET[1][1]) Centennial Committee began considering ways to celebrate the Society's 100th anniversary in 2008, an early interest was expressed in having a publication that presented the research history of the discipline.
An assessment of lightning or in situ instabilities as a source for whistler mode waves in the night ionosphere of Venus

Low-altitude data acquired on orbits 484-526 of the Pioneer Venus Orbiter are used to assess the most probable source of whistler mode waves in the nightside ionosphere of Venus. The effect of electron temperature on whistler mode propagation is discussed, with particular emphasis on the growth rate of gyroresonant instabilities. The wave intensity as observed with the Pioneer Venus Orbiter electric field detector is compared with various plasma parameters to determine if it is likely that the waves are generated by an in situ instability. It is shown that gyroresonant whistler mode instabilities do not explain the Pioneer Venus wave data. It is demonstrated that the magnetic field strength controls the wave intensity, rather than density, and it is concluded that the electron Beta(e) is the primary factor in the occurrence of the 100-Hz waves detected in the nightside ionosphere of Venus. The present analysis supports the interpretation that these waves are due to lightning in the Venus atmosphere.
Improper Shoulder Belt Use by Maryland Drivers

This study attempted to determine the types and frequency of improper shoulder belt use, with particular emphasis on belt slack, in a mandatory seat belt use state. Motion picture films of drivers approaching stop signs in Maryland were analyzed by a trained panel to ascertain belt use and misuse. Over half of the drivers of 1974-1987 model vehicles were observed to be belted. Slack in shoulder belts was the most common type of misuse and was much more prevalent among drivers of domestic cars; 27% had 1 to 2 inches as slack in their belts, and 8% had had three or more inches. In imported cars, only 5% of belted drivers had 1 to 2 inches of slack, and none had 3 or more inches. The window shade slack mechanism found only in domestic vehicles, was most often associated with the slack.
Allogeneic Alternatives to Autologous Bone Marrow: The MSC Combined Cell Strategies

The successful application of autologous and allogeneic stem cell therapy for heart disease has prompted more recent preclinical, and a few clinical, studies examining the safety and efficacy of combining two different types of stem cells. In virtually all instances, the combination worked better at reducing scar size and/or improving cardiac function than either cell type alone providing impetus for using two cell types together as a novel therapeutic strategy. This success is moving the field closer to combination therapy clinical trials, the first of which will examine a mix of mesenchymal and cardiac stem cells.
CONSERVATION LAWS AT NANO/MICRO SCALES

The atomic view of a crystal is as a periodic arrangement of local atomic bonding units. Each lattice point defines the location of the center of a unit. The space lattice is macroscopically homogeneous. Embedded in each lattice point is a group of bonded atoms, the smallest structural unit of the crystal. The structure of the unit together with the network of lattice points determines the crystal structure and hence the physical properties of the material. For crystals that have more than one atom in the unit cell, elastic distortions give rise to wave propagation of two types: acoustic and optic. In the acoustic type, all atoms in the unit cell move essentially in the same phase, resulting in deformation of the lattice. In the optical type, atoms move within the unit cell, leave the lattice unchanged, and give rise to internal deformations. In real material response, atomic vibrations usually include simultaneous lattice deformation and internal deformation. The displacement of the -th atom in the k-th unit cell, u(k, ) is in fact a sum of the lattice displacement u(k) and the internal displacement (k,
Face modeling and tracking with Gabor Wavelet Network prior

An efficient and accurate face modeling based on Garbor wavelet network (GWN) is introduced. GWN is very useful because it can create sparse representation of object for fast matching and it is a biologically motivated feature. However the beauty of GWN is offset by inefficient time-consuming modeling of objects. Therefore an efficient and accurate modeling method is needed for GWN. GWN prior for faces is learned from University of Essex Faces94 database using Levenberg-Marquardt optimization method and K-means clustering. Then, guided by GWN prior, the new modeling process efficiently achieves better modeling. To evaluate the quality of modeling, sum of squared difference is used and tracking algorithm is applied to the model as a verification of our proposed method.
Enzymic and molecular analysis of microbial communities associated with lotic particulate organic matter

SUMMARY 1. Most allochthonous plant detritus moves through stream ecosystems as fine particulate organic matter (FPOM), whose associated microbial communities, unlike those of coarse detritus, have received little scrutiny. 2. Benthic POM was collected from a fourth-order boreal river and two first-order tributaries in northern New York during July 1991, sorted it into eight size fractions ranging from 38 to >4000 μm, and assayed each fraction for ergosterol, DNA, and the activity of nine extracellular enzymes: β-1, 4-glucosidase, endocellulase, cellobiohydrolase, phenol oxidase, peroxidase, β-N-acetylglucosaminidase, acid phosphatase, alkaline phosphatase, and aryl sulphatase. In addition, DNA-DNA hybridization was used to investigate the structural similarity of the microbial communities associated with the FPOM fractions. 3. Various enzymes showed distinct activity patterns in relation to particle size as well as among sites. Half of the possible pairwise correlations among enzyme variables were statistically significant, but no enzyme activities were correlated with biomass indices (DNA and ergosterol concentration). DNA-DNA dot-blot hybridizations suggested extensive structural similarity among the microbial communities associated with FPOM fractions. 4. Cluster analysis was used to compare microbial functional similarity, measured by enzyme assays, and structural similarity, measured by DNA—DNA hybridization. Comparison of cluster coefficients showed a weak correlation between community structural similarity and functional similarity (r= 0.51) with fifteen of eighteen fractions grouped within a narrow range of distance. 5. The results suggest a convergence in microbially mediated FPOM processing despite system-level differences in litter and water quality.
Of mice and memory.

The recent paper by Tang et al. (1999) describing the genetic enhancement of learning and memory in mice sparked a media frenzy that even a reclusive scientist could not avoid. For a brief period we were saturated by stories from newspapers, television, and radio reporting on these “smart” mice and the “IQ gene” and, inevitably, the possibility of enhancing human intelligence. For those of us in the field of neuroscience, the hypothetical applications of this paper have encountered more skepticism, but the results of the project make a tangible contribution to our current understanding of learning and memory. The inspiration for the study of Tang et al. comes from the predominant theory on the cellular basis for learning, called Hebb’s rule, which states that synaptic transmission between two neurons will be strengthened if the two cells are simultaneously active and one cell repeatedly excites or causes the other cell to fire (Hebb 1949). This form of synaptic plasticity called long-term potentiation (LTP) clearly exists, as well as the reverse of LTP called long-term depression (LTD), a use-dependent decrease in synaptic strength. However, the relationship of these processes to memory is still in dispute. One implication of Hebb’s rule suggests that improved coincidence detection between neurons will result in improved learning. Tang et al. set out to test this hypothesis. They did this by altering the characteristics of the protein responsible for coincidence detection, the N-methyl-D-aspartate (NMDA) receptor. This receptor will only activate when it binds glutamate released by activity in the presynaptic cell and when it senses postsynaptic activity in the form of membrane depolarization. When the NMDA receptor detects these two events within a short time window, it allows calcium into the cell and this calcium is critical for inducing LTP. The NMDA receptor is composed of an obligatory NR1 subunit and a selection of NR2 subunits (A–D). The NR2 subunit confers different channel properties on the receptor complex. One intriguing subunit difference is the longer excitatory postsynaptic potential (EPSP) observed in NR2B-containing receptors in comparison to NR2A-containing receptors. This longer EPSP suggests that NR2B-containing receptors have a longer time window for detecting preand postsynaptic activity resulting in increased coincidence detection and enhanced LTP when activity is less synchronized. The developmental regulation of NR2B supports the relationship between this subunit and increased LTP because the expression of NR2B is highest when the animal is young and decreases in adulthood, correlating well with the higher amount of LTP
Role of neutrophils in BCG immunotherapy for bladder cancer

Bladder cancer accounts for approximately 13,000 deaths annually, and >60,000 new cases will appear this year, making it the fourth and tenth most common cancer among men and women, respectively. The majority of the newly diagnosed cases will be diagnosed prior to muscle invasion, and are thus potentially completely curable. Unfortunately, >20% of patients initially diagnosed with non-muscle invasive bladder cancer will eventually die of their disease despite local endoscopic surgery. Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used for the treatment of bladder cancer since 1976, and continues to be at the forefront of therapeutic options for this malignancy. Despite its success and worldwide acceptance, the antitumor effector mechanisms remain elusive. BCG therapy induces a massive local immune response characterized by the expression of multiple cytokines in the urine and bladder tissue, and the influx of granulocytes and mononuclear cells into the bladder wall. Findings from our laboratory have demonstrated that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is induced by BCG treatment, and TRAIL was expressed on polymorphonuclear neutrophils (PMN) in the urine obtained from patients after intravesical BCG instillation. Subsequently, we have determined that BCG and components of the mycobacterial cell wall can directly stimulate the release of soluble TRAIL from PMN through toll-like receptor-2 (TLR2) recognition that is augmented by interferon (IFN). Based on our work and that of others implicating the need for T helper type 1 (Th-1) cytokine responses to BCG therapy for therapeutic results, we propose that TRAIL is released by PMN migrating to the bladder in response to BCG treatment. In addition, IFN acts to augment and prolong the amount of TRAIL released by PMN, resulting in an effective therapeutic outcome.
Mining system audit data: opportunities and challenges

Intrusion detection is an essential component of computer security mechanisms. It requires accurate and efficient analysis of a large amount of system and network audit data. It can thus be an application area of data mining. There are several characteristics of audit data: abundant raw data, rich system and network semantics, and ever "streaming". Accordingly, when developing data mining approaches, we need to focus on: feature extraction and construction, customization of (general) algorithms according to semantic information, and optimization of execution efficiency of the output models. In this paper, we describe a data mining framework for mining audit data for intrusion detection models. We discuss its advantages and limitations, and outline the open research problems.
Type-sensitive control-flow analysis

Higher-order typed languages, such as ML, provide strong support for data and type abstraction. While such abstraction is often viewed as costing performance, there are situations where it may provide opportunities for more aggressive program optimization. Specifically, we can exploit the fact that type abstraction guarantees representation independence, which allows the compiler to specialize data representations. This paper describes a first step in supporting such optimizations; namely a control-flow analysis that uses the program's type information to compute more precise results. We present our algorithm as an extension of Serrano's version of 0-CFA and we show that it respects types. We also discuss applications of the analysis with examples of optimizations enabled by the analysis that would not be possible using normal CFA.
A Homotopy Theory of Orbispaces

An orbifold is a singular space which is locally modeled on the quotient of a smooth manifold by a smooth action of a finite group. It appears naturally in geometry and topology when group actions on manifolds are involved and the stabilizer of each fixed point is finite. The concept of an orbifold was first introduced by Satake under the name “V -manifold” in a paper where he also extended the basic differential geometry to his newly defined singular spaces (cf. [32]). The local structure of an orbifold – being the quotient of a smooth manifold by a finite group action – was merely used as some “generalized smooth structure”. A different aspect of the local structure was later recognized by Thurston, who gave the name “orbifold” and introduced an important concept – the fundamental group of an orbifold (cf. [37]). In 1985, physicists Dixon, Harvey, Vafa and Witten studied string theories on Calabi-Yau orbifolds (cf. [14]). An interesting discovery in their paper was the prediction that a certain physicist’s Euler number of the orbifold must be equal to the Euler number of any of its crepant resolutions. This was soon related to the so called McKay correspondence in mathematics (cf. [25]). Later developments include orbifold or stringy Hodge numbers (cf. [38, 40, 2]), mirror symmetry of Calabi-Yau orbifolds (cf. [29]), and most recently the Gromov-Witten invariants of symplectic orbifolds (cf. [11, 12]). One common feature of these studies is that certain contributions from singularities, which are called “twisted sectors” in physics, have to be properly incorporated. This is called the “stringy aspect” of an orbifold (cf. [30]). This paper makes an effort to understand the stringy aspect of orbifolds in the realm of “traditional mathematics”. Surprisingly, we were led to a refinement of Thurston’s discovery!
Notch Signaling: A Novel Therapeutic Target for Cancer

Aberrant Notch signaling has been implicated in the uncontrolled growth of malignant cells, which might function as an oncogene. The further understanding of Notch signaling in normal development and malignant transformation may open up a new avenue for developing novel cancer therapeutics. The first evidence for the involvement of Notch signaling in cancer came from T-cell acute lymphoblastic leukaemia (T-ALL). The progress in the characterization of the mechanisms that mediate the oncogenic activity of Notch signaling make it possible to develop new anti-Notch therapies in the treatment of T-ALL. The high prevailing of Notch1 mutations in T-ALL makes it an ideal target for small molecules therapy. In the gross, Notch signaling could be inhibited at several levels: ligand binding, endocytosis, proteolysis or transcriptional activity [2]. A multi-subunit protease,
Feeding Mechanisms, Body Size, and the Ecology and Evolution of SnakesIntroduction to the Symposium

The popular view of the Age of Reptiles as a Mesozoic phenomenon that closed with the extinction of dinosaurs does not consider the remarkable evolutionary success of one group of living reptiles, the snakes. This suborder of the Squamata is first known from Cretaceous fossils of extinct groups and boa-like forms (Hoffstetter, 1962). Ancestors of modern snakes, the Caenophidia, appeared in the Paleocene and their radiation in the second half of the Cenozoic has been so rapid and extensive that the Neogene could appropriately be known as "The Age of Snakes" (Stanley, 1979). What is it about snakes that has made them so successful? The elongate, legless serpentine body form is a distinctive characteristic of snakes and it influences all areas of their biology. Snakes differ markedly from their closest relatives, the lizards, in body size. Most lizards are small animals weighing less than 20 g as adults and feed on insects. Nearly 80% of living lizard species fit that description and morphological adaptations that appear to be related to insectivorism as a dietary specialty have characterized lizards from their initial appearance in the fossil record (Carroll, 1977: Pough, 1980). In contrast, nearly 75% of snake species have adult body masses greater than 20 g. Because most small mammals also have body masses of 20 g or more, the disparity of body sizes of snakes and lizards places these two suborders of squamate reptiles in quite different relationships with mammals. Lizards appear to avoid competition
A Unified Algorithmic Framework for Block-Structured Optimization Involving Big Data: With applications in machine learning and signal processing

This article presents a powerful algorithmic framework for big data optimization, called the block successive upper-bound minimization (BSUM). The BSUM includes as special cases many well-known methods for analyzing massive data sets, such as the block coordinate descent (BCD) method, the convex-concave procedure (CCCP) method, the block coordinate proximal gradient (BCPG) method, the nonnegative matrix factorization (NMF) method, the expectation maximization (EM) method, etc. In this article, various features and properties of the BSUM are discussed from the viewpoint of design flexibility, computational efficiency, parallel/distributed implementation, and the required communication overhead. Illustrative examples from networking, signal processing, and machine learning are presented to demonstrate the practical performance of the BSUM framework.
Responses of the pelvic vascular bed to intra-arterial stimulation of beta-adrenergic and cholinergic receptors in pregnant and nonpregnant sheep

Abstract The responses of different parts of the pelvic vascular bed to beta-adrenergic and cholinergic receptor stimulation were studied in chronically instrumented, unanesthetized pregnant and nonpregnant sheep. Isoproterenol and acetylcholine were administered intra-arterially in progressively increasing bolus injections, and dose-response curves were constructed for changes in blood flows, arterial pressure, and heart rate. Response to beta-adrenergic and cholinergic stimulation was measured before and after the agents reached the central circulation. In addition, data were obtained from the same animals before and after pharmacologic cardiac denervation. Results show: (1) Stimulation of beta-adrenergic and cholinergic receptors produced active vasodilatation in extrauterine vascular beds with minor changes in uterine blood flow of the pregnant horn; (2) the changes in uterine flow observed during beta-adrenergic and cholinergic stimulation were probably secondary and related to a shift of blood from the uterus to other vascular beds that were actively dilated; (3) the response of the pregnant animal to any given dose of the autonomic agonist was strikingly smaller to that of the nonpregnant animal. A number of physiologic factors peculiar to pregnancy may contribute to this difference; among these are: (1) dilution factor related to the greater volume flow; (2) near-maximal dilatation of some blood vessels and the presence of the low resistance system of placental circulation, and (3) the effect of progesterone on the vascular smooth muscle. (Am. J. Obstet. Gynecol. 141:599, 1981.)
Allied health workers in pediatrics.

An article summarizing the developments and concerns of the junior college1 may seem to be keeping strange company in a pediatric journal. Yet, the extraordinary growth spurt of this educational institution in recent years is far from remote to the issues facing pediatric practice in the United States. From global analyses of health manpower requirements and from the outcries of the consumer and health professional alike, comes the message that more personnel are needed to deliver health services to children. The growth of junior colleges and the development of "community" colleges as extensions of the public education system are healthy expressions of an American capacity for adjustment and innovation in the face of the personnel demands of a technological society.
Sensorimotor recalibration during split-belt walking: task-specific and multisensory?

Motor adaptations not only recalibrate movement execution but also can lead to altered movement perception in multiple sensory domains. Vazquez, Statton, Busgang, and Bastian (J Neurophysiol 114: 3...
The syndrome of a large drop in hematocrit in hospitalized patients: clinical features and gastrointestinal bleeding outcomes.

Background Hemoglobin/hematocrit decreases in hospitalized patients without evidence of obvious gastrointestinal (GI) bleeding are common and often attributed to GI lesions. We hypothesized that inpatients with hematocrit declines without clinically overt GI bleeding have distinct clinical features and hence aimed to evaluate this clinical syndrome. Methods We evaluated consecutive GI consults for patients with a decrease (drop) in hematocrit. Patients with documented prior GI bleeding, melena, hematochezia, hematemesis, and melenemesis were excluded. Hematocrit drops were calculated from preconsult zenith and nadir values and identified as acute (within 7 days), intermediate (7–30 days), or remote (beyond 30 days) on the basis of the shortest time to a hematocrit drop of at least 6%. Results We identified 101 patients having hematocrit drops without clinical evidence of GI bleeding. Seventy-six patients (75%) had an acute drop in hematocrit with a mean decline of 9.5%, whereas the 25 patients with an intermediate or remote drop in hematocrit had a mean decline of 12.5%. Endoscopic evaluation was performed in 55 patients. Five patients (5%) had a lesion consistent with GI bleeding; identified lesions included ischemic colitis, duodenal ulcer, esophageal varices, and postsphincterotomy ulcer. In the remaining 96 patients, a clinical explanation for the hematocrit drop was identified in 56 patients (58%), most commonly attributed to sepsis/shock, volume shifts, and postprocedure bleeding. Conclusions Hematocrit drops without visible GI bleeding were uncommonly caused by bleeding intestinal lesions, contrary to current dogma. Non-GI explanations for hematocrit drops were often identified, although the cause of hematocrit drop remained unexplained in many patients.
13C NMR Spectroscopy of Amorphous Hydrogenated Carbon and Amorphous Hydrogenated Boron Carbide

We report the 13 C NMR spectra of amorphous hydrogenated carbon and boron carbide. The amorphous hydrogenated carbon spectra consist primarily of a sp 2 carbon peak at 40 ppm and a sp 3 carbon peak at 140 ppm and are in reasonable agreement with recent theoretical calculations of Mauri, Pfrommer, and Louie, but there are some noteable discrepancies. The amorphous hydrogenated boron carbide spectra are very different from that of amorphous hydrogenated carbon, showing two sharp lines at 135 and 170 ppm at low boron concentrations and an intense, broader line at 15 ppm at high boron concentrations. We suggest the two sharp lines at 135 and 170 ppm could be due to carbon atoms in boron-containing aromatic rings, and the broader line at 15 ppm as due to carbon atoms in boron carbide icosahedra. These lines provide evidence of nanocrystalline structure imbedded in an amorphous hydrogenated boron carbide matrix.
A survey of central association members about the definition, management, and complications of shoulder dystocia.

OBJECTIVES To determine practice patterns for shoulder dystocia and concepts dealing with brachial plexus palsy. METHODS An Internet-based 25-question survey was electronically disseminated to all current members of the Central Association of Obstetricians and Gynecologists. For those individuals who did not respond, an additional opportunity to complete the assessment was provided during the 2009 annual meeting. RESULTS Of 429 Central Association of Obstetricians and Gynecologists members, 268 (62%) responded, with 192 (78%) filling out the survey online. Nearly 90% of those queried believed that shoulder dystocia was unpredictable and unpreventable. Thirty-seven percent felt that an elective cesarean delivery should be offered for an estimated fetal weight of 4,500 g among nondiabetics. Just 40% would have allowed a trial of labor with a documented history of shoulder dystocia. Slightly more than half answered that they never used either lateral or excessive traction and obstetrician-gynecologists were more likely than maternal-fetal medicine specialists to conclude that traction applied by the clinician doing the delivery was the cause of shoulder dystocia-related brachial plexus palsy (36% compared with 12%, P=.005). Maternal-fetal medicine specialists were more likely to believe that 40-50% of brachial plexus palsies occur without concomitant shoulder dystocia (21% compared with 9%, P=.015). CONCLUSION Differences in practice patterns exist among with regard to management recommendations of the American College of Obstetricians and Gynecologists' Practice Bulletin on shoulder dystocia. LEVEL OF EVIDENCE III.
Succinic cytochrome C reductase activity in kidney and liver tissue from starved and fed rabbits.

SummaryThe succinic cytochrome C reductase activity of rabbit kidney and liver homogenates is significantly greater in homogenates aged for 48 hours at 4°C than when freshly prepared. Enzyme activities are greater for freshly prepared kidney and liver homogenates in fed animals than in animals starved for 10 days, but the activity in aged preparations for tissues of fed or starved animals is not significantly different. These data suggest the need for caution in comparison of enzyme activities of tissues from animals in different physiological states.
Seeds for the Future. The Impact of Genetically Modified Crops on the Environment

Jenny Thomson presents cogent arguments in favor of the use of genetically modified organisms (GMOs), especially plants, for benefit of the environment and of human society. This is a somewhat contentious topic, termed “Frankenfoods” by opponents. As the transgenes are frequently of bacterial (for example those for Bt toxin) or viral (for plant resistance to viral infections) origin, these topics are of concern to ASM members. GMO plants are increasingly and widely planted in many major agricultural producing countries, so this is a global concern.
Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users.

Background Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. Methods and Findings A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. Conclusions These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population.
The Doctrine of Neural Correspondences

Publisher Summary This chapter discusses the doctrine of neural correspondences. According to the Principle of Correspondence, psychological events mimic physiological processes. Not only do mental events and brain processes match up, one for one, but they may even share fundamental characteristics. Underlying the gallery of analogies and common principles operating in different senses, there may exist, each for each, analogous and common neural mechanisms. A Principle of Correspondence cannot legislate analogy. It is possible that correspondence is a principal rule of nature, that some fundamental properties of the natural world do forge, even demand, structural similarities between physical and mental states. The Principle of Correspondence manifests the metaphorical imperative, the urge to discover or create similarities. However, it is not a natural law, which is to say that scientists are not bound to build only analog models. Through the Principle of Correspondence, analogy is compounded on top of analogy. The new set of analogies—neural analogies—work at two levels: (1) parallel to their psychological counterparts and (2) analogous to them.
The Changing Role for Tracheostomy in Patients Requiring Mechanical Ventilation

Tracheostomy is performed in patients who require prolonged mechanical ventilation or have upper airway instability. Percutaneous tracheostomy with Ciaglia technique is commonly used and rivals the surgical approach. Percutaneous technique is associated with decreased risk of stomal inflammation, infection, and bleeding along with reduction in health resource utilization when performed at bedside. Bronchoscopy and ultrasound guidance improve the safety of percutaneous tracheostomy. Early tracheostomy decreases the need for sedation and intensive care unit stay but may be unnecessary in some patients who can be extubated later successfully. A multidisciplinary approach to tracheostomy care leads to improved outcomes.