cssi/SciSciGPT-SciSciNet huggingface dataset:
Severe anaphylactic reactions to glutamic acid decarboxylase (GAD) self peptides in NOD mice that spontaneously develop autoimmune type 1 diabetes mellitus.

Insulin dependent (i.e., "type 1") diabetes mellitus (T1DM) is considered to be a T cell mediated disease in which TH1 and Tc autoreactive cells attack the pancreatic islets. Among the beta-cell antigens implicated in T1DM, glutamic acid decarboxylase (GAD) 65 appears to play a key role in the development of T1DM in humans as well as in non-obese diabetic (NOD) mice, the experimental model for this disease. It has been shown that shifting the immune response to this antigen from TH1 towards TH2, via the administration of GAD65 peptides to young NOD mice, can suppress the progression to overt T1DM. Accordingly, various protocols of "peptide immunotherapy" of T1DM are under investigation. However, in mice with experimental autoimmune encephalomyelitis (EAE), another autoimmune TH1 mediated disease that mimics human multiple sclerosis, anaphylactic shock can occur when the mice are challenged with certain myelin self peptides that initially were administered with adjuvant to induce the disease. Here we show that NOD mice, that spontaneously develop T1DM, can develop fatal anaphylactic reactions upon challenge with preparations of immunodominant GAD65 self peptides after immunization with these peptides to modify the development of T1DM. These findings document severe anaphylaxis to self peptide preparations used in an attempt to devise immunotherapy for a spontaneous autoimmune disease. Taken together with the findings in EAE, these results suggest that peptide therapies designed to induce a TH1 to TH2 shift carry a risk for the development of anaphylactic reactivity to the therapeutic peptides.
Drug-induced osteoporosis: from Fuller Albright to aromatase inhibitors

Many commonly prescribed medications, such as selective serotonin reuptake inhibitors, proton pump inhibitors, thiazolidinediones, aromatase inhibitors, and androgen deprivation therapy, have been associated with adverse skeletal effects. The levels of evidence in support of a causal relationship between drug use and the development of bone loss and fractures are variable. For some drugs, a causal relationship is suspected (but not proven) based on observational studies, while in others causality is firmly established with randomized, controlled clinical trials. The mechanism of action for skeletal damage is poorly understood for some drugs and well known for others. Guidelines for managing bone health in patients taking some medications with potential skeletal toxicity have been developed using the best available evidence and expert opinion. This is a review of selected medications that have been associated with bone loss and fractures, with recommendations for clinical care.
A dynamic mechanism for recovering from buffer overflow attacks

We examine the problem of containing buffer overflow attacks in a safe and efficient manner. Briefly, we automatically augment source code to dynamically catch stack and heap-based buffer overflow and underflow attacks, and recover from them by allowing the program to continue execution. Our hypothesis is that we can treat each code function as a transaction that can be aborted when an attack is detected, without affecting the application's ability to correctly execute. Our approach allows us to enable selectively or disable components of this defensive mechanism in response to external events, allowing for a direct tradeoff between security and performance. We combine our defensive mechanism with a honeypot-like configuration to detect previously unknown attacks, automatically adapt an application's defensive posture at a negligible performance cost, and help determine worm signatures. Our scheme provides low impact on application performance, the ability to respond to attacks without human intervention, the capacity to handle previously unknown vulnerabilities, and the preservation of service availability. We implement a stand-alone tool, DYBOC, which we use to instrument a number of vulnerable applications. Our performance benchmarks indicate a slow-down of 20% for Apache in full-protection mode, and 1.2% with selective protection. We provide preliminary evidence towards the validity of our transactional hypothesis via two experiments: first, by applying our scheme to 17 vulnerable applications, successfully fixing 14 of them; second, by examining the behavior of Apache when each of 154 potentially vulnerable routines are made to fail, resulting in correct behavior in 139 cases (90%), with similar results for sshd (89%) and Bind (88%).
Mass spectra of aromatic and acetylenic compounds. Part VI. The electron impact-induced rearrangements of substituted phenylacetylenes

The mass spectra of [2H1]phenylacetylene shows 100% H/D randomisation in the molecular ion prior to expulsion of an acetylene fragment. In analogous benzene-substituted phenylacetylenes 70–100% H/D randomisation occurs in the molecular ion or some subsequent fragment. Symmetrical intermediates are proposed to account for the scrambling and it seems likely that carbon–carbon bond fission takes place prior to formation of these intermediates.
The relationships between schizophrenia symptom dimensions and executive functioning components

Research investigating the relationships between executive functioning impairments and the positive, negative, and cognitive schizophrenia symptoms has produced inconsistent results. This inconsistency may be due to the tendency to view executive functioning as a unified process as opposed to multiple fractionated processes. A fractionated model of executive functioning has been supported in several studies of various populations, but few schizophrenia studies have used the factor analytic methods of these studies to empirically determine separate executive functioning components, causing conclusions regarding the relationships between these components and schizophrenia symptoms to be unreliable. The purposes of the present study were to (1) identify separate components of executive functioning by conducting a factor analysis of the performance of individuals with schizophrenia on the Delis Kaplan Executive Function System (D-KEFS) and (2) investigate the relationships between executive functioning components and the three schizophrenia symptom dimensions by correlating the derived factor scores with the scale scores of the Positive and Negative Symptom Scale (PANSS). An exploratory factor analysis revealed two separate components: inhibition/set shifting and mental flexibility. The results showed that the symptom dimensions were differentially related to impairments in executive functioning, with both negative and cognitive symptoms associated with the inhibition/set shifting component, cognitive symptoms alone associated with the mental flexibility component, and positive symptoms unrelated to either component.
Constraints on violating constraints: How languages reconcile the twin dicta of “Be different” and “Be recognizably language”

This paper examines the contradictory demands of using language expressively and still qualifying as language, proposing a functional explanation for the form of words in a linguistic word category. Being expressive requires expending more energy, emitting a more robust signal to convey additional information about the speaker, the perception of an event, etc. Doing so requires violating the common linguistic constraints of everyday language, yet to be recognized as language requires that one’s speech obey these same rules. How speakers satisfy these demands tells us about language in both its function and form. The resolution of this dilemma requires the use of suprasegmental rather than segmental features, e.g., a wider range of and more varied use of F0. Because prosodic features are more susceptible to manipulation, they provide the resources for expressivity. Segmental parameters cannot be so easily violated, though manipulating phonotactics remains fair game. Thus we see that there are constraints on violating constraints.
Evidence from mass spectra and X-ray photoelectron spectra concerning the structure of poly(aminoborane)

Abstract Thermal decomposition mass spectra of a new form of poly(aminoborane) exhibit ions containing -NH 2 BH 2 - chains up to nine atoms in length along with species arising from hydrogen elimination during decomposition of the compound. The XPS spectrum of poly(aminoborane) suggests the presence of equal numbers of B and N atoms each in a single chemical environment. A large cyclic structure for the compound is indicated.
Analysis of Monolithic and Microkernel Architectures: Towards Secure Hypervisor Design

This research focuses on hyper visor security from holistic perspective. It centers on hyper visor architecture - the organization of the various subsystems which collectively compromise a virtualization platform. It holds that the path to a secure hyper visor begins with a big-picture focus on architecture. Unfortunately, little research has been conducted with this perspective. This study investigates the impact of monolithic and micro kernel hyper visor architectures on the size and scope of the attack surface. Six architectural features are compared: management API, monitoring interface, hyper calls, interrupts, networking, and I/O. These subsystems are core hyper visor components which could be used as attack vectors. Specific examples and three leading hyper visor platforms are referenced (ESXi for monolithic architecture; Xen and Hyper-V for micro architecture). The results describe the relative strengths and vulnerabilities of both types of architectures. It is concluded that neither design is more secure, since both incorporate security tradeoffs in core processes.
Omniscopes: Large Area Telescope Arrays with only N log N Computational Cost

We show that the class of antenna layouts for telescope arrays allowing cheap analysis hardware (with correlator cost scaling as $N\mathrm{log}﻿N$ rather than ${N}^{2}$ with the number of antennas $N$) is encouragingly large, including not only previously discussed rectangular grids but also arbitrary hierarchies of such grids, with arbitrary rotations and shears at each level. We show that all correlations for such a 2D array with an $n$-level hierarchy can be efficiently computed via a fast Fourier transform in not two but $2n$ dimensions. This can allow major correlator cost reductions for science applications requiring exquisite sensitivity at widely separated angular scales, for example, 21 cm tomography (where short baselines are needed to probe the cosmological signal and long baselines are needed for point source removal), helping enable future 21 cm experiments with thousands or millions of cheap dipolelike antennas. Such hierarchical grids combine the angular resolution advantage of traditional array layouts with the cost advantage of a rectangular fast Fourier transform telescope. We also describe an algorithm for how a subclass of hierarchical arrays can efficiently use rotation synthesis to produce global sky maps with minimal noise and a well-characterized synthesized beam.
Electroless deposition of Sno2 and antimony doped SnO2 films

Abstract Thin polycrystalline films of SnO 2 and antimony doped SnO 2 have been prepared by simple economic electroless deposition technique. The transmittance in the visible range and the reflectance in the i.r. range for SnO 2 films are ∼80% and ∼70%, respectively, with resistivity ∼10 −2 Ω cm. On the other hand, antimony doped SnO 2 films have transmittance in the visible range and reflectance in the i.r. range, as good as ∼86% and ∼83%, respectively, with resistivity as low as ∼10 −3 Ω cm. By vacuum annealing, the resistivity of both types of films has been brought down as low as ∼10 −3 and ∼10 −4 Ω cm, respectively.
Early childhood co‐sleeping: Parent‐child and parent‐infant nighttime interactions

Cette etude a examine les interactions parent-enfant pendant le debut du sommeil et les reveils durant la nuit chez un echantillon d'enfants d'âge prescolaire d'une petite ville rurale. Le role du co-sommeil par rapport aux habitudes de sommeil et aux reveils la nuit a ete examine en utilisant des rapports etablis par les parents des patterns actuels et passes. Les resultats revelerent que les Dormeurs Solitaires s'engageaient dans des routines plus complexes au moment du sommeil, et faisaient preuve d'un attachement plus long et plus fort a des objects de securite et a des aides au sommeil que les Co-Dormeurs. Les facteurs precurseurs au co-sommeil dans la petite enfance etaient les suivants: l'allaitement, l'allaitement nocturne dans le lit des parents, et le retour au sommeil dans le lit des parents.
A multigrid method for the Poisson–Nernst–Planck equations

Abstract A computational technique for solving the Poisson–Nernst–Planck (PNP) equations is developed which overcomes the poor convergence rates of commonly used algorithms. The coupled Poisson and charge continuity equations are discretized using an unstructured cell-centered finite volume method. A Newton–Raphson linearization accounting for the coupling between the equations through boundary conditions, and the space charge and drift terms, is developed. The resulting linear system of equations is solved using an algebraic multigrid method, with coarse level systems being created by agglomerating finer-level equations based on the largest coefficients of the Poisson equation. A block Gauss–Seidel update is used as the relaxation method. The method is shown to perform well for the transport of K + and Cl - in a synthetic ion channel for driving voltages, surface charges, ion concentrations and channel aspect ratios ranging over several orders of magnitude.
State of Charge Estimation Error due to Parameter Mismatch in a Generalized Explicit Lithium Ion Battery Model

Model-based state of charge (SOC) estimation with output feedback of the voltage error is steadily augmenting more traditional coulomb counting or voltage inversion techniques in hybrid electric vehicle applications. In this paper, the state (SOC) estimation error in the presence of model parameter mismatch is calculated for a general lithium ion battery model with linear diffusion or impedance-based state dynamics and nonlinear output voltage equations. The estimation error due to initial conditions and inputs is derived for linearized battery models and also verified by nonlinear simulations. It is shown that in some cases of parameter mismatch, the state, e.g. SOC, estimation error will be significant while the voltage estimation error is negligible.Copyright © 2011 by ASME
New demographic history of the late 19th-century United States

Abstract Research in historical demography, and its relationship to economic history, has expanded rapidly in recent years. This paper presents a partial survey of work on the historical demography of the United States, emphasizing the late 19th century. The use of micro data sources and new methods are of particular interest. Fertility and mortality receive primary attention, although other areas are covered.
Preparation and characterization of rice protein isolates

Various enzymes were used to treat a protein-enriched rice flour for the production of rice protein isolates. The rice flour containing 49% protein was a by-product from the processing of brown rice for syrup production. The treatment sequence of α-amylase followed by glucoamylase was most effective, resulting in a product with 85% protein content. The product was then treated with a mixture of cellulase and xylanase, which raised the protein content in the insoluble fraction to 91%. Inorganic impurities, such as the metal manganese in the starting rice flour, were effectively removed. The recovered rice proteins, practically intact according to electrophoretic analysis, had relatively poor solubility and emulsification properties; however, these functional properties were improved substantially by adding xanthan gum as a functionality-enhancing agent.
Improvement of computer screen viewing in elderly patients

Abstract Patient with early cataracts or cloud posterior capsules often have problems with the reflected glare from the protective glass surface over the computer screen. This report describes a device which surrounds the computer screen and (a) decreases glare by shading the screen, thus increasing screen contrast, and (b) creates a new image of the computer screen at a lower position. This allows the bifocal wearer to read without tipping his or her head backward.
The Tortures of Mel Gibson Masochism and the Sexy Male Body

The long-standing tradition of male masochism in popular cinema represents a dilemma for psychoanalytically informed gender studies. The persistent image of heroic male bodies bruised, beaten, and displayed for the film audience challenges the gendered binaries that have characterized such moments of powerlessness as feminine. The excessive physical tortures endured by Mel Gibson's characters in such movies as Lethal Weapon, Braveheart, and most clearly Payback illustrate the importance of suffering as an essentially masculine trait. Instead of representing sadism as categorically masculine and masochism as categorically feminine, the torture of cinematic heroes, such as Gibson's Porter in Payback, signifies the necessity of both sides of the sadomasochistic continuum in constructing a superior and unified image of masculinity. Moreover, the visual evidence of physical suffering on display in Gibson's films enhances his sex symbol status by clearly positioning the character's masculinity as undeniably het...
Two in one: report of a patient with spinocerebellar ataxia types 2 and 10.

Objective To report a rare case of the coexistence of 2 spinocerebellar ataxia (SCA) mutations in a single patient. Design Case report. Setting University hospital, Movement Disorders Center. Patient A 54-year-old man of Mexican, American Indian, and French descent with an 11-year history of gait and limb ataxia. Main Outcome Measures Findings of clinical examination, magnetic resonance imaging, and video electroencephalographic monitoring. Results Neurologic history revealed a gradually progressive gait and limb ataxia along with muscle cramps and sensory symptoms in his distal extremities; examination revealed executive dysfunction, dysarthria, ataxia, and sensory neuronopathy. Episodes of loss of awareness were reported, but electroencephalograms were negative. Brain imaging demonstrated severe cerebellar and brainstem atrophy. Genetic evaluation of the case revealed mutations in both the SCA2 and SCA10 genes. Conclusion Our patient has a unique combination of genetic mutations for 2 different SCAs, types 2 and 10, which to our knowledge, has not been previously reported. His clinical phenotype is largely consistent with SCA2, but his possible seizures and Mexican heritage suggest influences of SCA10.
Corticotropin-releasing factor-related peptides, serotonergic systems, and emotional behavior.

Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide that is involved in stress-related physiology and behavior, including control of the hypothalamic-pituitary-adrenal (HPA) axis. Members of the CRF family of neuropeptides, including urocortin 1 (Ucn 1), Ucn 2, and Ucn 3, bind to the G protein-coupled receptors, CRF type 1 (CRF1) and CRF2 receptors. In addition, CRF binding protein (CRFBP) binds both CRF and Ucn 1 and can modulate their activities. There are multiple mechanisms through which CRF-related peptides may influence emotional behavior, one of which is through altering the activity of brainstem neuromodulatory systems, including serotonergic systems. Corticotropin-releasing factor and CRF-related peptides act within the dorsal raphe nucleus (DR), the major source for serotonin (5-HT) in the brain, to alter the neuronal activity of specific subsets of serotonergic neurons and to influence stress-related behavior. CRF-containing axonal fibers innervate the DR in a topographically organized manner, which may contribute to the ability of CRF to alter the activity of specific subsets of serotonergic neurons. CRF and CRF-related peptides can either increase or decrease serotonergic neuronal firing rates and serotonin release, depending on their concentrations and on the specific CRF receptor subtype(s) involved. This review aims to describe the interactions between CRF-related peptides and serotonergic systems, the consequences for stress-related behavior, and implications for vulnerability to anxiety and affective disorders.
Riding the crest of a new wave in memory [NOVORAM]

NOVORAM is a convenient new paradigm that may enable the Moore-law-type progress of semiconductor memory technology to be extended well into the nanoscale, terabit range. However, it still faces the challenges of CMOS-compatible deposition of high-quality, few-nanometer layers of wide-bandgap semiconductors.
Dynamic Load Balancing for Malleable Model Coupling

Dynamic load balancing both within and between constituent subsystems is required to achieve ultra scalability in coupled multi physics and multi scale models. Inter constituent dynamic load balancing requires runtime resizing -- or malleability -- of subsystem processing element (PE) cohorts. In our previous work, we developed and introduced the Malleable Model Coupling Toolkit with a load balance manager implementing and providing a runtime load-balancing algorithm using PE reallocation across subsystems. In this paper, we extend that work by adding the ability to adapt to coupled models that have changing loads during execution. We evaluate the algorithm through a synthetic coupled-model benchmark that uses the LogP performance model as applied to parallel LU decomposition.
Rethinking Guidelines for the Use of Palliative Sedation

Current guidelines treat palliative sedation to unconsciousness as an effective medical treatment for terminally ill patients who need relief from severe symptoms, yet also restrict its use in ways that are extraordinary for medical treatments. A closer look at the kinds of cases in which palliative sedation is used suggests a way of adjusting the guidelines to resolve this seeming contradiction.
Biochemical and ultrastructural effects of monensin on the processing, intracellular transport, and packaging of myeloperoxidase into low and high density compartments of human leukemia (HL-60) cells

Abstract The biosynthesis of myeloperoxidase in human promyelocytic leukemia HL-60 cells was studied by pulse-chase and immunoprecipitation methods and separation of subcellular organelles using Percoll density gradient fractionation. These studies revealed that in control and monensin (1 μ m ) treated cells, more than 85% of the total immunoprecipitable radiolabeled myeloperoxidase was present predominantly in precursor form ( M r 91,000) and resided in lower density compartments after an initial 3-h labeling period. Using biochemical and ultrastructural techniques, the lower density regions of the gradient were found to contain elements of the endoplasmic reticulum and the Golgi complex. Following a 16-h chase period, about 70% of the radiolabeled myeloperoxidase in untreated cells was found predominantly in denser regions of the gradient and was present mainly in the form of the mature large subunit ( M r 63,000). These dense regions were shown to contain azurophilic granules by means of the distribution of β-glucuronidase and myeloperoxidase activities and by electron microscopy. Processing of myeloperoxidase and its deposition into dense granules were blocked by monensin treatment. Following a 16-h chase period in the presence of monensin, approximately 80% of the radiolabeled myeloperoxidase continued to reside in lower density compartments and was predominantly in precursor ( M r 91,000) and intermediate ( M r 81,000 and 74,000) forms. Only about 10% of the radiolabeled myeloperoxidase was associated with dense azurophilic granules. Monensin treatment produced large, Golgi-derived vacuoles which were isolated using Percoll density centrifugation and identified by electron microscopy. These vacuoles were found to be essentially devoid of peroxidase activity and pulselabeled, newly synthesized radiolabeled myeloperoxidase species. The effects of monensin on transport and processing were reversible after a 3-h exposure and 16-h chase period in the absence of monensin. Taken together, these data indicate that maturation of myeloperoxidase is closely linked to its deposition into dense azurophilic granules via a monensin-sensitive process(es). The lower density compartments within which immature myeloperoxidase species accumulate in the presence of monensin appear to be functionally related to or associated with Golgi or endoplasmic reticulum structures distinct from the large monensin-induced vacuoles.
Metal and elastomer seal tests for accelerator applications

Abstract In excess of a thousand metal vacuum seals are used in the vacuum system of the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory. Numerous elastomer seals are used throughout the AGS to seal large beam component chambers. An accelerator upgrade program is being implemented to reduce the AGS operating pressure by a factor of 100 and improve the reliability of the vacuum system. This paper describes work in progress on metal and elastomer vacuum seals to help meet these two objectives. Tests are reported on the sealing properties of a variety of metal seals used with different sealing surfaces. Results are also given on reversible sorption properties of certain elastomers.
Scalar potential model of eddy-current interactions with three-dimensional flaws

Magnetic scalar potential theory is applied to a model of eddy-current detection of a surface-breaking flaw in a conductor. A general boundary integral equation for the potential is derived first in a form suitable for numerical solution. The problem is then specialized to a flaw in a perfectly conducting half-space. A solution algorithm based on the boundary element method is outlined and demonstrated by application to a three-dimensional rectangular slot. Methods for accounting for the effects of nonvanishing skin depth are discussed.
In vivo , Extracellular, Collagen Fibrillogenesis

In vitro collagen fibrillogenesis has been demonstrated by investigators1–3 from solutions of collagen obtained by various means. This communication presents what we believe to be the first evidence for extracellular, in vivo, aggregation of collagen fibrils.
The Effect of Positive Selection on a Sexual Reproduction Gene in Thalassiosira weissflogii (Bacillariophyta): Results Obtained from Maximum-Likelihood and Parsimony-Based Methods

Maximum-Likelihood-based and parsimony-based methods were used to test for potential effects of positive selection on the sexually induced gene 1 (Sig1) in Thalassiosira weissflogii. The Sig proteins are thought to play a role in mediating sperm-egg recognition during the sexual reproduction phase. The results obtained from parsimony-based analyses showed that none of the amino acid sites were influenced by positive selection. Maximum-likelihood analyses indicated that positive selection was affecting a maximum of seven and a minimum of four amino acid sites in the polypeptide derived from Sig1. It was concluded that the results obtained from the maximum-likelihood-based method are more reliable than those obtained from the parsimony-based approach. This is apparently the first study that has shown that reproductive proteins in unicellular eukaryotes are influenced by positive selection.
Orally delivered methadone as a reinforcer: Effects of the opioid antagonist naloxone

The effects of the opioid antagonist naloxone were studied with three monkeys under a mutually exclusive fixed-interval 15 s (FI 15 s) schedule of reinforcement. Under this schedule, at the end of each interval, the monkey could obtain one liquid delivery from either the spout that delivered methadone (0.8 mg/ml) or the spout that delivered vehicle (deionized water). Naloxone doses from 0.0125 to 0.2 mg/kg (IM daily 10 min prior to the session) were studied in an ascending then descending order. In the ascending series, low naloxone doses produced increases of methadone deliveries in the first hour of the session for three monkeys and increases over the entire 3-h session for two of the three monkeys. At higher doses naloxone decreased methadone deliveries in all three monkeys. Naloxone's effects were usually greater during the descending dose series than during the ascending series. These findings suggest that a history of naloxone injections is one determinant of response to the drug. Vehicle maintained responding was generally low and not changed by naloxone in a systematic way. The time course of methadone deliveries showed that naloxone's effects were greatest in the first hour of the session and were a direct function of dose. These experiments demonstrate that oral methadone reinforced behavior is sensitive to naloxone pretreatment and that the effects of naloxone are a direct function of dose.
Thermoperiodism in the Gulf killifish, Fundulus grandis

Male Gulf killifish, Fundulus grandis, were held on various photoperiodic and thermoperiodic regimens for 2 to 4 weeks and examined with respect to body fat stores and testes weights. Groups offish kept on a 24-hr (LD 12:12) photoperiodic regimen were provided a water temperature of 28°C except for a 4-hr daily interval of 20°C given at one of six different times during the photocycle. Similarly, fish kept on a 48-hr (LD 12:36) photocycle and 28–30°C were provided 4-hr cryophases (20°C) once during each photocycle in various phase relations to the photoperiodic regimen. In addition, some groups were held at 20°C and provided 4-hr thermophase (28–30°C) interruptions. Fat stores and gonad weights varied among the groups as a function of the time of day when the temperature interruptions occurred. The photoperiod appears to entrain a circadian rhythm of thermosensitivity, so that the coincidence of a temperature change with a thermosensitive phase alters metabolic and reproductive indices. The circadian mechanism in thermoperiodism appears similar to that involved in photoperiodism.
Comprehension in severe aphasics.

Summary Clinical examination of severely impaired aphasics suggests that despite their poor comprehension, they can still carry out some tasks such as whole body commands. They also seem to discriminate meaningful sentences from nonsense. These observations support the hypothesis that even in severe aphasia the processes of decoding messages are not unitary but complex, and that in some way aphasics have an ability to make discriminations. To investigate the hypothesis in detail, a test was devised of eighty-five items, consisting of familiar and difficult questions, commands, minimally ungrammatical English, semantic and phonologic jargon, and French. a list of criteria for describing aphasic responses was also drawn up, which included gestures as well as speech. Both the test and the scoring criteria were designed to help identify the processes of decoding that aphasics can still employ. Fifteen severe aphasics and two normals were tested. Responses were recorded by two independent judges, who noted down details of gesture and speech (for example, their facial expressions and their use of jargon). The procedure was easy to carry out; agreement between the judges was quite high. a comparison of normal and aphasic performance demonstrated a characteristic rejection by both groups of phonemic jargon and foreign language as incomprehensible. Items in semantic jargon were also rejected by normals while aphasics rejected them in only about 50% of the cases, often instead responding as if they were meaningful. Moreover, even though aphasics could not respond correctly to meaningful questions and commands, they nonetheless were able to distinguish in some way the syntactic forms of the test items. an analysis of jargon utterances demonstrated that they occurred significantly more often in response to information questions than to yes/no questions and to commands. Clearly, even the most severe aphasics tend to maintain an ability to discriminate phonological patterns (Is it English or not?) and over-all syntactic structures (Is it a question or a command?). Their inability to respond correctly, however, to the messages they perceived, suggests that detailed semantic analysis is a separate and later stage of comprehension.
Current Status of Mitoxantrone Combination Chemotherapy Programs: A Personal View

Mitoxantrone is effective therapy in acute leukemia. As a single agent it is well tolerated and at doses of 50–60 mg/m2 induces remission in acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and blastic transformation of chronic myelogenous leukemia (CML). Its toxicity profile suggested that it could be combined readily with other agents, and over the last five years effective combinations incorporating mitoxantrone have been developed. Future trials will be designed to take advantage of our ability to deliver high doses of mitoxantrone without appreciable toxicity and to combine it with the more effective doses of cytarabine.
Regional Brain Abnormalities in 22q11.2 Deletion Syndrome: Association With Cognitive Abilities and Behavioral Symptoms

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two q11DS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls, with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with ele...
Plasma "big" and "big-big" growth hormone (GH) in man: an oligomeric series composed of structurally diverse GH monomers.

Abstract Human GH (hGH) immunoreactivity in plasma can be separated into three species of different molecular size by gel filtration (little, big, and big-big hGH). In contrast to pituitary high mol wt GH forms, the molecular nature of the big hGH forms in blood is not known. Therefore, we purified these hGH size isomers from the plasma of L-dopa-stimulated normal subjects and acromegalic patients. Plasma was chromatographed on Sephadex G–100, and fractions containing big-big, big, and little hGH were generated. hGH was extracted and concentrated from these fractions by immunoadsorbent chromatography and analyzed by polyacrylamide gel electrophoresis (PAGE), sodium dodecyl sulfate-PAGE, and isoelectric focusing. The resulting gel profiles indicated that the majority (70%) of big and big-big hGH was converted to little hGH during extraction and storage. The remainder migrated as distinct species with mol wt of approximately 45, 62, 80, and 110 K in sodium dodecyl sulfate-PAGE. These forms could be converte...
On reversible subroutines and computers that run backwards

A computer design is described which permits subroutines to be executed backward as well as forward, either with their instructions unchanged or replaced with conjugate instructions. It is shown that using this concept a number of new subroutine types can be developed with rather unusual properties. Since these properties are analogous to certain matrix operations, a arallel nomenclature is suggested for their classification.
Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by slowpoke and shaker K+ channel mutations in Drosophila.

Abstract We report naturally occurring, systematic variations in synaptic strength at neuromuscular junctions along the dorsal–ventral (D-V) axis of the Drosophila larval body wall. These gradual changes were correlated with differences in presynaptic neurotransmitter release regulated by nerve terminal excitability and in postsynaptic receptor composition influencing miniature excitatory junctional potential (mEJP) amplitude. Surprisingly, synaptic strength and D-V differentials at physiological Ca2+ levels were not significantly altered in slowpoke (slo) and Shaker (Sh) mutants, despite their defects in two major repolarizing forces, Ca2+-activated Slo (BK) and voltage-activated Sh currents, respectively. However, lowering [Ca2+]o levels revealed greatly altered synaptic mechanisms in these mutants, indicated by drastically enhanced excitatory junctional potentials (EJPs) in Sh but paradoxically reduced EJPs in slo. Removal of Sh current in slo mutants by 4-aminopyridine blockade or by combining slo with Sh mutations led to strikingly increased synaptic transmission, suggesting upregulation of presynaptic Sh current to limit excessive neurotransmitter release in the absence of Slo current. In addition, slo mutants displayed altered immunoreactivity intensity ratio between DGluRIIA and DGluRIIB receptor subunits. This modified receptor composition caused smaller mEJP amplitudes, further preventing excessive transmission in the absence of Slo current. Such compensatory regulations were prevented by rutabaga (rut) adenylyl cyclase mutations in rut slo double mutants, demonstrating a novel role of rut in homeostatic plasticity, in addition to its well-established function in learning behavior.
Unstable Representation of Sound: A Biological Marker of Dyslexia

Learning to read proceeds smoothly for most children, yet others struggle to translate verbal language into its written form. Poor readers often have a host of auditory, linguistic, and attention deficits, including abnormal neural representation of speech and inconsistent performance on psychoacoustic tasks. We hypothesize that this constellation of deficits associated with reading disorders arises from the human auditory system failing to respond to sound in a consistent manner, and that this inconsistency impinges upon the ability to relate phonology and orthography during reading. In support of this hypothesis, we show that poor readers have significantly more variable auditory brainstem responses to speech than do good readers, independent of resting neurophysiological noise levels. Thus, neural variability may be an underlying biological contributor to well established behavioral and neural deficits found in poor readers.
An integral equation method in conformal mapping

This paper describes an integral equation method for computing the conformal mapping of a given simply-connected domain onto the interior of the unit circle. Simple error estimates are available when the given domain possesses symmetry, and results are presented for a number of trial problems of this form.
Conditional Epitopes: Is Your Antibody Always Specific?

In an accompanying article, Josephsen et al. (1999) describe the interesting observation that a monoclonal antibody (MAb) originally generated against purified porcine vimentin (V9) reacts with a novel epitope on an unrelated protein, an epitope that is generated only after glutaraldehyde fixation. These authors point out that such a well-characterized reaction, even though it was not the original target of the MAb generated, can be a useful reagent when used in the proper setting. They suggest that this is “nonspecific” but “selective.” To me, the semantic arguments about what “specific” and “nonspecific” mean are less interesting. I would argue that such reactions are highly “specific” as well as “selective” but, more importantly, that they are “useful.” This novel article highlights an important issue, however. Immunocytochemical methods are incredibly selective and sensitive. They enable us to detect avid reactions using the spectacularly “specific” properties of antibody molecules. The more these methods are used, the more we all must appreciate the power of these selective reactions and the resulting obligation to exercise care in their control and interpretation. I have personally had the experience of generating MAbs to complex mixtures of antigens, i.e., whole cells. This is a humbling experience because of the incredible diversity of high-avidity antibodies one can find. In the thousands of clones we isolated, I do not remember actually finding duplicates; that is, every new clone that showed reaction with something in a cell was unique. Sometimes these clones reacted with different parts of the same molecular species, such as complex elaborate carbohydrates, but each clone generated an antibody that recognized a different portion of such a molecule, i.e., a different epitope. Fixation Preservation of structure for immunocytochemistry using chemical fixatives is well-recognized to create problems. The major challenge with fixation has often been the subsequent lack of reaction of antigens with antibodies. In spite of a widespread interpretative dogma in the literature, most of these problems were not due to chemical alteration of antigen epitopes. They were more commonly a problem of inaccessibility (Willingham and Yamada 1979). This concept has finally gained some acceptance because of the success of antigen retrieval techniques demonstrating that the reactive epitopes were always there in the cells, but they were just inaccessible (Shi et al. 1995). Such a result is reported in the article by Josephsen et al. in their observation that high (2.5%) concentrations of glutaraldehyde resulted in no reaction in their cells, presumably because of inaccessibility of the epitope. In contrast, the generation of novel epitopes due to fixation is less common but is not without precedent. Unexpected crossreactions to other antigens are even more common.
Aplicabilidad de la tipología de funciones retóricas de las citas al género de la memoria de máster en un contexto transcultural de enseñanza universitaria

Resumen es: El objetivo de este articulo es comparar las funciones retoricas que adquieren las citas en 14 memorias de master escritas por 7 escritores espanoles y 7...
Are Banks Still Special? New Evidence on Their Role in the Corporate Capital‐Raising Process

Bankers appear to play a special role in providing commitment-based financing to corporations. This type of lending is important not only for small firms that lack access to public debt markets but for large and medium-size companies as well. For such companies, commitment-based financing provides access to debt capital that becomes valuable when the firm has an immediate need for funding but interest rates in public debt markets are prohibitively high, or the firm is undervalued by the market. A good example of this was provided by the Asian crisis in the last quarter of 1998, when $10 billion of commercial paper was retired and $20 billion of net new commercial loans were booked. The authors also suggest that the fact that commitment-based financing is used by larger companies when they believe themselves to be undervalued in the market is probably the best explanation of why announcements of these types of loans elicit a positive stock price reaction.
Analysis of N-glycosyl bond length in crystal structures of nucleosides and nucleotides.

A relationship was found between the N-glycosyl bond length in β-nucleosides and nucleotides and the spatial relationship of this bond with respect to the lone-pair orbitals on the furanose ring oxygen. This relationship may be relevant to the geometry involved in the hydrolysis of the glycosidic bond.
Biomarker-guided screening of Juzen-taiho-to, an oriental herbal formulation for immunostimulation.

Juzen-taiho-to is an immunostimulatory herbal formulation that is clinically used in East Asia for cancer patients undergoing chemotherapy and radiation. The formulation stimulates various leukocytes, including T, B, and NK cells and macrophages. Although Juzen-taiho-to is known to contain numerous compounds with various pharmacological activities, it is not clear which compounds are responsible for the stimulation of individual cell types. Here, we conducted what we call “biomarker-guided screening” to purify compounds responsible for the macrophages stimulatory activity. To this end, gene expression was analyzed by a DNA array for macrophages treated with Juzen-taiho-to and DMSO (vehicle control), which identified intercellular adhesion molecule 1 as a biomarker of macrophage stimulation by Juzen-taiho-to. A quantitative reverse transcription polymerase chain reaction assay of intercellular adhesion molecule 1 was then used to guide the purification of active compounds. The screening resulted in the purification of a glycolipid mixture, containing β-glucosylceramides. The glycolipid mixture potently stimulated intercellular adhesion molecule 1 expression in primary dendritic cells as well as in primary CD14+ (macrophages) cells. The identification of this glycolipid mixture opens up an opportunity for further studies to understand how plant-derived glycolipids stimulate macrophages and dendritic cells in a safe and effective manner as demonstrated by Juzen-taiho-to.
For the drugs we need

Purpose – To delineate confusions and uncertainties of the issues surrounding those criticisms. Critics assert that all marketing of medical products is abusive, while actual impacts are disputed.Design/methodology/approach – Pulling from past commentaries on pharmaceutical marketing and current criticisms of the practice, to indicate areas of confusion.Findings – The ills of pharmaceutical marketing are not as great as critics presume, but the practices are not as positive as the companies might wish to assert. With uncertainty on the actual impact of specific practices, the companies are engaging in a certain degree of warfare via ever‐increasing budgets of sometimes‐questionable value.Practical implications – Puts criticisms of pharmaceutical marketing in context.Originality/value – Perspectives for understanding pharmaceutical marketing.