cssi/SciSciGPT-SciSciNet huggingface dataset:
Crystal structure of streptokinase β-domain

Abstract Streptokinase, a 47 kDa secreted protein of hemolytic strains of streptococci, is a human plasminogen activator and contains three structural domains linked by flexible loops. We describe here the crystal structure of the isolated streptokinase middle (SKβ) domain determined at 2.4 A resolution. Among the functionally important structural features is a putative binding site for a kringle domain of plasminogen located at the tip of a fully exposed hairpin loop. The distribution of genetically conserved residues of SKβ is strongly correlated with their functions. The extensive interface of the SKβ dimer suggests that such dimers may also exist in solution for free SKβ.
Substance P immunoreactivity in periodontal tissues during orthodontic tooth movement

Abstract Neurotransmitters, such as substance P (SP), may mediate the biological response to mechanical stress applied to teeth during orthodontic treatment. This hypothesis was investigated immunohistochemically on maxillae of cats which had one maxillary canine tipped distally for a period of time ranging from 1 h to 14 days. Horizontal histological sections 5 μm thick, collected on adhesive tape while still frozen, then freeze-dried, were stained by an immunoglobulin-enzyme bridge method using rabbit anti-SP polyclonal antibodies. The specificity of the staining was evaluated either by using the serum of non-immunized rabbits in lieu of anti-SP serum, or by pre-incubating the anti-SP serum with the antigen. Only sparse SP-like immunoreactivity was detected in the dental pulp, near or in the walls of blood vessels, or in the periodontal ligament (PDL) of unstressed canines. However, the density of neuronal elements exhibiting positive staining for SP appeared to increase markedly after application of an orthodontic force. This phenomenon occurred rapidly (3 h) in the dental pulp, but later in the PDL (24 h to 14 days), mainly at compression sites. These results demonstrate that the stimulation of periodontal nerve terminals by means of orthodontic forces may induce the peripheral release of the neurotransmitter SP, suggesting that it may be an initial trigger for a biochemical cascade which comprises the activation of various types of PDL cells.
Light-induced electron transport in Chromatium strain D. I. Isolation and characterization of Chromatium chromatophores.

Abstract Fractionation of Chromatium Strain D chromatophores by centrifugation in sucrose density gradients results in two fractions, designated ‘light’ and ‘heavy’. The light particles are enriched in photosynthetic pigments, are relatively homogeneous and can be prepared reproducibly. They do not scatter light appreciably, contain 41% of the bacteriochlorophyll, 26% of the carotenoid, 25% of the heme and 4% of the protein found in intact cells, and are approx. 75% lipid, and 25% protein, 30% of which can be ascribed to cytochromes. The molecular weight is 12.9.10 6 . In contrast, the heavy particles are heterogeneous, can not be prepared reproducibly, scatter light and contain approx. 14% of the bacteriochlorophyll, 9% of the carotenoid, 8% of the heme and 6% of the protein present in intact cells. Three meso-heme proteins were identified in the light particles: cytochrome c −552, cytochrome cc′ , and cytochrome c −555. Both cytochrome c −552 and cytochrome cc′ bound CO when solubilized but not when bound in the light particles. No protoheme ( b - type cytochrome) was found, even in whole cells. These results permit characterization of the chemical and physical properties of a subcellular fraction of Chromatium Strain D, which does not appear to be an artifact of preparation.
ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia.

Sodium Block-Induced ST Segment Elevation. Three patients in whom Class IC sodium channel blockers induced ST segment elevation in leads V1 through V3 are described. The underlying electrophysiologic mechanism, implications for drug-induced proarrhythmia, and the relationship of the finding to the Brugada syndrome type of idiopathic ventricular fibrillation are discussed.
Staging of salivary gland neoplasms: Role of histopathologic and molecular factors

Cancer is a disease of altered cellular genes. These altered genes, in turn, produce the malignant phenotype by inducing changes in proliferation and differentiation during the cell cycle. The changes can be assessed by techniques to measure proliferation and by histologic grading to distinguish levels of differentiation. Since proliferation factors and differentiation end points reflect the net effect of genetic damage and include, therefore, the accumulated changes in genes, they more aptly qualify as potential prognostic indicators than do individual oncogene alterations. By using mucoepidermoid carcinoma of the major salivary glands as the test model, I strongly suggest that a reproducible (three-tiered) grading system and measurements of proliferation (nuclear markers: proliferating cell nuclear antigen and, possibly, Ki-67; and proliferation fraction as determined by flow cytometry) can serve as cellular/molecular factors worthy of inclusion in existing clinical staging systems of salivary gland neoplasms.
Synchrotron X-ray study of filled skutterudites CeFe4Sb12 and Ce0.8Fe3CoSb12

In situ synchrotron X-ray diffraction measurements are carried out on filled skutterudites CeFe{sub 4}Sb{sub 12} and Ce{sub 0.8}Fe{sub 3}CoSb{sub 12} up to 32 and 20 GPa, respectively, at room temperature. No phase transformation was observed for both samples in the pressure range. Fitting the pressure-volume data (up to 10 GPa) to the third-order Birch-Murnaghan equation of state, the bulk modulus B{sub 0} is determined to be 74(4) GPa, with the pressure derivative B'{sub 0} = 7(2) for CeFe{sub 4}Sb{sub 12}, and B{sub 0} = 71(2) GPa and B'{sub 0} = 8(2) for Ce{sub 0.8}Fe{sub 3}CoSb{sub 12}. The bulk moduli of filled skutterudites CeFe{sub 4}Sb{sub 12} and Ce{sub 0.8}Fe{sub 3}CoSb{sub 12} in our study are smaller than those from previous studies on unfilled skutterudite CoSb{sub 3}. The P-V curves of the unfilled skutterudite CoSb{sub 3} and filled skutterudites CeyFe{sub 4-x}Co{sub x}Sb{sub 12} showed good agreement, indicating that the Ce filling fraction and the replacement of Fe with Co have little effect on their compression behaviors.
Contrast-enhanced ultrasound reveals real-time spatial changes in vascular perfusion during early implantation in the macaque uterus.

Objective To use contrast-enhanced ultrasound (CEU) to quantify blood flow in the macaque uterus during early pregnancy. Design Prospective nonhuman primate study. Setting Oregon National Primate Research Center. Animals Naturally cycling female rhesus macaques ( Macaca mulatta ). Intervention(s) Female macaques were mated on days 11–14 of the cycle. Females were then imaged by CEU and Doppler ultrasound once every 3 days from day 21 through day 39 of the fertile cycle. Main Outcome Measure(s) Visualization and quantification of uterine vascular perfusion. Result(s) CEU identified the primary placental disc and underlying vessels approximately 2 days earlier than Doppler ultrasound was able to observe endometrial thickening. CEU revealed spatial differences in vascular perfusion between the endometrium, myometrium, and endometrial-myometrial (junctional) zone. Myometrium displayed the highest rate of blood flow (>10 mL/min/g tissue). There was less blood flow in the endometrium and junctional zone ( Conclusions CEU provides a sensitive, noninvasive method to assess vascular perfusion of the uterus during embryo implantation in macaques. We propose CEU as a new diagnostic tool to monitor vascular changes associated with early pregnancy in women.
“Cutting” on cancer: Attitudes about cancer spread and surgery among primary care patients in the USA

Many underserved groups in the United States experience disparities in cancer survival. Part of the disparity may be due to differences in treatment or treatment uptake. Previous studies uncovered patient beliefs that surgery could cause cancer to spread and have suggested that this belief may affect uptake of cancer treatment. We explored patients’ explanations about surgical treatment of cancer and cancer spread, as well as the perceived impact on decision-making among primary care patients from an underserved area. Focus groups and interviews were conducted with patients (n = 42) at a primary care federally qualified health center in 2006 and 2007. Focus groups/interviews were semi-structured and were audio-taped and transcribed. An inductive text analysis with multiple coders was used to analyze the data and extract themes. We found that nearly all respondents had heard that surgery (“cutting”) and exposing cancer to the air would hasten cancer spread and result in worse outcomes. Most participants expressed agreement with this belief. Many participants said this concern would influence their decision about whether to have surgery and/or reported that a family member had refused surgery for this reason. A smaller group of respondents disagreed with this belief and offered experiential evidence to the contrary or hypotheses about its origination. The idea that “cutting” and “air” during surgery can cause cancer to spread may be more prevalent among patients than suspected, based on this sample of predominantly African American patients. While we were unable to disentangle the ideas about “cutting” from those about “exposure to air”, this set of beliefs, when held strongly, can negatively influence patients’ or family members’ decisions to seek surgical care and, if it is more prevalent in underserved groups, may contribute to cancer disparities.
Optical damage and internal fields in pyroelectrics.

The physical conditions under which the models of optical damage in pyroelectrics suggested by Johnston and by Amodei might be valid are described. Whether the zero‐internal‐field final state described by Johnston or the no‐current‐flow steady state of Amodei can be reached depends on the pattern of excitation and the dynamics of the damage process. In view of the small carrier diffusion lengths, the one‐dimensional models generally used may not be entirely satisfactory for investigation of dynamics.
The $$R^N$$ Dirichlet Problem

In this chapter the notation is made simpler by considering harmonic functions which are complex valued functions and have real and imaginary parts satisfying the Laplace equation in \(N\)-variables. The Dirichlet problem is to find such a function of \(N\) variables, satisfying the Laplace equation in the interior of a domain \(D\) and being equal to a given continuous complex-valued function \(g\) on the boundary \(\Gamma \) of \(D\). The case of interest in applications is \(N\)=3, but there is no essential difference in considering general \(N\). In addition to specifying that the bounded open set \(D\) not have any holes, bubbles in three dimensions, which was enough in two dimensions, additional conditions are necessary in three or higher dimensions, and the relevant Poincare condition is discussed. The proof uses the Hahn-Banach Theorem applied in the space \(C(K)\) of complex-valued continuous functions defined on the boundary K of the domain. In the final result it is shown that there is an approximate solution using any one chosen function \(f(z)\), which is not a polynomial and which has a power series convergent (about z = 0). This approximate solution is a finite sum of the form \({c_n}f({a^{(n)}} \cdot x + {b^n} \cdot x + {d_n})\) where \({c_n}\) and \({d_n}\) are complex numbers, \(a^{(n)}\) and \(b^n\) are vectors in \(R^N\) with the same length, ||\({a^{(n)}}\)|| = ||\({b^{(n)}}\)||, which are perpendicular \(a^{(n)}\) \(\cdot \) \(b^n\) = 0, and x is a point in \(R^N\). The proof relies on a lemma which shows how to construct a harmonic function in \(N\) variables from a harmonic function in two variables, which will be applied to the real and imaginary parts of \(f(z)\), and a representation theorem for the space of harmonic polynomials in \(N\)-variables which are homogeneous of degree \(m\). Note that this result demonstrates the ability of a function of two variables, \(f(z)\), to generate an approximate solution of the Dirichlet problem in \(N\)-variables.
Inhibitors in hemophilia patients: Current status and management

The development of inhibitor antibodies is a long-standing, well-documented complication of coagulation factor replacement therapy and is difficult to treat. Previous estimates of 5-15% of patients developing inhibitors may be low, since newer data suggest a wider range of occurrence. Factors that appear to affect inhibitor development include the severity of hemophilia, age, genetics, and, possibly, the type of replacement therapy administered. Recent studies raise the concern that recombinant factor therapies may be associated with more rapid development and higher levels of inhibitors in previously untreated patients. However, results of different studies are often difficult to compare owing to differences in methodology and populations studied. Further studies standardized in design and methods are clearly needed. Management of patients with inhibitors involves control of acute bleeding episodes and, over the long term, induction of immune tolerance for the coagulation replacement therapy. Many with low or moderate levels of inhibitors may be treated simply by administering higher doses of clotting factor. Other therapies appropriate for those with high levels of inhibitors include porcine F VIII and factor VIII "bypassing" agents, such as recombinant factor VIIa. Long-term immune tolerance has been achieved through the high-dose "Bonn" regimen and immunosuppressive regimens such as the "Malmo" method. Although management of inhibitor patients has improved, it still represents a major challenge. Further research is needed to identify which patients will develop inhibitors and tolerance, as well as to develop better methods to manage, reduce, or eliminate inhibitors from these patients.
Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe.

Background & Aims HFE and transferrin receptor 2 (TFR2) are each necessary for the normal relationship between body iron status and liver hepcidin expression. In murine Hfe and Tfr2 knockout models of hereditary hemochromatosis (HH), signal transduction to hepcidin via the bone morphogenetic protein 6 (Bmp6)/Smad1,5,8 pathway is attenuated. We examined the effect of dietary iron on regulation of hepcidin expression via the Bmp6/Smad1,5,8 pathway using mice with targeted disruption of Tfr2 , Hfe , or both genes. Methods Hepatic iron concentrations and messenger RNA expression of Bmp6 and hepcidin were compared with wild-type mice in each of the HH models on standard or iron-loading diets. Liver phospho-Smad (P-Smad)1,5,8 and Id1 messenger RNA levels were measured as markers of Bmp/Smad signaling. Results Whereas Bmp6 expression was increased, liver hepcidin and Id1 expression were decreased in each of the HH models compared with wild-type mice. Each of the HH models also showed attenuated P-Smad1,5,8 levels relative to liver iron status. Mice with combined Hfe/Tfr2 disruption were most affected. Dietary iron loading increased hepcidin and Id1 expression in each of the HH models. Compared with wild-type mice, HH mice demonstrated attenuated ( Hfe knockout) or no increases in P-Smad1,5,8 levels in response to dietary iron loading. Conclusions These observations show that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via the Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver Bmp6 messenger RNA or steady-state P-Smad1,5,8 levels.
Some results on uniformly high-order accurate essentially nonoscillatory schemes

We continue the construction and the analysis of essentially nonoscillatory shock capturing methods for the approximation of hyperbolic conservation laws. These schemes share many desirable properties with total variation diminishing schemes, but TVD schemes have at most first-order accuracy in the sense of truncation error, at extrema of the solution. In this paper we construct an hierarchy of uniformly high-order accurate approximations of any desired order of accuracy which are tailored to be essentially nonoscillatory. This means that, for piecewise smooth solutions, the variation of the numerical approximation is bounded by that of the true solution up to O(h^R^ ^-^ ^1), for 0
A new animal model for fetal macrosomia in diabetic pregnancy.

Abstract Fetal macrosomia in human diabetic pregnancy has long been recognized. However, an animal model suitable for studying fetal macrosomia and other fetal anomalies in diabetic pregnancy has been lacking. In the present study the visually recognizable macrosomic fetus was compared with its normal weight litter mates obtained on the 19.5 day of gestation from mildly diabetic Sprague-Dawley rats. The mean body weights of macrosomic fetuses and the normal litter mates were 4.72 ± 0.45 g (mean ± SE) and 2.76 ± 0.18 g, respectively. The rate of [ 3 H]AIB influx from the maternal to fetal side for the macrosomic fetuses was approximately 50 times greater than the corresponding rate for the normal litter mates. The visual identification of macrosomia is thus verified by two different parameters (e.g., body weight and rate of metabolite influx). These results provide a rationale for comparing macrosomic fetuses with their litter mates for studying pathogenesis of macrosomia in diabetic pregnancies in an animal system. This model mimics the human fetal macrosomia more closely than those reported heretofore.
Hypophosphatemia during nutritional rehabilitation in anorexia nervosa: implications for refeeding and monitoring

Abstract Purpose To determine the incidence of hypophosphatemia in adolescents with anorexia nervosa (AN) hospitalized for nutritional rehabilitation and to examine factors predisposing to its development. Methods A retrospective chart review of 69 patients (66 female, 3 male) with AN consecutively admitted to an inpatient adolescent medical unit between July 1, 1998 and June 30, 2000. Mean age was 15.5 ± 2.4 (range 8 to 22) years and mean % ideal body weight (IBW) was 72.7 ± 7%. Serum phosphorus was measured daily for 1 week and then biweekly to weekly. Patients were started on 1200–1400 kcal/day and calories were increased by 200 kcal every 24–48 hours. Results Four (5.8%) patients developed moderate hypophosphatemia ( p = 0.02). Phosphorus nadirs were directly proportional to % IBW (r = 0.3, p = 0.01). Over three-quarters of the patients (81%) reached their phosphorus nadir within the first week of hospitalization. The patient with the lowest phosphorus level experienced short runs of ventricular tachycardia. No other severe complications were seen. Overall, 19 (27.5%) patients required phosphorus supplementation. Conclusions Phosphorus drops to its nadir during the first week of refeeding. We recommend daily monitoring of serum phosphorus with supplementation as needed during the first week of hospitalization, especially in those who are severely malnourished.
A Review of Plasma Apolipoprotein A-I Interactions with Phosphatidylcholines

This review starts with a brief introduction to the properties of plasma high-density lipoproteins and their major protein component, apolipoprotein A-I, followed, in the following sections, by an account of experimental work from our laboratory on the interactions of apolipoprotein A-I with synthetic and natural phosphatidylcholines. The spontaneous reactions of phosphatidylcholine vesicles with apolipoprotein A-I are described in terms of the methods of observation, the properties of the reaction products (vesicular or micellar complexes of protein and lipid), and the kinetic controlling factors in the formation of the micellar products. A general detergent reconstitution method for the preparation of micellar complexes is presented, and applications of these particles in studies of the apolipoprotein-lipid interface and of enzymatic reactions are discussed.
Dynamical Mechanisms for the South China Sea Seasonal Circulation and Thermohaline Variabilities

Abstract The seasonal ocean circulation and the seasonal thermal structure in the South China Sea (SCS) were studied numerically using the Princeton Ocean Model (POM) with 20-km horizontal resolution and 23 sigma levels conforming to a realistic bottom topography. A 16-month control run was performed using climatological monthly mean wind stresses, restoring-type surface salt and heat, and observational oceanic inflow/outflow at the open boundaries. The seasonally averaged effects of isolated forcing terms are presented and analyzed from the following experiments: 1) nonlinear dynamic effects removed, 2) wind effects removed, and 3) open boundary inflow/outflow set to zero. This procedure allowed analysis of the contribution of individual parameters to the general hydrology and specific features of the SCS: for example, coastal jets, mesoscale topographic gyres, and countercurrents. The results show that the POM model has the capability of simulating seasonal variations of the SCS circulation and thermoha...
Aircraft Identification by Moment Invariants

Although many systems for optical reading of printed matter have been developed and are now in wide use, comparatively little success has been achieved in the automatic interpretation of optical images of three-dimensional scenes. This paper is addressed to the latter problem and is specifically concerned with automatic recognition of aircraft types from optical images. An experimental system is described in which certain features called moment invariants are extracted from binary television images and are then used for automatic classification. This experimental system has exhibited a significantly lower error rate than human observers in a limited laboratory test involving 132 images of six aircraft types. Preliminary indications are that this performance can be extended to a wider class of objects and that identification can be accomplished in one second or less with a small computer.
Optical induction and detection of fast phase transition in VO2

Abstract We have optically induced the Insulator to Metal Phase transition in VO2 sputtered films within 20 nsec by using a Q-switched ruby laser. The phase transition was detected by monitoring a He-Ne probe beam reflected off the film surface. It is shown that this fast phase transition is induced by photon → electron → phonon energy transfer process. We also discuss the possibility of using similar measurements to deduce the physical origin of the transition.
Effect of acclimation temperature on the upper thermal tolerance of Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus: thermal limits of a North American salmonid

In an effort to explore the thermal limitations of Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus, the critical thermal maxima (T(cmax) ) of 1+ year Lake Nanita strain O. c. pleuriticus were evaluated when acclimated to 10, 15 and 20° C. The mean ±s.d.T(cmax) for O. c. pleuriticus acclimated to 10° C was 24·6 ± 2·0°C (n = 30), for 15° C-acclimated fish was 26·9 ± 1·5° C (n = 23) and for 20° C-acclimated fish was 29·4 ± 1·1° C (n = 28); these results showed a marked thermal acclimation effect (Q₁₀ = 1·20). Interestingly, there was a size effect within treatments, wherein the T(cmax) of larger fish was significantly lower than that of smaller fish acclimated to the same temperature. The critical thermal tolerances of age 0 year O. c. pleuriticus were also evaluated from three separate populations: Lake Nanita, Trapper Creek and Carr Creek reared under 'common-garden' conditions prior to thermal acclimation. The Trapper Creek population had significantly warmer T(cmax) than the Lake Nanita population, but that of the Carr Creek fish had T(cmax) similar to both Trapper Creek and Lake Nanita fish. A comparison of these O. c. pleuriticus T(cmax) results with those of other stream-dwelling salmonids suggested that O. c. pleuriticus are less resistant to rapid thermal fluctuations when acclimated to cold temperatures, but can tolerate similar temperatures when acclimated to warmer temperatures.
Coping with School Stress: A Comparison of Adolescents With and Without Learning Disabilities

The experience of school-related stress during the transition to junior high school is compared in a sample of 59 students with learning disabilities (27 females, 32 males) and 402 students without learning disabilities (241 females, 161 males). Using a checklist of 11 stressful school events, the authors found that adolescents with learning disabilities were more likely to report that they had failed a class and less likely to report they had been chosen for a school activity than their non-learning disabled peers. However, the two groups of students did not differ in their perceived stressfulness of any of the pertinent school events. Students with learning disabilities reported relying on cognitive avoidance as a coping strategy more heavily than did non-learning disabled students when coping with an academic stress event, and reported that they mobilized fewer peers for social support when dealing with an academic stressor or with an interpersonal problem. The implications of these differences for the students' well-being are discussed. It is also suggested that school policies need to be examined for their impact on the opportunity for students with special needs to form supportive peer relations within the school environment.
The Federal Trade Commission Redefinition of Deception and Public Policy Implications: Let the Buyer Beware

The current movement toward market deregulation in the United States is perhaps no better illustrated than by the proposals put forth by the Chairman of the Federal Trade Commission (FTC), James C. Miller, III. His far reaching suggestions would alter considerably the approach taken by the FTC toward the regulation of advertising. This paper reviews the current standards of deception in advertising regulation and compares them with Miller's proposals for new standards. Two recent cases settled under the current guidelines are presented. The probable outcome of these cases under the proposed guidelines is examined by employing a framework proposed by Miller and Hutt for analyzing the effects of regulatory policy. Based on that examination, the authors conclude that the current standards have allowed federal and state agencies to bring about elimination of false advertising claims that would not be possible to prove under the proposed guidelines. While the proposed changes may bring certain benefits to government, business, and consumers, their most significant effect could be to reintroduce the rule of caveat emptor.
Pharmacokinetic principles for dose-rate extrapolation of carcinogenic risk from genetically active agents.

Neither experimental animal exposures nor real-life human exposures are delivered at a constant level over a full lifetime. Although there are strong theoretical reasons why all pharmacokinetic processes must go linear at the limit of low dose rates, fluctuations in dose rate may produce nonlinearities that either increase or decrease actual risks relative to what would be expected for constant lifetime exposure. This paper discusses quantitative theory and specific examples for a number of processes that can be expected to give rise to pharmacokinetic nonlinearities at high dose rates--including transport processes (e.g., renal tubular secretion), activating and detoxifying metabolism, DNA repair, and enhancement of cell replication following gross toxicity in target tissues. At the extreme, full saturation of a detoxification or DNA repair process has the potential to create as much as a dose dependence of risk on dose delivered in a single burst, and if more than one detoxification step becomes fully saturated, this can be compounded. Effects via changes in cell replication rates, which appear likely to be largely responsible for the steep upward turning curve of formaldehyde carcinogenesis in rats, can be even more profound over a relatively narrow range of dosage. General suggestions are made formore » experimental methods to detect nonlinearities arising from the various sources in premarket screening programs. 46 references.« less
Salvage of a Thumb Replant Using a Bilobed Dorsal Metacarpal Artery Island Flap: Case Report and Literature Review

Amputations and degloving injuries of the hand are highly disabling, especially when they affect the thumb. Dorsal metacarpal artery (DMCA)-based flaps have been well-documented in the literature for use in extensive degloving injuries of both dorsal and palmar aspects of the thumb surface. Modifications on these flaps, such as the bilobed island flap, offer additional advantages when larger surface areas or more distal defects of the thumb are present. We present a review of the literature on the DMCA flap and describe its use to salvage a partial survival of a thumb amputation through the metacarpophalangeal joint.
Hemodynamic differences between the awake and anesthetized conditions in normal calves

There is insufficient information in the literature about baseline circulatory parameters in normal calves in the anesthetized versus postoperative awake conditions under which a large volume of medical research is conducted. Eleven calves (mean body weight, 78.1 ± 14.3 kg) were implanted with a flow probe and fluid-filled pressure lines to measure cardiac output (CO), aortic (AoP), central venous (CVP), pulmonary arterial (PAP), and left atrial pressures (LAP). Systemic (SVR) and pulmonary vascular resistance (PVR) were also calculated. We obtained the above hemodynamic data (n = 11) and epicardial echocardiography (n = 7) during open-chest surgery under isoflurane anesthesia. After full recovery from surgery, animals were evaluated in the awake condition on postoperative days 6–9 using transthoracic echocardiography (n = 7) and the hemodynamic monitoring lines and probes noted (n = 11). CO, AoP, and PAP levels in the anesthetized condition were significantly lower than in the awake condition. Other hemodynamic parameters (CVP, LAP, SVR, and PVR) were not significantly different. In conclusion, data from this study quantify changes in CO, AoP, and PAP in anesthetized calves that may affect the hemodynamic response to experimental therapeutics such as new cardiac assist devices, prosthetic valves, and surgical interventions. Our study also provides baseline data for the translation of the hemodynamic data obtained in acute in vivo calf studies to that of an awake subject.
PT-symmetric lattices with a local degree of freedom

Recently, open systems with balanced, spatially separated loss and gain have been realized and studied using non-Hermitian Hamiltonians that are invariant under the combined parity and time-reversal ($\mathcal{PT}$) operations. Here, we model and investigate the effects of a local, two-state, quantum degree of freedom, called a pseudospin, on a one-dimensional tight-binding lattice with position-dependent tunneling amplitudes and a single pair of non-Hermitian, $\mathcal{PT}$-symmetric impurities. We show that if the resulting Hamiltonian is invariant under exchange of two pseudospin labels, the system can be decomposed into two uncoupled systems with tunable threshold for $\mathcal{PT}$ symmetry breaking. We discuss implications of our results to systems with specific tunneling profiles, and open or periodic boundary conditions.
US FDA-approved disease-modifying treatments for multiple sclerosis: review of adverse effect profiles.

Several disease-modifying agents (DMAs) are approved for the treatment of multiple sclerosis, including three interferon (IFN)-β products, glatiramer acetate and mitoxantrone. This article reviews the adverse event profiles of these DMAs based on the pivotal phase III trials, and provides practical guidelines for managing adverse effects. In general, the most common adverse events associated with IFNβ therapy are flu-like symptoms, including fever, chills and myalgias, and headache. The flu-like symptoms typically resolve within 24 hours and may be mitigated by over-the-counter anti-inflammatory agents. Adverse events related to glatiramer acetate therapy include injection-site reactions and a systemic reaction consisting of flushing, chest tightness, palpitation, anxiety or dyspnoea. The systemic reaction is transient (30 seconds to 30 minutes) and self-limited. Mitoxantrone may cause nausea, vomiting, alopecia, amenorrhoea and myelosuppression; isolated cases of acute leukaemia and dose-related cardiotoxicity have been reported in the literature. Longer-term tolerability data on mitoxantrone as a treatment for multiple sclerosis are needed. It is important for physicians to counsel patients on DMA-related adverse effects, most of which are transient and of mild-to-moderate severity. Various strategies that can be employed to prevent or manage these adverse effects and lessen their impact on the patient are discussed.
A comparison of five different bone resorption markers in osteosarcoma-bearing dogs, normal dogs, and dogs with orthopedic diseases.

Background: Various bone resorption markers in humans are useful for supporting the diagnosis of malignant skeletal pathology, with certain bone resorption markers appearing to be more discriminatory for detecting cancer-induced osteolysis than others. Canine osteosarcoma (OSA) is characterized by focal bone destruction, but a systematic investigation for determining which bone resorption marker best supports the diagnosis of OSA in dogs has not been reported. Hypothesis: Dogs with OSA will have increased concentrations of bone resorption markers compared with healthy dogs and dogs with orthopedic disorders. Differences will exist among various bone resorption markers for their ability to support the diagnosis of malignant osteolysis in dogs with OSA. Animals: Single time point, cross-sectional, cohort study including dogs with OSA (n = 20) or orthopedic disorders (n = 20) and healthy dogs (n = 22). Methods: Basal concentrations of urine and serum N-telopeptide (NTx), urine and serum C-telopeptide (CTx), and urine deoxypyridinoline (DPD) were compared among all 3 groups. Results: Compared with healthy dogs and dogs with orthopedic disorders, urine NTx, serum NTx, and serum CTx concentrations were significantly increased in dogs with OSA. For urine NTx and serum NTx, the calculated lower and upper 95% confidence limits in dogs with OSA did not overlap with dogs diagnosed with orthopedic disorders or healthy dogs. Conclusions and clinical importance: Of the markers evaluated in this study, urine NTx and serum NTx appear to be the most discriminatory resorption markers supporting the diagnosis of focal malignant osteolysis in dogs with OSA.
A MELTING POINT FOR THE BIREFRINGENT COMPONENT OF MUSCLE

The A filament of the striated muscle sarcomere is an ordered aggregate of one or a few species of proteins. Ordering of these filaments into a parallel array is the basis of birefringence in the A region, and loss of birefringence is therefore a measure of decreased order. Heating caused a large decrease in the birefringence of glycerinated rabbit psoas muscle fibers over a narrow temperature range (∼3°C) and a large decrease in both the birefringence and optical density of the A region of Drosophila melanogaster fibrils. These changes were interpreted as a loss of A filament structure and were used to define a transition temperature (Ttr) as a measure of the stability of the A region. Since the transition temperature was sensitive to pH, ionic strength, and urea, solvent conditions which often affect protein structure, it is an experimentally useful indicator for factors affecting the structure of the A filament. Fibers from glycerinated frog muscle were less stable over a wide pH range than fibers from glycerinated rabbit muscle, a fact which demonstrates a species difference in structure. Glycerinated rabbit fibrils heated to 70°C shortened to about 40% of their initial length. The extent of shortening was not correlated with the loss of birefringence, and phase-contrast microscopy showed that this shortening occurred in the I region as well as in the A region. This response may be useful for studying the I filament and actin in much the same way that the decrease in birefringence was used for studying the A filament and myosin. The observations presented show that some properties of muscle proteins can be studied essentially in situ without the necessity of first dispersing the structure in solutions of high or low ionic strength.
Effect of film thickness and supercooling on the performance of cholesteryl cinnamate liquid crystal capillary columns

Improved separations of the isomers of olefinic aliphatic insect pheromones were obtained on cholesteryl cinnamate glass capillary columns by operating in the supercooled temperature range of the liquid crystal. Capillary columns were prepared with varying film thickness of the stationary phase; choice of the correct film thickness ensured optimum retention for a wide range of compounds within the most effective temperature range of the liquid crystal. The deactivation procedures described made the liquid crystal columns suitable for separation of the geometric isomers of polar and nonpolar compounds.
THE ORIGIN AND STRUCTURE OF ENDOGENOUS RETROVIRAL DNA

DNA related to the genomes of avian leukosis viruses (ALV) and mouse mammary tumor viruses (MMTV) is widely distributed among normal chickens and mice. We have used restriction mapping techniques to compare individuals from inbred and outbred populations with respect to genetically-transmitted proviral DNA, in efforts to understand its origins and functions. We have found that outbred animals have variable numbers of ALV and MMTV proviruses located at various sites in their host genomes, with some animals apparently free of such endogenous proviruses. Inbred or partially inbred animals have very similar or identical patterns, suggesting that proviruses behave as stable genetic elements once introduced into the germ line. Moreover, several cellular genes, including the homologous of the src gene of avian sarcoma virus, are invariant, or nearly so, in similar tests of these animals. We conclude that the proviruses under study have been introduced into the germ lines of chickens and mice long after speciation, that they are still segregating among contemporary animals, and that they are unlikely to provide essential functions to their hosts.
Reconstitution of an Infectious Human Endogenous Retrovirus

The human genome represents a fossil record of ancient retroviruses that once replicated in the ancestors of contemporary humans. Indeed, approximately 8% of human DNA is composed of sequences that are recognizably retroviral. Despite occasional reports associating human endogenous retrovirus (HERV) expression with human disease, almost all HERV genomes contain obviously inactivating mutations, and none are thought to be capable of replication. Nonetheless, one family of HERVs, namely HERV-K(HML-2), may have replicated in human ancestors less than 1 million years ago. By deriving a consensus sequence, we reconstructed a proviral clone (HERV-KCON) that likely resembles the progenitor of HERV-K(HML-2) variants that entered the human genome within the last few million years. We show that HERV-KCON Gag and protease proteins mediate efficient assembly and processing into retrovirus-like particles. Moreover, reporter genes inserted into the HERV-KCON genome and packaged into HERV-K particles are capable of infectious transfer and stable integration in a manner that requires reverse transcription. Additionally, we show that HERV-KCON Env is capable of pseudotyping HIV-1 particles and mediating entry into human and nonhuman cell lines. Furthermore, we show that HERV-KCON is resistant to inhibition by the human retrovirus restriction factors tripartite motif 5α and apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) 3G but is inhibited by APOBEC 3F. Overall, the resurrection of this extinct infectious agent in a functional form from molecular fossils should enable studies of the molecular virology and pathogenic potential of this ancient human retrovirus.
In appreciation of the contributions of Harry Searls Gradle.

Abstract The many contributions of Harry Searls Gradle (1883–1950) to ophthalmology are recalled by an author who was his protege. A former student of Anton Elschnig's, Gradle taught unique surgical skills to those who worked directly with him. Furthermore, he lent his insights and brilliant organizational talents to the development of institutions and programs for the betterment of ophthalmic education and practice.
Synergistic Effects of Potassium Sorbate and Sodium Benzoate on Thermal Inactivation of Yeasts

Experiments were conducted to evaluate and compare the combined effects of two preservatives, potassium sorbate and sodium benzoate, with heat on inactivation and injury of 12 strains of yeasts. There does not appear to be any correlation between ability to sporulate and z value or general heat sensitivity. Heat treatment caused an increase in sensitivities of 10 of the 12 strains to potassium sorbate (≤ 1000 ppm) as evidenced by inability to form colonies in the presence of the preservative in a recovery medium. Heated cells of five test strains had increased sensitivity to ≤ 1000 ppm of sodium benzoate. Whether exposed to potassium sorbate or not during heating, 100 ppm of the preservative in recovery broth severely retarded, and in some instances completely inhibited, growth of yeasts for a period of 10 hr post treatment. These results strongly suggest that yeasts possessing a wide range of physiological characteristics are subject to heat-injury and, furthermore, that postassium sorbate enhances injury during heating and retards or prevents repair of injury during recovery. Sensitivity to heat generally increased as the pH of the heating medium decreased from 7.0 to 2.5. Without exception, the presence of 500 ppm of potassium sorbate or sodium benzoate in the heating medium caused more rapid inactivation rates of yeasts compared to heating in the absence of preservatives. At comparable concentrations, sodium benzoate was less effective than was potassium sorbate, which exerted a significant (P ≤ 0.05) effect on increasing the rate of heat inactivation at concentrations as low as 50 ppm.
A Remediation Sequence to Improve Speech Intelligibility for Students With Down Syndrome

This paper describes an approach to remediation of speech intelligibility for students with Down syndrome. Proposed is a series of intervention techniques organized using a developmental framework....
The fixed charge problem—I: A new heuristic method

Abstract A new approximate method for finding optimal or near optimal solutions to the fixed charge problem is described. It is very rapid, compared with previous methods and achieves results which are at least as good or better than previously published results. The method is useful in its own right. However, it will also form the basis for the development of an exact solution method to be described in subsequent work.
Thermal spraying of reactive materials to form wear-resistant composite coatings

The dispersion of more than 20 vol.% submicrometer ceramic particles within a metallic matrix and the deposition of such a cermet to form a thick and tough coating presents problems. Most of the coating techniques have failed in attempting to homogeneously disperse very fine and hard particles in large amounts while avoiding their decomposition or reaction with the metal matrix during the deposition process. A simple and efficient method has been developed for producing ceramic-containing composite coatings. It consists in synthesizing cermet-based materials and in depositing them by a rapid solidification process such as thermal spraying. Boride- and carbide-based materials have been successfully obtained by plasma spraying reactive powders comprising the basic reagents. These materials, with a microstructure of submicrometer ceramic particles dispersed in a metallic matrix, exhibit good wear-resistant properties (abrasion and sliding wear). Finally, reactive core wire arc spraying is suggested as a flexible way to produce coatings containing up to 25 vol.% TiB2.
Standard Model Neutral Higgs Subgroup Summary

Various issues pertaining to the search for the high mass Higgs boson (mH~800 GeV) in the purely leptonic decays of Z pairs are studied. In addition, the usability of a high luminosity SSC (L= 1034/(cm2−s)) in this context is assessed.
A minimax problem for distributed parameter systems

The problem considered in this paper is the infinite dimensional analogue of Ho. We use the results of Ho and show that, under suitable conditions, the optimal pair of controls for finite dimensional systems converges to the optimal pair for infinite dimensional systems.
Vulnerability of the dentate gyrus to aging and intracerebroventricular administration of kainic acid.

The hippocampal formation is highly vulnerable to the aging process, demonstrating functional alterations in circuitry with aging. Aging may also change the sensitivity of the hippocampal formation to excitotoxic lesions. In this study, using young adult, middle aged, and aged Fischer 344 rats, we evaluated morphometric changes in the dentate gyrus as a function of age and also in response to an administration of an excitotoxin (kainic acid) into the right lateral ventricle. The dentate gyrus was measured for changes in the area of dentate hilus and the dentate granule cell layer, alterations in the width of the dentate granule cell layer, and degree of dentate hilar cell loss. With aging, the hilar area increased in size while the area and width of the dentate granule cell layer remained constant. However, the most striking change with aging was a significant reduction in the number of dentate hilar neurons. Intracerebroventricular kainic acid produced consistent lesions in the entire ipsilateral CA3 region, and the size of CA3 lesion was identical in all three ages of animals. Following the lesion, areas of both the dentate hilus and the granule cell layer were significantly decreased in only young adult and middle aged animals whereas the width of the dentate granule cell layer was significantly increased only in the middle aged group. In contrast, dentate hilar neurons were significantly reduced in all ages of animals with the maximum reductions in neuron number observed in the aged group. Thus, aging in the dentate gyrus is characterized by a significantly decreased number of dentate hilar neurons and also a significantly increased susceptibility of dentate hilar neurons to excitotoxic damage.
Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy

Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia.