cssi/SciSciGPT-SciSciNet huggingface dataset:
A Novel Method to Detect and Monitor Retinal Vasculitis Using Swept-Source OCT Angiography

Purpose To introduce a novel method for assessment of retinal vasculitis using swept-source OCT angiography (SS-OCTA). Design Retrospective case series. Participants Patients with retinal vasculitis. Methods The subjects were identified among the clinic population and imaged with 12 × 12-mm SS-OCTA scans centered on the fovea. A custom retina segmentation superimposed the color retinal thickness map on a modified en face flow scan. Findings from en face flow scans were correlated with localized perivascular retinal thickening on B-scans. Results from SS-OCTA were compared with fluorescein angiography (FA) to examine the proportion of perivascular thickening to retinal vascular leakage or staining. Results Twenty-one patients with retinal vasculitis underwent same-day FA and SS-OCTA. Visible retinal vascular leakage/staining on FA corresponded to increased perivascular retinal thickness on SS-OCTA in 17 patients. Five patients had a second examination with same-day FA and SS-OCTA after treatment of the vasculitis. Three of those 5 patients showed improved retinal vascular leakage/staining on post-treatment FA and decreased perivascular retinal thickness on SS-OCTA scans. Conclusions Swept-source OCT angiography detects structural retinal thickening secondary to inflammatory retinal vascular leakage. Further studies are required to confirm whether SS-OCTA may serve as a semiquantitative alternative to FA to diagnose and monitor the response to treatment in patients with retinal vasculitis.
Worldsheet Path Integral: Scattering Amplitudes

In this chapter, we generalize the worldsheet path integral to compute scattering amplitudes, which corresponds to insert vertex operators. The gauge fixing from the previous chapter is generalized to this case. In particular, we discuss the 2-point amplitude on the sphere. Finally, we introduce the BRST symmetry and motivate some properties of the BRST quantization, which will be performed in details later. The formulas in this chapter are all covariant: they will be rewritten in complex coordinates in the next chapter.
Photochemistry of carbon nitrides and heptazine derivatives

We explore the photochemistry of polymeric carbon nitride (C3N4), an archetypal organic photocatalyst, and derivatives of its structural monomer unit, heptazine (Hz). Through spectroscopic studies and computational analysis, we have observed that Hz derivatives can engage in non-innocent hydrogen bonding interactions with hydroxylic species. The photochemistry of these complexes is influenced by intermolecular nπ*/ππ* mixing of non-bonding orbitals of each component and the relative energy of intermolecular charge-transfer (CT) states. Coupling of the former to the latter appears to facilitate proton-coupled electron transfer (PCET), resulting in biradical products. We have also observed that Hz derivatives exhibit an extremely rare inverted singlet/triplet energy splitting (ΔEST). In violation of Hund's multiplicity rules, the lowest energy singlet (S1) is stabilized relative to the lowest triplet (T1) electronic excited state. Exploiting this unique inverted ΔEST character has obvious implications for transformational discoveries in solid-state OLED lighting and photovoltaics. Harnessing this inverted ΔEST, paired with light-driven intermolecular PCET reactions, may enable molecular transformations relevant for applications ranging from solar energy storage to new classes of non-triplet photoredox catalysts for pharmaceutical development. To this end, we have explored the possibility of optically controlling the photochemistry of Hz derivatives using ultrafast pump–push–probe spectroscopy. In this case, the excited state branching ratios among locally excited states of the chromophore and the reactive intermolecular CT state can be manipulated with an appropriate secondary “push” excitation pulse. These results indicate that we can predictively redirect chemical reactivity with light in this system, which is an avidly sought achievement in the field of photochemistry. Looking forward, we anticipate future opportunities for controlling heptazine photochemistry, including manipulating PCET reactivity with a diverse array of substrates and optically delivering reducing equivalents with, for example, water as a partial source of electrons and protons. Furthermore, we wholly expect that, over the next decade, materials such as Hz derivatives, that exhibit inverted ΔEST character, will spawn a significant new research effort in the field of thin-film optoelectronics, where controlling recombination via triplet excitonic states can play a critical role in determining device performance.
Canine comparative oncology for translational radiation research

PURPOSE Laboratory and clinical research are essential for advancing radiation research; however, there is a growing awareness that conventional laboratory animal models and early-phase clinical studies in patients have not improved the low success rates and late-stage failures in new cancer therapy efforts. There are considerable costs and inefficiencies in moving preclinical research into effective cancer therapies for patients. Canine translational models of radiation research can fill an important niche between rodent and human studies, ultimately providing valuable, predictive, translational biological and clinical results for human cancer patients. Companion dogs naturally and spontaneously develop cancers over the course of their lifetime. Many canine tumor types share important similarities to human disease, molecularly and biologically, with a comparable clinical course. Dogs receive state-of-the-art medical care, which can include radiotherapy, experimental therapeutics, and novel technologies, offering an important opportunity for radiobiology and radiation oncology research. Notably, the National Cancer Institute has developed the Comparative Oncology Program to promote this area of increased research interest. CONCLUSION In this review, the benefits and limitations of performing translational radiation research in companion dogs will be presented, and current research utilizing the canine model will be highlighted, including studies across research areas focusing on common canine tumor types treated with radiotherapy, comparative normal tissue effects, radiation and immunology research, and alternative radiation therapy approaches involving canine cancer patients.
Electronic health record-derived outcomes in obstructive sleep apnea managed with positive airway pressure tracking systems.

Study Objectives:To assess the effectiveness of CPAP management guided by CPAP machine downloads in newly diagnosed patients with OSA using electronic health record (EHR)-derived healthcare utiliza...
EXAFS Studies of Crystalline Materials

In recent years the extended x-ray absorption fine structure (EXAFS) technique has been applied to many problems including the structure of biological molecules, molecular structure of liquids, structure of amorphous semiconductors, and of supported catalysts. In view of the nature of this book and because other reviews on this subject exist (including a review by one of the authors1)), this Chapter will focus on the applications of the EXAFS technique to the study of crystalline materials. While there have been many studies of crystalline materials of known structures performed in order to establish the validity of the technique, little work has been done to obtain new information. In this chapter we will review some of this work. We assume that the reader has no prior knowledge of this technique and we will therefore review the theory of EXAFS, the methods of data analysis, and the experimental technique.
Combined epi- and subdural approach to carotid ophthalmic aneurysms

Surgery of carotid ophthalmic aneurysms, which was until recently a very demanding procedure, has become much safer and easier to perform by employing the combined epi- and subdural approach [8]. In this procedure a standard pterional craniotomy [55, 56] is used, following this is removal of the orbital roof together with the sphenoid wing and the ACP. Then the proximal, medial, and lateral part of the wall of the optic canal are removed to give the operative exposure of the ON from the dura to the entry point into the intraorbital tissue, in its entire segment in the optic canal. The orbital roof is removed on the anterior side of the SOF, as well as on its dorsal side. For this type of aneurysm it is enough if the anterior loop of the ICA in the anteromedial triangle is exposed. Therefore, it is not necessary to explore the ICA in the carotid canal in the petrous bone through the posterolateral triangle. The dissection of the ICA in the anteromedial triangle is essential and must be completed before the dissection of the aneurysm itself is commenced. With this type of aneurysm it is important that the dura is not damaged while operating epidurally and removing the bone. In addition, this is imperative when dealing with large or giant carotid ophthalmic aneurysms which are not thrombosed. Equally important is that the intradural pressure is not lowered by lumbar drainage which is contraindicated in this type of surgery. Maintaining the normal cerebrospinal fluid quantity and pressure by preserving the intact dura is the best protection of the underlying aneurysm, the brain, and the neural structures from mechanical injury during the drilling of the ACP. Care must be taken because the ACP is tightly attached to the dura.
High Cost Subsidies and Telephone Company Costs

Local telephone companies serving higher cost areas qualify for subsidies to defray many of their expenses. High Cost Loop Support assists companies with above-average loop expenses. Local Switching Support subsidizes switching expenses of companies with fewer than 50,000 lines. Both schemes encourage carriers to overbuild the network because a diminished portion of costs is recovered from the company's own customers. Technology choices may be skewed where network elements are subsidized at different rates. A cost model of the local telephone company demonstrates substantial excess expenditures, but the effect on technology choices appears modest.
Insight into Antibody Combining Sites Using Nuclear Magnetic Resonance and Spin Label Haptens

This chapter describes the structure and provides dynamic information on antibody combining sites using high–resolution nuclear magnetic resonance (NMR) spectroscopy together with suitable nitroxide free radicals called spin labels (SL). The methods are illustrated with work performed in this laboratory on the Fab fragment of the ANO2 antibody, which has specificity for haptens containing the dinitrophenyl (DNP) group. For many applications of the methods discussed in the chapter, it is important to have signal assignments— that is, to know which NMR signal corresponds to which amino acid proton. With a known antibody sequence, model building, various magnetic resonance technical strategies, and selective deuteration, it is sometimes possible to make plausible assignments. Three diamagnetic haptens DNP-SLH, DNP-Gly, and DNP-Gly2 have dissociation constants on the same order of magnitude as the paramagnetic hapten, DNP-SL, on the order of micromolar. These haptens are useful in the studies on the kinetics of hapten-antibody reactions and also in obtaining certain difference spectra.
Lattice Tests of Supersymmetric Yang-Mills Theory?

Supersymmetric Yang Mills theory is directly accessible to lattice simulations using current methodology, and can provide a non-trivial check of recent exact results in SQCD. In order to tune the lattice simulation to the supersymmetric point it is neccessary to understand the behavior of the theory with a small supersymmetry breaking gaugino mass. We introduce a soft breaking gaugino mass in a controlled fashion using a spurion analysis. We compute the gluino condensate, vacuum energy and bound-state masses as a function of the gaugino mass, providing more readily accessible predictions which still test the supersymmetric results. Finally we discuss diagnostics for obtaining the bare lattice parameters that correspond to the supersymmetric continuum limit.
Relation between survival and deoxyribonucleic acid replication in ultraviolet-irradiated resistant and sensitive strains of Escherichia coli B-r.

When arabinose-grown Escherichia coli B/r is ultraviolet (UV) irradiated in the logarithmic phase of growth, the dose inactivation curve for both colony formation and deoxyribonucleic acid (DNA) synthesis (based on the relative rates of synthesis) is exponential in nature. When protein synthesis is inhibited before UV-irradiation, both inactivation curves have a large shoulder. Pre-irradiation inhibition of protein synthesis increases considerably the colony-forming ability of a UV-irradiated Hcr− and Rec− strain of E. coli B/r. However, with the repair-deficient strains, both the shoulder and slope of the survival curve are affected. We investigated the effect of UV irradiation on DNA synthesis in Hcr− bacteria and found that pre-irradiation inhibition of protein synthesis increases UV resistance of DNA replication in this strain also. The results suggest that inhibition of protein synthesis before irradiation increases UV resistance in E. coli B/r by a mechanism which is independent of both the excision and recombination repair systems.
On the lumped capacitance approximation accuracy in RC network building models

Abstract Thermal resistor-capacitor networks are a popular method for control-oriented building modeling. A basic assumption underlying this method is that the continuous temperature distribution in a wall or window is well-approximated by a small number of lumped capacitances. In this paper, we explore the accuracy of this approximation when a single capacitance is used. We derive conditions on the dimensionless parameters that characterize the problem, called Biot numbers, that lead to small errors in approximating a wall or window's surface heat fluxes and internal energy. The lumped capacitance approximation can be surprisingly accurate for Biot numbers much larger than the conventional upper bound of 0.1. In particular, the approximation is nearly exact for window panes, and is often acceptable for uniform walls. A large Biot number at an indoor wall surface, however, leads to large lumped capacitance approximation errors.
Phosphorylation of the Na+-H+ Exchanger Isoform 1 Initiated by α1-Adrenergic Receptor Signaling Regulates Cell Growth and Movement

α1-adrenergic receptor signaling has been implicated in cancer progression through the stimulation of cell proliferation, cell migration and cell invasion. Conversely, blocking α1-adrenergic recept...
Mitogen-Induced Cell Proliferation and Cancer Promotion in the Liver

Abstract Numerous mitogenic compounds induce noncompensatory cell proliferation that increases liver mass and cell number. Such hyperplasia contrasts with liver regeneration, the compensatory growth and cell proliferation that replace the loss of liver mass following injury. Some forms of hyperplasia reflect the same signaling as liver regeneration, while others result from activation of particular nuclear receptors especially the constitutive androstane receptor and the peroxisome proliferator-activating receptor. The hyperplasia responses were originally studied because they promoted carcinogenesis in the liver. Contemporary analysis has shown that activation and progression of the cell cycle is distinctive for each stimulatory process. Moreover, each hyperplasia mechanism contributes a distinctive effect to cancer promotion.
Silurian and Lower Devonian of Southwestern Virginia: ABSTRACT

Thermal maturity of the Silurian and Lower Devonian rocks in Virginia west of New River decreases southwestward. Oil and gas shows are reported. The total thickness of Lower Devonian plus Silurian strata ranges from 52 to 1,000 ft (16 to 305 m), with a maximum in Buchanan County. Sandstones were derived from sources southeast of the central Appalachian basin, some from lands southeast of the outcrop belt, and some formed by reworking of sandstones within the outcrop area. Sandstones change northwestward to shales in the Clinch and Rose Hill Formations. In the Middle Silurian and Helderberg Group, sandstones grade northwestward to limestones. Limestones in the Hancock Formation change westward to dolomite. The Onesquethaw Stage is represented by sandstone, chert, and limestone assigned to the Wildcat Valley and Huntersville Formations. In the Middle Silurian (Keefer or "Big Six" sandstone) and Early Devonian (Wildcat Valley Sandstone), longshore currents carried sand across the southwest end of the basin toward Kentucky. Several regional unconformities are present. These unconformities are mostly related to sea level changes, but some are probably tectonic in origin. Five unconformities are significant: (1) at base of Silurian, (2) at base of upper Helderberg over much of the area, (3) at base of Oriskany Sandstone, (4) at base of Huntersville Formation, and (5) at base of Upper Devonian black shales in extreme western Virginia, where Chattanooga Shale overlies Middle Devonian to Middle Silurian strata. End_of_Article - Last_Page 1918------------
Gulf Stream–Generated Topographic Rossby Waves

Abstract An inverse ray tracing model is applied to observations of 40-day topographic Rossby waves on the continental slope off of Cape Hatteras, North Carolina, to determine their origin. The rays are traced seaward and extend into the deep Gulf Stream, where the bottom slope remains strong enough that topographic β dominates planetary β. This enable coupling to occur between eastward propagating Gulf Stream meanders and topographic waves with eastward phase speed and matching zonal wavelength. Previous satellite observations indicate that the most frequently occurring Gulf Stream meanders have a period of 40 days and the model reveals that, as these meanders pass a topographic bend near 71°–72°W, they are able to couple to the observed topographic waves traced back from Cape Hatteras. The 40-day Gulf Stream meanders occur in bursts, which leads to associated bursts of the topographic waves.
Compressive feedback based non-vector space control

A non-vector space control method based on compressive feedback is presented in this paper. The non-vector space means the control is not performed in traditional vector space but in the space of sets. Consider an initial set and a goal set, a stabilizing controller is designed to make the set dynamics converge to the goal set. The compressive feedback means the controller works even when only partial elements of the feedback set are available; that is, the same controller can still stabilize the set dynamics around the goal set with the compressive feedback. The controller is applied to visual servoing by considering images as sets. In this way, image processing for feature extraction is not required, which is an essential process in conventional servo methods. Moreover, the compressive feedback can reduce the size of feedback image. It is important when the sampling is time consuming such as imaging using atomic force microscopy (AFM). The visual servoing formulation of the controller is further applied to the motion control in nanomanipulations. Simulation results suggest good performance of the controller. The framework proposed in this paper can be extended to other systems where the signals can be represented as sets.
Pyrazole-induced cytochrome P-450 in rat liver microsomes: An isozyme with high affinity for dimethylnitrosamine

Abstract Treatment of rats with pyrazole elevated the hepatic microsomal dimethylnitrosamine demethylase activity (DMNd) by several fold. Methylethylnitrosamine demethylase activity was also increased by pyrazole, but some classical monooxygenase activities were not induced. The treatment induced a new protein species which has an apparent molecular weight of 52,000 dal and is believed to be a cytochrome P-450 isozyme. The involvement of a hemoprotein in the pyrazole-induced DMNd was demonstrated in an experiment with CoCl 2 which decreased both the microsomal cytochrome P-450 content and DMNd. The induced enzyme with a single K m value of 0.061 mM and V max of 12.1 nmol/min/mg is probably the most efficient enzyme known to metabolize nitrosamines. NADPH-cytochrome P-450 reductase was also demonstrated to be an essential component enzyme of the DMNd. These results further substantiate the idea that the P-450-containing monooxygenase is responsible for the metabolism of dimethylnitrosamine in both the control and pyrazole induced microsomes.
On the relation of latency of alpha attenuation to alpha rhythm frequency and the influence of age.

Abstract EEGs were recorded in 90 healthy males aged 17–91 years. The brain wave tracings were attenuated (“blocked”) by short, high-intensity flashes of white light (25 trials). Average latency of alpha attenuation and average period of the EEG, in the interval of time between flash and initiation of the involuntary response, were determined along with the number of times the stimulus failed to attenuate the EEG. 1. 1. The data yielded a significant positive regression of attenuation latency on EEG period which remained so when the effects of age were partialled out. 2. 2. A low but statistically significant positive correlation was found between age and latent time of alpha attenuation. 3. 3. EEG reactivity declines in old age, but the correlation in this case was also low.
Cell aggregation in Dictyostelium discoideum.

Abstract The capacity of small populations of myxamebas of Dictyostelium discoideum to aggregate, i.e., to form pseudoplasmodia, was investigated under contrasting cultural and environmental conditions, including: (1) populations developed in situ on washed or purified agar where growth of myxamebas was restricted by limiting the nutrient (bacteria), and (2) populations of pregrown myxamebas that were harvested, washed, and deposited in known numbers at predetermined densities upon washed or purified agar varying in composition and prepared in different ways. The investigations centered upon the type culture of Dictyostelium discoideum (strain NC-4) and certain substrains derived from it, but included also nine other isolations of this species unrelated to NC-4 in point of origin. Aggregative capacity was found to be similar in all these when small populations were grown and tested under like conditions. The conditions under which tests of aggregative capacity were made profoundly influenced the results obtained. Factors of primary importance to aggregation seemed to include the following: (1) the existence of a critical relationship between the number of myxamebas and their density per unit area of substrate; (2) the necessity for cells to remain within reasonable proximity over a period of several hours subsequent to nutrient depletion in undisturbed cultures or after deposition on agar of pregrown populations in minute drops of water or saline; (3) the removal by washing from normal agar of certain unidentified substances that permit spreading of implanted drops and accentuate cell dispersal; and (4) the optimal reconstitution and/or preparation of the agar gel. The ability of a small population of 100–150 myxamebas, or fewer, to aggregate was found to be independent of any special type of cell recognizable by the writers. Rather this capacity is thought to result from physiological changes emergent within the population as a whole following nutrient depletion, on the one hand, or implantation of a pregrown population on the other. Unusually large myxamebas, believed to represent the so-called “I-cells” reported in existing literature, were occasionally observed; but such did not occur in any reasonably definite ratio in our cultures, and their diverse characteristics seemed to suggest no common origin. Finally, their total absence from the great majority of our test populations fails to support the notion that they represent a unique cell type of special significance to pseudoplasmodium formation in Dictyostelium discoideum .
Control of immunologic abnormalities associated with aging

In an attempt to encourage more intensive studies on the control of immunologic abnormalities associated with aging, the six different approaches which have been attempted are reviewed briefly. They are as follows: (a) internal body temperature control, (b) tissue ablation, (c) dietary manipulation, (d) genetic manipulation, (d) genetic manipulation (e) cell therapy and (f) chemical therapy. The first four are preventive and the latter two are restorative in approach. Many of these studies are very preliminary, but overall, the findings are most encouraging. These studies should resolve the extent to which decline in immunologic vigor with age influences the disease pattern of aging individuals and on their life expectancy.
MtDNA population structure and gene flow in lingcod (Ophiodon elongatus): limited connectivity despite long-lived pelagic larvae

Lingcod, Ophiodon elongatus Girard, have a 3-month pelagic larval stage and are an important recreational and commercial species on the west coast of North America. Cytochrome-c oxidase I sequences from tissue samples were used to characterize population structure and infer patterns of gene flow from California to Alaska. No significant genetic structure was found when estimates of Wright’s FST (i.e., ΦST) were generated among all populations sampled. Nesting populations within regions, however, indicated that the inner coast of Washington State is distinct, a result corroborating previous allozyme work. Coalescent-based estimates of gene flow indicate that although migration can be high from an evolutionary perspective, nearly half of all comparisons among populations showed no gene flow in at least one direction. From an ecological perspective, moderate migration rates (Nm < 10) among most populations provide surprisingly limited connectivity at large (∼ 1,000 km) and small (∼100 km) spatial scales. Coalescent-based estimates also show that gene flow between the inner and the outer coasts is asymmetric, a result consistent with prevailing surface currents. Because the expected inter-locus variances for coalescent-based estimates of gene flow are likely large, future work will benefit from analyses of nuclear DNA markers. However, limited demographic connectivity on large spatial scales may help explain why stock recovery has been uneven, with greater recovery in the northern (87% rebuilt) than in the southern (24% rebuilt) fishery region, supporting a regional management strategy. These results suggest that despite a 3-month pelagic larval stage, some areas may be effectively closed with respect to both population dynamics and fishery management issues.
Echocardiographic detection of pneumomediastinum and pneumopericardium: The air gap sign

Six patients referred for echocardiographic evaluation in whom an unusual echocardiographic sign resulted from air within the mediastinum or pericardium are described. Three patients had a pneumomediastinum that occurred after chest trauma and three patients had a pneumopericardium induced during a therapeutic pericardiocentesis. Important features included a broad band of echoes (air) recorded during held respiration which obscured the normal cardiac structures and dropout (gap) of echoes posteriorly. Between the cyclic appearance of the “air gap” sign, intracardiac structures were normally visualized. Echocardiographic recording of the air gap sign was identical in the six cases; it disappeared after resolution of clinical signs and symptoms of the pneumopericardium or pneumomediastinum. The pattern most likely resulted from air within the anterior mediastinum or pericardium interfering with the echo-graphic beam and resulted in a cyclic appearance from systole to early diastole as the air was displaced by the changing cardiac size. Recognition of the air gap sign can be helpful in evaluating patients for pneumomediastinum or pneumopericardium after thoracic trauma.
Bedload sheets in heterogeneous sediment

Field observations in streams with beds of coarse sand and fine gravel have revealed that bedload moves primarily as thin, migrating accumulations of sediment, and coarse grains cluster at their leading edge. These accumulations are one or two coarse grains high and are much longer (0.2-0.6 m long in sand; 0.5-2.0 m in fine gravel) than their height. The authors propose the term bedload sheet for these features, and the authors argue that they result from an instability inherent to bedload movement of moderately and poorly sorted sediment. In essence, coarse particles in the bedload slow or stop each other, trap finer particles in their interstices, and thus cause the coarse particles to become mobile again. Bedload sheets develop on the stoss side of dunes, causing the dune to advance incrementally with the arrival of each sheet. Successive deposition of coarse sediment from the leading edge followed by fine sediment may generate the grain-size sorting that distinguishes cross-bedding. Available flume experiments and field observations indicate that bedload sheets are a common, but generally unrecognized, feature of heterogeneous sediment transport.
Effects of Fat Content on the Sensory Properties, Melting, Color, and Hardness of Ice Cream

Ice creams were prepared that varied only in the percentage of milk fat (0.1, 3, 7, or 10%) and the corresponding total solids. All mixes were formulated to have similar freezing points and percentages of water frozen. Quantitative descriptive analysis was used to develop a ballot, which was then used by a trained sensory panel to assess the appearance, flavor, and texture of the vanilla ice creams. The color, hardness, and melting characteristics of the ice creams were also measured. Melting time and sample hardness were not significantly different among the 0.1, 3, and 7% fat samples of ice cream, but these characteristics of the lower fat ice creams differed from those of the 10% fat samples. The 10% fat samples took longer to melt and were softer than the 7% fat samples. The sensory analysis was more sensitive than the analytical measurement for detecting textural differences between ice cream samples. The panelists determined that removing the fat from ice cream made it more icy and more crumbly with fewer visible air holes. Sweetness was not influenced by fat content below 7%. The creamy flavor increased as the fat content of the ice creams increased. The milk powder flavor increased as the fat content decreased, even though the sample with 0.1% fat had less milk powder than the sample with 10% fat. Milk powder flavor was the major flavor component that was distinguished by the panelists when they evaluated the lower fat samples for aftertaste. Corn syrup was more perceptible in the lower fat samples even though all samples had the same concentration of corn syrup solids (4.5%).
Blockade of Platelet GPIIb/IIIa Receptors as an Antithrombotic Strategy

Moving from bench to bedside in the development of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, from a basic science laboratory reagent to an antithrombotic drug was a long, incremental process. From the beginning, we hoped that this powerful new agent would allow us to define better the biochemistry of the GPIIb/IIIa receptor and its role in platelet physiology and pathology, and we dreamed that we might be able to use it to improve the therapy of patients with vascular disease. I first review the evolution of our understanding of platelet physiology since the 1960s and why the platelet GPIIb/IIIa receptor appeared to be a logical target for antithrombotic therapy. I then describe our studies with 7E3 to block the receptor in experimental animal models of thrombosis. The results of these studies encouraged us to try to develop 7E3 as a human therapeutic agent. The development was a monumental effort conducted by hundreds of people working for nearly a decade and culminated in the approval by the Food and Drug Administration of c7E3 Fab (abciximab [ReoPro]) in December 1994 as conjunctive therapy for use in patients undergoing high-risk coronary artery angioplasty and atherectomy. A detailed description of the developmental process is beyond the scope of this essay, so it is only briefly described. My experience in moving back and forth from the academic medical center research bench to the world of drug development has allowed me to reflect on the processes involved, and at the end of this essay, I share some of my thoughts and concerns. The choice of the GPIIb/IIIa receptor as a therapeutic target rests on an enormous amount of basic and clinical research by many investigators working in what might appear to be quite disparate fields, including platelet-fibrinogen interactions, the rare blood platelet …
Powerful Others, Nonwork Factors, and Organizational Stress

Data gathered through individual interviews and a survey questionnaire from 43 professionals in a single department indicated that variations in the reported organizational stress could be explaine...
The radiological impact of actinides discharged to the Irish Sea

Abstract This paper describes the radiological effects of releases of actinides to the Irish Sea from Sellafield, the major source. Exposure pathways to man since the commencement of discharges in 1952 are reviewed; the importance of actinides began to increase with increased discharges in the 1970s. With the demise of the porphyra/laverbread pathway due to transport difficulties, the pathway due to fish and shellfish consumption became critical, particularly for actinides through molluscan shellfish. A reassessment on the current basis of effective dose shows that peak exposures to the critical group of about 2 mSv yr -1 were received in the mid-1970s, about 30% of which was due to actinides. Effective doses have since reduced but the relative importance of actinides is greater, due to the interplay of discharges of radionuclides from Sellafield and their behaviour in the environment. Additive doses through sea food due to releases of natural radionuclides from the Marchon phosphate plant at Whitehaven are also considered, although the actinide component from this source has been small. Exposures due to actinides from Sellafield via other pathways are shown to be much lower than those involving sea food. Collective doses are also considered; these peaked at about 300 man-Sv to the European population (including the UK) in 1979, with only a few percent due to actinides. As in the case of critical group doses, the relative importance of actinides has increased in recent years within the decreasing total collective dose. For both critical group and collective doses, therefore, the actinide component needs to be kept under review.
Significant proteins affecting cerebral vasospasm using complementary ICPMS and MALDI-MS

Cerebral vasospasm (CV) following subarachnoid hemorrhagic stroke affects more than one million people each year. The etiology and prevention of CV is currently of great interest to researchers in various fields of medical science. More recently, the idea that selenium could be playing a major role in the onset of cerebral vasospasm has come into the spotlight. This study focused on using newly established metallomics techniques in order to explore the proteome associated with CV and if selenium might affect the discovered proteins. Size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, along with LC-MALDI-TOF/TOF were both essential in determining protein identifications in three different sample types; a control (normal, healthy patient, CSF control), SAH stroke patients (no vasospasm, CSF C) and SAH CV patients (CSF V). The results of this study, although preliminary, indicate the current methods are applicable and warrant further application to these clinically important targets.
Effects of low sodium, ouabain, and strophanthidin on the shedding of rod outer segment discs

1. To test if the light-evoked hyperpolarization of the rods or retinal pigment epithelium (RPE) is important for the light-evoked component of rod disc shedding, eyecups of the anuran,Xenopus, were incubated in media that have been reported to have different effects on the membrane potential of these cells. 2. Hyperpolarization was induced by transferral to medium with Na+ entirely replaced by choline+, or mostly replaced by Li+. Shedding in darkness was increased 4-fold in both cases (Figs. 1, 2 and 3). 3. To prevent light-evoked hyperpolarization, eyecups were transferred to medium containing 0.5 mmol/l ouabain. However, light-evoked shedding was not inhibited; instead, it was activated further (Fig. 4). Moreover, ouabain increased shedding in darkness by about 9-fold (Fig. 5). 4. Ouabain likewise activated shedding without light in eyecups of the frog,Rana (Fig. 6). InRana, shedding is entirely light-evoked, so that, unlike the case represented byXenopus eyecups, there was no question that inhibition of the light-evoked component could have been masked by over-whelming stimulation of an endogenous component. 5. Strophanthidin, which, in contrast to ouabain, binds reversibly to Na+-K+-ATPase, also activated shedding inXenopus eyecups kept in darkness, even when it was washed out 20 min after light onset (Fig. 7). 6. These results suggest that a particular change in the membrane potential of the rod or RPE cells is not directly responsible for the occurrence of light-evoked rod disc shedding. 7. In addition, the results identify pharmacological treatments that activate shedding in darkness. These treatments should provide a useful tool for future studies of rod disc shedding. It is noted that common effects of these treatments possibly include: (1) inhibition of Na+, K+-ATPase activity, with a resulting increase in ATP; (2) an increase in intracellular Ca2+; (3) alteration of melatonin levels.
Linac radiosurgery for locally recurrent nasopharyngeal carcinoma: rationale and technique

Background. Patients with locally recurrent nasopharyngeal carcinoma benefit from reirradiation. A main barrier to successful palliation or cure is dose limitation secondary to normal tissue tolerance. There are many strategies to increase the tolerated dose to the recurrent lesions. Stereotactic radiosurgery for the treatment of these lesions has rarely been reported. Methods. Three patients with recurrent nasopharyngeal carcinoma were treated with linac-based stereotactic radiosurgery. Results. One patient remained disease-free 1 year after radiosurgery; the second patient had neurologic deterioration of uncertain etiology (complication vs recurrence) 6 months after radiosurgery; and the third patient had local recurrence 6 months after radiosurgery. Conclusion. Stereotactic radiosurgery can be used to deliver a boost dose of radiation to recurrent nasopharyngeal carcinomas. The technique is increasingly available and may offer some advantages compared with other techniques. Treatment recommendations are presented. © 1995 Jons Wiley & Sons, Inc.
Fungal diseases of columbiformes and anseriformes

Because of the high incidence of aspergillosis, fungal disease is an important condition in the waterfowl. Although this is generally a disease of individual birds, epizootics have been reported when overwhelming spore loads are present. By contrast, the occurrence of fungal disease is quite sporadic in the pigeon. In both groups of birds, however, the zoonotic potential of fungal diseases such as cryptococcosis, histoplasmosis, and blastomycosis is clinically significant. The abundant creatinine levels in droppings serve as a nitrogen source for these organisms. This allows their numbers to increase dramatically, which in turn increases the risk of disease transmission. Because pigeons often live in close proximity to people, their role in disease transmission is considered particularly important.
ENRICHMENT OF FINITE ELEMENTS WITH NUMERICAL SOLUTIONS FOR SINGULAR STRESS FIELDS

Enriched 2-D and 3-D finite elements are formulated for analysis of solids having multi-material junction and wedge configurations that create singular stress fields due to the material and/or geometric discontinuities. The order and angular variation of the displacements associated with the singular fields are determined from a separate special finite element eigenanalysis and used in the enrichment process. The use of these numerically determined singular fields allows enriched elements to be developed for complex configurations for which analytical fields are not available. In addition to this added flexibility of application, the current formulation applies to elements that may or may not be in direct contact with the singular point. This allows multiple layers of enriched elements to be used around the singular point and traditional mesh refinement studies to be carried out in the enriched element region. Previous enriched formulations have not provided this important capability. For cases where analytical fields are available, such as cracked solids, the performance of elements developed with the current approach is shown to be equivalent to that obtained using analytically enriched elements. Mesh refinement techniques using enriched elements are described that allow accurate stress distributions and generalized stress intensity factors to be directly determined. The importance of high-order numerical integration, use of multiple layers of enriched elements, and proper choice of the size of the enriched region are demonstrated by comparison to existing solutions for solids with cracks. Application of enriched element modelling to a 2-D bi-material wedge and a 3-D stepped-thickness anisotropic composite laminate is demonstrated. © 1997 John Wiley & Sons, Ltd.
Specific humidity forecasting using recurrent Neural Network

This paper presents our research in building a virtual humidity sensor using recurrent Neural Networks. Recurrent Neural Networks are promising methods for the prediction of time series because they provide feedback connections from hidden layer to its inputs and, therefore, can store temporal information learned from previous time steps. This study applies Elman Recurrent Neural Network (ERNN) to forecast the specific humidity from three weather stations. In addition, this study examines the feasibility of applying ERNN in time series forecasting by comparing it with multilayer perceptron network. The experiment results indicate that ERNN is a promising alternative to specific humidity forecasting.
An interpretation of special and general isotopic anomalies in r-process nuclei.

My analysis of new discoveries by McCulloch and Wasserburg of Ba and Nd isotopic anomalies in inclusions of the Allende meteorite argues that (1) these anomalies contain special extinct radioactivities resulting from radioactive decay within grains formed in and ejected from the supernova interior, (2) the inclusions studied are fused assemblies of interstellar grains that were never totally vaporized, and (3) theoretical separation into r and s abundances suggests that fluctuations between r and s components has occurred during the accumulation processes. These points lend support to a new chemical picture of the early solar system that I have developed, although many interpretations remain possible. Measurements of the neutron-capture cross sections of Nd isotopes are urgently needed to experimentally validate these conclusions.
Ultrasonic Detection of Delamination and Material Characterization of Thermal Barrier Coatings

This article describes ultrasonic nondestructive evaluation (NDE) to detect the changes of material properties and provide early warning of delamination in thermal barrier coating (TBC) systems. NDE tests were performed on single-crystal Rene N5 superalloy coupons that were coated with a commercially available MCrAlY bond coat and an air plasma sprayed 7% yttria-stabilized zirconia (YSZ) top coat deposited by Air Plasma Spray method, as well as Haynes 230 superalloy coupons coated with MCrA1Y bond coat, and an electron beam physical vapor deposit of 7% YSZ top coat. The TBC coupons were subjected to either cyclic or isothermal exposure for various lengths of time at temperatures ranging from 900 to 1100 °C. The ultrasonic measurements performed on the coupons had provided an early warning of delamination along the top coat/TGO interface before exposure time, when delamination occurred. The material's property (Young’s modulus) of the top coat was estimated using the measured wave speeds. Finite element analysis (FEA) of the ultrasonic wave propagation was conducted on a simplified TBC system to verify experimental observations. The technique developed was also demonstrated on an as-manufactured turbine blade to estimate normalized top coat thickness measurements.
Ultrastructural study of neurotensin immunoreactivity in the superficial laminae of the dorsal horn of the rat

Abstract Neurotensin immunoreactivity was identified in cell bodies, dendrites, spines, axons, terminals and varicosities in superficial laminae of rat spinal cord with the electron microscope. Unlabeled terminals synapsed with neurotensin-immunoreactive cell bodies, dendrites and spines. Presynaptic terminals contained round or pleomorphic vesicles and generally made symmetrical contacts with medium-sized neurotensin-containing dendrites in outer lamina II, and asymmetrical or symmetrical contacts with large and small dendrites and spines in inner lamina II. Neurotensin immunoreactive axons were unmyelinated, and their terminals were presynaptic to unlabeled dendrites and spines in laminae I and II. Terminals contained small, round, clear vesciles (31 nm) and occasional large granular vesicles (78 nm). Contacts in outer lamina II were evenly distributed among dendrites of various sizes and spines, whereas the majority of labeled terminals in inner lamina II made contacts onto small dendrites and spines. These findings indicate that neurotensin effects in rat spinal cord are mediated by axodendritic synapses, and that neurotensin cells at the inner and outer borders of lamina II contact dendrites of efferent neurons or other interneurons in the dorsal horn.
Factors Related to Job Satisfaction and Autonomy as Correlates of Potential Job Retention for Rural Nurses

: This study of 167 nurses in 10 rural Georgia agencies examines the relationships among personal characteristics, factors of job satisfaction, autonomy, and job retention. The findings indicate that, contrary to expectations, personal characteristics (e.g., age, education, salary, marital status, and number of dependents) are not strong predictors of job retention in this sample. Some of the factors of job satisfaction do correlate negatively with indicators of impending job change, but the strongest relationships were those related to nursing autonomy. The study concludes that, of the variables studied, autonomy was the most effective predictor of job satisfaction and intention to remain in the current position.