cssi/SciSciGPT-SciSciNet huggingface dataset:
Glycoprotein IIb/IIIa Receptor Antagonists Inhibit the Development of Platelet Procoagulant Activity

Abstract We examined the effects of glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists c7E3 Fab and DMP728 on the development of platelet prothrombinase (PT) activity. c7E3 Fab dose-dependently inhibited the rate of thrombin-stimulated thrombin generation over a 1-minute reaction time. The IC50 was 11 nM with an IC90 of 1000 nM. DMP728 inhibited PT activity maximally by 60% at 100 nM. A similar profile was observed for the inhibition of platelet tenase activity. Inhibition was platelet specific up to approximately 200 nM c7E3 Fab. Above 200 nM, inhibition was platelet independent, as shown by the inhibition of activity assembled on PS/PC vesicles. c7E3 Fab and DMP728 did not inhibit calcium ionophore-induced activity. DMP728 potency diminished with reaction time (over 6 minutes) whereas c7E3 Fab potency did not. Inhibition by 2 μM DMP728 was not further increased by 20 nM c7E3 Fab. Heparin inhibition of platelet PT activity was additive to that of c7E3 Fab. Studies with added von Willebrand factor (vWf) indicate that in the context of thrombin activation vWf activates platelets through mechanisms independent of GPIIb/IIIa to promote PT activity. Thrombin activation induced binding of FITC-AnnexinV to a subpopulation of platelets which was reduced by approximately 50% by pretreatment with either c7E3 Fab or DMP728. Together, these data indicate that c7E3 Fab and DMP728 inhibit the development of GPIIb/IIIa-mediated platelet PT activity at events during platelet activation. The inhibitory activities are not additive, suggesting these agents compete for the same site or inhibit via the same mechanism. Inhibition accompanies a reduction in the number of phosphatidylserine binding sites, implying that GPIIb/IIIa receptor antagonists reduce platelet membrane scrambling induced by thrombin. The additivity of inhibition with heparin by c7E3 Fab suggests a combination of these agents might have a greater bleeding liability than the use of either agent alone.
The Case for Drug Abuse Treatment Effectiveness, Based on the DARP Research Program *

Summary The Drug Abuse Reporting Programme (DARP) is a large-scale evaluation project focused on the effectiveness of drug abuse treatment, based on almost 44,000 clients admitted to 52 treatment centres located throughout the United States and in Puerto Rico between June 1969 and March 1973. The present paper summarizes research on post-DARP follow-up data (representing up to six years after DARP) for a sample of 3,131 persons admitted to treatment during 1969 to 1972. Treatments included methadone maintenance (MM), therapeutic community (TC), out-patient drug-free (DF), and out-patient detoxification programmes (DT); a comparison group of intake only (10) clients with no DARP treatment was also followed up. The data showed in general that three treatments, MM, TC and DF, led to favourable results — MM and TC for heroin and other opioid addicts, and DF for non-addicts (users of opioids less-than-daily, usually in conjunction with other non-opioid drugs and users of non-opioids only)
Learning to build a better mousetrap.

The state of research on media effects is one of the most notable embarrassments of modern social science. The pervasiveness of the mass media and their virtual monopoly over the presentation of many kinds of information must suggest to reasonable observers that what these media say and how they say it has enormous social and political consequences. Nevertheless, the scholarly literature has been much better at refuting, qualifying, and circumscribing the thesis of media impact than at supporting it. (Bartels, 1993, p. 267) *As director, adjunct professor, and former student, respectively.
Digital watermarking and steganography via overlays of halftone images

Recently, several watermarking schemes have been proposed that embed a watermark into two halftone images such that the watermark can be extracted by overlaying these halftone images. The watermark images in these schemes are binary images and the pixels in the two halftone images are correlated or not depending on whether the corresponding pixel in the watermark is on or off. In these schemes, the watermark is binary and does not contain detailed features. Furthermore, the extracted watermark contains residual patterns from the two images which reduces the fidelity of the extracted watermark image. This paper proposes a watermarking algorithm that addresses these problems. In addition, the proposed scheme admits more general watermark extraction functions and allows embedding of multiple watermark images.
The normative basis of economic science

It is often thought that economics is a pure descriptive or analytic science without normative components. But the very idea of commercial exchange or trade rests on the concepts of ownership or property. Unless the actors own something, there can be no sale, exchange or trade. Ownership or property is a moral-political concept. To own something is to be the one who ought to have the authority to trade or exchange it on terms he or she negotiates with others. This is the bedrock of economics and it is a normative idea.
Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide.

Abstract Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K. Ramaiahet al.,1998,Toxicol. Appl. Pharmacol.150, 12–21) revealed that a 35% DR compared toad libitum(AL) feeding leads to a substantial increase in liver injury of thioacetamide (TA) at a low dose (50 mg/kg, ip). Higher liver injury was accompanied by enhanced survival. A prompt and enhanced tissue repair response in DR rats at the low dose (sixfold higher liver injury) occurred, whereas at equitoxic doses (50 mg/kg in DR and 600 mg/kg in AL rats) tissue repair in AL rats was substantially diminished and delayed. The extent of liver injury did not appear to be closely related to the extent of stimulated tissue repair response. The purpose of the present study was to investigate the time course (0–120 h) of liver injury and liver tissue repair at the high dose (600 mg TA/kg, ip, lethal in AL rats) in AL and DR rats. Male Sprague–Dawley rats (225–275 g) were 35% diet restricted compared to their AL cohorts for 21 days and on day 22 they received a single dose of TA (600 mg/kg, ip). Liver injury was assessed by plasma ALT and by histopathological examination of liver sections. Tissue repair was assessed by [3H]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry during 0–120 h after TA injection. In AL-fed rats hepatic necrosis was evident at 12 h, peaked at 60 h, and persisted thereafter until mortality (3 to 6 days). Peak liver injury was approximately twofold higher in DR rats compared to that seen in AL rats. Hepatic necrosis was evident at 36 h, peaked at 48 h, persisted until 96 h, and returned to normal by 120 h. Light microscopy of liver sections revealed progression of hepatic injury in AL rats whereas injury regressed completely leading to recovery of DR rats by 120 h. Progression of injury led to 90% mortality in AL rats vs 30% mortality in DR group. In the surviving AL rats, S-phase DNA synthesis was evident at 60 h, peaked at 72 h, and declined to base level by 120 h, whereas in DR rats S-phase DNA synthesis was evident at 36 h and was consistently higher until 96 h reaching control levels by 120 h. PCNA studies showed a corresponding increase in cells in S and M phase in the AL and DR groups. DR resulted in abolition of the delay in tissue repair associated with the lethal dose of TA inad libitumrats. Temporal changes and higher tissue repair response in DR rats (earlier and prolonged) are the conduits that allow a significant number of diet restricted rats to escape lethal consequence.
Metal concentrations in three Montana soils following 20 years of fertilization and cropping

The presence of metals in some agricultural fertilizers has raised the concern that fertilized soils may be accumulating potentially toxic metals. A number of studies have been undertaken to determine the extent and significance of this potential problem, yet results have been mixed and the studies were not conducted in the Northern Great Plains. Therefore, a study was undertaken to determine if fertilization has increased metal concentrations in selected Northern Great Plain soils. Two irrigated sites and one non-irrigated site were selected; each had at least 20 years of fertilization and cropping history. Paired (fertilized and non-fertilized) soils from three depths (0–15 cm, 15–30 cm, and 30–45 cm) were sampled in replicate (n=10) and analyzed for a range of plant available and total metals, pH, organic matter, and phosphorus. In general, fertilized soils were found to have significantly lower levels of available and total metals than those of non-fertilized soils, indicating that long-term fertiliza...
The role of cytochrome P450 epoxygenases in retinal angiogenesis.

Purpose The purpose of this study was to investigate the role(s) of cytochrome P450 epoxygenases (CYPs) and their products, the epoxyeicosatrienoic acids (EETs), in hypoxia-induced VEGF production and pathologic retinal angiogenesis. Methods Human retinal astrocytes, Muller cells, and retinal microvascular endothelial cells (HRMEC) were exposed to hypoxia, and relative CYP2C expression was measured by RT-PCR. Astrocyte and Muller cell VEGF production was measured by ELISA after exposure to hypoxia and treatment with the general CYP inhibitor, SKF-525a. Human retinal microvascular endothelial cells were treated with the CYP product, 11,12-epoxyeicosatrienoic acid [EET], or SKF-525a in the presence or absence of VEGF. Proliferation of HRMEC and tube formation were assayed. Oxygen-induced retinopathy (OIR) was induced in newborn rats. Retinal CYP2C11 and CYP2C23 expression were measured by RT-PCR. The OIR rats received SKF-525a by intravitreal injection and preretinal neovascularization (NV) was quantified. Retinal VEGF protein levels were measured by ELISA. Results Human retinal astrocytes were the only cells to exhibit significant induction of CYP2C8 and CYP2C9 mRNA expression by hypoxia. Astrocytes, but not Muller cells, exhibited reduced hypoxia-induced VEGF production when treated with SKF-525a. 11,12-EET induced HRMEC proliferation and tube formation, and SKF-525a inhibited VEGF-induced proliferation. Oxygen-induced retinopathy induced expression of CYP2C23, but had no effect on CYP2C11. SKF-525a inhibited retinal NV and reduced retinal VEGF levels in OIR rats. Conclusions The CYP-derived 11,12-EET may exhibit a proangiogenic biological function in the retina following stimulation by hypoxia in astrocytes. Inhibition of CYP may provide a rational therapy against retinal NV, because it can reduce VEGF production and VEGF-induced angiogenic responses in endothelial cells.
Characterization of vascular postsynaptic NPY receptor function and regulation and differential sensitivity of Y1 and Y2 receptor function to changes in extracellular calcium availability and prior in vitro peptide exposure.

Abstract Effects of calcium-free buffer, nifedipine, or prior cumulative neuropeptide Y (NPY) receptor agonist concentration exposure on vasoconstrictive responsiveness to the agonists were assessed in norepinephrine (NE)-conditioned isolated rat femoral artery rings. Calcium-free buffer and nifedipine partially inhibited responsiveness to initial NPY exposure; residual responsiveness to NPY re-exposure was unaffected. In contrast, these treatments markedly inhibited responsiveness to the Y 2 agonist NPY 13–36 , the calcium channel agonist BAY K 8644 (BAY) and the partial alpha 1 adrenoceptor agonist indanidine but did not alter that to the Y 1 agonist [Leu 31 , Pro 34 ]NPY. Responsiveness to NPY and NPY 13–36 but not to BAY or indanidine was markedly reduced 120 min following conditioning regardless of prior ring exposure to the same peptide; only prior exposure reduced responsiveness to [Leu 31 , Pro 34 ]NPY. Responsiveness changes to NPY at various times or after various numbers of NE and/or NPY exposures indicated that pre-exposure and time-related responsiveness reductions were discriminable and temporally unrelated to conditioning. Postsynaptic vascular Y 2 receptor activation therefore accounts for the known sensitivity of NPY-induced pressor and vasoconstrictive actions to nifedipine. The ‘time-dependent’ loss of Y 2 receptor function may also explain prior failures to observe postsynaptic arterial Y 2 receptors in vitro.
Preventing kidney cell suicide

Decreased levels of activated protein C allow for kidney cell death in a mouse model of diabetic nephropathy. The findings suggest that targeting the antiapoptotic protein C pathway could counteract kidney damage in individuals with diabetes (pages 1349–1358).
Effective pair interactions for a model binary transition metal alloy at point and extended defects

Abstract The coordination number effects on the effective-pair-interaction of a model binary transition metal alloy are calculated as a function of band-filling and concentration. A six moment expansion along with the maximum-entropy method is used to approximate the density of states of a d -band, nearest-neighbor, tight-binding Hamiltonian, and a decoupled form is used for the higher order correlation functions. We find that the coordination number effects are large. The effective-pair-interaction scales approximately as Z - 3 2 where Z is the coordination number.
Optical Properties of the Alloy System SnTeGeTe from Reflectance Measurements

The reflectance spectra of bulk samples of the alloy series Sn1−xGexTe are measured at room temperature in the wavelength range 0.2 to 50 μm. The principal optical constants are obtained using Kramers-Kronig analysis. The variations of the optical dielectric constant, the carrier effective mass, the optical mobility, and the optical energy gap are given as functions of the alloy fraction x. For the Sn-rich alloys (x < 0.3) the energy gap and the dielectric constant do not follow the trends established for the series at the Ge-rich side, and are possibly related to the cubic-rhombohedral phase transition that occurs in this system. The mobility and effective mass, though, behave reasonably for all alloy fractions. On a mesure les spectres de reflexion des echantillons en gros du systeme d'alliage Sn1−xGexTe a l'ambiante dans la gamme des ondes 0,2 a 50μm. Les constantes optiques principales ont ete obtenues en utilisant l'analyse Kramers-Kronig. Les variations de la constante dielectrique optique, la masse effective des porteurs, la mobilite optique, et l'ecart energetique optique sont presentees en fonction de la composition d'alliage x. Pour les alliages riches en Sn (x < 0,3) l'ecart energetique et la constante dielectrique ne suivent pas l'allure etablie pour la serie par les composes riches en Ge, un comportement peut-ětre lie a la transition de phase cubique–rhombohedrale qui se montre dans ce systeme. La mobilite et la masse effective, d'ailleurs, se comportent normalement pour toutes compositions d'alliage.
Automated Security Test Generation with Formal Threat Models

Security attacks typically result from unintended behaviors or invalid inputs. Security testing is labor intensive because a real-world program usually has too many invalid inputs. It is highly desirable to automate or partially automate security-testing process. This paper presents an approach to automated generation of security tests by using formal threat models represented as Predicate/Transition nets. It generates all attack paths, i.e., security tests, from a threat model and converts them into executable test code according to the given Model-Implementation Mapping (MIM) specification. We have applied this approach to two real-world systems, Magento (a web-based shopping system being used by many online stores) and FileZilla Server (a popular FTP server implementation in C++). Threat models are built systematically by examining all potential STRIDE (spoofing identity, tampering with data, repudiation, information disclosure, denial of service, and elevation of privilege) threats to system functions. The security tests generated from these models have found multiple security risks in each system. The test code for most of the security tests can be generated and executed automatically. To further evaluate the vulnerability detection capability of the testing approach, the security tests have been applied to a number of security mutants where vulnerabilities are injected deliberately. The mutants are created according to the common vulnerabilities in C++ and web applications. Our experiments show that the security tests have killed the majority of the mutants.
Sporotrichosis in childhood: report of ten cases.

Ten cases of sporotrichosis, an uncommon mycotic infection occurring in children, are described. This is the largest reported series of the disease in children. Various aspects of the epidemiologic, clinical, and laboratory findings in these patients are described.
An evaluation of the local anesthetic, mepivacaine hydrochloride, in operative dentistry

Abstract The purpose of this study was to compare a new local anesthetic with anesthetic solutions in routine use in the operative dentistry clinic at the School of Dentistry, University of Washington. Three local anesthetic solutions—the one under test containing mepivacaine hydrochloride 2 per cent with levonordefrin 1:20,000, and the two controls consisting of lidocaine hydrochloride 2 per cent with epinephrine 1:50,000, and a mixture of procaine hydrochloride 2 per cent, tetracaine hydrochloride 0.15 per cent with levonordefrin 1:20,000—were compared under blind test conditions on 751 patients.
Reduced Sialylation Impacts Ventricular Repolarization by Modulating Specific K+ Channel Isoforms Distinctly

Voltage-gated K+ channels (Kv) are responsible for repolarizing excitable cells and can be heavily glycosylated. Cardiac Kv activity is indispensable where even minimal reductions in function can extend action potential duration, prolong QT intervals, and ultimately contribute to life-threatening arrhythmias. Diseases such as congenital disorders of glycosylation often cause significant cardiac phenotypes that can include arrhythmias. Here we investigated the impact of reduced sialylation on ventricular repolarization through gene deletion of the sialyltransferase ST3Gal4. ST3Gal4-deficient mice (ST3Gal4−/−) had prolonged QT intervals with a concomitant increase in ventricular action potential duration. Ventricular apex myocytes isolated from ST3Gal4−/− mice demonstrated depolarizing shifts in activation gating of the transient outward (Ito) and delayed rectifier (IKslow) components of K+ current with no change in maximum current densities. Consistently, similar protein expression levels of the three Kv isoforms responsible for Ito and IKslow were measured for ST3Gal4−/− versus controls. However, novel non-enzymatic sialic acid labeling indicated a reduction in sialylation of ST3Gal4−/− ventricular Kv4.2 and Kv1.5, which contribute to Ito and IKslow, respectively. Thus, we describe here a novel form of regulating cardiac function through the activities of a specific glycogene product. Namely, reduced ST3Gal4 activity leads to a loss of isoform-specific Kv sialylation and function, thereby limiting Kv activity during the action potential and decreasing repolarization rate, which likely contributes to prolonged ventricular repolarization. These studies elucidate a novel role for individual glycogene products in contributing to a complex network of cardiac regulation under normal and pathologic conditions. Background: Glycosylation results from the coordinated activities of glycogene products that can modulate ion channel function. Results: Gene ablation of the sialyltransferase ST3Gal4 impacts sialylation and gating of specific cardiac voltage-gated K+ channel isoforms and thereby ventricular repolarization. Conclusion: Individual glycogene products serve unique roles in affecting cardiac voltage-gated K+ channel activity. Significance: Protein glycosylation significantly contributes to ventricular electrical signaling.
Submillimeter lightcurves of Vesta

Abstract Thermal lightcurves of Asteroid Vesta with significant amplitude have been observed at 870 μm (345 GHz) using the MPIfR 19-channel bolometer of the Heinrich–Hertz Submillimeter Telescope. Shape and albedo are not sufficient to explain the magnitude of this variation, which we relate to global variations in thermal inertia and/or other thermophysical parameters. Vesta's lightcurve has been observed over several epochs with the same general shape. However, there are some changes in morphology that may in part be related to viewing geometry and/or asteroid season. Inconsistent night-to-night variations exhibit the inherent difficulties in photometry at this wavelength. We are able to match the observed brightness temperatures with a relatively simple thermal model that integrates beneath the surface and assumes reasonable values of thermal inertia, loss tangent and refractive index, and without having to assume low values of emissivity in the submillimeter. High flux portions of the submillimeter lightcurve are found to correspond to regions with weak mafic bands observed in Hubble Space Telescope images.
Effect of diabetes mellitus on the presentation and triage of patients with acute chest pain without known coronary artery disease

Abstract PURPOSE: Patients with diabetes and acute chest pain may be admitted to hospitals more frequently than patients without diabetes because physicians suspect atypical presentations for ischemic heart disease. This study aimed to determine whether the presentation of acute myocardial infarction and risk for major cardiac complications differs among patients without known coronary artery disease who do or do not have diabetes. PATIENTS AND METHODS: Data from an emergency department of an urban teaching hospital on the medical histories, physical examinations, and electrocardiograms of 2,694 subjects with acute chest pain and without known coronary artery disease were prospectively recorded. RESULTS: Diabetes was present in 301 (11%) patients. Compared with patients without diabetes, patients with diabetes were more likely to be ≤60 years old (51% versus 20%) and to have a history of hypertension (70% versus 35%) or high blood cholesterol (35% versus 19%). A discharge diagnosis of acute myocardial infarction was made in 25 diabetic (8%) and in 148 nondiabetic (6%; P = 0.16) patients. A major cardiac complication occurred in two patients with diabetes (0.7%) and in 20 patients without diabetes (0.8%; P = 1.0). Patients with and without diabetes who had atypical chest pain complaints had similar rates of myocardial infarction (3% and 4%, respectively; P = 0.6). Patients with diabetes were more likely to be hospitalized (67% versus 47%; P = 0.001) both before and after adjusting for clinical and electrocardiographic data. CONCLUSIONS: For patients with acute chest pain without a prior history of coronary artery disease, diabetes was not associated with a higher rate of acute myocardial infarction or complications. However, diabetes was associated with a higher rate of hospitalization in this population, suggesting that physicians have a lower threshold for admission to the hospital of patients with diabetes.
Chemical Composition of Municipal Leaf Waste and Hand-Collected Urban Leaf Litter

Municipal leaf waste delivered to New Jersey farms was sampled to evaluate its chemical composition and suitability for land application. Freshly fallen leaf litter samples were also collected and analyzed from seven different urban landscape tree species. Municipal leaf waste data from 100 samples in this study was summarized using frequency distributions to characterize its variability in composition. The chemical composition of municipal leaf waste was found to be quite variable. The minimum-maximum and median values were as follows : (g kg -1 ) C, 363 to 516, 480 ; N, 6.6 to 16.2, 9.4 ; P, 0.2 to 2.9, 1.0 ; K, 0.9 to 8.8, 3.6 ; Ca 1.3 to 30.4, 17.3 ; Mg, 0.2 to 4.6, 2.4 ; S, 0.1 to 2.1, 1.1 ; (mg kg -1 ) B, 7 to 72, 38 ; Fe, 46 to 9800, 733 ; Al, 58 to 10554, 602 ; Mn, 19 to 1845, 406 ; Zn, 22 to 392, 67 ; Na, 36 to 325, 90 ; Cl, 68 to 3995, 1083 ; Cu, 2.8 to 31.5, 8.1 ; Co, 0.9 to 10.9, 2.7 ; Cd, 0.1 to 6.8, 1.3 ; Pb, 3 to 400, 18 ; Ni, 1 to 58, 5 ; Cr, 0.9 to 35.1, 6.6 ; Ba, 4.2 to 142.0, 49.4. Although municipal leaf waste contains significant amounts of valuable plant nutrients, the high C/N ratio (range : 26.8-71.8 ; median : 48.5) suggests that heavy applications are likely to cause immobilization of available soil N. Concentrations of Fe, Al, Pb, and Cd were generally higher and more variable in municipal leaf waste than in hand-collected leaf litter. This suggests that contamination with urban soil during collection contributes to elevated Pb and Cd concentrations in municipal leaf waste. Given careful attention to N-fertilizer practice, municipal leaf waste is a suitable material for application to farm land.
RADIOGRAPHIC, COMPUTED TOMOGRAPHIC AND MAGNETIC RESONANCE IMAGING EVALUATION OF A CHRONIC LONG DIGITAL EXTENSOR TENDON AVULSION IN A DOG

Long digital extensor tendon avulsion is reported in a 5 month old Great Dane. Clinically the dog presented with a unilateral weight-bearing pelvic limb lameness. Joint effusion was present and there was pain and crepitance associated with flexion of the stifle. Orthopedic evaluation and radiographs were suggestive of a long digital extensor tendon injury which was confirmed by computed tomography and magnetic resonance imaging. The injury was surgically repaired with screw and spiked washer fixation.
Class, gender, and coal smoke: gender ideology and environmental injustice in Pittsburgh, 1868-1914.

Gender, class, and race are standard analytical categories that structure much of contemporary social and cultural history. Environmental historians have employed these categories to trace differential impacts of pollution across social divisions in studies concerned with "environmental justice." With class and race, it is easy to see disproportionate impacts -pollution burdens are distributed along spatial lines, and residential segregation has, in varying degrees, historically characterized American cities. The relevance of gender to environmental justice is less clear.' How then do we talk about environmental justice and gender? Did gender differences influence concern about environmental justice with respect to race or class? Can we treat women or men as social groups who suffered unjust pollution burdens?2 How can we use "gender as a ... category of historical analysis" to treat the articulation of the power relations that gave rise to differential pollution burdens? These three dimensions of gender and environmental justice intersect in the history of air pollution (smoke) in Pittsburgh. Changing conceptions of values, virtues, and the human good determine the meaning that "environmental justice" can have in differing historical contexts. Since its days as manufacturing depot for the Ohio Valley migration, Pittsburgh was associated both with its heavy mantle of bituminous coal smoke and with the heavy industry that produced it.3 In i868, Atlantic Monthly columnist James Parton compared Pittsburgh's picturesque industrial spectacle to "hell with the lid taken off." Between the 186os and the i9ios, Pittsburghers began to organize to abate coal smoke, and concomitantly Pittsburgh's civic self-conception began to change. Although Pittsburgh remained both the Smoky City and the Iron City well into the twentieth century, by 1914, Pittsburghers of many backgrounds were less willing to accept smoke as their city's emblem. Early writers described smoke as ubiquitous and pervasive, but smoke burdens were distributed differentially with respect to both gender and class. Conditions of
Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia

The ability to sense and respond to changes in oxygen availability is critical for many developmental, physiological, and pathological processes, including angiogenesis, control of blood pressure, and cerebral and myocardial ischemia. Hypoxia-inducible factor-1α (HIF-1α) is a basic-helix–loop–helix (bHLH)containing member of the PER–ARNT–SIM (PAS) family of transcription factors that plays a central role in the response to hypoxia. HIF-1α, and its relatives HIF-2α/endothelial PAS domain protein (EPAS) and HIF-3α, are induced in response to hypoxia and serve to coordinately activate the expression of target genes whose products facilitate cell survival under conditions of oxygen deprivation. When cells are exposed to chronic hypoxia, the protective response can fail, resulting in apoptosis. This study shows that transcription of the gene encoding Nip3, a proapoptotic member of the Bcl-2 family of cell death factors, is strongly induced in response to hypoxia. The Nip3 promoter contains a functional HIF-1-responsive element (HRE) and is potently activated by both hypoxia and forced expression of HIF-1α. Exposure of cultured cells to chronic hypoxia results in the accumulation of a protein recognized by antibodies raised against Nip3. This study demonstrates a direct link between HIF-1α and a proapoptotic member of the Bcl-2 family and offers a reasonable physiological function for members of the Bcl-2 subfamily, including Nip3 and its close relative Nix. These observations indicate that Nip3 may play a dedicated role in the pathological progression of hypoxia-mediated apoptosis, as observed after ischemic injury.
Discussion of the fundamental problem of atmospheric electricity

The fundamental problem of atmospheric electricity is given by the question to the cause of the electrical current which can be observed everywhere in the terrestrial atmosphere. The ‘classical picture’ which emerged in the 1920's, also called sometimes the ‘spherical capacitor theory’, is shown to be unproven or even disproven by measuring results available until now. The constituting elements of the classical picture are investigated individually, and conclusions are drawn from these considerations. The outcome is that we indeed have a globally controlled current flow vertically through the atmosphere, but that the connection to the thunderstorm activity is tenuous and, in fact, contradicted by proper interpretation of available measurements. On the other hand, thunderstorms do generate electric currents which feed into the global current circuit, and the amount could very well be sufficient, but we do not have sufficient evidence to be able to decide this question.—The author stresses the necessity to improve the measurement techniques and indicates how to do it, he even calls for an abandonment of outmoded methods which are sometimes misleading and in their results often confusing, but nevertheless still practiced at many places. The Atmospheric Electricity Ten-Year Program is discussed as the natural consequence derived from the present situation.
Physical state of ices in the outer solar system

Comparison of the identity and abundances of ices observed around protostars and those associated with comets clearly suggests that comets preserve the heritage of the interstellar materials that aggregated to form them. However, the ability to identify these same species on icy satellites in the outer solar system is a complex function of the composition of the original ices, their subsequent thermal histories, and their exposure to various radiation environments. Our ability to identify the ices currently present on objects in the outer solar system relies upon observational and laboratory, and theoretical efforts. To date there is ample observational evidence for crystalline water ice throughout the outer solar system. In addition, there is growing evidence that amorphous ice may be present on some bodies. More volatile ices, e.g. N2, CH4. CO, and other species, e.g. ammonia hydrate, are identified on objects lying at and beyond Uranus. Both photolysis and radiolysis play important roles in altering the original surfaces due to chemical reactions and erosion of the surface. Ultraviolet photolysis appears to dominate alteration of the upper few hundred Angstroms, although sputtering the surface can sometimes be a significantly competitative process; dominating on icy surfaces embedded in a strong planetary magnetospheric field. There is growing observational evidence that the by-products of photolysis and radiolysis, suggested on a theoretical basis, are present on icy surfaces.
The effect of supraoptimal temperatures on the contents of krebs' cycle acids in Arabidopsis thaliana☆

Abstract The effect of supraoptimal temperatures on the contents of several Kreb's cycle acids in Arabidopsis thaliana (L.) Heynh was investigated. Plants grown at the higher temperatures (32° day and 25° night) were lower in dry and fresh weights than those grown at the optimal temperatures (25° day and 18° night). Citric, succinic, fumaric, and malic acid concentrations were measured at 2, 3 and 4 weeks after planting. Although the sum of the amounts of the four acids was generally higher in the shoots of plants grown at supraoptimal temperatures than in those grown at optimal temperatures, at 3 weeks after planting, the reverse was true. This latter result was due largely to changes in the fumaric and malic acid contents. From the second to the third week of growth, the contents of these two acids dropped in higher temperature plants and rose sharply in the optimal temperature plants with an exactly opposite trend occurring from the third to fourth weeks of growth. In the fourth week, the citric acid content decreased to a very low value under optimal conditions and increased under supraoptimal conditions. The results show that malic and succinic acids are strikingly different with respect to compartmentation or to the directness of their association with the Krebs' cycle. The data provide information on changes in organic acid content in shoots through most of the life cycle of a plant, and they further show that temperature can affect organic acid levels at any given time.
Sex-specific patterns of galanin, cholecystokinin, and substance P expression in neurons of the principal bed nucleus of the stria terminalis are differentially reflected within three efferent preoptic pathways in the juvenile rat.

Neurons in the principal bed nucleus of the stria terminalis (BSTp) integrate hormonal and sensory information associated with reproduction and transmit this information to hypothalamic nuclei that regulate neuroendocrine and behavioral functions. The neuropeptides galanin (GAL), cholecystokinin (CCK), and substance P (SP) are highly expressed in BSTp neurons and are differentially regulated by sex steroids. The current experiments investigated whether developmental or peripubertal hormone-mediated changes in GAL, CCK, and SP expression are reflected within efferent pathways to the preoptic structures that regulate gonadotropin secretion and sexual behavior. Anterograde labeling of projections from the BSTp of male and female juvenile rats combined with immunohistochemical labeling of GAL-, CCK-, and SP-containing fibers in the anteroventral periventricular preoptic nucleus (AVPV) and the central and medial divisions of the medial preoptic nucleus (MPNc, MPNm, respectively) revealed unique sex differences in each region. In the AVPV, Phaseolus vulgaris leucoagglutinin-labeled fibers were seen at a greater density in males than in females, and higher percentages of these fibers contained GAL in males than in females. In contrast, fibers projecting from the BSTp to the MPNc were more likely to contain SP in females than in males. Treatment of gonadectomized, peripubertal males and females with exogenous testosterone and estradiol did not alter the densities of GAL-, CCK-, or SP-containing fibers in any of the three brain areas examined. Collectively, these results suggest that patterns of neuropeptide expression in BSTp projections are established during development, resulting in a distinct, stable, and sex-specific chemoarchitectural profile for each projection pathway.
Ethical Advertising Research Standards: Three Case Studies

Abstract Demands for major changes in the regulation of advertising have come forth as a result of the December, 1991 publication of three articles concerning the cartoon character Joe Camel. The articles all appeared in the same issue of the Journal of the American Medical Association and received extensive coverage in major newpapers and magazines. This paper examines each article to determine its conformance with 15 ethical standards gleaned from various associations and journals; these standards represent the accepted professional norms of conduct for social science research. There is also a closer examination of one of the studies using discovery material from a law suit against the R.J. Reynolds firm. This affords a unique opportunity to examine the ethical standards used in that study. Five reviewers from different disciplines were asked to independently evaluate each of the papers. The results revealed major concerns about the quality of each study. When these reviews are laid against the ethical ...
Electronic energy self-exchange with macrocyclic chromium(III) complexes.

The luminescence lifetimes of N-deuterated Cr(III) complexes of macrocyclic tetraamine ligands, trans-CrN4X2n+, are substantially longer than those of their undeuterated counterparts in room temperature solution. Thus, excited-state emission quenching of the longer lived species by the shorter lived species may be studied by analyzing the decay profile following pulsed excitation. Flash photolysis experiments were carried out for three deuterated/undeuterated pairs of trans-CrN4X2n+ complexes (where X = CN-, NH3, and F-). For the trans-Cr(cyclam)(CN)2+ system in H2O, it was determined that energy transfer was occurring between the deuterated and undeuterated species. Although the rate constant of energy transfer was too fast to measure explicitly, it could be bracketed as ket ≫ 7 × 106 M-1 s-1. For this reaction it was possible to measure an equilibrium constant which was very near 1.0. For trans-Cr(cyclam)(NH3)23+ in DMSO, it was also established that energy transfer was occurring and rate constants of 2...
Tests of the mouse visual system

To apply the approach of forward genetics (e.g., gene identification with mutagenesis and screening, followed by positional cloning) to the mouse, it is necessary to have available screening tests that can be applied rapidly to individual mice and that give a reliable assessment of visual function. This paper reviews the strengths and limitations of two anatomical tests related to visual function, fundus examination and retinal histological examination. Two tests that do not depend on behavior of a conscious animal are reviewed: the electroretinogram and the visual evoked potentials of the cortex. Eight behavioral tests are also summarized: maze-based tests, cued fear conditioning, tests based on conditioned suppression, visual placing, optokinetic nystagmus, pupillary reflex, and light-induced shifts in circadian phase. It is recommended that retinal histology, the electroretinogram, and visual-evoked potentials be used at the present time for screening because they assess the function and structure of the visual system rapidly and reliably. In fact, the electroretinogram (or visually evoked potentials) can be recorded from several animals simultaneously in response to the same stimulus. It is also recommended that efforts be made to develop more appropriate, automated, behavioral tests of visual perception than are now available, particularly tests that rely solely on rewarding visually evoked behavior. Two other promising behavioral tests are cued fear conditioning and variants of maze tests.
Deterministic resolution of two aircraft conflict in free flight

This paper studies strategies for resolving two aircraft conflicts in a free flight environment for air traffic management. In a free flight environment, pilots of individual aircraft can change flight paths in real time. As a result, resolving conflicts among aircraft becomes a key priority for controllers. In this paper, a pointmass level flight aircraft model is used. Resolution of a two-aircraft conflict is formulated as deterministic nonlinear optimal control problems. Performance indices are selected to minimize deviations of both aircraft from their originally-intended flight paths or to minimize banking angles, subject to a minimum separation requirement. In addition, terminal constraints are included that force each aircraft to return to its original path after conflict avoidance maneuvers. In an unrestricted region, it is assumed that aircraft are originally flying with a constant heading. In general, the two aircraft would turn the same way (left or right) by roughly the same amount to avoid a conflict. When the intersecting angle is small, however, one aircraft needs to take a path stretching to avoid the other aircraft. In the terminal region where aircraft converge to the same gate, one aircraft needs to stretch its flight paths to avoid the other aircraft. If the two aircraft have the same speed, either aircraft can perform the path stretching. If the two aircraft have different speeds, the slower aircraft should perform the path stretching.
Pharmacologic Alternatives to Riboflavin Photochemical Corneal Cross-Linking: A Comparison Study of Cell Toxicity Thresholds

PURPOSE. The efficacy of therapeutic cross-linking of the cornea using riboflavin photochemistry (commonly abbreviated as CXL) has caused its use to become widespread. Because there are known chemical agents that cross-link collagenous tissues, it may be possible to cross-link tissue pharmacologically. The present study was undertaken to compare the cell toxicity of such agents. METHODS. Nine topical cross-linking agents (five nitroalcohols, glyceraldehyde [GLYC], genipin [GP], paraformaldehyde [FA], and glutaraldehyde [GLUT]) were tested with four different cell lines (immortalized human corneal epithelial cells, human skin fibroblasts, primary bovine corneal endothelial cells, and immortalized human retinal pigment epithelial cells [ARPE-19]). The cells were grown in planar culture and exposed to each agent in a range of concentrations (0.001 mM to 10 mM) for 24 hours followed by a 48-hour recovery phase. Toxicity thresholds were determined by using the trypan blue exclusion method. RESULTS. A semiquantitative analysis using five categories of toxicity/fixation was carried out, based on plate attachment, uptake of trypan blue stain, and cellular fixation. The toxicity levels varied by a factor of 10 3 with the least toxic being mononitroalcohols and GLYC, intermediate toxicity for a nitrodiol and nitrotriol, and the most toxic being GLUT, FA, GP, and bronopol, a brominated nitrodiol. When comparing toxicity between different cell lines, the levels were generally in agreement. CONCLUSIONS. There are significant differences in cell toxicity among potential topical crosslinking compounds. The balance between cross-linking of tissue and cell toxicity should be borne in mind as compounds and strategies to improve mechanical tissue properties through therapeutic tissue cross-linking continue to develop.
Response to Wong's Article

This commentary supports Wong's thesis regarding the potential of the risk and resilience framework for the field of learning disabilities (LD), while suggesting several specific areas in which longitudinal study with a risk and resilience framework would be particularly beneficial. It is recommended that focus be placed on identification of risk and protective factors for developmental outcomes in children already identified with LD. Application of this approach to analyzing friendship strategies is described, particularly as it might redirect study to the development of shared interests among children with and without LD. Using longitudinal research to identify positive, naturally occurring family practices, and translating these practices into interventions for families in which they do not naturally occur, is also discussed.
Activity analysis with activity switching

This study presents a multi-activity profit-maximization model which includes a set of zero-one activity switching variables. The contribution of these variables to total cost, in the form of fixed charges, provides a departure from the usual necessary and sufficient conditions for optimality. In particular, under certain conditions a system of penalties/subsidies emerges which facilitates the allocation of the firm's scarce resources.
Preservation of Ventricular Function by Adrenergic Influences during Metabolic Acidosis in the Cat

Although metabolic acidemia reduces the contractility of cardiac muscle in isolated preparations, it does not do so to the same extent in intact animals or those with a functioning sympathoadrenal system. The present study was designed to determine if the resistance of the heart to acidemia is the consequence of concurrent adrenergic influences on the myocardium. The function of the cat9s left ventricle was examined in a preparation that allowed control of aortic pressure, cardiac output, heart rate and temperature. The arterial blood pH, Po 2 , Pco 2 , and temperature were continuously measured. Acidemia was produced either endogenously by temporarily diminishing perfusion of peripheral tissues, or by infusion of 0.5N lactic acid. Studies were made before and after beta-receptor blockade with propranolol, 0.25 to 0.5 mg/kg iv or im. In eight control animals, reduction of pH from 7.34 to 7.08 failed to diminish contractility. In 14 animals with beta-receptor blockade, reduction of pH to 7.02 reduced contractility by about 25% ( P
Variation and Pearson correlation coefficients of Warner-Bratzler shear force measurements within broiler breast fillets

Measurements of texture properties related to tenderness at different locations within deboned broiler breast fillets have been used to validate techniques for texture analysis and establish correlations between different texture evaluation methods. However, it has been demonstrated that meat texture can vary from location to location within individual muscles. The objective of our study was to investigate the intramuscular variation and Pearson correlation coefficients of Warner-Bratzler (WB) shear force measurements within early deboned broiler breast fillets and the effect of deboning time and cold storage on the variation and correlation coefficients. Broiler breast fillets were removed from carcasses early postmortem (2 h) and later postmortem (24 h). Storage treatments of the 2 h samples included 0 d, 7 d at 3 degrees C, 7 d at -20 degrees C, and 6 d at -20 degrees C plus 1 d at 3 degrees C. The WB shears of cooked fillets were measured using a TA-XTPlus Texture Analyzer and a TA-7 WB shear type blade. Our results showed that although the average WB shear force values differed within the 0-d, 2-h fillets, compared with the variation among the fillets within the treatment, the difference within a fillet is still evidently small. The Pearson correlation coefficients were significant between the locations; however, values of the correlation coefficients depended on the paired locations. Location differences in the WB shear values and the correlation coefficient values between them changed with deboning time and cold storage. These results demonstrate that the variation of WB shear force measurements is substantial within early deboned broiler breast fillets and the Pearson correlation coefficient values of the measurements vary among the locations. Both the variation and the Pearson correlation coefficients can be affected by postmortem aging time and storage. The differences in the means between the locations in early deboned breasts are much smaller than the variation among the fillets.