cssi/SciSciGPT-SciSciNet huggingface dataset:
Late Triassic Texas uplift preceding Jurassic opening of the Gulf of Mexico: Evidence from U-Pb ages of detrital zircons

We use U-Pb ages for 2655 individual detrital zircon grains in 30 samples of Upper Triassic (Carnian‐Norian) sandstones of the southwestern USA (our data) and northern Mexico (other data) to infer regional Late Triassic provenance relations and tectonic features, which included a prerift uplift in Texas precursory to Jurassic opening of the Gulf of Mexico. Detrital zircons in sandstones from central paleorivers of the Chinle-Dockum fl uvial system on the High Plains (USA) and Colorado Plateau, and from the marine terminus of the fl uvial system along the eastern fl ank of the Auld Lang Syne backarc basin in the Great Basin, refl ect regional dispersal of sediment from the Ouachita orogen and adjacent Mesoproterozoic basement exposed on the northern fl ank of the rift uplift. The composite grain population of Ouachita-derived sands displays dominant U-Pb age peaks at 1100‐1050 Ma (Grenvillian) and subordinate Neoproterozoic (630‐550 Ma) and Paleozoic (475‐400 Ma) age peaks inferred to document recycling of sand grains from the Ouachita system. The Ouachita detritus was supplemented by contributions from Mesoproterozoic basement rocks of southwest Laurentia (compound 1805‐1655 Ma and unitary 1440 Ma age peaks) and from Permian‐Triassic arc assemblages of northeastern Mexico (composite 285‐215 Ma age peak). Master Chinle-Dockum paleodrainages extended east-southeast‐west-northwest for 2000 km from Texas to Nevada, fl owing along the axis of a backarc trough formed by dynamic subsidence behind the Cordilleran magmatic arc, from headwaters in the Texas prerift uplift to the sediment trap of the backarc marine basin where the Auld Lang Syne Group accumulated. Sandstones from peripheries of the linked fl uvial and marine depositional systems contain contrasting populations of detrital zircons derived either from the relict Amarillo-Wichita uplift, which fed abundant Cambrian zircons derived from an uplifted aulacogen-fl oor igneous assemblage, to selected basal units of the fl uvial system, or from the Cordilleran arc assemblage to the south and west. The youngest Dockum sample from the Ouachita foreland on the High Plains contains abundant Devonian zircons probably derived from the Ouachita metamorphic core zone now present only in the Texas subsurface. Sandstones along the southern fl ank of the Chinle backarc basin on the southern Colorado Plateau contain populations of detrital zircons similar to those in sandstones of the AntimonioBarranca forearc basin (Sonora) that was farther south beyond the arc axis. Sediment transported longitudinally from the Texas uplift to the El Alamar paleoriver and Potosi subsea fan of northeastern Mexico contains populations of detrital zircons similar but not identical to those in Chinle-Dockum fl uvial strata of the High Plains shed transversely from the rift uplift.
Hydrophobic interaction of fluorescent probes with fetuin, ovine submaxillary mucin, and canine tracheal mucins

The presence of hydrophobic sites in fetuin, ovine submaxillary mucin and two homogeneous canine tracheal mucins was established by fluorescence probe techniques. The interaction between the above-mentioned glycoproteins and two hydrophobic fluorescent compounds, sodium mansate and mansylphenylalanine, was accompanied by an enhancement in fluorescence and a shift of the fluorescence maxima to shorter wavelengths. The introduction of a phenylalanine residue to the mansyl group enhanced the binding affinity of the probe for the hydrophobic sites of these glycoproteins as evidenced by lower values for the dissociation constants. The high molecular weight (581 600) tracheal mucin, which had the highest carbohydrate content (80%) of all the glycoproteins investigated, exhibited the highest fluorescence enhancement and the largest number of binding sites for these fluorescent probes.
Functional morphology and evolution of early Paleozoic dasycladalean algae (Chlorophyta)

Biophysical modeling and morphologic data from the fossil record were used to investigate the functional significance of changes in thallus morphology during the early evolutionary history of dasycladalean algae (dasyclads), a clade of benthic marine macroalgae. Modeling results indicate that the addition of cylindrical appendages (laterals) to an upright main axis, a key morphological innovation in the evolution of dasyclad thallus form, can provide for large gains in light interception efficiency, near-maximum gains in this regard being achieved when the ratio of total lateral surface area to main axis surface area is 4 or greater. Among the 13 early Paleozoic study taxa, all but one was found to exceed this value. Modeling of surface area to volume ratios for early Paleozoic dasyclads indicates that laterals for these forms conveyed only modest gains in this regard and, therefore, likely played little role in improving nutrient uptake. For survivorship, it appears that increasing thallus complexity by developing laterals conveyed important benefits by imparting both compartmentalization and redundancy, thereby increasing the likelihood that lateral-bearing forms would survive attacks by early mesograzers. Trends and patterns in the fossil record support such a survival-enhancing role for laterals and are consistent with the initial evolution of these structures as an early manifestation of an evolutionary arms race between macroalgae and herbivores initiated near the Proterozoic/Phanerozoic boundary.
A conceptual approach to classifying sports fans

Develops a classification or typology of the sports fan. Specifically, contends that five different types of sports fans exist: temporary, local, devoted, fanatical, and dysfunctional. The need exists to identify the different types of fans due to the inadequacies of past theories to explain the totality of fan behavior. The usefulness of the typology is demonstrated by offering specific segmentation strategies for each classification. Finally, directions for future research are presented.
Thermal conductivity and thermally induced charge imbalance in heavy-fermion systems

We study the effects of a magnetic field and a supercurrent flow on the thermal conductivity of nonconventional superconductors with an energy gap vanishing at either points or on a line or lines on the Fermi surface. A study of the thermally induced charge imbalance is also presented. Our calculations are done using a Boltzmann equation approach, and elastic scattering by nonmagnetic impurities is assumed to be the main source of relaxation; the relaxation rate is calculated in the low-temperature limit, assuming the phase shift of the scatterers to be π/2 in the normal state. Our calculations indicate that the effects we predict are large enough to be experimentally observable.
A Photonic Crystal Hollow-Core Cavity for On-Chip Molecule Sensing

We design a hollow-core cavity in a three-layer photonic crystal with Q=1.7e5. The high air-energy ratio α_air≈67% of the cavity mode allows detection of small refractive index changes ~δn=3.4e5 induced by external substances.
Spatial mutation of the T cell immunological synapse

The hardware for intracellular signaling networks consists of cascades of chemical reactions. It is becoming increasingly apparent that the large-scale spatial organization of molecules in these networks can lead to differential outcomes from otherwise chemically equivalent systems. This has amplified interest in controlled spatial organization as a regulator of cellular signal transduction. In response, a new category of experimentation is developing, in which the spatial positions of signaling molecules in living cells are directly manipulated through mechanical means. These methodologies complement conventional genetic and pharmacological approaches, both of which are chemical in nature, by perturbing the system through exclusively physical mechanisms.
Pegylation: engineering improved pharmaceuticals for enhanced therapy.

Conjugating biomolecules with polyethylene glycol (PEG), a process known as pegylation, is now an established method for increasing the circulating half-life of protein and liposomal pharmaceuticals. Polyethylene glycols are nontoxic water-soluble polymers that, owing to their large hydrodynamic volume, create a shield around the pegylated drug, thus protecting it from renal clearance, enzymatic degradation, and recognition by cells of the immune system. Agent-specific pegylation methods have been used in recent years to produce pegylated drugs that have biologic activity that is the same as, orgreaterthan, that of the parent drug. These agents have distinct in vivo pharmacokinetic and pharmacodynamic properties, as exemplified by the self-regulated clearance of pegfilgrastim, the prolonged absorption half-life of pegylated interferon alpha-2a, and the altered tolerability profile of pegylated liposomal doxorubicin. Pegylated agents have dosing schedules that are more convenient and more acceptable to patients, and this can have a beneficial effect on the quality of life of patients with cancer.
Acoustooptical matrix-vector product processor: implementation issues

An acoustooptic technique was used to design and construct a prototype of a processor capable of multiplying a 128 x 128 complex-element matrix by a 128 complex-element vector. The device was specified to execute 10(5) matrix-vector products per second with 8-bit resolution. The performance of each component of the prototype was evaluated, as was the impact of component performance on system performance.
Modeling Extrinsic Apoptosis Regulatory Network Pathways Using A Rules-based Framework

We describe a systems approach to combine mathematical modeling and experimental measurement in the study of apoptosis in mammalian cells. The apoptotic signal is an important all-or-nothing mechanism which must be tightly regulated in the cell. Our focus will be on the role of pro and anti-apoptotic proteins in the extrinsic apoptosis signaling pathway leading to the formation of pores at the mitochondrial membrane by BAK and BAX proteins. This network is a prototypical cue-signal-response-feedback pathway of high biomedical importance. Construction of mathematical signal transduction models that recapitulate key features of signaling pathways as they exist in cells is currently very difficult, in large part because few tools are available to assemble, validate and update large dynamical models. We aim to implement novel methodologies based on “rules-based” techniques to allow for a flexible treatment of this complex network model. The calibration of such a model and application to ongoing experimental work in our laboratory is an important aspect of this work. We report our ongoing work on this subject paying particular attention to the rules-based building framework, the calibration steps and the use of experimental data for model calibration and validation.
Fault detection and isolation using parity relations

Abstract The design of dynamic parity (consistency) relations, for the detection and isolation of faults, is described. Both additive and multiplicative (parametric) faults are considered. Various isolation schemes are discussed and decoupling from disturbances and certain model errors is included. Links to diagnostic observers and parameter estimation are pointed out.
Does substantive democratization create more committed democrats? Surprising evidence from Africa

A growing body of evidence holds that citizens support democracy when they believe the regime has provided individual freedoms and political rights. Put simply, citizens develop legitimacy attitudes by learning about democracy. These findings, however, are based on citizens' evaluations of the procedural elements of democracy. Democratization also entails substantive reforms that likely impact legitimacy attitudes. This article provides the first test of how the success – and failure – of substantive democratization shapes legitimacy attitudes. Using data from the second round of Afrobarometer surveys, I find surprising results. Citizens who judge the regime to be more successful in substantive democratization are actually less likely to be committed democrats. I conclude with possible explanations of these surprising findings and reflect on the challenges for both future research and for the new democracies facing this situation.
Demonstration of npn InAs bipolar transistors with inverted base doping

We demonstrate np/sup +/n InAs bipolar transistors that operate under room temperature and cryogenic conditions. InAs transistors on an InP substrate were characterized as a function of temperature and exhibited good room temperature and low temperature common-emitter characteristics. Although the base doping density exceeded the emitter doping density by a factor of 20, current gains of 30 were achieved at room temperature. Junction leakage currents and contact resistance were identified as problems to address.
Predictive current mode control of single phase dual active bridge DC to DC converter

In this digest a review of various current control strategies in a bidirectional isolated DC to DC converter is shown. Average current control, peak current control and predictive current control is proposed for the single phase topology. A comparison between the controllers is shown with simulation results and experimental verification.
DUAL-LEVEL DIRECT DYNAMICS CALCULATIONS OF THE REACTION RATES FOR A JAHN-TELLER REACTION : HYDROGEN ABSTRACTION FROM CH4 OR CD4 BY O(3P)

We report calculations of the reaction rates of O(3P) + CH4 → OH + CH3 and O(3P) + CD4 → OD + CD3 over the temperature range 300−2500 K. The calculations are based on variational transition state t...
Visual Evoked Potentials in Occipital Lobe Lesions

• Recording of visual evoked potentials (VEPs) to pattern reversal is considered to be a reliable diagnostic procedure for examining patients with anterior visual pathway lesions (optic nerves and chiasm). Less consistent results have been reported in studies of more posterior lesions. The VEPs were recorded in 20 patients with occipital lobe lesions. A maximal VEP response (P 94 ) was recorded at the scalp electrodes situated over the involved occipital lobes and contralateral to the hemianoptic visual field defect, indicating a positive correlation of unilateral occipital lobe lesions, homonymous visual field loss, and the VEP abnormality.
Physiological basis for mechanical time-variance in the heart: special consideration of non-linear function.

A relationship between ventricular pressure and volume is developed starting from basic cardiac muscle mechanics. The known and measurable properties of myocardium, such as the Hill law, the periodic excitation-contraction mechanism, and non-linear elasticity of the surrounding elastin and collagen structure, are formulated into a myofibril unit. A cylindrical geometry is chosen to represent the structure of the ventricle, using the myofibril unit as the basic building block. Pressure-volume isochrones computed from this model illustrate non-linear function in the heart which arises from both geometric effects and muscle effects. The above theory and model is linearized to provide a special study case. The behavior that resulted is that of a time-varying elastance, E ( t ), and, hence, can help in the interpretation of its meaning. It is found that the minimum in E ( t ) is the consequence of the stiffness of the myocardial fibrous network, adjusted by a geometric factor. In addition, the magnitude of E ( t ) is governed by myocardial contractility, a geometric factor, and the excitation-contraction mechanism, where time-dependency is imparted by periodic excitation. Since the elastic fibers are the only true elastic elements, the quantity of elastance is determined by controlled volume feedback. A circuit model is provided to illustrate this concept. The non-linear active and passive heart function curves are specified independently. These curves are required to intersect below the resting volume and result in a negative pressure at the intersection. This is found to explain the phenomenon of ventricular suction. In addition, they lead to a time-varying dead volume by virtue of time-dependent isochronal slope. Non-linear function is introduced to the model and is found to explain the variation in curvature of the ventricular isochrones.
Comparison of KRAS mutation analysis and FISH for detecting pancreatobiliary tract cancer in cytology specimens collected during endoscopic retrograde cholangiopancreatography

Pancreatobiliary tract strictures result either from malignancies of the biliary tract and pancreas or from nonmalignant etiopathogenesis. The goal of this study was to determine whether KRAS mutations could be identified in residual pancreatobiliary stricture brushings and to compare the performance characteristics of KRAS mutation analysis to cytology and fluorescence in situ hybridization (FISH) for the detection of carcinoma. Residual brushing cytology cell pellets were retrieved from 132 patients with subsequent clinicopathologic follow-up of cholangiocarcinoma (n = 41), pancreatic adenocarcinoma (n = 35), gallbladder cancer (n = 2), and nonmalignant strictures (n = 54). All specimens had a prior cytology and FISH UroVysion results as part of clinical practice. KRAS mutation analysis was performed using the quantitative PCR DxS KRAS Mutation Test Kit. KRAS mutation analysis was successful in 130 of 132 specimens. KRAS mutations and polysomic (ie, positive) FISH results were identified in 24 (69%) and 22 (63%) pancreatic adenocarcinoma specimens, respectively, with a combined sensitivity of 86% (30/35). KRAS mutations and polysomic FISH results were identified in 12 (29%) and 17 (41%) cholangiocarcinoma specimens, with a combined sensitivity of 54% (22/41). KRAS mutations were identified in two patients with primary sclerosing cholangitis, and benign follow-up. Residual cytology specimens can be used to detect KRAS mutations by quantitative PCR. Combined KRAS mutation and FISH analysis appear to increase the cancer detection rate in patients with pancreatobiliary strictures.
Allografts and xenografts of oviduct to the cheek pouch of the Syrian hamster.

ATTEMPTS1–3 to transplant oviduct tissue have been relatively unsuccessful with one notable exception4. Successful transplantation of rabbit oviduct segments to the hamster cheek pouch has, however, been reported5. Further experiments have been conducted to refine the technique. Since this investigation, we have also used the cheek pouch successfully for transplantation and physiological studies of the uterus6,7 and anterior pituitaries8. The transplantation terminology used here is that proposed by Snell9.
Sensitization following Hymenoptera whole body extract therapy

Treatment of an insect-sensitive patient with Hymenoptera whole body extracts (WBE) led, on five occasions, to a serum sickness--like syndrome which did not recur after therapy was stopped. The patient was found to be sensitive by skin test, histamine release, and radioallergosorbent test (RAST) to both venom and WBE as well as to venomless bee body preparations. Subsequent therapy with honeybee and yellow jacket venoms was without sequelae, and after treatment the patient did not react to a sting. In order to assess the frequency of sensitivity to irrelevant body proteins in patients treated with WBE we carried out WBE RASTs on sera from 15 such patients and compared them with those from 15 nontreated insect-allergic patients who had similar venom-specific IgE antibody levels. None of the patients allergic to insects who had not been treated with WBE had detectable IgE anti-WBE antibodies, while about 50% of those treated with WBE had developed IgE antibodies against these proteins. It appears that sensitization to nonvenom WBE proteins in terms of the development of IgE antibody is a common result of this therapy, and, rarely, repeated challenge with this complex antigenic mixture can also lead to clinical illness.
Removal Of Mask Registration Errors Using Full-Field Mask Aligners

One of the key components of a full-field 150-mm exposure system is a properly specified and fabricated mask. The Micralign Model 661 HT uses a 71/4-inch diameter mask substrate with a 150-mm patterned field. While low distortion, electron beam generated full-field masks for 150-mm wafers will become more common in the future, it is expected that many of those masks fabricated in the near term will be optically stepped. Present 71/4-inch fabrication techniques can meet the critical dimension and defect density requirements consistent with the specified lithographic capabilities of the Micralign system. Pattern registration is the primary requirement affecting the specification of optically stepped masks. Die placement results in a random error, a systematic error (runout), and an orthogonality error. This distortion is commonly measured for each mask, and the relative magnitude is part of the specification. The burden on optically stepped masks can be minimized by relaxing this registration specification based on the Micralign's ability to correct for isotropic and anisotropic runout, as well as for orthogonality errors. A description of mask registration errors, how they are measured and subsequently compensated for by the offset and magnification capabilities of the Micralign exposure system, and the experiment designed to quantify those capabilities, is presented. Design characteristics of the Micralign subsystems providing error compensation are outlined. Experimental techniques and results demonstrating the correction of actual mask registration errors are described and data presented.
Effect of heparin on the detection of human isoantigens by the cytotoxicity technique.

IT has been suggested that the anticoagulant heparin might block antigenic sites or otherwise interfere with the expression of antigen–antibody interaction1–6. Of particular relevance is the effect of heparin on transplantation behaviour and cytotoxicity reactions in mice7,8, and on human mixed lymphocyte cultures9. We have studied the possible influence of heparin on human isoantigen typing by the cytotoxicity technique.
Optical design for testing and aligning lightweight grazing incidence x-ray mirrors

Test and alignment of light weight X-ray optics have been a challenge for two reasons: (1) that the intrinsic mirror quality and distortions caused by handling can not be easily separated, and (2) the diffraction limits of the visible light become a severe problem at the order of one arc- minute. Traditional methods of using a normal incident pencil or small parallel beam which monitors a tiny fraction of the mirror in question at a given time can not adequately monitor those distortions. We are developing a normal incidence setup that monitors a large fraction, if not the whole, of the mirror at any given time. It allow us to test and align thin X-ray mirrors to an accuracy of a few arc seconds or to a limit dominated by the mirror intrinsic quality.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Genetic relatedness and spatial associations of dusky-footed woodrats (Neotoma fuscipes)

We studied the association between space sharing and kinship in a solitary rodent, the dusky-footed woodrat (Neotoma fuscipes). Genetic relatedness was inversely correlated with geographic distance for female woodrats but not for males, a pattern consistent with female philopatry and male dispersal. However, some female neighbors were unrelated, suggesting the possibility of female dispersal. Relatedness of female dyads was positively correlated with overlap of their home ranges and core areas, indicating that females were more likely to share space with relatives, whereas males showed no correlation between relatedness and the sharing of either home ranges or core areas. However, some females that shared space were not close relatives, and some closely related males shared space. House sharing was exhibited both by close relatives and by distantly related or unrelated woodrats, and was not correlated with relatedness. The kin structuring we describe likely resulted from a pattern of female philopatry and male dispersal, but also may have resulted from kin-directed behaviors by females.
FTO genotype is associated with exercise training-induced changes in body composition

The fat mass (FM) and obesity-associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known whether regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test whether the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO single-nucleotide polymorphism (SNP) rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (P = 0.004) but not in women (P = 0.331; gene-by-sex interaction P = 0.0053). The FTO genotype was associated with body fat responses to regular exercise (P < 0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C allele showed three times greater FM and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.
Lithium binding in fluorinated phosphazene trimers

Abstract Density functional theory is used to model a series of cyclic phosphazenes, with and without coordinated Li + . Two pendant groups are used, ethoxy and 2,2,2-trifluoroethoxy, in varying combinations to generate phosphazenes with 0, 1, 2, 3, or 6 trifluoro groups. In all cases, Li + sits in a pocket on the ring, always bonding to a ring nitrogen, and can be three- or four-coordinate, depending on the local environment. Three-coordinate occurs when no fluorines are close enough to interact, with the lithium bonding to a ring nitrogen and the two adjacent oxygens. When Li + is four-coordinate, the bonding varies between the ring nitrogen, two adjacent oxygens, and one fluorine, or the ring nitrogen, one adjacent oxygen, and two fluorines. All of the possible symmetry unique structures have been calculated. The binding strength of Li + steadily decreases, from 74.93 kcal/mol with no trifluoro groups, to 58.01 kcal/mol when 6 trifluoro groups are present. The decrease is attributed to the electron withdrawing effect of the trifluoro groups, and also to distortions in the geometry to accommodate Li–F interactions.
Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions

AbstractBackground: Patients presenting with acetaminophen toxicity and vomiting are often treated with antiemetics so that orally administered N-acetylcysteine can be retained. The policy at the West Virginia Poison Center is to reserve ondansetron, an antiemetic with a higher cost than other antiemetics, as a second line agent for patients presenting within 8 hours of an acetaminophen ingestion. Methods: A retrospective study of cases between January 1993 and December 1995, in which the primary or secondary drug ingested was an adult-strength, acetaminophen-only formulation and the ingestion resulted in vomiting. Seventy-eight patients with laboratory-verified acetamin-ophen toxicity and vomiting were evaluated for the type of antiemetics used and the antiemetic's effectiveness. Results: Of the 78 acetaminophen toxic patients with vomiting, 17/51 patients (33.3%) who received a nonondansetron antiemetic failed therapy and required IV ondansetron. Of the 24 patients who received ondansetron, 4 patients (...
The adsorptive characteristics of proteins for polystyrene and their significance in solid-phase immunoassays

Abstract The adsorptive characteristics of polystyrene tubes for seven proteins of different molecular weight and ionic charge have been studied. The stability of these adsorbed proteins was monitored throughout the various steps of the amplified-enzyme-linked immunosorbent assay (a-ELISA). Using 125I-labeled proteins, it was observed that each had a characteristic adsorptive behavior not explainable by simple charge differences. The proportion of protein bound to a 6.5-cm2 tube surface was independent of the amount added up to an input of about 100 ng. Binding increased proportionately with temperature and incubation time. Beyond the range of concentrations where the proportion bound was independent of input, i.e., the region of independence, the kinetics of adsorption changed. The amount of protein adsorbed at the upper limit of the region of independence was inversely proportional to molecular weight for all except α-lactalbumin. Quantitative measurement of bound protein using the a-ELISA suggests that beyond the region of independence, protein-to-protein rather than protein-to-polystyrene adsorption occurred. This was suggested by computation using the Stokes radii of the proteins which implied that the amount of protein bound at the upper limit of the region of independence was a layer of protein one molecule thick. The upper limit of the region of independence determines, therefore, the maximun amount of functional antigen for such assays. Once adsorbed, proteins remained stably bound throughout the assay steps. The presence of competing proteins had no effect on the adsorptive characteristics of a given protein provided that the total protein concentration of the mixture was within the range of independence. The results indicate that the adsorptive characteristics of proteins for polystyrene tubes routinely used in solid-phase immunoassays should be taken into consideration when designing and interpreting data obtained with such assays.
ELECTRON MICROSCOPIC STUDIES ON THE RED PULP OF THE RABBIT SPLEEN.

Electron microscopic studies reveal that the red pulp of the rabbit spleen is composed of reticular cells, reticulum and elements of the blood circulating through it. The three types of reticular cells described follow no definite pattern as to types of spaces they line and are not always adjacent to a basement membrane. Similar or dissimilar cells may line a basement membrane on the same or opposing sides. The entire red pulp area is intercommunicating through pores and junctions of the several spaces and in that area in which no basement membrane exists, the cytoplasmic projections of the reticular cells form a meshwork of spaces. Terminal arterioles are seen to end in collapsed type channels with a change from endothelium to Type I reticular cells. These rapidly join dilated areas. The reticular network of the spleen appears as four types: homogeneous, fibrillar, a combination of these, and reticular cells only. Isolated cilia are found in the reticular cell cytoplasm and are shown to be associated with a basal body and a centriole. The investigation supported the hypothesis that the red pulp of the spleen in the adult rabbit is a functionally dynamic area constantly changing its histological structure, both regarding cells and state of the vascular channels.
Lipid unsaturation influences melittin-induced leakage of vesicles.

Abstract Investigation of vesicles composed of different phosphatidylcholines revealed that the extent of leakage of internal contents induced by the lytic agent melittin can range from practically none to essentially complete, depending upon the fatty acyl chain composition of the phospholipid. The extent of leakage increases with the number of double bonds in the series dioleoylphosphatidylcholine
Verapamil inhibits influenza A virus replication

Calcium channel blockers reduce Ca++ flux through membrane channels and may inhibit intracellular Ca++-dependent synthetic and regulatory activities by binding to calmodulin. We have found that Verapamil, a calcium channel blocker, inhibits influenza virus replication in Madin-Darby canine kidney cells and in murine pulmonary macrophages and that this antiviral effect occurs with drug addition late in the replication cycle. Chlorpromazine, a drug which binds to calmodulin, also inhibited influenza virus replication in these tissue culture systems. We suggest that Verapamil and chlorpromazine inhibit influenza virus replication by interfering with calmodulin-dependent intracellular activities necessary for late synthetic steps or virus assembly steps and that calcium channel blockers provide a new probe for investigating influenza virus replication.
A method to quantify spontaneous and in vivo induced thioguanine-resistant mouse lymphocytes.

A clonogenic assay to quantify thioguanine (TG)-resistant (TGr) spleen lymphocytes in the mouse has been developed to support studies of in vivo mutation affecting the hypoxanthine phosphoribosyltransferase (hprt) locus. Lymphocytes are cultured in 96-well microtiter plates for 9 days with proliferation initiated by the mitogen concanavalin A and supported thereafter by conditioned medium containing interleukin-2. Lymphocytes are plated at high densities (4–8 × 105/well) with TG and irradiated L5178Y lymphoma cells (104/well) to detect the presence of TGr cells. To determine the cloning efficiency without TG lymphocytes are plated at a low density (10/well) with irradiated L5178Y cells and irradiated lymphocytes (4–8 × 105/well). Proliferation of cells is detected by [3H]thymidine incorporation and scintillation spectrometry. Spontaneous frequencies of TGr clones are independent of TG dose from 0.2 to 10 μg/ml and independent of cell density over the range cited. The TGr clones tested have < 10% hypoxanthine incorporation in vivo relative to unselected clones and have stable phenotypes i n the absence of selection. The spontaneous frequency of TGr cells ranged from 1 to 3 × 10−6. In vivo treatment of mice intraperitoneally with ethylnitrosourea 15 days prior to in vitro culture resulted in a linear dose-related increase of TGr cells, with 70.2 mg/kg inducing a frequency of TGr cells of 2 × 10−5.
Evidence for local production of acute phase response apolipoprotein serum amyloid A in Alzheimer's disease brain

Acute phase serum amyloid A (A-apoSAA), but not constitutive apoSAA (C-apoSAA), was identified by Western blotting experiments in brain protein extracts from eight of nine patients with Alzheimer's disease (AD), one with a brain tumor and one with multiple sclerosis. A-apoSAA was not detected in six subjects with Pick's or Lewy Body disease or three other non-AD brain specimens. Apolipoprotein A-I and albumin were not found in any of the brain protein extracts. A-apoSAA mRNA was detected in AD brain by reverse transcription-polymerase chain reaction (RT-PCR). These data suggest that apoSAA is locally produced in AD brain and that investigation of the neuroinflammatory effects of this injury specific apolipoprotein is warranted.
Economic Theory and Government Technology Policy

Recent federal proposals and program experiments aimed at improving the innovative performance of American industry have been based on an inappropriate analytic framework. The neoclassical microeconomic analysis upon which these proposals are based emphasizes the undersupply of R & D. However, a more crucial problem in this context is the utilization of complex research results by firms and industries with low levels of in-house research expertise. This problem is a central concern of an alternative approach to the analysis of innovation, termed the information processing framework. This analytic approach, which receives empirical support from an examination of previous cooperative research programs in the United States and Great Britain and an analysis of independent consulting firms' operations, suggests that cooperative or extramural research does not function effectively as a substitute for in-house research. Public policies to encourage innovation should be attentive to the distribution, as well as the supply, of R & D.
Very long chain fatty acid β-oxidation by subcellular fractions of normal and Zellweger syndrome skin fibroblasts

Abstract Very long chain fatty acid (VLCFA) β-oxidation was compared in homogenates and subcellular fractions of cultured skin fibroblasts from normal individuals and from Zellweger patients who show greatly reduced numbers of peroxisomes in their tissues. β-Oxidation of lignoceric (C24:0) acid was greatly reduced compared to controls in the homogenates and the subcellular fractions of Zellweger fibroblasts. The specific activity of C24:0 acid β-oxidation was highest in the crude peroxisomal pellets of control fibroblasts. Fractionation of the crude mitochondrial and the crude peroxisomal pellets on Percoll density gradients revealed that the C24:0 acid oxidation was carried out entirely by peroxisomes, and the peroxisomal β-oxidation activity was missing in Zellweger fibroblasts. In contrast to the β-oxidation of C24:0 acid, the β-oxidation of C24:0 CoA was observed in both mitochondria and peroxisomes. We postulate that a very long chain fatty acyl CoA (VLCFA CoA) synthetase, which is different from long chain fatty acyl CoA synthetase, is required for the effective conversion of C24:0 acid to C24:0 CoA. The VLCFA CoA synthetase appears to be absent from the mitochondrial membrane but present in the peroxisomal membrane.
Studies on the inhibition of neutral proteases by 1,10-phenanthroline.

Abstract 1. 1. The inhibition of the thermolysin and Bacillus subtilis neutral protease catalyzed hydrolysis of 3-(2-furylacryloyl)glycyl- l -leucine amide (FaGlyLeuNH2) by 1,10-phenanthroline has been studied. 2. 2. The mechanism of inhibition appears to involve the removal of zinc from the enzyme to yield inactive apoenzyme. 3. 3. Kinetic analysis of the inhibition curves yielded estimates of the enzyme-metal dissociation constants. 4. 4. Chelator-equilibrated gel filtration columns have proved useful for rapid preparation of apoenzyme.
Solution Dynamics of Thallium−Metal Carbonyl Compounds Using 205Tl NMR Spectroscopy

A 205Tl NMR study to probe the solution structure and dynamics of a series of thallium-containing metal complexes has been conducted. The following compounds were examined: Tl{Co(CO)4}3 (Ia), [BnMe3N]3[Tl{Fe(CO)4}3] ([BnMe3N]3[Ib]), Tl{M(CO)3Cp}3 (Ic, M = Cr; Id, M = Mo; Ie, M = W), TlFp3 (If; Fp = CpFe(CO)2), [PPN]2[Tl2Fe6(CO)24] ([PPN]2[II]), [Et4N]2[Tl2Fe4(CO)16] ([Et4N]2[III]), [Et4N][L2Tl{Fe(CO)4}2] ([Et4N][IV]: [IVa]-, L2 = bipy; [IVb]-, L2 = en; [IVc]-, L2 = phen; [IVd]-, L2 = tmeda; [IVe]-, L2 = dien), [Et4N]4[Tl4Fe8(CO)30] ([Et4N]4[V]), and TlCo(CO)4 (VI). The 205Tl NMR technique was used to probe the dynamic behavior of the Tl−metal cluster complexes [II]2-, [III]2-, and [V]4- in solution and the formation of Lewis base adducts of [III]-, as well as the possibility of formation of carbonylate anion adducts of Ia, Ic, Id, and If. [IVb]- reacted with acetone and formed, after fortuitous oxidation, [{(CO)4FeL2‘Tl}2Fe(CO)4] (L2‘ = Me2CNCH2CH2NCMe2) (VII). The initially formed complex [L2‘Tl{Fe(CO)...
Aging rat neuromuscular junnctions: A morphometric study of cholinesterase-stained whole mounts and ultrastructure

Previous morphological studies of the adult rat soleus neuromuscular junction (NMJ) indicate that its ultrastructure changes with age, a consequence of a dynamic, ongoing remodeling of pre- and postsynaptic elements. With aging, the balance between axonal sprouting and withdrawal appears to shift in favor of denervation. Here we have examined the extent and direction of the remodeling process during the adult life of the rat (5–111 weeks) by quantificatation and morphometry of NMJ structure as seen in electron microscopic composites and in cholinesterase (ChE) stained whole mounts. We have found that the net effect of axonal sprouting and withdrawal on the entire NMJ region varies with age: at 5–12 weeks there is rapid growth and maturation; at 12–48 weeks slower growth occurs, and at 48–82 weeks there is a gradual shift in direction to result in progressive loss of synaptic contact in individual NMJs; finally, at 82–111 weeks, there is loss of entire NMJs with some continued reinnervation at others. The diaphragm NMJ also exhibits continuous structural remodeling; however, between 82–111 weeks many changes in the ChE staining pattern appear abruptly.
Synthesis, crystal structures and chemical bonding of RE(5-x)Li(x)Ge4 (RE = Nd, Sm and Gd; x ≃ 1) with the orthorhombic Gd5Si4 type.

The syntheses and single-crystal and electronic structures of three new ternary lithium rare earth germanides, RE5−xLixGe4 (RE = Nd, Sm and Gd; x ≃ 1), namely tetra­samarium lithium tetra­germanide (Sm3.97Li1.03Ge4), tetra­neodymium lithium tetra­germanide (Nd3.97Li1.03Ge4) and tetra­gadolinium lithium tetra­germanide (Gd3.96Li1.03Ge4), are reported. All three compounds crystallize in the ortho­rhom­bic space group Pnma and adopt the Gd5Si4 structure type (Pearson code oP36). There are six atoms in the asymmetric unit: Li1 in Wyckoff site 4c, RE1 in 8d, RE2 in 8d, Ge1 in 8d, Ge2 in 4c and Ge3 in 4c. One of the RE sites, i.e. RE2, is statistically occupied by RE and Li atoms, accounting for the small deviation from ideal RE4LiGe4 stoichiometry.
Characterization of GABAergic Neurons in the Mouse Lateral Septum: A Double Fluorescence In Situ Hybridization and Immunohistochemical Study Using Tyramide Signal Amplification

Gamma-aminobutyric acid (GABA) neurotransmission in the lateral septum (LS) is implicated in modulating various behavioral processes, including emotional reactivity and maternal behavior. However, identifying the phenotype of GABAergic neurons in the CNS has been hampered by the longstanding inability to reliably detect somal immunoreactivity for GABA or glutamic acid decarboxylase (GAD), the enzyme that produces GABA. In this study, we designed unique probes for both GAD65 (GAD2) and GAD67 (GAD1), and used fluorescence in Situ hybridization (FISH) with tyramide signal amplification (TSA) to achieve unequivocal detection of cell bodies of GABAergic neurons by GAD mRNAs. We quantitatively characterized the expression and chemical phenotype of GABAergic neurons across each subdivision of LS and in cingulate cortex (Cg) and medial preoptic area (MPOA) in female mice. Across LS, almost all GAD65 mRNA-expressing neurons were found to contain GAD67 mRNA (approximately 95-98%), while a small proportion of GAD67 mRNA-containing neurons did not express GAD65 mRNA (5-14%). Using the neuronal marker NeuN, almost every neuron in LS (> 90%) was also found to be GABA-positive. Interneuron markers using calcium-binding proteins showed that LS GABAergic neurons displayed immunoreactivity for calbindin (CB) or calretinin (CR), but not parvalbumin (PV); almost all CB- or CR-immunoreactive neurons (98-100%) were GABAergic. The proportion of GABAergic neurons immunoreactive for CB or CR varied depending on the subdivisions examined, with the highest percentage of colocalization in the caudal intermediate LS (LSI) (approximately 58% for CB and 35% for CR). These findings suggest that the vast majority of GABAergic neurons within the LS have the potential for synthesizing GABA via the dual enzyme systems GAD65 and GAD67, and each subtype of GABAergic neurons identified by distinct calcium-binding proteins may exert unique roles in the physiological function and neuronal circuitry of the LS.
SOCIAL SCIENCE RESEARCH AND SOCIAL POLICY: BRIDGING THE GAP

Clinical examples of misapplications of social science research are reviewed with an emphasis on what can be learned with regard to dealing with and preventing such misuse of this type of knowledge. The differences in language and culture that characterize scientific research as separate from advocacy and social policy are also examined, with recommendations for improved cross-cultural communication.
Electrophysiological indices of orienting attention toward pain

This study examined the effects of orienting on two pain-related components of the sural nerve-evoked somatosensory evoked potential: the NDP (80-230 ms), which is generated in part by the anterior cingulate cortex (ACCc), and SP6 (280-340 ms). NDP and SP6 amplitudes were larger when subjects oriented their attention away from an invalidly cued location and toward the sural nerve pain than when their attention remained focused on the pain. These results and our earlier studies suggest that the ACCc activity generating the NDP is involved in detecting transient painful stimuli. This activity is enhanced when the pain occurs outside the focus of attention, and it may signal other brain areas that attention should be oriented away from its current focus and toward the pain. SP6 appears to be a pain-evoked P3a event-related potential, with an anterior component involved in orienting attention away from some other task and toward the pain, and an posterior component involved in evaluating the pain.
The molecular basis of susceptibility to rheumatoid arthritis: the conformational equivalence hypothesis.

This is an interpretive review of recent immunologic and molecular biologic data concerning the molecular basis of susceptibility to rheumatoid arthritis. The central point of view was taken that the :major histocompatibility complex (MHC) class II molecules encoding disease susceptibility function in an immune recognition event involving an antigen “X” that currently eludes characterization. The problem of understanding the meaning of the association of susceptibility with diverse MHC alleles such as DR4 (Dw4 and Dw14), DR1, and DRw10 is approached by detailed biochemical analysis that led to the identification of common stretches of amino acid sequence, presumably encoding conformationally equivalent structures. Non-classic MHC polymorphisms related to disease susceptibility but not associated with particular alleles such as identified by Ab109d6 proved especially valuable in suggesting new directions for attempting to understand the significance of these associations. Consideration is given to the possibility that a family of either slightly different or identical conformations encoded in eithercis ortrans cumulatively confer the liability to develop rheumatoid arthritis, and implying a highly non-classic mode of inheritance. The, available data do not permit a distinction between the possibilities that an antigen “X” was being presented to T cells or whether the distinctive conformations of the MHC class 11 molecule serve the same role as antigen “X” but are directly recognized by T cells. However, with additional data, some limited insight should be able to be inferred about the nature of an antigen “X” that specifically binds to the MHC conformation with a complementary interaction. It seems reasonable to consider the pathogenesis of rheumatoid arthritis as a typical immune response resulting from a simple immune recognition event of a single antigenic: molecule.
Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors☆

Fibroblast growth factor (FGF)-2 regulates chondrocyte proliferation in the growth plate. Heparan sulfate (HS) proteoglycans bind FGF-2. Perlecan, a heparan sulfate proteoglycan (HSPG) in the developing growth plate, however, contains both HS and chondroitin sulfate (CS) chains. The binding of FGF-2 to perlecan isolated from the growth plate was evaluated using cationic filtration (CAF) and immunoprecipitation (IP) assays. FGF-2 bound to perlecan in both the CAF and IP assays primarily via the HS chains on perlecan. A maximum of 123 molecules of FGF-2 was calculated to bind per molecule of perlecan. When digested with chondroitinase ABC to remove its CS chains, perlecan augmented binding of FGF-2 to the FGFR-1 and FGFR-3 receptors and also increased FGF-2 stimulation of [ 3 H]-thymidine incorporation in BaF3 cells expressing these FGF receptors. These data show that growth plate perlecan binds to FGF-2 by its HS chains but can only deliver FGF-2 to FGF receptors when its CS chains are removed.