Showing papers by "University of Rochester published in 1992"

Fiber-Optic Communication Systems

Abstract: Preface. 1 Introduction. 1.1 Historical Perspective. 1.2 Basic Concepts. 1.3 Optical Communication Systems. 1.4 Lightwave System Components. Problems. References. 2 Optical Fibers. 2.1 Geometrical-Optics Description. 2.2 Wave Propagation. 2.3 Dispersion in Single-Mode Fibers. 2.4 Dispersion-Induced Limitations. 2.5 Fiber Losses. 2.6 Nonlinear Optical Effects. 2.7 Fiber Design and Fabrication. Problems. References. 3 Optical Transmitters. 3.1 Semiconductor Laser Physics. 3.2 Single-Mode Semiconductor Lasers. 3.3 Laser Characteristics. 3.4 Optical Signal Generation. 3.5 Light-Emitting Diodes. 3.6 Transmitter Design. Problems. References. 4 Optical Receivers. 4.1 Basic Concepts. 4.2 Common Photodetectors. 4.3 Receiver Design. 4.4 Receiver Noise. 4.5 Coherent Detection. 4.6 Receiver Sensitivity. 4.7 Sensitivity Degradation. 4.8 Receiver Performance. Problems. References. 5 Lightwave Systems. 5.1 System Architectures. 5.2 Design Guidelines. 5.3 Long-Haul Systems. 5.4 Sources of Power Penalty. 5.5 Forward Error Correction. 5.6 Computer-Aided Design. Problems. References. 6 Multichannel Systems. 6.1 WDM Lightwave Systems. 6.2 WDM Components. 6.3 System Performance Issues. 6.4 Time-Division Multiplexing. 6.5 Subcarrier Multiplexing. 6.6 Code-Division Multiplexing. Problems. References. 7 Loss Management. 7.1 Compensation of Fiber Losses. 7.2 Erbium-Doped Fiber Amplifiers. 7.3 Raman Amplifiers. 7.4 Optical Signal-To-Noise Ratio. 7.5 Electrical Signal-To-Noise Ratio. 7.6 Receiver Sensitivity and Q Factor. 7.7 Role of Dispersive and Nonlinear Effects. 7.8 Periodically Amplified Lightwave Systems. Problems. References. 8 Dispersion Management. 8.1 Dispersion Problem and Its Solution. 8.2 Dispersion-Compensating Fibers. 8.3 Fiber Bragg Gratings. 8.4 Dispersion-Equalizing Filters. 8.5 Optical Phase Conjugation. 8.6 Channels at High Bit Rates. 8.7 Electronic Dispersion Compensation. Problems. References. 9 Control of Nonlinear Effects. 9.1 Impact of Fiber Nonlinearity. 9.2 Solitons in Optical Fibers. 9.3 Dispersion-Managed Solitons. 9.4 Pseudo-linear Lightwave Systems. 9.5 Control of Intrachannel Nonlinear Effects. Problems. References. 10 Advanced Lightwave Systems. 10.1 Advanced Modulation Formats. 10.2 Demodulation Schemes. 10.3 Shot Noise and Bit-Error Rate. 10.4 Sensitivity Degradation Mechanisms. 10.5 Impact of Nonlinear Effects. 10.6 Recent Progress. 10.7 Ultimate Channel Capacity. Problems. References. 11 Optical Signal Processing. 11.1 Nonlinear Techniques and Devices. 11.2 All-Optical Flip-Flops. 11.3 Wavelength Converters. 11.4 Ultrafast Optical Switching. 11.5 Optical Regenerators. Problems. References. A System of Units. B Acronyms. C General Formula for Pulse Broadening. D Software Package.

The need for a new medical model: A challenge for biomedicine.

Abstract: The dominant model of disease today is biomedical, and it leaves no room within tis framework for the social, psychological, and behavioral dimensions of illness. A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.

On the Estimation of Beta-Pricing Models

Abstract: An integrated econometric view of maximum likelihood methods and more traditional two-pass approaches to estimating beta-pricing models is presented. Several aspects of the well-known errors-in-variables problem are considered, and an earlier conjecture concerning the merits of simultaneous estimation of beta and price of risk parameters is evaluated. The traditional inference procedure is found, under standard assumptions, to overstate the precision of price of risk estimates and an asymptotically valid correction is derived. Modifications to accommodate serial correlation in market-wide factors are also discussed. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.

Tests for Parameter Instability in Regressions With I(1) Processes

Abstract: This article derives the large-sample distributions of Lagrange multiplier (LM) tests for parameter instability against several alternatives of interest in the context of cointegrated regression models. The fully modified estimator of Phillips and Hansen is extended to cover general models with stochastic and deterministic trends. The test statistics considered include the SupF test of Quandt, as well as the LM tests of Nyblom and of Nabeya and Tanaka. It is found that the asymptotic distributions depend on the nature of the regressor processes—that is, if the regressors are stochastic or deterministic trends. The distributions are noticeably different from the distributions when the data are weakly dependent. It is also found that the lack of cointegration is a special case of the alternative hypothesis considered (an unstable intercept), so the tests proposed here may also be viewed as a test of the null of cointegration against the alternative of no cointegration. The tests are applied to three data se...

Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor

Abstract: NITRIC oxide is an important bioregulatory molecule, being responsible, for example, for activity of endothelium-derived relaxing factor (EDRF)1–4. Acute hypertension5, diabetes6, ischaemia7and atherosclerosis8 are associated with abnormalities of EDRF. Nitric oxide is thought to be a retrograde messenger in the central nervous system9. The technology is not yet available for rapid detection of NO released by a single cell in the presence of oxygen and/or nitrite, so the release, distribution and reactivity of endogenous NO in biological systems cannot be analysed. Here we describe a porphyrinic microsensor that we have developed and applied to monitoring NO release in a microsystem. We selectively measured in situ the NO released from a single cell with a response time of less than 10 ms. The microsensor consists of p-type semiconducting polymeric porphyrin and a cationic exchanger (Nation) deposited on a thermally sharpened carbon fibre with a tip diameter of ∼0.5 (μm. The microsensor, which can be operated in either the amperometric or voltammetric mode, is characterized by a linear response up to 300 μM and a detection limit of 10 nM. Nitric oxide at the level of 10−20 mols can be detected in a single cell.

Analysis of gene expression in single live neurons.

Abstract: We present here a method for broadly characterizing single cells at the molecular level beyond the more common morphological and transmitter/receptor classifications. The RNA from defined single cells is amplified by microinjecting primer, nucleotides, and enzyme into acutely dissociated cells from a defined region of rat brain. Further processing yields amplified antisense RNA. A second round of amplification results in greater than 10(6)-fold amplification of the original starting material, which is adequate for analysis--e.g., use as a probe, making of cDNA libraries, etc. We demonstrate this method by constructing expression profiles of single live cells from rat hippocampus. This profiling suggests that cells that appear to be morphologically similar may show marked differences in patterns of expression. In addition, we characterize several mRNAs from a single cell, some of which were previously undescribed, perhaps due to "rarity" when averaged over many cell types. Electrophysiological analysis coupled with molecular biology within the same cell will facilitate a better understanding of how changes at the molecular level are manifested in functional properties. This approach should be applicable to a wide variety of studies, including development, mutant models, aging, and neurodegenerative disease.

cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase

Abstract: The antiinflammatory glucocorticoids are potent inhibitors of cyclooxygenase, a key regulator of prostaglandin synthesis; yet, the mechanism(s) by which this occurs is not fully understood. We have cloned a 4.1-kilobase (kb) cDNA, distinct from the previously cloned cyclooxygenase (2.8 kb), that confers cyclooxygenase activity to transfected cells. The mRNA for this newly discovered cyclooxygenase is unique for its long 3' untranslated region containing many AUUUA repeats. Levels of the 4.1-kb cyclooxygenase mRNA are rapidly increased by serum or interleukin 1 beta in mouse fibroblasts and human monocytes, respectively, and decreased by glucocorticoids, whereas levels of the 2.8-kb cyclooxygenase mRNA do not change. Similar effects are seen in the presence of cycloheximide where the 4.1-kb, but not the 2.8-kb, mRNA is greatly superinduced. Thus, there are both constitutive (2.8 kb) and regulated (4.1 kb) cyclooxygenase species, the latter most likely being a major mediator of inflammation.

Pulmonary Retention of Ultrafine and Fine Particles in Rats

Abstract: In aerosol research, particle size has been mainly considered in the context of the role it plays in particle deposition along the respiratory tract. The possibility that the primary particle size may affect the fate of particles after they are deposited was explored in this study. Rats were exposed for 12 wk to aerosolized ultrafine (∼21 nm diameter) or fine (∼250 nm diameter) titanium dioxide (TiO2) particles. Other rats were exposed to TiO2 particles of various sizes (12, 21, 230, and 250 nm) by intratracheal instillation. After the rat lungs were extensively lavaged, analysis of particle content in the lavaged lungs, lavage fluid, and of lymphatic nodes was performed. Electron and light microscopy was also performed using unlavaged lungs. Both acute instillation and subchronic inhalation studies showed that ultrafine particles (∼20 nm) at equivalent masses access the pulmonary interstitium to a larger extent than fine particles (∼250 nm). An increasing dose in terms of particle numbers and a decreasin...

Flexible tubular device for use in medical applications

Abstract: An apparatus for use as a catheter, a guidewire, a catheter sheath for use with catheter introducers or a drug infusion catheter/guidewire. The apparatus (20) including a flexible metallic tubular member (22) with an encasing (26) covering the tubular member that creates a fluid-tight seal around the periphery of the tubular member. In one embodiment, the tubular member can be a coiled metallic hypotube design. This coiled design can include either a single filament or multi-filament wire wrap. In a second embodiment, the flexible tubular member can be formed by cutting a predetermined configuration of slots into a single hollow thin-walled metal tube at predetermined spacings, depth and patterns.

Social Comparison in Everyday Life

Abstract: Ninety-four college students recorded details of their social comparisons over 2 weeks using a new instrument, the Rochester Social Comparison Record. Major results were (a) comparison direction varied with relationship with the target; (b) precomparison negative mood led more often to upward comparison than to downward comparison, supporting a selective affect-cognition priming model in which dysphoria primes negative thoughts about the self (Bower, 1991; Forgas, Bower, & Moylan, 1990) rather than a motivational self-enhancement model (Wills, 1981,1991); (c) upward comparison decreased subjective well-being, whereas downward comparison increased it; and (d) high self-esteem individuals engaged in more self-enhancing comparison. Festinger's theory of social comparison processes (Festinger, 1954) continues to be an active arena for theory and research. A new edited book (Suls & Wills, 1991), a symposium at the 1990 meeting of the Society for Experimental Social Psychology (SESP), and frequent journal articles attest to this vigor. Yet underlying the vitality is a feeling of uneasiness, obvious in the comments occasioned by the SESP symposium, in which a group of extraordinari ly knowledgeable participants showed little agreement about such apparently basic questions as "Do people compare at all (or very much)? When do people compare? How do people balance upward and downward comparisons? How much does similarity count in comparison? Do people compare with actual targets, or are all comparisons constructed in people's heads? The problem is that there are many measures of social comparison, and they do not agree well with one another, leading to theoretical proliferation lacking a coherent empirical base. These measures may not agree with one another because of difficulties with the measures themselves (Wood, 1991), because they measure different motives for social comparison (cf. Wood & Taylor, 1991), or because they have been used in different contexts. The one thing on which there is general agreement is that social comparison is a wonderfully flexible process that can best be studied under naturalistic

Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315.

Abstract: Between 1983 and 1987 the Radiation Therapy Oncology Group conducted a prospective phase II study to evaluate survival in primary non-Hodgkin's lymphoma of the brain treated with whole brain irradiation to 40 Gy and a 20 Gy boost to tumor plus a 2 cm margin. Forty-one patients are reported. Full follow-up is available on 35/41 who have died. Six are alive at 8.8-67.2 months from start of radiation therapy with a median followup of 53.9 months. Overall median survival was 11.6 months from start of radiation therapy and 12.2 months from diagnosis, with 48% surviving 1 year and 28% surviving 2 years. Karnofsky Performance Status and age were significant prognostic factors. Patients with a Karnofsky Performance Status of 70-100 had a median survival of 21.1 months compared to 5.6 months for patients with a status of 40-60 (p less than .001). Fourteen patients less than 60 years of age had a median survival of 23.1 months, while 27 patients greater than or equal to 60 years of age had a median survival of 7.6 months (log-rank p = .001). Disease recurred in the brain in 25/41 (61%) of the patients, (21/41 in the brain only and 4/41 in the brain plus distant metastases). Despite high dose and large volume irradiation, primary Central Nervous System lymphoma still exhibits excessive mortality, especially in older patients. This paradox of the relative radioresistance of primary Central Nervous System lymphoma remains unresolved.

Alternative excitotoxic hypotheses.

Abstract: The concept of excitotoxicity, neuronal death produced by overstimulation of excitatory amino acid receptors, has become a popular way of explaining the pathogenesis of neuronal death in a variety of acute and chronic neurologic diseases. While there is strong evidence supporting the role of excitotoxicity in acute processes such as hypoxia/ischemia and hypoglycemia, the role of excitotoxicity in chronic neurologic disease is not firmly established. To account for the inter- and intraregional variations in pathology of different neurodegenerative disorders, we suggest two modified forms of the excitotoxic hypothesis in which specific populations of neurons become more vulnerable to excitotoxic insult either by (1) possessing abnormal excitatory amino acid receptor subtypes or (2) being afflicted by any disease process that impairs cellular energy metabolism or otherwise decreases neuronal membrane potential. In these ways, excitotoxicity may be a final common pathway of neuronal death in a variety of neurodegenerative diseases.

Visual response latencies in striate cortex of the macaque monkey

Abstract: 1 Many lines of evidence suggest that signals relayed by the magnocellular and parvocellular subdivisions of the primate lateral geniculate nucleus (LGN) maintain their segregation in cortical processing We have examined two response properties of units in the striate cortex of macaque monkeys, latency and transience, with the goal of assessing whether they might be used to infer specific geniculate contributions Recordings were made from 298 isolated units and 1,129 multiunit sites in the striate cortex in four monkeys Excitotoxin lesions that selectively affected one or the other LGN subdivision were made in three animals to demonstrate directly the magnocellular and parvocellular contributions An additional 435 single units and 551 multiunit sites were recorded after the ablations 2 Most units in striate cortex had visual response latencies in the range of 30-50 ms under the stimulus conditions used The earliest neuronal responses in striate cortex differed appreciably between individuals The shortest latency recorded in the four animals ranged from 20 to 31 ms Comparable values were obtained from both single unit and multiunit sites After lesions were made in the magnocellular subdivision of the LGN in two animals, the shortest response latencies were 7 and 10 ms later than before the ablations A larger lesion in the parvocellular subdivision of another animal produced no such shift Thus it appears that the first 7-10 ms of cortical activation can be attributed to activation relayed by the magnocellular layers of the LGN 3 The units with the shortest latencies were all found in layers 4C or 6 and their responses were among the most transient in striate cortex Furthermore, their responses all showed a pronounced periodicity at a frequency of 50-100 Hz This periodicity was stimulus locked, and the responses of all short-latency units oscillated in phase 4 An index of response transience was computed for the units recorded in striate cortex The distribution of this index was unimodal and gave no suggestion of distinct contributions from the geniculate subdivisions Magnocellular and the parvocellular lesions affected the overall transience of responses in striate cortex The changes, however, were very small; extremely transient responses and extremely sustained responses survived both types of lesions 5 A characteristic profile was observed in the response latencies in superficial layers Latencies appeared to increase monotonically from layer 4 toward the surface of cortex, with the most superficial neurons not becoming active until 15 ms after responses were observed in layer 4C(ABSTRACT TRUNCATED AT 400 WORDS)

More evidence on income distribution and growth

Abstract: It has been suggested that inequality is an unpleasant precondition for growth. This paper shows that the empirical evidence strongly supports the opposite view: that inequality is negatively correlated with growth. This result is robust across different inequality measures, and to many different specifications of the growth regression. Furthermore, inequality appears to have a negative effect on both democracies and non-democracies. Interaction terms between inequality and regime type, when included in the base regression, do not affect the sign or significance of the inequality variables.

Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease.

Abstract: Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-alpha) and interleukin 1 beta (IL-1 beta) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-beta, IL-1 alpha, IL-6, interferon alpha (IFN-alpha), and IFN-gamma were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, > 2.5-fold, the levels of TNF-alpha. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes.

Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.

Abstract: Purpose: The influence of tumor site, size, and extent of surgery on the survival of patients withglioblastoma multiforme treated on three consecutive prospectively randomized Radiation Therapy Oncology Group trials employing surgery and irradiation plus or minus chemotherapy was studied. Methods and Materials: Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%6, between 5–10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. Results: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) ( p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: Conclusion: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.

Method for encouraging purchase of executable and non-executable software

Abstract: A method and apparatus of encouraging distribution, registration, and purchase of free copyable software and other digital information which is accessed on a User's System via a Programmer's Program Software tools which can be incorporated into a Programmer's Program allow the User to access Advanced Features of the Programmer's Program only in the presence of a valid Password which is unique to a particular Target ID generated on an ID-Target such as the User's system Advanced features will thus re-lock if the Password is copied to another ID-target If a valid Password is not present, the User is invited to obtain one, and provided with the means of doing so, and of installing that Password in a place accessible to the User's System on subsequent occasions The present invention also provides Programmers with means to invoke business operations as well as computational operations with their programs, and thus to automatically obtain payment from Users who elect to obtain passwords

Facilitating the Gibbs Sampler: The Gibbs Stopper and the Griddy-Gibbs Sampler

Abstract: The article briefly reviews the history, literature, and form of the Gibbs sampler. An importance sampling device is proposed for converting the output of the Gibbs sampler to a sample from the exact posterior. This Gibbs stopper technique is also useful for assessing convergence of the Gibbs sampler for moderate sized problems. Also presented is an approach for implementing the Gibbs sampler in nonconjugate situations. The basic idea is to approximate the true cdf of each conditional distribution by a piecewise linear function and then sample from the approximation. Questions relating to the number of nodes in the approximation, gap size between successive nodes, and the treatment of unbounded intervals for a given conditional are discussed. The methodology is illustrated using a genetic linkage model, a nonlinear regression model, and the Cox model.

Market segmentation, cannibalization, and the timing of product introductions

Abstract: Consider a seller who faces two customer segments with differing valuations of quality of a durable product. Demand is stationary and known, the technology exists to release two products simultaneously, and the seller can commit in advance to subsequent prices and qualities. Should he introduce two differentiated products at once or one at a time? Under the simultaneous strategy, the lower quality would cannibalize demand for the higher quality. To reduce cannibalization, the seller could lower the quality of the low-end model and reduce the price of the high-end. Alternatively, he could increase the quality of the low-end model, but delay its release. Sequential introduction, however, would mean that the profits from the low-end model arrive later. We show that sequential introduction is better than simultaneous introduction when cannibalization is a problem and customers are relatively more impatient than the seller. However, when the seller cannot pre-commit, sequential selling is much less attractive because then he cannot use his product designs to alleviate cannibalization.

Role of the alveolar macrophage in lung injury: studies with ultrafine particles.

Abstract: We conducted a series of experiments with ultrafine particles (approximately 20 nm) and larger particles (less than 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle translocation in rats. After intratracheal instillation of both ultrafine particles and larger particles of TiO2, we found a highly increased interstitial access of the ultrafine particles combined with a large acute inflammatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal instillation of phagocytized ultrafine TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and the interstitial access of the ultrafine particles. Another experiment showed that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses of ultrafine particles, whereas alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelial permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area of the retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflammatory events induced by particles in the interstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We conclude that the increased pulmonary toxicity of ultrafine particles is related to their larger surface area and to their increased interstitial access.(ABSTRACT TRUNCATED AT 250 WORDS)

Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca2+-permeable channel

Abstract: Receptor-mediated increases in the cytosolic free calcium ion concentration in most mammalian cells result from mobilization of Ca2+ from intracellular stores as well as transmembrane Ca2+ influx. Inositol 1,4,5-trisphosphate (InsP3) releases calcium from intracellular stores by opening a Ca(2+)-permeable channel in the endoplasmic reticulum. But the mechanism and regulation of Ca2+ entry into nonexcitable cells has remained elusive because the entry pathway has not been defined. Here we characterize a novel inositol 1,3,4,5-tetrakisphosphate (InsP4) and Ca(2+)-sensitive Ca(2+)-permeable channel in endothelial cells. We find that InsP4, which induces Ca2+ influx into acinar cells, enhances the activity of the Ca(2+)-permeable channel when exposed to the intracellular surface of endothelial cell inside-out patches. Our results suggest a molecular mechanism which is likely to be important for receptor-mediated Ca2+ entry.

Aged Heterogeneity: Fact or Fiction? The Fate of Diversity in Gerontological Research

Abstract: Studies examining age-related changes typically report findings as age-based generalizations that neglect the phenomenon of variability in gerontological research. This paper examines the degree of attention given in 185 studies to individual differences and the empirical patterns of variability reported in those studies that present measures of dispersion. Measures of dispersion were reported in 43% of the gerontological studies reviewed and in 24% of the developmental studies. Overall, a majority of all gerontological studies presenting data reported increases in variability with increasing age (65%). This pattern was more pronounced in longitudinal studies than in cross-sectional ones.