Showing papers by "Boston University published in 1996"

The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure

Abstract: Background Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined. Methods We enrolled 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions ≤0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696); background therapy with digoxin, diuretics, and an angiotensin-converting–enzyme inhibitor remained constant. Patients were observed for the occurrence of death or hospitalization for cardiovascular reasons during the following 6 months (12 months for the group with mild heart failure). Results The overall mortality rate was 7.8 percent in t...

P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature

Abstract: We provide here a list of 481 P450 genes and 22 pseudogenes, plus all accession numbers that have been reported as of October 18,1995. These genes have been described in 85 eukaryote (including vertebrates, invertebrates, fungi, and plants) and 20 prokaryote species. Of 74 gene families so far descr

Self-similarity in World Wide Web traffic: evidence and possible causes

Abstract: Recently the notion of self-similarity has been shown to apply to wide-area and local-area network traffic. In this paper we examine the mechanisms that give rise to the self-similarity of network traffic. We present a hypothesized explanation for the possible self-similarity of traffic by using a particular subset of wide area traffic: traffic due to the World Wide Web (WWW). Using an extensive set of traces of actual user executions of NCSA Mosaic, reflecting over half a million requests for WWW documents, we examine the dependence structure of WWW traffic. While our measurements are not conclusive, we show evidence that WWW traffic exhibits behavior that is consistent with self-similar traffic models. Then we show that the self-similarity in such traffic can be explained based on the underlying distributions of WWW document sizes, the effects of caching and user preference in file transfer, the effect of user "think time", and the superimposition of many such transfers in a local area network. To do this we rely on empirically measured distributions both from our traces and from data independently collected at over thirty WWW sites.

The Financial Accelerator and the Flight to Quality

Abstract: Adverse shocks to the economy may be amplified by worsening credit-market conditions-- the financial 'accelerator'. Theoretically, we interpret the financial accelerator as resulting from endogenous changes over the business cycle in the agency costs of lending. An implication of the theory is that, at the onset of a recession, borrowers facing high agency costs should receive a relatively lower share of credit extended (the flight to quality) and hence should account for a proportionally greater part of the decline in economic activity. We review the evidence for these predictions and present new evidence drawn from a panel of large and small manufacturing firms.

Photobook: content-based manipulation of image databases

Abstract: We describe the Photobook system, which is a set of interactive tools for browsing and searching images and image sequences. These query tools differ from those used in standard image databases in that they make direct use of the image content rather than relying on text annotations. Direct search on image content is made possible by use of semantics-preserving image compression, which reduces images to a small set of perceptually-significant coefficients. We discuss three types of Photobook descriptions in detail: one that allows search based on appearance, one that uses 2-D shape, and a third that allows search based on textural properties. These image content descriptions can be combined with each other and with text-based descriptions to provide a sophisticated browsing and search capability. In this paper we demonstrate Photobook on databases containing images of people, video keyframes, hand tools, fish, texture swatches, and 3-D medical data.

Blood Pressure as a Cardiovascular Risk Factor: Prevention and Treatment

Abstract: Objective. —To examine the prevalence, incidence, predisposing factors for hypertension, its hazards as an ingredient of the cardiovascular risk profile, and the implications of this information for prevention and treatment. Methods. —Prospective longitudinal analysis of 36-year follow-up data from the Framingham Study of the relation of antecedent blood pressure to occurrence of subsequent cardiovascular morbidity and mortality depending on the metabolically linked burden of associated risk factors. Results. —Hypertension is one of the most prevalent and powerful contributors to cardiovascular diseases, the leading cause of death in the United States. There is, on average, a 20 mm Hg systolic and 10 mm Hg diastolic increment increase in blood pressure from age 30 to 65 years. Isolated systolic hypertension is the dominant variety. There is no evidence of a decline in the prevalence of hypertension over 4 decades despite improvements in its detection and treatment. Hypertension contributes to all of the major atherosclerotic cardiovascular disease outcomes increasing risk, on average, 2- to 3-fold. Coronary disease, the most lethal and common sequela, deserves highest priority. Hypertension clusters with dyslipidemia, insulin resistance, glucose intolerance, and obesity, occurring in isolation in less than 20%. The hazard depends on the number of these associated metabolically linked risk factors present. Coexistent overt cardiovascular disease also influences the hazard and choice of therapy. Conclusion. —The absence of a decline in the prevalence of hypertension indicates an urgent need for primary prevention by weight control, exercise, and reduced salt and alcohol intake. The urgency and choice of therapy of existing hypertension should be based on the multivariate cardiovascular risk profile that more appropriately targets hypertensive persons for treatment and prevention of cardiovascular sequelae. ( JAMA . 1996;275:1571-1576)

Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury.

Abstract: The discovery that some cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creation and characterization of mice completely deficient for this enzyme. These animals develop normally and show no overt motor deficits by 6 months in age. Histological examination of the spinal cord reveals no signs of pathology in animals 4 months in age. However Cu/Zn SOD-deficient mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury.

Intercultural Communication: A Discourse Approach

Abstract: Intro -- Intercultural Communication -- Contents -- Figures -- Series Editor's Preface -- Preface to the First Edition -- Preface to the Second Edition -- Preface to the Third Edition -- 1: What Is a Discourse Approach? -- The Problem with Culture -- Culture is a verb -- Discourse -- Discourse systems -- What Is Communication? -- Language is ambiguous by nature -- We must draw inferences about meaning -- Our inferences tend to be f ixed, not tentative -- Our inferences are drawn very quickly -- Interdiscourse communication and English as a global language -- What This Book Is Not -- Researching Interdiscourse Communication -- Four processes of ethnography -- Four types of data in ethnographic research -- Choosing a site of investigation -- Discussion Questions -- References for Further Study -- 2: How, When, and Where to Do Things with Language -- Sentence Meaning and Speaker's Meaning -- Speech Acts, Speech Events, and Speech Situations -- Grammar of Context -- Seven main components for a grammar of context -- Scene -- Key -- Participants -- Message form -- Sequence -- Co-occurrence patterns, marked and unmarked -- Manifestation -- Variation in context grammar -- "Culture" and Context -- High context and low context situations -- Researching Interdiscourse Communication -- Using the "grammar of context" as a preliminary ethnographic audit -- Discussion Questions -- References for Further Study -- 3: Interpersonal Politeness and Power -- Communicative Style or Register -- Face -- The "self" as a communicative identity -- The Paradox of Face: Involvement and Independence -- Politeness strategies of involvement and independence -- Linguistic strategies of involvement: some examples -- Linguistic strategies of independence: some examples -- Face Systems -- Three Face Systems: Deference, Solidarity, and Hierarchy -- Deference face system (−P, +D).

Stroke Severity in Atrial Fibrillation The Framingham Study

Abstract: Background and Purpose Stroke occurring with atrial fibrillation (AF) is more likely to be fatal or more severe than non-AF stroke based on clinical series, but data from prospective epidemiological studies are sparse and inconsistent Methods Over 40-year follow-up of the original 5070 Framingham cohort, 501 initial ischemic strokes, including 103 with AF, were analyzed Stroke severity was rated as none, mild, moderate, severe, or fatal Since 1981, functional status indicated by the Barthel index has been evaluated acutely and at 3, 6, and 12 months Severity and functional status of AF strokes were compared with non-AF strokes using χ2 test and Student's t test Thirty-day mortality was assessed by logistic regression analyses Results AF was associated with increased stroke severity (P=048) Thirty-day mortality was greater in AF strokes than in non-AF strokes (25% versus 14%) The multivariate-adjusted odds ratio for 30-day mortality for AF subjects was 184 (95% confidence interval, 104 to 327)

Lévy flight search patterns of wandering albatrosses

Abstract: LeVY flights are a special class of random walks whose step lengths are not constant but rather are chosen from a probability distribution with a power-law tail. Realizations of Levy flights in physical phenomena are very diverse, examples including fluid dynamics, dynamical systems, and micelles1,2. This diversity raises the possibility that Levy flights may be found in biological systems. A decade ago, it was proposed that Levy flights may be observed in the behaviour of foraging ants3. Recently, it was argued that Drosophila might perform Levy flights4, but the hypothesis that foraging animals in natural environments perform Levy flights has not been tested. Here we study the foraging behaviour of the wandering albatross Diomedea exulans, and find a power-law distribution of flight-time intervals. We interpret our finding of temporal scale invariance in terms of a scale-invariant spatial distribution of food on the ocean surface. Finally, we examine the significance of our finding in relation to the basis of scale-invariant phenomena observed in biological systems.

Quantum Privacy Amplification and the Security of Quantum Cryptography over Noisy Channels

Abstract: Existing quantum cryptographic schemes are not, as they stand, operable in the presence of noise on the quantum communication channel. Although they become operable if they are supplemented by classical privacy-amplification techniques, the resulting schemes are difficult to analyze and have not been proved secure. We introduce the concept of quantum privacy amplification and a cryptographic scheme incorporating it which is provably secure over a noisy channel. The scheme uses an “entanglement purification” procedure which, because it requires only a few quantum controllednot and single-qubit operations, could be implemented using technology that is currently being developed. [S0031-9007(96)01288-4] Quantum cryptography [1 ‐ 3] allows two parties (traditionally known as Alice and Bob) to establish a secure random cryptographic key if, first, they have access to a quantum communication channel, and second, they can exchange classical public messages which can be monitored but not altered by an eavesdropper (Eve). Using such a key, a secure message of equal length can be transmitted over the classical channel. However, the security of quantum cryptography has so far been proved only for the idealized case where the quantum channel, in the absence of eavesdropping, is noiseless. That is because, under existing protocols, Alice and Bob detect eavesdropping by performing certain quantum measurements on transmitted batches of qubits and then using statistical tests to determine, with any desired degree of confidence, that the transmitted qubits are not entangled with any third system such as Eve. The problem is that there is in principle no way of distinguishing entanglement with an eavesdropper (caused by her measurements) from entanglement with the environment caused by innocent noise, some of which is presumably always present. This implies that all existing protocols are, strictly speaking, inoperable in the presence of noise, since they require the transmission of messages to be suspended whenever an eavesdropper (or, therefore, noise) is detected. Conversely, if we want a protocol that is secure in the presence of noise, we must find one that allows secure transmission to continue even in the presence of eavesdroppers. To this end, one might consider modifying the existing pro

Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

Abstract: Glucocorticoid-induced bone loss should be prevented, and if present, should be treated (Table 2). Supplementation with calcium and vitamin D at a dosage of 800 IU/day, or an activated form of vitamin D (e.g., alfacalcidiol at 1 microg/day or calcitriol at 0.5 microg/day), should be offered to all patients receiving glucocorticoids, to restore normal calcium balance. This combination has been shown to maintain bone mass in patients receiving long-term low-to-medium-dose glucocorticoid therapy who have normal levels of gonadal hormones. However, while supplementation with calcium and vitamin D alone generally will not prevent bone loss in patients in whom medium-to-high-dose glucocorticoid therapy is being initiated, supplementation with calcium and an activated form of vitamin D will prevent bone loss. There are no data available to support any conclusion about the antifracture efficacy of the combination of calcium supplementation plus an activated form of vitamin D. Antiresorptive agents are effective in the treatment of glucocorticoid-induced bone loss. All of these agents either prevent bone loss or modestly increase lumbar spine bone mass and maintain hip bone mass. While there are no randomized controlled trials of prevention of glucocorticoid-induced bone loss or radiographic vertebral fracture outcomes with HRT or testosterone, patients receiving long-term glucocorticoid therapy who are hypogonadal should be offered HRT. The bisphosphonates are effective for both the prevention and the treatment of glucocorticoid-induced bone loss. Large studies have demonstrated that bisphosphonates also reduce the incidence of radiographic vertebral fractures in postmenopausal women with glucocorticoid-induced osteoporosis. Treatment with a bisphosphonate is recommended to prevent bone loss in all men and postmenopausal women in whom long-term glucocorticoid treatment at > or =5 mg/day is being initiated, as well as in men and postmenopausal women receiving long-term glucocorticoids in whom the BMD T-score at either the lumbar spine or the hip is below normal. While there is little information on the prevention or treatment of bone loss in premenopausal women, these women, too, may lose bone mass if they are being treated with glucocorticoids, so prevention of bone loss with antiresorptive agents should be considered. If bisphosphonate therapy is being considered for a premenopausal woman, she must be counseled regarding use of appropriate contraception. The therapies to prevent or treat glucocorticoid-induced bone loss should be continued as long as the patient is receiving glucocorticoids. Data from large studies of anabolic agents (e.g., PTH) and further studies of combination therapy in patients receiving glucocorticoids are eagerly awaited so additional options will be available for the prevention of this serious complication of glucocorticoid treatment.

A real-time matching system for large fingerprint databases

Abstract: With the current rapid growth in multimedia technology, there is an imminent need for efficient techniques to search and query large image databases. Because of their unique and peculiar needs, image databases cannot be treated in a similar fashion to other types of digital libraries. The contextual dependencies present in images, and the complex nature of two-dimensional image data make the representation issues more difficult for image databases. An invariant representation of an image is still an open research issue. For these reasons, it is difficult to find a universal content-based retrieval technique. Current approaches based on shape, texture, and color for indexing image databases have met with limited success. Further, these techniques have not been adequately tested in the presence of noise and distortions. A given application domain offers stronger constraints for improving the retrieval performance. Fingerprint databases are characterized by their large size as well as noisy and distorted query images. Distortions are very common in fingerprint images due to elasticity of the skin. In this paper, a method of indexing large fingerprint image databases is presented. The approach integrates a number of domain-specific high-level features such as pattern class and ridge density at higher levels of the search. At the lowest level, it incorporates elastic structural feature-based matching for indexing the database. With a multilevel indexing approach, we have been able to reduce the search space. The search engine has also been implemented on Splash 2-a field programmable gate array (FPGA)-based array processor to obtain near-ASIC level speed of matching. Our approach has been tested on a locally collected test data and on NIST-9, a large fingerprint database available in the public domain.

Scaling behaviour in the growth of companies

Abstract: A SUCCESSFUL theory of corporate growth should include both the external and internal factors that affect the growth of a company1–18. Whereas traditional models emphasize production-related influences such as investment in physical capital and in research and development18, recent models10–20 recognize the equal importance of organizational infrastructure. Unfortunately, no exhaustive empirical account of the growth of companies exists by which these models can be tested. Here we present a broad, phenomenological picture of the dependence of growth on company size, derived from data for all publicly traded US manufacturing companies between 1975 and 1991. We find that, for firms with similar sales, the distribution of annual (logarithmic) growth rates has an exponential form; the spread in the distribution of rates decreases with increasing sales as a power law over seven orders of magnitude. A model wherein the probability of a company's growth depends on its past as well as present sales accounts for the former observation. As the latter observation applies to companies that manufacture products of all kinds, organizational structures common to all firms might well be stronger determinants of growth than production-related factors, which differ for companies producing different goods.

From HMM's to segment models: a unified view of stochastic modeling for speech recognition

Abstract: Many alternative models have been proposed to address some of the shortcomings of the hidden Markov model (HMM), which is currently the most popular approach to speech recognition. In particular, a variety of models that could be broadly classified as segment models have been described for representing a variable-length sequence of observation vectors in speech recognition applications. Since there are many aspects in common between these approaches, including the general recognition and training problems, it is useful to consider them in a unified framework. The paper describes a general stochastic model that encompasses most of the models proposed in the literature, pointing out similarities of the models in terms of correlation and parameter tying assumptions, and drawing analogies between segment models and HMMs. In addition, we summarize experimental results assessing different modeling assumptions and point out remaining open questions.

Carvedilol Inhibits Clinical Progression in Patients With Mild Symptoms of Heart Failure

Abstract: Background We tested the hypothesis that carvedilol inhibits clinical progression in patients with mildly symptomatic heart failure due to left ventricular (LV) systolic dysfunction. Methods and Results Patients (n=366) who had mildly symptomatic heart failure with an LV ejection fraction (LVEF) ≤0.35, had minimal functional impairment (defined as the ability to walk 450 to 550 m on a 6-minute walk test), and were receiving optimal standard therapy, including ACE inhibitors, were randomized double-blind to carvedilol (n=232) or placebo (n=134) and followed up for 12 months. The primary end point was clinical progression, defined as death due to heart failure, hospitalization for heart failure, or a sustained increase in heart failure medications. Clinical progression of heart failure occurred in 21% of placebo patients and 11% of carvedilol patients, reflecting a 48% (P=.008) reduction in the primary end point of heart failure progression (relative risk, 0.52; CI, 0.32 to 0.85). This effect of carvedilol ...

Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids.

Abstract: The differentiation of 3T3 preadipocytes into adipocytes is accompanied by a transient induction of C/EBPbeta and C/EBPdelta expression in response to treatment of the cells with methylisobutylxanthine (MIX) and dexamethasone (DEX), respectively. In this report, we demonstrate that peroxisome proliferator-activated receptor gamma (PPARgamma) expression in 3T3-L1 preadipocytes is induced by MIX and DEX, suggesting that C/EBPbeta and C/EBPdelta may be involved in this process. Using a tetracycline-responsive expression system, we have recently shown that the conditional ectopic expression of C/EBPbeta in NIH 3T3 fibroblasts (beta2 cells) in the presence of DEX activates the synthesis of peroxisome PPARgamma mRNA. Subsequent exposure of these cells to PPAR activators stimulates their conversion into adipocytes; however, neither the expression of C/EBPbeta nor exposure to DEX alone is capable of inducing PPARgamma expression in the beta2 cell line. We find that unlike the case for 3T3 preadipocytes, C/EBPdelta is not induced by DEX in these 3T3 fibroblasts and therefore is not relaying the effect of this glucocorticoid to the PPARgamma gene. To define the role of glucocorticoids in regulating PPARgamma expression and the possible involvement of C/EBPdelta, we have established an additional set of NIH 3T3 cell lines expressing either C/EBPdelta alone (delta23 cells) or C/EBPdelta and C/EBPbeta together (beta/delta39 cells), using the tetracycline-responsive system. Culture of these cells in tetracycline-deficient medium containing DEX, MIX, insulin, and fetal bovine serum shows that the beta/delta39 cells express PPARgamma and aP2 mRNAs at levels that are almost equivalent to those observed in fully differentiated 3T3-L1 adipocytes. These levels are approximately threefold higher than their levels of expression in the beta2 cells. Despite the fact that these beta/delta39 cells produce abundant amounts of C/EBPbeta and C/EBPdelta (in the absence of tetracycline), they still require glucocorticoids to attain maximum expression of PPARgamma mRNA. Furthermore, the induction of PPARgamma mRNA by exposure of these cells to DEX occurs in the absence of ongoing protein synthesis. The delta23 cells, on the other hand, are not capable of activating PPARgamma gene expression when exposed to the same adipogenic inducers. Finally, attenuation of ectopic C/EBPbeta production at various stages during the differentiation process results in a concomitant inhibition of PPARgamma and the adipogenic program. These data strongly suggest that the induction of PPARgamma gene expression in multipotential mesenchymal stem cells (NIH 3T3 fibroblasts) is dependent on elevated levels of C/EBPbeta throughout the differentiation process, as well as an initial exposure to glucocorticoids. C/EBPdelta may function by synergizing with C/EBPbeta to enhance the level of PPARgamma expression.

Double-Blind, Placebo-Controlled Study of the Effects of Carvedilol in Patients With Moderate to Severe Heart Failure The PRECISE Trial

Abstract: Background Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. Methods and Results We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction ≤0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n=145) or carvedilol (n=133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P=.014) or by a global assessment of progress judged either by the patient (P=.002) or by the physician (P<.001). In addition, treatment with carvedilol...

Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells.

Abstract: Apoptosis of the WEHI 231 immature B cell lymphoma line following membrane interaction with an antibody against the surface IgM chains (anti-IgM) is preceded by dramatic changes in Nuclear Factor-kappaB (NF-kappaB)/ Rel binding activities. An early transient increase in NF-kappaB/Rel binding is followed by a significant decrease in intensity below basal levels. Here we have explored the role of these changes in Rel-related factors in B cell apoptosis. Treatment of WEH1 231 cells with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a protease inhibitor which prevents degradation of the inhibitor of NF-kappaB (IkappaB)-alpha, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF-kappaB/Rel factor binding and induced apoptosis. Bcl-XL expression protected WEHI 231 cells from apoptosis induced by these agents. Microinjection of WEHI 231 cells with either IkappaB-alpha-GST protein or a c-Rel affinity-purified antibody induced apoptosis. Ectopic c-Rel expression ablated apoptosis induced by TPCK or anti-IgM. Treatment of BALENLM 17 and A20 B lymphoma cells or normal murine splenic B lymphocytes with either TPCK or PDTC also resulted in apoptosis. These findings indicate that the drop in NF-kappaB/Rel binding following anti-IgM treatment activates apoptosis of WEHI 231 cells; furthermore, they implicate the NF-kappaB/Rel family in control of apoptosis of normal and transformed B cells.

Apolipoprotein E alleles and risk of coronary disease. A meta-analysis.

Abstract: A meta-analysis was undertaken to assess the impact of apolipoprotein E (apo E) alleles (e2, e3, and e4) on coronary disease in 14 published observational studies (9 clinical coronary disease and 5 coronary angiography). In comparison with e3, the e4 allele was associated with greater odds for coronary heart disease, and summary estimates of the odds ratios (ORs) and (95% confidence intervals) for both sexes combined were OR=0.98 (0.85-1.14) for e2 and OR=1.26 (1.13-1.41) for e4. Separate analyses for men and women showed similar associations. In angiographic studies the relative odds for significant coronary artery disease among both sexes combined was OR=0.76 (0.55-1.05) for e2 and OR=1.11 (0.88-1.40) for e4. The overall impression is that e4 is associated with clinical and coronary disease and that results are similar in men and women.

Characterizing reference locality in the WWW

Abstract: The authors propose models for both temporal and spatial locality of reference in streams of requests arriving at Web servers. They show that simple models based on document popularity alone are insufficient for capturing either temporal or spatial locality. Instead, they rely on an equivalent, but numerical, representation of a reference stream: a stack distance trace. They show that temporal locality can be characterized by the marginal distribution of the stack distance trace, and propose models for typical distributions and compare their cache performance to the traces. They also show that spatial locality in a reference stream can be characterized using the notion of self-similarity. Self-similarity describes long-range correlations in the data set, which is a property that previous researchers have found hard to incorporate into synthetic reference strings. They show that stack distance strings appear to be strongly self-similar, and provide measurements of the degree of self-similarity in the traces. Finally, they discuss methods for generating synthetic Web traces that exhibit the properties of temporal and spatial locality measured in the data.

On the relationship between file sizes, transport protocols, and self-similar network traffic

Abstract: Measurements of LAN and WAN traffic show that network traffic exhibits variability on different scales. We examine a mechanism that gives rise to self-similar network traffic and discuss performance. The mechanism we study is the transfer of files or messages whose size is drawn from a heavy-tailed distribution. In a realistic client/server network the degree to which file sizes are heavy-tailed can directly determine the degree of traffic self-similarity at the link level. This causal relationship is robust relative to changes in network resources, network topology, the influence of cross-traffic, and the distribution of interarrival times. Properties of the transport layer play an important role in preserving and modulating this relationship. The reliable transmission and flow control mechanisms of TCP serve to maintain the long-range dependency structure induced by heavy-tailed file size distributions. In contrast, if a non-flow-controlled and unreliable (UDP-based) transport protocol is used, the resulting traffic shows little self-similarity: although still bursty at short time scales, it has little long-range dependence. Performance implications of self-similarity are discussed as represented by various performance measures. Increased self-similarity as expected, results in degradation of performance. Queueing delay, in particular is discussed. Throughput-related measures such as packet loss and retransmission rate, however increase only gradually with increasing traffic self-similarity as long as reliable, flow-controlled transport protocol is used.