Showing papers by "University of Cologne published in 2003"

MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer.

Abstract: Early-stage non-small cell lung cancer (NSCLC) can be cured by surgical resection, but a substantial fraction of patients ultimately dies due to distant metastasis. In this study, we used subtractive hybridization to identify gene expression differences in stage I NSCLC tumors that either did or did not metastasize in the course of disease. Individual clones (n=225) were sequenced and quantitative RT-PCR verified overexpression in metastasizing samples. Several of the identified genes (eIF4A1, thymosin beta4 and a novel transcript named MALAT-1) were demonstrated to be significantly associated with metastasis in NSCLC patients (n=70). The genes' association with metastasis was stage- and histology specific. The Kaplan-Meier analyses identified MALAT-1 and thymosin beta4 as prognostic parameters for patient survival in stage I NSCLC. The novel MALAT-1 transcript is a noncoding RNA of more than 8000 nt expressed from chromosome 11q13. It is highly expressed in lung, pancreas and other healthy organs as well as in NSCLC. MALAT-1 expressed sequences are conserved across several species indicating its potentially important function. Taken together, these data contribute to the identification of early-stage NSCLC patients that are at high risk to develop metastasis. The identification of MALAT-1 emphasizes the potential role of noncoding RNAs in human cancer.

From 1970 until present: the Keller-Segel model in chemotaxis and its consequences

Abstract: This article summarizes various aspects and results for some general formulations of the classical chemotaxis models also known as Keller-Segel models. It is intended as a survey of results for the most common formulation of this classical model for positive chemotactical movement and offers possible generalizations of these results to more universal models. Furthermore it collects open questions and outlines mathematical progress in the study of the Keller-Segel model since the first presentation of the equations in 1970.

Multi-colour organic light-emitting displays by solution processing.

Abstract: Organic light-emitting diodes (OLEDs) show promise for applications as high-quality self-emissive displays for portable devices such as cellular phones and personal organizers. Although monochrome operation is sufficient for some applications, the extension to multi-colour devices--such as RGB (red, green, blue) matrix displays--could greatly enhance their technological impact. Multi-colour OLEDs have been successfully fabricated by vacuum deposition of small electroluminescent molecules, but solution processing of larger molecules (electroluminescent polymers) would result in a cheaper and simpler manufacturing process. However, it has proved difficult to combine the solution processing approach with the high-resolution patterning techniques required to produce a pixelated display. Recent attempts have focused on the modification of standard printing techniques, such as screen printing and ink jetting, but those still have technical drawbacks. Here we report a class of electroluminescent polymers that can be patterned in a way similar to standard photoresist materials--soluble polymers with oxetane sidegroups that can be crosslinked photochemically to produce insoluble polymer networks in desired areas. The resolution of the process is sufficient to fabricate pixelated matrix displays. Consecutive deposition of polymers that are luminescent in each of the three RGB colours yielded a device with efficiencies comparable to state-of-the-art OLEDs and even slightly reduced onset voltages.

A plea for DNA taxonomy

Abstract: Taxonomy underpins all biological research, with implications for many basic scientific and applied fields. Insights into the stability or change of animal and plant guilds require species identification on a broad scale and biodiversity questions have become a major public issue. But this comes at a time when taxonomy is facing a crisis, because ever fewer specialists are available. Here, we explore the possibility of using DNA-based methodology to overcome these problems. The utility of DNA sequences for taxonomic purposes is well established. However, all current taxonomic approaches intend to use DNA, at best, as an auxiliary criterion for identifying a species or a taxon, but have not given it a central role. We propose a scheme in which DNA would be the scaffold of a taxonomic reference system, whilst maintaining the importance of the morphological information associated with whole specimens.

Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin's Disease

Abstract: BACKGROUND: Faced with unsatisfactory results of treatment for advanced Hodgkin's disease, we investigated three combinations of chemotherapy. METHODS: From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or increased-dose BEACOPP, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results. RESULTS: For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP group and P<0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP. CONCLUSIONS: Increased-dose BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD.

Near-infrared flares from accreting gas around the supermassive black hole at the Galactic Centre

Abstract: Recent measurements of stellar orbits1,2,3 provide compelling evidence that the compact radio source Sagittarius A* (refs 4, 5) at the Galactic Centre is a 3.6-million-solar-mass black hole. Sgr A* is remarkably faint in all wavebands other than the radio region6,7, however, which challenges current theories of matter accretion and radiation surrounding black holes8. The black hole's rotation rate is not known, and therefore neither is the structure of space-time around it. Here we report high-resolution infrared observations of Sgr A* that reveal ‘quiescent’ emission and several flares. The infrared emission originates from within a few milliarcseconds of the black hole, and traces very energetic electrons or moderately hot gas within the innermost accretion region. Two flares exhibit a 17-minute quasi-periodic variability. If the periodicity arises from relativistic modulation of orbiting gas, the emission must come from just outside the event horizon, and the black hole must be rotating at about half of the maximum possible rate.

ARAMEMNON, a Novel Database for Arabidopsis Integral Membrane Proteins

Abstract: A specialized database (DB) for Arabidopsis membrane proteins, ARAMEMNON, was designed that facilitates the interpretation of gene and protein sequence data by integrating features that are presently only available from individual sources Using several publicly available prediction programs, putative integral membrane proteins were identified among the approximately 25,500 proteins in the Arabidopsis genome DBs By averaging the predictions from seven programs, approximately 6,500 proteins were classified as transmembrane (TM) candidate proteins Some 1,800 of these contain at least four TM spans and are possibly linked to transport functions The ARAMEMNON DB enables direct comparison of the predictions of seven different TM span computation programs and the predictions of subcellular localization by eight signal peptide recognition programs A special function displays the proteins related to the query and dynamically generates a protein family structure As a first set of proteins from other organisms, all of the approximately 700 putative membrane proteins were extracted from the genome of the cyanobacterium Synechocystis sp and incorporated in the ARAMEMNON DB The ARAMEMNON DB is accessible at the URL http://aramemnonbotanikuni-koelnde

General relativistic boson stars

Abstract: There is accumulating evidence that (fundamental) scalar fields may exist in nature. The gravitational collapse of such a boson cloud would lead to a boson star (BS) as a new type of a compact object. As with white dwarfs and neutron stars, a limiting mass exists similarly, below which a BS is stable against complete gravitational collapse to a black hole. According to the form of the self-interaction of the basic constituents and spacetime symmetry, we can distinguish mini-, axidilaton, soliton, charged, oscillating and rotating BSs. Their compactness prevents a Newtonian approximation; however, modifications of general relativity, as in the case of Jordan?Brans?Dicke theory as a low-energy limit of strings, would provide them with gravitational memory. In general, a BS is a compact, completely regular configuration with structured layers due to the anisotropy of scalar matter, an exponentially decreasing 'halo', a critical mass inversely proportional to the constituent mass, an effective radius and a large particle number. Due to the Heisenberg principle, a completely stable branch exists, and as a coherent state, it allows for rotating solutions with quantized angular momentum. In this review, we concentrate on the fascinating possibilities of detecting the various subtypes of (excited) BSs: possible signals include gravitational redshift and (micro-)lensing, emission of gravitational waves, or, in the case of a giant BS, its dark matter contribution to the rotation curves of galactic halos.

Current Trends in the Epidemiology of Nosocomial Bloodstream Infections in Patients with Hematological Malignancies and Solid Neoplasms in Hospitals in the United States

Abstract: A total of 2340 patients with underlying malignancy were identified among 22,631 episodes of nosocomial bloodstream infections (BSIs) in a prospectively collected database for 49 hospitals in the United States (Surveillance and Control of Pathogens of Epidemiologic Importance [SCOPE] Project). Data were obtained for the period of March 1995 through February 2001. Gram-positive organisms accounted for 62% of all BSIs in 1995 and for 76% in 2000 (P<.001), and gram-negative organisms accounted for 22% and 14% of all BSIs for these years, respectively. Neutropenia was observed in 30% of patients, so neutropenic and nonneutropenic patients were compared. In both, the predominant pathogens were coagulase-negative staphylococci (32% of isolates recovered from neutropenic patients and 30% of isolates recovered from nonneutropenic patients). The source of BSI was not determined for 57% of patients. The crude mortality rate was 36% for neutropenic patients and 31% for nonneutropenic patients.

B cells under influence: transformation of B cells by Epstein–Barr virus

Abstract: Epstein-Barr virus (EBV) is an extremely successful virus, infecting more than 90% of the human population worldwide. After primary infection, the virus persists for the life of the host, usually as a harmless passenger residing in B cells. However, EBV can transform B cells, which can result in the development of malignant lymphomas. Intriguingly, the three main types of EBV-associated B-cell lymphoma - that is, Burkitt lymphoma, Hodgkin lymphoma and post-transplant lymphomas - seem to derive from germinal-centre B cells or atypical survivors of the germinal-centre reaction in most, if not all, cases, indicating that EBV-infected germinal-centre B cells are at particular risk for malignant transformation.

Friction effects and clogging in a cellular automaton model for pedestrian dynamics.

Abstract: We investigate the role of conflicts in pedestrian traffic, i.e., situations where two or more people try to enter the same space. Therefore a recently introduced cellular automaton model for pedestrian dynamics is extended by a friction parameter mu. This parameter controls the probability that the movement of all particles involved in a conflict is denied at one time step. It is shown that these conflicts are not an undesirable artifact of the parallel update scheme, but are important for a correct description of the dynamics. The friction parameter mu can be interpreted as a kind of an internal local pressure between the pedestrians which becomes important in regions of high density, occurring, e.g., in panic situations. We present simulations of the evacuation of a large room with one door. It is found that friction has not only quantitative effects, but can also lead to qualitative changes, e.g., of the dependence of the evacuation time on the system parameters. We also observe similarities to the flow of granular materials, e.g., arching effects.

A model of desynchronizing deep brain stimulation with a demand-controlled coordinated reset of neural subpopulations

Abstract: The coordinated reset of neural subpopulations is introduced as an effectively desynchronizing stimulation technique. For this, short sequences of high-frequency pulse trains are administered at different sites in a coordinated way. Desynchronization is easily maintained by performing a coordinated reset with demand-controlled timing or by periodically administering resetting high-frequency pulse trains of demand-controlled length. Unlike previously developed methods, this novel approach is robust against variations of model parameters and does not require time-consuming calibration. The novel technique is suggested to be used for demand-controlled deep brain stimulation in patients suffering from Parkinson's disease or essential tremor. It might even be applicable to diseases with intermittently emerging synchronized neural oscillations like epilepsy.

Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx.

Abstract: Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin-fixed, paraffin-embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV-16. Greater risk of HPV infection was associated with males (OR = 2.9, 95% CI = 1.0-8.6), a history of oral-genital sex (OR = 4.2, 95% CI = 1.5-11.7), and oropharyngeal tumors (OR = 10.4, 95% CI = 3.5-31.2). As tobacco usage increased, the odds of HPV detection decreased (OR = 0.97/pack-year, 95% CI = 0.96-0.99). HPV infected patients had better overall survival (RR = 0.3, 95% CI = 0.1-0.8) than those with HPV-negative tumors. There was an interaction between gender and HPV for overall (p = 0.05) and disease-specific (p = 0.03) survival that suggested that HPV infected males had better prognosis than HPV-negative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender-specific, suggesting the need for further study of the interaction between HPV and gender on survival.

Stellar Dynamics in the Central Arcsecond of Our Galaxy

Abstract: With 10 years of high-resolution imaging data now available on the stellar cluster in the Galactic center, we present proper motions for more than 40 stars at projected distances ≤12 from Sagittarius A* (Sgr A*). We find evidence on a ≥2 σ level for radial anisotropy of the cluster of stars within 1'' of Sgr A*. For a brightness limit of K ~ 15.5, we find no evidence for a stationary source at the position of Sgr A* or for a source at this position that would be variable on a timescale of at least several hours to days. On timescales of seconds to tens of minutes, we find no variability at the Sgr A* position on brightness levels K ≤ 13.5. We confirm/find accelerated motion for six stars, with four stars having passed the pericenter of their orbits during the observed time span. We calculated/constrained the orbital parameters of these stars. All orbits have moderate to high eccentricities. We discuss the possible bias in detecting preferentially orbits with high eccentricities and find that measured values of e > 0.9 might be detected by about a factor of 1.5-2 more frequently. We find that the center of acceleration for all the orbits coincides with the radio position of Sgr A*. From the orbit of the star S2, the currently most tightly constrained one, we determine the mass of Sgr A* to be × 106 M☉ and its position to 2.0 ± 2.4 mas east and 2.7 ± 4.5 mas south of the nominal radio position. The mass estimate for the central dark mass from the orbit of S2 is fully consistent with the mass estimate of × 106 M☉ obtained from stellar proper motions within 12 of Sgr A* using a Leonard-Merritt mass estimator. We find that radio astronomical observations of the proper motion of Sgr A*, in combination with its intrinsic source size, place at the moment the tightest constraints on the mass density of Sgr A*, which must exceed ρ > 3 × 1019 M☉ pc-3.

Involved-Field Radiotherapy Is Equally Effective and Less Toxic Compared With Extended-Field Radiotherapy After Four Cycles of Chemotherapy in Patients With Early-Stage Unfavorable Hodgkin’s Lymphoma: Results of the HD8 Trial of the German Hodgkin’s Lymphoma Study Group

Abstract: Purpose: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy. Patients and Methods: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). Results: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after s...

Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus.

Abstract: Recent analyses of head and neck squamous cell carcinomas revealed frequent infections by oncogenic human papillomavirus (HPV) type 16 in tonsillar carcinomas. Concerning involvement of risk factors, clinical course of the disease, and prognosis there are strong indications arguing that the HPV-positive tonsillar carcinomas may represent a separate tumor entity. Looking for a surrogate marker, which in further epidemiological studies could replace the laborious and expensive HPV detection and typing we analyzed p16 protein expression in 34 tonsillar carcinoma for correlation to HPV status and load of viral DNA. p16 has been shown to be of diagnostic value for clinical evaluation of cervical dysplasia. We found 53% of the tested tonsillar carcinomas to be HPV-positive. Fifty-six percent of all tumors tested were immunohistochemically positive for the p16 protein. In 16 of 18 of the HPV-positive carcinomas diffuse p16 expression was observed. In contrast, only one of the HPV-negative carcinomas showed focal p16 staining (P < 0.001). As determined by laser-assisted microdissection and quantitative real-time polymerase chain reaction, p16 expression correlated with the presence of HPV-DNA in the individual tumor specimens. Clinical outcome analysis revealed significant correlation of p16 expression with increased disease-free survival (P = 0.02). These data indicate that p16 is a technically simple immunohistological marker, applicable for routine pathological histology, and its prognostic value for survival is fully equivalent to HPV-DNA detection.

Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke.

Abstract: The therapeutical potential of transplantation of undifferentiated and predifferentiated murine embryonic stem cells for the regeneration of the injured brain was investigated in two rodent stroke models. Undifferentiated embryonic stem cells xenotransplanted into the rat brain at the hemisphere opposite to the ischemic injury migrated along the corpus callosum towards the damaged tissue and differentiated into neurons in the border zone of the lesion. In the homologous mouse brain, the same murine embryonic stem cells did not migrate, but produced highly malignant teratocarcinomas at the site of implantation, independent of whether they were predifferentiated in vitro to neural progenitor cells. The authors demonstrated a hitherto unrecognized inverse outcome after xenotransplantation and homologous transplantation of embryonic stem cells, which raises concerns about safety provisions when the therapeutical potential of human embryonic stem cells is tested in preclinical animal models.

HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53.

Abstract: The RING finger proteins HdmX and Hdm2 share significant structural and functional similarity. Hdm2 is a member of the RING finger family of ubiquitin-protein ligases E3 and targets the tumor suppressor protein p53 for degradation. Although HdmX also binds to p53, HdmX does not induce p53 degradation. Moreover, HdmX has been reported to interfere with p53 degradation in overexpression experiments. To obtain insight into the mechanism by which HdmX interferes with p53 degradation, we studied the effect of HdmX on the E3 activity of Hdm2 in vitro. Surprisingly, this revealed that HdmX stimulates Hdm2-mediated ubiquitination of p53 and that HdmX facilitates ubiquitination of Hdm2 and vice versa. In addition, down-regulation of HdmX expression within cells results in the accumulation of both p53 and Hdm2. Because HdmX alone does not have appreciable E3 activity, these data indicate that HdmX acts as a stimulator, rather than as an inhibitor, of the E3 activity of Hdm2 and that, at least under certain conditions, HdmX is actively involved in the degradation of both p53 and Hdm2.

Outcome in psychogenic nonepileptic seizures: 1 to 10-year follow-up in 164 patients.

Abstract: Our knowledge of longer term outcome in psychogenic nonepileptic seizures (PNESs) patients is limited; we know less still about factors predicting prognosis. This study was intended to describe outcome in a large cohort and to identify predictive clinical and psychological factors to generate new ideas for treatment. One hundred sixty-four adult patients with PNESs (66.7%) responded to outcome, personality, and psychosymptomatology questionnaires (Dimensional Assessment of Personality Pathology-Basic Questionnaire [DAPP-BQ], Dissociative Experiences Scale, and Screening Test for Somatoform Symptoms) a mean of 11.9 years after manifestation and 4.1 years after diagnosis of PNES. Additional clinical data were retrieved from hospital records. The responses showed that 71.2% of patients continued to have seizures and 56.4% were dependent on social security. Dependence increased with follow-up. Outcome was better in patients with greater educational attainments, younger onset and diagnosis, attacks with less dramatic features, fewer additional somatoform complaints, and lower dissociation scores. Better outcome was associated with lower scores of the higher order personality dimensions "inhibitedness," "emotional dysregulation," and "compulsivity" but not "dissocial behavior" (DAPP-BQ). Outcome in PNESs is poor but variable. Clinical and personality factors can be used to provide an individualized prognosis. By generating a patient-specific profile, they show particular maladaptive traits or tendencies that can identify goals for psychological therapy.

The Arteriovenous Fistula

Abstract: The ground-breaking article by Brescia and Cimino in 1966 ([1][1]) revolutionized the creation of the vascular access, and the Cimino fistula was soon used in almost all dialysis patients. Unfortunately, subsequent wide-spread use of PTFE grafts instead of AV fistulae occurred because of the ease of

Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities.

Abstract: Background.We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients in the US Prospective surveillance for nosocomial bloodstream infections at 49 hospitals during a 6-year period [Surveillance and Control of Pathogens of Epi

SMEs, co-opetition and knowledge sharing: the role of information systems

Abstract: Co-opetition, simultaneous cooperation and competition, is a recent phenomenon. Co-opetition entails sharing knowledge that may be a key source of competitive advantage. Yet, the knowledge gained by cooperation may also be used for competition. However, there is little investigation of how this problem may be modelled and, hence, managed. A game-theoretic framework for analysing interorganisational knowledge sharing under co-opetition and guidelines for the management of explicit knowledge predicated on coordination and control theory has been proposed, but remains untested. This research empirically investigates these issues in the context of small and medium-sized enterprises (SMEs). SMEs provide an interesting setting as they are knowledge generators, but are poor at knowledge exploitation. The paper uses data from U.K. SMEs to investigate co-opetition, management of knowledge sharing and the role of IS.

Chapter 8: Human papillomavirus and skin cancer.

Abstract: A high prevalence of human papillomavirus (HPV) DNA, particularly in squamous cell skin carcinoma of immunosuppressed but also of immunocompetent patients, has renewed great interest in a possible etiologic role of HPV in nonmelanoma skin cancer. It is difficult, however, to interpret these findings against a background of low-level infections with multiple HPV types from supergroup B (HPV4-related and epidermodysplasia verruciformis [EV] HPV), probably acquired by everyone early in and throughout life. Thus far, no high-risk HPV types have been identified. Because of the low copy numbers of HPV DNA in skin cancers, probably not every tumor cell contains a viral genome, which is compatible with cutaneous HPV being possibly important for tumor initiation and progression, but not for maintenance of the malignant phenotype. The question with regard to high-risk types should, therefore, be readdressed in case-control studies on the basis of serology, which can reveal viral activities over years. The viruses lingering in all people are apparently activated by sunlight (UV) exposure, by immunosuppression, and by hyperproliferation of the epithelium (psoriasis) and/or in the specific genetic background of the host (EV). It is intriguing that most of these factors are established risk factors in skin carcinogenesis. The weak transforming activity of cutaneous HPV in vitro compared with the transforming activity of genital HPV may explain the need for activators and synergistic factors. The antiapoptotic activities of E6 proteins of cutaneous HPV could be relevant to oncogenesis in the interplay with UV exposure. Prospective studies should determine the kinetics of HPV activation relative to tumor development.

Late and Multiple Bidding in Second Price Internet Auctions: Theory and Evidence Concerning Different Rules for Ending an Auction

Abstract: In second price internet auctions with a fixed end time, such as those on eBay, many bidders "snipe", i.e., they submit their bids in the closing minutes or seconds of an auction. Late bids of this sort are much less frequent in auctions that are automatically extended if a bid is submitted very late, as in auctions conducted on Amazon. We propose a model of second price internet auctions, in which very late bids have a positive probability of not being successfully submitted, and show that sniping in a fixed deadline auction can occur even at equilibrium in auctions with private values, as well as in auctions with uncertain, dependent values. Sniping in fixed-deadline auctions also arises out of equilibrium, as a best reply to incremental bidding. However, the strategic advantages of sniping are eliminated or severely attenuated in auctions that apply the automatic extension rule. The strategic differences in the auction rules are reflected in the field data. There is more sniping on eBay than on Amazon, and this difference grows with experience. We also study the incidence of multiple bidding, and its relation to late bidding. It appears that one substantial cause of late bidding is as a strategic response to incremental bidding.