Humoral and cellular immunopathology of hepatic and cardiac hamster-into-rat xenograft rejection: Marked stimulation of IgM^++bright/IgD^+dull splenic B cells

Normal Lewis rat serum contains antibodies (IgM > IgG) that bind to hamster leukocytes and endothelial cells. Transplantation of either the heart or liver from hamster rat results in release of hamster hematolymphoid cells from the graft, which lodge in the recipient spleen (cell migration), where recipient T- and B-cell populations initiate DNA synthesis within one day. There is marked stimulation of splenic IgM++(bright)/IgD+(dull) B cells in the marginal zone and red pulp, which account for 48% of the total splenic blast cell population by 4 days after liver transplantation. CD4+ predominant T-cell proliferation in the splenic periarterial lymphatic sheath and paracortex of peripheral lymph nodes occurs almost simultaneously. The effector phase of rejection in cardiac recipients is dominated by complement-fixing IgM antibodies, which increase daily and result in graft destruction in 3 to 4 days, even in animals treated with FK506. In liver recipients, combined antibody and cellular rejection, associated with graft infiltration by OX8+ natural killer, and fewer W3/25+ (CD4) lymphocytes, are responsible for graft failure in untreated recipients at 6 to 7 days. FK506 inhibits the T-cell response in liver recipients and significantly prolongs graft survival, but does not prevent the rise or deposition of IgM antibodies in the graft. However, a single injection of cyclophosphamide 10 days before transplantation effectively depletes the splenic IgM++(bright)/IgD+(dull) cells and in combination with FK506, results in 100% survival of both cardiac and hepatic xenografts for more than 60 days. Although extrapolation of morphological findings to functional significance is fraught with potential problems, we propose the following mechanisms of xenograft rejection. The reaction initially appears to involve primitive host defense mechanisms, including an IgM-producing subpopulation of splenic B cells and natural killer cells. Based on the reaction and distribution of OX8+ and W3/25+ cells, antibody dependent cell cytotoxicity and delayed-type hypersensitivity responses seem worthy of further investigation as possible effector mechanisms. Effective control of xenograft rejection is likely to require a dual pharmaceutical approach, one to contain T-cell immunity and another to blunt the primitive B-cell response

Resonant Processes in a Frozen Gas

We present a theory of resonant processes in a frozen gas of atoms interacting via dipole-dipole potentials that vary as $r^{-3}$, where $r$ is the interatomic separation. We supply an exact result for a single atom in a given state interacting resonantly with a random gas of atoms in a different state. The time development of the transition process is calculated both on- and off-resonance, and the linewidth with respect to detuning is obtained as a function of time $t$. We introduce a random spin Hamiltonian to model a dense system of resonators and show how it reduces to the previous model in the limit of a sparse system. We derive approximate equations for the average effective spin, and we use them to model the behavior seen in the experiments of Anderson et al. and Lowell et al. The approach to equilibrium is found to be proportional to $\exp (-\sqrt{\gamma_{eq}t}$), where the constant $\gamma _{eq}$ is explicitly related to the system's parameters.Comment: 30 pages, 6 figure

Evolution of Conversations in the Age of Email Overload

Email is a ubiquitous communications tool in the workplace and plays an important role in social interactions. Previous studies of email were largely based on surveys and limited to relatively small populations of email users within organizations. In this paper, we report results of a large-scale study of more than 2 million users exchanging 16 billion emails over several months. We quantitatively characterize the replying behavior in conversations within pairs of users. In particular, we study the time it takes the user to reply to a received message and the length of the reply sent. We consider a variety of factors that affect the reply time and length, such as the stage of the conversation, user demographics, and use of portable devices. In addition, we study how increasing load affects emailing behavior. We find that as users receive more email messages in a day, they reply to a smaller fraction of them, using shorter replies. However, their responsiveness remains intact, and they may even reply to emails faster. Finally, we predict the time to reply, length of reply, and whether the reply ends a conversation. We demonstrate considerable improvement over the baseline in all three prediction tasks, showing the significant role that the factors that we uncover play, in determining replying behavior. We rank these factors based on their predictive power. Our findings have important implications for understanding human behavior and designing better email management applications for tasks like ranking unread emails.Comment: 11 page, 24th International World Wide Web Conferenc

Flux profile scanners for scattered high-energy electrons

The paper describes the design and performance of flux integrating Cherenkov scanners with air-core reflecting light guides used in a high-energy, high-flux electron scattering experiment at the Stanford Linear Accelerator Center. The scanners were highly radiation resistant and provided a good signal to background ratio leading to very good spatial resolution of the scattered electron flux profile scans.Comment: 22 pages, 17 figure

The clinical translation of plastic scintillation dosimetry

Contemporary radiotherapy focuses on achieving the best patient outcomes by delivering highly targeted treatments that often include small fields and high dose gradients. Plastic scintillators outperform traditional dosimeters in these fields as they are close to water-equivalent. However, the translation of scintillation dosimeters into the clinic has been limited by three roadblocks. The generation of Cerenkov radiation in an optic fibre irradiated by megavoltage radiation contaminates the scintillation signal. Two Cerenkov removal methods (spectral discrimination and air core) were found to be accurate in accounting for Cerenkov radiation and their clinical robustness was improved. The light readout system is often the limiting factor for the accuracy of scintillators. PMTs outperform camera-based systems, though their implementation for array dosimetry is complex. A novel system with a multianode PMT was constructed and enabled multiple light signals from an array to be simultaneously measured. Arrays of scintillation dosimeters are difficult to create due to the complex arrangement of detectors and their optical pathways. Two innovative approaches (square waveguides and 3D printing) were used to build prototype scintillation dosimeter arrays. These arrays showed that scintillation dosimeters can measure dose distributions with high spatial and temporal resolution. Addressing these roadblocks has enabled the clinical translation of scintillation dosimeters. In small field dosimetry, an air core dosimeter was used as a reference to calculate and predict correction factors for existing dosimeters. For brachytherapy, an array of scintillators provided real-time dose measurements that improved the safety of the treatment. For rotational treatments, a cylindrical array was used to verify the dose delivered during simulated stereotactic treatments. Traditional dosimeters cannot be used in these applications and this demonstrates the potential of scintillation dosimetry

Chronic Obstructive Pulmonary Disease and Lung Cancer: A Review for Clinicians

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are common global causes of morbidity and mortality. Because both diseases share several predisposing risks, the two diseases may occur concurrently in susceptible individuals. The diagnosis of COPD has important implications for the diagnostic approach and treatment options if lesions concerning for LC are identified during screening. Importantly, the presence of COPD has significant implications on prognosis and management of patients with LC. In this monograph, we review the mechanistic linkage between LC and COPD, the impact of LC screening in patients at risk, and the implications of the presence of COPD on the approach to the diagnosis and treatment of LC. This manuscript succinctly reviews the epidemiology and common pathogenetic factors for the concurrence of COPD and LC. Importantly for the clinician, it summarizes the indications, benefits, and complications of LC screening in patients with COPD, and the assessment of risk factors for patients with COPD undergoing consideration of various treatment options for LC