cssi/SciSciGPT-SciSciNet huggingface dataset:
638 Plasma proteome analysis in patients with immune checkpoint inhibitors related arthritis and pneumonitis

Background Immune checkpoint inhibitors (ICIs) have resulted in unprecedented advances in the treatment of cancer. By disinhibiting the immune system, they enhance anti-tumor immunity, but provoke off-target inflammatory and immune-related adverse events (irAEs) which can seriously impact morbidity and mortality. The exact immunobiology of irAEs is not completely understood, but may involve specific immune pathways. To date, there is no validated biomarker test to predict the development of irAEs in patients treated with ICIs. Methods To identify possible biomarkers of irAEs, we performed in-depth proteomic profiling of blood samples obtained from cancer patients receiving ICIs. The plasmas were processed with Hu-14 immuno-depletion column (Agilent Technologies) and the samples were labeled with TMT (Thermo Scientific). The proteins were next pre-fractionated with HPLC, trypsin digested and analyzed by nanoAQUITY LC coupled Synapt G2-Si ion-mobility mass spectrometry (WATERS). Results A total of 12 patients were enrolled in the study; all were receiving anti-programmed cell death-1 (PD-1) agents. Cancer types included melanoma (n=9), renal cell carcinoma (n=2), and non-small cell lung cancer (n=1). Eight patients had irAEs with active toxicity symptoms at blood draw (4 with pneumonitis-irAE and 4 with arthritis-irAE); 6 of those patients were receiving corticosteroids (ranging from 5 to 60 mg/d), and 1 was receiving tocilizumab (an anti-IL-6 receptor antibody). Four patients who completed a minimum of one year of anti-PD1 treatments without irAEs were enrolled as control group. Median time from ICI initiation until blood draw was 16 months (range, 4–31) among patients with irAEs and 23 months (range, 17–28) among controls.We identified 925 protein gene products from 2.5 million mass spectra that can cover 107 dynamic range of plasma proteins. Among them, 19 proteins showed statistically significant differences between patients with and without irAEs (P Conclusions In-depth plasma proteome analysis identified possible biomarkers of adverse events modulated by ICI treatment. We plan a prospective validation cohort study of melanoma patients initiating treatment with ICIs to further evaluate the potential clinical utility of the identified biomarkers and their association with immune toxicity, and tumor response to ICI therapy. Ethics Approval The study was approved by The Institutional Review Board at The University of Texas MD Anderson Cancer Center, approval number PA16-0928 Consent Written informed consent was obtained from all patients who agreed to participate in the study
The effect of incorporating an arterial pH target during apnea test for brain death determination

Persistent apnea despite an adequate rise in arterial pressure of CO2 is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO2 threshold) on brain death declarations. We performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed. Ninety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation [SD] 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17, p = 0.01), lower PaO2 (47 vs 145, p < 0.01), and a lower PaCO2 (55 vs 73, p = 0.01). Among patients with a positive AT using PaCO2 threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87). Implementing a BD criteria requiring both arterial pH and PaCO2 thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.
Does plain radiography still have a role in cases of fish bone ingestion in emergency rooms? A retrospective analysis

Fish bones are the most common aerodigestive foreign bodies found in adults. Most cases of fish bone impaction improve after primary management by emergency physicians with a mirror laryngoscopy using a tongue depressor, before otolaryngologists perform a fiberoptic nasendoscopy. A computed tomography scan usually follows to determine the next step. Studies have recently been concerned about overdoses of radiation from computed tomography. However, clear algorithms remain unavailable for fish bone ingestion management to date. A retrospective review was conducted on 180 patients who visited the emergency department with complaints of fish bone impaction between January 2017 and January 2019. A total of 81.6% of patients with fish bone impaction got symptomatic relief after primary management by emergency physicians and otolaryngologists. Out of 180 patients, 33 (18.3%) needed an endoscopic procedure due to persistent symptoms. Only one (0.56%) required an operation due to perforation. In the group failing primary management, the plain radiography of eight patients showed a positive finding and an esophagogastroscopy was done to remove the fish bones. Lateral neck radiography is still beneficial to patients with fish bone ingestion failure from primary management. Positive lateral soft tissue radiography in cases with persistent symptoms post primary management may directly suggest esophagogastroscopy without confirmation from a computed tomography, unless complications are suspected. For patients aged below 40, following up on their conditions after post management radiography shows negative results may increase their safety.
Exploring Cognitive Process in Extended Data Mining

With the growing popularity of big data and data mining research, the relationship between human cognition and data mining deserves a lot of attention, and it is an important aspect of technology on a human scale. In this paper, we examine this interesting issue. We first provide a brief review on selected work related to this topic and point out that there are several different aspects involved. The focus of this paper is on the human cognitive activities in the process of identifying and acquiring additional online resources for effective data mining (which is referred to as extended data mining). We present a detailed case study and report what we have learned from this process. Our experimental study shows that cognitive process in data mining is a rich research area to explore, and such kind of study will not only enhance the future practice of data mining, but also serve as an important step toward better understanding of man–machine symbiosis.
What is the mechanism behind biological ferroelectricity

Abstract Biological tissues are soft, amorphous and often appear to possess a high degree of material symmetry. This would appear to preclude a phenomenon like ferroelectricity which, in the world of hard materials, only occurs in selected crystalline materials that are non-centrosymmetric. Recent experiments, however, indicate the presence of ferroelectricity in soft biological entities such as the protein elastin—a large biopolymer found in the extracellular domains of most tissues. In this letter, we present a model and an explanation for this intriguing observation. Based on a very simple physical hypothesis, we develop an analytical statistical mechanics model that, coupled with insights from molecular dynamics, provides a plausible mechanism underpinning biological ferroelectricity. Furthermore, we predict for the first time, piezoelectric properties of tropoelastin, a precursor/monomer of elastin—properties that are not easily obtained from experiments. Specifically we find that the piezoelectric constant of tropoelastin is larger than any known polymer.
A family of model problems in plasticity

We look for the simplest configuration which will lead to the problems most characteristic of plasticity—the contrast between incremental flow laws and deformation theory, and between the collapse of a perfectly plastic structure and its continued stresses and strains when hardening is allowed. The problems are to be continuous rather than discrete, and not one-dimensional; they will be governed by linear partial differential equations with inequality constraints. Each has a primal form in which the stresses are the unknowns, and a dual in terms of velocities or displacements. Our main goal is to clarify these different possibilities, in the case known as antiplane shear.
Trichinella spiralis (Railliet 1896)

Trichinella spiralis is capable of infecting all mammals. The disease it causes is referred to as trichinellosis. Some 10 million to 15 million people in North America are infected with T. spiralis.1 Its prevalence is also high in Europe and in Asia, and there have even been epidemics in Japan and China.2 The infection has been diagnosed in most parts of the world, with Puerto Rico and Australia among the exceptions.
Metabolism of dihalomethanes to formaldehyde and inorganic halide--II. Studies on the mechanism of the reaction.

Abstract Metabolism of dihalomethanes by rat liver cytosol fractions yielded formaldehyde and inorganic halide as products. Glutathione is a known cofactor in this reaction. The first step in the reaction appears to be an enzyme catalyzed nucleophilic attack by glutathione on the dihalomethane. The expected product of this reaction would be an S -halomethyl glutathione intermediate which should undergo a rapid hydrolysis to yield S -hydroxymethyl glutathione. This compound is the hemimercaptal of formaldehyde and glutathione and provides a mechanism for the formation of formaldehyde from dihalomethanes. Glutathione is required by this mechanism but is not consumed, and no primary isotope effect was seen when d 2 -dibromomethane was used. S -hydroxymethyl glutathione is known to serve as a substrate for hepatic NAD + -dependent formaldehyde dehydrogenase. This enzyme converts the hemimercaptal of glutathione and formaldehyde (S-hydroxy-methyl glutathione) to S -formyl glutathione which is enzymatically hydrolyzed to yield formic acid and glutathione. Thus, addition of NAD + decreased formaldehyde yields with a concomitant increase in formic acid production. Enzyme fractionation studies further substantiate the role of formaldehyde dehydrogenase in this biotransformation.
Historicism, Originalism and the Constitution: The Use and Abuse of the Past in American Jurisprudence

The following is the Preface to "Historicism, Originalism and the Constitution." The publisher's description is as follows: The use of history in law is a time honored tradition. Over the years the practice has assumed many forms, including historicism, intentionalism, interpretivist history, law office history, historical narrative, originalism, etc. This book picks up where past commentators have left off in this time honored debate. The different historically based approaches to adjudicating constitutional questions are weighed and considered, particularly originalism, and asserts that history in law is only legitimate if it leads to accurate results. The book then proposes an approach to accomplish the objectives of historical accuracy and objectivity, and therefore legitimacy. Known as the historical guidepost approach, it respects historical methodologies, places text and events in their historical context, is honest about what the evidentiary record does and does not provide, mitigates judicial mythmaking, and applies history as more of a guide to legal reasoning than a strict outcome-determinative tool.
Challenges for the prediction of solder joint life in long term vibration

In the absence of manufacturing defects the ultimate life of a microelectronics assembly in long-term vibration is likely to be limited by solder joint fatigue. So far relatively limited efforts have been dedicated to the quantitative prediction of this life. However, even day to day ‘engineering tests’ may not be very useful if they do not offer at least a ranking of alternative materials, designs or processes in terms of performance in service.
Experiential Learning: Improving The Efficacy Of An Undergraduate Business Degree

This article deals with a subject that is extremely important to the success of future graduates of any college or University – specifically Critical Thinking and Decision Making. Our article explains the research results and observations of critical thinking research conducted at two different colleges in the fall semester of 2011. The research prompts were used at two different colleges (Wagner College and Monmouth University) with different student profiles during the same semester. The purpose of the research was to test how critical thinking skills were affected by two different experiential programs and how “Ex-Ed” is a critical part of a student’s total education. Experimental Education (Ex-Ed) is a very hot topic among academics these days and our research at Wagner College involved testing the improvement in critical thinking skills in a “marketing incubator” system during a Consumer Behavior class with 34 registered students in the fall semester in 2011. In this case, some of the students participated in the marketing incubator (18), while some did not (16), essentially providing a control groups for comparison. At Monmouth University, the research was testing the improvement in critical thinking skills in two entrepreneurial studies classes with a total of 67 students. Qualitative observations are included as the research is conducted, and suggestions for future related research are proposed. Our feeling is that to form a definitive conclusion, the subsequent research needs to be done in the area of both decision making and the creation of a value proposition.
Paranemin and the organization of desmin filament networks

De novo expression of vimentin, GFAP or peripherin leads to the assembly of an extended intermediate filament network in intermediate filament-free SW13/cl.2 cells. Desmin, in contrast, does not form extended filament networks in either SW13/cl.2 or intermediate filament-free mouse fibroblasts. Rather, desmin formed short thickened filamentous structures and prominent spot-like cytoplasmic aggregates that were composed of densely packed 9-11 nm diameter filaments. Analysis of stably transfected cell lines indicates that the inability of desmin to form extended networks is not due to a difference in the level of transgene expression. Nestin, paranemin and synemin are large intermediate filament proteins that coassemble with desmin in muscle cells. Although each of these large intermediate filament proteins colocalized with desmin when coexpressed in SW-13 cells, expression of paranemin, but not synemin or nestin, led to the formation of an extended desmin network. A similar rescue of desmin network organization was observed when desmin was coexpressed with vimentin, which coassembles with desmin, or with keratins, which formed a distinct filament network. These studies demonstrate that desmin filaments differ in their organizational properties from the other vimentin-like intermediate filament proteins and appear to depend upon coassembly with paranemin, at least when they are expressed in non-muscle cells, in order to form an extended filament network.
Updated ice core record captures industrial era carbon variability

In 1999, researchers published data from ice cores collected at Law Dome, a research site in East Antarctica. These data are distinguished by their high time resolution and by their overlap with modern measurements, providing one of the most important records of how the atmosphere's chemical composition changed over the past 1000 years. Air trapped in bubbles in the ice core let researchers measure the concentration of carbon dioxide and other gases and analyze the ratio of carbon-13 to carbon-12 isotopes in the atmospheric carbon dioxide. Burning fossil fuel releases carbon dioxide that is depleted in carbon-13 isotopes, and the Law Dome record provided evidence that modern increases in atmospheric carbon dioxide are due to anthropogenic activity. In a new study, Rubino et al., a team that includes some of the authors from the original analysis, use novel tools and techniques to update their ice core record.
Effects of short-term ozone exposure on net photosynthesis, dark respiration, and transpiration of three eastern white pine clones

Abstract Net photosynthesis, dark respiration, and transpiration rates were determined during ozone (O 3 ) exposure for three clones of eastern white pine ( Pinus strobus L.) differing in sensitivity to O 3 . Fumigations for 4 h with 0.10, 0.20, and 0.30 μL/L O 3 inhibited net photosynthesis of all three clones. Light transpiration was inhibited in both the sensitive and the tolerant clones and was not affected in the intermediate clone. Recovery of net photosynthesis and light transpiration occurred 1 h after the termination of ozonation, with the degree of recovery depending upon clonal sensitivity to O 3 and the O 3 concentration used. Dark respiration increased in the O 3 -sensitive clone only, and dark transpiration was unaffected in all three clones after 4-h exposure to 0.30 μL/L O 3 . Ozone-induced inhibition of net photosynthesis and stimulation of dark respiration are discussed in relation to clonal sensitivity to O 3 .
Waniyetu Wówapi: Native American Records of Weather and Climate

Pictographic calendars called waniyetu wowapi or “winter counts” kept by several Great Plains Indian cultures (principally the Sioux or Lakota) preserve a record of events important to these peoples from roughly the seventeenth through the nineteenth centuries. A number of these memorable events include natural phenomena, such as meteor storms, eclipses, and unusual weather and climate. Examination of a selection of the available winter count records and related interpretive writings indicates that the Lakota and other native plains cultures recorded many instances of unusual weather or climate and associated impacts. An analysis of the winter count records in conjunction with observational and proxy climate records and other historical documentation suggests that the winter counts preserve a unique record of some of the most unusual and severe climate events of the early American period and provide valuable insight into the impacts upon people and their perceptions of such events in the ethnographically ...
Estrogen receptor pathways in lung cancer.

Lung cancer is the leading cause of death from neoplasia in men and women in the United States. Some studies suggest that women are more susceptible than men to tobaccoinduced carcinogenesis and may show higher risk than men for lung cancer development from smoking. More recently, increasing biochemical and genetic data have supported this male-female difference in response to tobacco. Estrogens may be involved in lung carcinogenesis, and estrogen receptors (ERs), mainly ERâ, are present and functional in normal lung and tumor cell lines and tissues. Estrogen can directly stimulate the transcription of estrogen-responsive genes in the nucleus of lung cells, and it can also transactivate growth factor signaling pathways, in particular the epidermal growth factor pathway. Lung cancer patients currently have few effective therapeutic options. An understanding of these new developments in estrogen signaling and crosstalk pathways may pave the way for innovative combinatorial approaches for treatment of lung cancer and possibly chemoprevention.
Dynamic aspects regarding the mechanical behavior of multilayered thin films and their measurements

Abstract The dynamic aspects of the mechanical properties of multilayered thin films are reviewed. Such aspects can affect the measurement of ostensibly “static” properties such as Young’s modulus, and can also result in novel “dynamic” properties such as an enhanced internal friction and increased fatigue resistance.
Web-Based Machine Translation as a Tool for Promoting Electronic Literacy and Language Awareness

This article addresses a pervasive problem of concern to teachers of many foreign languages: the use of Web-Based Machine Translation (WBMT) by students who do not understand the complexities of this relatively new tool. Although networked technologies have greatly increased access to many language and communication tools, WBMT is still ineffective for translating text into another language, especially when the user of the software is not able to make grammaticality and acceptability judgments in the target language. This article explains some specific limitations of WBMT (with examples from French) and provides a pedagogical plan for teachers to present this tool to students in order to promote language awareness and electronic literacy, which could help reduce the widespread misuse of this tool by students.
ATC Beacon Interference Characteristics in the New York Area

An experimental program is described that had the objective of measuring the effects of the time-dependent structure of downlink (air craft to ground) interference generated by the Air Traffic Control Radar Beacon System (ATCRBS) in an active air traffic terminal area that are relevant to system and ground controller response time. The results of this program indicate a number of interesting details concerning the correlation of the level of the downlink interference with changes in the arrival and departure rates of aircraft at the local terminal sites.
Time dependent changes in anterograde scopolamine-induced amnesia in rats

These experiments studied the effect of scopolamine on memory formation and subsequent memory recall. Different groups of rats were trained on a Y-maze brightness discrimination task 20 min after IP injection of 2 mg/kg scopolamine HBr, an anticholinergic. Retention tests were then conducted 1 day or 2, 4, or 6 weeks after training. Deficits in retention performance were observed at 1 day and 2 weeks after training but not at the longer intervals. In addition, other rats were trained in the same manner and after the same dose of scopolamine but were then retention tested 20 min after 0.5 mg/kg physostigmine salicylate, a cholinesterase inhibitor. These subjects also showed deficits at 1 day and 2 weeks but were not different from controls at the longer intervals. Amnesia was not, however, produced after treatment with scopolamine methyl nitrate or by injections of scopolamine HBr administered immediately after training. These results suggest that scopolamine, present in the central nervous system during training or within the first few moments thereafter, modifies the formation of the memory trace in such a way that memory is not available for recall for a period of weeks.
Protein domain mapping by λ phage display: The minimal lactose-binding domain of galectin-3

Mapping of protein domains having a distinct function is essential to understanding the protein's structure–function relationship. We used a bacteriophage λ surface expression vector, λfoo, in order to determine the minimal carbohydrate-binding domain of human galectin-3 (Gal-3). Gal-3 cDNA was randomly digested by DNase I and cloned into the phage vector. The library generated was screened by affinity selection using lactose immobilized on agarose beads. DNA sequence analysis of a set of isolated clones defined the minimal folding domain of Gal-3 required for lactose binding, which consisted of 136 amino-acid residues. Using the phage clones isolated, we also determined relative dissociation constants in solution between lactose and the minimal domain expressed on the phage surface. This technique does not require either purified or labeled proteins, and bacteriophage λ surface display may, therefore, be useful for protein domain mapping and in vitro studies of various macromolecular interactions.
Adaptively Localized Continuation-Newton Method—Nonlinear Solvers That Converge All the Time

Summary Growing interest in understanding, predicting, and controlling advanced oil-recovery methods emphasizes the importance of numerical methods that exploit the nature of the underlying physics. The fully implicit method offers unconditional stability of the discrete approximations. This stability comes at the expense of transferring the inherent physical stiffness onto the coupled nonlinear residual equations that are solved at each timestep. Current reservoir simulators apply safeguarded variants of Newton’s method that can neither guarantee convergence nor provide estimates of the relation between convergence rate and timestep size. In practice, timestep chops become necessary and are guided heuristically. With growing complexity, such as in thermally reactive compositional flows, convergence difficulties can lead to substantial losses in computational effort and prohibitively small timesteps. We establish an alternative class of nonlinear iteration that converges and associates a timestep to each iteration. Moreover, the linear solution process within each iteration is performed locally. By casting the nonlinear residual equations for a given timestep as an initial-value problem, we formulate a continuation-based solution process that associates a timestep size with each iteration. Subsequently, no iterations are wasted and a solution is always attainable. Moreover, we show that the rate of progression is as rapid as that for a convergent standard Newton method. Moreover, by exploiting the local nature of nonlinear wave propagation typical to multiphase-flow problems, we establish a linear solution process that performs computation only where necessary. That is, given a linear convergence tolerance, we identify a minimal subset of solution components that will change by more than the specified tolerance. Using this a priori criterion, each linear step solves a reduced system of equations. Several challenging examples are presented, and the results demonstrate the robustness and computational efficiency of the proposed method.
Orbital mapping of the lunar magnetic field.

Magnetometer data obtained during the first four lunations after the deployment of the Apollo 15 subsatellite have been used to construct contour maps of the lunar magnetic field referred to 100 km altitude. These contour maps cover a relatively small band on the lunar surface. Within the region covered there is a marked near side-far side asymmetry. The near-side field is generally weaker and less structured than the far-side field. The strongest intrinsic lunar magnetic field detected is between the craters Van de Graaff and Aitken, centered at 20°S and 172°E. The variation in field strength with altitude for this feature suggests that its scale size is on the order of 80 km. A magnetization contrast between this region and its surroundings of the order of 6 × 10−5 emu-cm−3 is obtained assuming a 10-km thick slab. Preliminary Apollo 16 magnetometer data at extremely low altitude (0 to 10 km) show a very structured magnetic field with field strengths up to 56γ. Large compressions in the magnetic field magnitude, just above the lunar limb regions, are occasionally detected when the Moon is in the solar wind. The occurrence of limb compressions is strongly dependent on the selenographic coordinates of the lunar region on the solar wind terminator beneath the orbit of the sub-satellite. The discovery of remanent magnetization of varying strength over much of the lunar surface and its correlation with limb compression source regions supports the hypothesis that limb compressions are due to the deflection of the solar wind by regions of strong magnetization at the lunar limbs. If this hypothesis is correct, then the map of lunar regions associated with compressions indicates that the northerly equatorial region on the far side is less strongly magnetized than the southerly equatorial region on the far side.
Trace amines and cocaine abuse.

Cocaine addiction remains a clinical challenge with no effective pharmacotherapy available. Trace amine associated receptor (TAAR) 1 represents a promising drug target for the modulation of dopaminergic system and stimulant abuse. This Viewpoint discusses the emerging data which strongly suggest that TAAR 1 functions as a molecular “brake” that controls the addiction-related effects of cocaine and could be a novel drug target for the development of efficacious pharmacotherapy to treat cocaine addiction.
The Cross System Product application generator: an evolution

An application generator is a generalized application development tool with which professional programmers develop applications using a fourth-generation language. This paper describes the requirements that led to the Cross System Product application generator, and how the product progressed from a single-environment product to the current multienvironment product. Also described are how the Cross System Product fits within Systems Application Architecture and how that may affect the future of the Cross System Product.
From clinical trials to public health policy: the path from imaging to screening

T abundance of new health-care technology is among the greatest achievements in today’s stateof-the-art field of cardiovascular medicine. Marked reductions in mortality have directly resulted from improved treatment and use of an array of imaging modalities in cardiovascular medicine.1 Although several available modalities are used for the assessment of ischemia in treating obstructive coronary disease, recent developments in imaging have focused on risk markers for the development of subclinical disease. Electron-beam computed tomography (EBCT) is such a modality and has been advocated as a new diagnostic test and screening tool over the past decade.2 Other imaging modalities that have been used for atherosclerosis detection include magnetic resonance imaging, intravascular ultrasound, and carotid ultrasound.
Gamma-interferon administration after 90yttrium radiolabeled antibody therapy: Survival and hematopoietic toxicity studies

Purpose: Hematopoietic toxicity is the dose-limiting factor for radioimmunotherapeutic regimens. Cytokines have been shown to decrease hematopoietic toxicity in animals exposed to whole-body irradiation. The purpose of this study was to investigate the effects of murine gamma-interferon (γ-IFN) on survival and hematopoietic toxicity in mice treated with high dose 90 yttrium labeled anticarcinoembryonic antigen (CEA) monoclonal antibody. Methods and Materials: Balb/c nu/nu mice were injected intravenously with 250 Ci 90 Y-T84.66 (a murine anti-CEA monoclonal antibody). Thirty thousand units of γ-IFN was administered IV 24 h later. Control mice received either 250 Ci 90 Y-T84.66 alone or 30,000 units γ-IFN alone. Survival, antibody biodistribution, and bone marrow histologic studies were then performed. Results: Only 7% of the animals treated with 90 Y-T84.66 survived up to 40 days posttreatment, when the study was terminated. In contrast, 52% of the mice treated with both 90 Y-T84.66 and γ-IFN survived 40 days posttherapy. No toxic deaths were seen in the control group administered γ-interferon alone. Histologic examination of the bone marrow of animals receiving 90 Y-T84.66 and γ-IFN showed cellular depletion of 40-70% of the hematopoietic cells by 48 h. Cell depletion was 50-70% and 20% by 72 h and 8 days posttherapy, respectively. The marrow of the 90 Y-T84.66-treated control group was depleted to a level of 50-80% at 48 h, and remained depleted at 90% at 72 h and 8 days posttherapy. No marrow cell reduction was seen in the γ-IFN-only treated group. Biodistribution studies showed no alterations in antibody biodistribution or kinetics that could account for the changes in bone marrow toxicity after γ-IFN. Conclusion: These results demonstrate that γ-IFN can reduce the hematologic toxicity resulting from high dose radioimmunotherapy. Histologic studies of bone marrow suggest that γ-IFN acts primarily to accelerate myelorestoration of the bone marrow. Further studies exploring the use of γ-IFN as an adjunct to radioimmunotherapy are therefore warranted
Determination of junction avidity of cytolytic T cell and target cell

A direct measurement of the avidity of the junction between a cytotoxic T lymphocyte and its target cell was achieved by using a biophysical approach. A micromanipulation technique was used to determine the force required to separate a cytotoxic T cell (human clone F1, with specificity for HLA-DRw6) from its specific target cell (JY: HLA-A2, -B7, -DR4, w6) prior to delivery of the lethal hit. The force required to separate the F1-JY pair is 1.5 X 10(4) dynes per square centimeter. This junction avidity for F1-JY pairs is 6 to 13 times greater than that for F1-F1 and JY-JY pairs; the F1-JY conjugate requires a stronger separating force and is more easily rejoined than the homologous cell pairs. This study provides an estimate of the avidity of cytotoxic T cells for their target cells and insights into the biophysical correlates of the molecular complexes formed in the interaction of cytotoxic T cells and their targets during the cytotoxic process.
Morphologic correlates of coronary angiographic patterns at the site of percutaneous transluminal coronary angioplasty

Over the last 10 years considerable interest has been paid in the angiographic recognition of successful percutaneous transluminal coronary artery angioplasty (PTCA), complication of the technique, and angiographic predictors of restenosis. This report summarizes various angiographic patterns visualized at the site of angioplasty and correlates these patterns with morphologic findings. Of 66 patients undergoing PTCA for chronic or unstable angina pectoris, 76 PTCA sites were available for analysis. The two most common angiographic patterns at the angioplasty site (intimal flap = 43%, intraluminal haziness = 38%) correlated morphologically with intimal-medial splits with localized dissections (79%). Shallow, superficial intimal lesions, laminated thrombus, and adventitial tears accounted for the remaining morphologic changes. Eight PTCA sites without morphologic injury corresponded to smooth wall changes and spasm at angiography.
A practical hierarchical model of parallel computation I. The model

Abstract We introduce a model of parallel computation that retains the ideal properties of the PRAM by using it as a submodel, while simultaneously being more reflective of realistic parallel architectures by accounting for and providing abstract control over communication and synchronization costs. The Hierarchical PRAM (H-PRAM) model controls conceptual complexity in the face of asynchrony in two ways: First, by providing the simplifying assumption of synchronization to the design of subalgorithms, but allowing the subalgorithms to work asynchronously with each other, and by organizing this “control asynchrony” via an implicit hierarchy relation; Second, by restricting “communication asynchrony” in order to obtain determinate algorithms. It is shown that the model is reflective of a variety of existing and proposed parallel architectures, particularly ones that can support massive parallelism. Relationships to programming languages are discussed. Since the PRAM is a submodel, results that have been established with respect to the PRAM are transferable to this new model. The H-PRAM represents general degrees of locality (“neighborhoods” of activity) in problems, considering communication and synchronization simultaneously. This gives the potential of obtaining algorithms that map more efficiently to architectures, and of increasing the number of processors that can efficiently be used on a problem (in comparison to a PRAM that charges for communication and synchronization). The model presents a framework in which to study the extent that general locality can be exploited in parallel computing. A companion paper demonstrates the usage of the H-PRAM via the design and analysis of various algorithms for complete binary tree and FFT/butterfly graph structured computations.
AFM Studies of High-Generation PAMAM Dendrimers at the Liquid/Solid Interface

The structural distortion of high-generation poly(amidoamine) (PAMAM) dendrimers at the liquid/solid interface was investigated in situ using tapping mode atomic force microscopy (AFM). With a substantial compression along the surface normal but minor lateral expansion, isolated PAMAM dendrimers at the water/mica interface exhibit dimensions similar to those reported for the same species in dense, dried arrays, rather than those of isolated, dried units. On graphite substrates, adsorbed dendrimers exhibit weaker adhesion forces than on mica. AFM images of lower generation dendrimers at the water/graphite interface reveal additional features interpreted as large three-dimensional aggregates.
Ultrastructure of the ductus ejaculatoris duplex of the mediterranean flour moth, Anagasta Kühniella (Zeller) (Lepidoptera : Pyralidae)

Abstract The ductus ejaculatoris duplex serves as the major sperm storage organ in male Anagasta kuhniella (Zeller). The distribution of sperm is not uniform, however. Eupyrene sperm bundles remain near the openings of the vasa deferentia; individual apyrene sperm cells occur throughout the length of the 2 duplex arms. The duplex wall is composed of a columnar epithelium under rather thin layers of visceral muscle. In virgin males, the epithelial cells contain large numbers of dense secretory granules in and around the numerous Golgi complexes. Phagosomes are rather numerous near the apices of the cells, the apparent result of fusion of pinocytotic vesicles. After the duplex is emptied during mating, extensive apocrine and merocrine secretion occurs that results in the accumulation in the lumen of large numbers of dense granules within a mass of fibrous material thought to represent cell lysate formed during apocrine secretion. Pinocytotic activity and phagosome formation also increase greatly after mating. In virgin males there appears to be limited secretion of dense granules, but there is no evidence of apocrine secretion. The duplex secretions may have less to do with sperm storage as such than with the spatial distribution of the components of the semen and the events in the spermatophore after mating. Axons in the muscle layer contain large numbers of neurosecretory granules. Septa at either end of the duplex are composed in part of the secretory cells of the duplex and adjacent organs and in part of specialized partition cells.
Low temperature radiation pyrometry in industry.

Problems encountered in the application of radiation pyrometry in industry are discussed with particular emphasis being placed on the measurement of low surface temperatures (100–400°F). A low range radiation pyrometer for use on such applications is described.
Astrocyte membrane responses and potassium accumulation during neuronal activity

Older studies suggest that astrocytes act as potassium electrodes and depolarize with the potassium efflux accompanying neuronal activity. Newer studies suggest that astrocytes depolarize in response to neuronal glutamate release and the activity of electrogenic glial glutamate transporters, thus casting doubt on the fidelity with which astrocytes might sense extracellular potassium rises. Any K(+)-induced astrocyte depolarization might reflect a spatial buffering effect of astrocytes during neuronal activity. For these reasons, we studied stimulus-evoked currents in hippocampal CA1 astrocytes. Hippocampal astrocytes exhibited stimulus-evoked transient glutamate transporter currents and slower Ba(2+)-sensitive inward rectifier potassium (K(ir)) currents. In whole-cell astrocyte recordings, Ba(2+) blocked a very weakly rectifying component of the astrocyte membrane conductance. The slow stimulus-elicited current, like measurements from K(+)-sensitive electrodes under the same conditions, predicted small bulk [K(+)](o) increases (<0.5 mM) following the termination of short-stimulus trains. These currents indicate the potential for astrocyte spatial K(+) buffering. However, Ba(2+) did not significantly affect resting [K(+)](o) or the [K(+)](o) rises detected by the K(+)-sensitive electrode. To test whether local K(+) rises may be significantly higher than those detected by glial recordings or by K(+) electrodes, we assayed EPSCs and fiber volleys, two measures very sensitive to K(+) increases. We found that Ba(2+) had little effect on neuronal axonal or synaptic function during short-stimulus trains, indicating that K(ir)s do not influence local [K(+)](o) rises enough, under these conditions to affect synaptic transmission. In conclusion, our results indicate that hippocampal astrocytes are faithful sensors of [K(+)](o) rises, but we find little evidence for physiologically relevant spatial K(+) buffering during brief bursts of presynaptic activity.
Energetics of intercalation specificity. I. Backbone unwinding.

An empirical partitioned-potential function with optimized parameters was employed to investigate the basis of intercalation specificity recently observed by experimental techniques. The nature of this specificity is discussed in terms of component interactions for all non-truncated complementary dinucleoside triphosphate mini- (or miniature) helices. Our calculations agree with available evidence indicating the preference of Pyr(3′-5′)Pur sequences over Pur(3′-5′)Pyr sequences to change from the B-DNA to the intercalated conformation. Base–base (stacking) and base–phosphate interactions control the specificity. The extent of net electrostatic charge on the phosphate groups play an important but limited role in establishing the observed specificity. These results should apply for the class of aromatic agents involved in nonspecific intercalation with nucleic acids but not necessarily for aromatic agents involved in specific reactions with a particular nucleotide base.
Developmental changes in carbachol-stimulated inositolphosphate release in pigmented rat retina.

Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, ...
Isothermal and thermomechanical finite-element analysis of the tube drawing process using a fixed tapered plug

Quality is a very important feature in the manufacturing of products such as tube. Nonhomogeneous deformation, common to most metalforming operations, leaves the product in a cold worked state, resulting in a pattern of residual stresses. Depending on the nature and magnitude of residual stresses, they may be detrimental or beneficial to the strength and reliability of the product. To evaluate the residual stresses in the product, a complete stress analysis of the workpiece throughout the deformation history is required. In this study, a large deformation, nonlinear, elastic-plastic finite-element code was used to investigate the effect of friction, drawing speed, degree of plastic work (reduction in area), and the die/plug geometry on the extent of temperature increase, induced residual stresses, and the required drawing load in the drawing of oxygen-free high-conductivity (OFHC) copper tube using a fixed, tapered plug. Complete simulations of the tube drawing process were conducted by tracing its deformation history from the point at which it entered the die area until it exited the die. The resulting thermal effects were then used to determine the required drawing loads and induced residual stress distributions throughout the tube wall thickness. Similar simulations were conducted without taking into account the thermal effects. Equivalent plastic strain, equivalent stress, longitudinal stress, and circumferential residual stresses are presented and compared for both the isothermal and the thermally coupled analysis.
Endothelin receptor-mediated attenuation of carcinoma-induced nociception is opioid-dependent in mice

Author(s): Quang, Phuong Ngoc | Advisor(s): Damsky, Caroline; Schmidt, Brian L | Abstract: Cancer pain is a frequent and disabling consequence for many patients yet the mechanism of cancer pain remains unknown largely due to its complex etiology. The objective of this thesis work was to investigate the potential of a peptide produced by carcinoma cells, endothelin, as a novel target for cancer pain management. This study provided evidence in support of Hypothesis 1: Oral squamous carcinoma cells produce endogenous opioids in response to changes in endothelin-1 signaling. Effects of endothelin-1 (ET-1) signaling on secretion of opioids by oral squamous cell carcinoma (SCC) were studied in vitro. Oral SCC cell line HSC-3 produces abundant ET-1 that can act in both an autocrine or paracrine manner. In the untreated oral SCC cells, endogenous opioids were detected in both cultured media and cell lysates. When treated with Endothelin-A receptor antagonist, secreted levels of abeta-endorphin and leu-enkephalin were increased; whereas treatment with Endothelin-B receptor agonist increased production of only abeta-endorphin. This apparent regulation of endogenous opioid levels by endothelin receptor drugs in vitro procured evidence suggesting that Hypothesis 2: Endothelin-A receptor antagonist and Endothelin-B receptor agonist attenuate carcinoma-induced nociception in cancer animals through regulation of endogenous opioids. Endothelin-A (ET-AR) antagonism has been demonstrated previously to attenuate carcinoma-mediated hyperalgesia in an orthotopic cancer pain mouse model. In this study, effects of ET-BR agonist in vivo were evaluated and determined to also result in significant increase in paw withdrawal thresholds, indicating attenuation of cancer-induced nociception. When peripheral amu- or adelta-opioid receptor antagonists were administered following ET-AR antagonism, nociceptive attenuation was completely reversed. Attenuation from ET-BR agonism was likewise reversed upon administration of amu-opioid receptor antagonist. Combined results demonstrate that endogenous opioids are the likely mediators responsible for attenuation of carcinoma-induced nociception with either ET-AR antagonist or ET-BR agonist.These novel findings suggest that there exist innate modulation of pain by SCCs involving endogenous opioids that can be exploited through manipulation of endothelin activity in the cancer micro-environment. Regulation of ET-AR or ET-BR signaling may be targets for future innovations for cancer pain management.