cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract PL03-03: Taming the beast: Strategies to target the immune-suppressive macrophage to enhance cancer immune therapy

Advances in basic, translational and clinical research have revealed the power of cancer immune therapy. Checkpoint inhibitors and adoptive T cell therapies are novel, FDA approved therapeutic strategies that promote recruitment to and activation of tumor-reactive cytotoxic T cells. While promising, these strategies are not effective in all cancer patients, and resistance to therapy often develops. Recent advances in the study of the tumor microenvironment have revealed that tumor-associated myeloid cells accumulate rapidly in tumors where they promote resistance to checkpoint inhibitor therapy and adoptive T cell therapy, inhibit immune responses to tumor cells, and stimulate tumor progression. The most abundant of these myeloid cells, macrophages, usually serve as a first line of defense against pathogenic insults to tissues. These innate immune cells mount pro-inflammatory responses to pathogens and repair damaged tissues. However, in tumors, macrophages (TAMs) accumulate rapidly and potently suppress anti-tumor immunity and promote tumor progression. Preclinical studies have identified crucial pathways that regulate the recruitment, polarization, transcription and metabolism of TAMs during tumor progression. We have found that an isoform of PI3Kinase, PI3Kgamma, controls these pathways by activating mTORC1-mediated transcriptional and metabolic pathways that suppress cytotoxic T cell recruitment and activation. Targeting PI3Kgamma and its downstream effectors inhibits immune suppressive polarization and promotes NFkappaB activation and pro-inflammatory transcription in macrophages, thereby recruiting CD8+ T cells and stimulating T cell activation and memory. Novel therapeutics targeting PI3Kgamma stimulate cytotoxic T cell activation and recruitment and synergize with checkpoint inhibitors and chemotherapy in preclinical studies. Clinical trials with PI3Kgamma inhibitors such as IPI-549 (Infinity Pharmaceuticals) are currently underway and offer the promise of improved cancer outcomes for many tumor types. Citation Format: Judith A. Varner. Taming the beast: Strategies to target the immune-suppressive macrophage to enhance cancer immune therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr PL03-03.
Learning Curve of Zero Fluoroscopy

Catheter ablation of tachyarrhythmias without the use of fluoroscopy is, at present, performed only in a minority of laboratories. While the tools exist to allow fluoroless procedures in most instances, experience is lacking. While the learning curve will require time, and may slow the productivity of the lab down for a while, the benefits to both the patients and the staff are worth the investment. If one visits an experienced lab doing fluoroless procedures, they will recognize that, not only is the risk of radiation decreased, but also the comfort level of the staff is increased by the absence of lead protective gear. It is the authors’ personal observation that elimination of lead aprons has been the number one motivation to obtain staff buy-in, making them willing to endure the learning curve. This chapter reviews the experiences of multiple labs, and their approach to overcoming the hurdles of radiation elimination. Hopefully, the reader will find sufficient references to make their own learning curve as smooth as possible.
Large-Signal-Network-Analyzer Phase Calibration on an Arbitrary Grid

We have developed a method for improving the synchronization of large-signal network analyzers and transferring "cross-frequency" phase calibrations from a calibrated sampling oscilloscope to the large-signal network analyzer on an arbitrary frequency grid. The approach can be applied to the measurement of modulated signals and other waveforms on arbitrary and fine frequency grids. This translates into the ability to measure complex and arbitrarily long signals traceably with high dynamic range.
RbFox1 up-regulation impairs BDNF-dependent hippocampal LTP by dysregulating TrkB isoform expression levels

Brain-derived neurotrophic factor (BDNF) is a potent modulator of brain synaptic plasticity. Signaling defects caused by dysregulation of its Ntrk2 (TrkB) kinase (TrkB.FL) and truncated receptors (TrkB.T1) have been linked to the pathophysiology of several neurological and neurodegenerative disorders. We found that upregulation of Rbfox1, an RNA binding protein associated with intellectual disability, epilepsy and autism, increases selectively hippocampal TrkB.T1 isoform expression. Physiologically, increased Rbfox1 impairs BDNF-dependent LTP which can be rescued by genetically restoring TrkB.T1 levels. RNA-seq analysis of hippocampi with upregulation of Rbfox1 in conjunction with the specific increase of TrkB.T1 isoform expression also shows that the genes affected by Rbfox1 gain of function are surprisingly different from those influenced by Rbfox1 deletion. These findings not only identify TrkB as a major target of Rbfox1 pathophysiology but also suggest that gain or loss of function of Rbfox1 regulate different genetic landscapes.
Association of Placenta Growth Factor with Hemolysis and Inflammation in Sickle Cell Disease (SCD)

BACKGROUND: Placenta Growth Factor (PlGF) is a member of the vascular endothelial growth factor family of cytokines. Although expressed at high levels by the placenta during pregnancy, PlGF is also released by immature erythrocytes and is elevated in SCD. PlGF appears to play a role in inflammation and may be associated with the frequency of pain episodes in SCD. More recently, PlGF has been reported to increase the expression of endothelin-1 and endothelin-B receptor in human pulmonary microvascular endothelial cells and monocytes, and therefore may play a role in the development of SCD-associated pulmonary hypertension (PHT). OBJECTIVE: We have previously reported that SCD patients with PHT exhibit higher levels of inflammatory markers compared to patients without PHT. The purpose of this study was to evaluate the association of PlGF with PHT (and other SCD-related complications), and to explore the link between PlGF and laboratory markers of hemolysis and inflammation in SCD patients. METHODS: We performed a cross-sectional study of patients followed at the Sickle Cell Clinic at UNC-Chapel Hill. Doppler echocardiography was used to determine the pulmonary artery systolic pressure, and PHT was subsequently defined using an age-, sex-and BMI-adjusted reference range. Nitric oxide metabolites (NOx), PlGF and soluble VCAM (all quantified by ELISA), as well as laboratory markers of hemolysis were obtained at the time of patient evaluation. Student’s t-tests (a = 0.05) were used to compare mean values of PlGF in patients with SCD-related complications. Furthermore, Spearman’s correlation coefficient was used to assess for correlations between PlGF and laboratory variables. RESULTS: Plasma samples were available in 71 of the 74 subjects evaluated. Levels of PlGF were significantly higher in patients with PHT (12.3 ng/ml vs. 8.9 ng/ml, p = 0.005), and patients with a history of stroke (12.8 ng/ml vs 9.3 ng/ml p = 0.027) compared to those patients without these complications. There was however no association of PlGF with the frequency of acute pain episodes, acute chest syndrome, leg ulcers, priapism or retinopathy. We observed significant positive correlations between lactate dehydrogenase (r 2 = 0.13, p = 0.002), reticulocyte counts (r 2 = 0.08, p = 0.02), soluble VCAM (r 2 = 0.09, p = 0.009), NT-proBNP (r 2 = 0.13, p = 0.003), and absolute monocyte count (r 2 = 0.08, p = 0.02) with PlGF. There were significant negative correlations between PlGF and hemoglobin (r 2 = 0.19, p 2 = 0.05, p = 0.08). CONCLUSIONS: Our results indicate that PlGF is strongly associated with PHT and stroke, and correlates with soluble VCAM in SCD patients. This suggests that inflammation may play a role in the pathogenesis of SCD-associated vasculopathy. The correlation of PlGF with laboratory measures of hemolysis and NOx suggests that hemolysis, possibly with associated scavenging of nitric oxide, contributes to the inflammatory state in SCD.
Uncertainty quantification in materials modeling

Abstract Integrated Computational Materials Engineering (ICME) has been widely articulated and pursued over the past decade. Recognition of the need to ensure reliability and robustness of simulation predictions subject to various sources of uncertainty is central to ICME. Discrepancy between models and the physical world, as well as numerical approximation to facilitate computation, is the major source of model form uncertainty. Data fitting and model calibration processes introduce additional input uncertainty owing to systematic and random errors inherited in experimental data. Various uncertainty quantification (UQ) methods can be applied to assess the impacts of uncertainty. However, given the high cost of simulations, dimensionality is the major challenge for the application of UQ methods. In this chapter, sources of uncertainty in materials modeling and simulation are discussed. An overview is provided regarding major UQ methods and their applications to materials modeling. Their applications in simulation-assisted materials design are also reviewed.
Influence of Hydropower Outflow Characteristics on Riverbank Stability: Case of the Lower Osage River (Missouri, USA)

This research examined the influences of outflow characteristics affecting riverbank stability. The 130-km stretch of the Lower Osage River downstream from Bagnell Dam (Missouri, USA) provided an e...
Choroid Plexus Organoids: Harnessing CSF Gatekeepers for Brain Therapeutics

Summary Barrier properties of the choroid plexus (ChP) help protect the brain from the external world. In Science, Pellegrini et al. (2020) report the successful creation of human ChP organoids, which produce a cerebrospinal fluid-like secretion and recapitulate barrier functions, thereby inspiring new advances for targeted brain therapeutics.
E-224 Comparing efficacy of platelet inhibition in patient treated with clopidogrel versus prasugrel undergoing cerebral aneurysm stent-assisted embolization with flow diversion

Clopidogrel and Prasugrel are both platelet inhibitors that act on the P2Y12 adenosine diphosphate receptor. Clopidogrel utilizes a multi-step inhibition process while Prasugrel inhibits platelet functioning in a single step. In part due to these differences in mechanisms of action, an estimated 30% of patients treated with Clopidogrel are non-responders as compared to Prasugrel that has a very low rate of non-respondance. Inadequate platelet inhibition is associated with delay of care, often requiring operative rescheduling, and increased incidence of ischemic events. In our study, we compare a cohort of patients undergoing cerebral aneurysm embolization with flow diversion in matched controls who were treated with Clopidogrel. We compare P2Y12 reaction unit (PRU) levels at sets of time point pre, peri and post-operatively, to measure response to Prasugrel versus Clopidogrel. We also evaluate if sub-optimal responses to Prasugrel or Clopidogrel resulted in delay of patient care. Early findings suggest that treatment with Prasugrel results in faster time to therapeutic PRU levels and more consistent PRU levels as compared to Clopidogrel resulting in less delay of care and operative rescheduling. Disclosures E. Milosavljevic: None. C. McKinney: None. D. Hoss: None.
Enforcing Security and Privacy in Distributed Ledgers by Intel SGX

Distributed Ledger Technology (DLT) utilizes an architecture that can host a large number of nodes without pre-established trust to provide decentralized services. The blockchain is the most widely used architecture of distributed ledger, where transactions across the whole network are visible to all participants in a chain to prevent tampering. However, transactions may contain sensitive information such as business contract. To secure the system and protect user privacy, we propose a multi-channel architecture that leverages Intel Software Guard Extensions (SGX). We illustrate how SGX capabilities help to defend against attacks on distributed ledgers, by way of SGX enforcement on the participating machines. We adopt the design and implementation of a two layer architecture for securing the blockchain mining process and enhancing the transaction privacy. The security analysis and performance evaluation show that the design and protocols are capable of protecting privacy, defending against adversarial attacks and scalable.
When hematologic malignancies meet COVID-19 in the United States: Infections, death and disparities.

Scientific data is limited on the risks, adverse outcomes and racial disparities for COVID-19 illness in individuals with hematologic malignancies in the United States. To fill this void, we screened and analyzed a nation-wide database of patient electronic health records (EHRs) of 73 million patients in the US (up to September 1st) for COVID-19 and eight major types of hematologic malignancies. Patients with hematologic malignancies had increased odds of COVID-19 infection compared with patients without hematologic malignancies for both all-time diagnosis (malignancy diagnosed in the past year or prior) (adjusted Odds ratio or AOR: 2.27 [2.17-2.36], p < 0.001) and recent diagnosis (malignancy diagnosed in the past year) (AOR:11.91 [11.31-12.53], p < 0.001), with strongest effect for recently diagnosed acute lymphoid leukemia (AOR: 31.03 [25.87-37.27], p < 0.001), essential thrombocythemia (AOR: 20.65 [19.10-22.32], p < 0.001), acute myeloid leukemia (AOR: 18.94 [15.79-22.73], p < 0.001), multiple myeloma (AOR: 14.21 [12.72-15.89], p < 0.001). Among patients with hematologic malignancies, African Americans had higher odds of COVID-19 infection than Caucasians with largest racial disparity for multiple myeloma (AOR: 4.23 [3.21-5.56], p < 0.001). Patients with recently diagnosed hematologic malignancies had worse outcomes (hospitalization: 51.9%, death: 14.8%) than COVID-19 patients without hematologic malignancies (hospitalization: 23.5%, death: 5.1%) (p < 0.001) and hematologic malignancy patients without COVID-19 (hospitalization: 15.0%, death: 4.1%) (p < 0.001).
Christian Ideas Influencing US Food Movements

The US food system is not environmentally, socially, or economically sustainable. And yet improvements have occurred, thanks to nineteenth- and twentieth-century reformers, many of whom based their campaigns on Christian ideas. Their ideas continue to support the drive to make the US food system sustainable. This chapter is about the ideas of food movement leaders who linked Christianity to sustainability since the late 1700s. I consider leaders in five movements: food safety, vegetarianism, organic farming, food justice, and the local food movement. The locally-focused agrarianism of the late twentieth century, led by Wendell Berry, builds on these ideas and on the four older movements. In this synthesis, we can see how both place and Christian ideas become critical to sustainability discourses.
Effects of Marathon Running on Platelet Activation Markers

We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet count consistent with dehydration and leukocytosis indicative of demargination of neutrophils or inflammation secondary to tissue destruction (eg, rhabdomyolysis). The number of RBC fragments was increased after the race ( P = .008), consistent with exercise-induced hemolysis. The mean platelet component, a measure of platelet granularity, was decreased ( P < .0001), and the number of platelet clumps was increased ( P = .0026), providing evidence for in vivo platelet activation during the marathon. By using direct measurement of platelet granularity, our study confirms the in vivo activation of platelets by vigorous exercise and establishes the usefulness of automated cell counters for the assessment of platelet activation and of RBC fragmentation in this setting.
Leveraging Digital Medicine to Support Providers and Their Patients in Managing Serious Mental Illness.

Recent national statistics show that an estimated 11.2 million American adults live with serious, chronic forms of mental illness. The burden of mental illness is considerable for these individuals...
Dealing with a Paradigm Shift.

Recent changes in policies by insurance companies with respect to mandating home sleep apnea testing rather than in-laboratory studies have a large impact on the financial viability of clinical sle...
Uncertainty in white matter fiber tractography

In this work we address the uncertainty associated with fiber paths obtained in white matter fiber tractography. This uncertainty, which arises for example from noise and partial volume effects, is quantified using a Bayesian modeling framework. The theory for estimating the probability of a connection between two areas in the brain is presented, and a new model of the local water diffusion profile is introduced. We also provide a theorem that facilitates the estimation of the parameters in this diffusion model, making the presented method simple to implement.
Games of Drones: The Uneasy Future of the Soldier-Hero in Call of Duty: Black Ops II

In this article, I argue that the first-person shooter video game, Call of Duty: Black Ops II, reflects the U.S. military‟s transition as it reimagines the soldier‟s role in war. In the age of drone technology, this role shifts from a position of strength to one of relative weakness. Although video games that feature future combat often “function as virtual enactments and endorsements for developing military technologies,” Black Ops II offers a surprisingly complex vision of the future of drones and U.S. soldiers (Smicker 2009: 107). To explore how the game reflects a contemporary vision of the U.S. military, I weave together a close textual reading of two levels in Black Ops II with actual accounts from drone pilots and politicians that illuminate the nature of drone combat. Although there are moments in Black Ops II in which avatars combat enemies with first-hand firepower, the experience of heroic diegetic violence is superseded by a combat experience defined by powerlessness, boredom, and ambiguous pleasure. The shift of the soldier from imposing hero to a banal figure experiences its logical conclusion in Unmanned, an independent video game that foregrounds the mundane, nonviolent nature of drone piloting. Instead of training soldiers to withstand emotionally devastating experiences of death and violence first-hand (or to physically enact such violence), games like Black Ops II and Unmanned train actual and potential soldiers to tolerate monotony and disempowerment.
Numerical Simulations of Random Walk in Random Environment

This paper is concerned with the numerical simulation of a random walk in a random environment in dimension d = 2. Consider a nearest neighbor random walk on the 2-dimensional integer lattice. The transition probabilities at each site are assumed to be themselves random variables, but fixed for all time. This is the random environment. Consider a parallel strip of radius R centered on an axis through the origin. Let XR be the probability that the walk that started at the origin exits the strip through one of the boundary lines. Then XR is a random variable, depending on the environment. In dimension d = 1, the variable XR converges in distribution to the Bernoulli variable, X∞ = 0, 1 with equal probability, as R → ∞. Here the 2-dimensional problem is studied using Gauss-Seidel and multigrid algorithms.
Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose.

The main objectives of this investigation were to study the binding of a lectin from navy beans with the epithelial cells of the rat intestine and to assess the effect of such binding on the ability of the intestine to absorb glucose. A Scatchard plot, based on the binding of /sup 125/I-labeled lectin to isolated intestinal epithelial cells, was used to calculate an association constant (Ka) of 15 x 10(6)M-1 and the number of binding sites per cell, 12 x 10(6). Metabolic studies were conducted over a period of 5 d on groups of rats fed raw or autoclaved navy bean flour and casein with or without the purified lectin. Growth, protein digestibility, biological value and net protein utilization were significantly lower in animals that had been fed raw navy bean flour or casein plus lectin than in control groups fed diets containing autoclaved navy bean flour or casein alone. Vascular perfusion was used to measure the rate of uptake of glucose by the intestines of rats that had received the various dietary treatments. The rate of absorption of (/sup 14/C)glucose by intestines from rats fed raw navy bean flour or casein plus lectin was approximately one-half that of theirmore » counterparts fed the autoclaved flour or casein alone. These results provide evidence that the lectin, by virtue of its interference with intestinal absorption, is responsible, at least in part, for the nutritional inferiority of raw navy beans.« less
Finite-temperature superconducting correlations of the Hubbard model

We utilize numerical linked-cluster expansions (NLCEs) and the determinantal quantum Monte Carlo algorithm to study pairing correlations in the square-lattice Hubbard model. To benchmark the NLCE, we first locate the finite-temperature phase transition of the attractive model to a superconducting state away from half filling. We then explore the superconducting properties of the repulsive model for the $d$-wave and extended $s$-wave pairing symmetries. The pairing structure factor shows a strong tendency to $d$-wave pairing and peaks at an interaction strength comparable to the bandwidth. The extended $s$-wave structure factor and correlation length are larger at higher temperatures but clearly saturate as temperature is lowered, whereas the $d$-wave counterparts, which start off lower at high temperatures, continue to rise near half filling. This rise is even more dramatic in the $d$-wave susceptibility. The convergence of NLCEs breaks down as the susceptibilities and correlation lengths become large, so we are unable to determine the onset of long-range order. However, our results extend the conclusion, previously restricted to only magnetic and charge correlations, that NLCEs offer a unique window into pairing in the Hubbard model at strong coupling.
Responding to the Interests of Children Whose Parents Face Deportation

While current family-based US immigration policy is among the most generous in the world for adult citizens and their non-citizen family members seeking admission to the United States, it is not responsive to the interests of citizen and permanent resident children in remaining together in their country of birth with their families. In this paper, I will propose and consider a possible response that involves recasting the parent's permission to remain in the country to care for their citizen and/or permanent resident children as a duty to the state and to their children with conditions attached to their residence that ensure this responsibility is fulfilled. This marks a departure from past US immigration policy that provided parents who are successful in obtaining cancellation of removal on the basis of exceptional and extremely unusual hardship to their citizen-children with an unrestricted individual right to remain. Instead, the parent's permission to remain would be tied to the interests of the state and its citizens in foregoing the long-term social and economic costs of raising an abandoned child as a ward of the state, or reintegrating a citizen-child who left with her parents into American society as an adult. In this way, we can reconceptualize the interest in allowing an unauthorized parent to remain in the United States as pertaining to the community which claims an interest in deporting her, rather than as a humanitarian gesture or an individual rights claim.
Ductal Carcinoma In Situ: Treatment Update and Current Trends

Ductal carcinoma in situ (DCIS) traditionally has been managed through various combinations of surgery, radiation, and endocrine therapy. However, concern for under- or over-treatment of DCIS has led many surgeons to question historically standardized approaches and instead begin to tailor treatment based on individual prognostic indicators. Recent and ongoing clinical trials have investigated the potential for active surveillance in DCIS, the possibility of eliminating radiation therapy (RT), and ways in which adjuvant systemic therapy may be refined. This review will summarize the current trends in the treatment of DCIS, as well as highlight the most pertinent clinical trials that are shaping management today.
Are pregnancy planning and timing associated with preterm or small for gestational age births

Objective To investigate whether unplanned or poorly timed pregnancies (self-reported at enrollment) are associated with preterm or small for gestational age births. Design Prospective cohort study. Setting Not applicable. Patient(s) Two thousand six hundred fifty-four pregnant women Intervention(s) None. Main Outcome Measure(s) Preterm and small for gestational age births. Result(s) In adjusted analyses, pregnancy planning was not statistically significantly associated with preterm (odds ratio [OR] 1.18; 95% confidence interval [CI], 0.85–1.65) or small for gestational age birth (OR 1.17; 95% CI, 0.69–1.97). Similarly, poorly timed pregnancies were not statistically significantly associated with preterm (OR 0.85; 95% CI, 0.53–1.38) or small for gestational age birth (OR 0.92; 95% CI, 0.65–1.29). Combining pregnancy planning (yes/no) and timing (yes/no) into a 4-level category showed no statistically significant association with preterm birth or small for gestational age. Conclusion(s) In a large cohort with antenatally assessed pregnancy planning and timing, outcome data collected from medical record abstraction, and robust analysis adjusting for multiple confounding factors including maternal demographics, medical conditions, and other risk factors, neither pregnancy planning nor pregnancy timing showed a statistically significant association with preterm or small for gestational age infants. This study improves upon previous analyses that lacked adjustment for confounding and used retrospective self-reporting to assess pregnancy planning and timing, and preterm and small for gestational age births. Findings may differ in higher risk populations with higher prevalence of preterm or small for gestational age births.
Neurite outgrowth in individual neurons of a neuronal population is differentially regulated by calcium and cyclic AMP

In identified Helisoma neurons, intracellular calcium can regulate neurite elongation and growth cone motility. Neurotransmitters such as 5-HT suppress both neurite elongation and the filopodial and lamellipodial movements of growth cones by causing increases in intracellular calcium (Haydon et al., 1984; Cohan et al., 1987; Mattson and Kater, 1987). Since an additional second messenger, cyclic AMP (cAMP), is known to mediate many physiological effects of neurotransmitters, we tested (1) the possible involvement of cAMP in the regulation of neurite outgrowth from Helisoma buccal neurons and (2) calcium-cAMP interrelationships in the regulation of outgrowth. The cAMP-elevating agents forskolin (5 x 10(-6)-10(-4) M) and dibutyryl cAMP (dbcAMP; 5 x 10(-3)-10(-2) M) suppressed neurite elongation and growth cone movements in identified neurons B19 (5-HT sensitive) and B5 (5-HT insensitive); the suppression was reversible. Exposure of these particular identified neurons to the calcium channel blocker La3+ (10(- 5) M) or a culture medium with reduced calcium prevented and reversed the suppressive effects of forskolin and dbcAMP. In order to determine if the results on neurons B5 and B19 were representative of all neurons or only a subset, we examined a larger population of neurons. Calcium ionophore A23187 suppressed outgrowth from all neurons in mass dissociate cultures of buccal neurons, while forskolin or dbcAMP plus IBMX suppressed outgrowth from only one-half of buccal neurons. Finally, we found that 2 subpopulations exist among the neurons whose outgrowth is suppressed by cAMP: One subpopulation requires calcium influx for cAMP to act, while the other does not. Thus, even within the relatively small population of neuronal types comprising the buccal ganglion of Helisoma, second messengers within different neurons can act and interact in different ways to regulate outgrowth.
Human histocompatibility proteins

Summary: Transplantation antigens (later called histocompatibility proteins) were named by Peter Gorer in the 1930s. After 4 decades of immunological work emphasizing their importance in immunobiology, structural work on these proteins began about 1970. During the first decade, HLA proteins were isolated and then separated into two groups. Biochemical studies established the close structural relationships of these groups (now called class I and class II MHC proteins). These structures both contained four domains, although the domains were linked differently. Two of these domains were immunoglobulin-like. They were the first proteins (aside from immunoglobulins) identified as members of the immunoglobulin superfamily of proteins. The crystallization of these proteins in the second decade led to elucidation of the structures of class I and class II MHC proteins, which has changed the way we think about immunology. These molecules each present peptides (8–9mers in the case of class I and 13–14mers in the case of class II) to initiate the immune response.
Reinforcing effects of D2 dopamine receptor agonists and partial agonists in rhesus monkeys.

Dopamine (DA) receptors play a role in the reinforcing effects of psychomotor stimulants and other drugs. Both D1 and D2 DA receptor agonists have been reported to function as positive reinforcers in maintaining self-administration in non-human subjects. The purpose of the present study was to evaluate, in monkeys, the reinforcing effects of DA D2 receptor agonists that vary in their efficacy as D2 agonists. Rhesus monkeys were prepared with venous catheters and lever pressing was maintained by i.v. cocaine (n=5, 0.03 mg/kg/inj) in daily baseline sessions (2 h/day, fixed ratio 25). Various doses of cocaine or D2 agonists were then made available for at least four to seven sessions, and until responding was stable. At least one dose of the higher-efficacy D2 agonists, R(-)-propylnorapomorphine (NPA) (n=4, 0.001-0.01 mg/kg/inj), R(-)-apomorphine (APO) (n=4, 0.003-0.1 mg/kg/inj) and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine HCl [R(+)-3-PPP] (n=4, 0.03-0.3 mg/kg/inj), functioned as a positive reinforcer in all the monkeys tested. In contrast, no dose of the lower-efficacy D2 agonists, R(+)-terguride (n=4, 0.001-0.3 mg/kg/inj) and S(-)-3-(3-hydroxyphenyl)-N-propylpiperidine HCl [S(-)-3-PPP] (n=4, 0.001-0.3 mg/kg/inj), maintained self-administration. In in vitro binding studies with monkey brain tissue NPA and terguride had high affinities for the D2 receptor, while APO had intermediate affinity, and the 3-PPPs had low affinity. Among the compounds that were reinforcers potency as a reinforcer was directly related to D2 affinity in three of the four monkeys, consistent with D2 receptor involvement in the reinforcing effect of these compounds. The data suggest that the efficacy at D2 receptors is directly related to the reinforcing effect.
Organization and development of horizontal cells in the goldfish retina, II: Use of monoclonal antibody MH1.

We have produced and characterized a monoclonal antibody, AT101, which selectively labels both viable and formaldehyde-fixed horizontal cell axon terminals, but not their somas or axons, of the goldfish (Carassius auratus) retina. The antigen recognized by AT101 appears to be a cell surface glycoprotein with a molecular weight of about 35,000 Daltons, and is present exclusively or predominantly in nervous tissues of all vertebrate species examined. We have used AT101 as a probe to analyze immunocytochemically the organization of horizontal cell axon terminals (HCATs) in the adult goldfish retina, and the emergence and maturation of these terminals during retinal development. Because of continued growth at the retinal margin in adult goldfish, there is a peripheral-to-central gradient in the age of cells, with the most mature in the center and the youngest in the periphery. In the center and near periphery of the adult retina, HCATs have a fusiform morphology and form a dense network in the middle and proximal part of the inner nuclear layer. In the far peripheral retina, the axon terminals appear round or ellipsoid. The retina closest to the retinal margin is devoid of AT101 staining, indicating that either HCATs are absent or the antigen recognized by AT101 is not present on HCATs at this stage. A similar sequence of changes in staining pattern is seen during development. Although AT101 staining can first be demonstrated in the larval retina at 1 month after hatching, it appears mostly as punctate structures. At a later stage, there are round or ellipsoid structures that resemble in morphology and location (in the inner nuclear layer) those found in the far peripheral adult retina. Double-labeling experiments with AT101 and antiserum against tubulin also indicate that AT101 labels the HCATs when they first appear during development. These data suggest that the emergence and maturation of HCAT is a late event in retinal development.
Analysis of relaxation kinetics data by a nonlinear least squares method.

Abstract Recent improvements in measuring and data acquisition techniques have increased greatly the precision of chemical relaxation data. This has necessitated more accurate methods for data analysis in cases of complex relaxation spectra, as is often observed in biochemical systems. We have developed and applied a method capable of decomposing a wave form containing up to three overlapping exponentials. The method is based upon a nonlinear least squares algorithm. Analysis of the method shows that when it is applied to a two exponential function where the signal-to-noise ratio, ΔS/N, is fifty, using 100 data points, the resulting four coefficients (two amplitudes and two relaxation times) are each accurate to within 5–10 % over a wide range of conditions, i.e., relative amplitudes from 10–90 % and ratios of relaxation times of 2.5 or greater. The influence of the number of data points and of random noise is as expected from statistical theory. Applications of the curve fitting methods to experimental temperature-jump data from oxygen binding to hemoglobin and hemocyanin yields internally consistent results. The values of the root-meansquare of the residuals of the fit approach those expected on the basis of the experimental signal-to-noise ratios.
Serological and vaccination studies with bloodstream and culture forms of Trypanosoma musculi.

Abstract Khazindar S. H. and Dusanic D. G. 1982. Serological and vaccination studies with blood-stream and culture forms for Trypanosoma musculi . International Journal for Parasitology 12 : 257–264. Trypanosoma musculi bloodstream forms (BSF) were collected from immunosuppressed infected mice and extracted with phosphate buffered saline (PBS). ML-15, O'Daly's and LMC media, each containing 5% fetal calf serum (FCS) and a dialysate medium were investigated to identify the medium providing the optimal growth of T. musculi culture forms (CF). Because of the ease of preparation, ML-15 containing 5% FCS was selected and the culture forms were harvested when the parasites attained concentrations of at least 1 × 10 7 trypanosomes/ml. Cellular antigens present in PBS extracts of the BSF and CF parasites were analyzed with rabbit antisera by crossed immunoelectrophoresis and tandem crossed immuno-electrophoresis. Absorptions of rabbit antisera with CF, BSF, media and normal mouse blood extracts were performed on immunoabsorbent affinity columns prior to crossed immunoelectrophoresis to further study the unique and shared antigens of the parasites. A minimum of 13 antigens were shared by these trypanosomes. Four antigens appeared to be unique to BSF and a single antigen to CF. In immunization studies, two groups of C3H/Anf mice were immunized with the equivalent of 1 × 10 8 frozen-thawed BSF or CF/injection. Two groups of five animals injected with PBS or uninoculated medium and one untreated group served as controls. Animals in each group received 6 injections administered at 3-day intervals. Three days following the last injection, all animals were challenged with 1 × 10 4 BSF. Hemacytometer counts were performed every 4 days until no parasites were seen in wet blood preparations of the untreated group. None of the animals inoculated with BSF homogenate displayed parasitemias, while animals inoculated with CF homogenate were found to be infected. Parasitemias in mice immunized with CF were lower than those of the control mice.
Caspase signalling in the absence of apoptosis drives Jnk‐dependent invasion

Tumours evolve several mechanisms to evade apoptosis, yet many resected carcinomas show significantly elevated caspase activity. Moreover, caspase activity is positively correlated with tumour aggression and adverse patient outcome. These observations indicate that caspases might have a functional role in promoting tumour invasion and metastasis. Using a Drosophila model of invasion, we show that precise effector caspase activity drives cell invasion without initiating apoptosis. Affected cells express the matrix metalloprotinase Mmp1 and invade by activating Jnk. Our results link Jnk and effector caspase signalling during the invasive process and suggest that tumours under apoptotic stresses from treatment, immune surveillance or intrinsic signals might be induced further along the metastatic cascade.
Determination Of SO 2 Concentrations From A Coal-Burning Power Plant Stack By Fourier Spectrometry

A measurement and analysis program to determine the concentration of SO2 in a coal-burning power plant stack was conducted by a passive remote sensing technique, utilizing a PFS-201 Fourier Transform Spectrometer. SO2 concentrations were determined by measuring the radiance of the (w1 + w2) combination band at 2499.0 cm-1 (4.0 μm), while the exhaust gas temperatures were determined by measurement of the peak CO2 radiance at 2396.4 cm-1. Results of the remote measurements compared favorably with the in-stack Du-Pont Analyzer data.© (1976) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Cocaine withdrawal and neuro-adaptations in ion channel function.

Chronic exposure to psychostimulants induces neuro-adaptations in ion channel function of dopamine (DA)-innervated cells localized within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Although neuroplasticity in ion channel function is initially found in drug-sensitized animals, it has recently been believed to underlie the withdrawal effects of cocaine, including craving that leads to relapse in human addicts. Recent studies have also revealed remarkable differences in altered ion channel activities between mPFC pyramidal neurons and medium spiny NAc neurons in cocaine-withdrawn animals. In response to psychostimulant or certain “excitatory” stimuli, increased intrinsic excitability is found in mPFC pyramidal neurons, whereas decreased excitability is observed in medium spiny NAc cells in drug-withdrawn animals compared to drug-free control animals. These changes in ion channel function are modulated by interrupted DA/Ca2+ signaling with decreased DA D2 receptor function but increased D1 receptor signaling. More importantly, they are correlated to behavioral changes in cocaine-withdrawn human addicts and sensitized animals. Based on growing evidence, researchers have proposed that cocaine-induced neuro-adaptations in ion channel activity and DA/Ca2+ signaling in mPFC pyramidal neurons and medium spiny NAc cells may be the fundamental cellular mechanism underlying the cocaine withdrawal effects observed in human addicts.
Interhemispheric synchrony in the EEGs of full-term newborns☆

Cross correlations between 4 homologous pairs of ear-reference derivations were calculated for 45-sec digitized samples of typical active and quiet sleep in 19 selected normal newborns at 21--70 h after term birth. Repeat recordings were obtained in 9 subjects 24 h after the original recordings and another set of cross correlations was calculated. For comparison, similar recordings were obtained from 4 asymptomatic young adults and cross correlations were calculated for 45-sec samples of typical stage 4 and stage REM sleep and for stage W both before and after sleep. Mean cross-correlation coefficients at zero time lag were generally higher for the adult sleep data than for the newborn data, but the differences were smaller than had been anticipated. The coefficients for active sleep data in the newborns were higher than for quiet sleep data, while in the adults the coefficients were higher for stage 4 than for stage REM. Coefficients were higher for convexity derivations than for temporal derivations in both newborns and adults. A review of the small available literature suggests that recording and analysis techniques may be significant variables determining the results obtained in such studies. The cross-correlation method of measuring interhemispheric synchrony may prove useful in identifying brain disorders in the postnatal period.
Retrograde net transfer reaction insurance for pressure-temperature estimates

Retrograde net transfer reactions significantly affect compositions of metamorphic minerals, yet are rarely considered when determining pressure-temperature (P-T) conditions. Two natural amphibolite facies metapelites from the central Himalaya of Nepal exhibit extremely common compositional patterns, including increases in Mn and Fe/(Fe + Mg) at the rims of garnets, which are the result of retrograde garnet dissolution and Fe-Mg exchange with biotite. However, typical thermobarometric approaches for these rocks result in errors of hundreds of degrees and 3–6 kbar compared with thermobarometry of nearby rocks and petrogenetic grids. These large errors result because dissolution of high-Fe garnet has strongly affected the Fe/Mg ratio of matrix biotite. X-ray maps help evaluate the extent and chemical effects of retrograde reactions in these samples by identifying mineral regions that retain highest-T compositions, or, through a new data-processing approach, by permitting correction of mineral compositions to original high-T values. These approaches ensure against retrograde net transfer reactions and should be applied routinely in thermobarometric studies—they ultimately yield P-T estimates that are more petrologically reasonable, and permit rapid screening of samples for those least affected by retrograde reactions. Reconsideration of thermobarometry in the central and eastern Himalaya indicates that retrograde net transfer reactions are extremely common. Therefore, previous thermobarometric studies based on garnet major element compositions from that region should be reevaluated.
A camera shutter used in high resolution bubble chamber photography

Abstract A cylindrical rotating shutter for a high resolution bubble chamber camera is described. It eliminates several undesirable effects of interference from the low resolution photography system.
Gender and sex-role appropriateness: Bias in the judgment of disturbed behavior

Male and female undergraduate raters made attributions of mental disorder, personality traits, and diagnostic and treatment judgments for four case studies in which sex of client and sex-role appropriateness of client behavior were manipulated. Significant interactions of sex-role appropriateness with both client sex and rater sex highlighted the significance of sex-role stereotypes in the attribution of mental disorder by nonprofessionals. The data indicated that these cultural sex-role definitions had the strongest negative effect for females and the female sex role. Implications of these findings for the clinical judgment process and female self-perception are discussed.
Findings from observational studies of collaborative work

Abstract The work activity of small groups of three to four people was videotaped and analysed in order to understand collaborative work and to guide the development of tools to support it. The analysis focused on the group's shared drawing activity—their listing, drawing, gesturing and talking around a shared drawing surface. This analysis identified specific features of collaborative work activity that raise design implications for collaborative technology: (1) collaborators use hand gestures to uniquely communicate significant information; (2) the process of creating and using drawings conveys much information not contained in the resulting drawings; (3) the drawing space is an important resource for the group in mediating their collaboration; (4) there is a fluent mix of activity in the drawing space; and (5) the spatial orientation among the collaborators and the drawing space has a role in structuring their activity. These observations are illustrated with examples from the video data, and the design implications they raise are discussed.
Fever, rash, and myalgias of disseminated candidiasis during antifungal therapy.

• A patient with acute lymphocytic leukemia was seen initially with the signs of fever, rash, and myalgias that occurred sequentially despite antifungal therapy. Culture- and necropsy-proved Candida tropicalis infection was responsible. The appearance of myositis in a patient receiving adequate amphotericin B therapy for a sensitive C tropicalis infection suggests a poor prognosis. ( Arch Intern Med 1981;141:1233)
Applying human and system reliability analysis to the design and analysis of written procedures in high-risk industries

The importance and prevalence of written work procedures in industries, especially high-risk industries, has resulted in a renewed interest in the design of these procedures. Most of the concern has focused on the formatting, organization, and readability of the procedures. Although these are important issues, it is also important that advantage be taken of the richness in detail and knowledge contained in many of these procedures. Without an understanding of the relationship between the work context, which is largely reflected in written procedures, and behavioral tendencies, a fundamental problem related to the design of written procedures remains unresolved. Specifically, this problem concerns how written procedures can contribute to human error, procedural violations, and ultimately adverse system outcomes. In this article, a contextual modeling perspective to human and system reliability analysis is presented. The application of this approach directly to the process of designing and analyzing written procedures is discussed. In particular, this article discusses how applying this perspective can benefit designers and writers of procedures by increasing their ability to anticipate how written procedures could contribute to human error and adverse outcomes. Examples illustrating these ideas are presented throughout. © 1998 John Wiley & Sons, Inc.
Expense preference behavior in trucking: An empirical note

This note offers a statistical model which points out that the goal of publicly regulated firms often deviates from profit-maximization. Using a large firm-level panel data set from the trucking industry, we offer estimates which suggest that firm managers of the more heavily regulated common carriers practice utility maximization through higher salaries and more lucrative benefits than the managers (CEOs) of less regulated contract carriers. Our results add to the body of empirical work which supplements the theory of the firm developed by Ronald Coase.