cssi/SciSciGPT-SciSciNet huggingface dataset:
Matrix and Modifier Effects in the Supercritical Fluid Extraction of Cocaine and Benzoylecgonine from Human Hair

The supercritical fluid extraction (SFE) behavior of cocaine and its major metabolite benzoylecgonine (BZE) was investigated and found to be highly dependent upon the chemical nature of the matrix and the manner in which the target drug analytes are incorporated into or on the matrix. The recovery of cocaine from Teflon wool, filter paper, drug-fortified hair, and drug user hair was studied using a variety of CO2/modifier mixtures. Incorporation of a triethylamine (TEA)/water modifier mixture provided dramatic improvements in the recovery of cocaine from interactive matrixes. The results suggest that the SF extractability of cocaine is not limited by analyte solubility; rather, desorption of cocaine from hair binding sites is a rate-limiting step in the SFE process. A displacement SFE mechanism is hypothesized in which TEA (as the triethylammonium cation) competes with cocaine for negatively charged hair binding sites. The dependence of extractability on hair/drug binding interactions allows the different...
Prospects of low temperature co-fired ceramic (LTCC) based microfluidic systems for point-of-care biosensing and environmental sensing

Low temperature co-fired ceramic (LTCC) based microfluidic devices are being developed for point-of-care biomedical and environmental sensing to enable personalized health care. This article reviews the prospects of LTCC technology for microfluidic device development and its advantages and limitations in processing capabilities compared to silicon, glass and polymer processing. The current state of the art in LTCC-based processing techniques for fabrication of microfluidic components such as microchannels, chambers, microelectrodes and valves is presented. LTCC-based biosensing applications are discussed under the classification of (a) microreactors, (b) whole cell-based and (c) protein biosensors. Biocompatibility of LTCC pertaining to the development of biosensors and whole cell sensors is also discussed. Other significant applications of LTCC microfluidic systems for detection of environmental contaminants and toxins are also presented. Technological constraints and advantages of LTCC-based microfluidic system are elucidated in the conclusion. The LTCC-based microfluidic devices provide a viable platform for the development of point-of-care diagnostic systems for biosensing and environmental sensing applications.
Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.
Family experience survey in the surgical intensive care unit

The experience of critical care is stressful for both patients and their families. This is especially true when patients are not able to make their own care decisions. This article details the creation of a Family Experience Survey in a surgical intensive care unit (SICU) to capture and improve overall experience. Kolcaba's "Enhanced Comfort Theory" provided the theoretical basis for question formation, specifically in regards to the four aspects of comfort: "physical," "psycho-spiritual," "sociocultural" and "environmental." Survey results were analyzed in real-time to identify and implement interventions needed for issues raised. Overall, there was a high level of satisfaction reported especially with quality of care provided to patients, communication and availability of nurses and doctors, explanations from staff, inclusion in decision making, the needs of patients being met, quality of care provided to patients and cleanliness of the unit. It was noted that 'N/A' was indicated for cultural needs and spiritual needs, a chaplain now rounds on all patients daily to ensure these services are more consistently offered. In addition, protocols for doctor communication with families, palliative care consults, daily bleach cleaning of high touch areas in patient rooms and nurse-led progressive mobility have been implemented. Enhanced comfort theory enabled the opportunity to identify and provide a more 'broad' approach to care for patients and families.
Painful Diabetic Neuropathy

The podiatric physician often encounters complex painful neuropathies in daily practice. Diabetic neuropathy is one form of chronic neuropathic pain dealt with on a regular basis. The goal of this article is to review the pathophysiology, diagnosis, and treatment options of this complaint. Medical and surgical interventions are discussed, with a clinical emphasis on patient selection and prevention.
Application of the finite-element method to the radial forging of large diameter tubes

Abstract Previous investigations of large-diameter tube forging using the radial-forging process have been based on highly simplified slab and upper-bound process models. In order to make accurate predictions of the thermal and mechanical history of the workpiece, more detailed models are required. In this paper, a model of the tube-forging process based on the rigid-thermoviscoplastic finite-element method is considered. The results that are presented include the effective strain, strain rates, and temperature distributions in the forged tube. The deformation was found to be uniform but sensitive to the axial feed-rate. Strain rates were found to be sensitive to the axial feed rate and were within the range typical for a mechanical press. Large temperature gradients across the wall thickness were predicted in the tube. These temperature gradients were generated during forging due to contact with the mandrel and are thought to give rise to variation in the mechanical properties in the forged tube.
Monoclonal antibodies conjugated with radioisotopes for the treatment of Non-Hodgkin's lymphoma.

Objectives To describe the use of monoclonal antibodies labeled with iodine-131 tositumomab and yttrium-90 ibritumomab-tiuxetan as treatment for non-Hodgkin's lymphoma. Data Sources Literature review of trials of radioimmunotherapy. Conclusions Radiolabeled monoclonal antibodies recognize and react with specific antigens to provide targeted therapy to tumor cells, particularly hematopoietic tumor cells. This therapy delivers greater amounts of radiation to malignant cells than normal cells and spares critical organs that do not express the antigen. Strict safety and patient precautions must be in place with the use of radiotherapy. Implications for Nursing Practice As the use of radiommunotherapy in the treatment of non-Hodgkin's lymphoma grows, the role of nursing in the care of these patients will also grow. Nurses will play an important part in patient and family education, as well as staff preparation.
Translating patient self-management research into primary care: challenges and successes with group medical visits

Essential to the implementation of a patient-centered medical home is use of evidence-based interventions by a well-coordinated team of providers in a cost-effective manner. Group Medical Visits (GMVs), designed to increase self-management behaviors in patients with chronic illness, have shown inconsistently to be efficacious. Despite the modest results reported thus far in the literature, GMVs have been promoted by the American Academy of Family Physicians as an important component in the patient-centered medical home. This paper describes the challenges of translating GMVs into clinical practice when research support is not available. A review of 5+ years experience in conducting GMVs in clinical practice, including the numerous barriers, is presented through a “three-world view” model utilized by collaborative care leaders. This review is followed by a comparison of variables extracted from patients' electronic health records of those who participated in GMVs to similar patients who did not participate in GMVs. Results suggest that outcomes often reported in efficacy trials are not easily obtained in real clinical practice. Overcoming the operational and financial obstacles to offering GMVs is necessary before they can be promoted as essential elements in a patient-centered medical home.
Barriers to treatment and service utilization in an internet sample of individuals with obsessive–compulsive symptoms

Background: Despite the increasing dissemination of treatment for Obsessive–Compulsive Disorder (OCD) in the past decade, the majority of individuals with OCD are not receiving appropriate treatment. This study examined rates of treatment utilization and barriers to treatment in an internet sample of individuals with self-reported OCD. Methods: One hundred and seventy-five participants completed an online survey examining OCD symptoms, psychosocial measures, barriers to treatment, and treatment utilization. Results: Sixty percent of the sample reported receiving treatment for their OCD symptoms. The majority of participants who sought pharmacotherapy received SSRIs, whereas the majority who sought psychotherapeutic treatment received “talk therapy.” The cost of treatment, lack of insurance coverage, shame, and doubt that treatment would be effective were the most commonly endorsed barriers to treatment among the sample. Conclusions: Findings demonstrated relatively low treatment utilization rates among the sample, with many participants receiving treatments other than the gold-standard medication and psychotherapy treatments (i.e. SSRIs and cognitive behavioral therapy, respectively). Furthermore, a large portion of the sample endorsed many barriers to treatment seeking, such as logistic and financial barriers; stigma, shame, and discrimination barriers; and treatment perception and satisfaction barriers. This study highlights the need for more effective treatment dissemination in OCD. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.
Aureomycin in Treatment of Pneumococcal Pneumonia and Meningococcemia.

Aureomycin is a new antibiotic which is active in vitro and in experimental animals against gram-positive and gram-negative bacteria and is also effective against experimental infections with rickettsias and with viruses of the psittacosis lymphogranuloma venereum group.† The findings in 4 cases of pneumococcal pneumonia and in one case of meningo-coccemia are presented here briefly. The bac-teriologic methods are described elsewhere.1, 2The cases of lobar pneumonia were of moderate severity and a single lobe was involved in each instance. All were in males ranging in age from 16 to 65 years. Pneumo-cocci were identified and typed from the sputum in each instance and from the blood in one case before oral aureomycin therapy was started. One patient received an initial dose of 0.5 g followed by 0.25 g every 6 hours for a total of 5 g; the others received 0.5 g every 6 or 8 hours for a total of 10 g in 2 cases and 20 g in the oldest patient. No other chemotherapy or antibiotic was used. Some of the relevant...
L-selectin-mediated lymphocyte rolling on MAdCAM-1

THE L-selectin, a cell surface C-type lectin, directs lymphocyte traffic to lymph nodes1, and contributes to lymphocyte homing to Peyer's patches2,3 and to leukocyte interactions with inflamed venules4,5. Here we report that the mucosal vascular addressin MAdCAM-1, a mucosal endothelial adhesion molecule with immunoglobulin- and mucin-like domains6, is a facultative ligand for L-selectin. MAdCAM-1 isolated from mesenteric lymph nodes, but not from cultured endothelioma cells, bears N-glycanase-resistant sialic acid-containing carbohydrate which supports adhesion of L-selectin-transfected lymphoid cells under shear. Interacting lymphoid cells display a 'rolling' behaviour similar to the selectin-dependent rolling of neutrophils observed in inflamed venules. MAdCAM-1 is also a ligand for the lymphocyte integrin homing receptor for Peyer's patches, α4βll (ref. 7), and may be uniquely adapted to support both selectin-mediated lymphocyte rolling and integrin-mediated adhesion and arrest in vivo.
A survey of gastroenterologists' perceptions and practices related to Helicobacter pylori infection.

Abstract OBJECTIVE: The aim of this study was to assess the current practice of gastroenterologists in the United States concerning Helicobacter pylori ( H. pylori ) infection. METHODS: We mailed a structured questionnaire to 1000 gastroenterologists chosen at random from a national database. We asked about personal and practice demographics and practices relating to testing for, and treating, H. pylori infection. RESULTS: A total of 922 questionnaires were delivered, from which we received 286 responses (31%). Respondents used many different tests for H. pylori infection, but only 10% each had used either the 13 C- or 14 C-urea breath test. Testing for H. pylori infection was usually for appropriate reasons, although 21% indicated that they might not treat a patient with a positive test result. Different multiple treatment regimens were used; the most frequent were combinations of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole. Estimates of the prevalence of antibiotic resistance were highly variable and often inaccurate. Most respondents would not check asymptomatic individuals for the infection; however, in the absence of symptoms, 38% would personally undergo testing and treatment if positive. CONCLUSIONS: Gastroenterologists usually test for H. pylori infection in appropriate conditions, but may not always treat the infection based on a positive test result. Most use efficacious regimens to treat the infection although many have inaccurate information on resistance rates, which may adversely influence prescribing. Many would have testing and, if positive, treatment in the absence of symptoms or a specific diagnosis, but do not recommend this for their patients.
Experimental observation of neoclassical currents in a plasma

Experimental observations of the bootstrap and Pfirsch-Schl\"uter currents, predicted by neoclassical transport theory, are presented. Detailed measurements of the parallel plasma currents in a toroidal octupole agree, within the separatrix, with theoretical predictions. Observations of the spatial structure, collisionality, and toroidal field dependence of the complete current and the ion portion of the current are discussed.
Ethanol withdrawal in the rat: involvement of noradrenergic neurons.

Abstract Ethanol dependence was induced in rats by maintaining them for 3 weeks on a liquid diet containing ethanol. When ethanol was abruptly replaced with sucrose in the diet, animals showed withdrawal symptoms. Eight hours later, the accumulation in brain and heart of 3H-norepinephrine synthesized from 3H-tyrosine, and of 3H-norepinephrine metabolites was greater than in animals not undergoing withdrawal. An injection of ethanol (3 g/kg) 1 1 2 or 5 hours after the initiation of withdrawal resulted in less accumulation of newly synthesized 3H-norepinephrine and of 3H-norepinephrine metabolites in both brain and heart. If the rate of ethanol withdrawal was slow, i.e., the ethanol in the diet was replaced gradually with sucrose over a 3-day period, less accumulation of 3H-norepinephrine and 3H-norepinephrine metabolites occured in heart and brain than as a result of abrupt withdrawal. Also, no behavioral symptoms of withdrawal were observed. These results indicate that (a) gross withdrawal symptoms and the accompanying activation of noradrenergic neurons can be blocked during withdrawal by an acute dose of ethanol, and (b) ethanol withdrawal can be modified by altering the rate of withdrawal, a finding that may prove useful in clinical situations. We conclude that the withdrawal symptoms and the activation of noradrenergic neurons during withdrawal are caused by the sudden lack of ethanol in the system.
How specific is specific impairment

ABSTRACT Objective To describe the usefulness of impairment items placed at the end of each diagnostic section of a structured instrument (the Diagnostic Interview Schedule for Children Version 2.3) in an attempt to link impairment to specific diagnoses. Method Data from 3 sites of the Methods for the Epidemiology of Child and Adolescent Mental Disorders Study were used to assess the reliability of the specific impairment measures by diagnosis, the extent to which global and specific measures of impairment impact on prevalence rates, the concordance between global and specific impairment, and the degree to which there may be a “halo effect” among specific impairment ratings. Results Test-retest reliability was better for parent than youth ratings. Fewer children were rated as impaired on well-validated global scales than on specific impairment ratings, suggesting that the threshold for specific ratings needs to be reevaluated. Agreement between specific and global ratings was poor. Most subjects with 2 or more diagnoses for which impairment was attributed to one diagnosis also had impairment attributed to other diagnoses for which they met symptom criteria, suggesting a halo effect in these ratings of specific impairment. Conclusions Impairment measures are important in diagnostic assessments to distinguish those individuals whose psychopathology is of clinical significance. Specific impairment ratings used in structured instruments could be improved by including parameters of impairment that are diagnosis-specific.
Comparative efficacy and tolerance of esmolol to propranolol for control of supraventricular tachyarrhythmia

This multicenter, double-blind, randomized, parallel study compared the effectiveness and tolerance of intravenous esmolol with intravenous propranolol in patients with supraventricular tachyarrhythmia (heart rate [HR] greater than 120 beats/min). Efficacy was evaluated in 53 patients receiving esmolol and in 57 patients receiving propranolol. Patients randomized to esmolol received infusions of various doses of esmolol ranging from 50 to 300 micrograms/kg/min (each dose infused for 5 minutes) over a 30-minute titration period with intermittent placebo boluses of propranolol. Those randomized for propranolol received 1 mg/min for the first 3 minutes, and then another 3 mg from minutes 5 to 8 with continuous placebo esmolol infusion during the 30-minute titration period. A therapeutic response, defined by 20% or greater reduction in HR, HR less than 100 beats/min or conversion to normal sinus rhythm, was achieved in 72% of patients on esmolol compared with 69% of patients on propranolol (difference not significant). The therapeutic response was maintained in 67% of patients on esmolol and 58% of patients on propranolol (difference not significant) during a 4-hour maintenance period. Conversion to normal sinus rhythm occurred in 14% of esmolol patients and 16% of propranolol patients during titration and 10% of esmolol and 8% of propranolol patients during maintenance. After discontinuation of study drugs, a more rapid reversal of the reduction in HR was observed in esmolol patients compared with those patients receiving propranolol. Adverse reactions were seen in 29 (45%) patients on esmolol and 11 (18%) patients on propranolol. The principle adverse reaction was hypotension, which was predominantly asymptomatic and found in 23 patients receiving esmolol and 4 receiving propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Tensile-strained growth on low-index GaAs

We present a comparative study of the growth of tensile-strained GaP on the four low-index surfaces of GaAs: (001), (110), (111)A, and (111)B. For each surface orientation we outline the growth conditions required for smooth GaAs homoepitaxy. We are able to predict the resulting surface morphology when GaP is deposited onto these four GaAs surfaces by considering the influence of surface orientation on tensile strain relief. GaP deposited on GaAs(001) forms extremely smooth, planar layers. In contrast, the elastic relief of tensile strain on both GaAs(110) and GaAs(111)A leads to the three-dimensional self-assembly of GaP into dislocation-free nanostructures. Similarities between tensile and compressive self-assembly suggest that the kinetics governing many aspects of self-assembled growth is independent of the sign of strain. We show that differences in self-assembly on GaAs(110) and (111)A are the result of unequal adatom diffusion lengths. Tensile-strained self-assembly also occurs on GaAs(111)B, altho...
Relationships between adaptive minimum variance beamforming and optimal source localization

For many years, the popular minimum variance (MV) adaptive beamformer has been well known for not having been derived as a maximum likelihood (ML) estimator. This paper demonstrates that by use of a judicious decomposition of the signal and noise, the log-likelihood function of source location is, in fact, directly proportional to the adaptive MV beamformer output power. In the proposed model, the measurement consists of an unknown temporal signal whose spatial wavefront is known as a function of its unknown location, which is embedded in complex Gaussian noise with unknown but positive definite covariance. Further, in cases where the available observation time is insufficient, a constrained ML estimator is derived here that is closely related to MV beamforming with a diagonally loaded data covariance matrix estimate. The performance of the constrained ML estimator compares favorably with robust MV techniques, giving slightly better root-mean-square error (RMSE) angle-of-arrival estimation of a plane-wave signal in interference. More importantly, however, the fact that such optimal ML techniques are closely related to conventional robust MV methods, such as diagonal loading, lends theoretical justification to the use of these practical approaches.
Is Democratic Regulation of High Finance Possible

C Ford’s paper is about the strengths and limitations of applying sophisticated regulatory design—flexible regulation as opposed to hard and fast traditional forms—to increasingly complex financial systems. The argument itself is complex. Ford is neither an apologist for flexible regulation nor a generalist for or against some grand program. Rather, she increases the magnification: “The main regulatory failures implicated in the crisis,” she writes, “were a function of gaps in regulation, extraordinarily inadequate resources and execution, and an ill-informed and insufficiently skeptical regulatory mindset.” A trio of missteps, then: gaps in regulation, that is, practice or application of law; inadequate resources, that is, vulnerabilities in our regulatory infrastructure; and an insufficiently skeptical mindset, that is, institutional culture. Hers is a multidimensional and robust explanation. Ford is also not a naive traditionalist who thinks we can pour new wine into old wineskins. We “regulate a fluid object such as financial engineering with a fluid form of regulation. I do not suggest that we really can do otherwise,” she writes. A new regulatory approach is needed for a world itself quite new. What can we do then? “What we can do,” Ford says, “is [to] understand the consequences of our regulatory choices and make better-informed and more conscious decisions about what we want the financial sector to achieve.” So what Ford is, is a pragmatist. And like all good pragmatists, a democratic impulse courses through her article.
A statistical analysis of the effect of substrate utilization and shear stress on the kinetics of biofilm detachment

One of the least understood processes affecting biofilm accumulation is detachment. Detachment is the removal of cells and cell products from an established biofilm and subsequent entrainment in the bulk liquid. The goal of this research was to determine the effects of shear stress and substrate loading rate on the rate of biofilm detachment. Monopopulation Pseudomonas aeruginosa and undefined mixed population biofilms were grown on glucose in a RotoTorque biofilm reactor. Three levels of shear stress and substrate loading rate were used to determine their effects on the rate of detachment. Suspended cell concentrations were monitored to determine detachment rates, while other variables were measured to determine their influence on the detachment rate. Results indicate that detachment rate is directly related to biofilm growth rate and that factors which limit growth rate will also limit detachment rate. No significant influence of shear on detachment rate was observed. A new kinetic expression that incorporates substrate utilization rate, yield, and biofilm thickness was compared to published detachment expressions and gives a better correlation of data obtained both in this research and from previous research projects, for both mono- and mixed-population biofilms. © John Wiley & Sons, Inc.
Autophagy-Inducing Protein Beclin-1 in Dendritic Cells Regulates CD4 T Cell Responses and Disease Severity during Respiratory Syncytial Virus Infection

Recent work demonstrated the importance of macroautophagy in dendritic cell (DC) maturation and innate cytokine production upon viral infection through delivery of cytoplasmic viral components to intracellular TLRs. To study the functional consequences of impaired autophagosome formation during a respiratory syncytial virus (RSV) infection, mice harboring significant autophagy defects due to Beclin-1 haploinsufficiency (Beclin-1(+/-)) were used. Upon RSV infection in vivo, lungs of Beclin-1(+/-) mice showed increased Th2 cytokine production, mucus secretion, and lung infiltration of eosinophils and inflammatory DCs. Although isolated airway epithelial cells from Beclin-1(+/-) mice demonstrated little change compared with wild-type mice, Beclin-1(+/-) pulmonary and bone marrow-derived DCs showed decreased expression of MHC class II and innate cytokine production upon RSV infection. Further examination indicated that Beclin-1(+/-) DCs stimulated less IFN-γ and IL-17 production by cocultured CD4(+) T cells and increased Th2 cytokine production in comparison with wild-type controls. Finally, adoptive transfer of RSV-infected Beclin-1(+/-) DCs into the airways of wild-type mice produced severe lung pathology and increased Th2 cytokine production upon subsequent RSV challenge compared with wild-type DC transfer controls. These results indicate a critical role for autophagy in DCs during pulmonary viral infection, facilitating appropriate antiviral adaptive immune responses.
Assessment of dezocine for morphine‐like subjective effects and miosis

Dezocine is an analgesic soon to be marketed in the United States. In this study we examined the abuse potential of dezocine. Subjective and miotic effects of single subcutaneous doses of dezocine, morphine, and placebo were assessed under double-blind conditions in 10 adult male nondependent drug abusers. Dezocine and morphine were equipotent in inducing a constellation of effects typical of opioid agonists, including miosis and increases in opioid signs and symptoms, liking, and euphoria. Both drugs were consistently identified by subjects as being “dope” (opiates). Thus the profile of effects of single doses of dezocine indicate that the drug has the potential to be abused. However, the agonist-antagonist activities of dezocine demonstrated by others suggest that its abuse potential is less than that of morphine. Clinical Pharmacology and Therapeutics (1985) 38, 544–548; doi:10.1038/clpt.1985.221
Curriculum Differentiation and Comprehensive School Reform: Challenges in Providing Educational Opportunity.

Given the efforts of comprehensive school reform to improve the quality of educational opportunities for students by providing a standards based curriculum, this analysis examines the issue of tracking and its implications regarding curriculum differentiation. Using data from middle schools involved with the comprehensive school reform model, America’s Choice, this mixed method analysis shows a complex manifestation of curriculum differentiation where schools had multiple types of academic tracks that responded to students differences including comprehensive learning groups, subject-specific groups, and temporary learning groups used for test preparation. Although school-level reports indicated that most regular education and gifted students were exposed to the America’s Choice English Language Arts and mathematics units, special education students and English Language learners were least likely to gain access to this content. Individual teacher responses to tracking were idiosyncratic where some modified...
Page frame segmentation for contextual advertising in print on demand books

The Web, TV and print publishing are the top three advertisement media. With the technology breakthroughs in digital printing, scanning and data processing, print on demand emerges into a multi-billion dollar business that is due to revolutionize the traditional publishing industry. With the rapid growth of print-on-demand, a whole new advertising media is born, that is, print on demand books. We discuss some unique characteristic of this new media that enables user-targeted contextual advertising, which is more effective than traditional print media. In this paper, we first proposed a contextual-matching based advertising model for print on demand books, and then concentrate on using the page frame segmentation algorithm to solve the problem of where to insert the selected contextual ads in print on demand books. Our page segmentation algorithm shows significant improvement over existing methods in its robustness against noisy background.
T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity

T cell self-tolerance is thought to involve peripheral tolerance and negative selection, involving apoptosis of autoreactive thymocytes. However, evidence supporting an essential role for negative selection is limited. Loss of Bim, a Bcl-2 BH3-only protein essential for thymocyte apoptosis, rarely results in autoimmunity on the C57BL/6 background. Mice with T cell-specific over-expression of Bcl-2, that blocks multiple BH3-only proteins, are also largely normal. The nuclear receptor Nur77, also implicated in negative selection, might function redundantly to promote apoptosis by associating with Bcl-2 and exposing its potentially pro-apoptotic BH3 domain. Here, we report that T cell-specific expression of a Bcl2 BH3 mutant transgene results in enhanced rescue of thymocytes from negative selection. Concomitantly, Treg development is increased. However, aged BH3 mutant mice progressively accumulate activated, autoreactive T cells, culminating in development of multi-organ autoimmunity and lethality. These data provide strong evidence that negative selection is crucial for establishing T cell tolerance.
Achieving Very-Low-Dose Radiation Exposure in Cardiac Computed Tomography, Single-Photon Emission Computed Tomography, and Positron Emission Tomography

During the past several years, the need to reduce radiation has become a central issue in cardiac imaging. During this time, radiation dose to the patient in cardiac computed tomography (CT), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) has seen significant reductions without compromising image quality, primarily because of new developments in scanner hardware and reconstruction software. Sub-mSv radiation doses have been reported for cardiac CT.1–5 Stress and rest SPECT myocardial perfusion imaging (MPI) traditionally required ≈15 minutes to register the required number of photon events. New SPECT camera instrumentation and software have now enabled acquisition times as short as 2 minutes, to increase counting efficiency by up to a factor of 7.6 These new systems can also be used to reduce radiation exposure to patients during the MPI scan, allowing a corresponding marked reduction in the administered dose of radioactivity when used with the standard imaging time.7 It is important to keep radiation exposure as low as reasonably achievable. In this review, therefore, we briefly summarize recent technical advances in scanner hardware and reconstruction software, as well as the steps recommended to achieve very low radiation dose in cardiac imaging. We also review the current status of radiation in cardiac CT, SPECT, and PET as reported in multicenter studies and registries, as well as current clinical reports of radiation dose reduction, which illustrate the potential of the newest technology. Direct imaging of the coronary arteries is challenging because of their small sizes and rapid motion. Cardiac CT requires high temporal resolution to freeze such motion and therefore has benefited from steadily increasing CT gantry rotation speed. Imaging of the coronary arteries also requires high spatial resolution and reconstruction of submillimeter slices. Multiple transaxial slices need to be acquired simultaneously for complete …
Sulfite Reductase Structure at 1.6 Å: Evolution and Catalysis for Reduction of Inorganic Anions

Fundamental chemical transformations for biogeochemical cycling of sulfur and nitrogen are catalyzed by sulfite and nitrite reductases. The crystallographic structure of Escherichia coli sulfite reductase hemoprotein (SiRHP), which catalyzes the concerted six-electron reductions of sulfite to sulfide and nitrite to ammonia, was solved with multiwavelength anomalous diffraction (MAD) of the native siroheme and Fe 4S4 cluster cofactors, multiple isomorphous replacement, and selenomethionine sequence markers. Twofold symmetry within the 64-kilodalton polypeptide generates a distinctive three-domain α/β fold that controls cofactor assembly and reactivity. Homology regions conserved between the symmetry-related halves of SiRHP and among other sulfite and nitrite reductases revealed key residues for stability and function, and identified a sulfite or nitrite reductase repeat (SNiRR) common to a redox-enzyme superfamily. The saddle-shaped siroheme shares a cysteine thiolate ligand with the Fe4S4 cluster and ligates an unexpected phosphate anion. In the substrate complex, sulfite displaces phosphate and binds to siroheme iron through sulfur. An extensive hydrogen-bonding network of positive side chains, water molecules, and siroheme carboxylates activates S-O bonds for reductive cleavage.
Somatic growth of children of diabetic mothers with reference to birth size.

In this study of the effects of maternal diabetes on the growth of offspring, 52 diabetic mothers were enrolled prenatally in the Providence cohort of the Perinatal Collaborative Study during 1960–1963. Among the offspring, there were 12 perinatal deaths. We were able to enroll 34 survivors and 34 matched controls in an adolescent follow-up study. Of the 34 diabetic mothers, six were insulin dependent, six had chemical diabetes, 13 had gestational diabetes, and nine were suspects. As part of the Collaborative Project, sequential follow-up evaluations had been done at four months, one year, four years, and seven years. A positive relationship was found between maternal pre-pregnant weight, weight gain during pregnancy, and the neonatal weight/height index in both diabetic and control subjects. At 7 years of age, eight of 19 offspring of diabetic mothers who were large for gestation at birth were obese, whereas only one of 14 infants who were appropriate for gestation at birth were obese (P
Transcriptional profiling of Mycoplasma hyopneumoniae during iron depletion using microarrays

Mycoplasma hyopneumoniae, the causative agent of swine enzootic pneumonia and a major component of the porcine respiratory disease complex, continues to confound swine producers despite control programmes worldwide. The disease is chronic and self-limiting, but the host is subject to immunopathological changes that potentiate respiratory disease associated with other pathogens. The response of M. hyopneumoniae to environmental stress is of interest because of its relevance to virulence mechanisms in other bacterial pathogens. One of these stressors, iron deprivation, is a prominent feature of the host innate immune response, and most certainly impacts growth of mycoplasmas in vivo. To study this, microarray technology was applied to the transcriptome analysis of M. hyopneumoniae during iron deprivation. An array consisting of 632 of the 698 ORFs in the genome was used to compare the mRNA isolated from organisms grown under normal laboratory conditions with that from organisms subjected to iron deprivation with the chelator 2,2′-dipyridyl. This analysis identified 27 genes that were either up- or down-regulated in response to low-iron growth conditions (P<0·01), with an estimated false discovery rate below 10 %. These included genes encoding transport proteins, enzymes involved in energy metabolism, and components of the translation process. Ten of the 27 identified genes had no assigned function. These studies indicate that M. hyopneumoniae can respond to changes in environmental conditions, but the mechanism employed remains unknown.
Mid-frequency ventilation: unconventional use of conventional mechanical ventilation as a lung-protection strategy.

BACKGROUND: Studies have found that increasing the respiratory frequency during mechanical ventilation does not always improve alveolar minute ventilation and may cause air-trapping. OBJECTIVE: To investigate the theoretical and practical basis of higher-than-normal ventilation frequencies. METHODS: We used an interactive mathematical model of ventilator output during pressure-control ventilation to predict the frequency at which alveolar ventilation is maximized with the lowest tidal volume (VT) for a given pressure. We then tested our predicted optimum frequencies and VT values with various lung compliances and higher-than-normal frequencies, with a lung simulator and 5 mechanical ventilators (Drager Evita XL, Hamilton Galileo, Puritan Bennett 840, Siemens Servo 300 and Servo-i). RESULTS: Compliances between 10 mL/cm H2O and 42 mL/cm H2O yielded VT between 4.1 mL/kg (optimum frequency 75 cycles/min) and 6.0 mL/kg (optimum frequency 27 cycles/min). The intrinsic positive end-expiratory pressure at the optimum frequency was always less than 2 cm H2O. All the ventilators except the Hamilton Galileo had an optimum frequency near 50 cycles/min, whereas the predicted optimum frequency was 60 cycles/min. CONCLUSIONS: With these ventilators and pressure-control ventilation, alveolar minute ventilation can be optimized with higher-than-normal frequency and lower VT than is commonly used in patients with acute respiratory distress syndrome. We call this strategy mid-frequency ventilation.
Preliminary Detection and Analysis of Lung Cancer on CT images using MATLAB: A Cost-effective Alternative

Cancer is the second leading cause of death worldwide. Lung cancer possesses the highest mortality, with non-small cell lung cancer (NSCLC) being its most prevalent subtype of lung cancer. Despite gradual reduction in incidence, approximately 585720 new cancer patients were diagnosed in 2014, with majority from low-and-middle income countries (LMICs). Limited availability of diagnostic equipment, poorly trained medical staff, late revelation of symptoms and classification of the exact lung cancer subtype and overall poor patient access to medical providers result in late or terminal stage diagnosis and delay of treatment. Therefore, the need for an economic, simple, fast computed image-processing system to aid decisions regarding staging and resection, especially for LMICs is clearly imminent. In this study, we developed a preliminary program using MATLAB that accurately detects cancer cells in CT images of lungs of affected patients, measures area of region of interest (ROI) or tumor mass and helps determine nodal spread. A preset value for nodal spread was used, which can be altered accordingly.
Liquidity and Simulation: A Survey of Liquidity Measures Using TraderEx

This paper examines a number of widely used liquidity measures to assess the consistency and reliability of the measures across different liquidity scenarios. A review is conducted of the various measures (based on Gabrielsen, Marzo and Zagaglia, 2011). This paper expands upon their review, by simulating liquidity scenarios using TraderEx software and comparing the sensitivity of the measures to the simulated data. Additionally, empirical data are tested on low and high liquidity assets from the S&P 500 to assess if the differences in empirical data are transferrable (and consistent) with differences in the simulations. Results indicate that the current measures are quite limited due to the inflexibility they exhibit with respect to number of assets, time dependence and time structure dependence. This paper proposes to design new measures for liquidity identification and measurement in simulated environments, which can then be applied to empirical markets, which do not require the rigid assumptions associated with traditional time-series methods.
Effects of Predation and Hunting on Adult Sage Grouse Centrocercus urophasianus in Idaho

Although sage grouse Centrocercus urophasianus have declined throughout their range in North America, little is known about annual mortality patterns of this species. Thus, we summarize a long-term data set on timing and causes of mortality of sage grouse. Predation was the most common cause of death for radio-marked sage grouse. For adult males, 83% of deaths were attributed to predation and 15% to hunting. However, for adult females, 52% of deaths were caused by predation while 42% were attributed to hunting. We rejected the hypothesis that type of mortality (predation vs hunting) was independent of gender of sage grouse. For males, 70% of deaths occurred during spring and summer (March-August) and 28% occurred in September-October. For females, 52% of mortalities occurred during spring and summer and 46% occurred in September-October. We rejected the hypothesis that time of death is independent of the gender of sage grouse. In six of 15 years (40%), harvest rates for adult females may have exceeded 10% while this rate was only exceeded in two of 15 years (13%) for adult males.
A Comparison of Transects and Spot Mapping in Oak-Pine Woodlands of California

We compared density estimates of birds using the spot-mapping and transect methods in grazed and ungrazed habitats in foothill woodlands of the western Sierra Nevada, California. As judged by the percentage error of transect estimates in relation to those from spot mapping, the exponential polynomial estimator from program TRANSECT (Laake et al. 1979) consistently gave better estimates of density than either the Fourier series or exponential power series estimators. Distance estimates grouped into bands of some specified width consistently performed better than ungrouped data, although no single band width was best in all cases. Although several alternatives tested in this study gave density estimates with errors only about half those by a variety of previous methods, even the best alternatives had mean errors of about 25% and maximum errors ranging from 37% to 109%. Errors involved both overand underestimation of density in relation to spot-mapping estimates, even for the same species on the same site in different months or by different observers. The two habitats affected TRANSECT estimates of density differently, and observers differed significantly in the accuracy of their estimates. Because of these problems, transect methods could lead to misinterpretation of real abundance patterns by masking differences between years or sites, even to the extent of suggesting that a species was more abundant in a given year or site than another when the reverse was true. As sample sizes increased, both overestimates and underestimates of density by transect methods converged on density estimates by spot mapping, suggesting a real correspondence in density estimation by these two methods. Empirical assessment of the sample size needed to use program TRANSECT indicated that a data set should include at least 100 records per species--far more than the number normally used to estimate densities by transects.
Neutral proteases confined to one class of lysosomes of human polymorphonuclear leukocytes.

SummaryWe find that protease and esterase activity of human PMN exist in a latent form in a class of membrane-bound particles which sediment at a distinctive density. Readily separated from these granules by sucrose density gradient centrifugation is a separate class of particles, which is associated with an aminopeptidase not previously described in human PMN lysosomal granules. Protease, esterase, and aminopeptidase act optimally at or near pH 7.2.
Conditions of a successful status graduation ceremony: Formerly incarcerated urban youth and their tenuous grip on success:

This article offers an ethnographic examination of a graduation ceremony from ‘Santana School’, a reform school targeting youthful drug offenders. After returning to the facility with five former r...
Risk Behavior and HIV Infection Among New Drug Injectors in the Era of AIDS in New York City

OBJECTIVE To examine HIV risk behavior and HIV infection among new initiates into illicit drug injection in New York City. DESIGN AND METHODS Cross-sectional surveys of injecting drug users (IDUs) recruited from a large detoxification treatment program (n=2489) and a street store-front research site (n=2630) in New York City from 1990 through 1996. Interviews covering demographics, drug use history, and HIV risk behavior were administered; serum samples were collected for HIV testing. Subjects were categorized into two groups of newer injectors: very recent initiates (just began injecting through 3 years) and recent initiates (injecting 4-6 years); and long-term injectors (injecting > or = 7 years). RESULTS 954 of 5119 (19%) of the study subjects were newer injectors, essentially all of whom had begun injecting after knowledge about AIDS was widespread among IDUs in the city. New injectors were more likely to be female and white than long-term injectors, and new injectors were more likely to have begun injecting at an older age (median age at first injection for very recent initiates, 27 years; median age at first injection for recent initiates, 25 years; compared with median age at first injection for long-term injectors, 17 years). The newer injectors generally matched the long-term injectors in frequencies of HIV risk behavior; no significant differences were found among these groups on four measures of injection risk behavior. HIV infection was substantial among the newer injectors: HIV prevalence was 11% among the very recent initiates and 18% among the recent initiates. Among the new injectors, African Americans, Hispanics, females, and men who engaged in male-male sex were more likely to be infected. CONCLUSIONS The new injectors appear to have adopted the reduced risk injection practices of long-term injectors in the city. HIV infection among new injectors, however, must still be considered a considerable public health problem in New York City.