cssi/SciSciGPT-SciSciNet huggingface dataset:
LTBP3 promotes early metastatic events during cancer cell dissemination

Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are important for the secretion, activation, and function of mature TGFβ, especially so in cancer cell physiology. However, specific roles of the LTBPs remain understudied in the context of the primary tumor microenvironment. Herein, we investigated the role of LTBP3 in the distinct processes involved in cancer metastasis. By using three human tumor cell lines of different tissue origin (epidermoid HEp-3 and prostate PC-3 carcinomas and HT-1080 fibrosarcoma) and several metastasis models conducted in both mammalian and avian settings, we show that LTBP3 is involved in the early dissemination of primary cancer cells, namely in the intravasation step of the metastatic cascade. Knockdown of LTBP3 in all tested cell lines led to significant inhibition of tumor cell intravasation, but did not affect primary tumor growth. LTBP3 was dispensable in the late steps of carcinoma cell metastasis that follow tumor cell intravasation, including vascular arrest, extravasation, and tissue colonization. However, LTBP3 depletion diminished the angiogenesis-inducing potential of HEp-3 cells in vivo, which was restorable by exogenous delivery of LTBP3 protein. A similar compensatory approach rescued the dampened intravasation of LTBP3-deficient HEp-3 cells, suggesting that LTBP3 regulates the induction of the intravasation-supporting angiogenic vasculature within developing primary tumors. Using our recently developed microtumor model, we confirmed that LTBP3 loss resulted in the development of intratumoral vessels with an abnormal microarchitecture incompatible with efficient intravasation of HEp-3 carcinoma cells. Collectively, these findings demonstrate that LTBP3 represents a novel oncotarget that has distinctive functions in the regulation of angiogenesis-dependent tumor cell intravasation, a critical process during early cancer dissemination. Our experimental data are also consistent with the survival prognostic value of LTBP3 expression in early-stage head and neck squamous cell carcinomas, further indicating a specific role for LTBP3 in cancer progression toward metastatic disease.
Towards Optimal Denoising of Image Contrast

Most conventional imaging modalities detect light indirectly by observing high-energy photons. The random nature of photon emission and detection is often the dominant sources of noise in imaging. Such case is referred to as photon-limited imaging, and the noise distribution is well modeled as Poisson. Multiplicative multiscale innovation (MMI) presents a natural model for Poisson count measurement, where the inter-scale relation is represented as random partitioning (binomial distribution) or local image contrast. In this paper, we propose a nonparametric empirical Bayes estimator that minimizes the mean square error of MMI coefficients. The proposed method achieves better performance compared with state-of-the-art methods in both synthetic and real sensor image experiments under low illumination.
Interleukin-35: A Novel Mediator of Peripheral Tolerance

Interleukin-35 is a potent suppressive cytokine of the IL-12 family. Although other members of the IL-12 family are produced mainly by antigen-presenting cells (APCs), IL-35 is produced by regulatory T (Treg) cells and suppresses cell proliferation. It has been shown to play an important role in many disease models and has been recently shown to have additional functions aside from inhibition of proliferation, including inducing its own expression in non-Treg cells. In this chapter, we discuss the history and current status of IL-35 biology, as well as suggest where the field might move in the future.
Industry Competition and Total Factor Productivity Growth

This paper analyzes the impact of changes in the competitive market structure on an industry's total factor productivity (TFP) growth. The impact of horizontal mergers on TFP growth is of particular interest. The number of proposed horizontal mergers among U.S. firms totaled 28,818 from 1996 to 2005, while the number of U.S. Department of Justice investigations of proposed mergers totaled 1,303 during the same time period. The impact of mergers upon total factor productivity growth is rightly a topic for consideration. Merger participants routinely claim that mergers will result in welfare improving efficiency gains. If true, these gains should translate into increased TFP growth. This paper estimates this effect and others after presenting a model of TFP growth as a function of changes in the competitive market structure of an industry, changes in production diversification measured at the establishment level, and changes in output per establishment and the number of establishments. Mergers are found to have a positive impact upon TFP growth, accounting for 0.36 percentage points of total factor productivity growth between census years. JEL Classification: D2, L1, L4.
Development of the Relational Ageism Scale: Confirmatory Test on Survey Data:

The objective of the study is to test a refined measure of attitudes about aging as a multidimensional construct reflective of a relational process that includes personal identity (i.e., beliefs about oneself), social identity (i.e., self-conception based on group membership), and collective identity (i.e., self-conception based on comparison of groups) as well as capturing awareness of ageism and its impact. Researchers refined the Aging Anxiety Scale and recruited a convenience sample of 329 participants via a social media platform. A principal component factor analysis revealed the specification of three latent factors: personal, relational, and collective aging anxiety. Awareness of ageism as a problem in society was lower than awareness of other forms of discrimination, and awareness of the negative impacts of ageism was low. The findings support the incorporation of this new measure of relational aging anxiety as a by-product of social identity and construction in future ageism studies.
Functional and Structural Studies on Artemia Polypeptide Chain Initiation Factor 2. Cloning and Sequencing of eIF-2α cDNA

The eukaryotic polypeptide chain initiation factor 2 (eIF-2) plays a significant role in the regulation of protein synthesis [1,2]. The first step in polypeptide chain initiation is the formation of a ternary complex containing eIF-2, GTP and the initiator tRNA. This complex is transferred to a 40S ribosomal subunit [1–4] which later combines with a 60S ribosomal subunit and other initiation factors to form an 80S initiation complex, thereby setting the stage for polypeptide chain elongation. Upon formation of the 80S initiation complex, GTP is hydrolyzed and eIF-2 is released as the eIF-2·GDP binary complex [5,6]. In mammalian systems, this binary complex is stable in the presence of Mg2+ and is functionally inactive [7,8]. Regeneration of eIF-2·GTP·Met-tRNAf species require the guanine nucleotide exchange factor (GEF), which facilitates the exchange of elF-2-bound GDP for GTP and facilitates the recycling of eIF-2 [9–12]. It is at this point in the eIF-2 cycle (Fig. 1) that regulation of polypeptide chain initiation occurs. Most of our understanding about this step in protein synthesis in eukaryotes is derived from studies with rabbit reticulocyte lysates. We have previously observed that dormant and developing embryos of Artemia contain equivalent amounts of eIF-2 activity [13]. Similar to reticulocyte eIF-2, the Artemia factor eIF-2 has 100 to 300-fold higher affinity for GDP than GTP [13] and its α-subunit gets phosphorylated by the rabbit reticulocyte heme-controlled repressor (HCR) [14].
Predictive accuracy of the low erythropoietin level for the diagnosis of polycythemia vera

7060Background: A low erythropoietin (EPO) level is a minor diagnostic criterion for Polycythemia Vera (PV) based on the updated 2016 World Health Organization (WHO) diagnostic criteria for myelopr...
Learning Not to Judge a Book By Its Cover: A Case Series of Malignancy Masquerading As Common Presentations of Sickle Cell Disease

Abstract Background: Sickle cell disease affects 100,000 people in the United States. Cancer does not appear to be more common in individuals with sickle cell disease however many presenting signs and symptoms of cancer overlap with signs and symptoms of sickle cell disease, complicating diagnosis. Furthermore, sickle cell disease can complicate surgical, chemo- and radio- therapies for malignancy. Methods: We reviewed the past 46 years experience of cancers in children with sickle cell at a large urban pediatric referral center. We identified 5 cases and reviewed the presentations, treatments, response to therapy, sickle cell complication and laboratory values, including transfusion needs and effect of chemotherapy on fetal hemoglobin levels. Results: We identified five cases of malignancies in children with sickle cell disease including cases of acute lymphoblastic leukemia (ALL), Hodgkin's lymphoma, Non-Hodgkin's lymphoma (NHL), Wilms tumor and renal cell carcinoma. An additional patient with sickle cell trait was diagnosed with metastatic renal medullary carcinoma. The patients were ages 6-18 years old at diagnosis and 4 were female. All had delays in diagnosis as their initial signs and symptoms overlapped with sickle cell disease (abdominal mass mimicking splenomegaly, low blood counts, fever and posterior reversible encephalopathy syndrome, hematuria). All five achieved complete remission with multi-modality therapy (excluding stem cell transplants) and are currently doing well 1- 20 years after treatment. Admissions for pain were reduced during and for some period after cancer therapy and 2 patients had marked, and in one case, prolonged elevation of fetal hemoglobin after therapy. Discussion: Children with sickle cell develop cancers that can be confused for sickle cell related complications. Cancer therapy can be well tolerated and successful in children with sickle cell. Sickle cell complications are decreased during cancer therapy likely secondary to frequent therapy related transfusion and therapy induced increases in fetal hemoglobin. Disclosures Callaghan: Biogen: Honoraria; Bayer: Honoraria; CSL Behring: Honoraria; Baxalta: Honoraria, Research Funding; Grifols: Honoraria; Roche: Honoraria, Research Funding.
A study on the effect of genotypes, plant growth regulators and sugars in promoting plant regeneration via organogenesis from soybean cotyledonary nodal callus

We have developed an efficient protocol for callus induction and plant regeneration in three elite soybean cultivars (Williams 82, Loda and Newton). The technique is most novel in that the shoot buds developed from the nodal callus. Callus induction and subsequent shoot bud differentiation were achieved from the proximal end of cotyledonary explants on modified Murashige and Skoog (MS) media containing 2.26 μM 2,4-dichlorophenoxy-acetic acid (2,4-D) and 8.8 μM benzyladenine (BAP), respectively. Varying the carbon source optimized the regeneration system further. Among the various carbon sources tested, sorbitol was found to be the best for callus induction and maltose for plant regeneration.
Improving Generalizability of Fake News Detection Methods using Propensity Score Matching.

Recently, due to the booming influence of online social networks, detecting fake news is drawing significant attention from both academic communities and general public. In this paper, we consider the existence of confounding variables in the features of fake news and use Propensity Score Matching (PSM) to select generalizable features in order to reduce the effects of the confounding variables. Experimental results show that the generalizability of fake news method is significantly better by using PSM than using raw frequency to select features. We investigate multiple types of fake news methods (classifiers) such as logistic regression, random forests, and support vector machines. We have consistent observations of performance improvement.
Thermochromic Fibers Via Electrospinning

Cholesteryl ester liquid crystals exhibit thermochromic properties related to the existence of a twisted nematic phase. We formulate ternary mixtures of cholesteryl benzoate (CB), cholesteryl pelargonate (CP), and cholesteryl oleyl carbonate (COC) to achieve thermochromic behavior. We aim to achieve thermochromic fibers by incorporating the liquid crystal formulations into electrospun fibers. Two methods of incorporating the liquid crystal (LC) are compared: (1) blend electrospinning and (2) coaxial electrospinning using the same solvent system for the liquid crystal. For blend electrospinning, intermolecular interactions seem to be important in facilitating fiber formation since addition of LC can suppress bead formation. Coaxial electrospinning produces fibers with higher nominal fiber production rates (g/hr) and with higher nominal LC content in the fiber (wt. LC/wt. polymer assuming all of the solvent evaporates) but larger fiber size distributions as quantified by the coefficient of variation in fiber diameter than blend electrospinning with a single nozzle. Importantly, our proof-of-concept experiments demonstrate that coaxially electrospinning with LC and solvent in the core preserves the thermochromic properties of the LC so that thermochromic fibers are achieved.
Social Motivations for College Hookups

Hookups are a normative experience for college students with 72% of college students reporting hooking up by their Senior year. Although there is over a decade of research on hookups, what motivates college students to participate in hookups is not clear, with prior research focused mostly on psychological rather than social motivations, and differences by gender, but not exploring whether students differ in hookup motivations by other factors. This study explored whether students hooked up and hookup motivations among a random sample of 180 heterosexual college students at a Southeast university, and differences by demographic characteristics, marital age expectations, and parent and peers’ marital status. Results showed the majority of participants hookup up to feel sexual pleasure, with a significant minority motivated by relationship formation and the ‘college experience.’ Significant predictors of hookup motivations include gender, mother’s education, religiosity, parent’s coupled status, and friends’ marital status, while race and age differences were not significant. Results of a latent class analyses showed five distinct classes of social hookup motivations: older and younger abstainers, relationship seekers, pleasure pathway, and college scripts. Implications for future research are discussed.
A Case of Chronic Eosinophilic Leukemia in a Patient With Recurrent Cough, Dyspnea, and Eosinophilia.

We report the case of a 40-year-old man with no significant past medical history who had been hospitalized multiple times over the course of one year with recurring cough, dyspnea, pruritic rash, and variable degrees of eosinophilia. He was variably diagnosed with asthma and pneumonia. After his last hospitalization with severe symptoms, the patient was referred for pulmonary evaluation where hypereosinophilia (HE) led to a hematologic workup. Fluorescence in situ hybridization revealed the FIP1L1-PDGFRA gene fusion and bone marrow analysis confirmed a diagnosis of chronic eosinophilic leukemia. The patient was treated with daily imatinib and prednisone and he was symptom-free at a four-week follow-up examination.
Ozanimod, an S1PR1 ligand, attenuates hypoxia plus glucose deprivation-induced autophagic flux and phenotypic switching in human brain VSM cells

Vascular smooth muscle (VSM) cell phenotypic expression and autophagic state are dynamic responses to stress. Vascular pathologies, such as hypoxemia and ischemic injury, induce a synthetic VSM phe...
Fetal liver and lung volume index of neonatal survival with congenital diaphragmatic hernia

Magnetic resonance imaging (MRI) assesses pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). Neonatal mortality may occur with CDH. To quantify MRI parameters associated with neonatal survival in fetuses with isolated CDH. Fetal MRI for assessing CDH included region of interest (ROI) measurements for total lung volume (TLV), herniated liver volume, herniated other organ volume and predicted lung volume. Ratios of observed lung volume and liver up volume to predicted lung volume (observed to predicted TLV, percentage of the thorax occupied by liver) were calculated and compared to neonatal outcomes. Analyses included Wilcoxon rank sum test, multivariate logistic regression and receiver operating characteristic (ROC) curves. Of 61 studies, the median observed to predicted TLV was 0.25 in survivors and 0.16 in non-survivors (P=0.001) with CDH. The median percentage of the thorax occupied by liver was 0.02 in survivors and 0.22 in non-survivors (P 28 weeks was greater compared to GA ≤28 weeks. The ROC analysis demonstrated an area under the curve of 0.96 (95% confidence interval 0.91–1.00) for the combined observed to predicted TLV, percentage of the thorax occupied by liver and GA. The percentage of the thorax occupied by liver and observed to predicted TLV was predictive of neonatal survival in fetuses with CDH.
Sexual Health Education in Obstetrics and Gynecology (Ob-Gyn) Residencies—A Resident Physician Survey

ABSTRACT Background Many women will experience a sexual health concern and present to their Obstetrics and Gynecology (Ob-Gyn) care provider, yet a large portion of graduating Ob-Gyn resident physicians in the United States may not feel comfortable helping patients with some sexual health issues. Aim To perform a cross-sectional study of U.S. Ob-Gyn resident physicians that assesses sexual health education didactic sessions and comfort level with sexual health clinical vignettes. Methods A 32-item anonymous survey was sent to all 4,065 Ob-Gyn residents on June 7, 2016. Respondents voluntarily completed the survey electronically. Outcomes The primary outcome measures are the comfort level of Ob-Gyn resident physicians in taking a sexual history and providing counseling to patients represented in clinical vignettes, which were based on sexual health learning objectives from the Council on Resident Education in Obstetrics and Gynecology (CREOG). Results Of the 4,065 eligible U.S. examinees, 968 (23.8%) agreed to participate in the study, and 802 (19.7%) completed the survey and were included in the final analysis. Nearly two-thirds of the residents indicated that sexual health training was a priority in residency. However, more than half were not able to describe the disorders of sexual function or list common medications that effect sexual function. When posed with clinical vignettes, residents felt very comfortable obtaining a sexual history (98.5%) and providing counseling (97.0%) for a 16-year-old seeking contraception, yet fewer felt very comfortable obtaining a history and providing counseling for a 26-year-old who is a refugee from Somalia (77.2% and 73.8%). Smaller cohorts felt prepared to take a sexual history and provide counseling for a 17-year-old who discloses that she is a victim of sex trafficking (61.2% and 57.7%), and for a 58-year-old transgender patient planning hormone therapy and surgery (49.9% and 37.9%). In logistic regression analysis, the factors that were influential in an Ob-Gyn resident physician's program to prepare them to describe the disorders of sexual function were post-graduate year (OR 1.387, 95% CI 1.189, 1.618; P = .0001), those that rated the importance of a sexual health curriculum highly (OR 0.701, 95% CI 0.569, 0.864; P = .0012), and a greater number of didactic sessions on sexual health in the residency curriculum (OR 0.685, 95% CI 0.626, 0.750; P Conclusion These findings highlight strengths in the comfort of Ob-Gyn resident physicians about sexual health and illustrate areas of opportunity to engage resident learners by improving the sexual health curriculum. Worly B, Manriquez M, Stagg A, et al. Sexual Health Education in Obstetrics and Gynecology (Ob-Gyn) Residencies—A Resident Physician Survey. J Sex Med 2021;18:1042–1052.
Assessing Clinical Outcomes in Autologous Fat Grafting: A Current Literature Review

Autologous fat grafting, first described in the 1890s, has since undergone many modifications to optimize safety and efficacy. These changes have resulted in the technique that we now consider standard of care, one that is applied to reconstruction and cosmetic enhancement of the breast and the face both independently and in conjunction with surgical treatment. There is a growing body of evidence that this application has positive outcomes for patient satisfaction, surgeon satisfaction, and overall aesthetic appearance. This article summarizes the body of literature regarding these outcomes, reviews complications of fat grafting in the face and breast, and discusses controversies including radiologic imaging changes and longevity of grafting. Level of Evidence: 4.
Trends in Geriatric Ground-Level Falls: Report from the National Trauma Data Bank.

ABSTRACT Introduction Ground-level falls (GLF) are typically reported as a minor mechanism of injury; however, they represent a significant portion of hospitalized geriatric trauma patients as they can result in multisystem injury in this subset of the population. Our study aimed to analyze trends in geriatric trauma falls on the national level. Methods We performed a 5-y (2011-2015) analysis of the American College of Surgeons National Trauma Data Bank (ACS-NTDB) and included all geriatric trauma patients (age ≥ 65 y) who presented with GLF. GLF was identified using ICD-9 E CODES. Our outcome measures were national incidence of GLF, and overall discharge disposition and trauma center level discharge disposition following GLF. We used Cochran Armitage test and multivariate regression analysis. Results We analyzed a total of 1,017,326 geriatric trauma patients, of which 39% had had a fall as a mechanism of injury. Among those who fell, mean age was 78 ± 7, 63% were females, and 85% were whites. The incidence of falls significantly increased over the study period, and was noted to be proportional to age, with a plateau beyond age 85 y old. The rate of discharge to SNF and/or Rehab significantly increased over the study period; however, discharge to home and mortality rates trended downwards over the study period. Discharge to SNF and/or Rehab was significantly lower among level I trauma centers compared to other level trauma centers. Conversely, discharge to home was higher in level I trauma centers compared to other level trauma centers. Conclusion Around one in three elderly trauma patients were admitted following a GLF with an overall increased incidence of falls over time. Although overall mortality rates decreased, there was an increase in adverse discharge disposition and loss of functional independence over the study period, mostly among those admitted to non-level I trauma centers.
Mechanistic understanding of methane-to-methanol conversion on graphene-stabilized single-atom iron centers

The functionalization of methane to value-added liquid chemicals remains as one of the “grand challenges” in chemistry. In this work, we provide insights into the direct methane-to-methanol conversion mechanisms with H2O2 as an oxidant on single Fe-atom centers stabilized on N-functionalized graphene, using first principles calculations. By investigating a series of different reaction paths on various active centers and calculating their turnover frequencies, we reveal that a H2O2-mediated radical mechanism and a Fenton-type mechanism are energetically the most plausible pathways taking place on di- and mono-oxo centers, respectively. Due to the thermodynamic preference of the mono-oxo center formation over the di-oxo under reaction conditions, the Fenton-type mechanism appears to determine the overall catalytic activity. On the other hand, the hydroxy(oxo) center, which is thermodynamically the most favorable center, is found to be catalytically inactive. Hence, the high activity is attributed to a fine balance of keeping the active centers as oxo-species during the reaction. Moreover, we reveal that the presence of solvent (water) can accelerate or slow down different pathways with the overall turnover of the dominant Fenton-type reaction being decreased. Importantly, this work reveals the nature of active sites and a gamut of reaction mechanisms for the direct conversion of methane to methanol rationalizing experimental observations and aiding the search for room temperature catalysts for methane conversion to liquid products.
Astrochemistry Library with Artificial Intelligence for Quality Control

Libraries of reactions used in astrochemistry modeling have seen an explosive increase in size in recent years. Their quality control by manual effort is almost impossible. Expert systems with artificial intelligence are now needed to ensure the quality of large scale astrochemistry libraries.
Effects of nozzle design parameters on the extent of quiet test flow at Mach 3.5

To advance boundary-layer stability and transition research and to ultimately provide reliable predictions of transition for supersonic flight vehicles, a wind tunnel is required with much lower stream disturbance levels than in conventional supersonic tunnels. Recent results from a Mach 3.5 pilot quiet tunnel at the NASA Langley Research Center have shown that very low stream noise levels can be achieved only when the nozzle wall boundary layers are laminar. Transition Reynolds numbers measured on a slender cone were then in the same range as flight data. The linear amplification of both Tollmien-Schlichting (TS) and Gortler type instabilities was calculated for the wall boundary layers in this Mach 3.5 pilot nozzle. By using an eN method, it was determined that amplified Gortler vortices were involved in the transition process. The resulting transition criteria were then applied to several nozzles with different expansion rates and wall curvatures. By manipulation of these parameters, the calculations indicate that it may be possible to increase significantly the size of the quiet test regions compared with those observed in the pilot nozzle.
Solubilization of a mannose-polymerizing enzyme from Phaseolus aureus.

A soluble enzyme preparation, which catalyses the polymerization of mannose, was obtained by Triton X-100 extraction of a particulate fraction derived from Phaseolus aureus hypocotyls. The product that resulted when GDP-α-d-mannose was used as a substrate was a β-(1→4)-linked mannan, about three-quarters of which was alkali-insoluble. The mannose-polymerizing enzyme activity was at least as great in the soluble preparation as in the particulate preparation, and the specific activity of the solubilized enzyme was greater by a factor of at least 3.5. Kinetic studies of the soluble enzyme indicate that the apparent Km is 55–62μm, and a disproportionate increase in rate is observed at high concentrations. GDP-α-d-glucose is a strong competitive inhibitor of the mannose-polymerizing reaction, with an apparent Ki of 6.2μm. The soluble enzyme is relatively unstable, losing about two-thirds of its original activity in 5h at 0°C or in 24h at −20°C. A solvent (acetone, butanol, diethyl ether)-extracted particulate preparation, which also exhibits the same enzyme activity, is more stable, retaining full activity for at least 5 days at −20°C. There was no polymerizing-enzyme activity in the soluble enzyme preparation when UDP-d-glucose, UDP-d-galactose, UDP-d-xylose, UDP-l-arabinose or UDP-d-glucuronic acid were used as substrates. However, the soluble enzyme preparation would catalyse the polymerization of glucose, with GDP-d-glucose as substrate.
A Learning Method for Automated Polyp Detection

Adenomatous polyps in the colon have a high probability of developing into subsequent colorectal carcinoma, the second leading cause of cancer deaths in United States. In this paper, we propose a new method for computer-aided diagnosis of polyps. Initial work with shape detection has shown high sensitivity for polyp detection, but at a cost of too many false positive detections. We present a statistical approach that uses support vector machines to distinguish the differentiating characteristics of polyps and healthy tissue, and subsequently uses this information for the classification of the new cases. One of the main contributions of the paper is a new 3-D pattern analysis approach, which combines the information from many random images to generate reliable signatures of the shapes. At 80% polyp detection rate, the proposed system reduces the false positive rate by 80% compared to previous work.
Proteolytic activity within lysosomes and turnover of pinocytic vesicles. A kinetic analysis.

Degradation of exogenous [1 2 5I] ribonuclease by renal lysosomes follows first-order kinetics in ribonuclease concentration. To demonstrate this, it was necessary to apply corrections for the presence of labeled but digestively inactive particles, either pinocytic vesicles or lysosomes damaged during preparation. Such kinetics were not observed under conditions favoring lysosomal breakdown, i.e., in isotonic KCl, or in the absence of EDTA. The kinetic analysis allows determination of half-times for lysosomal protein digestion. This facilitates comparison of different lysosome preparations, or of in vitro degradation rates with results of in vivo metabolism studies. Degradation of [1 2 5I] ribonuclease showed a half-time of about 1112 minutes in isotonic sucrose or saline media. This is less than the half-time for decrease of kidney radioactivity in vivo after uptake of [1 2 5I] ribonuclease. The proportion of exogenous, labeled protein contained within secondary lysosomes was determined as a function of time after injection of ribonuclease, to monitor transfer of the protein from pinocytic vesicles to lysosomes. Ribonuclease molecules remained in pinocytic vesicles for approximately three minutes after uptake, before passage into the lysosomes.
Hering-Breuer evoked regulation of respiratory rhythm variability in rats (686.25)

Hering-Breuer-related afferent activity affects respiratory patterning in disparate ways: constant mechanical ventilation entrains the respiratory rhythm; yet removal of vagal feedback reduces respiratory rhythm variability. We hypothesize that these effects are mechanistically linked and test this hypothesis by closing the Hering Breuer Reflex feedback loop via rhythmic vagal nerve stimulation in situ before and after suppressing activity in the nucleus tractus solitarii (nTS) or Kolliker-Fuse nuclei (KFn) by microinjection of muscimol, a GABAAR agonist. We measured feedback-evoked entrainment of respiration and the variability of the rhythm in the presence or absence of periodic vagal feedback. Rhythmic vagal feedback evoked periods of entrainment interposed by phase slips. Analysis of respiratory rhythm variability revealed that vagal feedback amplified intrinsic respiratory rhythm variability via the transitions from a phase slip to stable entrainment. Suppressing nTS activity eliminated both entrainm...
Dissolution kinetics of synthetic and natural meta‐autunite minerals, X3−n(n)+ [(UO2)(PO4)]2 · xH2O, under acidic conditions

[1] Mass transport within the uranium geochemical cycle is impacted by the availability of phosphorous. In oxidizing environments, in which the uranyl (UO22+) ionic species is typically mobile, formation of sparingly soluble uranyl phosphate minerals exerts a strong influence on uranium transport. Autunite group minerals, X3 − n(n)+ [(UO2)(PO4)]2 · xH2O, have been identified as the long-term uranium-controlling phases in many systems of geochemical interest. Anthropogenic operations related to uranium mining operations have created acidic environments exposing uranyl phosphate minerals to low-pH groundwaters. Investigations regarding the dissolution behavior of autunite group minerals under acidic conditions have not been reported; consequently, knowledge of the longevity of uranium-controlling solids is incomplete. The purpose of this investigation was threefold: (1) to quantify the dissolution kinetics of natural calcium meta-autunite, Ca[(UO2)2(PO4)2] · 3H2O, and synthetic sodium meta-autunite, Na2[(UO2)2(PO4)2] · 3H2O, under acidic conditions; (2) to measure the effect of temperature and pH on meta-autunite mineral dissolution; and (3) to investigate the formation of secondary uranyl phosphate phases as long-term controls on uranium migration. Single-pass flow-through (SPFT) dissolution tests were conducted over the pH range of 2 to 5 and from 5° to 70°C. Results presented here illustrate meta-autunite dissolution kinetics are strongly dependent on pH but are relatively insensitive to temperature variations. In addition, the formation of secondary uranyl-phosphate phases such as uranyl phosphate, (UO2)3(PO4)2 · x H2O, may serve as a secondary phase limiting the migration of uranium in the environment.
From Requirements to Code: Model Based Development of a Medical Cyber Physical System

The advanced use of technology in medical devices has improved the way health care is delivered to patients. Unfortunately, the increased complexity of modern medical devices poses challenges for development, assurance, and regulatory approval. In an effort to improve the safety of advanced medical devices, organizations such as FDA have supported exploration of techniques to aid in the development and regulatory approval of such systems. In an ongoing research project, our aim is to provide effective development techniques and exemplars of system development artifacts that demonstrate state of the art development techniques.
Molecular Heterogeneity of Midbrain Dopaminergic Neurons – Moving Toward Single Cell Resolution

Since their discovery, midbrain dopamine (DA) neurons have been researched extensively, in part because of their diverse functions and involvement in various neuropsychiatric disorders. Over the last few decades, reports have emerged that midbrain DA neurons were not a homogeneous group, but that DA neurons located in distinct anatomical locations within the midbrain had distinctive properties in terms of physiology, function, and vulnerability. Accordingly, several studies focused on identifying heterogeneous gene expression across DA neuron clusters. Here we review the importance of understanding DA neuron heterogeneity at the molecular level, previous studies detailing heterogeneous gene expression in DA neurons, and finally recent work which brings together previous heterogeneous gene expression profiles in a coordinated manner, at single cell resolution.
Matched weight loss induced by sleeve gastrectomy or gastric bypass similarly improves metabolic function in obese subjects.

Objective The effects of marked weight loss, induced by Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgeries, on insulin sensitivity, β-cell function and the metabolic response to a mixed meal were evaluated. Methods Fourteen nondiabetic insulin-resistant patients who were scheduled to undergo SG (n = 7) or RYGB (n = 7) procedures completed a hyperinsulinemic-euglycemic clamp procedure and a mixed-meal tolerance test before surgery and after losing ∼20% of their initial body weight. Results Insulin sensitivity (insulin-stimulated glucose disposal during a clamp procedure), oral glucose tolerance (postprandial plasma glucose area under the curve), and β-cell function (insulin secretion in relationship to insulin sensitivity) improved after weight loss, and were not different between surgical groups. The metabolic response to meal ingestion was similar after RYGB or SG, manifested by rapid delivery of ingested glucose into the systemic circulation and a large early postprandial increase in plasma glucose, insulin, and C-peptide concentrations in both groups. Conclusions When matched on weight loss, RYGB and SG surgeries result in similar improvements in the two major factors involved in regulating plasma glucose homeostasis, insulin sensitivity and β-cell function in obese people without diabetes.
Impermissible Ratemaking in Health-Insurance Reform: Why the Reid Bill is Unconstitutional

One of the most neglected features in the debate over HR-SA 3590, the Reid Bill, is the level of systematic coercion that it places on health insurance issuers, especially in the individual and small group market. This paper concludes that the combined impact of these restrictions severely compromises the likelihood that these health insurers can remain in business under legislation that eliminates virtually all underwriting discretion in the selection of covered parties and the rates that they charge, imposes minimum restrictions on the services that they supply, and imposes heavy global mandates on the administrative costs that they must bear. This extensive level of regulation rests on the flawed premise that price controls can achieve efficiencies that are not otherwise attainable in markets. The full weight of the Reid Bill is tantamount to treating these insurers as public utilities, who should, but do not receive anything close to, the constitutionally mandated, risk-adjusted rate of return.
Effects of Feeding Formate-Treated Alfalfa Silage or Red Clover Silage on the Production of Lactating Dairy Cows

In trial 1, 15 Holsteins were fed 3 total mixed rations (TMR) with 33% neutral detergent fiber in 3 x 3 Latin squares (28-d periods). Two TMR contained (dry matter basis): 40% control alfalfa silage (CAS) or 40% ammonium tetraformate-treated alfalfa silage (TAS), 20% corn silage (CS), 33% high-moisture shelled corn (HMSC), 6% solvent soybean meal (SSBM), and 18% crude protein (CP); the third TMR contained 54% red clover silage (RCS), 6% dried molasses, 33% HMSC, 6% SSBM, and 16.3% CP. Silages differed in nonprotein N (NPN) and acid detergent insoluble N (ADIN; % of total N): 50 and 4% (CAS); 45 and 3% (TAS); 27 and 8% (RCS). Replacing CAS with TAS increased intake, yields of milk, fat-corrected milk, protein, and solids-not-fat, and apparent dry matter and N efficiency. Replacing CAS with RCS increased intake and N efficiency but not milk yield. Replacing CAS or TAS with RCS lowered milk urea N, increased apparent nutrient digestibility, and diverted N excretion from urine to feces. In trial 2, 24 Holsteins (8 ruminally cannulated) were fed 4 TMR in 4 x 4 Latin squares (28-d periods). Diets included the CAS, TAS, and RCS (RCS1) fed in trial 1 plus an immature RCS (RCS2; 29% NPN, 4% ADIN). The CAS, TAS, and RCS2 diets contained 36% HMSC and 3% SSBM and the RCS1 diet contained 31% HMSC and 9% SSBM. All TMR had 50% legume silage, 10% CS, 27% neutral detergent fiber, and 17 to 18% CP. Little difference was observed between cows fed CAS and TAS. Intakes of DM and yields of milk, fat-corrected milk, fat, protein, lactose, and solids-not-fat, and milk fat and protein content were greater on alfalfa silage vs. RCS. Blood urea N, milk urea N, ruminal ammonia, and total urinary N excretion were reduced on RCS, suggesting better N utilization on the lower NPN silage. Apparent N efficiency tended to be higher for cows fed RCS but there was no difference when N efficiency was expressed as kilograms of milk yield per kilogram of total N excreted.
Adverse perinatal outcome in parturients who use crack cocaine.

Objective: To determine the risk of adverse pregnancy outcome among crack cocaine users in a large homogeneous prenatal population with objective documentation of drug use. Methods: A retrospective cohort study was performed on a population of inner-city women who were offered routine voluntary urine drug screening and who delivered between January and December 1992 at a large county hospital. The study population consisted of 483 users (positive drug screens) and 3158 non-users (negative drug screens). Univariate analysis and multiple logistic regression were used to identify the relation between crack cocaine use and adverse perinatal outcome. Results: Users were significantly more likely than nonusers to deliver low birth weight (LBW) infants (31.3% versus 14.9%, crude odds ratio [OR] 2.6, 95% confidence interval [CI] 2.1, 3.2), growth-restricted infants (29.0% versus 13.0%; crude OR 2.7; 95% CI 2.2, 3.4), and preterm infants (28.2% versus 17.1%, crude OR 1.9; 95% CI 1.5, 2.4). In addition, users were more likely to have abruptions (3.3% versus 1.1% crude OR 3.0; 95% CI 1.6, 5.6) and infants with low 5-minute Apgar scores (7.9% versus 4.5%; crude OR 1.8, 95% CI 1.2, 2.7). After adjusting for confounders (including alcohol use and smoking), only the risks of LBW and fetal growth restriction (FGR) remained significant, with adjusted OR 1.6 (95% CI 1.03, 2.4) and adjusted OR 1.7 (95% CI 1.2, 2.3), respectively. Although there was no significant difference in the rate of low 5-minute Apgar scores between users and non-users after controlling for confounders, users with a positive urine drug screen within 1 week of delivery were significantly more likely than non-users to deliver infants with low 5-minute Apgar scores: crude OR 2.4; adjusted OR 2.0 (95% CI 1.1, 3.7). Conclusion: In this inner-city population, crack cocaine use is associated with adverse pregnancy outcomes, as noted by increased risks of LBW and FGR.
On the relationship between response probability and redundancy in teams of collaborating agents

One of the expected benefits of multi-agent systems is their capacity for redundancy which is expected to promote system robustness. We examine the impact agents' probabilistic action has on generating redundancy in multi-agent systems with no direct inter-agent communication. We present a mathematical model of such a system, analyze the factors that influence it, and empirically examine its effects on multi-agent systems under perturbations such as removal and insertion of agents. Results indicate that agents' probabilistic action can allow a team of collaborating agents to build a pool of agents with experience and this redundant pool can promote system robustness under perturbations.
Measurement of airborne nanoparticle surface area using a filter-based gas adsorption method for inhalation toxicology experiments

AbstractMeasurement of the surface area of airborne nanoparticles as administered to an experimental subject is critical for characterizing exposures during inhalation experiments. A filter-based surface area measurement methodology is described herein that allows for such determinations. Krypton gas adsorption was used to determine total particle surface area. Track-etched polycarbonate 0.4 μm pore filters were chosen as the collection substrate for metal oxide particles due to their highly reproducible surface areas and low background weights. The subject nanomaterials included two different batches of ultrafine TiO2, TiO2 nanorods, and SiO2. The instrument detection limit for surface area was 200 cm2 (0.02 m2). Ninety percent confidence interval estimates of method accuracy were 17.7–23.5% with a point estimate of 20.8%. The filter-based surface area measurement strategy is demonstrated to be a viable sampling and analysis methodology that provides much needed physical characterization information of p...
Comparison of methods for numerical differentiation

Abstract Numerical differentiation can uncover hidden features in chemical data, but the limitations of the technique used should be understood. A method based on fitting data to a quadratic polynomial gives good signal-to-noise ratios, but systematically low derivative intensities. Central difference methods are more accurate but less tolerant of noise.
Early In Vitro Differentiation of Mouse Definitive Endoderm Is Not Correlated with Progressive Maturation of Nuclear DNA Methylation Patterns

The genome organization in pluripotent cells undergoing the first steps of differentiation is highly relevant to the reprogramming process in differentiation. Considering this fact, chromatin texture patterns that identify cells at the very early stage of lineage commitment could serve as valuable tools in the selection of optimal cell phenotypes for regenerative medicine applications. Here we report on the first-time use of high-resolution three-dimensional fluorescence imaging and comprehensive topological cell-by-cell analyses with a novel image-cytometrical approach towards the identification of in situ global nuclear DNA methylation patterns in early endodermal differentiation of mouse ES cells (up to day 6), and the correlations of these patterns with a set of putative markers for pluripotency and endodermal commitment, and the epithelial and mesenchymal character of cells. Utilizing this in vitro cell system as a model for assessing the relationship between differentiation and nuclear DNA methylation patterns, we found that differentiating cell populations display an increasing number of cells with a gain in DNA methylation load: first within their euchromatin, then extending into heterochromatic areas of the nucleus, which also results in significant changes of methylcytosine/global DNA codistribution patterns. We were also able to co-visualize and quantify the concomitant stochastic marker expression on a per-cell basis, for which we did not measure any correlation to methylcytosine loads or distribution patterns. We observe that the progression of global DNA methylation is not correlated with the standard transcription factors associated with endodermal development. Further studies are needed to determine whether the progression of global methylation could represent a useful signature of cellular differentiation. This concept of tracking epigenetic progression may prove useful in the selection of cell phenotypes for future regenerative medicine applications.
Overcoming Barriers to Implementing the International Code of Marketing of Breast Milk Substitutes—The Rosebud Experience

Professional Issues Poster Presentation Purpose for the Program In response to unethical marketing practices of infant artificial substances, such as formula, The World Health Organization (WHO) and the United Nations International Children's Emergency Fund (UNICEF) drafted the International Code of Marketing of Breast Milk Substitutes (the code) in an effort to promote breastfeeding all around the world. Proposed Change The code was officially endorsed by WHO and UNICEF 1981 as an official stance against the unethical marketing and promotion of breast milk substitutes. However, within the United States, no formal legislation exists that requires compliance with the code, and violations of the code that inhibit breastfeeding initiation, duration, and exclusivity occur every day. Courageously, the staff and healthcare providers at the Rosebud PHS Indian Hospital (Rosebud) have taken a unique stand against unethical marketing practices within their facility and have overcome many barriers to implementing the code. Implementation, Outcomes, and Evaluation Rosebud has been successful at implementing the code in its entirety to include exclusion of artificial substances and infant feeding materials as gifts, creating a commercial free patient education curriculum, and educating the entire hospital staff about their roles and responsibilities related to the promotion of breastfeeding and compliance with the code. Implications for Nursing Practice This poster will highlight successful strategies used to overcome barriers of code implementation and create an environment where the promotion of breastfeeding is a priority. These strategies include removal of noncommercialized patient gift packs, acquisition of feeding supplies and artificial substances at fair market value, and education and motivation of staff members about code compliance. Through the implementation of this code, breastfeeding initiation and exclusivity rates have risen significantly at Rosebud. Therefore, the implementation of the code is an evidence‐based paradigm for hospitals all over the world.