Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of in vitro erythropoiesis from bone marrow derived progenitors to detect and study genotoxicity

Assays that predict toxicity are an essential part of drug development and there is a demand for efficient models to better predict human responses. The in vivo micronucleus (MN) assay is a robust toxicity test that assesses the genotoxic effect of drugs on adult bone marrow (BM) using the metric of genotoxic damage to the reticulocyte population in mice. An in vitro correlate to this assay might facilitate extension to human cells and thus provide a highly predictive genotoxicity assay. As first steps in developing a toxicity assay, this thesis work (a) adapted a fetal liver-based in vitro erythropoietic culture system to induce optimized erythropoietic growth from the lineage-marker-negative (Lin) population in adult BM, as adult hematopoietic tissue is ultimately a feasible source of cells; and (b) demonstrated that exposure to alkylating agents induces physiological MN-formation in erythroid populations derived in vitro. The potential for increased efficiency in this in vitro model depends on the ability to stimulate terminal erythroid differentiation at an optimal level from adult BM. With this goal in mind, this thesis work employed experimental design strategies, erythroid-specific growth measurements, and multilinear regression to model erythropoietic growth in this system and thus estimate the relative sensitivity of Lin7 BM to erythropoietic growth parameters, including Erythropoietin, Stem Cell Factor, p02, and Fibronectin, among others. From these erythroid-specific growth measurements, it is estimated that >1500 MN assays can be conducted using the BM of a single mouse. This throughput represents a significant improvement over the current in vivo test, which assays a single condition per mouse. This thesis work then quantified the genotoxic response to three alkylating agents (1,3-bis(2-chloroethyl)1-nitrosourea [BCNU], N-methyl-N -nitro-Nnitrosoguanidine [MNNG], and methylmethane sulfonate [MMS]) in this culture system and detected a significant cytotoxic response and concomitant increase in MN incidence in reticulocytes. This increase in MN frequency provides a clear signal of the genotoxic events that likely lead to global toxicity, and thus mimics the physiological hematopoietic response to alkylating chemotherapeutics. In addition, this thesis work determined that DNA repair-deficient (MGMT" -) BM displayed sensitivity to genotoxic exposure in vivo compared with wild-type (WT) BM, and that this phenotypic response was reflected in erythropoietic cultures. These findings suggest that this in vitro erythroid MN assay is capable of screening for genotoxicity on BM in a physiologically reflective manner. Finally, responses to genotoxicants during erythroid differentiation varied with exposure time, facilitating the study of genotoxic effects at specific developmental stages. Thesis Supervisor: Linda G. Griffith Title: Professor of Biological and Mechanical Engineering Thesis Supervisor: Leona D. Samson Title: Professor of Biology and Biological Engineering
Point of care testing to improve glycemic control.

PURPOSE The purpose of this paper is to pilot-test the feasibility and impact of protocol-driven point-of-care HbAlc testing on levels of glycemic control and on rates of diabetic regimen intensification in an urban community health center serving low-income patients. DESIGN/METHODOLOGY/APPROACH The paper suggests a primary care process re-design, using point of care finger-stick HbA1c testing under a standing order protocol that provided test results to the provider at patient visit. FINDINGS The paper finds that the protocol was well received by both nurses and physicians. HbA1c testing rates increased from 73.6 percent to 86.8 percent (p = 0.40, n = 106). For the 69 patients who had both pre- and post-intervention results, HbAlc levels decreased significantly from 8.55 to 7.84 (p = 0.004, n = 69). At baseline, the health center as a system was relatively ineffective in responding to elevated HbA1c levels. An opportunity to intensify, i.e. a face-to-face visit with lab results available, occurred for only 68.6 percent of elevated HbAlc levels before the intervention, vs. 100 percent post-intervention (p < 0.001). Only 28.6 percent of patients with HbAlc levels >8.0 had their regimens intensified in the pre-intervention phase, compared with 53.8 percent in the post-intervention phase (p = 0.03). RESEARCH LIMITATIONS/IMPLICATIONS This was a pilot-study in one urban health center. Larger group-randomized controlled trials are needed. PRACTICAL IMPLICATIONS The health center's performance as a system, improved significantly as a way of intensifying diabetic regimens thereby achieving improved glycemic control. ORIGINALITY/VALUE This intervention is feasible, replicable and scalable and does not rely on changing physician behaviors to improve primary care diabetic outcomes.
Bildungsressourcen, Bildungsinstitutionen und Bildungsqualität: Makroökonomische Relevanz und mikroökonomische Evidenz

Nach dem sogenannten PISA-Schock wird insbesondere in Deutschland intensiv diskutiert, wie die Qualitat der schulische Ausbildung verbessert werden kann. Dabei herrscht die Uberzeugung vor, dass die Qualitat der schulischen Ausbildung eine wichtige Determinante des langfristigen makrookonomischen Produktivitatswachstums ist, die zumindest teilweise mit einer Variation der staatlichen Bildungsausgaben gesteuert werden kann. Investitionen in Humankapital gelten folgerichtig ganz allgemein als wirtschaftspolitischer Schlussel fur den Erhalt der internationalen Wettbewerbsfahigkeit einer zunehmend wissensbasierten Volkswirtschaft. Daruber hinaus wird auch diskutiert, ob nicht eher institutionelle Reformen statt weiterer Ausgabensteigerungen im Schulsektor notig sind, um die Qualitat der schulischen Ausbildung zu verbessern. Im Gegensatz zur offentlichen Diskussion ist man in der makrookonomischen empirischen Forschung in verschiedenen neueren Studien haufig zu dem Ergebnis gekommen, dass andere Faktoren als das Humankapital fur die grosen internationalen Unterschiede in der Produktivitat des Faktors Arbeit verantwortlich sein mussen. Danach ware von wirtschaftspolitischen Masnahmen im Bildungssektor, wie etwa einer verbesserten finanziellen Ausstattung oder gar einer grundlegenden institutionellen Reform, kein wesentlicher Beitrag zum langfristigen Produktivitatswachstum der Volkswirtschaft zu erwarten. Die aktuelle Debatte zu PISA und den Folgen ware dann lediglich fur eine effiziente Gestaltung des Bildungssektors von Bedeutung, aber nicht daruber hinaus. Als Ausgangspunkt fur unseren Beitrag versuchen wir deshalb zunachst, den aktuellen Stand der internationalen empirischen Forschung zur makrookonomischen Rolle des Humankapitals nachzuzeichnen. In der makrookonomischen empirischen Forschung wird Humankapital im Wesentlichen anhand des durchschnittlichen schulischen Ausbildungsstandes der Arbeitskrafte erfasst. Nicht berucksichtigt wird dabei in der Regel, dass sich die Qualitat der schulischen Ausbildung von Land zu Land zum Teil erheblich unterscheidet, was nicht erst seit PISA bekannt ist. Von daher gesehen ist es kein unbedingt uberraschendes Ergebnis, dass ein rein quantitatives Konzept des Humankapitals nur wenig zu einer statistischen Aufklarung der grosen internationalen Einkommensunterschiede beitragen kann.
Evaluation of testosterone response to intramuscular injection of GnRH and its correlation with sperm quality parameters in cockerels.

Eight 40-week-old New Hampshire cockerels (average liveweight: 3.10 +/- 0.2 kg) were used for studying the testosterone response to a single intramuscular dose (5 micrograms/kg b.w.) of exogenous 6D-Phe gonadotropin releasing hormone (GnRH). Serum samples were collected at 15-min intervals during the first hour and at half-hour intervals up to two hours post injection. The semen samples were collected 24 h before GnRH treatment. Testosterone peaks were found 45 to 60 min after the treatment. The coefficient of correlation between the semen quality parameters and the testosterone response to GnRH was evaluated both by Rank correlation and by multiple regression analyses. Rank correlation showed moderate but not significant values while multiple regression analyses showed a close correlation (multiple R = 0.72). The results show that testosterone response to GnRH may be used as a marker of semen quality in cockerels.
Near-infrared Raman Microspectroscopy Detects High-risk Human Papillomaviruses.

BACKGROUND Detecting human papillomaviruses (HPVs) infection in cervical cells is an exceedingly important part of the clinical management of cervical dysplasia. Current guidelines in women's health outline the need for both the Papanicolaou test as well as high-risk HPV testing. Testing for HPV is expensive, is time-consuming, and requires experienced technicians. METHODS Two sets of near-infrared Raman microspectroscopy experiments were conducted using a Raman confocal microscope system. First, Raman spectra were acquired from four different cell culture lines, two positive for HPV (HeLa, SiHa), one negative for HPV, but malignant (C33A), and one normal, HPV-negative line (NHEK). The three malignant lines were all derived from cervical cells. Second, Raman spectra were acquired from deidentified patient samples that were previously tested for the presence of high-risk HPV. RESULTS The spectra from the cell culture lines and the patient samples contained many statistically significant differences. Using sparse multinomial logistic regression to classify the data led to classification accuracies of 89% to 97% for the cell culture samples and 98.5% for the patient samples. CONCLUSIONS Raman micro-spectroscopy can be used to detect HPV and differentiate among specific HPV strains. This technique may provide health providers with a new method for quickly testing cell samples for the presence of HPV.
Observer-based robust fault diagnosis for a class of uncertain nonlinear systems

Robust fault diagnosis is investigated for a class of uncertain nonlinear flight control systems based on the adaptive observer. A new general fault updating law is presented to relax the assumption conditions of the adaptive observer. In addition, a simplified fault updating law is further presented for the case of constant faults. The asymptotical stability of the adaptive observer and the uniform ultimate boundedness of the fault estimation error vector are proved by Lyapunov theorem. The effectiveness of the proposed scheme is demonstrated through the numerical simulation of a flight control system.
AMERICIUM IN THE BEAGLE DOG: BIOKINETIC AND DOSIMETRIC MODEL

A biokinetic model of the systemic distribution of americium in the beagle dog is presented. The model is based on a previous biokinetic model of plutonium. The data sets used for the development of the model were the measurements of excreted activity (urine and feces) and organ burdens (skeleton, liver, and other soft tissues) for different levels of initial injected activity. In developing the model, the compartmental structure of the skeleton of the plutonium model was adopted, and only the numerical values of parameters were adapted. The model well describes the fractions of americium in the skeleton, liver, and soft tissues and the total fraction excreted in urine and feces. The tuning of the liver clearance parameter provides a realistic description of the change in the partitioning between liver and skeleton for different injection levels. The most significant features of the biokinetics and dosimetry of americium and plutonium in beagles are compared. The total fractions of the clearance to the skeleton and the liver are roughly equal to the value for plutonium, but the partitioning of americium between these organs is reversed with respect to the partitioning of plutonium. 241Am doses to liver and skeleton are similar to 239Pu doses, owing to some counteracting factors. For the highest injection level, the liver mass is dependent on the time post injection. For the skeletal tissues, the dose to the cortical endosteum by far exceeds the dose to the trabecular endosteum and the red marrow. The model provides the basis for statistical survival analyses and risk estimates.
Power-aware inductor analysis in resonant clock networks

The clock distribution network in a synchronous digital circuit delivers the clock signal to every storage element (i.e., clock sink) in the circuit. With the continued increase of clock frequency and clock resources, the clock networks consume substantially large dynamic power. Resonant clock network is one of efficient structures to reduce clock power consumption by storing electric energy to the inserted inductors rather than dissipating through nMOS elements of clock buffers. In the resonant clock network, LC tank placement and sizing are two of the most important problems to minimize power consumption and area overhead. We analyze power consumption of 3-level H-tree by varying the operation frequencies, LC tank placements, and sizes. Through the analyses, we show that the calculation of LC resonant frequency based on the conventional formulation causes a less power reduction than what we normally expect, especially the accuracy of the calculation becomes worse as the clock frequency (> 5GHz) increases.
A 0.6‐V sub‐mW X‐band RFSOI CMOS LNA with novel complementary current‐reused technique

A fully integrated 0.6 V low‐noise amplifier (LNA) for X‐band receiver application based on 0.18 μm RFSOI CMOS technology is presented in this paper. To achieve low noise and high gain with the constraint of low voltage and low power consumption, a novel modified complementary current‐reused LNA using forward body bias technique is proposed. A diode connected MOSFET forward bias technique is employed to minimize the body leakage and improve the noise performance. A notch filter isolator is constructed to improve the linearity of low voltage. The measured results show that the proposed LNA achieves a power gain of 11.2 dB and a noise figure of 3.8 dB, while consuming a DC current of only 1.6 mA at supply voltage of 0.6 V. Copyright © 2017 John Wiley & Sons, Ltd.
An holistic ecological analysis of the diet of Cory's shearwaters using prey morphological characters and DNA barcoding

Knowledge of the dietary choices and trophic niches of organisms is the key to understanding their roles in ecosystems. In seabird diet studies, prey identification is a difficult challenge, often yielding results with technique‐specific biases. Additionally, sampling efforts are often not extensive enough to reveal intrapopulational variation. Immature animals, which may constitute up to 50% of a population, may occupy a significantly different trophic niche to more experienced birds, but this remains largely unexplored. We investigated the diet of Cory's shearwater (Calonectris diomedea) from Selvagem Grande, an island located off the northwest African coast, collecting a total of 698 regurgitate samples over three consecutive breeding seasons. The diet was assessed using two complementary approaches for prey identification: conventional morphological analysis (using fish vertebrae, otoliths and cephalopod beaks) and DNA barcoding of the 16S rRNA mitochondrial gene, in cases where a positive identification could not be retrieved. Species assignments employed BLAST and distance‐based methods, as well as direct optimization of the tree length based on unaligned sequences in POY. This method resulted in robust tree estimates and species assignments, showing its potential for DNA barcoding of stomach contents using hypervariable markers such as the 16S. The molecular approach increased taxonomic resolution and revealed an additional 17 taxa. Diet differed significantly according to breeding status, sex, breeding phase (prelaying and chick rearing) and year. Such direct evidence of trophic segregation within the same population has rarely been shown in seabirds and highlights the importance of including such variables in ecosystem‐based management approaches.
Large Scale Screening for Novel Rab Effectors Reveals Unexpected Broad Rab Binding Specificity*S

Small GTPase Rab is generally thought to control intracellular membrane trafficking through interaction with specific effector molecules. Because of the large number of Rab isoforms in mammals, however, the effectors of most of the mammalian Rabs have never been identified, and the Rab binding specificity of the Rab effectors previously reported has never been thoroughly investigated. In this study we systematically screened for novel Rab effectors by a yeast two-hybrid assay with 28 different mouse or human Rabs (Rab1–30) as bait and identified 27 Rab-binding proteins, including 19 novel ones. We further investigated their Rab binding specificity by a yeast two-hybrid assay with a panel of 60 different GTP-locked mouse or human Rabs. Unexpectedly most (17 of 27) of the Rab-binding proteins we identified exhibited broad Rab binding specificity and bound multiple Rab isoforms. As an example, inositol-polyphosphate 5-phosphatase OCRL (oculocerebrorenal syndrome of Lowe) bound the greatest number of Rabs (i.e. 16 distinct Rabs). Others, however, specifically recognized only a single Rab isoform or only two closely related Rab isoforms. The interaction of eight of the novel Rab-binding proteins identified (e.g. INPP5E and Cog4) with a specific Rab isoform was confirmed by co-immunoprecipitation assay and/or colocalization analysis in mammalian cell cultures, and the novel Rab2B-binding domain of Golgi-associated Rab2B interactor (GARI) and GARI-like proteins was identified by deletion and homology search analyses. The findings suggest that most Rab effectors (or Rab-binding proteins) regulate intracellular membrane trafficking through interaction with several Rab isoforms rather than through a single Rab isoform.
Late Holocene Subsistence Practices Among Cis-Baikal Pastoralists, Siberia: Zooarchaeological Insights from Sagan-Zaba II

Roughly 3000 years ago, nomadic pastoralists began to arrive in the Cis-Baikal region of eastern Siberia. While the archaeological record of these groups is quite extensive, most research on pastoralists here has focused on mortuary traditions while questions about subsistence practices have been left largely unaddressed. Few habitation sites from the late Holocene here contain stratified deposits, and virtually none have been subject to modern excavation methods or zooarchaeological analyses. We present new faunal data from the recently excavated Sagan-Zaba II site located on the west coast of Lake Baikal. This site offers a unique opportunity to examine diachronic patterns in diet and subsistence practices of local pastoralists. It contains stratified deposits associated with different periods of pastoralist occupation spanning much of the late Holocene. Significantly, it is the first site of this period in the region to be screened with fine-meshed sieves and to be systematically studied by zooarchaeologists. The results of our research reveal a series of new insights on pastoralist subsistence practices. First, the primary domesticates in all periods were sheep, goats, cattle, and horses. Cattle appear to increase through time at the site while horses remained relatively rare. Second, pastoralists at Sagan-Zaba regularly hunted Lake Baikal's freshwater seals, long after the introduction of domesticated livestock. Third, hunting of terrestrial mammals, particularly roe deer and red deer, was also common at the site. Finally, our data demonstrate that pastoralists here also regularly fished. This subsistence practice was previously unrecognized in the region, likely due to lack of sieving of sites. Furthermore, these data suggest that historically documented fishing by modern local pastoralists and increases in sedentism were not completely the result of Russian-period settlement of the region but instead were occurring in Cis-Baikal long prior to the modern era.
Coexpressionof pyruvate decarboxylaseandalcohol dehydrogenasegenes inLactobacillusbrevis

Lactobacillus brevis ATCC367 was engineered to express pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) genes in order to increase ethanol fermentation from biomass-derived residues. First, a Gram-positive Sarcina ventriculi PDC gene (Svpdc) was introduced into L. brevis ATCC 367 to obtain L. brevis bbc03. The SvPDC was detected by immunoblot using an SvPDC oligo peptide antiserum, but no increased ethanol was detected in L. brevis bbc03. Then, an ADH gene from L. brevis (Bradh) was cloned behind the Svpdc gene that generated a pdc/adh-coupled ethanol cassette pBBC04. The pBBC04 restored anaerobic growth and conferred ethanol production of Escheirichia coli NZN111 (a fermentative defective strain incapable of growing anaerobically). Approximately 58 kDa (SvPDC) and 28 kDa (BrADH) recombinant proteins were observed in L. brevis bbc04. These results indicated that the Gram-positive ethanol production genes can be expressed in L. brevis using a Gram-positive promoter and pTRKH2 shuttle vector. This work provides evidence that expressing Grampositive ethanol genes in pentose utilizing L. brevis will further aid manipulation of this microbe toward biomass to ethanol production.
Role of Nutrient Limitation and Stationary-Phase Existence in Klebsiella pneumoniae Biofilm Resistance to Ampicillin and Ciprofloxacin

ABSTRACT Biofilms formed by Klebsiella pneumoniae resisted killing during prolonged exposure to ampicillin or ciprofloxacin even though these agents have been shown to penetrate bacterial aggregates. Bacteria dispersed from biofilms into medium quickly regained most of their susceptibility. Experiments with free-floating bacteria showed that stationary-phase bacteria were protected from killing by either antibiotic, especially when the test was performed in medium lacking carbon and nitrogen sources. These results suggested that the antibiotic tolerance of biofilm bacteria could be explained by nutrient limitation in the biofilm leading to stationary-phase existence of at least some of the cells in the biofilm. This mechanism was supported by experimental characterization of nutrient availability and growth status in biofilms. The average specific growth rate of bacteria in biofilms was only 0.032 h−1 compared to the specific growth rate of planktonic bacteria of 0.59 h−1 measured in the same medium. Glucose did not penetrate all the way through the biofilm, and oxygen was shown to penetrate only into the upper 100 μm. The specific catalase activity was elevated in biofilm bacteria to a level similar to that of stationary-phase planktonic cells. Transmission electron microscopy revealed that bacteria were affected by ampicillin near the periphery of the biofilm but were not affected in the interior. Taken together, these results indicate that K. pneumoniae in this system experience nutrient limitation locally within the biofilm, leading to zones in which the bacteria enter stationary phase and are growing slowly or not at all. In these inactive regions, bacteria are less susceptible to killing by antibiotics.