Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiation Arrest by Hypoxia*

The stem cell niche is a unique tissue microenvironment that regulates the self-renewal and differentiation of stem cells. Although several stromal cells and molecular pathways have been identified, the microenvironment of the stem cell niche remains largely unclear. Recent evidence suggests that stem cells are localized in areas with low oxygen. We have hypothesized that hypoxia maintains the undifferentiated phenotype of stem/precursor cells. In this report, we demonstrate that hypoxia reversibly arrests preadipocytes in an undifferentiated state. Consistent with this observation, hypoxia maintains the expression of pref-1, a key stem/precursor cell gene that negatively regulates adipogenic differentiation. We further demonstrate that the hypoxia-inducible factor-1 (HIF-1) constitutes an important mechanism for the inhibition of adipogenic differentiation by hypoxia. Our findings suggest that hypoxia in the stem cell niche is critical for the maintenance of the undifferentiated stem or precursor cell phenotype.
Quantitative structure–pharmacokinetic relationships

Importance of the field: Quantitative structure–pharmacokinetic relationships (QSPKR) modeling is a valuable tool in drug discovery and development. It can provide insights into the molecular determinants of processes governing the time course of drug exposure and response. Areas covered in this review: Empirical and mechanism-based QSPKR models are discussed, including specific examples for oral absorption, nonspecific protein binding, volume of distribution, total metabolic stability and specific interactions with drug metabolizing enzymes. Emphasis is placed on state-of-the-art techniques, including new approaches for the direct simulation of concentration–time profiles from molecular descriptors (temporal QSPKR). What the reader will gain: Reviewing the application of current QSPKR modeling techniques will place these methods in context and highlight their respective advantages and limitations, as well as opportunities for further refinement. Take home message: The expansion of readily available molecular descriptors and advanced algorithms has improved empirical models and enabled the development of robust models for non-congeneric series. Empirical models focus on point estimates of global PK processes and physiologically-based models may be more desirable than data-driven methods. Further integration of relevant biological and pharmacological mechanisms will improve the ability to predict the full time course of drug concentration and effect profiles for diverse compounds and experimental conditions.
A Simulation Model for Decision Support in Business Continuity Planning

Enterprises with a global supply network are at risk of lost revenue as a result of disruptive disasters at supplier locations. Various strategies exist for addressing this risk, and a variety of types of research has been done regarding the identification, assessment and response to the risk of disruption in a supply chain network. This thesis establishes a decision model to support Business Continuity Planning at the first-tier supplier level. The decision model incorporates discrete-event simulation of supply chain networks (through Simio software), Monte Carlo simulation, and risk index optimization. After modeling disruption vulnerability in a supply chain network, costs of implementing all combinations of Business Continuity Plans are ranked and then tested in discrete-event simulation for further insight into inventory levels, unmet customer demand, production loss and related costs. A case study demonstrates the implementation of the decision support process and tests a historical set of data from a large manufacturing company. Discrete-event simulation modeling of loss is confirmed to be accurate. The relevance of the model concept is upheld and recommendations for future work are made. v ACKNOWLEDGMENTS I want to thank my family for their constant support, advisor Dr. Reza Pouraghabagher for his " Sky's the limit " attitude, and Dr. Tali Freed who believed in my potential and encouraged me to explore uncharted waters.
Infrared spectroscopic study of C7 intramolecular hydrogen bonds in peptides

The ir‐spectra in the NH stretching region of Piv‐Pro‐NHMe and Boc‐Pro‐NHMe have been studied in carbon tetrachloride and chloroform solutions over a wide range of concentrations. Based on the concentration dependence of the NH stretching bands, it has been shown that the characteristic NH stretching band due to the C7 intramolecular hydrogen bond is around 3335 cm−1. Intermolecular hydrogen bonding also occurs to a small extent in these peptides, giving rise to a slight concentration dependence of the NH stretching bands. The band around 3335 cm−1 need not necessarily be due to C7 hydrogen bonds alone as proposed by Tsuboi et al. or to intermolecular hydrogen bonding alone as proposed by Maxfield et al.; this conclusion is supported by studies on Boc‐Leu‐NHMe, which undergoes only intermolecular hydrogen bonding. We have shown that Z‐Aib‐Aib‐OMe and Z‐Aib‐Ala‐OMe form C7 intramolecular hydrogen bonds in addition to C5 intramolecular hydrogen bonds. The present studies also show that all the peptides studied exist in more than one conformation in solution.
A novel high step-up interleaved DC-DC converter with ZVZCS

A novel high step-up interleaved DC-DC converter with ZVZCS is proposed. Based on the coupled-inductor and switching-capacitor topology, this converter is designed by combining interleave technique and active clamp together, which can realize soft switching and high output power in the same time. During steady-state modes, the leakage inductance will resonate with two switching capacitors. Under different resonant frequencies, ZVS and ZCS can be realized for certain switches and diodes, respectively. Therefore, the switching loss and reverse recovery are alleviated, which improves the efficiency of the converter. In addition, the mode boundary map for distinguishing soft-switching modes are derived and depicted. A prototype with 24 V input voltage, 400 V output voltage and 800 W output power is implemented in the laboratory to verify the performance of the proposed converter.
Design of a PM Vernier Machine with Consideration for Modulation Flux and Comparison with Conventional PM motors

This study deals with the core design of a PM vernier machine considering modulation flux effects, and the comparative investigation on volume and performance characteristics of the vernier over conventional PM machines are addressed. To these ends, for a PM vernier machine in operation at the base-speed, the flux density equations for teeth and yokes considering the flux modulation effects are derived, where the air gap harmonic permeance function is used. Using the derived equations, a PM vernier motor with specified yoke flux densities is designed. To identify the predicted flux yoke densities, the flux distribution and iron losses in core parts are analyzed through time-step finite element (FE) simulations. Through Fourier series expansion of the air gap flux waves obtained by FE analysis at several specified times, the harmonic components constituting the flux waves are investigated and their speeds are also evaluated in numerical ways. Finally, to estimate the competitiveness of vernier machines versus conventional machines, the designed PM vernier motor is compared against two different conventional PM motors designed through the same design procedures in various aspects such as volume, torque capacity, efficiency, and power factor, in which, in particular, the core losses are included in efficiency calculation.
A random graph model for terrorist transactions

We present a simple model for transactional evidence of terrorist activities that occur in the midst of massive amounts of "transactional noise". The theory is based on random graphs. We consider two random graph processes: an uncorrelated noise model G(n,p) and a target plus noise model G/sub H/(n,p) that prescribes a threat subgraph H within the generated evidence graph. We derive a closed form expression for the likelihood ratio statistic that discriminates between the two processes. The results are extended to other random graph processes, including one in which some of the edges are not visible to the observer. The results suggest that pattern detection in structured, linked data requires pattern matching and that detection with imperfect observability requires hypotheses management.
Mikroekonomiczne optimum alokacji praw własności – próba konceptualizacji

Streszczenie: W artykule zaprezentowano dyskurs na temat równowagi właściciela pod względem wyboru metody (sposobu) wykorzystania posiadanych uprawnień do zarządzania obiektem własności. Wskazano jak właściciel powinien dzielić się swoją wiązką praw do zarządzania, aby z posiadanych uprawnień uzyskać optymalny efekt. Wyznaczono też próg oddzielenia funkcji zarządczych od funkcji właścicielskich podmiotu decyzyjnego, jak również wskazano implikacje optimum właścicielskiego dla nauk o zarządzaniu. Celem dodatkowym artykułu było wykazanie możliwości wyjaśniania zjawisk społeczno-ekonomicznych na gruncie symbiozy ekonomii neoklasycznej i nowej ekonomii instytucjonalnej.
Orally administered pimonidazole to label hypoxic tumor cells.

Pimonidazole, a "hypoxia marker" normally delivered i.v. or i.p., was instead administered in the drinking water of tumor-bearing mice. As pimonidazole exposure was increased from 3-96 h ad libitum, both the fraction of hypoxic tumor cells and the relative number of pimonidazole adducts in those cells increased. Furthermore, the sustained ingestion of pimonidazole revealed a larger hypoxic fraction than did a single injection of an alternative hypoxia marker, CCI-103F. The "additional" hypoxia seen with longer-term oral administration apparently reflects the inclusion of transiently hypoxic tumor cells. Thus, in addition to its convenience and versatility when compared with hypoxia marker injection, oral administration of pimonidazole appears to permit identification of all of the physiologically and therapeutically relevant hypoxic tumor cells.
Dimensional Analysis, Leverage Neutrality, and Market Microstructure Invariance

Market microstructure is the subfield of finance and econophysics1 which studies how prices result from the process of trading securities. Large trades move prices2 and incur trading costs. Here we combine dimensional analysis, leverage neutrality, and a principle of market microstructure invariance to derive scaling laws which express transaction costs functions, bid-ask spreads, bet sizes, number of bets, and other financial variables in terms of trading volume and volatility. For example, market liquidity is proportional to the cube root of the ratio of dollar volume to return variance. We illustrate the scaling by showing that bid-ask spreads in Russian stocks indeed scale with the cube root. In addition to being of interest to risk managers and traders, these scaling laws provide scientific benchmarks for evaluating controversial issues related to high frequency trading, market crashes, and liquidity measurement as well as guidelines for designing policies in the aftermath of financial crisis.
Why bacteria matter in animal development and evolution

While largely studied because of their harmful effects on human health, there is growing appreciation that bacteria are important partners for invertebrates and vertebrates, including man. Epithelia in metazoans do not only select their microbiota; a coevolved consortium of microbes enables both invertebrates and vertebrates to expand the range of diet supply, to shape the complex immune system and to control pathogenic bacteria. Microbes in zebrafish and mice regulate gut epithelial homeostasis. In a squid, microbes control the development of the symbiotic light organ. These discoveries point to a key role for bacteria in any metazoan existence, and imply that beneficial bacteria‐host interactions should be considered an integral part of development and evolution.
Self-Renewal and Cancer of the Gut: Two Sides of a Coin

The intestinal epithelium follows the paradigms of stem cell biology established for other self-renewing tissues. With a unique topology, it constitutes a two-dimensional structure folded into valleys and hills: the proliferative crypts and the differentiated villi. Its unprecedented self-renewal rate appears reflected in a high susceptibility to malignant transformation. The molecular mechanisms that control homeostatic self-renewal and those that underlie colorectal cancer are remarkably symmetrical. Here, we discuss the biology of the intestinal epithelium, emphasizing the roles played by Wnt, bone morphogenic protein, and Notch signaling cascades in epithelial self-renewal and cancer.
The Impact of Entrepreneurial Characteristics and Organisational Culture on Innovativeness in Tourism Firms

Entrepreneurial characteristics and organisational culture have an impact on the innovative capability of a company. Therefore, our research tries to examine the influence of different individual entrepreneurial characteristics and organisational culture dimensions on corporate innovativeness and any direct subsequent company growth. This paper proposes the classification and measurement of five dimensions of entrepreneurial orientation; risk taking, proactiveness, competitive aggressiveness, autonomy and customer orientation and 3 dimensions of organisational culture; power distance, uncertainty/avoidance and individualism/collectivism with the objective of explaining service innovation performance. Specifically, we try to show the differences between the importance of different entrepreneurial characteristic and each organisational culture dimension on a product/service innovation. To this end, a survey was performed on a sample of tourism companies in Slovenia. The data was analysed by employing univariate and multivariate data analyses techniques. Data gathered fromthe survey suggests that entrepreneurial orientation and organisational culture dimensions positively influence innovativeness in tourism companies. Empirical evidence supports the view that a company with more developed entrepreneurial characteristics and organisational culture will be more innovative. This paper is one of the first to find empirical support for the role of entrepreneurial characteristics and organisational culture in tourism companies in Slovenia. Despite a number of limitations, it offers a picture of how these dimensions should be developed in order to enhance innovation. It also presents managerial implications, as managers are responsible for the forming of these dimensions.
Do employees accept the information systems that management buy ? : A BPM implementation case study

Although the contribution of user participation to information sys-tems/information technology (IS/IT) project success is generally acknowledged in the literature, empirical evidence of the different attributes of user participation practices and the role of management in this process is still largely absent. This paper addresses two research questions: first, what determines the attitudes of users to ‘go with a new workflow’ in the case of a Business Process Management (BPM) system implementation? Second, how are these attitudes related to their user satisfaction and use of a BPM system? Based on theories of user participa-tion, management support and implementation effectiveness, a conceptual model is developed that defines a relationship between user participation, user attitudes and success metrics. To test the model, different research methods were used. First, survey data was collected among 78 end-users. Second, nine in-depth open interviews were held with the project manager, key-users and devel-opers. All respondents were employed by a large Dutch administrative social in-surance organisation that had customised and implemented a new and integra-tive BPM system.
Reallocation of Price Risk among Cooperative Members

The purpose of this paper is to explore the theoretical possibility of reallocation of price risk among members of processing cooperatives in the Danish hog and dairy sectors. Based on the observation that no effective price risk management institutions exist for Danish hog and dairy farmers, possible explanations for this are discussed and the possibility of cooperatives to reallocate risk among members is analyzed. Use of futures to hedge individual farmer price risk is absent, which may be due to prohibitively high basis risk. Farmers are exposed to the cooperative price. Endowing members with proportional forward contracts and organizing the exchange of these contracts via a double auction mechanism will reallocate risk, realizing gains depending on member heterogeneity and transaction costs. Most research on risk transfer focuses on vertical reallocations of risk in the value chain, whereas this paper explores the possibility of horizontal risk transfer.
Current Implications of Drug Resistance in Spinal Cord Injury

Murphy DP, Lampert V: Current implications of drug resistance in spinal cord injury. Am J Phys Med Rehabil 2003;82:72–75. A 54-yr-old man with C6 quadriplegia and a neurogenic bowel and bladder was evaluated for clearance of a urinary tract infection after treatment for organisms susceptible to the antibiotics used, and an organism resistant to all antibiotics on the panel grew on the initial follow-up urine culture. Multidrug-resistant organisms present increasing challenges and risks in the management of the neurogenic bladder in patients with spinal cord injury. In an effort to control and reduce the impact and risk associated with these organisms, management methods of the neurogenic bladder and infection control policies should be adjusted according to guidelines from the Centers for Disease Control and related research; such policies could include surveillance for multidrug-resistant organisms and isolation of patients who test positive for these organisms.
Functional Regions of Human Telomerase Reverse Transcriptase and Human Telomerase RNA Required for Telomerase Activity and RNA-Protein Interactions

ABSTRACT Telomerase is a specialized reverse transcriptase (RT) that is minimally composed of a protein catalytic subunit and an RNA component. The RNA subunit contains a short template sequence that directs the synthesis of DNA repeats at the ends of chromosomes. Human telomerase activity can be reconstituted in vitro by the expression of the human telomerase protein catalytic subunit (hTERT) in the presence of recombinant human telomerase RNA (hTR) in a rabbit reticulocyte lysate (RRL) system. We analyzed telomerase activity and binding of hTR to hTERT in RRL by expressing different hTERT and hTR variants. hTRs containing nucleotide substitutions that are predicted to disrupt base pairing in the P3 helix of the pseudoknot weakly reconstituted human telomerase activity yet retained their ability to bind hTERT. Our results also identified two distinct regions of hTR that can independently bind hTERT in vitro. Furthermore, sequences or structures between nucleotides 208 and 330 of hTR (which include the conserved CR4-CR5 domain) were found to be important for hTERT-hTR interactions and for telomerase activity reconstitution. Human TERT carboxy-terminal amino acid deletions extending to motif E or the deletion of the first 280 amino acids abolished human telomerase activity without affecting the ability of hTERT to associate with hTR, suggesting that the RT and RNA binding functions of hTERT are separable. These results indicate that the reconstitution of human telomerase activity in vitro requires regions of hTERT that (i) are distinct from the conserved RT motifs and (ii) bind nucleotides distal to the hTR template sequence.
Increased transvascular escape rate and lymph drainage of albumin in pigs during intravenous diuretic medication. Relations to treatment in man and transport mechanisms.

Transvascular escape rate of albumin (TERalb, i.e. the fraction of intravascular mass of albumin (IVMalb) passing to (or during steady state returning from) the extravascular space per unit time) was determined from the initial disappearance rate of i.v. injected radioiodinated serum albumin in anaesthetized pigs during control conditions and during diuretic medication (furosemide i.v. 20 mg/15 min, total 160-200 mg). During diuretic medication TERalb (mean 17.1% IVMalb X h-1, range 11.5-21, n = 6) increased significantly above the control period (mean 12.3% IVMalb X h-1, range 9.5-16.5, P less than 0.05). Pressures in artery, right atrium, hepatic and portal veins did not change significantly from control to diuretic period. TERalb equals the lymphatic return rate of albumin provided the transport mechanisms are filtrative-convective (i.e. no local back transport). Additional measurements in five pigs with proteins of different molecular size confirmed a dominating filtrative-convective transport. The increased TERalb during diuretic medication is best explained by an increased lymph drainage, which may decrease interstitial fluid pressure and thereby increase the transmural capillary pressure difference being essential for a filtrative-convective transvascular albumin transport. Increased lymph drainage may contribute to the therapeutic effect of diuretic treatment in oedema and ascites.
Integration of Endocrine Signals That Regulate Insect Ecdysis

The extremely large number of insects and members of allied groups alive today suggests that molting--shedding of an old cuticle--may be one of the most commonly performed behaviors on our planet. Removal of an old cuticle in insects is associated with stereotyped, species-specific patterns of behavior referred to as ecdysis. It has been recognized for decades that the initiation of ecdysis is under hormonal control, but until recently many of the key peptides that regulate ecdysis were unknown. The report in 1996 of a new ecdysis-triggering hormone (ETH) sparked an era of significant advances in our understanding of the regulation of molting. This article summarizes the current model of peptide regulation of ecdysis, a model that is based on a positive feedback loop between ETH and a brain peptide, eclosion hormone. Then the relationship of these regulatory peptides to the neural circuitry that is the ultimate driver of the behavior are described. Because insects can undergo both status quo (larval-larval) and metamorphic (larval-pupal and pupal-adult) molts, differences in ecdysis behavior at different life stages are described and potential sources of these differences are identified. Most of the work described is based on studies of ecdysis in the hawkmoth, Manduca sexta, but results from studies of ecdysis in the fruit fly Drosophila melanogaster are also discussed.