gebhart/patrepeval huggingface dataset:
The clinical development of the bryostatins (2002)

The bryostatins are a group of novel macrocyclic lactones derived from the marine bryozoan, Bugula neritina. In vitro evidence indicates that their main mechanism of action is modulation of protein kinase C (PKC) activity. Phase I studies suggested significant antineoplastic activity against several tumor types and defined the main dose-limiting toxicity as myalgia. Bryostatin-1 has subsequently been investigated extensively in phase II clinical trials as a single agent, although trial design has been hampered by lack of human pharmacokinetic data. Results have been generally disappointing but in vitro and animal data suggests an important role for bryostatin-1 in combination with cytotoxic agents. Preliminary results of phase I studies support these observations but further work needs to be done to define the future role of the bryostatins in the clinic.
Tunable narrow linewidth high power erbium:ytterbium co-doped fiber laser (2004)

We present a narrow linewidth cladding-pumped erbium: ytterbium co-doped large-core fiber laser with output power up to 70W at 1560nm, and tunable from 1550 to 1602 nm using a narrow-band fiber Bragg grating.
Learning to Order Things (2011)

There are many applications in which it is desirable to order rather than classify instances. Here we consider the problem of learning how to order instances given feedback in the form of preference judgments, i.e., statements to the effect that one instance should be ranked ahead of another. We outline a two-stage approach in which one first learns by conventional means a binary preference function indicating whether it is advisable to rank one instance before another. Here we consider an on-line algorithm for learning preference functions that is based on Freund and Schapire's 'Hedge' algorithm. In the second stage, new instances are ordered so as to maximize agreement with the learned preference function. We show that the problem of finding the ordering that agrees best with a learned preference function is NP-complete. Nevertheless, we describe simple greedy algorithms that are guaranteed to find a good approximation. Finally, we show how metasearch can be formulated as an ordering problem, and present experimental results on learning a combination of 'search experts', each of which is a domain-specific query expansion strategy for a web search engine.
Heparin potentiates the action of acidic fibroblast growth factor by prolonging its biological half‐life (1989)

The mechanism(s) by which heparin influences the biological activities of acidic and basic fibroblast growth factors (aFGF and bFGF) is not completely understood. One mechanism by which heparin could alter the biological activities of aFGF and bFGF is by altering their biological half-lives. We investigated the possibility that heparin potentiates aFGF-induced neurite outgrowth from PC12 cells by prolonging its biological half-life. Under conditions where heparin potentiated aFGF-induced neurite outgrowth, we observed that heparin increased the biological half-life of aFGF from 7 to 39 hr. We determined that greater than 25 hr of exposure to active aFGF was required for induction of neurite outgrowth. If aFGF activity was maintained for greater than 25 hr by periodic readdition of factor, heparin no longer potentiated aFGF-induced neurite outgrowth. These observations strongly suggest that heparin potentiates the activity of aFGF by prolonging its biological half-life. The protease inhibitors hirudin, leupeptin, and pepstatin A did not potentiate aFGF-induced neurite outgrowth, indicating that proteases inhibited by these inhibitors are not responsible for the loss of aFGF activity that we observed. However, aprotinin potentiated aFGF neurite-promoting activity approximately sevenfold, indicating that proteases that are inhibited by aprotinin are at least partially responsible for aFGF inactivation. These observations suggest that heparin regulates the activity of aFGF by regulating its proteolytic degradation, thereby regulating its biological half-life.
Interleukin‐12 is produced by dendritic cells and mediates T helper 1 development as well as interferon‐γ production by T helper 1 cells (1996)

Interleukin-12 (IL-12), a 70-kDa heterodimeric cytokine composed of covalently linked p35 and p40 chains, is to date the most critical factor for skewing the immune response towards a T helper 1 (Th1) of cytokine profile [high interferon-gamma (IFN-gamma), low IL-4]. Established sources of IL-12 are stimulated macrophages, neutrophils and B cells. As dendritic cells (DC) process antigen in the periphery and then migrate to lymphoid organs to sensitize T cells and induce cell mediated immunity, we reasoned that DC should constitute a critical source of IL-12. The criteria used to detect IL-12 in DC were the demonstration of p40 and p35 mRNA (semiquantitative polymerase chain reaction, northern blotting, and in situ hybridization) as well as IL-12 protein (p70 enzyme-linked immunosorbent assay, p70 antigen capture followed by IFN-gamma bioassay, free p40 chain radioimmunoassay or immunoprecipitation). We found that conventional stimuli such as Staphylococcus aureus induced production of IL-12 by murine as well as human DC in amounts comparable to spleen cells, peritoneal macrophages or peripheral mononuclear cells. DC exhibited, however, features that had not been seen with other antigen-presenting cells: they produced bioactive IL-12 upon antigen-specific interaction with T cells without any other stimuli; in an allogeneic mixed leukocyte reaction model, neutralizing anti-IL-12 antibodies showed that DC-derived IL-12 was critical for optimal proliferation and IFN-gamma production by activated Th1 blasts; and finally, the priming of resting, naive allogeneic T cells by DC, followed by restimulation of primed T blasts by DC, skewed the response to Th1 without the need for any exogenous cytokines or stimuli such as microorganisms. This skewing to Th1 cytokine production, which depended on DC-derived IL-12, but did not require anti-IL-4, exogenous IL-12, or microbes, might be a major function of DC.
Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells. (2010)

Chemotherapy-resistant B-cell hematologic malignancies may be cured with allogeneic hematopoietic stem cell transplantation (HSCT), demonstrating the potential susceptibility of these tumors to donor T-cell mediated immune responses. However, high rates of transplant-related morbidity and mortality limit this approach. For this reason, there is an urgent need for less-toxic forms of immune-based cellular therapy to treat these malignancies. Adoptive transfer of autologous T cells genetically modified to express chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens represents an attractive means of overcoming the limitations of conventional HSCT. To this end, investigators have generated CARs targeted to various antigens expressed by B-cell malignancies, optimized the design of these CARs to enhance receptor mediated T cell signaling, and demonstrated significant anti-tumor efficacy of the resulting CAR modified T cells both in vitro and in vivo mouse tumor models. These encouraging preclinical data have justified the translation of this approach to the clinical setting with currently 12 open clinical trials and one completed clinical trial treating various B-cell malignancies utilizing CAR modified T cells targeted to either the CD19 or CD20 B-cell specific antigens.
Experimental Investigation of TDD Reciprocity-Based Zero-Forcing Transmit Precoding (2010)

We describe an implementation of TDD reciprocity based zero-forcing linear precoding on a wireless testbed. A calibration technique which self-calibrates the base-station without the need for help from other nodes is described. Performance results in terms of downlink channel estimation error as well as bit error rate (BER) and signal to interference noise and distortion ratio (SINDR) are presented for a scenario with two base-stations and two mobile stations, with two antennas at the base-stations and a single antenna at the mobile-station. The results show considerable performance improvements over reference schemes (such as maximum ratio transmission). However, our analysis also reveals that the hardware impairments significantly limit the performance achieved. We further investigate how to model these impairments and attempt to predict the SINDR, such as what would be needed in a coordinated multipoint (CoMP) scenario where scheduling is performed jointly over the two cells. Although the results are obtained for a MISO scenario the general conclusions are relevant also for MIMO scenarios.
Calculating the electrostatic potential of molecules in solution: Method and error assessment (1988)

Abstract We present a numerical method for calculating the electrostatic potential of molecules in solution, using the linearized Poisson‐Boltzmann equation. The emphasis in this work is on applications to biological macromolecules. The accuracy of the method is assessed by comparisons with analytic solutions for the case of a single charge in a dielectric sphere (Tanford‐Kirkwood theory), which serves as a model for a macromolecule. We find that the solutions are generally accurate to within 5%. Larger errors occur close to the charge and the dielectric boundary, but the maximum error found at ion‐bonding distance (3 Å) from a charge close to the boundary (1 Å deep) is only ∼15%. Several algorithmic improvements, described here, contribute to the accuracy of the method. The programs involved compose a coherent software package, called Del Phi, which goes from a Brookhaven Protein Data Bank format file to calculated electrostatic fields.
Frequency space environment map rendering (2002)

We present a new method for real-time rendering of objects with complex isotropic BRDFs under distant natural illumination, as specified by an environment map. Our approach is based on spherical frequency space analysis and includes three main contributions. Firstly, we are able to theoretically analyze required sampling rates and resolutions, which have traditionally been determined in an ad-hoc manner. We also introduce a new compact representation, which we call a spherical harmonic reflection map (SHRM), for efficient representation and rendering. Finally, we show how to rapidly prefilter the environment map to compute the SHRM---our frequency domain prefiltering algorithm is generally orders of magnitude faster than previous angular (spatial) domain approaches.
Novel Spectrophotometric Method for the Quantitation of Urinary Xanthurenic Acid and Its Application in Identifying Individuals with Hyperhomocysteinemia Associated with VitaminB6Deficiency (2013)

A novel spectrophotometric method for the quantification of urinary xanthurenic acid (XA) is described. The direct acid ferric reduction (DAFR) procedure was used to quantify XA after it was purified by a solid-phase extraction column. The linearity of proposed method extends from 2.5 to 100.0 mg/L. The method is precise, yielding day-to-day CVs for two pooled controls of 3.5% and 4.6%, respectively. Correlation studies with an established HPLC method and a fluorometric procedure showed correlation coefficients of 0.98 and 0.98, respectively. Interference from various urinary metabolites was insignificant. In a small-scale screening of elderly conducted at Penghu county in Taiwan (n = 80), we were able to identify a group of twenty individuals having hyperhomocysteinemia (>15 μ mole/L). Three of them were found to be positive for XA as analyzed by the proposed method, which correlated excellently with the results of the activation coefficient method for RBC's AST/B₆ functional test. These data confirm the usefulness of the proposed method for identifying urinary XA as an indicator of vitamin B₆ deficiency-associated hyperhomocysteinemic condition.
Expansion of BCR-ABL Positive Leukemic Stem Cells Is Dependent on Hedgehog Pathway Activation. (2007)

Abstract Chronic Myeloid Leukemia is characterized by the expansion of a leukemic stem cell clone carrying a Philadelphia translocation, which outgrows the non-malignant haematopoietic stem cells. Here we show that BCR-ABL directly enhances self renewal of haematopoietic stem and progenitor cells by activating the hedgehog signaling pathway through upregulation of SMO. Induction of hedgehog signaling in regular bone marrow by overexpression of SMO or loss of PTCH induces expansion of short term repopulating cells, but also enhances the expansion of long term repopulating haematopoietic stem cells. Pharmacological inhibition of SMO activity in BCR-ABL positive bone marrow cultures induced apoptosis in BCR-ABL positive differentiated cells and inhibited colony forming capacity of BCR-ABL positive self renewing cells in vitro. While loss of SMO in regular haematopoiesis only impacts the reconstitution of CD8 positive T-cells and short term repopulating cells (transplantation of SMO−/− fetal liver cells), the development of BCR-ABL positive leukemias was impaired and retransplantability abolished in the absence of SMO expression. Combined treatment of leukemic mice with AMN107 (Abl inhibitor) and Cyclopamine (SMO inhibitor) lead to a reduction of Bcr-Abl positive self-renewing cells in vivo and enhanced the time to relapse more than 3-fold compared to mice treated with AMN107 alone. Thus we conclude that BCR-ABL enhances the self renewal of leukemic stem cells through intrinsic activation of hedgehog signaling by upregulation of SMO. Therefore Hh pathway inhibition alone or in combination with Abl inhibitors could serve as an effective therapeutic strategy to reduce the malignant stem cell pool in BCR-ABL positive leukemias.
What Size Net Gives Valid Generalization? (1989)

We address the question of when a network can be expected to generalize from m random training examples chosen from some arbitrary probability distribution, assuming that future test examples are drawn from the same distribution. Among our results are the following bounds on appropriate sample vs. network size. Assume 0 &lt; ∊ ≤ 1/8. We show that if m ≥ O(W/∊ log N/∊) random examples can be loaded on a feedforward network of linear threshold functions with N nodes and W weights, so that at least a fraction 1 − ∊/2 of the examples are correctly classified, then one has confidence approaching certainty that the network will correctly classify a fraction 1 − ∊ of future test examples drawn from the same distribution. Conversely, for fully-connected feedforward nets with one hidden layer, any learning algorithm using fewer than Ω(W/∊) random training examples will, for some distributions of examples consistent with an appropriate weight choice, fail at least some fixed fraction of the time to find a weight choice that will correctly classify more than a 1 − ∊ fraction of the future test examples.
Motor responses of the urinary bladder and skeletal muscle in Botulinum intoxicated rats (1967)

1. Type A or type D botulinum toxin administered to rats did not produce a generalized paralysis of skeletal muscles at the time of ventilatory arrest. However, if survival was extended by artificial ventilation complete blockade of neuromuscular transmission developed 6.5 hr after 100 MLD of type D and 5 hr after 1000 MLD of type A toxin. The onset of paralysis of a muscle was shortened by repetitive stimulation of the motor nerves.2. There was no consistent blockade of parasympathetically innervated viscera in animals dying after type A toxin. Animals given type D toxin displayed mydriasis and urinary retention before death.3. Motor responses to electrical stimulation, of bladder preparations in vitro were more vulnerable to type D than to type A toxin. When somatic paralysis was complete in animals treated with type A or type D toxin the excised bladders produced pressure elevations 45 and 25%, respectively, of control preparations.4. During electrical stimulation of bladder preparations nearly paralysed by either toxin, the ACh release was significantly diminished from controls. In the rat bladder botulinum toxin specifically disrupted the liberation of mediator from post-ganglionic nerve endings.
The SLam calculus (1998)

The SLam calculus is a typed λ-calculus that maintains security information as well as type information. The type system propagates security information for each object in four forms: the object's creators and readers, and the object's indirect creators and readers (i.e., those agents who, through flow-of-control or the actions of other agents, can influence or be influenced by the content of the object). We prove that the type system prevents security violations and give some examples of its power.
Whole genome amplification increases the efficiency and validity of buccal cell genotyping in pediatric populations. (2001)

The collection of buccal cells provides a noninvasive method for obtaining DNA for genetic studies. Here we report the results on buccal cell genotyping from our ongoing study of childhood leukemia in Northern California. We have collected buccal samples from children ranging in age from 4 months to 15 years using an interviewer- or nurse-administered protocol using a cytology brush. Initial results of the genotyping, including the glutathione S-transferase mu, glutathione S-transferase theta, NAD(P)H:quinone oxidoreductase, and methylenetetrahydrofolate reductase polymorphisms, were disappointing because many specimens contained little DNA, failed repeated attempts at PCR amplification, and produced unreliable results. Here we evaluate a solution to the problem that involves whole genome amplification using the improved primer extension preamplification methodology. Sixty cases of pediatric acute leukemia were studied; five PCR-based genotypes were attempted using buccal cell DNA and whole genome amplified (WGA) buccal DNA. Results were compared with genotyping results using DNA isolated from peripheral whole blood or bone marrow for each child. The standard buccal protocol failed to yield successful PCR reactions in 30-57% of specimens, whereas WGA-buccal was markedly more efficient (2-5% failed PCR). A success rate of 100% was achieved with one repeat test of the failed WGA-PCR reactions. Misclassification of genotype was common for the glutathione S-transferase theta marker using the standard buccal procedure. The WGA-buccal protocol, however, produced genotyping results fully concordant with the referent blood or bone marrow DNA results for all five loci. DNA yields were increased by WGA to allow for approximately 900 PCR reactions/brush. WGA is very useful for improving the efficiency and validity of PCR-based genotyping in pediatric populations.
The Development and Test of the Public Speaking Competence Rubric (2012)

Abstract In response to the demand for increased accountability within the university classroom, there have been calls for a new generation of rubrics that effectively assess students' competence in several areas, including public speaking. This article describes the development, test, and factor analyses of the Public Speaking Competence Rubric (PSCR), an 11-item descriptive rubric designed to be comprehensible to audiences both inside and outside the communication discipline. Study 1, which involved an assessment by five coders of 45 speeches, revealed a complex factor structure and a need to clarify two of the items. Study 2, in which three undergraduate students and one communication faculty person coded 50 speeches, revealed a relatively simple three-factor solution. Comparison of PSCR scores with student speech grades also supported the measure's predictive validity. The last part of the paper describes the potential pedagogical and assessment applications for the PSCR, the limitations of the study, and directions for future research. Overall, the PSCR appears to be a consistent and accurate measure of public speaking ability. Keywords: Public SpeakingSpeechCompetenceEffectivenessAssessmentRubricPedagogy Acknowledgments The authors wish to thank Jennifer Wood, Adam Lawrence, Marjorie Warmkessel, Morgan Hartranft, Nash Doud, and Burns Foster, for their assistance with this research project. The authors also wish to thank the two anonymous reviewers for their helpful comments and suggestions Additional informationNotes on contributorsLisa M. Schreiber Lisa Schreiber (Ph.D. University of Nebraska-Lincoln, 2002) is Assistant Professor of Communication at Millersville University Gregory D. Paul Gregory Paul (Ph.D. Texas A&M, 2009) is Assistant Professor of Communication at Millersville University Lisa R. Shibley Lisa R. Shibley (Ph.D. Penn State, 2004) is the Assistant Vice President of Institutional Advancement and Planning at Millersville University
Therapeutic approach to peptic ulcer relapse. (1989)

The ideal aim of ulcer treatment is to avoid relapse. However, to date it has only been possible to reduce the annual number of relapses following maintenance therapy using different drugs. All prolonged treatments using drugs at doses usually below those used in treating acute outbreaks have shown statistically significant differences in the number of resulting relapses when compared with placebo trials. Reports comparing the results obtained with the different drugs available are contradictory. However, at present the H2 antagonists agents constitute the treatment of choice in preventing relapse, in view of their easy administration and single nocturnal dose requirements. Moreover, there are monitored groups of patients with over five years administration of these drugs, with results being satisfactory and secondary effects very few. Elective surgery to counter relapse is currently less common in cases of uncomplicated ulcers, as the less aggressive and more functional forms of surgery lead to an important percentage of relapse that tends to increase with time. Because of discomfort to the patient, little experience has been accumulated on the administration of associated drugs. In the future, the ideal drug will not only exhibit antisecretory activity, but will also protect the gastric mucosa and prevent ulcer relapse once administration is discontinued.
[Development of laser systems in the treatment of hyperpigmented skin lesions]. (1989)

Laser beams have been in common use for the treatment of hyperpigmented skin lesions. However, therapeutic efficacy has been limited mainly because the output is circular with a Gaussian distribution of intensity, which makes it difficult to apply a uniformly distributed dose to the lesions. We have developed a technique whereby a laser beam is converted to have a square and uniform output intensity distribution. The principle of this technique is that the divergent laser beam enters a glass square pillar, propagates through the pillar repeating the total reflection and emerges with a uniform intensity distribution over the cross-section at the end of the pillar. The device applied this technique is incorporated in a hand-piece and both ruby and argon laser systems have been developed. The ruby laser has been used for the treatment of the melanistic skin lesions such as nevus cell nevus and nevus spilus. In clinical application, 36 of 67 cases have shown remarkably effective results with an improvement rate of 53.7%. The argon laser has been used for the treatment of vasogenic skin lesions such as portwine stain. In clinical application, 44 of 66 cases have shown effective results and the improvement rate is 66.7%. These results are excellent when compared with the other methods of treatment and with laser therapy previously used.