gebhart/patrepeval huggingface dataset:
Pancreatic Carcinogenesis (2004)

Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future.
A discourse-pragmatic explanation for the subject-object asymmetry in early null arguments (1998)

The present paper assesses discourse-pragmatic factors as a potential explanation for the subject-object assymetry in early child language. It identifies a set of factors which characterize typical situations of informativeness (Greenfield &amp; Smith, 1976), and uses these factors to identify informative arguments in data from four children aged 2;0 through 3;6 learning Inuktitut as a first language. In addition, it assesses the extent of the links between features of informativeness on one hand and lexical vs. null and subject vs. object arguments on the other. Results suggest that a pragmatics account of the subject-object asymmetry can be upheld to a greater extent than previous research indicates, and that several of the factors characterizing informativeness are good indicators of those arguments which tend to be omitted in early child language.
Evaluation of some anthracycline antibiotics in an in vivo model for studying drug-induced human leukemia cell differentiation. (1983)

Human acute promyelocytic leukemia cells (HL-60) were induced to undergo terminal differentiation by treatment in vivo with marcellomycin. This was accomplished by cloning HL-60 cells in 0.3% agar in diffusion chambers, which were subsequently implanted in the peritoneal cavities of mice. These animals were given injections i.v. with anthracycline antibiotics, and the chambers were transferred to a second recipient 24 hr later. After an additional 8 days, the chambers were removed, the cloning efficiency was determined, and colonies were scored for the presence of differentiated cells based on their ability to reduce nitro blue tetrazolium (NBT). Marcellomycin produced dose-dependent decreases in cloning efficiency and increases in the number of differentiated cells present in chambers. At all dose levels of marcellomycin tested, three types of colonies were observed; these were colonies consisting entirely of undifferentiated cells and approximately equal numbers of colonies consisting of solely differentiated cells and those with mixtures of both differentiated and undifferentiated cells. An 8-fold increase in colonies containing differentiated cells (both pure and mixed) was observed after a single injection of marcellomycin (10 mg/kg), a dose which reduced cloning efficiency by 40%. At that dosage level, aclacinomycin A also induced differentiation, while doxorubicin was ineffective, a finding consistent with the effects of these anthracyclines on HL-60 cells in suspension culture. In addition to the functional changes accompanying differentiation, commitment was characterized by a limitation in proliferative potential. Thus, the average size of uniform NBT-positive colonies was approximately 16 cells, and few clones of NBT-positive cells greater than 32 cells in number were observed; this contrasted with NBT-negative clones which contained up to 100 cells. This finding suggests that HL-60 cells undergo an average of four and a maximum of five divisions upon commitment to granulocytic differentiation. The in vivo system described may be useful in further evaluation of differentiation-inducing agents for therapeutic potential after an initial in vitro screen to identify active compounds.
Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double‐blind, placebo‐controlled trial (2007)

The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.
Enhanced ion signals in desorption electrospray ionization using surfactant spray solutions (2010)

Solvent optimization is an important procedure in desorption electrospray ionization (DESI) and in this study the effects of solvent surface tension are explored. Data are presented for methanol/water/surfactant solvent systems, which show increases in ion signals of more than an order of magnitude when low concentrations of surfactants are added to the standard methanol/water (1:1) spray solvent. Examples of analytes tested include food chemicals, peptides, pharmaceuticals, and drugs of abuse. The improvement in ion intensity is mainly attributed to the effect of surface tension in producing smaller spray droplets, which are shown to cover a larger surface area. Surfactant-containing spray solutions allowed extension of DESI-MS analysis to previously intractable analytes like melamine and highly hydrophobic compounds like the sudan dyes.
Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor. (1996)

DNA-damaging agents arrest cell cycle progression at either G1 or G2. A variety of agents such as caffeine have been shown to abrogate the DNA damage-dependent G2 checkpoint and enhance cytotoxicity. Unfortunately, this strategy has not enhanced therapeutic activity because adequate concentrations of these modulators are not tolerated in vivo. Here, using Chinese hamster ovary cell lines, we show that the potent protein kinase inhibitor 7-hydroxy-staurosporine (UCN-01) abrogates the G2 arrest induced by the DNA-damaging agent cisplatin. UCN-01 not only was effective at inducing mitosis when added to G2-arrested cells but also prevented cells from arresting in G2 when added to S-phase cells. Furthermore, UCN-01 did not cause premature mitosis of S-phase cells; rather, the cells progressed to G2 before undergoing mitosis. These effects were observed at noncytotoxic concentrations of UCN-01 that alone had no effect on cell cycle passage. Furthermore, the same concentrations of UCN-01 that resulted in abrogation of the cisplatin-induced G2 arrest also enhanced cisplatin-induced cytotoxicity, as determined by a colony formation assay. UCN-01 enhanced cisplatin cytotoxicity up to 60-fold and reduced by 3-fold the concentration of cisplatin required to kill 90% of the cells. The concentrations of UCN-01 required for this enhancement have been shown to be well tolerated in animal models, suggesting that this combination may represent an effective strategy for enhancing cisplatin-based chemotherapeutic regimens.
Roles of Sildenafil in Enhancing Drug Sensitivity in Cancer (2011)

The phenomenon of multidrug resistance (MDR) has decreased the hope for successful cancer chemotherapy. The ATP-binding cassette (ABC) transporter superfamily is the largest transmembrane family. The overexpression of ABC transporters is a major determinant of MDR in cancer cells both in vitro and in vivo. Unfortunately, until recently, most of the strategies used to surmount ABC-transporter-mediated MDR have had limited success. An ideal modulator of MDR would be one that has a low liability to induce toxicity and alter the pharmacokinetic profile of antineoplastic drugs. Sildenafil, an inhibitor of cGMP-specific phosphodiesterase type 5, was found to significantly reverse ABC-transporter-mediated MDR. Our results indicate that sildenafil has differential inhibitory effects on ABC transporters: It significantly decreases the efflux activity of ABCB1 and ABCG2, but has no significant effects on ABCC1. Emerging evidence indicates that sildenafil and other phosphodiesterase type 5 inhibitors may enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs.
Long range channel prediction for adaptive OFDM systems (2005)

In this paper, different techniques for long-range channel prediction for OFDM systems are investigated. Frequency domain channel prediction on each OFDM data subcarrier is first explored and it is shown that the optimum prediction filter depends only on the time-domain channel statistics for the wide-sense stationary uncorrelated scattering (WSSUS) wireless channel. Frequency domain prediction on the pilot subcarriers is investigated next, where the optimum prediction filter is determined for each pilot subcarrier and is reused for all the nearby data subcarriers. Finally, time-domain channel prediction on the multipath taps is explored. It is shown that frequency domain prediction on the pilot subcarriers performs almost identically to prediction using all subcarriers. Furthermore, it is also shown that time-domain prediction outperforms the frequency domain prediction methods.
Preferred functionalization of metallic and small-diameter single walled carbon nanotubes via reductive alkylation (2008)

A selectivity investigation of the covalent sidewall functionalization of SWNTs by reductive alkylation (Billups reaction) is reported. The functionalized tubes Rn-SWNT were characterized by UV-vis-nIR absorption, nIR emission and Raman spectroscopy. The reduction of SWNTs with sodium and the subsequent alkylation of the reduced tubes SWNTn− with butyl iodide reveal a pronounced SWCNT diameter dependence, that is, SWNTs with smaller diameter are considerably more reactive than tubes with larger diameter. Moreover, this reaction sequence also favours the preferred functionalization of metallic over semiconducting tubes. Treatment of the reduced intermediates SWNTn− with protons, via the use of ethanol, instead of alkyl iodide leads to hydrogenated tubes. However, in this case the degree of functionalization is considerably lower than that observed for the corresponding alkylation. Also no pronounced preference of the reaction of metallic and small diameter tubes was observed during the hydrogenation process.
Gentamicin-Impregnated Polymethylmethacrylate Beads Compared With Systemic Antibiotic Therapy in the Treatment of Chronic Osteomyelitis (1993)

A model of chronic osteomyelitis was used to evaluate the efficacy of treatment with debridement alone; debridement plus gentamicin-polymethylmethacrylate (PMMA) bead implantation; debridement plus systemic antibiotic therapy; and debridement plus systemic antibiotics and bead implantation. Debridement with the implantation of gentamicin-PMMA beads and debridement followed by systemic antibiotics were significantly more successful forms of treatment for chronic osteomyelitis than debridement alone or debridement with the implantation of PMMA beads not impregnated with antibiotics. Debridement followed by the implantation of PMMA-gentamicin beads and the use of systemic antibiotics produced the greatest success rate. Treatment with a combination of gentamicin-PMMA beads and systemic antibiotics resulted in a 100% success rate, which, although not statistically better than either treatment alone, suggests a trend.
Augmenting conversations using dual-purpose speech (2004)

In this paper, we explore the concept of dual-purpose speech: speech that is socially appropriate in the context of a human-to-human conversation which also provides meaningful input to a computer. We motivate the use of dual-purpose speech and explore issues of privacy and technological challenges related to mobile speech recognition. We present three applications that utilize dual-purpose speech to assist a user in conversational tasks: the Calendar Navigator Agent, DialogTabs, and Speech Courier. The Calendar Navigator Agent navigates a user's calendar based on socially appropriate speech used while scheduling appointments. DialogTabs allows a user to postpone cognitive processing of conversational material by proving short-term capture of transient information. Finally, Speech Courier allows asynchronous delivery of relevant conversational information to a third party.
The potential for nanoparticle-based drug delivery to the brain: overcoming the blood–brain barrier (2009)

The development of blood-brain barrier (BBB)-targeting technologies is a very active field of research: targeting therapeutic actives to the central nervous system by means of systemic administration means crossing the BBB, and this is now one of the most challenging problems in drug development. The BBB is a unique regulatory system that protects the brain environment by separating it from direct contact with the circulating blood. In doing so, it impedes at the same time the access of a large number of diagnostic and therapeutic agents into the brain parenchyma. One of the possibilities of bypassing this barrier relies on specific properties of nanoparticulate vectors designed to interact with BBB-forming cells at a molecular level, as a result of which the transport of drugs or other molecules (such as nucleic acids, proteins or imaging agents) could be achieved without interfering with the normal function of the brain. This article summarises several recent example applications, presents emerging work and highlights the directions for further developments in this area.
Structural Requirements of Lipid a for Endotoxicity and Other Biological Activities (1989)

For the past ten years, several groups were engaged in synthetic studies of lipid A, namely the lipid portion of bacterial lipopolysaccharides (LPS) that has been assumed to be the bioactive center of LPS, but has not been unanimously approved. Among them, Shiba, Kusumoto, and colleagues, Osaka, Japan have synthesized most energetically and successfully a variety of counterparts of lipid As, biosynthetic lipid A precursors, and their analogs. The endotoxic and related bioactivities of these synthetic compounds were studied by Japanese and German groups, including ours. In 1985, one of the compounds, having an acylation and phosphorylation pattern in beta(1-6)-D-glucosamine disaccharide which was proposed for Escherichia coli F515 lipid A was found to be exhibit full endotoxic and related bioactivities identical to those of the bacterial product. The study was extended by synthesis and examination of bioactivities of variously acylated D-glucosamine di- and monosaccharide phosphates, which correspond to structural components of lipid As, and their analogs or derivatives. Thus, structural requirements have been fairly well elucidated. In this article, first we will review the progress of synthetic and biological studies, with particular emphasis on chemical structure--bioactivities relationships of lipid As, and then we will discuss possible usefulness of some less or nontoxic lipid A-related synthetic compounds in clinical and preventive medicine.
Biologic Responses of Autogenous Bone and Beta-tricalcium Phosphate Ceramics Transplanted into Bone Defects to Orthodontic Forces (1996)

This study was conducted to evaluate biologic responses of autogenous bone (particulate marrow and cancellous bone; PMCB) and beta-tricalcium phosphate ceramics (TCPC) to orthodontic stimuli. Nine dogs served as the experimental animals; three dogs underwent orthodontic tooth movement after grafting, three dogs received PMCB grafting without tooth movement, and three dogs received TCPC grafting without tooth movement. Immediately after extraction of the upper second and/or third incisors, the maxillary alveolar bone was resected bilaterally. Autogenous PMCB obtained from the iliac bone and TCPC were transplanted into each bone defect. Experimental tooth movement was initiated 2 to 4 weeks after the grafting and continued for 9 to 15 weeks. Sectional archwires with open-coll springs were used for distal movement of the upper first incisors into the extraction sites. Oxytetracycline and calcein were employed as bone markers. Sections of grafted areas including the teeth were prepared for light and fluorescence microscopy. The results revealed that both autogenous bone and TCPC presented similar adaptive changes to the original alveolar bone without any external stimuli. TCPC exhibited more prominent biodegradative responses to orthodontic force in association with new cementum formation. Root resorption was also less in the TCPC area than in the PMCB region. It is shown that TCPC is biodegradative in nature and adaptive for remodeling during orthodontic tooth movement. This finding indicates that TCPC may be a better biocompatible alternative to autogenous bone transplanted into bone defects subjected to orthodontic tooth movement.
X-ray diffraction and time-resolved fluorescence analyses of Aequorea green fluorescent protein crystals. (1988)

The energy transfer protein, green fluorescent protein, from the hydromedusan jellyfish Aequorea victoria has been crystallized in two morphologies suitable for x-ray diffraction analysis. Hexagonal plates have been obtained in the P6122 or P6522 space group with a = b = 77.5, c = 370 A, and no more than three molecules per asymmetric unit. Monoclinic parallel-epipeds have been obtained in the C2 space group with a = 93.3, b = 66.5, c = 45.5 A, beta = 108 degrees, and one molecule per asymmetric unit. The monoclinic form is better suited for use in a structure determination, and a data set was collected from the native crystal. Time-resolved fluorescence measurements of large single crystals are possible due to the unique, covalently bound chromophore present in this molecule. Fluorescence emission spectra of Aequorea green fluorescent protein in solution and from either the hexagonal or monoclinic single crystal show similar profiles suggesting that the conformations of protein in solution and in the crystal are similar. Multifrequency phase fluorimetric data obtained from a single crystal were best fit by a single fluorescence lifetime very close to that exhibited by the protein in solution. The complementary structural data obtained from fluorescence spectroscopy and x-ray diffraction crystallography will aid in the elucidation of this novel protein's structure-function relationship.
Large scale metric learning from equivalence constraints (2012)

In this paper, we raise important issues on scalability and the required degree of supervision of existing Mahalanobis metric learning methods. Often rather tedious optimization procedures are applied that become computationally intractable on a large scale. Further, if one considers the constantly growing amount of data it is often infeasible to specify fully supervised labels for all data points. Instead, it is easier to specify labels in form of equivalence constraints. We introduce a simple though effective strategy to learn a distance metric from equivalence constraints, based on a statistical inference perspective. In contrast to existing methods we do not rely on complex optimization problems requiring computationally expensive iterations. Hence, our method is orders of magnitudes faster than comparable methods. Results on a variety of challenging benchmarks with rather diverse nature demonstrate the power of our method. These include faces in unconstrained environments, matching before unseen object instances and person re-identification across spatially disjoint cameras. In the latter two benchmarks we clearly outperform the state-of-the-art.
Playing hide and seek with poorly tasting paediatric medicines: Do not forget the excipients (2014)

The development of paediatric medicines can be challenging since this is a diverse patient population with specific needs. For example, the toxicity of excipients may differ in children compared to adults and children have different taste preferences. Acceptable palatability of oral paediatric medicinal products is of great importance to facilitate patient adherence. This has been recognised by regulatory authorities and so is becoming a key aspect of paediatric pharmaceutical development studies. Many active pharmaceutical ingredients (APIs) have aversive taste characteristics and so it is necessary to utilise taste masking techniques to improve the palatability of paediatric oral formulations. The aim of this review is to provide an overview of different approaches to taste masking APIs in paediatric oral dosage forms, with a focus on the tolerability of excipients used. In addition, where possible, the provision of examples of some marketed products is made.
Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas (2005)

A monoclonal antibody (Rituximab) directed against the B-cell surface antigen, CD20, is increasingly used as a therapy for B-cell lymphomas. However, CD20 is expressed on all normal mature B cells and hence is not a specific tumor target. In contrast, CD70 is expressed on highly activated lymphocytes as well as on many B-cell and T-cell lymphomas but is not expressed on the great majority of B cells and T cells. In this report, we have explored the potential utility of anti-CD70 monoclonal antibodies for treatment of CD70+ EBV+ B-cell lymphomas. Using two Burkitt's lymphoma lines (Raji and Jijoye) that express surface CD70 and a CD70- Burkitt's lymphoma line (Akata), we show that two different monoclonal antibodies directed against human CD70 allow rabbit and human complement to kill EBV+ B cells in a CD70-dependent manner in vitro. In the absence of complement, neither anti-CD70 antibody induced in vitro killing of CD70+ cell lines. Importantly, i.p. injection of anti-CD70 antibodies also inhibited the growth of CD70+ Burkitt's lymphoma cells in severe combined immunodeficient mice but did not inhibit the growth of CD70- Burkitt's lymphoma cells. These results suggest that anti-CD70 antibodies may be useful for the treatment of CD70+ B-cell lymphomas.
Saccharomyces cerevisiae -Based Molecular Tool Kit for Manipulation of Genes from Gram-Negative Bacteria (2006)

A tool kit of vectors was designed to manipulate and express genes from a wide range of gram-negative species by using in vivo recombination. Saccharomyces cerevisiae can use its native recombination proteins to combine several amplicons in a single transformation step with high efficiency. We show that this technology is particularly useful for vector design. Shuttle, suicide, and expression vectors useful in a diverse group of bacteria are described and utilized. This report describes the use of these vectors to mutate clpX and clpP of the opportunistic pathogen Pseudomonas aeruginosa and to explore their roles in biofilm formation and surface motility. Complementation of the rhamnolipid biosynthetic gene rhlB is also described. Expression vectors are used for controlled expression of genes in two pseudomonad species. To demonstrate the facility of building complicated constructs with this technique, the recombination of four PCR-generated amplicons in a single step at >80% efficiency into one of these vectors is shown. These tools can be used for genetic studies of pseudomonads and many other gram-negative bacteria.