gebhart/patrepeval huggingface dataset:
Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. (2002)

Lung cancer is the leading cause of cancer-related death in the United States. There was rapidprogress in the treatment of lung cancer duringpast decades, but local control and survival rates are still poor. Radiation therapy has been an indispensable part of the management of lung cancer, and a recent paradigm is concurrent chemoradiation therapy. Many novel chemotherapeutic agents were recently developed to improve both local and systemic control of cancer, including camptothecin derivatives, which are topoisomerase I inhibitors. Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of camptothecin. Irinotecan is active as a single agent against lung cancer, and is also a potent radiosensitizing agent in human lung cancer cell lines and xenografts. There have been many phase I and II clinical trials demonstrating promising results of single-agent irinotecan and combination with concurrent therapy. This article reviews irinotecan's mechanism of action of cytotoxicity and of radiation-sensitizing effects, as well as recent clinical data regarding combining radiation therapy and irinotecan for both non-small-cell and small-cell lung cancer.
Fiber to the Home Using a PON Infrastructure (2006)

Traffic patterns in access networks have evolved from voice- and text-oriented services to video- and image-based services. This change will require new access networks that support high-speed (> 100 Mb/s), symmetric, and guaranteed bandwidths for future video services with high-definition TV quality. To satisfy the required bandwidth over a 20-km transmission distance, single-mode optical fiber is currently the only practical choice. To minimize the cost of implementing an FTTP solution, a passive optical network (PON) that uses a point-to-multipoint architecture is generally considered to be the best approach. There are several multiple-access techniques to share a single PON architecture, and the authors addressed several of these approaches such as time-division multiple access, wavelength-division multiple access, subcarrier multiple access, and code-division multiple access. Among these multiple techniques, they focus on time-division multiplexing (TDM)-PON and wavelength-division multiplexing (WDM)-PON, which will be the most promising candidates for practical future systems. A TDM-PON shares a single-transmission channel with multiple subscribers in time domain. Then, there exists tight coupling between subscribers. A WDM-PON provides point-to-point optical connectivity using a dedicated pair of wavelengths per user. While a TDM-PON appears to be a satisfactory solution for current bandwidth demands, the combination of future data-rate projections and traffic patterns coupled with recent advances in WDM technology may result in WDM-PON becoming the preferred solution for a future proof fiber-based access network
Bioequivalence of a Dolutegravir, Abacavir, and Lamivudine Fixed-Dose Combination Tablet and the Effect of Food (2014)

The BE of the dolutegravir/abacavir/lamivudine FDC tablet was demonstrated; it may be administered without regard to meals.
Inhibition of CD28‐mediated T cell costimulation by the phosphoinositide 3‐kinase inhibitor wortmannin (1995)

T lymphocyte activation requires at least two signals, one via the antigen-specific T cell receptor and a second via the surface molecule CD28 which provides signals critical to interleukin-2 (IL-2) production and T cell proliferation. We have previously shown (Ward S. G., Westwick, J., Hall N. and Sansom D. M. Eur. J. Immunol. 1993. 23: 2572) that CD28 stimulates phosphoinositide (PI) 3-kinase activity, indicating that D-3 phosphoinositides may act as mediators of CD28-induced T cell costimulation. Here, we report that immunoprecipitation of CD28 molecules from Jurkat cells stimulated with the CD28-ligand B7, results in a ligand-dependent association of CD28 with PI 3-kinase. This association correlates with the appearance of PI 3-kinase enzymatic activity in CD28 immunoprecipitates and the formation of D-3 phosphoinositides. Consistent with the hypothesis that D-3 phosphoinositides are important mediators of CD28 signaling, treatment of T cells with the PI 3-kinase inhibitor wortmannin, inhibited both T cell proliferation and production of IL-2, but not the response of T cells to exogenous IL-2. Hence, abrogation of PI 3-kinase activity by wortmannin, appears sufficient to disrupt the costimulatory pathway utilized by CD28, indicating a central role for this enzyme in the CD28 signaling pathway.
Silencing disease genes in the laboratory and the clinic (2011)

Synthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology.
High focal depth with a pure-phase apodizer (2001)

High-density optical data storage requires high-numerical-aperture (NA) lenses and short wavelengths. But, with increasing NA and decreasing wavelength, the depth of focus (DOF) decreases rapidly. We propose to use pure-phase superresolution apodizers to optimize the axial intensity distribution and extend the DOF of an optical pickup. With this kind of apodizer, the expected DOF can be 2-4.88 times greater than that of the original system, and the spot size will be smaller than that of the original system.
Binaural reverberation using a modified Jot reverberator with frequency- dependent interaural coherence matching (2009)

An extension of the Jot reverberator is presented, producing binaural late reverberation where the interaural coherence can be controlled as a function of frequency such that it matches the frequency-dependent interaural coherence of a reference binaural room impulse response (BRIR). The control of the interaural coherence is implemented using linear filters outside the reverberatorâs recursive loop. In the absence of a reference BRIR, these filters can be calculated from an HRTF set.
Using sensor networks and data fusion for early detection of active worms (2003)

Identification of an Internet worm is a manual process where security analysts must observe and analyze unusual activity on multiple firewalls, intrusion-detection systems or hosts. A worm might not be positively identified until it already has spread to most of the Internet, eliminating many defensive options. In this paper, we present an automated system that can identify active worms seconds or minutes after they first begin to spread, a necessary precursor to halting the spread of a worm, rather than simply cleaning up afterward. Our implemented system collects ICMP Unreachable messages from instrumented network routers, identifies those patterns of unreachable messages that indicate malicious scanning activity, and then searches for patterns of scanning activity that indicate a propagating worm. In this paper, we examine the problem of active worms, describe our ICMP-based detection system, and present simulation results that illustrate the speed with which it can detect a worm.
Work Attitudes in Windowedvs.Windowless Environments (1981)

"Work Attitudes in Windowed vs. Windowless Environments." The Journal of Social Psychology, 115(2), pp. 291–292
Neurotrophins and their receptors in chicken neuronal development (1995)

A review on current studies of chicken neurotrophins and their receptors is given. Chicken NGF, BDNF and NT-3 have been cloned and sequences have been used to synthesize oligonucleotides for specific localization of expression during development. Also, chicken TrkA, TrkB and TrkC have been cloned, sequenced and studied by in situ hybridization. Recombinant NT-3 was applied to chicken ganglia at different developmental stages to examine acquirement of responsiveness to NT-3 compared to NGF. Phylogenetic analyses of the chicken neurotrophins and Trk receptors were carried out based on parsimony. Finally, some data on apoptosis in chicken embryo sympathetic ganglia are presented.
The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair (2004)

Alveolar epithelial type I cells cover most of the internal surface area of the lungs. Ultrastructural studies demonstrate that alveolar epithelial type I cell damage is frequently observed in acute and chronic lung diseases. This article discusses the use of cell-selective proteins as markers for the investigation of injury and repair of the alveolar epithelium. The utility of proteins specific to alveolar epithelial type I cells as diagnostic markers of alveolar epithelial injury in acute lung injury is considered, and expression of proteins selective for alveolar epithelial type I cells in lungs following injury and in fibrosis are discussed.
Extraction of impacted mandibular third molars: postoperative complications and their risk factors. (2007)

Surgical removal of impacted mandibular third molars should be carried out well before the age of 24 years, especially for female patients. Older patients are at greater risk of postoperative complications and permanent sequelae. A surgeon's lack of experience could also be a major factor in the development of postoperative complications.
Distinct genetic alterations occur in ovarian tumor cells selected for combined resistance to carboplatin and docetaxel (2012)

Ovarian tumor cells can acquire resistance to both carboplatin and docetaxel when selected in the presence of both agents. Distinct changes in gene expression occur in the dual resistant cell line indicating that dual resistance is not a simple combination of the changes observed in cell lines exhibiting single agent resistance.
NOD2 mutations and Crohn’s disease: are Paneth cells and their antimicrobial peptides the link? (2004)

There is evidence that CARD15/NOD2 variants in Crohn’s disease are associated with diminished mucosal α-defensin production, resulting in impaired innate immunity

Paneth cells (reviewed by Cunliffe and colleagues1,2) are granulated epithelial cells found at the base of small intestinal crypts. They are most numerous in the terminal ileum and are not found in the normal colon. They secrete a variety of antimicrobial peptides and proteins, including α-defensins, lysozyme, and secretory phospholipase A2 (sPLA2), in response to bacterial products and cholinergic agents. There is a link between intestinal inflammation and Paneth cell number. In mouse models of enteric infection, Paneth cell hyperplasia occurs in response to signals from activated T cells, in mouse models of ileocolitis there is Paneth cell metaplasia, and in inflammatory bowel disease, Paneth cell metaplasia is also seen in the colon. Parasite infestations also induce an increase in the number of Paneth cells in the murine small intestine.

Defensins (reviewed by Ganz3) are a family of small (29–45 amino acid) cationic antimicrobial peptides that are divided into two main classes, the α- and β-defensins, on the basis of their disulphide bond pairing pattern. They are encoded by single genes as prepropeptides, which are then processed to mature active forms. The mammalian defensin genes probably evolved from a single ancestral gene but because of selection pressure and rapid evolution, comparisons between species is difficult.4

Six α-defensins have been identified in humans: four are neutrophil peptides and two human defensins (HD-5 and HD-6) are expressed in intestinal Paneth cells. HD-5 is expressed in Paneth cells of the duodenum, jejunum, and ileum, but is not found in the normal stomach or colon. In cases of gastritis, Crohn’s colitis, and ulcerative colitis, HD-5 is expressed in metaplastic Paneth cells.

In vitro, α-defensins have broad spectrum …
Topical treatment of melasma (2009)

Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ) is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma.
Treatment with Indinavir, Zidovudine, and Lamivudine in Adults with Human Immunodeficiency Virus Infection and Prior Antiretroviral Therapy (1997)

In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.
Survivin, a cancer target with an emerging role in normal adult tissues (2006)

Abstract Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with chemotherapy resistance, increased tumor recurrence, and shorter patient survival, making antisurvivin therapy an attractive cancer treatment strategy. However, growing evidence indicates that survivin is expressed in normal adult cells, particularly primitive hematopoietic cells, T lymphocytes, polymorphonuclear neutrophils, and vascular endothelial cells, and may regulate their proliferation or survival. In preclinical animal models, targeted antisurvivin therapies show efficacy without overt toxicity. However, consequences of prolonged survivin disruption in normal cells, particularly those associated with continuous renewal, have not been clearly determined. Understanding the role of survivin in normal versus malignant cells will be important in identifying strategies that maximally disrupt survivin in cancer cells with minimal effect on normal tissues. In this review, we summarize the prognostic relevance of survivin in cancer that justifies the pursuit of antisurvivin therapies and discuss differences in survivin expression between normal and cancer cells. We subsequently review expression of survivin in normal adult tissues and evaluate preclinical antisurvivin therapies reported to date in light of emerging roles for survivin in normal physiology, particularly hematopoiesis, angiogenesis, and immune function. [Mol Cancer Ther 2006;5(5):1087–98]
Increased expression of FLIP, an inhibitor of Fas‐mediated apoptosis, in stomach cancer (2003)

Despite the cell surface expression of Fas (Apo-1/CD95), many types of tumor cells, including stomach cancer cells, are resistant to Fas-mediated apoptosis, indicating the presence of inactivating mechanisms of Fas signaling. Expression of FLICE-like inhibitory protein (FLIP), one of the inhibitory proteins of Fas-mediated apoptosis, has been reported in several cancer types, but not in stomach cancer. In the present study, we analyzed the expression of Fas and FLIP in 60 advanced gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. Immunopositivity (defined as >/=30% of the neoplastic cells) was observed for Fas in 58 (97%) and FLIP in 54 (90%) of the 60 cancers. All of the tumors with FLIP immunostaining also showed Fas immunostaining. Loss of cell surface Fas immunostaining, another mechanism of Fas resistance, was observed in 45 tumors (75%). By contrast, normal gastric mucosal cells showed no or weak expression of both Fas and FLIP. Taken together, these results indicate that increased expression of FLIP is a frequent event in stomach carcinomas, and suggest that for evading apoptosis stomach carcinoma cells in vivo may need FLIP expression, which might contribute to tumor development.
Coal Fly Ash: From Waste to Industrial Product (2007)

Abstract Coal fly ash is a beautiful material in the sense of being mainly composed of nearly perfect spheres of Al‐silicate glass that disserves applications making use of such properties, rather than to be used as an inert filler. However, leaching of mobile components restricts applications to bound form in which the leachable components are immobilized, as for example in cement and concrete products. Therefore, research has been undertaken to improve the technical and environmental quality of this material by applying forced leaching methods. Results show that quality can be improved but that new environmental problems are likely to appear and that the economics of the proposed process seems at the moment not favorable. However, some examples of successful application of fly ash as fillers in the polymer industry are given. Further, fly ash is a major source of Si and Al for the synthesis of industrial minerals. Using this line, zeolites and geopolymers are possible products to be synthesized. Finally, in order to assist the promotion of fly ash in other applications than cement and concrete, a scheme for developing specifications is given.
Use of Leeches in Plastic and Reconstructive Surgery: A Review (1988)

Leeches possess properties that make them uniquely able to assist with venous compromised tissue. Their saliva contains an anticoagulant and a histamine-like vasodilator that promote local bleeding, a local anesthetic, and hyaluronidase that promotes the local spread of the other leech salivary secretions into the wound/bite. In addition, active pharyngeal peristalsis further promotes the egress of venous blood. Resurgence in the use of leeches has been stimulated by Upton in the United States and Mahaffey in Europe. Currently, leeches are used at many microsurgical centers to provide critical venous outflow for compromised tissue replantations and transfers that might otherwise be unsalvageable. As the use of leeches becomes more widespread, knowledge of leech biology and physiology is important. This review reports on Hirudo medicinalis, the species used most often medically in Europe and the United States.
Saliency Detection: A Boolean Map Approach (2013)

A novel Boolean Map based Saliency (BMS) model is proposed. An image is characterized by a set of binary images, which are generated by randomly thresholding the image's color channels. Based on a Gestalt principle of figure-ground segregation, BMS computes saliency maps by analyzing the topological structure of Boolean maps. BMS is simple to implement and efficient to run. Despite its simplicity, BMS consistently achieves state-of-the-art performance compared with ten leading methods on five eye tracking datasets. Furthermore, BMS is also shown to be advantageous in salient object detection.
Probing the Mechanism of Exocytosis at the Hair Cell Ribbon Synapse (2007)

Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs). Postsynaptic recordings from this synapse in prehearing animals had delivered strong indications for synchronized release of several vesicles. The underlying mechanism, however, remains unclear. Here, we used presynaptic membrane capacitance measurements to test whether IHCs release vesicles in a statistically independent or dependent (coordinated) manner. Exocytic changes of membrane capacitance (deltaC(m)) were repeatedly stimulated in IHCs of prehearing and hearing mice by short depolarizations to preferentially recruit the readily releasable pool of synaptic vesicles. A compound Poisson model was devised to describe hair cell exocytosis and to test the analysis. From the trial-to-trial fluctuations of the deltaC(m) we were able to estimate the apparent size of the elementary fusion event (C(app)) at the hair cell synapse to be 96-223 aF in immature and 55-149 aF in mature IHCs. We also approximated the single vesicle capacitance in IHCs by measurements of synaptic vesicle diameters in electron micrographs. The results (immature, 48 aF; mature, 45 aF) were lower than the respective C(app) estimates. This indicates that coordinated exocytosis of synaptic vesicles occurs at both immature and mature hair cell synapses. Approximately 35% of the release events in mature IHCs and approximately 50% in immature IHCs were predicted to involve coordinated fusion, when assuming a geometric distribution of elementary sizes. In summary, our presynaptic measurements indicate coordinated exocytosis but argue for a lesser degree of coordination than suggested by postsynaptic recordings.
Cellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides (2011)

Significant progress is being made concerning the development of oligonucleotides as therapeutic agents. Studies with antisense, siRNA, and other forms of oligonucleotides have shown promise in cellular and animal models and in some clinical studies. Nonetheless, our understanding of how oligonucleotides function in cells and tissues is really quite limited. One major issue concerns the modes of uptake and intracellular trafficking of oligonucleotides, whether as "free" molecules or linked to various delivery moieties such as nanoparticles or targeting ligands. In this review, we examine the recent literature on oligonucleotide internalization and subcellular trafficking in the context of current insights into the basic machinery for endocytosis and intracellular vesicular traffic.
Genetic transformation of dinoflagellates (Amphidinium and Symbiodinium): expression of GUS in microalgae using heterologous promoter constructs (1998)

Summary Genetic transformation of two dinoflagellates ( Amphidinium sp., Symbiodinium microadriaticum ) was achieved using plasmid constructs containing the neomycin phosphotransferase gene ( nptII ) fused to the Agrobacterium nos promoter, or the hygromycin B phosphotransferase gene ( hpt ) fused to the bidirectional Agrobacterium p1′2′ promoter. Gene transfer into intact (walled) dinoflagellate cells was achieved by agitation in the presence of silicon carbide (SiCa) whiskers. Transformation rates of 5–24 transformants per 10 7 cells were obtained. Southern hybridization of transformants revealed stable integration of multiple copies of the constructs. Activity of integrated copies of the β‐glucoronidase (GUS) reporter gene coupled to the cauliflower mosaic virus 35S promoter or the p1′2′ promoter was confirmed both histochemically and fluorometrically. This is the first report of successful application of heterologous and widely used promoter and reporter genes in microalgae, and is the first demonstration of transformation of a dinoflagellate. There appear to be no substantial barriers to transformation of Amphidinium and Symbiodinium , which must now be considered as the first of the dinoflagellate genera accessible to genetic manipulation.