gebhart/patrepeval huggingface dataset:
Antigen Presenting Cells Transfected with LMP2a RNA Induce CD4 + LMP2a-specific Cytotoxic T Lymphocytes which Kill via a Fas-independent Mechanism (2002)

Recent reports have demonstrated that EBV can be used as a target of specific CTL-based treatments in severe chronic EBV, immunoblastic B cell lymphoma and Hodgkin's disease (HD). Based upon the promising results form these in vivo studies, it has been suggested that an antigen-specific CTL-based immunotherapy may be of benefit in treating EBV-associated tumors such as HD and nasopharyngeal carcinoma (NPC) which express the potentially immunogenic antigens, LMP1 and LMP2a. Recent work form our group has demonstrated that LMP2a-specific CTLs may be generated in vitro using autologous antigen presenting cells which have been transfected with polyadenylated LMP2a RNA in the presence of a cationic lipid. In this study, we demonstrate that the presence of the lipid enhances dendritic cell (DC) transfection efficiency and appears to protect the intracellular LMP2a RNA from degradation by cellular RNAses. Significantly, these improvements resulted in the transfected DCs having a superior ability to stimulate autologous T cell proliferation. These LMP2a + DCs were used to stimulate LMP2a-specific effector cells which were predominantly a mixture of cytotoxic and helper CD4+ T cells. The molecular mechanisms whereby these CD4+ T cells lyzed their LMP2a-expressing targets was investigated and we show that, although expressing Fas ligand on their surface, LMP2a-specific CD4+ effector cells kill their targets using the Ca2+-dependent perforin/granzyme pathway which is the same mechanism used by CD8+ CTLs.
Bladder cancer-associated nuclear matrix proteins. (1996)

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes, including the regulation of DNA replication and gene expression. Previous investigations into prostate and breast cancer have revealed that nuclear matrix protein (NMP) composition undergoes alterations with transformation and that the nuclear matrix can serve as a marker for the malignant phenotype. In this study, we have identified NMPs with which it is possible to differentiate human bladder tumors from normal bladder epithelial cells. We examined the NMP composition of 17 matched tumor and normal samples from patients undergoing surgery for bladder cancer. We have identified six proteins present in all tumor samples that are not present in the corresponding normal samples and three proteins that are unique to the normal bladder tissues in comparison with the tumor samples. Five of the six bladder cancer-associated proteins were also identified in three human bladder cancer cells lines examined (253j, UMUC-2, and T24). Therefore, we have demonstrated that nuclear matrix composition is able to differentiate bladder cancer from normal bladder tissue and may provide useful tools for early detection and recurrence of the disease. Importantly, these markers may provide valuable tools for cytopathological screening for bladder carcinoma.
Determination of Disk Diffusion and MIC Quality Control Guidelines for GSK2140944, a Novel Bacterial Type II Topoisomerase Inhibitor Antimicrobial Agent (2014)

GSK2140944 is a novel bacterial type II topoisomerase inhibitor in development for the treatment of conventional and biothreat pathogens, including Gram-positive pathogens and methicillin-resistant Staphylococcus aureus. This quality control study was performed to establish ranges for selected control strains: S. aureus ATCC 29213 and ATCC 25923, Escherichia coli ATCC 25922, Haemophilus influenzae ATCC 49247, and Streptococcus pneumoniae ATCC 49619. The control ranges will be crucial for the accurate evaluation of GSK2140944 potency as it progresses through clinical trial development.
[(NHC)AuI]-Catalyzed Acid-Free Alkyne Hydration at Part-per-Million Catalyst Loadings (2008)

A highly efficient [(NHC)Au(I)]-based (NHC = N-heterocyclic carbene) catalytic system for the hydration of an array of alkynes that operates under acid-free conditions and at very low catalyst loadings (typically 50-100 ppm and as low as 10 ppm) was developed. Terminal and internal alkynes possessing any combination of alkyl and aryl substituents (alkyl/H, aryl/H, alkyl/alkyl, alkyl/aryl, and aryl/aryl) were found suitable substrates in the present catalytic system.
Design and evaluation of a wide-area event notification service (2001)

The components of a loosely coupled system are typically designed to operate by generating and responding to asynchronous events. An event notification service is an application-independent infrastructure that supports the construction of event-based systems, whereby generators of events publish event notifications to the infrastructure and consumers of events subscribe with the infrastructure to receive relevant notifications. The two primary services that should be provided to components by the infrastructure are notification selection (i. e., determining which notifications match which subscriptions) and notification delivery (i.e., routing matching notifications from publishers to subscribers). Numerous event notification services have been developed for local-area networks, generally based on a centralized server to select and deliver event notifications. Therefore, they suffer from an inherent inability to scale to wide-area networks, such as the Internet, where the number and physical distribution of the service's clients can quickly overwhelm a centralized solution. The critical challenge in the setting of a wide-area network is to maximize the expressiveness in the selection mechanism without sacrificing scalability in the delivery mechanism. This paper presents SIENA, an event notification service that we have designed and implemented to exhibit both expressiveness and scalability. We describe the service's interface to applications, the algorithms used by networks of servers to select and deliver event notifications, and the strategies used to optimize performance. We also present results of simulation studies that examine the scalability and performance of the service.
Optical Detection of DNA Conformational Polymorphism on Single-Walled Carbon Nanotubes (2006)

The transition of DNA secondary structure from an analogous B to Z conformation modulates the dielectric environment of the single-walled carbon nanotube (SWNT) around which it is adsorbed. The SWNT band-gap fluorescence undergoes a red shift when an encapsulating 30-nucleotide oligomer is exposed to counter ions that screen the charged backbone. The transition is thermodynamically identical for DNA on and off the nanotube, except that the propagation length of the former is shorter by five-sixths. The magnitude of the energy shift is described by using an effective medium model and the DNA geometry on the nanotube sidewall. We demonstrate the detection of the B-Z change in whole blood, tissue, and from within living mammalian cells.
Laser turns silicon superwicking (2010)

Using high-intensity femtosecond laser pulses, we create a novel surface pattern that transforms regular silicon to superwicking. Due to the created surface structure, water sprints vertically uphill in a gravity defying way. Our study of the liquid motion shows that the fast self-propelling motion of water is due to a supercapillary effect from the surface structures we created. The wicking dynamics in the produced surface structure is found to follow the classical square root of time dependence.
Diabetes and advanced glycation endproducts (2002)

Bio-reactive advanced glycation endproducts (AGE) alter the structure and function of molecules in biological systems and increase oxidative stress. These adverse effects of both exogenous and endogenously derived AGE have been implicated in the pathogenesis of diabetic complications and changes associated with ageing including atherosclerosis, renal, eye and neurological disease. Specific AGE receptors and nonreceptor mechanisms contribute to these processes but also assist in the removal and degradation of AGE. The final disposal of AGE depends on renal clearance. Promising pharmacologic strategies to prevent AGE formation, reduce AGE toxicity, and/or inactivate AGE are under investigation.
A 1-Gb/s, four-state, sliding block Viterbi decoder (1997)

To achieve unlimited concurrency and hence throughput in an area-efficient manner, a sliding block Viterbi decoder (SBVD) is implemented that combines the filtering characteristics of a sliding block decoder with the computational efficiency of the Viterbi algorithm. The SBVD approach reduces decode of a continuous input stream to decode of independent overlapping blocks, without constraining the encoding process. A systolic SBVD architecture is presented that combines forward and backward processing of the block interval. The architecture is demonstrated in a four-state, R=1/2, eight-level soft decision Viterbi decoder that has been designed and fabricated in double-metal CMOS. The 9.21 mm/spl times/8.77 mm chip containing 150 k transistors is fully functional at a clock rate of 83 MHz and dissipates 3.0 W under typical operating conditions (V/sub DD/=5.0 V, T/sub A/=27/spl deg/C). This corresponds to a block decode rate of 83 MHz, equivalent to a decode rate of 1 Gb/s. For low-power operation, typical parts are fully functional at a clock rate of greater than 12 MHz, equivalent to a decode rate of 144 Mb/s, and dissipate 24 mW at V/sub DD/=1.5 V, demonstrating extremely low power consumption at such high rates.
Two alleles of a neural protein gene linked to scrapie in sheep. (1990)

Sheep are the natural hosts of the pathogens that cause scrapie, an infectious degenerative disease of the central nervous system. Scrapie-associated fibrils [and their major protein, prion protein (PrP)] accumulate in the brains of all species affected by scrapie and related diseases. PrP is encoded by a single gene that is linked to (and may be) the major gene controlling the incubation period of the various strains of scrapie pathogens. To investigate the role of PrP in natural scrapie, we have determined its gene structure and expression in the natural host. We have isolated two sheep genomic DNA clones that encode proteins of 256 amino acids with high homology to the PrPs of other species. Sheep PrPs have an arginine/glutamine polymorphism at position 171 that may be related to the alleles of the scrapie incubation-control gene in this species.
Gpc3 expression correlates with the phenotype of the Simpson‐Golabi‐Behmel syndrome (1998)

Interest in glypican-3 (GPC3), a member of the glypican-related integral membrane heparan sulfate proteoglycans (GRIPS) family, has increased with the finding that it is mutated in the Simpson-Golabi-Behmel overgrowth syndrome (Pilia et al. [1996] Nat. Genet. 12:241–247). The working model suggested that the membrane-bound protein acts locally to limit tissue and organ growth and that it may function by interacting with insulin-like growth factor 2 (IGF2) to limit its local effective level. Here we have tested two predictions of the model. In situ hybridization with the mouse gene cDNA was used to study the expression pattern during embryonic and fetal development. In agreement with predictions, the gene is expressed in precisely the organs that overgrow in its absence; and the patterns of expression of Gpc3 and those reported for Igf2 are strictly correlated. Dev. Dyn. 1998; 213:431–439. © 1998 Wiley-Liss, Inc.
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies (2017)

The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death. CM-272 significantly prolongs survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series as a promising therapeutic tool for unmet needs in haematological tumours.
A screen-space formulation for 2D and 3D direct manipulation (2009)

Rotate-Scale-Translate (RST) interactions have become the de facto standard when interacting with two-dimensional (2D) contexts in single-touch and multi-touch environments. Because the use of RST has thus far focused almost entirely on 2D, there are not yet standard techniques for extending these principles into three dimensions. In this paper we describe a screen-space method which fully captures the semantics of the traditional 2D RST multi-touch interaction, but also allows us to extend these same principles into three-dimensional (3D) interaction. Just like RST allows users to directly manipulate 2D contexts with two or more points, our method allows the user to directly manipulate 3D objects with three or more points. We show some novel interactions, which take perspective into account and are thus not available in orthographic environments. Furthermore, we identify key ambiguities and unexpected behaviors that arise when performing direct manipulation in 3D and offer solutions to mitigate the difficulties each presents. Finally, we show how to extend our method to meet application-specific control objectives, as well as show our method working in some example environments.
Development of a novel enzyme-targeting radiosensitizer (KORTUC) containing hydrogen peroxide for intratumoral injection for patients with low linear energy transfer-radioresistant neoplasms (2010)

The therapeutic effect of radiotherapy using linear accelerators for relatively large tumors of more than several centimeters in diameter is reduced to one third due to a large number of hypoxic tumor cells and a significant amount of anti-oxidative enzymes including peroxidase/catalase. The most effective method by which to inject hydrogen peroxide into tumor tissue was examined. This proved difficult as 3% w/v hydrogen peroxide solution (Oxydol) is an antiseptic agent for skin lesions. Thus, injection into an affected lesion may result in hydrogen peroxide soaking into a body cavity, possibly causing an intra-arterial oxygen embolism. This study aimed to identify the most effective combination of drugs containing hydrogen peroxide in order to relieve local pain at the injection site and preserve high intratumoral oxygen concentration. Hyaluronate-hydrogen peroxide was identified as the most effective combination of drugs containing hydrogen peroxide for the preservation of high intratumoral oxygen concentration for 24 h following intratumoral injection with the agent. Based on the results, the clinical application of a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC), was initiated for malignant tumors including advanced breast cancer, soft tissue sarcoma and cervical lymph node metastasis. Moreover, we have developed KORTUC III for locally advanced hepatocellular carcinoma and KORTUC IV for locally advanced pancreas cancer (stage IVa).
Isolation of oxygen‐evolving phycobilisome—photosystem II particles from Porphyridium cruentum (1983)

Photosystem II phycobilisome particles were isolated from the red alga Porphyridium cruentum in a sucrose—phosphate—citrate—magnesium medium. These particles showed high rates of oxygen evolution in the water‐to‐silicomolybdate reaction (2300 μmol O 2 .mg chl ‐1 .h ‐1 ). Photosystem I, according to fluorescence emission spectra (−196°C), was greatly reduced or absent. The results demonstrate a close physical relationship of photosystem II with the phycobilisomes which are the major light harvesting antennae in this organism.
A Case–Control Study of Screening Sigmoidoscopy and Mortality from Colorectal Cancer (1992)

Screening by sigmoidoscopy can reduce mortality from cancer of the rectum and distal colon. A screening once every 10 years may be nearly as efficacious as more frequent screening.
The Sulfone Linker in Solid-Phase Synthesis:  Preparation of 3,5-Disubstituted Cyclopent-2-enones (2002)

The preparation of functionalized 3,5-disubstituted cyclopent-2-enones via a solid-phase sulfone linker strategy is described. Polystyrene/divinylbenzene sulfinate 1 underwent S-alkylation followed by alpha,alpha-dialkylation with cis-1,4-dichloro-2-butene to form polymer-bound 3-phenylsulfonylcyclopentenes 8. Subsequent epoxidation of the cyclopentene moiety in 8 was accomplished by treatment of mCPBA, and the resulting oxirane ring in resin 9 was opened with various nucleophiles, i.e., Grignard and cuprate reagents, azide ion, and amines. To complete the sulfone-based linker strategy, Swern or TPAP oxidation of 10 gave a transient gamma-ketosulfone, which underwent sulfinate elimination, thus cleaving the sulfone linker. Eleven 3,5-disubstituted cyclopent-2-enones (11) were prepared with this five-step process in 18-40% overall yield from solid-phase benzene sulfinate 1.
Catheter-mediated pulmonary vascular gene transfer and expression. (1994)

The study and treatment of pulmonary diseases may be greatly facilitated by in vivo expression of specific recombinant genes in the pulmonary vasculature and lung parenchyma. To evaluate the feasibility of gene transfer to the pulmonary vasculature, cationic liposomes and adenoviral vectors encoding a human placental alkaline phosphatase (hpAP) gene were delivered into a pulmonary artery of 24 pigs by percutaneous right heart catheterization. Pulmonary tissue was harvested within 20 minutes or 5, 14, or 28 days later and was analyzed for gene transfer and expression. Five days after exposure to liposomes or adenoviral vectors, transfer of DNA and expression of mRNA were demonstrated in transfected lung tissue. Recombinant alkaline phosphatase protein was observed in both the vasculature and in alveolar septa but not in the bronchi. Expression of hpAP protein was observed at 5 days, was diminished at 14 days, and was absent 28 days after gene transfer with both liposome and adenoviral vectors. No major adverse effects of gene expression were detected by histological examination of the transfected lung segments compared with control segments. Gene transfer to the lung by either vector was not associated with significant biochemical abnormalities or histological changes 5, 14, or 28 days later in other organs, including carotid artery, heart, liver, spleen, kidney, skeletal muscle, ovary, and testes. These studies demonstrate that after intravascular gene delivery to the lung, recombinant genes are expressed in the vasculature and alveoli. This approach may provide a useful model for the experimental study of pulmonary vascular diseases, including pulmonary fibrosis and pulmonary thrombosis disorders.
MMAPSS Marshals Maritime Memories (2010)

Now in its fifteenth year, our annual heritage-project grant scheme is casting its net wider than ever. MMAPSS administrator Clare Power gives an insight into the maritime projects supported in the latest round of grants - including the conservation of some charming art works by a World War II sailor.
Human pegivirus molecular epidemiology in Argentina: Potential contribution of Latin American migration to genotype 3 circulation (2014)

In order to determine the human pegivirus (HPgV) genotypic diversity in Argentina taking into account the potential contribution of human migration from neighboring countries, samples from 130 Argentine injecting drug users, 116 Argentine- and 50 immigrant-pregnant women were analyzed. HPgV RNA prevalence among human immunodeficiency virus (HIV)-positive injecting drug users was similar to HIV-positive pregnant women, as was the case when comparing HIV-negative injecting drug users and HIV-negative pregnant women (P > 0.05). HPgV genotype 2 (HPgV/2) was prevalent among both Argentine injecting drug users and pregnant women, in contrast to HPgV/3 observed among pregnant women from Latin American countries with predominant indigenous populations and who had experienced their initial sexual intercourses--and possibly their source of infection--in those countries (P < 0.01). In addition, HPgV vertical and horizontal transmission was proven by molecular analysis of E2 gene and construction of identity matrixes with epidemiologically non-related isolates. This study shows that human migration from neighboring Latin American countries with predominant indigenous populations might contribute to HPgV/3 circulation in Argentina.
World Health Organization reference values for human semen characteristics*‡ (2009)

The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.