gebhart/patrepeval huggingface dataset:
Combination of interleukins 3 and 6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells. (1989)

The effects of several hematopoietic growth factors on primitive murine bone marrow progenitor cells [colony-forming unit(s)-spleen (CFU-S)] have been investigated during culture for 2-6 days. Interleukin 3 (IL-3) was required for CFU-S survival in culture, and the combination of IL-3 and interleukin 6 (IL-6) increased the number of CFU-S in culture 10-fold over the number obtained with IL-3 alone. Stem cell function was measured by competitive repopulation; IL-3 was required, and IL-3 and IL-6 appear to act synergistically to enhance stem cell recovery from these cultures. These data appear to be relevant for retroviral-mediated gene transfer into stem and progenitor cells. Murine bone marrow cells were infected with a retrovirus containing the human beta-globin gene in the presence of various growth factors. Only 2 of 17 mice reconstituted with cells infected in the presence of IL-3 alone showed long-term expression of the human beta-globin gene (12 months), as opposed to 6 of 11 mice reconstituted with cells infected in the presence of IL-3 and IL-6. Medium conditioned by 5637 bladder carcinoma cells, a source of several hematopoietic growth factors, increased the frequency of infection of CFU-S but did not enhance stem cell infection or the repopulating potential of cultured bone marrow cells. Stem cells containing the human beta-globin provirus from these animals were shown to be capable of reconstituting secondary recipients in which the human beta-globin gene was expressed.
[Radiotherapy: a significant treatment option in management of prostatic cancer]. (1998)

In the management of patients with localized prostate cancer, both radical prostatectomy and radiotherapy are shown in the U.S. to be equally effective to control a local disease but associate with different types of toxicity. Therefore, both treatments are recommended for patients to choose freely. Recently, mainly in western countries, radiotherapy has achieved technological innovation so as to increase target tumor doses and to decrease the volume and dose of peritumoral normal tissues, by which the treatment outcome is further improved. Major innovative techniques include three-dimensional conformal radiotherapy (3D CRT) and a high dose-rate (HDR) brachytherapy system. Three-D CRT focuses radiation on the tumor through multiple portals minutely tailored to the tumor volume determined by computed tomography, in conjunction with a sophisticated treatment planning system. A HDR brachytherapy system provides high-tech interstitial radiotherapy; a remote afterloading system precludes radiation exposure of hospital workers and a computer-controlled source-scanning system enables optimization of dose distribution. In order to provide a variety of effective treatment options for Japanese patients, radiation oncologists must master these techniques in practice, in cooperation with urologists.
Critical reflections on end-of-life care for people with intellectual disabilities: a single case study approach (2012)

People with intellectual disabilities (ID) are enjoying increasing longevity, but are simultaneously having to cope with the additional health problems associated with ageing. Even though people with ID are reported to have worse health than the rest of the population, resulting in greater health-care needs, they also have poorer health care than the average person, including including-end-of-life care. The aim of this paper is to explore the challenges to providing effective end-of-life care for a person with an ID by using critical reflection from a nursing care perspective on an illustrative case study. Death never occurs in a vacuum but rather occurs in a social context, and the social context here was crucial to providing appropriate end-of-life care. It is hoped that the paper will promote discussion both around end-of-life care generally and in relation to this marginalized population.
The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer (2008)

We conclude that CT-322 is an effective anti-VEGFR2 agent and that further investigation of CT-322 for the treatment of pancreatic cancer is warranted.
Opsonic and Protective Properties of Antibodies Raised to Conjugate Vaccines Targeting Six Staphylococcus aureus Antigens (2012)

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections for which a vaccine is greatly desired. Antigens found on the S. aureus outer surface include the capsular polysaccharides (CP) of serotype 5 (CP5) or 8 (CP8) and/or a second antigen, a β-(1→6)-polymer of N-acetyl-D-glucosamine (PNAG). Antibodies specific for either CP or PNAG antigens have excellent in vitro opsonic killing activity (OPKA), but when mixed together have potent interference in OPKA and murine protection. To ascertain if this interference could be abrogated by using a synthetic non-acetylated oligosaccharide fragment of PNAG, 9GlcNH(2), in place of chemically partially deacetylated PNAG, three conjugate vaccines consisting of 9GlcNH(2) conjugated to a non-toxic mutant of alpha-hemolysin (Hla H35L), CP5 conjugated to clumping factor B (ClfB), or CP8 conjugated to iron-surface determinant B (IsdB) were used separately to immunize rabbits. Opsonic antibodies mediating killing of multiple S. aureus strains were elicited for all three vaccines and showed carbohydrate antigen-specific reductions in the tissue bacterial burdens in animal models of S. aureus skin abscesses, pneumonia, and nasal colonization. Carrier-protein specific immunity was also shown to be effective in reducing bacterial levels in infected lungs and in nasal colonization. However, use of synthetic 9GlcNH(2) to induce antibody to PNAG did not overcome the interference in OPKA engendered when these were combined with antibody to either CP5 or CP8. Whereas each individual vaccine showed efficacy, combining antisera to CP antigens and PNAG still abrogated individual OPKA activities, indicating difficulty in achieving a multi-valent vaccine targeting both the CP and PNAG antigens.
Modulation of RNA splicing as a potential treatment for cancer (2011)

Close to 90% of human genes are transcribed into pre-mRNA that undergoes alternative splicing, producing multiple mRNAs and proteins from single genes. This process is largely responsible for human proteome diversity, and about half of genetic disease-causing mutations affect splicing. Splice-switching oligonucleotides (SSOs) comprise an emerging class of antisense therapeutics that modify gene expression by directing pre-mRNA splice site usage. Bauman et al. investigated an SSO that up-regulated the expression of an anti-cancer splice variant while simultaneously eliminating an over-expressed cancer-causing splice variant. This was accomplished by targeting pre-mRNA of the apoptotic regulator Bcl-x, which is alternatively spliced to express anti- and pro-apoptotic splice variants Bcl-xL and Bcl-xS, respectively. High expression of Bcl-xL is a hallmark of many cancers and is considered a general mechanism used by cancer cells to evade apoptosis. Redirection of Bcl-x pre-mRNA splicing from Bcl-xL to -xS by SSO induced apoptotic and chemosensitizing effects in various cancer cell lines. Importantly, the paper shows that delivery of Bcl-x SSO using a lipid nanoparticle redirected Bcl-x splicing and reduced tumor burden in melanoma lung metastases. This was the first demonstration of SSO efficacy in tumors in vivo. SSOs are not limited to be solely potential anti-cancer drugs. SSOs were first applied to repair aberrant splicing in thalassemia, a genetic disease, they have been used to create novel proteins (e.g., ∆7TNFR1), and they have recently progressed to clinical trials for patients with Duchenne muscular dystrophy.
High Order Compact Finite Difference Schemes for a Nonlinear Black-Scholes Equation (2003)

A nonlinear Black-Scholes equation which models transaction costs arising in the hedging of portfolios is discretized semi-implicitly using high order compact finite difference schemes. A new compact scheme, generalizing the compact schemes of Rigal [29], is derived and proved to be unconditionally stable and non-oscillatory. The numerical results are compared to standard finite difference schemes. It turns out that the compact schemes have very satisfying stability and non-oscillatory properties and are generally more efficient than the considered classical schemes.
Structure and novel exons of the human .tau. gene (1992)

The microtubule-binding protein tau is important in establishing and maintaining neuronal morphology and is a major component of the neurofibrillary tangles (NFTs) characteristic of Alzheimer's brain. The neuron-specific tau transcript undergoes complex alternative splicing. The human tau gene has been cloned and mapped. The restriction analysis and partial sequencing of the gene shows that it contains (1) four alternatively spliced exons previously described in rodent and bovine but not in human tau cDNAs and (2) two CpG islands, one associated with the promoter region, the other with exon 9. Examination of human tau mRNA indicates that the human cerebrocortical splicing pattern differs from that previously reported for the murine and bovine tau mRNAs, despite conserved exon organization in all three genes.
Effect of Light on Glucose Utilization by Euglena gracilis (1980)

The effect of light on glucose consumption by wild-type Euglena gracilis Z. and mutant cells has been studied. When dark- or light-grown wild-type cells are transferred from a medium containing sodium butyrate as the only carbon source to a glucose-containing medium, glucose consumption is blocked for 6 to 7 days when cultures are incubated under a light intensity of at least 600 lux. During this time cells multiply at the same rate as controls kept on media devoid of any utilizable organic carbon source. This light-induced inhibition of glucose consumption and of growth on glucose-containing medium is not related to photosynthesis since: (a) glucose consumption is inhibited by light intensities much lower than those required for high phototrophic growth; (b) the inhibition of photosynthesis by 3-(3,4-dichlorophenyl)-1, 1-dimethylurea does not overcome the inhibition of glucose consumption; and (c) nonphototrophic-growing mutants also show light-induced inhibition of glucose consumption and of growth on glucose-containing medium. This inhibition of growth by light might be explained by modification in the permeability of the cellular membrane.
A Combinatorial Code for Gene Expression Generated by Transcription Factor Bach2 and MAZR (MAZ-Related Factor) through the BTB/POZ Domain (2000)

Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the BTB/POZ domain, MAZR possesses Zn finger motifs that are closely related to those of the Myc-associated Zn finger (MAZ) protein. MAZR mRNA was coexpressed with Bach2 in B cells among hematopoietic cells and in developing mouse limb buds, suggesting a cooperative role for MAZR and Bach2 in these cells. MAZR forms homo- and hetero-oligomers with Bach2 through the BTB domain, which oligomers bind to guanine-rich sequences. Unlike MAZ, MAZR functioned as a strong activator of the c-myc promoter in transfection assays with B cells. However, it does not possess a typical activation domain, suggesting a role for it as an unusual type of transactivator. The fgf4 gene, which regulates morphogenesis of limb buds, contains both guanine-rich sequences and a Bach2 binding site in its regulatory region. In transfection assays using fibroblast cells, the fgf4 gene was upregulated in the presence of both MAZR and Bach2 in a BTB/POZ domain-dependent manner. The results provide a new perspective on the function of BTB/POZ domain factors and indicate that BTB/POZ domain-mediated oligomers of transcription factors may serve as combinatorial codes for gene expression.
Cell Distance Mapping Identifies Functional T Follicular Helper Cells in Inflamed Human Renal Tissue (2014)

T follicular helper (TFH) cells are critical for B cell activation in germinal centers and are often observed in human inflamed tissue. However, it is difficult to know if they contribute in situ to inflammation. Expressed markers define TFH subsets associated with distinct functions in vitro. However, such markers may not reflect in situ function. The delivery of T cell help to B cells requires direct cognate recognition. We hypothesized that by visualizing and quantifying such interactions, we could directly assess TFH cell competency in situ. Therefore, we developed computational tools to quantify spatial relationships between different cell subtypes in tissue [cell distance mapping (CDM)]. Analysis of inflamed human tissues indicated that measurement of internuclear distances between TFH and B cells could be used to discriminate between apparent cognate and noncognate interactions. Furthermore, only cognate-competent TFH cell populations expressed high levels of Bcl-6 and interleukin-21. These data suggest that CDM can be used to identify adaptive immune cell networks driving in situ inflammation. Such knowledge should help identify diseases, and disease subsets, that may benefit from therapeutic targeting of specific T cell-antigen-presenting cell interactions.
Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver (2004)

Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the biosynthesis of monounsaturated fatty acids. Mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased energy expenditure, and up-regulated expression of several genes encoding enzymes of fatty acid beta-oxidation in liver. The mechanisms by which SCD deficiency leads to these metabolic changes are presently unknown. Here we show that the phosphorylation and activity of AMP-activated protein kinase (AMPK), a metabolic sensor that regulates lipid metabolism during increased energy expenditure is significantly increased (approximately 40%, P < 0.01) in liver of SCD1 knockout mice (SCD1-/-). In parallel with the activation of AMPK, the phosphorylation of acetyl-CoA carboxylase at Ser-79 was increased and enzymatic activity was decreased (approximately 35%, P < 0.001), resulting in decreased intracellular levels of malonyl-CoA (approximately 47%, P < 0.001). An SCD1 mutation also increased AMPK phosphorylation and activity and increased acetyl-CoA carboxylase phosphorylation in leptin-deficient ob/ob mice. Lower malonyl-CoA concentrations are known to derepress carnitine palmitoyltransferase 1 (CPT1). In SCD1-/- mice, CPT1 and CPT2 activities were significantly increased (in both cases approximately 60%, P < 0.001) thereby stimulating the oxidation of mitochondrial palmitoyl-CoA. Our results identify AMPK as a mediator of increased fatty acid oxidation in liver of SCD1-deficient mice.
Vehicle Detection Using Normalized Color and Edge Map (2007)

This paper presents a novel vehicle detection approach for detecting vehicles from static images using color and edges. Different from traditional methods, which use motion features to detect vehicles, this method introduces a new color transform model to find important "vehicle color" for quickly locating possible vehicle candidates. Since vehicles have various colors under different weather and lighting conditions, seldom works were proposed for the detection of vehicles using colors. The proposed new color transform model has excellent capabilities to identify vehicle pixels from background, even though the pixels are lighted under varying illuminations. After finding possible vehicle candidates, three important features, including corners, edge maps, and coefficients of wavelet transforms, are used for constructing a cascade multichannel classifier. According to this classifier, an effective scanning can be performed to verify all possible candidates quickly. The scanning process can be quickly achieved because most background pixels are eliminated in advance by the color feature. Experimental results show that the integration of global color features and local edge features is powerful in the detection of vehicles. The average accuracy rate of vehicle detection is 94.9%.
Molecular characterization of TUB, TULP1 , and TULP 2, members of the novel tubby gene family and their possible relation to ocular diseases (1997)

Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function. Database searches revealed that sequences corresponding to the C terminus of the tub protein were highly conserved across a number of species including humans, mice, Caenorhabditis elegans, Arabidopsis, rice, and maize, and that tub was a member of a gene family. We describe here, TUB, the human homolog of mouse tub, and two newly characterized family members, TULP1 for tubby like protein 1 and TULP2. These three family members, which differ in the N-terminal half of the protein, share 60-90% amino acid identity across their conserved C-terminal region and have distinct tissue expression patterns. Alternatively spliced transcripts with 5' variable sequences, three of which have been identified for the tubby gene, may mediate tissue specific expression. We also report that TUB, TULP1, and TULP2 map to human chromosomes 11p15.4, 6p21.3, and 19q13.1, respectively. TULP1 and TULP2 map within the minimal intervals identified for retinitis pigmentosa 14 on chromosome 6p21.3 and cone-rod dystrophy on chromosome 19q13.1. TULP1 and TULP2, which are expressed in the retina, make excellent candidates for these ocular diseases as a mutation within the tub gene is known to lead to early progressive retinal degeneration.
Drug delivery and nanoparticles: Applications and hazards (2008)

Abstract: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. Keywords: drug delivery, cancer therapy, nanoparticles, toxicology, pharmaceuticals
Elastase-type proteases on the surface of human blood monocytes: possible role in amyloid formation. (1980)

A group of DFP-inhibitable serine proteases that are associated with the cell surface of human peripheral blood monocytes and degrade the amyloid precursor protein SAA has been partially characterized. Enzymes that resemble elastases in being inhibitable by Ac-Ala-Ala-Pro-Val-CH2Cl but differ from the secreted macrophage elastase in m.w. can be recovered from SDS gels in the region ranging from 58 to 72 x 10(3) daltons. These enzymes degrade SAA to a product similar in m.w. and antigenic properties to the amyloid A protein. When intact cells are labeled with 3H Ac-Ala-Ala-Pro-Val-CH2Cl at 4 degrees C for 3 min, a major 58 x 10(3) and two minor 48 and 65 x 10(3) dalton bands are seen. Another group of enzymes that digests SAA completely through a transient AA-like intermediate can be recovered from the 40 to 58 x 10(3) dalton region of the gels. These enzymes are only minimally inhibited by Ac-Ala-Ala-Pro-Val-CH2Cl. We suggest that both types of enzymes may be involved in the proteolytic processes that lead to amyloid formation in secondary amyloidosis.
Isolation, characterization, and properties of a labile hydrolysis product of the antitumor nucleoside, 5-azacytidine (1978)

The antitumor nucleoside, 5-azacytidine (5-AC), is best administered clinically by prolonged intravenous infusion to minimize toxic effects. In opposition to this administration technique is facile drug decomposition in aqueous formulations giving products of unknown toxicity. Analysis of 24-h-old water solutions of 5-AC with high-pressure liquid chromatography (HPLC) indicated a threefold mixture of 5-AC, N-(formylamidino)-N'-beta-D-ribofuranosylurea (RGU-CHO), and 1-beta-D-ribofuranosyl-3-guanylurea (RGU). Preparative HPLC allowed the isolation and subsequent identification of each component in the mixture, including RGU-CHO which until now has not been available for chemical and biological study. It was shown that RGU-CHO in water solution readily equilibrates to 5-AC and more slowly deformylates to give RGU irreversibly. The latter hydrolysis produce exhibited no pronounced toxicity when tested either in vitro or in vivo. Although RGU-CHO showed considerable antitumor activity against murine L1210 leukemia, hydrolysis studies indicated that all of the observed activity could be attributed to 5-AC formed by in vivo equilibration from RGU-CHO. Moreover, RGU-CHO seemed to impart to test animals a toxicity which was no greater than that anticipated from its ability to generate 5-AC.