gebhart/patrepeval huggingface dataset:
Place of cryotherapy, brachytherapy and photodynamic therapy in therapeutic bronchoscopy of lung cancers (2006)

Cryotherapy, brachytherapy and photodynamic therapy (PDT) are three different methods proposed in the endoluminal treatment of lung cancers. The current article presents an overview of the specific indications and limits of each technique. These three methods were first proposed with palliative intent in inoperable patients with centrally located lung cancers. Now, the best indication is a curative intent in early stage lung cancers. Of the three, cryotherapy is the cheapest method. It induces cell necrosis in a 3-mm radius around the probe, and is suitable for treatment of superficial tumours. However, clinical trials are limited. In contrast, many clinical studies have confirmed the efficacy of PDT in treatment of superficial lung cancers. Brachytherapy can cure more aggressive tumours with deeper invasion into the bronchial wall. Unfortunately, no comparative studies have been published. Each of these methods induces a delayed tumour necrosis, and thus neither is indicated in the treatment of obstructive tumours with acute dyspnoea. In many situations, these methods should be complementary, particularly cryotherapy and brachytherapy or PDT and brachytherapy. The combination of these endoscopic methods with chemotherapy should be widely tested to promote the adjuvant role of the endoscopic methods in the treatment of lung cancers.
Lipids of the rat liver mitochondrial membrane: effect of x-irradiation. (1961)

An investigation of the lipids of the mitochondrial membrane from rat liver indicates that the mole % lipid composition of the membrane is cephalin 55%, lecithin 34%, cholesterol 3%, and glycerides 8%. The phosphatides are phosphatidyl choline, phosphatidyl ethanolamine, and a small amount of phosphatidyl serine. The fatty acid composition of the membrane phospholipids were determined by gas chromatography. Evidence in the literature indicates that liver mitochondria are damaged as a result of whole-body irradiation. Data obtained in the present study show that irradiation does not cause a loss of any of the major classes of lipids from the mitochondrial membrane during the first 40 minutes following 1000 r whole-body x irradiation. Because x irradiation is known to destroy unsaturated fatty acids, it is of interest that there was no loss of unsaturated fatty acids from the membrane phospholipids. Rather, irradiation caused an increase in the amounts of the unsaturated fatty acids, linoleic and arachidonic acid, in the phosphatidyl choline fraction of the membrane. It is clear that whatever the mechanism is, whereby liver mitochondria are altered during an early period following irradiation, it does not involve major destruction of lipids in the mitochondrial membrane. (auth)
Proteoglycans in Atherosclerosis and Restenosis (2004)

The proteoglycan versican is one of several extracellular matrix (ECM) molecules that accumulate in lesions of atherosclerosis and restenosis. Its unique structural features create a highly interactive molecule that binds growth factors, enzymes, lipoproteins, and a variety of other ECM components to influence fundamental events involved in vascular disease. Versican is one of the principal genes that is upregulated after vascular injury and is a prominent component in stented and nonstented restenotic lesions. The synthesis of versican is highly regulated by specific growth factors and cytokines and the principal source of versican is the smooth muscle cell. Versican interacts with hyaluronan, a long chain glycosaminoglycan, to create expanded viscoelastic pericellular matrices that are required for arterial smooth muscle cell (ASMC) proliferation and migration. Versican is also prominent in advanced lesions of atherosclerosis, at the borders of lipid-filled necrotic cores as well as at the plaque-thrombus interface, suggesting roles in lipid accumulation, inflammation, and thrombosis. Versican influences the assembly of ECM and controls elastic fiber fibrillogenesis, which is of fundamental importance in ECM remodeling during vascular disease. Collectively, these studies highlight the critical importance of this specific ECM component in atherosclerosis and restenosis.
Use of recombinant human erythropoietin for management of anemia in dogs and cats with renal failure (1998)

Anemia contributes to clinical manifestations of chronic renal failure in dogs and cats. Administration of r-HuEPO has the potential to resolve anemia and improve clinical well-being. However, its administration poses risks of antibody production and adverse effects associated with correction of RBC mass. Use of r-HuEPO in dogs and cats requires conscientious assessment of risks and benefits until homologous forms of erythropoietin are available.
IL-7 supports the generation of cytotoxic T lymphocytes from thymocytes. Multiple lymphokines required for proliferation and cytotoxicity. (1990)

Current data suggest that the combination of IL-2 plus IL-6 or IL-4 supports the generation of a CTL response. In this report, we investigated whether IL-7 alone or in combination with other lymphokines supports the generation of active CTL from murine thymocytes. Added alone, IL-7 produced a modest CTL response, and this response was augmented (more than an additive response) by the addition of either IL-2, IL-6, or IL-4. After culture with IL-7, the removal of CD8+ cells correlated with a marked decrease in killing, whereas removal of the CD4+ population resulted in an enhanced CTL response. IL-7 generated a proliferative response to which the addition of other lymphokines resulted in an additive increase at best. To determine if the CTL response was found with IL-7 was dependent on the presence of endogenous lymphokines, we added blocking mAb and found that anti-IL-2 or anti-IL-6 blocked the level of CTL generated in the presence of IL-7. In contrast, anti-IL-4 was unable to inhibit CTL generation. The effect of the mAb on proliferation was somewhat paradoxical. The addition of anti-IL-2, anti-IL-6, or anti-IL-4 to cultures containing IL-7 all caused a significant decrease in proliferation that was overcome by the addition of the corresponding human lymphokines for IL-2 and IL-6. If thymocytes were fractionated and then cultured in the presence of IL-7, the double negative population gave the greatest proliferative response, the single positive thymocytes gave a response that was approximately 40% less, and the double positive thymocytes did not proliferate. These data indicate that IL-7 supports the induction of a cytotoxic response, however, this appears to require the presence of both IL-2 and IL-6.
The NS3 Protein of Bluetongue Virus Exhibits Viroporin-like Properties (2004)

Viroporins compose a group of small hydrophobic transmembrane proteins that can form hydrophilic pores through lipid bilayers. Viroporins have been implicated in promoting virus release from infected cells and in affecting cellular functions including protein trafficking and membrane permeability. Nonstructural protein 3 (NS3) of bluetongue virus has been shown previously to be important for efficient release of newly made virions from infected cells. In this report, we demonstrate that NS3 possesses properties commonly associated with viroporins. Our findings indicate that: (i) NS3 localizes to the Golgi apparatus and plasma membrane in transfected cells, (ii) NS3 can homo-oligomerize in transfected cells, (iii) targeting of NS3 to the Golgi apparatus and plasma membrane correlates with the enhanced permeability of cells to the translation inhibitor hygromycin B (hyg-B), (iv) amino acids 118-148 comprising transmembrane region 1 (TM1) of NS3 are critical for Golgi targeting and hyg-B permeability, and (v) deletion of amino acids 156-181 comprising transmembrane region 2 (TM2) of NS3 has little to no affect on Golgi targeting and hyg-B permeability. These viroporin-like properties may contribute to the role of NS3 in virus release and may have important implications for pathogenicity of bluetongue virus infections.
Heparin Affinity: Purification of a Tumor-Derived Capillary Endothelial Cell Growth Factor (1984)

A tumor-derived growth factor that stimulates the proliferation of capillary endothelial cells has a very strong affinity for heparin. This heparin affinity makes it possible to purify the growth factor to a single-band preparation in a rapid two-step procedure. The purified growth factor is a cationic polypeptide, has a molecular weight of about 18,000, and stimulates capillary endothelial cell proliferation at a concentration of about 1 nanogram per milliliter.
Color image retrieval based on hidden Markov models (2002)

A new approach to retrieving images from a color image database is proposed in this paper. Each image in the database is represented by a pseudo two-dimensional hidden Markov model (2D PHMM), where both the chromatic and spatial information about the image could be adequately involved. In addition, a pictorial querying method is used, by which the users can paint only rough contents of the desired images if their information concerning the desired images is not crisp. The use of the flexible querying mechanism and 2D PHMMs eliminates the drawbacks of utilizing textual descriptions to retrieve images. Furthermore, effective statistical matching between the query picture and each image in the database can be achieved. The probability of the query picture generated by each 2D PHMM is just considered as the matching score between the query and the corresponding image. The images which best satisfy the query can thus be retrieved. Promising experimental results show the feasibility and effectiveness of the proposed approach.
Iterativer Aufbau von Oxazolringen über α‐Chlorglycinate: Totalsynthese von (−)‐Muscorid A (2003)

Eine effiziente iterative Synthese von Oxazolen gelingt über die Cyclisierung von 2-Alkinylglycinaten (siehe Schema), die bei der Reaktion von 1-Alkinylaluminiumreagentien mit α-Chlorglycinaten entstehen. Eine Totalsynthese des Bisoxazol-Naturstoffs (−)-Muscorid A illustriert das Verfahren. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2003/z50331_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Molecular Cloning of Osmotin and Regulation of Its Expression by ABA and Adaptation to Low Water Potential (1989)

In response to adaptation to NaCl, cultured tobacco cells (Nicotiana tabacum L. cv Wisconsin 38) synthesize a major 26 kilodalton protein which has been named osmotin due to its induction by low water potentials. To help characterize the expression of osmotin in adapted cells, a cDNA clone for osmotin has been isolated. Abscisic acid induces messenger RNA encoding osmotin. Levels of this mRNA in adapted cells are approximately 15-fold higher than in unadapted cells. Message for osmotin is present at constant levels through the growth cycle of adapted cells, while in unadapted cells, the level decreases during exponential phase of growth and increases again when the cells approach stationary phase. While abscisic acid induces the message for osmotin, a low water potential environment appears to be required for accumulation of the protein. An osmotic shock to unadapted cells does not increase the amount of message or protein present most likely because this treatment does not induce immediately the accumulation of abscisic acid. The increased expression of osmotin in adapted cells is not correlated with an increase in osmotin gene copy number. Osmotin is homologous to a 24 kilodalton NaCl-induced protein in tomato, as well as thaumatin, maize alpha-amylase/trypsin inhibitor and a tobacco mosaic virus-induced pathogenesis-related protein.
Preeclampsia and Future Cardiovascular Disease: Potential Role of Altered Angiogenesis and Insulin Resistance (2004)

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/- 6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr postpartum. These factors may contribute to their risk of future CVD.
Training For Tomorrow: Ten Tips for a Successful Transition from Law School to Law Practice (2011)

I figured out quickly that I had better figure out how to become a lawyer, and quickly. So I did. But the road from law school graduate to useful member of a deal team was a bumpy one for me, as it was for many of my colleagues. In an effort to make other lawyers' transitions from law school graduate to lawyer a bit smoother, I now offer my list of 10 things lawyers wish they had known on the first day of practice. In the spirit of full disclosure, I am a transactional lawyer by training, and now teach business law and skills classes, so much of the list is geared toward transactional lawyers. That said, easy conversions exist, I suspect, to modify the list as needed for my litigating brethren.\nIn the spirit of still more full disclosure, I note that many of the topics lend themselves equally to my other project--parenting (and by that I mean refereeing the various combinations and permutations of disputes between and among my three kids). I will leave the philosophical question of why this significant overlap between lawyering and parenting exists to others to explore--perhaps we really did learn all we needed to know to be good lawyers in elementary school, but have since forgotten it all.\nSo here goes--the top 10 things law graduates need to figure out before becoming a useful transactional lawyer.
Synthesis and Cytotoxicity Studies of Novel [1,2,4]Triazolo[1,5-a]pyrimidine-7-amines (2008)

A series of novel N-anilino-5-methyl-2-(3-(5-(alkylaminomethyl)furan-2-yl-methylthio)propyl)-[1,2,4]triazolo-[1,5-a]pyrimidine-7-amine derivatives were synthesized and evaluated for their in vitro cytotoxicity against two cancer cell lines, Bel-7402 and HT-1080. Compounds 9, 14, 19 and 23 possessed marked cytotoxicity, especially 23 (with IC(50) values of 15.0 microM and 7.8 microM against Bel-7402 and HT-1080 cell lines, respectively), which had emerged as lead compound. The activity was found to depend strongly on substitution pattern of the side chains at C-2 position, and 4-triflouromethylanilino substituent at C-7 position was an option for anticancer potency.
Eye models for the prediction of contrast vision in patients with new intraocular lens designs (2004)

Theoretical calculations of the polychromatic modulation transfer function (MTF) and wave-front aberration were performed with physiological eye models. These eye models have an amount of spherical aberration that is representative of a normal population of pseudophakic eyes implanted with two different types of intraocular lens (IOL) made from high-refractive-index silicone. These theoretical calculations were compared with the measured contrast sensitivity function (CSF) under mesopic lighting conditions and with wave-front aberration (obtained with a Hartmann-Shack wave-front sensor) collected from 37 patients bilaterally implanted with the same types of lens. The relationships between the ocular wave-front aberration and the MTF predicted by the eye models and the CSF and the ocular wave-front aberration measured in eyes implanted with IOLs were investigated. The predicted improvements in MTF and wave-front aberration correlated well with the improvements measured in practice. Physiological eye models are therefore useful tools for IOL design.
Molecular Analysis of Resistance to Streptogramin A Compounds Conferred by the Vga Proteins of Staphylococci (2005)

The Vga and Msr resistance determinants, encoded by mobile genetic elements in various staphylococcal strains, belong to a family of ATP-binding cassette (ABC) proteins whose functions and structures are ill defined. Their amino acid sequences are similar to those of proteins involved in the immunity of streptomycetes to the macrolide-lincosamide-streptogramin antibiotics that they produce. Sequence analysis of the genomes of the gram-positive bacteria with low G+C contents revealed that Lmo0919 from Listeria monocytogenes is more closely related to Vga variants than to Msr variants. In the present study we compared the antibiotic resistance profiles conferred by the Vga-like proteins in two staphylococcal hosts. It was shown that Vga(A), the Vga(A) variant [Vga(A)v], and Lmo0919 can confer resistance to lincosamides and streptogramin A compounds, while only Vga(B) is able to increase the level of resistance to pristinamycin, a mixture of streptogramin A and streptogramin B compounds. By using polyclonal antibodies, we found that the Vga(A) protein colocalized with the beta subunit of the F(1)-F(0) ATPase in the membrane fractions of staphylococcal cells. In order to identify functional units in these atypical ABC proteins, such as regions that might be involved in substrate specificity and/or membrane targeting, we analyzed the resistance phenotypes conferred by various plasmids carrying parts or modified versions of the vga(A) gene and we determined the subcellular localization of the gene products. Only polypeptides composed of two ABC domains were detected in the cell membranes. No region of drug specificity was identified. Resistance properties were dependent on the integrities of both Walker B motifs.
Use of modified U1 snRNAs to inhibit HIV-1 replication (2006)

Control of RNA processing plays a central role in regulating the replication of HIV-1, in particular the 3' polyadenylation of viral RNA. Based on the demonstration that polyadenylation of mRNAs can be disrupted by the targeted binding of modified U1 snRNA, we examined whether binding of U1 snRNAs to conserved 10 nt regions within the terminal exon of HIV-1 was able to inhibit viral structural protein expression. In this report, we demonstrate that U1 snRNAs complementary to 5 of the 15 regions targeted result in significant suppression of HIV-1 protein expression and viral replication coincident with loss of viral RNA. Suppression of viral gene expression is dependent upon appropriate assembly of a U1 snRNP particle as mutations of U1 snRNA that affect binding of U1 70K or Sm proteins significantly reduced efficacy. However, constructs lacking U1A binding sites retained significant anti-viral activity. This finding suggests a role for these mutants in situations where the wild-type constructs cause toxic effects. The conserved nature of the sequences targeted and the high efficacy of the constructs suggests that this strategy has significant potential as an HIV therapeutic.
12(R)-hydroxyeicosatetraenoic acid, an endogenous corneal arachidonate metabolite, lowers intraocular pressure in rabbits. (1990)

12(R)-hydroxyeicosatetraenoic acid (12(R)HETE) is an endogenous corneal epithelial arachidonic acid metabolite formed by the cytochrome P450 system and a potent inhibitor of Na(+)-K(+)-ATPase activity. We studied the effect of topically applied 12(R)HETE, either derived endogenously from corneal epithelium or synthetically prepared, on the IOP of the rabbit eye and compared it to its stereoisomer 12(S)HETE. Topical application of 1 microgram of biologically derived 12(R)HETE to both eyes of rabbits resulted in a marked reduction in IOP: a reduction of 4-7 mmHg occurred within 30-120 min. The IOP reduction effect of a single application of 12(R)HETE was long-lasting (9 days), whereas no effect on IOP was found for the vehicle control. Using synthetic compound, we demonstrated that the effect of 12(R)HETE on IOP is dose-dependent. Single topical application of 1, 10, and 50 micrograms of 12(R)HETE caused a reduction in IOP of 4, 6, and 12 mmHg, respectively. The stereoisomer, 12(S)HETE, did not have any effect on IOP at doses up to 5 micrograms. The IOP reduction effect of 12(R)HETE was not associated with hyperemia, appearance of flare, miotic response, or increased protein concentration of the aqueous humor. This study was the first to demonstrate that an endogenous inhibitor of Na(+)-K(+)-ATPase generated by the corneal epithelium potently and specifically lowers IOP in rabbits. Further studies are needed to elucidate the mechanism by which 12(R)HETE lowers IOP.
Chaperone-like Antibodies Targeting Misfolded Tau Protein: New Vistas in the Immunotherapy of Neurodegenerative Foldopathies (2008)

Neurodegenerative foldopathies are characterized by aberrant folding of proteins leading to the intracellular and extracellular accumulation of insoluble misfolded proteins. One of the most prominent protein folding disorders is Alzheimer's disease (AD). In AD, there were identified two major driving forces behind neurodegeneration, misfolded proteins tau and amyloid-beta. Tau belongs to a family of intrinsically disordered proteins that are characterized by the absence of a rigid three-dimensional structure in their natural environment. However, in disease condition, tau truncation and hyperphosphorylation could lead to tau transformation from intrinsically disordered protein into highly ordered soluble and insoluble misfolded structures. Increased understanding of the molecular mechanism underlying pathological transformation of tau protein has opened up the possibility of targeting misfolded tau for therapeutic purposes. Pharmacological research has identified several therapeutic approaches targeting directly or indirectly tau cascade. Novel promising field of AD treatment represent monoclonal antibodies with chaperon like activities that will be able to neutralize the toxic gain of function of misfolded tau and thus increase its degradation. We suggest that chaperon like antibodies targeting disease modified tau may hold promise for the successful treatment of AD and related foldopathies.
DNA Topoisomerase II as a Target for Cancer Chemotherapy (2002)

DNA topoisomerases are nuclear enzymes that play essential roles in DNA metabolic processes. These enzymes carry out strand passage to maintain appropriate DNA structure during semi-conservative DN...
In Vitro Selection of Allosteric Ribozymes that Sense the Bacterial Second Messenger c-di-GMP (2014)

Recently, a number of study have shown the ligand-dependent allosteric ribozymes can be harnessed as biosensors, high-throughput screening, and agents for the control of gene expression in vivo, called artificial riboswitches. In this chapter, we describe how in vitro selection can be used to create an allosteric ribozyme that senses bacterial second messenger cyclic-di-GMP (c-di-GMP). A hammerhead ribozyme was joined to a natural c-di-GMP class I riboswitch aptamer via communication modules. Both c-di-GMP-activating and -inhibiting ribozyme can be obtained by this approach.
Overcoming independent extensibility challenges (2002)

Independent extensibility requires a strong handle on versioning through precise names.