gebhart/patrepeval huggingface dataset:
Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH‐P‐Na(I), which is devoid of photosensitivity (2007)

To improve the efficacy of sonodynamic therapy of cancer using photosensitizers, we developed a novel porphyrin derivative designated DCPH-P-Na(I) and investigated its photochemical characteristics and sonotoxicity on tumor cells. DCPH-P-Na(I) exhibited a minimum fluorescent emission by excitation with light, compared with a strong emission from ATX-70, which is known to reveal both photo- and sonotoxicity. According to this observation, when human tumor cells were exposed to light in the presence of DCPH-P-Na(I) in vitro, the least phototoxicity was observed, in contrast to the strong phototoxicity of ATX-70. However, DCPH-P-Na(I) exhibited a potent sonotoxicity on tumor cells by irradiation with ultrasound in vitro. This sonotoxicity was reduced by the addition of L-histidine, but not D-mannitol, thus suggesting that singlet oxygen may be responsible for the sonotoxicity of DCPH-P-Na(I). DCPH-P-Na(I) demonstrated significant sonotoxicity against a variety of cancer cell lines derived from different tissues. In addition, in a mouse xenograft model, a potent growth inhibition of the tumor was observed using sonication after the administration of DCPH-P-Na(I) to the mouse. These results suggest that sonodynamic therapy with DCPH-P-Na(I) may therefore be a useful clinical treatment for cancers located deep in the human body without inducing skin sensitivity, which tends to be a major side-effect of photosensitizers.
Catalysis of ATP-Dependent Homologous DNA Pairing and Strand Exchange by Yeast RAD51 Protein (1994)

The RAD51 gene of Saccharomyces cerevisiae is required for genetic recombination and DNA double-strand break repair. Here it is demonstrated that RAD51 protein pairs circular viral single-stranded DNA from phi X 174 or M13 with its respective homologous linear double-stranded form. The product of synapsis between these DNA partners is further processed by RAD51 to yield nicked circular duplex DNA, which indicates that RAD51 can catalyze strand exchange. The pairing and strand exchange reaction requires adenosine triphosphate, a result consistent with the presence of a DNA-dependent adenosine triphosphatase activity in RAD51 protein. Thus, RAD51 is a eukaryotic recombination protein that can catalyze the strand exchange reaction.
Considerations for Single Event Immune VLSI Logic (1983)

The applicability of resistive decoupling and other hardening techniques to circuits and chip level systems at very large scales of integration and at very high signal speeds is considered. Circuits may sustain soft errors due to ion interactions with non-RAM logic. The modes of ion-induced error production in non-memory circuitry are identified and methods of upset reduction or prevention determined to produce single event immune circuit designs. The applicability of hardening methods to logic of smaller size and/or higher speed is identified. Established computer simulation methods are used to predict limitations for single event immune integrated circuits. The single event problem is defined and characterized at a chip level, and criteria are suggested for optimizing designs for use in ion environments. (LEW)
EC-cache: load-balanced, low-latency cluster caching with online erasure coding (2016)

Data-intensive clusters and object stores are increasingly relying on in-memory object caching to meet the I/O performance demands. These systems routinely face the challenges of popularity skew, background load imbalance, and server failures, which result in severe load imbalance across servers and degraded I/O performance. Selective replication is a commonly used technique to tackle these challenges, where the number of cached replicas of an object is proportional to its popularity. In this paper, we explore an alternative approach using erasure coding.EC-Cache is a load-balanced, low latency cluster cache that uses online erasure coding to overcome the limitations of selective replication. EC-Cache employs erasure coding by: (i) splitting and erasure coding individual objects during writes, and (ii) late binding, wherein obtaining any k out of (k + r) splits of an object are sufficient, during reads. As compared to selective replication, EC-Cache improves load balancing by more than 3× and reduces the median and tail read latencies by more than 2×, while using the same amount of memory. EC-Cache does so using 10% additional bandwidth and a small increase in the amount of stored metadata. The benefits offered by EC-Cache are further amplified in the presence of background network load imbalance and server failures.
Propacetamol Vs. Tramadol For Post-Operative Pain Management After Urologic Surgery (2006)

Paracetamol (acetaminophen) is a safe and effective analgesic that is used for relieving mild to moderate pain. Tramadol, a synthetic opioid of aminocyctohexanol group, is an analgesic with central effect and weak opioid agonistic properties. This drug is also effective on noradrenergic and serotonergic neurotransmission. The aim of this study was to compare the analgesic and side effects of Propacetamol (ProdafalganTM,UPSA, France) and Tramadol (Aburaihan Pharmaceutical, Iran) after urologic open surgeries. A total number of 40 surgical patients were prospectively randomized into two equal groups of 20 and were entered into single blinded clinical trial. Anesthesia protocol was similar for all patients. Pain intensity was measured based on a 4-point verbal rating scale (VRS). VRS was obtained before analgesic administration (T) and at 0.5, 1.5, 3, 4.5, 6, 12, 18 and 24 hours. Patients received either Tramadol 100 mg IV or Propacetamol 2 gr IV at T0 and then 50 mg Tramadol or 1.5 gr Propacetamol at 6, 12, 18 and 24 hours if pain was present. Pain relief score was measured after 24 hours based on a 5 point scale. The results of this study showed that Propacetamol could be considered as a safe alternative post-operatively for pain management; however its use for severe pain management leads to inefficient pain control, necessitating supplementary analgesics.
Analysis and correction of crosstalk effects in pathway analysis (2013)

Identifying the pathways that are significantly impacted in a given condition is a crucial step in understanding the underlying biological phenomena. All approaches currently available for this purpose calculate a P-value that aims to quantify the significance of the involvement of each pathway in the given phenotype. These P-values were previously thought to be independent. Here we show that this is not the case, and that many pathways can considerably affect each other's P-values through a "crosstalk" phenomenon. Although it is intuitive that various pathways could influence each other, the presence and extent of this phenomenon have not been rigorously studied and, most importantly, there is no currently available technique able to quantify the amount of such crosstalk. Here, we show that all three major categories of pathway analysis methods (enrichment analysis, functional class scoring, and topology-based methods) are severely influenced by crosstalk phenomena. Using real pathways and data, we show that in some cases pathways with significant P-values are not biologically meaningful, and that some biologically meaningful pathways with nonsignificant P-values become statistically significant when the crosstalk effects of other pathways are removed. We describe a technique able to detect, quantify, and correct crosstalk effects, as well as identify independent functional modules. We assessed this novel approach on data from four experiments involving three phenotypes and two species. This method is expected to allow a better understanding of individual experiment results, as well as a more refined definition of the existing signaling pathways for specific phenotypes.
Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1 (2012)

Bortezomib (Velcade) is used widely for the treatment of various human cancers; however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that bortezomib induces proteasome-independent degradation of the TRAF6 protein, but not mRNA, in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of bortezomib due to down-regulation of the proteasomal subunit α-1 (PSMA1). To determine the molecular consequences of loss of TRAF6 in MDS/AML cells, in the present study, we applied gene-expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe herein novel mechanisms by which TRAF6 is regulated through bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to bortezomib by controlling PSMA1 expression.
B-lymphocyte mitogenicity in vitro of a synthetic lipopeptide fragment derived from bacterial lipoprotein. (1982)

Lipoprotein from the outer membrane of Escherichia coli is a potent mitogen towards lymphocytes of different species. A lipopeptide fragment corresponding to the N-terminal part of the lipoprotein was prepared by chemical synthesis. The mitogenicity of the compound was demonstrated by measuring the incorporation of both [3H]thymidine into DNA and [3H]uridine into RNA at various times after the addition of lipopeptide to mouse spleen cell cultures. The lipopeptide also activated B-lymphocyte development into immunoglobulin secreting cells, as shown by a hemolytic plaque assay. The mitogenicity of the synthetic compound was comparable to the activity of the B-lymphocyte mitogens lipoprotein and lipopolysaccharide. Thus, it was shown that a fragment of a bacterial surface component prepared by chemical synthesis, exhibits a marked biological activity.
Suppression of Laser-Induced Choroidal Neovascularization by Subconjunctival Injection of 9.ALPHA.-Fluoromedroxyprogesterone Acetate (FMPA), an Anti-angiogenic Agent, in Rats (2006)

9α-Fluoromedroxyprogesterone acetate (FMPA) is a synthetic analog of medroxyprogesterone acetate (MPA). FMPA exhibited more potent anti-tumor and anti-angiogenic activities in some assay systems than the parent agent, MPA. Exudative age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). Anecortave acetate, an angiostatic steroid, is clinically efficacious in patients with exudative AMD. Betamethasone is an anti-angiogenic steroid. Therefore, we examined the effects of FMPA, anecortave acetate and betamethasone on laser-induced CNV in rats. Anecortave acetate and betamethasone were included as positive controls. Crypton laser was applied to the fundus in Brown Norway rats. Laser photocoagulations were performed in each eye between the major retinal vessels of the superior retina. Subconjunctival injection of FMPA, anecortave acetate or betamethasone was performed once just after the photocoagulation (on day 0). The incidence of CNV formation was evaluated by fluorescein angiography (FAG) on day 14. On the next day, examination of the retinal function was performed by electro retinogram (ERG). Subconjunctival injection of FMPA at doses of 300, 1000 and 3000 μg/eye dose-dependently inhibited the incidence of CNV formation. Significant differences were observed at doses of 1000 and 3000 μg/eye of FMPA as compared with the control group. Anecortave acetate and betamethasone significantly inhibited the incidence of CNV formation. FMPA at the doses used in this study did not affect the retinal function in rats, as determined by ERG. FMPA appeared to be effective in a rat model of CNV, so it was demonstrated that FMPA might be useful in the treatment of AMD.
Resistance of Watermelon Seedlings and Fruit to the Fruit Blotch Bacterium (1993)

Seedlings of 22 watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] cultivars and two plant introductions were screened in the greenhouse for resistance to the fruit blotch bacterium. There were significant differences in disease severity among cultivars, but no cultivar was immune to the bacterium. In field tests, fruit of 18 commercial cultivars were inoculated individually or became infected naturally from diseased foliage. Cultivars with relatively resistant fruit included `Sugar Baby', `Jubilation', `Mirage', `Calsweet', `Crimson Sweet', `Royal Sweet', and `Sangria'. The more susceptible cultivars generally had a light-colored rind. Cultivar level of resistance to bacterial fruit blotch may not be sufficient under conditions conducive to severe disease development.
Insights from Modeling the 3D Structure of DNA−CBF3b Complex (2005)

A 3-dimensional model for a DNA-protein interaction has been developed. The protein component is the 61-residue fragment (res. 11-71) of subunit b of the yeast centromeric DNA binding factor 3, CBF3b. The CBF3b fragments bind to the 17 base pairs (5'-CGGAGGACTGTCCTCCG-3') as a symmetric homodimer, with each folded into three distinct conformations: a compact, zinc-binding domain (res. 11-44); an extended linker (res. 45-57); and an alpha-helical dimerization element (res. 58-71). The DNA fragment in the complex is featured by a relatively straight conformation with only slight deviation from a standard B-structure, and a large part of the major groove not blocked by the protein. The large DNA open area provides the necessary space for the other subunits of CBF3 to bind coordinately with CBF3b, fully consistent with the observation that the cooperation of all four CBF3 components is absolutely required to constitute an activity that specifically interacts with centromere DNA. The model also provides a footing for further considering the possible binding arrangements of the other three subunits, namely CBF3a, CBF3c, and CBF3d.
Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus (1987)

Four strains of human immunodeficiency virus (HIV) manifest consistent differences in biologic behavior after infection of the X50-7 line of human umbilical cord lymphocytes immortalized by Epstein-Barr virus (EBV). Some dilutions of the first strain examined, human T-cell lymphotropic virus type III B, which is derived from a pool of patient isolates propagated in H9 cells, caused transient cytopathic effects (CPE) followed by recovery of a subpopulation of X50-7 cells which became virus carrier cultures. Other dilutions of the same virus stock completely lysed X50-7 cells. Two other strains, RF2 and YW, both from individual patients with acquired immune deficiency syndrome, always induced complete cytolysis of X50-7 cells at all dilutions which infected the cells. However, RF2 did establish persistent infection of H9 cells. A fourth strain, PH1-MN, from a child with acquired immune deficiency syndrome-related complex, induced only transient CPE in X50-7 and H9 cells, which thereafter always recovered to form carrier cultures. For all four strains, the dilutions of HIV stocks which caused CPE corresponded to dilutions which resulted in the detection of HIV polypeptides by immunoblot. Cytolysis in HIV-infected X50-7 cells was accompanied by a decrease in the amount of EBV nuclear antigen; however, HIV infection did not induce EBV replication. Thus CPE in X50-7 cells is due to replication of HIV per se and not to activation of EBV. The observations indicate that there are differences in the cytolytic properties of HIVs and that these differences are influenced by the target cell.
Increased expression of ceruloplasmin in the retina following photic injury. (2003)

Ceruloplasmin, a retinal ferroxidase, is upregulated at the mRNA and protein levels upon light damage. The increased protein is primarily in Muller cells. Ceruloplasmin is considerably more abundant in retina than in brain. The retina expresses both the GPI-linked and secreted forms of ceruloplasmin, and since vitreous ceruloplasmin increases following photic injury, some of the retinal ceruloplasmin may be secreted into the vitreous. Ceruloplasmin may protect the retina from oxidative stress by decreasing the amount of ferrous iron available to produce reactive oxygen species.
Complementary addressed modification of double‐stranded DNA within a ternary complex (1988)

Double-stranded DNA containing a d(pG)18.d(pC)18 sequence was shown to be selectively alkylated in the vicinity of this fragment using the 5'-p-(N-2-chloroethyl-N-methylamino)benzylamide of deoxyribooligocytidylate, CIRCH2NH(pdC)n (n = 9,15), in conditions favouring triple-stranded complex formation.
Response of broiler chickens to microbial phytase supplementation as influenced by dietary phytic acid and non-phytate phosphorous levels. II. Effects on apparent metabolisable energy, nutrient digestibility and nutrient retention (2000)

1. Male broilers (n=900) were fed on wheat-sorghum-soyabean meal based diets containing 3 concentrations of phytic acid (10.4, 13.2 and 15.7 g/kg; equivalent to 2.9, 3.7 and 4.4 g/kg phytate P), 2 concentrations of non-phytate (or available) phosphorus (2.3 and 4.5 g/kg) and 3 concentrations of microbial phytase (0, 400 and 800 FTU/kg) from day 7 to 25 post-hatch. The dietary concentrations of phytic acid were manipulated by the inclusion of rice pollards. All diets contained celite (20 g/kg) as a source of acid-insoluble ash. 2. The apparent metabolisable energy (AME) concentrations of the diets were determined using a classical total collection procedure during the 3rd week of the trial. On d 25, digesta from the terminal ileum were collected and analysed for phosphorus, nitrogen and amino acids. Nutrient digestibilities were calculated using acid-insoluble ash as the indigestible marker. 2. Ileal digestibilities of nitrogen and essential amino acids were negatively influenced by increasing dietary levels of phytic acid but these negative effects were overcome by the addition of phytase. 3. Supplemental phytase increased AME, ileal digestibilities of phosphorus, nitrogen and amino acids and the retention of dry matter, phosphorus and nitrogen in broilers. There were no differences in the phytase responses between additions of 400 and 800 FTU/kg. 4. The responses in all variables, except AME, were greater in low non-phytate phosphorus diets. 5. In the case of AME, the response to added phytase was greater in adequate non-phytate phosphorus diets. Supplemental phytase increased AME values from 13.36 to 13.54 MJ/kg dry matter in low non-phytate phosphorus diets and from 12.66 to 13.38 MJ/kg dry matter in adequate non-phytate phosphorus diets.
Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux (1998)

We and others have recently shown that loss of the mitochondrial membrane potential (Deltapsi) precedes apoptosis and chemical-hypoxia-induced necrosis and is prevented by Bcl-2. In this report, we examine the biochemical mechanism used by Bcl-2 to prevent Deltapsi loss, as determined with mitochondria isolated from a cell line overexpressing human Bcl-2 or from livers of Bcl-2 transgenic mice. Although Bcl-2 had no effect on the respiration rate of isolated mitochondria, it prevented both Deltapsi loss and the permeability transition (PT) induced by various reagents, including Ca2+, H2O2, and tert-butyl hydroperoxide. Even under conditions that did not allow PT, Bcl-2 maintained Deltapsi, suggesting that the functional target of Bcl-2 is regulation of Deltapsi but not PT. Bcl-2 also maintained Deltapsi in the presence of the protonophore SF6847, which induces proton influx, suggesting that Bcl-2 regulates ion transport to maintain Deltapsi. Although treatment with SF6847 in the absence of Ca2+ caused massive H+ influx in control mitochondria, the presence of Bcl-2 induced H+ efflux after transient H+ influx. In this case, Bcl-2 did not enhance K+ efflux. Furthermore, Bcl-2 enhanced H+ efflux but not K+ flux after treatment of mitochondria with Ca2+ or tert-butyl hydroperoxide. These results suggest that Bcl-2 maintains Deltapsi by enhancing H+ efflux in the presence of Deltapsi-loss-inducing stimuli.
Can GLP-1 preparations be used in children and adolescents with diabetes mellitus? (2014)

The number of young diabetics is increasing and therapeutic options for these patients are limited. Glucagon-like peptide-1 (GLP-1) is secreted from the gut after meals and enhances glucose-induced insulin secretion, inhibits glucagon secretion, suppresses appetite, and delays the gastric-emptying rate. GLP-1 analogs are already widely used in the adult population to improve glycemic control and induce weight loss in overweight subjects with type 2 diabetes. The glucose-lowering effects resulting from the inhibition of glucagon secretion and the gastric-emptying rate could be of clinical importance in type 1 diabetes. In this article we review clinical data regarding the use of GLP-1 receptor agonists in youth and address the potential benefits and safety aspects of these compounds. Large scale clinical trials are still needed in the pediatric population.
Identification of non-immunoglobulin A-Fc-binding forms and low-molecular-weight secreted forms of the group B streptococcal beta antigen (1989)

The beta antigen expressed on the surfaces of certain strains of group B streptococci has been reported to bind to the Fc region of human immunoglobulin A (IgA). In this study, we screened 100 isolates of group B streptococci for expression of both beta antigen and IgA-Fc-binding activity. We identified two isolates which expressed the beta antigen but could not bind human IgA Fc fragments and also observed variability in IgA-Fc-binding activity among other beta-antigen-expressing strains. Novel low-molecular-weight forms of beta antigen were secreted by four beta-antigen surface-negative isolates and included IgA-Fc-binding (Mrs, 55,000 and 53,000) and non-IgA-Fc-binding (Mr, 38,000) molecules. These results suggest that the IgA-Fc-binding site represents a unique domain of the beta antigen. The 55,000- and 53,000-Mr forms of secreted beta antigen were functionally and antigenically representative of the size-heterogeneous (Mr, up to 145,000) beta-antigen molecules expressed by surface-positive strains. The cell surface-localized IgA-Fc-binding molecules could bind only human serum IgA efficiently; however, once solubilized, these molecules could bind both human serum and secretory IgAs.