gebhart/patrepeval huggingface dataset:
Structure of a Plasmodium yoelii gene-encoded protein homologous to the Ca2+-ATPase of rabbit skeletal muscle sarcoplasmic reticulum (1990)

A cation-transporting ATPase gene of Plasmodium yoelii was cloned from the parasite genomic library using an oligonucleotide probe derived from a conserved amino acid sequence of the phosphorylation domain of the aspartyl phosphate family of ATPases. The complete nucleotide sequence was determined and it predicts a 126,717 Mr encoded protein composed of 1115 amino acids. Northern blot analysis revealed that the gene is transcribed during the asexual stages of parasite development. The P. yoelii protein contains functional and structural features common to the family of aspartyl phosphate cation-transporting ATPases. The parasite protein shows the highest overall homology in amino acid sequence (42%) to the Ca2(+)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum. Homologies to other aspartyl phosphate cation-transporting ATPases including a plasma membrane Ca2(+)-ATPase were between 13 and 24%. The structure predicted from a hydropathy plot also shows 10 transmembrane domains, the number and location of which correlated well with the sarcoplasmic reticulum Ca2(+)-ATPase. On the basis of these results, we conclude that the parasite gene encodes an organellar, but not plasma membrane, Ca2(+)-ATPase. The P. yoelii protein, furthermore, contains all six amino acid residues in the transmembrane domains that were recently identified as comprising a high-affinity Ca2(+)-binding site. It follows that organellar Ca2(+)-ATPases of rabbit and Plasmodium conserve functionally important amino acid residues, even though they are remote from each other phylogenetically.
Long-term effects of continuous intrathecal opioid treatment in chronic pain of nonmalignant etiology (1996)

In the present retrospective investigation, the long-term effects of continuous intrathecal opioid therapy via implantable infusion pump systems were examined in 120 patients with chronic, nonmalignant pain syndromes. The follow-up period was 6 months to 5.7 years (mean 3.4 years +/- 1.3 standard error of the mean). Deafferentation pain and neuropathic pain showed the best long-term results, with 68% and 62% pain reduction (visual analog scale), respectively. The mean morphine dosage initially administered was 2.7 mg/day (range 0.3-12 mg/day); after an average of 3.4 years, it was 4.7 mg/day (range 0.3-12 mg/day). In a long-term observation of 28 patients who received intrathecal morphine for longer than 4 years. 18 patients (64.3%) had a constant dosage history and 10 patients (35.7%) showed an increase in morphine dosage to more than 6 mg/day 1 year after dosage determination. In seven cases, a tolerance developed: in four patients the tolerance was controlled by means of "drug holidays"; but in three patients it was necessary to remove the pump systems. Explantation of the pump system occurred in 22 additional cases for other reasons. Throughout the follow-up period, 74.2% of the patients profited from the intrathecal opiate therapy: the average pain reduction after 6 months was 67.4% and, as of the last follow-up examination, it was 58.1%. Ninety-two percent of the patients were satisfied with the therapy and 81% reported an improvement in their quality of life. The authors' 6-year experience with administration of intrathecal opioid medications for nonmalignant pain should encourage the use of this method in carefully selected patients.
Food and eating on television: impacts and influences (2000)

Describes the background to and main findings from a three‐year MAFF‐funded research project on the role of television in the food choices of young people. The project examined the nature and extent of television’s portrayal of food and eating and investigated young people’s interpretations of this. The findings indicate that food and eating are portrayed very frequently on UK television, but that the “message” in programmes contrasts with the “message” in advertising in terms of the nutritional content of the foods depicted. This disorder and contradiction are reflected in young viewers’ accounts of their own eating habits.
From Three-Photon Greenberger-Horne-Zeilinger States to Ballistic Universal Quantum Computation (2015)

Single photons, manipulated using integrated linear optics, constitute a promising platform for universal quantum computation. A series of increasingly efficient proposals have shown linear-optical quantum computing to be formally scalable. However, existing schemes typically require extensive adaptive switching, which is experimentally challenging and noisy, thousands of photon sources per renormalized qubit, and/or large quantum memories for repeat-until-success strategies. Our work overcomes all these problems. We present a scheme to construct a cluster state universal for quantum computation, which uses no adaptive switching, no large memories, and which is at least an order of magnitude more resource efficient than previous passive schemes. Unlike previous proposals, it is constructed entirely from loss-detecting gates and offers a robustness to photon loss. Even without the use of an active loss-tolerant encoding, our scheme naturally tolerates a total loss rate ∼1.6% in the photons detected in the gates. This scheme uses only 3 Greenberger-Horne-Zeilinger states as a resource, together with a passive linear-optical network. We fully describe and model the iterative process of cluster generation, including photon loss and gate failure. This demonstrates that building a linear-optical quantum computer needs to be less challenging than previously thought.
Delivery of RNA Interference (2006)

Over the last few years, RNA Interference (RNAi), a naturally occurring mechanism of gene regulation conserved in plant and mammalian cells, has opened numerous novel opportunities for basic research across the field of biology. While RNAi has helped accelerate discovery and understanding of gene functions, it also has great potential as a therapeutic and potentially prophylactic modality. Challenging diseases failing conventional therapeutics could become treatable by specific silencing of key pathogenic genes. More specifically, therapeutic targets previously deemed "undruggable" by small molecules, are now coming within reach of RNAi based therapy. For RNAi to be effective and elicit gene silencing response, the double-stranded RNA molecules must be delivered to the target cell. Unfortunately, delivery of these RNA duplexes has been challenging, halting rapid development of RNAi-based therapies. In this review we present current advancements in the field of siRNA delivery methods, including the pros and cons of each method.
Human β‐mannosidase deficiency: Biochemical findings in plasma, fibroblasts, white cells and urine (1987)

Marked deficiencies of beta-mannosidase activity were demonstrated in plasma, leukocytes, fibroblasts and urine of a patient with beta-mannosidosis, similar deficiencies were observed in the proband's sibling. All other lysosomal enzymes measured, including sulphamidase, exhibited normal activity. Both parents showed reduced plasma and leukocyte beta-mannosidase activity. Urinary glycosaminoglycan excretion was normal but TLC of urinary oligosaccharides revealed an abnormal band with the mobility of a disaccharide. This finding was confirmed by Bio-Gel P2 column chromatography. Further purification of this compound revealed two disaccharides, both of which yielded mannose and glucosamine following acid hydrolysis and mannose and N-acetylglucosamine following enzymic digestion. These two compounds are thought to be structural isomers of the disaccharide Man beta-GlcNAc.
Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavalin A. (1980)

The protein here named gelonin was extracted from the seeds of Gelonium multiflorum by a buffered phosphate solution and purified in a single step by chromatography on a carboxymethyl cellulose column.Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and gel filtration on Sephacryl 300 superfine showed that gelonin consists of one polypeptide chain with a molecular weight of about 28,000 to 30,000.Gelonin bound to a column containing immobilized concanavalin A and could be eluted with amethylmannoside.Pretreatment of gelonin with jackbean mannosidase prevented this binding, indicating that it is a glycoprotein containing terminal mannose residues.The protein proved t o be extremely stable, as measured by its biological activity, toward treatment with sodium dodecyl sulfate, urea, acid, base, and heat.Gelonin strongly inhibited protein synthesis in a reticulocyte lysate.It inactivated the 60 S ribosomal subunit with no effect on the 40 S ribosomal subunit.A t a concentration of 100 pg/ml, gelonin only slightly inhibited protein synthesis in intact HeLa cells and it gave no microscopically visible cytopathogenic effect.When the inhibitor was linked by a disulfide bridge to concanavalin A, the complex gave 50% inhibition of cellular protein synthesis at a concentration of about 1 pg/ml, corresponding to about 0.2 pg/ml of gelonin.The results show that gelonin is a single chain protein which acts in a cell-free system like the A chains of abrin, ricin, and modeccin and suggest that it lacks the ability to bind to the cell surface and to enter intact cells.When coupled through a disulfide bond to a protein capable of binding to cells, it is rendered toxic to intact cells.
High-speed, burst-mode, packet-capable optical receiver and instantaneous clock recovery for optical bus operation (1994)

This paper describes an enhanced performance version of a high-speed burst-mode compatible optical receiver and its application to 622-Mb/s optical bus operation in conjunction with an instantaneous clock recovery scheme. The receiver is fabricated in a 12 GHz f/sub t/ silicon bipolar technology and consists of a differential transimpedance amplifier with an auto-threshold level controller and a high-speed quantizer. Using an InGaAs avalanche photodiode, the typical burst mode sensitivity is around /spl minus/34 dBm (10/sup /spl minus/9/ BER) at bit rates up to 1.5 Gb/s with a dynamic range of 26 db for both pseudorandom and burst signals. The results using a laser beam modulated by a high-speed external modulator indicate that the receiver can be operated at bit rates higher than 2 Gb/s. With a worst-case self-resetting time <50 ns for the threshold control circuit, the receiver is usable for optical packet communication where data signals with varying optical power are employed. This receiver was demonstrated in a 622-Mb/s optical bus application where the clock signal was recovered from the packet data signal using a novel high-speed CMOS instantaneous clock recovery IC.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Efficient Isolation and Solubilization of Pristine Single‐Walled Nanotubes in Bile Salt Micelles (2004)

Abstract We have investigated a wide variety of surfactants for their efficiency in dissolving isolated single‐walled carbon nanotubes (SWNTs) in water. In doing so, we have completely avoided the harsh chemical or mechanical conditions, such as acid or ultrasonic treatments, that are known to damage SWNTs. Bile salts in particular are found to be exceptionally effective in dissolving individual tubes, as evidenced by highly resolved optical absorption spectra, bright bandgap fluorescence, and the unprecedented resolution (∼ 2.5 cm –1 ) of the radial breathing modes in Raman spectra. This is attributed to the formation of very regular and stable micelles around the nanotubes providing an unusually homogeneous environment. Quantitative information concerning the degree of solubilization is obtained from absorption spectroscopy.
Analysis of purity of Clostridium difficile toxin A derived by affinity chromatography on immobilized bovine thyroglobulin (1988)

Clostridium difficile toxin A separated by bovine thyroglobulin affinity chromatography was analysed for its purity by fast protein liquid anion-exchange chromatography (FPLC). By testing each FPLC fraction for cytotoxicity the affinity-purified toxin A specimen was shown to contain small amounts of contaminating toxin B. Coldhaemagglutination activity was detected in FPLC fractions corresponding to toxin A but not in those corresponding to toxin B. Toxin A obtained from bovine thyroglobulin affinity chromatography should be further purified to remove traces of toxin B.
High Density Lipoprotein Phospholipid Composition Is a Major Determinant of the Bi-directional Flux and Net Movement of Cellular Free Cholesterol Mediated by Scavenger Receptor BI (2000)

The role of high density lipoprotein (HDL) phospholipid in scavenger receptor BI (SR-BI)-mediated free cholesterol flux was examined by manipulating HDL(3) phosphatidylcholine and sphingomyelin content. Both phosphatidylcholine and sphingomyelin enrichment of HDL enhanced the net efflux of cholesterol from SR-BI-expressing COS-7 cells but by two different mechanisms. Phosphatidylcholine enrichment of HDL increased efflux, whereas sphingomyelin enrichment decreased influx of HDL cholesterol. Although similar trends were observed in control (vector-transfected) COS-7 cells, SR-BI overexpression amplified the effects of phosphatidylcholine and sphingomyelin enrichment of HDL 25- and 2.8-fold, respectively. By using both phosphatidylcholine-enriched and phospholipase A(2)-treated HDL to obtain HDL with a graded phosphatidylcholine content, we showed that SR-BI-mediated cholesterol efflux was highly correlated (r(2) = 0.985) with HDL phosphatidylcholine content. The effects of varying HDL phospholipid composition on SR-BI-mediated free cholesterol flux were not correlated with changes in either the K(d) or B(max) values for high affinity binding to SR-BI. We conclude that SR-BI-mediated free cholesterol flux is highly sensitive to HDL phospholipid composition. Thus, factors that regulate cellular SR-BI expression and the local modification of HDL phospholipid composition will have a large impact on reverse cholesterol transport.
Genetics of Parkinsonism: a review. (2001)

Idiopathic Parkinson's disease (IPD), a progressive neurodegenerative disorder, is a common cause of disability. No current therapies modify disease progression. The pathological hallmarks are the presence of Lewy bodies and massive loss of dopaminergic neurons in the pars compacta of the substantia nigra. Two genes (SNCA and parkin) as well as two gene loci have now been implicated in the pathogenesis of familial PD. These represent significant progress in our understanding of the disease, considering the rarity of large families, low heritability in the general population and genetic heterogeneity. Mutations in a further gene, UCHL1, have been described in familial PD although the evidence for its role in PD is less clear. Knowledge of the genes described in PD to date should help to define molecular mechanisms of neurodegeneration in PD, as well as in other diseases where defects in protein handling may be a common feature. Nigral degeneration with Lewy body formation and the resulting clinical picture of PD may represent a final common pathway of a multifactorial disease process in which both environmental and genetic factors have a role. This review discusses the major advances in the field to date and illustrates how the existence of genetic factors has now become firmly established.
Peroxisome Proliferator-Activated Receptors γ and α Mediate in Vivo Regulation of Uncoupling Protein (UCP-1, UCP-2, UCP-3) Gene Expression (1998)

A role for peroxisome proliferator-activated receptors, PPAR gamma and PPAR alpha, as regulators of energy homeostasis and lipid metabolism, has been suggested. Recently, three distinct uncoupling protein isoforms, UCP-1, UCP-2, and UCP-3, have also been identified and implicated as mediators of thermogenesis. Here, we examined whether in vivo PPAR gamma or PPAR alpha activation regulates the expression of all three UCP isoforms. Rats or lean and db/db mice were treated with PPAR gamma [thiazolidinedione (TZD)] or PPAR alpha (WY-14643) agonists, followed by measurement of messenger RNAs (mRNAs) for UCP-1, UCP-2, and UCP-3 in selected tissues where they are expressed. TZD treatment (AD 5075 at 5 mg/kg x day) of rats (14 days) increased brown adipose tissue (BAT) depot size and induced the expression of each UCP mRNA (3x control levels for UCP-1 and UCP-2, 2.5x control for UCP-3). In contrast, UCP-2 and UCP-3 mRNA levels were not affected in white adipose tissue or skeletal muscle. Chronic (30 days) low-dose (0.3 mg/kg x day) TZD treatment induced UCP-1 mRNA and protein in BAT (2.5x control). In contrast, chronic TZD treatment (30 mg/kg x day) suppressed UCP-1 mRNA (>80%) and protein (50%) expression in BAT. This was associated with further induction of UCP-2 expression (>10-fold) and an increase in the size of lipid vacuoles, a decrease in the number of lipid vacuoles in each adipocyte, and an increase in the size of the adipocytes. TZD treatment of db/db mice (BRL 49653 at 10 mg/kg x day for 10 days) also induced UCP-1 and UCP-3 (but not UCP-2) expression in BAT. PPAR alpha is present in BAT, as well as liver. Treatment of rats or db/db mice with WY-14643 did not affect expression of UCP-1, -2, or -3 in BAT. Hepatic UCP-2 mRNA was increased (4x control level) in db/db and lean mice, although this effect was not observed in rats. Thus, in vivo PPAR gamma activation can induce expression of UCP-1, -2, and -3 in BAT; whereas chronic-intense PPAR gamma activation may cause BAT to assume white adipose tissue-like phenotype with increased UCP-2 levels. PPAR alpha activation in mice is sufficient to induce liver UCP-2 expression.
Observations on the Mechanism of Action of Penicillin. (1942)

SummaryPenicillin acts either as a bacteriostatic or bactericidal agent depending on the experimental conditions. The number of organisms decreases at a constant rate until 99% of the organisms have been destroyed. The rate of killing varies with different organisms. The action of penicillin on hemolytic streptococci is not accompanied by lysis of the organisms. No detectable amount of penicillin is destroyed or absorbed from solution by the organisms. It appears to be effective only when active multiplication takes place.
Transfusion-Associated Hepatitis Not Due to Viral Hepatitis Type A or B (1975)

Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.
G/C-modified oligodeoxynucleotides with selective complementarity: synthesis and hybridization properties (1996)

Modified oligodeoxyribonucleotides (ODNs) that have unique hybridization properties were designed and synthesized for the first time. These ODNs, called selective binding complementary ODNs (SBC ODNs), are unable to form stable hybrids with each other, yet are able to form stable, sequence specific hybrids with complementary unmodified strands of nucleic acid. To make SBC ODNs, deoxyguanosine (dG) and deoxycytidine (dC) were substituted with deoxyinosine (dI) and 3-(2'-deoxy-beta-D-ribofuranosyl)pyrrolo-[2,3-d]-pyrimidine-2-(3H)-one (dP), respectively. The hybridization properties of several otherwise identical complementary ODNs containing one or both of these nucleoside analogs were studied by both UV monitored thermal denaturation and non-denaturing PAGE. The data showed that while dI and dP did form base pairs with dC and dG, respectively, dI did not form a stable base pair with dP. A self-complementary ODN uniformly substituted with dI and dP acquired single-stranded character and was able to strand invade the end of a duplex DNA better than an unsubstituted ODN. This observation implies that SBC ODNs should effectively hybridize to hairpins present in single-stranded DNA or RNA.
Gelation of liposome interior A novel method for drug encapsulation (1992)

Liposomes can be loaded with weak acids and bases, which exist in solutions in equilibrium with membrane permeable uncharged form, using various gradients across their membranes. Because in some cases the estimated drug concentration in the loaded liposomes exceeds their aqueous solubility we investigated the physical state of the liposome encapsulated anticancer drug Doxorubicin. X-Ray diffraction, electron microscopy, and test tube solubility experiments have shown that upon encapsulation the drug molecules form a gel-like phase.
RNA Interference Knockdown of hU2AF35Impairs Cell Cycle Progression and Modulates Alternative Splicing of Cdc25 Transcripts (2006)

U2AF is a heterodimeric splicing factor composed of a large (U2AF65) and a small (U2AF35) subunit. In humans, alternative splicing generates two U2AF35 variants, U2AF35a and U2AF35b. Here, we used RNA interference to specifically ablate the expression of each isoform in HeLa cells. Our results show that knockdown of the major U2AF35a isoform reduced cell viability and impaired mitotic progression, leading to accumulation of cells in prometaphase. Microarray analysis revealed that knockdown of U2AF35a affected the expression level of approximately 500 mRNAs, from which >90% were underrepresented relative to the control. Among mRNAs underrepresented in U2AF35a-depleted cells we identified an essential cell cycle gene, Cdc27, for which there was an increase in the ratio between unspliced and spliced RNA and a significant reduction in protein level. Furthermore, we show that depletion of either U2AF35a or U2AF35b altered the ratios of alternatively spliced isoforms of Cdc25B and Cdc25C transcripts. Taken together our results demonstrate that U2AF35a is essential for HeLa cell division and suggest a novel role for both U2AF35 protein isoforms as regulators of alternative splicing of a specific subset of genes.
Galectin‐3: differential expression between small‐cell and non‐small‐cell lung cancer (2004)

This differential expression of galectin-3 between histological types of lung carcinoma suggests that galectin-3 may have an important influence on tumour cell adhesion, apoptosis and the response of tumours to chemotherapy.
Epigenetic Analysis of RASSF1A Gene in Cell-Free DNA in Amniotic Fluid (2007)

Cell-free fetal nucleic acids exist not only in the maternal circulation (1) but also in amniotic fluid samples (2). Evidence suggests that DNA in maternal plasma that bears the fetal genotype is predominantly derived from the placenta (3). Although the cells in amniotic fluid are widely known to have originated from fetal urogenital, respiratory, and alimentary tracts, skin and amnion, the origin of cell-free fetal DNA in amniotic fluid remains unclear (2). It has been speculated that the latter might originate from the same sources as amniotic fluid cells or the placenta (2). Here, we applied the recent developments in epigenetics to this area of research (4)(5).

The promoter of RASSF1A has been shown to be hypermethylated in the placenta but essentially unmethylated in maternal blood cells and other fetal tissues (4). Chan et al. (5) adopted hypermethylated RASSF1A as a placental-specific epigenetic marker and developed an assay for its detection in maternal plasma as a sex-independent fetal DNA marker. The assay involved digestion by Bst UI, a methylation-sensitive restriction enzyme, …