gebhart/patrepeval huggingface dataset:
Genetically determined hypercholesterolemia in a rhesus monkey family due to a deficiency of the LDL receptor. (1988)

A family of rhesus monkeys comprising a sire, a dam, and four male offspring were fed a cholesterol-free Purina Chow diet for several months. The sire, 431-J, and two of the offspring, B-8204 and B-8806, had persistent plasma cholesterol levels in the range of 100-130 mg/dl, whereas the dam, 766-I, and the two other offspring, B-1000 and B-7643, exhibited a marked hypercholesterolemia in the 250-300 mg/dl range associated with an elevation of plasma LDL and apoB. When fed for 12 weeks a diet containing 12.5% lard and 0.25% cholesterol, sire, dam, B-1000 and B-7643 exhibited a marked hypercholesterolemia (500-800 mg/dl range), whereas B-8204 and B-8806 developed only a modest hypercholesterolemia (200-250 mg/dl). All animals were Lp[a]+. Skin fibroblasts from each animal and from control cells were grown in 10% fetal calf serum, transferred to 10% lipoprotein-deficient serum for 48 hr, and then incubated at 4 degrees C or 37 degrees C with 125I-labeled Lp[a]-free LDL. The fibroblasts from dam and offspring B-1000 and B-7643 bound and internalized 125I-labeled LDL less efficiently than control cells. Mathematical analyses of the 4 degrees C binding data indicated that there were no significant differences in LDL binding affinity between test and control cells suggesting that cells from the animals with a spontaneous hypercholesterolemia had a decreased number of LDL receptors. This conclusion was supported by the results of ligand and immunoblot analyses carried out on cell lysates separated by gradient gel electrophoresis. We conclude that a genetically determined LDL receptor deficiency was responsible, in part, for the spontaneous hypercholesterolemia observed in three out of the six family members and that this deficiency accounted for the hyperresponsiveness to a dietary fat and cholesterol challenge by the dam and the two offspring, B-1000 and B-7643. The hyperresponsiveness noted in the sire that had no evidence for LDL-receptor deficiency illustrates that factors other than the LDL receptor were responsible for the hypercholesterolemia attending the fat challenge.
Malignant transformation of nontrophoblastic cells is associated with the expression of chorionic gonadotropin beta genes normally transcribed in trophoblastic cells. (1997)

The beta subunit of human chorionic gonadotropin (hCGbeta) is encoded by four nonallelic CGbeta genes. An assay was developed for distinguishing type I CGbeta allelic genes beta7 and beta6, which possess a GCC codon corresponding to an alanine at position 117 of hCGbeta, from type II CGbeta genes beta8, beta5, and beta3 and its allele beta9, which possess a GAC codon corresponding to an aspartic acid at the same position. In normal trophoblast, hCGbeta is encoded by type II CGbeta genes, whereas normal nontrophoblastic tissues of differing histological origin (breast, prostate, skeletal muscle, bladder, adrenal glands, thyroid, colon, and uterus) express only type I CGbeta genes. We studied the expression of CGbeta genes in 86 tumor specimens collected from patients with breast, bladder, prostate, and thyroid cancer and found that up to 61% of these nontrophoblastic tumors expressed type II CGbeta genes. Experiments performed on tumor tissues and their normal counterparts confirmed that the malignant transformation of nontrophoblastic cells is associated with the expression of type II CGbeta genes. These findings provide the basis for a simple test (the CG117 assay) that may be useful for the diagnosis of the most frequent malignancies.
The Structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) from Pseudomonas aeruginosa (2004)

Type II fatty acid biosynthesis systems are essential for membrane formation in bacteria, making the constituent proteins of this pathway attractive targets for antibacterial drug discovery. The third step in the elongation cycle of the type II fatty acid biosynthesis is catalyzed by beta-hydroxyacyl-(acyl carrier protein) (ACP) dehydratase. There are two isoforms. FabZ, which catalyzes the dehydration of (3R)-hydroxyacyl-ACP to trans-2-acyl-ACP, is a universally expressed component of the bacterial type II system. FabA, the second isoform, as has more limited distribution in nature and, in addition to dehydration, also carries out the isomerization of trans-2- to cis-3-decenoyl-ACP as an essential step in unsaturated fatty acid biosynthesis. We report the structure of FabZ from the important human pathogen Pseudomonas aeruginosa at 2.5 A of resolution. PaFabZ is a hexamer (trimer of dimers) with the His/Glu catalytic dyad located within a deep, narrow tunnel formed at the dimer interface. Site-directed mutagenesis experiments showed that the obvious differences in the active site residues that distinguish the FabA and FabZ subfamilies of dehydratases do not account for the unique ability of FabA to catalyze isomerization. Because the catalytic machinery of the two enzymes is practically indistinguishable, the structural differences observed in the shape of the substrate binding channels of FabA and FabZ lead us to hypothesize that the different shapes of the tunnels control the conformation and positioning of the bound substrate, allowing FabA, but not FabZ, to catalyze the isomerization reaction.
<title>Modeling phase-shifting masks</title> (1991)

An algebraic image perturbation model is introduced which used the point spread function of the lens and the mutual coherence of the illumination to give insight into the interactions of auxiliary patterns with features for the phase shifting mask technology. The model is based on adding electric field contributions and the cross term is shown to characterize the dominant interaction as a function of the number of auxiliary features, the relative coherence of the illumination, and the spreading of the image of the auxiliary pattern toward the feature. Data on the point/line spread functions and the mutual coherence are given and used to verify the accuracy of quantitative predictions of the change in peak intensity for lines and contacts when nonprinting phase shifting auxiliary patterns are added.
Use of a cancer register for monitoring and evaluating a breast cancer screening programme (1989)

To monitor the effectiveness of a breast cancer screening service accurate information is necessary on the incidence of breast cancer before and after screening is introduced. The Wessex Cancer Register has been used to provide data on the incidence prior to screening and arrangements are being made for the exchange of information between the Register and each screening service in Wessex in order that future registrations can be divided into screen-detected and symptomatically-detected cases. Since changes in mortality will not be apparent for some years and are not detectable in small populations, other indicators of effectiveness are required. Stage at presentation predicts mortality; a change in stage distribution as a result of screening would indicate future changes in mortality. The Cancer Register has been used to analyse stage distribution before the advent of screening. Procedures have been adopted for collecting staging data on all breast cancers diagnosed in the future, both within and without the screening service. In this way stage distribution will be compared before and after the implementation of the service and predictions made on the effect on mortality in the future. In addition, information on the incidence of interval cancers will be analysed using the Cancer Register so that, in the long term, an assessment can be made of the appropriate length of the interval between screens. These cancers will be notified to the screening office for review. A Cancer Register can provide the population base from which to measure the true effectiveness of a breast screening service on the community it serves.
Low-loss dispersion equaliser operable over theentire erbium window (1996)

The authors report on a novel design of etalon type dispersion compensating filter which is compact, low-loss, polarisation-insensitive, and trackable to any wavelength from 1530 to 1565 nm. In system tests we demonstrated nearly penalty-free transmission over 160 km of conventional singlemode fibre at 10 Gbit/s, and 40 km at 20 Gbit/s.
Role of lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts. (1978)

The low density lipoprotein (LDL) cell surface receptors on human fibroblasts grown in culture bind specific plasma lipoproteins, initiating a series of events which regulate intracellular cholesterol metabolism. Specificity for the interaction with the receptors resides with the protein moieties of the lipoproteins, specifically with the B and E apoproteins of LDL and certain high density lipoproteins (HDLc HDLl), respectively. It was previously established that the amino acid arginine is a functionally significant residue in or near the recognition sites on the B and E apoproteins and that modification of this residue abolishes the ability of these apolipoproteins to bind to the receptor. The present study indicates that lysine residues are also involved in the lipoprotein-receptor interaction. Chemical modification of 15% of the lysine residues of LDL by carbamylation with cyanate or 20% by acetoacetylation with diketene prevents the LDL from competitively displacing unmodified 125I-LDL from the high affinity receptor sites or from binding directly to the receptor. Moreover, quantitative reversal of the aceto-acetylation of the lysine residues of LDL by hydroxylamine treatment regenerates the lysyl residues and reestablishes greater than 90% of the original binding activity of the LDL. The reversibility of this reaction establishes that the loss of binding activity which follows lysine modification is not due to an irreversible alteration of the LDL or HDLc but is probably due to an alteration of a property of the recognition site associated with specific lysine residues. While acetoacetylation and carbamylation neutralize the positive charge on the epsilon-amino group of lysine, reductive methylation selectively modifies lysine residues of LDL and HDLc without altering the positive charge, yet abolishes their ability to bind to the receptor. Preservation of the charge but loss of binding activity following reductive methylation of the lipoproteins suggests that the specificity of the recognition site does not reside simply with the presence of positive charges but depends on other more specific properties of the site determined by the presence of a limited number of the lysine (and arginine) residues. The precise role of lysine remains to be defined, but its function may be to establish and maintain the conformation of the recognition site or the alignment of reactive residues, or both, or to chemically react, through its epsilon-amino group, with the receptor (hydrogen bond formation would be such a possibility).
Circulation persistence and biodistribution of lyophilized liposome-encapsulated hemoglobin: An oxygen-carrying resuscitative fluid (1994)

The mean circulation half-life of liposome-encapsulated hemoglobin in mice injected at a dose of 1.0 g phospholipid/kg mouse and 1.95 g hemoglobin/kg was approximately 10.4 +/- 0.5 (SD) hrs. The circulation half-life of lyophilized liposome-encapsulated hemoglobin was 10.7 +/- 0.7 hrs. The circulation profiles demonstrate a rapid removal phase over the first 4 hrs after injection, followed by a secondary slow removal measured up to 24 hrs. The rapid removal phase of liposome-encapsulated hemoglobin and lyophilized liposome-encapsulated hemoglobin in the rabbit (injected at the same dose) indicated that lyophilized liposome-encapsulated hemoglobin persists longer than the unlyophilized form in the first 4 hrs after injection. The organ biodistributions of unlyophilized 99mTc-liposome-encapsulated hemoglobin and lyophilized 99mTc-liposome-encapsulated hemoglobin in the rabbit demonstrate that the reticuloendothelial system is the primary site of removal, with significant uptake of lyophilized 99mTc-liposome-encapsulated hemoglobin by the liver (15.6 +/- 1.0%), bone marrow (12.6 +/- 1.6%), and spleen (9.7 +/- 1.1%). The kidneys showed little accumulation of unlyophilized 99mTc-liposome-encapsulated hemoglobin or lyophilized 99mTc-liposome-encapsulated hemoglobin (1.6 +/- 0.2% and 1.8 +/- 0.1%, respectively), an important result for the efficacy and safety of this hemoglobin-based blood substitute. (ABSTRACT TRUNCATED)
Self‐Rupturing Microcapsules (2005)

Self-rupturing microcapsules are prepared by layer-by-layer coating of degradable dextran-hydroxyethyl methacrylate microgels with the polyelectrolytes poly(allylamine hydrochloride) and sodium poly(styrene sulfonate). When the microgel core degrades, the swelling pressure increases and, at a critical value of the swelling pressure, the surrounding membrane suddenly ruptures (see Figure). This type of microcapsule could be very promising for pulsed drug delivery. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2005/c1951_s.html 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.
Collapsibility of the human upper airway during normal sleep (1989)

Upper airway resistance (UAR) increases in normal subjects during the transition from wakefulness to sleep. To examine the influence of sleep on upper airway collapsibility, inspiratory UAR (epiglottis to nares) and genioglossus electromyogram (EMG) were measured in six healthy men before and during inspiratory resistive loading. UAR increased significantly (P less than 0.05) from wakefulness to non-rapid-eye-movement (NREM) sleep [3.1 +/- 0.4 to 11.7 +/- 3.5 (SE) cmH2O.1-1.s]. Resistive load application during wakefulness produced small increments in UAR. However, during NREM sleep, UAR increased dramatically with loading in four subjects although two subjects demonstrated little change. This increment in UAR from wakefulness to sleep correlated closely with the rise in UAR during loading while asleep (e.g., load 12: r = 0.90, P less than 0.05), indicating consistent upper airway behavior during sleep. On the other hand, no measurement of upper airway behavior during wakefulness was predictive of events during sleep. Although the influence of sleep on the EMG was difficult to assess, peak inspiratory genioglossus EMG clearly increased (P less than 0.05) after load application during NREM sleep. Finally, minute ventilation fell significantly from wakefulness values during NREM sleep, with the largest decrement in sleeping minute ventilation occurring in those subjects having the greatest awake-to-sleep increment in UAR (r = -0.88, P less than 0.05). We conclude that there is marked variability among normal men in upper airway collapsibility during sleep.
Intercepting mobile communications (2001)

The 802.11 standard for wireless networks includes a Wired Equivalent Privacy (WEP) protocol, used to protect link-layer communications from eavesdropping and other attacks. We have discovered several serious security flaws in the protocol, stemming from mis-application of cryptographic primitives. The flaws lead to a number of practical attacks that demonstrate that WEP fails to achieve its security goals. In this paper, we discuss in detail each of the flaws, the underlying security principle violations, and the ensuing attacks.
Triacylglycerol structure of plant and fungal oils containing ψ‐linolenic acid (1988)

The triacylglycerol stereospecific structure was determined for the major plant oils containing ψ-linolenic acid (GLA): evening primrose oil (EPO), black currant oil (BCO), borage oil (BO), andMucor javanicus fungal oil (MJO). It was found that GLA, although not α-linolenic acid, resisted pancreatic lipase hydrolysis. Therefore, the 2-position analysis was determined using phospholipase C-generated 1,2-diacylglycerol and phospholipase A2-generated lysophosphatidylcholine. GLA was found to be concentrated in the 3-position of EPO and BCO, the 2-position of BO, and the 2- and 3-positions of MJO. In BCO, octadecatetraenoic acid (n-3), also a †-6 fatty acid, was distributed similarly to GLA, but α-linolenic acid was found predominantly in the 1-position. Linoleic acid was nearly evenly distributed in all positions of EPO and BCO but was concentrated in the 1-position of BO and the 2-position of MJO. Both palmitic and stearic acids were found predominantly in the 1-position of all of the oils. The results demonstrate similarities and differences in the positional distribution of fatty acids in GLA-containing oils.
Clonal Dominance of Hematopoietic Stem Cells Triggered by Retroviral Gene Marking (2005)

Gene marking with replication-defective retroviral vectors has been used for more than 20 years to track the in vivo fate of cell clones. We demonstrate that retroviral integrations themselves may trigger nonmalignant clonal expansion in murine long-term hematopoiesis. All 29 insertions recovered from clones dominating in serially transplanted recipients affected loci with an established or potential role in the self-renewal or survival of hematopoietic stem cells. Transcriptional dysregulation occurred in all 12 insertion sites analyzed. These findings have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover.
Uptake of low density lipoproteins by rat tissues. Special emphasis on the luteinized ovary. (1986)

The aim of this study was to determine how luteal cells of the hormone-primed (luteinized) ovary process low density lipoproteins (LDL). Ovary uptake of perfused 125I-LDL was assessed by tissue levels of radioactivity; the distribution of LDL protein in cells was assessed on autoradiograms of the fixed tissue; and the level of stimulation of steroidogenesis, as well as degradation of LDL protein, was assessed on effluent perfusion samples. Human LDL ligand used in these studies was rigorously defined biochemically and physiologically. Homologous (rat) LDL was used as a special ligand control. Other tissue controls included the use of perfused or in vivo-infused luteinized ovaries from animals pretreated to reduce circulating lipoprotein levels, perfused ovaries from a second hormone-primed model, perfused liver from estrogen-treated rats, and isolated and cultured cells from the same ovarian tissues used in the perfusion experiments. The results show that perfused LDL promptly stimulates steroidogenesis. However, the labeled protein moiety of the LDL is not interiorized by the luteal cells, nor is there evidence of LDL protein degradation in the effluent samples. In contrast, internalization of the ligand occurs when luteal cells are incubated with the ligand in vitro. We have observed also that uptake of the 125I-LDL by the ovary can be displaced equally well by excess unlabeled LDL or HDL3. Overall, these experiments suggest that in the intact luteinized ovary, LDL binds to the same sites on the cell surface where HDL "binds," and that LDL cholesterol must be obtained by these steroid hormone-producing cells by a mechanism that does not require internalization of the intact lipoprotein particle.
Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab (2008)

Combined with earlier observations that synovial lymphoid aggregates are unaltered by rituximab treatment, these data suggest that lymphoid aggregates may provide a protective niche for autoantibody-producing cells.
Suramin: a reversible P2‐purinoceptor antagonist in the mouse vas deferens (1988)

The trypanocide Suramin was tested as a possible antagonist at the P2-purinoceptor of the mouse vas deferens. At a concentration of 100 microM, Suramin antagonized the response to alpha,beta-methylene ATP, while responses to carbachol and noradrenaline were unaffected. These results suggest that Suramin may provide a starting point for the development of specific antagonists for P2-purinoceptors.
Red Wine Inhibits Monocyte Chemotactic Protein-1 Expression and Modestly Reduces Neointimal Hyperplasia After Balloon Injury in Cholesterol-Fed Rabbits (1999)

Long-term consumption of red wine and white wine inhibits MCP-1 expression, and in the small number of animals studied, red wine modestly reduces neointimal hyperplasia. Since red wine exhibits higher antioxidant capacity than does white wine, the decreased intimal response might be partly attributed to its antioxidant effects.
Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation (2009)

Hydrogen sulfide (H(2)S) is synthesized by 2 enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). L-Cysteine (L-Cys) acts as a natural substrate for the synthesis of H(2)S. Human penile tissue possesses both CBS and CSE, and tissue homogenates efficiently convert L-Cys to H(2)S. CBS and CSE are localized in the muscular trabeculae and the smooth-muscle component of the penile artery, whereas CSE but not CBS is also expressed in peripheral nerves. Exogenous H(2)S [sodium hydrogen sulfide (NaHS)] or L-Cys causes a concentration-dependent relaxation of strips of human corpus cavernosum. L-Cys relaxation is inhibited by the CBS inhibitor, aminoxyacetic acid (AOAA). Electrical field stimulation of human penile tissue, under resting conditions, causes an increase in tension that is significantly potentiated by either propargylglycine (PAG; CSE inhibitor) or AOAA. In rats, NaHS and L-Cys promote penile erection, and the response to L-Cys is blocked by PAG. Our data demonstrate that the L-Cys/H(2)S pathway mediates human corpus cavernosum smooth-muscle relaxation.
Melatonin and Human Chronobiology (2007)

With the development of accurate and sensitive assays for measuring melatonin in plasma and saliva, it has been possible to advance our understanding of human chronobiology. In particular, the dim light melatonin onset (DLMO) is expected to have an increasingly important role in the diagnosis of circadian phase disorders and their treatment with appropriately timed bright light exposure and/or low-dose melatonin administration. The phase angle difference (PAD) between DLMO and mid-sleep can be used as a marker for internal circadian alignment and may also be used to differentiate individuals who are phase advanced from those who are phase delayed (a long interval indicates the former and a short interval indicates the latter). To provide a corrective phase delay, light exposure should be scheduled in the evening and melatonin should be administered in the morning. To provide a corrective phase advance, light exposure should be scheduled in the morning and melatonin should be administered in the afternoon/evening. The study of patients with seasonal affective disorder (SAD), as well as individuals who are totally blind, has resulted in several findings of interest to basic scientists, as well as psychiatrists and sleep specialists.
Nutritional management of patients with urea cycle disorders (2007)

The nutritional management of patients with urea cycle disorders (UCDs) involves restriction of dietary protein along with provision of adequate protein-free energy, essential amino acid supplements, and vitamins and minerals in combination with nitrogen-scavenging drugs. The present paper discusses nutrition therapy for a range of circumstances: during an acute hyperammonaemic episode and at hospital discharge; before, during, and after surgery; and for lifelong chronic management of UCDs.