gebhart/patrepeval huggingface dataset:
3-Mercaptopropionic acid, a potent inhibitor of fatty acid oxidation in rat heart mitochondria. (1985)

The effects of several short-chain mercapto acids on the rate of respiration supported by either palmitoylcarnitine, octanoate, or pyruvate was studied with coupled rat heart mitochondria. 3-Mercaptopropionic acid was found to be a potent inhibitor of respiration sustained by palmitoylcarnitine or octanoate, whereas under identical conditions respiration with pyruvate as a substrate was unaffected. 2-Mercaptoacetic acid also inhibits palmitoylcarnitine-supported respiration, but only at much higher concentrations of the inhibitor. 2-Mercaptopropionic acid has virtually no effect. Incubation of mitochondria with 3-mercaptopropionic acid did not cause the irreversible inactivation of any beta-oxidation enzyme. Since 3-mercaptopropionic acid did not inhibit beta-oxidation in uncoupled mitochondria, it appears that this compound must first be metabolized in an energy-dependent reaction before it becomes inhibitory. 3-Mercaptopropionyl-CoA and three of its S-acyl derivatives, all of which are likely mitochondrial metabolites of 3-mercaptopropionic acid, were tested for their capacity to inhibit the individual enzymes of beta-oxidation. 3-Mercaptopropionyl-CoA inhibits only acyl-CoA dehydrogenase, whereas S-myristoyl-3-mercaptopropionyl-CoA inhibits reversibly several beta-oxidation enzymes. All observations together lead us to suggest that the inhibition of beta-oxidation by 3-mercaptopropionic acid in coupled rat heart mitochondria is most likely a consequence of the reversible inhibition of acyl-CoA dehydrogenase by long-chain S-acyl-3-mercaptopropionyl-CoA thioesters and possibly by 3-mercaptopropionyl-CoA.
Fibrodysplasia Ossificans Progressiva-like Condition in a Cat (2006)

Fibrodysplasia ossificans progressiva (FOP)-like condition was diagnosed in a Japanese domestic cat with stiffness, marked atrophy of the muscles, and limited mobility of all joints in both the pelvic limbs. Etretinate, a retinoid, was used for medical management; however, no improvement in the clinical signs was observed. Inheritance of the disorder has not yet been demonstrated. Furthermore, the clinical signs and histopathological findings of feline FOP-like condition in the present case differed from those of the previously reported cases.
In Vivo Gene Therapy of Cancer with E. coli Purine Nucleoside Phosphorylase (1997)

We have developed a new strategy for the gene therapy of cancer based on the activation of purine nucleoside analogs by transduced E. coli purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1). The approach is designed to generate antimetabolites intracellularly that would be too toxic for systemic administration. To determine whether this strategy could be used to kill tumor cells without host toxicity, nude mice bearing human malignant D54MG glioma tumors expressing E. coli PNP (D54-PNP) were treated with either 6-methylpurine-2'-deoxyriboside (MeP-dR) or arabinofuranosyl-2-fluoroadenine monophosphate (F-araAMP, fludarabine, a precursor of F-araA). Both prodrugs exhibited significant antitumor activity against established D54-PNP tumors at doses that produced no discernible systemic toxicity. Significantly, MeP-dR was curative against this slow growing solid tumor after only 3 doses. The antitumor effects showed a dose dependence on both the amount of prodrug given and the level of E. coli PNP expression within tumor xenografts. These results indicated that a strategy using E. coli PNP to create highly toxic, membrane permeant compounds that kill both replicating and nonreplicating cells is feasible in vivo, further supporting development of this cancer gene therapy approach.
Multibeam laser manipulation and fixation of microparticles (1992)

A multibeam laser trapping–reaction system was developed to demonstrate independent manipulation of plural microparticles as well as to induce photochemical reaction in a laser-trapped particle(s). Photopolymerization of vinyl monomers dissolved in a sample solution was employed to fix polystyrene latex particles regularly aligned by laser trapping. Integrated latex structures created by the successive manipulation/polymerization procedures were also shown to be freely manipulated by laser beams.
Modulation of High Affinity Hormone Binding (1998)

The lutropin/choriogonadotropin receptor is a seven-transmembrane receptor and consists of two major domains of similar size, an extracellular exodomain and a membrane-associated endodomain which includes 3 exoloops. The uniquely large exodomain is responsible for high affinity hormone binding whereas receptor activation occurs at the endodomain. However, little is known about the relationship between the exodomain and endodomain. It was reported that hormone binding to the exodomain was improved when the endodomain was truncated. This result suggests that hormone binding to the exodomain was influenced by the endodomain. To test this hypothesis, amino acids of exoloop 2 were examined by Ala substitutions. The binding affinity was enhanced by some Ala substitutions but attenuated by others. These results indicate that exoloop 2 influences the hormone binding to the exodomain. Particularly, the high affinity hormone binding at the exodomain is constrained by a group of amino acids, Ser484, Asn485, Lys488, Ser490, and Ser499. Computer modeling suggests these residues may be positioned on one side of exoloop 2. It also influences the affinity for cAMP induction and the maximal cAMP production in distinct ways, in addition to its influence on the hormone binding affinity. The distinct ways of influencing these functions are sometimes in conflict and compromised to attain the maximal affinity for cAMP induction. As a result, the exodomain attains the maximal affinity for hormone binding when the endodomain is truncated and cAMP induction is disengaged.
Enteral Feeding and Early Outcomes of Patients Undergoing Allogeneic Stem Cell Transplantation Following Myeloablative Conditioning (2006)

The purpose of this study was to evaluate the impact of enteral nutrition on early outcome of patients after myeloablative allogeneic stem cell transplantation (allo-SCT). From January 2001 to January 2003, 22 patients agreed to receive enteral nutrition via a nasogastric feeding tube; the remaining 23 patients received parenteral nutrition (n=22) or standard oral feeding (n=1). Early complications and factors influencing 100-day overall survival (OS) were investigated. Patients who received enteral nutrition developed less often acute-grade III/IV graft-versus-host disease (18%) than those who did not (35%) (P=0.011). In addition, this group showed lower mortality from infection during the first 100 days after transplantation. In multivariate analyses, only the absence of enteral nutrition was found to adversely influence 100-day OS with a hazard ratio of 8.3. Enteral nutrition is a safe and effective method for feeding allo-SCT patients. A randomized trial is warranted to confirm its advantage on early patient outcome.
Circulating Immunoreactive Interleukin-6 in Cystic Fibrosis (1998)

We measured circulating and sputum-sol concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase-alpha1-antiproteinase complex (NEAPC), and C-reactive protein (CRP) in an exacerbation, after antibiotic treatment, and in clinically stable patients with cystic fibrosis and chronic pulmonary infection with Pseudomonas aeruginosa. The aim was to determine the compartmental patterns of a proinflammatory and anti-inflammatory cytokine compared with other markers of inflammatory activity in cystic fibrosis. IL-6, NEAPC, CRP, and absolute neutrophil count were reduced after antibiotic treatment, p < 0.01. IL-6 and CRP concentrations were greater, p = 0.007, and p = 0.01, respectively, in a stable group of patients compared with those at the end of an exacerbation. IL-6 and CRP concentrations were related (r = 0.836, p < 0.0001), and both were greater than in matched control subjects (p < 0.001) at all times studied. Sputum-sol concentrations of IL-6 after treatment were positively related to FEV1 and FVC and inversely related to concentrations of neutrophil elastase. The separation between patients and healthy subjects, and the reduction of IL-6 after antibiotic treatment indicates it could be used as a marker of inflammation, but its relationship to other markers depends on the compartment in which it is measured.
Identification of Philadelphia-negative granulocyte-macrophage colony- forming units generated by stroma-adherent cells from chronic myelogenous leukemia patients (1994)

Chronic myelogenous leukemia (CML) is a clonal disorder of the hematopoietic stem cell characterized by the coexistence of Philadelphia-negative (Ph-) with Ph+ progenitors. CML progenitor cells have been shown to be defective in adherence to marrow stroma. The present study investigated at the cytogenetic level marrow-derived CML clonogenic cells generated from the stroma-adherent cell fraction. On direct cytogenetic analysis, the overall mean (+/- SEM) percentage of Ph- metaphases was 3% +/- 1%. Mononuclear marrow cells from CML patients (n = 18) were incubated with mafosfamide (100 micrograms/mL) or control medium, seeded onto marrow stromal layers and allowed to adhere (2 hours, 37 degrees C). After a short-term (3-day) liquid culture, the cells were harvested, incorporated in methyl-cellulose, and individual colonies were analyzed by single colony karyotyping. The mean (+/- SEM) percentage of Ph- colonies generated from the stroma- adherent fraction was 35% +/- 6%. As compared with marrow colony- forming unit granulocyte-macrophage plated before any manipulation, the mean (+/- SEM) percentage of Ph- clones was significantly increased by stroma adherence (35% +/- 6% v 15% +/- 4%, P &lt; or = .005) and mafosfamide (100 micrograms/mL) incubation of marrow cells before stroma adherence (58% +/- 9% v 35% +/- 6%, P &lt; or = .005). An additive effect was observed by combining mafosfamide treatment and stroma adherence. Single-colony transfer experiments showed that 50% +/- 4% stroma-adherent and 70% +/- 4% stroma-adherent mafosfamide-treated progenitors gave rise to secondary colonies. To further characterize the stroma-adherent fraction, experiments were performed in which CD34+ marrow cells were used. The mean (+/- SEM) output of progenitors generated by 10,000 CD34+, stroma-adherent cells was 888 +/- 188 and 570 +/- 258 for untreated and mafosfamide-treated cells, respectively. Individual colonies were analyzed by single-colony karyotyping and fluorescent in situ hybridization using a biotinylated cosmid DNA probe that hybridize to abl oncogene. The CD34+, stroma-adherent fraction contained 38% +/- 14% (untreated) and 56% +/- 18% (mafosfamide-treated) (P &lt; or = .025) Ph- progenitors. In conclusion, the present data show the possibility to select Ph- clones that (1) have a maintained capability of stroma adherence, (2) are mafosfamide resistant, (3) are derived from the CD34+ fraction, and (4) have high-replating potential.
Visualization of supercoiled DNA with atomic force microscopy  in situ (1997)

Tertiary structure of supercoiled DNA is a significant factor in a number of genetic functions and is apparently affected by environmental conditions. We applied atomic force microscopy (AFM) for imaging the supercoiled DNA deposited at different ionic conditions. We have employed a technique for the sample preparation that permits high-resolution AFM imaging of DNA bound to the surface in buffer solutions without drying the sample (AFM in situ). The AFM data show that at low ionic strength, DNA molecules are loosely interwound supercoils with an irregular shape. Plectonemic superhelices are formed in high-concentration, near-physiological salt solutions. At such ionic conditions, superhelical loops are typically separated by regions of close helix-helix contacts. The data obtained show directly and unambiguously that overall geometry of supercoiled DNA depends dramatically on ionic conditions. This fact and the formation of close contacts between DNA helices are important features of supercoiled DNA related to its biological functions.
Noninvasive Optical Screening for Diabetes (2009)

These results suggest that noninvasive measurement of dermal fluorescence may be an effective tool to identify individuals at risk for diabetes and its complications. The noninvasive technology yields immediate results, and since measuring dermal fluorescence requires no blood draws or patient fasting, the instrument may be well suited for opportunistic screening.
A Novel Tetravalent Dengue Vaccine Is Well Tolerated and Immunogenic against All 4 Serotypes inFlavivirus‐Naive Adults (2010)

Background. Sanofi Pasteur has developed a tetravalent dengue vaccine (TDV) against the world's most common arbovirus infection. Methods. We assessed the safety and immunogenicity of the TDV in healthy adults randomized into 2 groups. Group 1 received 3 TDV injections at months 0, 4, and 12–15; group 2 received saline placebo at month 0 and then 2 TDV injections at months 4 and 12–15. Adverse events were recorded, and biological parameters and viremia levels were measured. Neutralizing antibodies against 4 World Health Organization (WHO) reference strains were measured before and after vaccinations. Results. A total of 33 participants were enrolled in each group. Demographic characteristics were comparable. No vaccine-related serious adverse event was reported. The most common systemic reactions were headache, malaise, and myalgia. Low viremia levels were detected, mainly of serotype 4. Immune response increased with successive vaccine doses. All participants seroconverted against all 4 serotypes after receiving 3 doses at 0, 4, and 12–15-months, and almost all seroconverted after 2 doses given 8–11 months apart. Conclusions. Sanofi Pasteur's TDV was well tolerated and induced full seroconversion against all WHO reference strain serotypes after 3 doses.
N6-methyladenine: the other methylated base of DNA (2006)

Contrary to mammalian DNA, which is thought to contain only 5-methylcytosine (m5C), bacterial DNA contains two additional methylated bases, namely N6-methyladenine (m6A), and N4-methylcytosine (m4C). However, if the main function of m5C and m4C in bacteria is protection against restriction enzymes, the roles of m6A are multiple and include, for example, the regulation of virulence and the control of many bacterial DNA functions such as the replication, repair, expression and transposition of DNA. Interestingly, even if adenine methylation is usually considered a bacterial DNA feature, the presence of m6A has been found in protist and plant DNAs. Furthermore, indirect evidence suggests the presence of m6A in mammal DNA, raising the possibility that this base has remained undetected due to the low sensitivity of the analytical methods used. This highlights the importance of considering m6A as the sixth element of DNA.
Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. (1993)

The nuclear hormone receptors called PPARs (peroxisome proliferator-activated receptors alpha, beta, and gamma) regulate the peroxisomal beta-oxidation of fatty acids by induction of the acyl-CoA oxidase gene that encodes the rate-limiting enzyme of the pathway. Gel retardation and cotransfection assays revealed that PPAR alpha heterodimerizes with retinoid X receptor beta (RXR beta; RXR is the receptor for 9-cis-retinoic acid) and that the two receptors cooperate for the activation of the acyl-CoA oxidase gene promoter. The strongest stimulation of this promoter was obtained when both receptors were exposed simultaneously to their cognate activators. Furthermore, we show that natural fatty acids, and especially polyunsaturated fatty acids, activate PPARs as potently as does the hypolipidemic drug Wy 14,643, the most effective activator known so far. Moreover, we discovered that the synthetic arachidonic acid analogue 5,8,11,14-eicosatetraynoic acid is 100 times more effective than Wy 14,643 in the activation of PPAR alpha. In conclusion, our data demonstrate a convergence of the PPAR and RXR signaling pathways in the regulation of the peroxisomal beta-oxidation of fatty acids by fatty acids and retinoids.
The movement of wild sea trout, Salmo trutta L., smolts through a river estuary (1994)

Abstract The movement of sea trout. Salmo trutta L., smolts through the estuary of the River Avon, southern England was studied using miniature 300 kHz acoustic transmitters and an array of strategically placed acoustic sonar buoys. Sea trout smolts were trapped 3.25 km above the head of tide as they moved downstream and the transmitters were surgically implanted into the peritoneal cavity of the fish. Subsequent movement of the smolts through the estuary was predominantly nocturnal and occurred mainly during an ebb tide or the period of slack water between two high waters. During the hours of darkness the ground speed of the smolts through the estuary was similar to that of passively drifting objects. However, where movement did occur during daylight hours ground speeds of smolts were significantly slower. Vertical salinity profile measurements of the estuary indicated that individual smolts may have experienced salinities ranging from fresh to 100% sea water during their migration. The behaviour of the smolts is discussed in relation to the possible environmental and physiological cues controlling the estuarine migration.
Polyvalent Immunostimulatory Nanoagents with Self‐Assembled CpG Oligonucleotide‐Conjugated Gold Nanoparticles (2011)

Delivery vehicles: Gold nanoparticles (AuNPs) have been used as a nanocarrier to non-invasively deliver synthetic cytosine–phosphate–guanosine (CpG) oligodeoxynucleotides (ODNs) into cells. Compared to unconjugated single-stranded CpG ODNs, self-assembled polyvalent CpG-AuNP conjugates enhance the efficiency of cellular uptake and stimulate secretion of cytokines (see picture). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. 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.
Brain metastases in breast cancer--an in vitro study to evaluate new systemic chemotherapeutic options. (2005)

Topotecan, Cisplatin, Vincristine and Caelyx seem to be suitable candidates for further clinical evaluation. The data and the "liposomal packaging" suggest that Caelyx might be effective in the CNS. Since pulmonary metastases are often associated with brain metastases, evaluatingprimary cell cultures from malignant pleural effusions could be a valuable approach for the testing of new cytostatic drugs for brain metastases.
A Best-Case Network Performance Model (1992)

Network performance measures usually focus on average throughput. We, however, were concerned with best-case behavior: how fast could a packet traverse the network if there were no contention for resources. By subtracting the path time to a node from the path time through the node, we were able to develop a simple best-case delay model. This model was sensitive enough to determine the board-level configuration of a router 750 miles away.
Toward a New Genetic System with Expanded Dimensions:  Size-Expanded Analogues of Deoxyadenosine and Thymidine (2004)

We describe the design, preparation, and properties of two key building blocks of a size-expanded genetic system. Nucleoside analogues of the natural nucleosides dA and dT are reported in which the fusion of a benzo ring increases their size by ca. 2.4 A. The expanded dA analogue (dxA), having a tricyclic base, was first reported by Leonard nearly three decades ago. We describe a shortened and more efficient approach to this compound. The expanded dT analogue (dxT), a methylquinazolinedione C-glycoside, was previously unknown; we describe its preparation in eight steps from 5-methylanthranilic acid. The key glycoside bond formation employed Pd-mediated coupling of an aryl iodide precursor with a dihydrofuran derivative of deoxyribose. Both nucleosides are shown to be efficient fluorophores, emitting light in the blue-violet range. The base-protected phosphoramidite derivatives were prepared, and short oligonucleotides containing them were characterized. The two size-expanded nucleosides are key components of a new four-base genetic system designed to form helical paired structures having a diameter greater than that of natural DNA. Elements of the design of this expanded genetic molecule, termed xDNA, are discussed, including the possibility of up to eight base pairs of information storage capability.
An oversampling analog-to-digital converter topology for high-resolution signal acquisition systems (1987)

High-precision analog-to-digital converters (ADC's) which periodically sample continuous time waveforms are required in many "signal acquisition" applications such as digital audio and instrumentation. This paper describes a specific topology for an oversampling differential pulse code modulation (DPCM)-type ADC that requires neither an analog anti-aliasing filter nor a sample-and-hold. Dithering techniques are presented which cause the quantization error to resemble an additive Gaussian white-noise source whose mean and variance are independent of the input. A smoothing technique is presented which improves the linearity of the ADC's transfer function. Results presented are based on both simulations and measurements of a test system constructed from discrete components. The potential for integration in a standard digital CMOS process is discussed.
Exploring Microbial Diversity and Taxonomy Using SSU rRNA Hypervariable Tag Sequencing (2008)

Massively parallel pyrosequencing of hypervariable regions from small subunit ribosomal RNA (SSU rRNA) genes can sample a microbial community two or three orders of magnitude more deeply per dollar and per hour than capillary sequencing of full-length SSU rRNA. As with full-length rRNA surveys, each sequence read is a tag surrogate for a single microbe. However, rather than assigning taxonomy by creating gene trees de novo that include all experimental sequences and certain reference taxa, we compare the hypervariable region tags to an extensive database of rRNA sequences and assign taxonomy based on the best match in a Global Alignment for Sequence Taxonomy (GAST) process. The resulting taxonomic census provides information on both composition and diversity of the microbial community. To determine the effectiveness of using only hypervariable region tags for assessing microbial community membership, we compared the taxonomy assigned to the V3 and V6 hypervariable regions with the taxonomy assigned to full-length SSU rRNA sequences isolated from both the human gut and a deep-sea hydrothermal vent. The hypervariable region tags and full-length rRNA sequences provided equivalent taxonomy and measures of relative abundance of microbial communities, even for tags up to 15% divergent from their nearest reference match. The greater sampling depth per dollar afforded by massively parallel pyrosequencing reveals many more members of the "rare biosphere" than does capillary sequencing of the full-length gene. In addition, tag sequencing eliminates cloning bias and the sequences are short enough to be completely sequenced in a single read, maximizing the number of organisms sampled in a run while minimizing chimera formation. This technique allows the cost-effective exploration of changes in microbial community structure, including the rare biosphere, over space and time and can be applied immediately to initiatives, such as the Human Microbiome Project.