gebhart/patrepeval huggingface dataset:
Intestinal absorption and liver uptake of medium-chain fatty acids in non-anaesthetized pigs (1993)

In order to study the rate of intestinal absorption and hepatic uptake of medium-chain fatty acids (MCFA), six growing pigs, mean body weight 65 kg, were fitted with a permanent fistula in the duodenum and with three catheters in the portal vein, carotid artery and hepatic vein respectively. Two electromagnetic flow probes were also set up, one around the portal vein and one around the hepatic artery. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and a nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the three vessels at regular intervals for 12 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentration of non-esterified octanoic and decanoic acids in the portal blood rose sharply after the beginning of each infusion and showed a biphasic time-course with two maximum values, one after 15 min and a later one between 75 and 90 min. Only 65% of octanoic acid infused into the duodenum and 54% of decanoic acid were recovered in the portal flow throughout each experiment. The amounts of non-esterified MCFA taken up per h by the liver were close to those absorbed from the gut via the portal vein within the same periods of time, showing that the liver is the main site of utilization of MCFA in pigs. These results have been discussed with a special emphasis laid on the possible mechanisms of the biphasic time-course of MCFA absorption and the incomplete recovery in the portal blood of the infused fatty acids.
Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies (2016)

Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. Cancer Res; 76(16); 4850-60. ©2016 AACR.
Expression in mammalian cells of a gene fromStreptomyces albonigerconferring puromycin resistance (1986)

The gene encoding a puromycin N-acetyl transferase from Streptomyces alboniger has been cloned next to the SV40 early promoter in a mammalian cells-Escherichia coli shuttle vector. When this construction was introduced into VERO cells it expressed the relevant enzymic activity. Moreover, the puromycin N-acetyl transferase gene has been used as a dominant marker for the selection of transformed mammalian cells able to grow in the presence of the antibiotic.
Two Distinct Chondroitin Sulfate ABC Lyases (1997)

Crude enzyme obtained from chondroitin sulfate-induced Proteus vulgaris NCTC 4636 has been fractionated into 1) an endoeliminase capable of depolymerizing chondroitin sulfate and related polysaccharides to produce, as end products, a mixture of Delta4-unsaturated tetra- and disaccharides and 2) an exoeliminase preferentially acting on chondroitin sulfate tetra- and hexasaccharides to yield the respective disaccharides. Isolation of the two enzymes was achieved by a simple two-step procedure: extracting the enzymes from intact P. vulgaris cells with a buffer solution of nonionic surfactant and then treating the extract by cation-exchange chromatography. Each of the enzymes thus prepared was apparently homogeneous as assessed by SDS-polyacrylamide gel electrophoresis and readily crystallized from polyethylene glycol solutions. Both enzymes acted on various substrates such as chondroitin sulfate, chondroitin sulfate proteoglycan, and dermatan sulfate at high, but significantly different, initial rates. They also attacked hyaluronan but at far lower rates and were inactive to keratan sulfate, heparan sulfate, and heparin. Our results show that the known ability of the conventional enzyme called "chondroitinase ABC" to catalyze the complete depolymerization of chondroitin sulfates to unsaturated disaccharides may actually result from the combination reactions by endoeliminase (chondroitin sulfate ABC endolyase) and exoeliminase (chondroitin sulfate ABC exolyase).
The N-terminal Sequence Affects Distant Helix Interactions in Hemoglobin (1998)

The N-terminal 18-amino acid sequence of the beta-chain of hemoglobin, as far as the end of the A helix, has been replaced by the corresponding sequence of the gamma-chain of fetal hemoglobin with the remaining sequence of the beta-chain retained (helices B through H). The gamma-beta-chain had the correct mass, and its entire sequence was established by mass spectrometric analysis of its tryptic peptides; the alpha-chain also had the correct mass. This recombinant hemoglobin (named Hb Felix) retains cooperativity and has an oxygen affinity like that of HbA both in the presence and absence of the allosteric regulators, 2,3-diphosphoglycerate or chloride but differs from HbF in its 2,3-diphosphoglycerate response. However, Hb Felix has some features that resemble fetal hemoglobin, i.e. its significantly decreased tetramer-dimer dissociation and its circular dichroism spectrum, which measure the strength of the tetramer-dimer interface in the oxy conformation and its rearrangement to the deoxy conformation, respectively. Even though Hb Felix contains the HbA amino acids at its tetramer-dimer interface, which is located at a distance from the substitution sites, its interface properties resemble those of HbF. Therefore, the N-terminal sequence and not just those amino acids directly involved at the subunit interface contacts with alpha-chains must have a strong influence on this region of the molecule. The results reinforce the concept of fluid long range relationships among various parts of the hemoglobin tetramer (Dumoulin, A., Manning, L. R., Jenkins, W. T., Winslow, R. M., and Manning, J. M. (1997) J. Biol. Chem. 272, 31326-31332) and demonstrate the importance of the N-terminal sequence, especially in some mutant hemoglobins, in influencing its overall structure by affecting the relationship between helices.
Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages (2003)

The adult hair follicle dermal papilla (DP) and dermal sheath (DS) cells are developmentally active cell populations with a proven role in adult hair follicle-cycling activity and unique inductive powers. In stem cell biology, the hair follicle epithelium has recently been the subject of a great deal of investigation, but up to now, the follicle dermis has been largely overlooked as a source of stem cells. Following the sporadic appearance of muscle, lipid and bone-type cells in discretely isolated follicle DP and DS cell primary cultures, we demonstrated that cultured papilla and sheath cell lines were capable of being directed to lipid and bone differentiation. Subsequently, for the first time, we produced clonal DP and DS lines that had extended proliferative capabilities. Dye exclusion has been reported to be an identifying feature of stem cells; therefore, clonal papilla and sheath lines with differing capacity to exclude rhodamine 123 were cultured in medium known to induce adipocyte and osteocyte differentiation. Both DS- and DP-derived clones showed the capacity to make lipid and to produce calcified material; however, different clones had varied behaviour and there was no obvious correlation between their stem cell capabilities and dye exclusion or selected gene expression markers. As a highly accessible source, capable of being discretely isolated, the follicle has important potentially as a stem cell source for tissue engineering and cell therapy purposes. It will also be interesting to compare follicle dermal stem cell properties with the broader stem cell capabilities discovered in skin dermis and investigate whether, as we believe, the follicle is a key dermal stem cell niche. Finally, the discovery of stem cells in the dermis may have implications for certain pathologies in which abnormal differentiation occurs in the skin.
Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC (2005)

Abstract Bacoside A, the putative bioactive component of the Indian medicinal plant Bacopa monnieri , was found to be a mixture of saponins with bacoside A 3 (1), bacopaside II (2), jujubogenin isomer of bacopasaponin C (3) and bacopasaponin C (4) as major constituents. An HPLC method together with an optimised extraction procedure was developed for the estimation of 1–4 in B. monnieri to enable standardisation of the latter. Concentration ranges of the analytes in samples of B. monnieri collected from different regions of India were 0.14–0.85% (w/w) (1), 0.12–0.69% (2), 0.05–0.72% (3) and 0.05–0.44% (4). The importance of using bacoside A, with known concentrations of 1–4, as a reference standard for the routine analysis of B. monnieri is highlighted. Two common ﬂavonoids, luteolin and apigenin, were present in all samples of B. monnieri . Copyright © 2005 John Wiley &amp; Sons, Ltd.
Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia (2012)

Comprehensive quantitative DNA methylation analysis of the ZAP-70 gene in CLL identified important regions responsible for transcriptional regulation. In addition, loss of methylation at a specific single CpG dinucleotide in the ZAP-70 5' regulatory sequence is a highly predictive and reproducible biomarker of poor prognosis in this disease. This work demonstrates the feasibility of using quantitative specific ZAP-70 methylation analysis as a relevant clinically applicable prognostic test in CLL.
Fidelity Assurance Mechanisms of the Brain With Special Reference to Its Immunogenic CNS Compartment: Their Role in Aging and Aging-Associated Neurological Disease (1997)

The greater longevity of humans over other mammalian species is provided, in large part, by the complex neural circuitry of the brain. Assurance of the integrity of this circuitry is partly provided by its neural plasticity. The brain is also protected from adverse systemic phenomena by the blood-brain and blood-cerebrospinal fluid barriers. However, these barriers do not protect the brain from adverse phenomena that originate within the central nervous system. The brain and immune systems share many analogous characteristics; and an immunogenic compartment of the brain is described here that also has the capacity to assure the integrity of its neural circuits and its autonomy. Finally, the role of this compartment in aging and in aging-dependent diseases is discussed.
Frontline: Optimal T cell activation requires the engagement of CD6 and CD166 (2004)

The T cell surface glycoprotein, CD6 binds CD166 in the first example of an interaction between a scavenger receptor cysteine-rich domain and an immunoglobulin-like domain. We report that in human these proteins interact with a K(D) =0.4-1.0 microM and K(off) > or =0.4-0.63 s(-1), typical of many leukocyte membrane protein interactions. CD166 also interacts in a homophilic manner but with around 100-fold lower affinity (K(D) =29-48 microM and K(off) > or = 5.3 s(-1)). At concentrations, that will block the CD6/CD166 interaction, soluble monomeric CD6 and CD166 inhibit antigen-specific human T cell responses. This is consistent with extracellular engagement between CD6 and CD166 being required for an optimal immune response.
Reverse transcriptase inhibits Taq polymerase activity (1992)

Detection of viral RNA by polymerase chain reaction (PCR) requires the prior reverse transcription of the viral RNA. In order to minimise the number of manual manipulations required for processing large numbers of samples, we attempted to design a system whereby all the reagents required for both reverse transcription and amplification can be added to one tube and a single, non-interrupted thermal cycling program performed. Whilst attempting to set up such a one-tube system with Taq polymerase (Taq; Biotech International) and avian myoblastosis virus (AMV) reverse transcriptase (RT), we noticed a substantial decrease in the sensitivity of detection of viral RNA. Investigation of this phenomenon has revealed direct interference of RT with Taq polymerase. Evidence supporting this conclusion includes the following observations: (1) increasing the ratio of Taq to RT improves sensitivity; (2) adding non-homologous RNA improves sensitivity; (3) RT that has been heat inactivated prior to Taq addition does not exert this effect; (4) the effect is not sequence restricted; (5) the Mg2+ ions are not sequestered by RT. In addition, the effect is not limited to AMV RT, Moloney murine leukaemia virus RT also affects Taq activity.
A Mechanistic Study of the Alkaline Hydrolysis of Diaryl Sulfate Diesters (2004)

Nearly all of the reported studies of reactions of sulfate diesters are for dialkyl or alkyl aryl diesters, which undergo reaction by carbon-oxygen bond fission. Sulfuryl transfer reactions of sulfate diesters (RO-SO(2)-OR') proceeding by attack at sulfur have been little explored. When both ester groups are aryl groups the hydrolysis reaction (sulfuryl transfer to water) occurs by way of attack at sulfur. The alkaline hydrolysis of diaryl sulfate diesters was shown to obey first-order kinetics with respect to [(-)OH] and proceed through S-O bond fission, in a mechanism that is most likely concerted. Activation parameters for 4-chloro-3-nitrophenyl phenyl sulfate and 4-nitrophenyl phenyl sulfate gave the following respective values: Delta H(++) = 88.0 +/- 0.1 and 84.83 +/- 0.06 kJ mol(-)(1) and Delta S(++) = -37 +/- 1 and -50.2 +/- 0.5 J mol(-)(1) deg(-)(1). The dependence of the second-order rate constant for hydrolysis on leaving group pK(a) was analyzed giving a beta(lg) slope of -0.7 +/- 0.2 and a Leffler alpha parameter value of 0.36. A (15)k kinetic isotope effect (KIE) for the hydroxide attack on 4-nitrophenyl phenyl sulfate of 1.0000 +/-0.0005 and an (18)k(lg) KIE value of 1.003+/-0.002 were obtained.
HemoQuant, A New Quantitative Assay for Fecal Hemoglobin (1984)

HemoQuant, an assay based on heme-derived porphyrin, quantifies both total fecal hemoglobin and that fraction already converted to porphyrin by gut flora (the intestinal converted fraction). Recovery by HemoQuant of blood added to stools exceeded 99% and was not affected by ascorbic acid, iron, or other additives. HemoQuant was used to evaluate the performance of Hemoccult on 1018 stools. Hemoccult sensitivity differed widely, remaining negative with up to 42.5 mg hemoglobin per gram of stool (about 43 mL/d of blood) but positive with only 0.04 mg of hemoglobin per gram of stool. Driest stools tended to be Hemoccult-negative and the wettest Hemoccult-positive. Hemoccult-negative stools became positive after aqueous dilution independent of hemoglobin concentration. The intestinal converted fraction, not detected by guaiac tests, often constituted most of the fecal hemoglobin equivalents and was significantly higher in Hemoccult-negative than in Hemoccult-positive stools. Hemoccult lost reactivity during fecal storage due to progressive heme degradation. Frequent false-negative and false-positive reactions of Hemoccult were explained largely by variations in stool liquidity and heme degradation.
Results of Sacral Neuromodulation Therapy for Urinary Voiding Dysfunction: Outcomes of a Prospective, Worldwide Clinical Study (2007)

This long-term study demonstrates that InterStim therapy is safe and effective for restoring voiding in appropriately selected cases refractory to other forms of treatment.
Multimodal Machine Learning: A Survey and Taxonomy (2018)

Our experience of the world is multimodal - we see objects, hear sounds, feel texture, smell odors, and taste flavors. Modality refers to the way in which something happens or is experienced and a research problem is characterized as multimodal when it includes multiple such modalities. In order for Artificial Intelligence to make progress in understanding the world around us, it needs to be able to interpret such multimodal signals together. Multimodal machine learning aims to build models that can process and relate information from multiple modalities. It is a vibrant multi-disciplinary field of increasing importance and with extraordinary potential. Instead of focusing on specific multimodal applications, this paper surveys the recent advances in multimodal machine learning itself and presents them in a common taxonomy. We go beyond the typical early and late fusion categorization and identify broader challenges that are faced by multimodal machine learning, namely: representation, translation, alignment, fusion, and co-learning. This new taxonomy will enable researchers to better understand the state of the field and identify directions for future research.
Intracellular calcium and force in single mouse muscle fibres following repeated contractions with stretch. (1995)

1. The role of the myoplasmic free Ca2+ concentration ([Ca2+]i) in the reduction of muscle force following contractions with stretch was investigated in single fibres from mouse toe muscle. Muscle fibres were either stretched by 25% of their optimum length (Lo) for ten tetani (Protocol I) or stretched by 50% of Lo for between ten and thirty tetani (Protocol II). Indo-1 was used to measure [Ca2+]i. 2. In each protocol the stretch series was compared with isometric controls; the stretch series always resulted in greater changes in muscle properties than in the isometric controls. The observed changes were (i) reduced tetanic force, (ii) reduced tetanic [Ca2+]i, (iii) increased resting [Ca2+]i and (iv) the greater relative reduction in force at low stimulus frequencies (30 and 50 Hz) compared with high (100 Hz). These changes were maintained for up to 60 min. 3. Stretching a resting muscle fibre had no effect on the subsequent [Ca2+]i or force. 4. Following Protocol I 10 mM caffeine restored tetanic force to pre-stretch levels. Tetanic [Ca2+]i vs. force curves were constructed pre- and post-stretch and showed that neither the maximum Ca(2+)-activated force nor the Ca2+ sensitivity of the muscle fibres post-stretch was significantly different from control. The force reduction, therefore, appears to be the result of reduced tetanic [Ca2+]i. 5. The more severe stretching regimen of Protocol II resulted in a much greater reduction in force than Protocol I. Ten millimolar caffeine did not restore control force. Comparison of the [Ca2+]i-force relationships pre- and post-stretch showed that the reduction in tetanic force was caused by a combination of a reduced tetanic [Ca2+]i, reduced maximum Ca(2+)-activated force and reduced Ca2+ sensitivity. 6. Following both protocols the resting [Ca2+]i showed a small rise which persisted for at least 60 min. This elevated [Ca2+]i was associated with a reduction in the pump rate of the sarcoplasmic reticulum Ca2+ pump. 7. This study establishes that reduced Ca2+ release and reduced Ca2+ sensitivity contribute to the reduction in force generating capacity of single mammalian muscle fibres following active stretches.
Effects of Translocations on Transcription from PVT (1990)

We have previously described a transcription unit on human chromosome 8, designated as PVT, that is consistently disrupted by the minority forms of translocations [t(2;8) and t(8;22)] in Burkitt's lymphoma. PVT begins 57 kilobase pairs downstream of the proto-oncogene MYC and is more than 200 kilobase pairs in length. In order to explore the pathogenic impact of translocations affecting PVT, we have characterized further the structure and transcription of the locus. In normal cells, PVT is transcribed into a variety of RNAs, the diversity of which remains unexplained. Alleles of PVT affected by translocations give rise to additional RNAs. These RNAs arise from a fusion of the first exon of PVT on chromosome 8 to the constant region of an immunoglobulin light chain on either chromosome 2 or chromosome 22. We have found no evidence that any of the normal or abnormal transcripts of PVT give rise to a protein. Our results suggest that the pathogenic effects of the variant translocations in Burkitt's lymphoma are not executed by a gene situated in a vicinity of the chromosomal breakpoints. Instead, our data leave open the possibility that the effects of the translocations may be mediated by activation of the relatively distant MYC gene.
Selective inability of spleen antigen presenting cells from Leishmania donovani infected hamsters to mediate specific T cell proliferation to parasite antigens (1992)

Golden hamsters (Mesocricetus auratus) infected with Leishmania donovani develop a disease similar to human kala-azar. There is conspicuous hypergammaglobulinaemia and their T cells do not respond to stimulation by parasite antigens. The impairment of the cellular immune response seems to be restricted to parasite antigens since infected animals are able to develop a T cell response to the mitogen Concanavalin A (Con-A) and, after sensitization, to the antigens keyhole limpet haemocyanin (KLH) and human serum albumin (DNP-HSA). In the present investigations we studied the role played by infected macrophages in the development of the cellular unresponsiveness present in visceral leishmaniasis. Adherent spleen cells from infected hamsters were unable to present L. donovani antigens to antigen specific T cells, however they were able to present KLH. Conversely, T cells from infected animals did not respond to parasite antigens even when these antigens were presented by normal syngeneic macrophages. Interestingly, lymphocytes from inguinal lymph nodes of infected animals sensitized in their foot pad with parasite antigens proliferated well when stimulated in vitro with L. donovani antigens. These results suggest that the defect in the cellular immune response of the L. donovani infected hamsters is a consequence of a selective inability of their antigen presenting cells to process and present parasite antigens to T cells.