gebhart/patrepeval huggingface dataset:
Manipulation of the anti‐αGal antibody‐αGal epitope system in experimental discordant xenotransplantation (1996)

Abstract: In 1991, evidence was provided to indicate that hyperacute rejection of pig organs by humans and baboons was initiated by the binding of anti‐agalactosyl (αGal) antibodies to the vascular endothelium. A search for suitable donor species that do not express aGal epitopes has demonstrated their absence in birds, including ratites (e.g., ostrich, emu) and a reptile (alligator), and very weak expression in a large rodent (the capybara). Studies on ratites would suggest that they are unlikely to be suitable organ donors for humans. In 1991, it was also proposed that anti‐aGal antibody‐antigen binding could be prevented either by depletion of antibody using an immunoaffinity column of the specific aGal oligosaccharide, or by the continuous intravenous infusion of the oligosaccharide, leading to binding (and thus inactivation) of the antibody to the aGal hapten. Synthetic aGal oligosaccharides have recently become available in sufficient quantities to allow experience to be gained with immunoaffinity columns, which have demonstrated complete, but temporary, elimination of baboon serum cytotoxicity to pig PK15 cells in vivo. A search for a natural and inexpensive source of aGal has revealed a subfraction of porcine stomach mucin that demonstrates high potency in inhibiting anti‐aGal antibodies both in vitro and in vivo. As an alternative therapeutic option, anti‐idiotypic antibodies have been produced in mice that are specific for human and baboon anti‐aGal antibodies. Their intravenous administration to baboons results in immediate reduction in serum cytotoxicity for 24 hr. Their use in delivering a toxin, such as ricin, to the B lymphocytes that produce the antibody (and express the same idiotype) is suggested. Studies on complement depletion by the administration of purified cobra venom factor (CVF) to baboons have demonstrated that, even in the absence of measurable levels of CH50, both Clq and properdin are deposited on the vascular endothelium, and that IgM, IgG, and IgA bind to the endothelium of a transplanted pig heart. The prior identification of anti‐αGal IgM, IgG, and IgA by our group suggests that these antibodies might be playing a role in both classical (by IgM and IgG) and alternative (by IgA) complement pathway activation in this experimental model and in pig‐to‐human xenotransplantation. CVF contains a terminal aGal structure, and its administration to an otherwise unmodified baboon leads to a massive increase in anti‐αGal level, suggesting that anti‐CVF antibodies may, at least in part, comprise anti‐aGal. The important role of anti‐aGal antibodies in xenograft rejection has now been clearly established, and techniques for preventing expression of aGal epitopes in donor animals, either by genetic engineering or by gene therapy, are discussed.
Effects of nitrogenous fertiliser on the chemical composition of short‐rotation ryegrass and its subsequent digestion by sheep (1965)

“Nitrolime” was applied to a pure sward of short‐rotation ryegrass ( Lolium perenne × L. multiflorum ) at high (HN) and low (LN) rates. The grass was fed to rumen‐fistulated sheep housed indoors. Total, non‐protein, protein, and nitrate nitrogen contents of the HN grass, were greater than in the LN grass on the first three of four sampling days. Total soluble sugar and water‐soluble polysaccharide contents of the HN grass were lower than in the LN grass on the first two sampling days. Compared with the LN grass, the rumen liquor of the sheep on the HN grass contained higher concentrations of soluble nitrogen, soluble non‐protein nitrogen, ammonia, and nitrate, lower total VFA concentration and proportions of butyric acid, and higher proportions of acetic acid. The difference in the proportion of propionic acid depended on the time of sampling. It was concluded that even though large treatment differences in grass composition were obtained, there were no marked deleterious effects en animal health or intake.
RNase L in Health and Disease-What Did We Learn Recently? (2003)

The 2′,5′-oligoadenylate-dependent ribonuclease L (RNase L) is central to the innate cellular defense mechanism induced by type I interferons during intracellular infection. The protein, activated by 2′,5′-oligoadenylates, precludes the replication of the infectious agent by cleaving single-stranded RNA and, along with the double-stranded RNA-dependent protein kinase, its spreading by inducing the cell to undergo suicide (apoptosis). In absence of infection, the protein remains dormant. Recent evidence indicates, however, that the protein is activated in absence of infection and may play a role in cell differentiation, immune activation, and act as a tumor-suppressor. A deregulation in this pathway has been documented in immune cells of chronic fatigue syndrome patients which involves the presence of a catalytically active truncated RNase L. This protein escapes the normal regulation which implies the development of a cascade of unwanted cellular events. The present article reviews our current understanding of this deregulation, enlightens its relevance in the pathological process and proposes new targets for therapeutic development.
(1S)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethylammonium Benzoate, A Versatile Building Block for Chiral 2-Aminoalkanols:  Concise Synthesis and Application to Nelfinavir, a Potent HIV-Protease Inhibitor (2000)

A concise synthesis of a versatile chiral C4 building block for 2-aminoalkanols, (1S)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethylammo nium benzoate (1a), was described. 1 (1a and its enantiomer 1b) acted as four stereoisomers of optically active 2-amino-1,3,4-butanetriol. The versatility of 1 was demonstrated by its application to the practical synthesis of nelfinavir (2), a potent HIV-protease inhibitor, as well as by the stereospecific synthesis of three diastereomers of 2.
Structure of the DNA Ligase-Adenylate Intermediate: Lysine (ε-amino)-Linked Adenosine Monophosphoramidate (1971)

Proteolytic degradation of the Escherichia coli DNA ligase-adenylate intermediate releases adenosine 5'-monophosphate linked to the epsilon-amino group of lysine by a phosphoamide bond. Measurements of the rate of hydroxylaminolysis of the ligase-adenylate provide further support for a phosphoamide linkage in the native enzyme. Lysine (epsilon-amino)-linked adenosine monophosphoramidate has also been isolated from the T4 phage-induced ligase-adenylate intermediate. These results indicate that an initial step of the DNA ligase reaction consists of the nucleophilic attack of the epsilon-amino group of a lysine residue of the enzyme on the adenylyl phosphorus of DPN or ATP that leads to the formation of enzyme-bound lysine (epsilonamino)-linked adenosine monophosphoramidate.
On performance limits of switched-capacitor multi-phase charge pump circuits. Remarks on papers of Starzyk et al. (2008)

Important contributions on multi-phase charge pumps of Starzyk et al posed a question about a maximum voltage gain in a circuit containing k capacitors. We comment on Starzyk's conjecture of 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k-1</sup> gain and give general limit value theorems. We conclude that Starzykpsilas conjecture is true however, in general terms it gives a condition that is necessary but not sufficient. A note on circuit realizations is given.
Efficient targeted DNA editing and replacement in Chlamydomonas reinhardtii using Cpf1 ribonucleoproteins and single-stranded DNA (2017)

The green alga <i>Chlamydomonas reinhardtii</i> is an invaluable reference organism to research fields including algal, plant, and ciliary biology. Accordingly, decades-long standing inefficiencies in targeted nuclear gene editing broadly hinder <i>Chlamydomonas</i> research. Here we report that single-step codelivery of CRISPR/Cpf1 ribonucleoproteins with single-stranded DNA repair templates results in precise and targeted DNA replacement with as much as ∼10% efficiency in <i>C. reinhardtii</i> We demonstrate its use in transgene- and selection-free generation of sequence-specific mutations and epitope tagging at an endogenous locus. As the direct delivery of gene-editing reagents bypasses the use of transgenes, this method is potentially applicable to a wider range of species without the need to develop methods for stable transformation.
Controlled biosynthesis of odd-chain fuels and chemicals via engineered modular metabolic pathways (2012)

Microbial systems are being increasingly developed as production hosts for a wide variety of chemical compounds. Broader adoption of microbial synthesis is hampered by a limited number of high-yielding natural pathways for molecules with the desired physical properties, as well as the difficulty in functionally assembling complex biosynthetic pathways in heterologous hosts. Here, we address both of these challenges by reporting the adaptation of the butanol biosynthetic pathway for the synthesis of odd-chain molecules and the development of a complementary modular toolkit to facilitate pathway construction, characterization, and optimization in engineered Escherichia coli. The modular feature of our pathway enables multientry and multiexit biosynthesis of various odd-chain compounds at high efficiency. By varying combinations of the pathway and toolkit enzymes, we demonstrate controlled production of propionate, trans-2-pentenoate, valerate, and pentanol, compounds with applications that include biofuels, antibiotics, biopolymers, and aroma chemicals. Importantly, and in contrast to a previously used method to identify limitations in heterologous amorphadiene production, our bypass strategy was effective even without the presence of freely membrane-diffusible substrates. This approach should prove useful for optimization of other pathways that use CoA-derivatized intermediates, including fatty acid β-oxidation and the mevalonate pathway for isoprenoid synthesis.
pp60c-src Activation in gastric carcinoma: a preliminary study (2000)

TO THE EDITOR: Gastric carcinoma is the most common malignancy in Japan. Although some genes such as the protooncoge c-erbB2, K-sam, K-ras, and c-met are overexpressed in gastric carcinoma (1), little is known about molecular events leading to malignant transformation of gastric epithelia. The protooncogene product pp60c-src is the cellular homolog of the Rous sarcoma transforming gene, v-src (2). Both c-src and v-src encode 60 kDa membrane–associated protein tyrosine kinases. For pp60c-src, a close correlation exists between elevated activity of tyrosine kinase and cell transformation (3). To be sure, we know that pp60c-src expression and its activity are increased in a limited number of cases in human cancers (4), including our cases (5). However, the role of pp60c-src in gastric cancer has not been investigated. In the present study, we determined the activity of pp60c-src in gastric carcinoma by measuring the in vitro protein kinase activity of pp60c-src using gastric tissues of tumorous (T) and adjacent normal mucosa (N) obtained from surgery of 12 patients (mean age 65.0 11.5 yr, range 42–78 yr). The samples used in this study came from 12 cases, including six well differentiated, four moderately differentiated, and two poorly differentiated gastric carcinomas.
Enzymology of butyrate formation by Butyrivibrio fibrisolvens (1979)

Butyrivibrio fibrisolvens is a major butyrate-forming species in the bovine and ovine rumen. The enzymology of butyrate formation from pyruvate was investigated in cell-free extracts of B. fibrisolvens D1. Pyruvate owas oxidized to acetylcoenzyme A (CoA) in the presence of CoA.SH and benzyl viologen or flavin nucleotides. The bacterium uses thiolase, beta-hydroxybutyryl-CoA dehydrogenase, crotonase, and crotonyl-CoA reductase to form butyryl-CoA from acetyl-CoA. Reduction of acetoacetyl-CoA to beta-hydroxybutyryl-CoA was faster with NADH than with NADPH. Crotonyl-CoA was reduced to butyryl-CoA by NADH, but not by NADPH, only in the presence of flavin nucleotides. Reduction of flavin nucleotides by NADH was much slower than the flavin-dependent reduction of crotonyl-CoA. This indicates that flavoproteins rather than free flavin participated in the reduction of crotonyl-CoA. Butyryl-CoA was converted to butyrate by phosphate butyryl transferase and butyrate kinase.
Human and Mouse Induced Pluripotent Stem Cells Are Differentially Reprogrammed in Response to Kinase Inhibitors (2011)

Conventional human induced pluripotent stem cells (hiPSCs), reprogrammed from somatic cells by induced expression of Oct4, Sox2, Klf4, and c-Myc, are phenotypically different from mouse embryonic stem cells (ESCs). In mice, culture in N2B27 serum-free 2i media (mitogen-activated protein kinase/extracellular signal-regulated kinase and glycogen synthase kinase 3 inhibitors; PD0325901 and CHIR99021) plus leukemia inhibitory factor (LIF) (2i+LIF medium) enriches for germline competent ESCs. Here, we demonstrate that flat-shaped hiPSC colonies can be reprogrammed into bowl-shaped multi-potent stem cells (2i-hiPSCs) by using 2i+LIF medium. Mechanical dissociation of 2i-hiPSC colonies enables stable maintenance for >20 passages. Importantly, gene expression profiling demonstrated that 2i-hiPSCs more closely resemble primitive neural stem cells (PNSCs). Notably, this 2i-induced phenotype was generated from conventional hiPSCs, but not human ESCs (hESCs), thus correlating with the observation of neuroectodermal SOX1-positive colonies in conventional hiPSCs, but not hESCs in 2i+LIF medium. Thus, 2i-hiPSCs, which are nonteratoma forming PNSCs, may represent a safe source of cells for neural research and regenerative medicine.
Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a New Biomarker for Non – Acute Kidney Injury (AKI) Diseases (2011)

Neutrophil gelatinase-associated lipocalin, or NGAL, an acute phase protein, is part of the lipocalin family. NGAL is highly induced in inflammatory conditions and ischemia, and is a critical component of innate immunity to bacterial infection. Recently, NGAL has been proven as an emerging biomarker for predicting acute kidney injury (AKI). Meanwhile, numerous studies have also demonstrated that NGAL may be a potential biomarker for the diagnosis, prediction, prevention, and prognosis of non--AKI diseases such as chronic kidney diseases, vascular disorders, cancer, preeclampsia, and allergies. This article systematically reviews the clinical utilities of NGAL as a new biomarker for non--AKI diseases.
Drug therapy for the management of cancer-related fatigue (2010)

There is increasing evidence that psychostimulant trials provide evidence for improvement in CRF at a clinically meaningful level. There is still a requirement for a large scale RCT of methylphenidate to confirm the preliminary results from this review. There is new safety data which indicates that the haemopoietic growth factors are associated with increased adverse outcomes. These drugs can no longer be recommended in the treatment of CRF. Readers of the first review should re-read the document in full.
Centrosomal Kinases, HsAIRK1 and HsAIRK3, are Overexpressed in Primary Colorectal Cancers (2000)

Members of the recently identified family of Homo sapiens Aurora / Ipl1-related kinases (HsAIRKs), homologous to chromosome segregation kinases, fly Aurora and yeast Ipl1, are highly expressed during M phase, and have been suggested to regulate centrosome function, chromosome segregation, and cytokinesis. In the present study, immunohistochemical analyses were performed of HsAIRK1 and HsAIRK3 expression in 78 primary colorectal cancers and 36 colorectal adenomas as well as 15 normal colorectal specimens. In normal colon mucosa, some crypt cells showed weak positive staining in 10 and 12 out of 15 cases for HsAIRK1 and HsAIRK3, respectively, the remaining cases being negative. Elevated expression of HsAIRK1 was observed in 53 (67.9%) of the colorectal cancers, and of HsAIRK3 in 40 (51.3%). Furthermore, colorectal adenomas showed high expression of HsAIRK1 and HsAIRK3 in 11 (30.6%) and 7 (19.4%) cases, respectively, thus being intermediate between colorectal cancers and normal colorectal mucosa. Interestingly, HsAIRK1 overexpression was significantly associated with pT (primary tumor invasion) and p53 accumulation in colorectal cancers. There was no significant correlation between proliferating cell nuclear antigen-labeling index (PCNA-LI) and the levels of these proteins. The results suggest that overexpression of HsAIRK1 and HsAIRK3 might be involved in tumorigenesis and / or progression of colorectal cancers.
A Novel Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice from Pandemic H1N1 and Highly Pathogenic H5N1 Virus Challenges (2013)

Vaccination is an effective means to protect against influenza virus. Although inactivated and live-attenuated vaccines are currently available, each vaccine has disadvantages (e.g., immunogenicity and safety issues). To overcome these problems, we previously developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2 protein-expressing cells. Here, we generated two PB2-KO viruses whose PB2-coding regions were replaced with the HA genes of either A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1). The resultant viruses comparably, or in some cases more efficiently, induced virus-specific antibodies in the serum, nasal wash, and bronchoalveolar lavage fluid of mice relative to a conventional formalin-inactivated vaccine. Furthermore, mice immunized with these PB2-KO viruses were protected from lethal challenges with not only the backbone virus strain but also strains from which their foreign HAs originated, indicating that PB2-KO viruses with antigenically different HAs could serve as bivalent influenza vaccines.
Thermostable alanine dehydrogenase from thermophilic Bacillus sphaericus DSM 462 (1990)

Alanine dehydrogenase (L-alanine: NAD+ oxidoreductase, deaminating) was simply purified to homogeneity from a thermophile, Bacillus sphaericus DSM 462, by ammonium sulfate fractionation, red-Sepharose 4B chromatography and preparative slab gel electrophoresis. The enzyme had a molecular mass of about 230 kDa and consisted of six subunits with an identical molecular mass of 38 kDa. The enzyme was much more thermostable than that from a mesophile, B. sphaericus, and retained its full activity upon heating at 75 degrees C for at least 60 min and with incubation in pH 5.5-9.5 at 75 degrees C for 10 min. The enzyme can be stored without loss of its activity in a frozen state (-20 degrees C, at pH 7.2) for over 5 months. The optimum pH for the L-alanine deamination and pyruvate amination were around 10.5 and 8.2, respectively. The enzyme exclusively catalyzed the oxidative deamination of L-alanine in the presence of NAD+, but showed low amino acceptor specificity; hydroxypyruvate, oxaloacetate, 2-oxobutyrate and 3-fluoropyruvate are also aminated as well as pyruvate in the presence of NADH and ammonia. Initial velocity and product inhibition studies showed that the reductive amination proceeded through a sequential mechanism containing partially random binding. NADH binds first to the enzyme, and then pyruvate and ammonia bind in a random fashion. The products are sequentially released from the enzyme in the order L-alanine then NAD+. A dead-end inhibition by the formation of an abortive ternary complex which consists of the enzyme, NAD+ and pyruvate was included in the reaction. A possible role of the dead-end inhibition is to prevent the enzyme from functioning in the L-alanine synthesis. The Michaelis constants for the substrates were as follows: NADH, 0.10 mM; pyruvate, 0.50 mM; ammonia, 38.0 mM; L-alanine, 10.5 mM and NAD+, 0.26 mM.
An image storage system using complex-valued associative memories (2002)

A gray scale image storage system applying a complex-valued associative memory (CAM) combined with a 2-dimensional discrete Fourier transform (2-D DFT) process is proposed. In the proposed system, input images are transformed to a quantized phase matrix through processing including 2-D DFT then provided to CAM. In addition, the elements corresponding to the high frequency, bands in the matrices are omitted in order to reduce the number of neurons of CAM at the degree in which the image degradation is not conspicuous. When a noisy or an imperfect image of a memorised one is input into the system, the corresponding perfect one is output. The image quality memorized into CAM depends on the numbers of both neurons and states of each neuron, respectively. The image quality in changing those numbers and the restoring process of CAM are demonstrated using practical images.
A synthetic glucagon-like peptide-1 analog with improved plasma stability (1998)

Glucagon-like peptide-1 (GLP-1) is the most potent endogenous insulin-stimulating hormone. In the present study the plasma stability and biological activity of a GLP-1 analog, [Ser]GLP-1(7-36)amide, in which the second N-terminal amino acid alanine was replaced by serine, was evaluated in vitro and in vivo. Incubation of GLP-1 with human or rat plasma resulted in degradation of native GLP-1(7-36)amide to GLP-1(9-36)amide, while [Ser]GLP-1(7-36)amide was not significantly degraded by plasma enzymes. Using glucose-responsive HIT-T15 cells, [Ser]GLP-1(7-36)amide showed strong insulinotropic activity, which was inhibited by the specific GLP-1 receptor antagonist exendin-4(9-39)amide. Simultaneous i.v. injection of [Ser]GLP-1(7-36)amide and glucose in rats induced a twofold higher increase in plasma insulin levels than unmodified GLP-1(7-36)amide with glucose and a fivefold higher increase than glucose alone. [Ser]GLP-1(7-36)amide induced a 1.5-fold higher increase in plasma insulin than GLP-1(7-36)amide when given 1 h before i.v. application of glucose. The insulinotropic effect of [Ser]GLP-1(7-36)amide was suppressed by i.v. application of exendin-4(9-39)amide. The present data demonstrate that replacement of the second N-terminal amino acid alanine by serine improves the plasma stability of GLP-1(7-36)amide. The insulinotropic action in vitro and in vivo was not impaired significantly by this modification.
An experimental comparison of the head/disk interface dynamics in 5¼- and 8-inch disk drives (1985)

A laser Doppler vibrometer is used to measure the head/disk interface dynamics in computer disk drives. The stability of the head under steady operating conditions is compared between a 5¼-inch and two different 8-inch “Winchester” drives. In the larger drives, high-frequency vibrations (between 5 and 10 kHz) are detected on the slider which are not present in the smaller drive. These vibrations have amplitudes on the order of magnitude of the head/disk spacing and are related to the rolling and pitching modes of the slider. The vibrations of the disk, suspension, and actuator arm are also investigated and correlated with the results obtained on the slider.
Crystal structure of the large fragment of Thermus aquaticus DNA polymerase I at 2.5-A resolution: structural basis for thermostability. (1995)

The crystal structure of the large fragment of the Thermus aquaticus DNA polymerase (Klentaq1), determined at 2.5-A resolution, demonstrates a compact two-domain architecture. The C-terminal domain is identical in fold to the equivalent region of the Klenow fragment of Escherichia coli DNA polymerase I (Klenow pol I). Although the N-terminal domain of Klentaq1 differs greatly in sequence from its counterpart in Klenow pol I, it has clearly evolved from a common ancestor. The structure of Klentaq1 reveals the strategy utilized by this protein to maintain activity at high temperatures and provides the structural basis for future improvements of the enzyme.