gebhart/patrepeval huggingface dataset:
Deep Sequencing of Serum Small RNAs Identifies Patterns of 5′ tRNA Half and YRNA Fragment Expression Associated with Breast Cancer (2014)

Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions. We have previously described tRNA- and YRNA-derived small RNAs circulating as components of larger complexes in the blood of humans and mice; the characteristics of these small RNAs imply specific processing, secretion, and physiological regulation. In this study, we have asked if changes in the serum abundance of these tRNA and YRNA fragments are associated with a diagnosis of cancer. We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5' tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes. This prompted us to look at existing sequence datasets of serum small RNAs from 42 breast cancer cases, taken at the time of diagnosis. We find significant changes in the levels of specific 5' tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer. Although these findings do not establish causality, they suggest that circulating 5' tRNA halves and YRNA fragments with known cellular functions may participate in breast cancer syndromes and have potential as circulating biomarkers. Larger studies with multiple types of cancer are needed to adequately evaluate their potential use for the development of noninvasive cancer screening.
Association between Increases in Urinary Neutrophil Gelatinase–associated Lipocalin and Acute Renal Dysfunction after Adult Cardiac Surgery (2006)

Patients developing postoperative ARD had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of ARD after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.
Improved protection against cholera in adult rabbits with a combined flagellar-toxoid vaccine (1980)

Ligated ileal loops of adult rabbits were used to evaluate the prophylactic potential against cholera of a combined vaccine consisting of toxin-free crude flagella (CF) and glutaraldehyde-derived cholera toxoid (TV). The resulting fluid accumulation ratios were compared with those in rabbits immunized with saline (controls) and with CF and TV alone. Data for single vaccines confirmed the superior protection effect of CF over TV. In rabbits vaccinated with both CF and TV, maximal fluid accumulation ratios were not obtained with a challenge dose as high as 5 X 10(9) colony-forming units (CFU). Two rabbits similarly immunized failed to produce positive loops with challenges of 6.3 X 10(8) and 5 X 10(9) CFU, respectively. The vibriocidal titer of serum from rabbits immunized with a killed commercial vaccine in addition to those listed above was determined at intervals for a period of 164 days. No vibriocidal activity was detected in serum of control rabbits and of rabbits vaccinated with TV. Serum from animals given CF or commercial vaccine had similar vibriocidal titers even when the test bacteria were nonflagellated. Protection against challenge as evaluated by ileal loops did not, however, correlate with vibriocidal titer.
Verification of the position of a central venous catheter by intra‐atrial ECG. When does this method fail? (1993)

The purpose of this study was to determine why intra-atrial ECG tracing for checking the position of a central venous catheter fails in certain patients. Three hundred and fifty prospective and consecutive patients scheduled for central venous catheterization using various puncture sites and techniques were investigated. The catheters were 20 cm in length. After its introduction, the catheter was connected to an Alphacard (Sterimed, Saarbrücken) for the intra-atrial ECG tracing. The method failed in 29 patients, of whom nine had manifest myocardial pathology. In two patients the catheter looped, while in the remaining 18 the catheter proved to be too short. In these 18 patients, the cannulation was mainly performed via the external jugular vein and/or from the left side. Most of the patients were elderly males, and 11 of the 18 patients showed radiological signs of pulmonary emphysema. In such individuals it is advisable to use a catheter longer than 20 cm.
Pathogenesis of simian immunodeficiency virus infection. (1999)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Characterization of Adeno-Associated Viral Vector-Mediated Human Factor VIII Gene Therapy in Hemophilia A Mice (2017)

Adeno-associated viral (AAV) vectors are promising vehicles for hemophilia gene therapy, with favorable clinical trial data seen in the treatment of hemophilia B. In an effort to optimize the expression of human coagulation factor VIII (hFVIII) for the treatment of hemophilia A, an extensive study was performed with numerous combinations of liver-specific promoter and enhancer elements with a codon-optimized hFVIII transgene. After generating 42 variants of three reduced-size promoters and three small enhancers, transgene cassettes were packaged within a single AAV capsid, AAVrh10, to eliminate performance differences due to the capsid type. Each hFVIII vector was administered to FVIII knockout (KO) mice at a dose of 10<sup>10</sup> genome copies (GC) per mouse. Criteria for distinguishing the performance of the different enhancer/promoter combinations were established prior to the initiation of the studies. These criteria included prominently the level of hFVIII activity (0.12-2.12 IU/mL) and the pattern of development of anti-hFVIII antibodies. In order to evaluate the impact of capsid on hFVIII expression and antibody formation, one of the enhancer and promoter combinations that exhibited high hFVIII immunogenicity was evaluated using AAV8, AAV9, AAVrh10, AAVhu37, and AAVrh64R1 capsids. The capsids subdivided into two groups: those that generated anti-hFVIII antibodies in ≤20% of mice (AAV8 and AAV9), and those that generated anti-hFVIII antibodies in >20% of mice (AAVrh10, AAVhu37, and AAVrh64R1). The results of this study, which entailed extensive vector optimization and in vivo testing, demonstrate the significant impact that transcriptional control elements and capsid can have on vector performance.
Antitumor Activity of Thalidomide in Refractory Multiple Myeloma (1999)

Thalidomide is active against advanced myeloma. It can induce marked and durable responses in some patients with multiple myeloma, including those who relapse after high-dose chemotherapy.
Cardiac-Specific Overexpression of Caveolin-3 Induces Endogenous Cardiac Protection by Mimicking Ischemic Preconditioning (2008)

Expression of caveolin-3 is both necessary and sufficient for cardiac protection, a conclusion that unites long-standing ultrastructural and molecular observations in the ischemic heart. The present results indicate that increased expression of caveolins, apparently via actions that depend on phosphoinositide 3-kinase, has the potential to protect hearts exposed to ischemia/reperfusion injury.
RNA structure of trinucleotide repeats associated with human neurological diseases (2003)

The tandem repeats of trinucleotide sequences are present in many human genes and their expansion in specific genes causes a number of hereditary neurological disorders. The normal function of triplet repeats in transcripts is barely known and the role of expanded RNA repeats in the pathogenesis of Triplet Repeat Expansion Diseases needs to be more fully elucidated. Here we have described the structures formed by transcripts composed of AAG, CAG, CCG, CGG and CUG repeats, which were determined by chemical and enzymatic structure probing. With the exception of the repeated AAG motif, all studied repeats form hairpin structures and these hairpins show several alternative alignments. We have determined the molecular architectures of these co-existing hairpin structures by using transcripts with GC-clamps which imposed single alignments of hairpins. We have provided experimental evidence that CCUG repeats implicated in myotonic dystrophy type 2 also form hairpin structures with properties similar to that composed of the CUG repeats.
Differential diagnosis of bipolar disorder and major depressive disorder (2014)

The overview of demographic and clinical characteristics provided by this review may help medical professionals distinguish between major depressive disorder and bipolar disorder. Several validated, easily administered screening instruments are available and can greatly improve the recognition of bipolar disorder in patients with depression.
Crystal structure of RuvC resolvase in complex with Holliday junction substrate (2013)

The key intermediate in genetic recombination is the Holliday junction (HJ), a four-way DNA structure. At the end of recombination, HJs are cleaved by specific nucleases called resolvases. In Gram-negative bacteria, this cleavage is performed by RuvC, a dimeric endonuclease that belongs to the retroviral integrase superfamily. Here, we report the first crystal structure of RuvC in complex with a synthetic HJ solved at 3.75 Å resolution. The junction in the complex is in an unfolded 2-fold symmetrical conformation, in which the four arms point toward the vertices of a tetrahedron. The two scissile phosphates are located one nucleotide from the strand exchange point, and RuvC approaches them from the minor groove side. The key protein-DNA contacts observed in the structure were verified using a thiol-based site-specific cross-linking approach. Compared with known complex structures of the phage resolvases endonuclease I and endonuclease VII, the RuvC structure exhibits striking differences in the mode of substrate binding and location of the cleavage site.
A key step in the formation of acrylic acid from CO2and ethylene: the transformation of a nickelalactone into a nickel-acrylate complex (2006)

The reaction of a nickelalactone with dppm, resulting in the formation of a stable binuclear Ni(I) complex with an acrylate, a Ph2P- and a dppm bridge, models a key step in the formation of acrylic acid from CO2 and ethylene.
Retroviral Gene Therapy: Safety Issues and Possible Solutions (2005)

The recent incidents of leukemia development in X-SCID patients after a successful treatment of the disease with retroviral gene therapy raised concerns regarding the safety of the use of retroviral vectors in clinical gene therapy. In this review, we have tried to re-evaluate the safety issues related to the use of retroviral vectors in human clinical trials and to suggest possible appropriate solutions to the issues. As revealed by the X-SCID incident, oncogenesis caused by retroviral insertional activation of host genes is one of the most prominent risks. An ultimate solution to this problem will be in re-engineering retroviral vectors so that the retroviral insertion takes place only at the desired specific sites of the host cell chromosome. This is, however, a technically demanding tasks, and it will take years to develop retroviral vectors with targeted insertion capability. In the mean time, the use of chromatin insulators can reduce chances for retrovirus-mediated oncogenesis by inhibiting non-specific activation of nearby cellular proto-oncogenes. Co-transduction of a suicidal gene under the control of an inducible promoter could also be one of the important safety features, since destruction of transduced cells can be triggered if abnormal growth is observed. Additionally, conditional expression of the transgene only in appropriate target cells via the combination of targeted transduction, cell type-specific expression, and targeted local administration will increase the overall safety of the retroviral systems. Finally, splitting of the viral genome, use of self-inactivating (SIN) retroviral vectors, or complete removal of the coding sequences for gag, pol, and env genes is desirable to virtually eliminate the possibility of generation of replication competent retroviruses (RCR).
Selective localization and growth of Bifidobacterium bifidum in mouse tumors following intravenous administration. (1980)

A strain of domestic bacteria, Bifidobacterium bifidum (Lac B), which is nonpathogenic and anerobic, selectively localized and proliferated in several types of mouse tumors following i.v. administration. None of the same bacilli could be detected in the tissues of healthy organs such as the liver, spleen, kidney, lung, blood, bone marrow, and muscle 48 or 96 hr after i.v. administration into tumor-bearing mice. Proliferation of Lac B in the tumor was artifically stimulated by i.p. administration of DDD-H-2s mice of a synthesized disaccharide, lactulose (4-O-beta-D-galactopyranosyl-D-fructofuranose), a sugar which is not metabolized by mammalian tissue cells. Lac B, which survices and proliferates selectively in the tumor following i.v. administration into the tumor-bearing host, should aid in diagnosis and selective therapy for cancer.
Highly Stable Self-Assembly in Water:  Ion Pair Driven Dimerization of a Guanidiniocarbonyl Pyrrole Carboxylate Zwitterion (2002)

The synthesis of a novel water-soluble guanidiniocarbonyl pyrrole carboxylate zwitterion 2 is described, and its self-association in aqueous solutions is studied. Zwitterion 2 forms extremely stable 1:1 dimers which are held together by an extensive hydrogen bonding network in combination with two mutual interacting ion pairs as could be shown by ESI MS and X-ray structure determination. NMR dilution studies in different highly polar solvents showed that dimerization is fast on the NMR time scale with association constants ranging from an estimated 10(10) M(-1) in DMSO to a surprisingly high 170 M(-1) in water. Hence, zwitterion 2 belongs to the most efficient self-assembling systems solely on the basis of electrostatic interactions reported so far. Furthermore, an amidopyridine pyrrole carboxylic acid 10 was developed as a neutral analogue of zwitterion 2, which also dimerizes with an essentially identical hydrogen bonding pattern (according to ESI MS and X-ray structure determination) but lacking the ionic interactions. NMR binding studies demonstrated that the solely hydrogen-bonded neutral dimer of 10 is stable only in organic solvents of low polarity (K > 10(4) M(-1) in CDCl3 but <10 M(-1) in 5% DMSO in CDCl3). The comparison of both systems impressively underlines the importance of ion pair interactions for stable self-association of such H-bonded binding motifs in water.
Polyhydroxy and polyethyleneglycol (meth)acrylate polymers: Physical properties and general studies for their use as electrophoresis matrices (1992)

A new series of materials have been tested for their suitability as electrophoresis matrices. The mechanical and optical properties of gels composed of polyethyleneglycol (meth)acrylate esters or polyhydroxy (meth)acrylate esters in water and in various concentrations of organic solvents are described. Several crosslinkers including polyethyleneglycol and polyhydroxy di(meth)acrylates, piperazine diacrylate, and bisacrylamide were used in these studies. Electrophoretic migration and separation of a series of protein standards through polyethyleneglycol methacrylate (PEGM) 200, PEGM 400, and glyceryl methacrylate is demonstrated. Further, copolymerization of all of the monomers with acrylamide was performed and the distribution of monomer incorporation into the polymer network calculated. All monomers and copolymers that were examined by IR spectroscopy showed greater than 99% polymerization. These results justify their further study for biomolecule separations.
Hypergolic fuel detection using individual single walled carbon nanotube networks (2010)

Accurate and reliable detection of hypergolic fuels such as hydrazine (N2H4) and its derivatives is vital to missile defense, aviation, homeland security, and the chemical industry. More importantly these sensors need to be capable of operation at low temperatures (below room temperature) as most of the widely used chemical sensors operate at high temperatures (above 300 °C). In this research a simple and highly sensitive single walled carbon nanotube (SWNT) network sensor was developed for real time monitoring of hydrazine leaks to concentrations at parts per million levels. Upon exposure to hydrazine vapor, the resistance of the air exposed nanotubes (p-type) is observed to increase rapidly while that of the vacuum-degassed nanotubes (n-type) is observed to decrease. It was found that the resistance of the sample can be recovered through vacuum pumping and exposure to ultraviolet light. The experimental results support the electrochemical charge transfer mechanism between the oxygen redox couple of the ambient and the Fermi level of the SWNT. Theoretical results of the hydrazine-SWNT interaction are compared with the experimental observations. It was found that a monolayer of water molecules on the SWNT is necessary to induce strong interactions between hydrazine and the SWNT by way of introducing new occupied states near the bottom of the conduction band of the SWNT.
Processing of concatemers of bacteriophage T7 DNA in vitro. (1987)

The T7 chromosome is a double-stranded linear DNA molecule flanked by direct terminal repeats or so-called terminal redundancies. Late in infection bacteriophage T7 DNA accumulates in the form of concatemers, molecules that are comprised of T7 chromosomes joined in a head to tail arrangement through shared terminal redundancies. To elucidate the molecular mechanisms of concatemer processing, we have developed extracts that process concatemeric DNA. The in vitro system consists of an extract of phage T7-infected cells that provides all T7 gene products and minimal levels of endogenous concatemeric DNA. Processing is analyzed using a linear 32P-labeled substrate containing the concatemeric joint. T7 gene products required for in vitro processing can be divided into two groups; one group is essential for concatemer processing, and the other is required for the production of full length left-hand ends. The products of genes 8 (prohead protein), 9 (scaffolding protein), and 19 (DNA maturation) along with gene 18 protein are essential, indicating that capsids are required for processing. In extracts lacking one or more of the products of genes 2 (Escherichia coli RNA polymerase inhibitor), 5 (DNA polymerase), and 6 (exonuclease), full length right-hand ends are produced. However, the left-hand ends produced are truncated, lacking at least 160 base pairs, the length of the terminal redundancy. Gene 3 endonuclease, required for concatemer processing in vivo, is not required in this system. Both the full length left- and right-hand ends produced by the processing reaction are protected from DNase I digestion, suggesting that processing of the concatemeric joint substrate is accompanied by packaging.
New Ionization Method for Analysis on Atmospheric Pressure Ionization Mass Spectrometers Requiring Only Vacuum and Matrix Assistance (2013)

Matrix assisted ionization vacuum (MAIV) is a new ionization method that does not require high voltages, a laser beam, or applied heat and depends only the proper matrix, 3-nitrobenzonitrile (3-NBN), and the vacuum of the mass spectrometer to initiate ionization. Analyte ions of volatile as well as nonvolatile compounds are formed by simply exposing the matrix-analyte to the vacuum of a mass spectrometer. The reduced pressure at the inlet of an atmospheric pressure ionization mass spectrometer suffices to produce analyte ions, but unlike the previously reported matrix assisted ionization inlet method, with MAIV, heating the inlet is not necessary. Singly and multiply charged ions are formed similar to electrospray ionization but from a surface. Mass spectrometers in which a heated inlet tube is not available can be used for ionization using the 3-NBN matrix. We demonstrate rapid, high-sensitivity analyses of drugs, peptides, and proteins in the low femtomole range. The potential for high-throughput analyses is shown using multiwell plates and paper strips.
Reduction of Carboxylic Acids by Nocardia Aldehyde Oxidoreductase Requires a Phosphopantetheinylated Enzyme (2006)

Aldehyde oxidoreductase (carboxylic acid reductase (Car)) catalyzes the magnesium-, ATP-, and NADPH-dependent reduction of carboxylic acids to their corresponding aldehydes. Heterologous expression of the car gene in Escherichia coli afforded purified recombinant enzyme with a specific activity nearly 50-fold lower than that of purified native Nocardia sp. enzyme. The 5-fold increase in specific activity obtained by incubating purified recombinant Car with CoA and Nocardia cell-free extracts indicated that post-translational phosphopantetheinylation of Car is required for maximum enzyme activity. Nocardia phosphopantetheine transferase (PPTase) expressed in E. coli was isolated and characterized. When incubated with [(3)H]acetyl-CoA and Nocardia PPTase, the labeled acetylphosphopantetheine moiety was incorporated into recombinant Car. Coexpression of Nocardia Car and PPTase in E. coli gave a reductase with nearly 20-fold higher specific activity. Site-directed mutagenesis in which Ser(689) was replaced with Ala resulted in an inactive Car mutant. The results show that Car expressed in Escherichia coli is an apoenzyme that is converted to a holoenzyme by post-translational modification via phosphopantetheinylation. Doubly recombinant resting E. coli cells efficiently reduce vanillic acid to vanillin.
A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium (2004)

Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca(2+) imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30microM). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing.