gebhart/patrepeval huggingface dataset:
Biologically Closed Electric Circuits: Activation of Vascular Interstitial Closed Electric Circuits for Treatment of Inoperable Cancers (1984)

Normal metabolic potential differences between tissue regions supply energy for chemical transports. Some of these transports take place via a circulatory system that is coupled to the non-selective bulk transports of blood and lymph circulation. It is called the vascular-interstitial closed circuit (VICC) and represents a key mechanism for healing of injured tissue. By applying direct current between electrodes implanted into tissues it is possible to enhance the VICC transports and to induce healing in inoperable cancers in the lungs, e.g., multiple metastases. To date 26 pulmonary cancers in 20 patients have been treated, 12 of which have regressed, without subsequent regrowth (2 to 5 year follow-up period). the technique of treatment is relatively simple and only slightly distressing to the patients. No fatalities have occurred.
Nicotine as a potential neuroprotective agent for Parkinson's disease (2012)

Converging research efforts suggest that nicotine and other drugs that act at nicotinic acetylcholine receptors (nAChRs) may be beneficial in the management of Parkinson's disease. This idea initially stemmed from the results of epidemiological studies that demonstrated that smoking is associated with a decreased incidence of Parkinson's disease. The subsequent finding that nicotine administration protected against nigrostriatal damage in parkinsonian animal models led to the idea that nicotine in tobacco products may contribute to this apparent protective action. Nicotine most likely exerts its effects by interacting at nAChRs. Accumulating research indicates that multiple subtypes containing nAChRs, including α4β2, α6β2, and/or α7, may be involved. Stimulation of nAChRs initially activates various intracellular transduction pathways primarily via alterations in calcium signaling. Consequent adaptations in immune responsiveness and trophic factors may ultimately mediate nicotine's ability to reduce/halt the neuronal damage that arises in Parkinson's disease. In addition to a potential neuroprotective action, nicotine also has antidepressant properties and improves attention/cognition. Altogether, these findings suggest that nicotine and nAChR drugs represent promising therapeutic agents for the management of Parkinson's disease.
Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity (2020)

ABSTRACT The spike (S) glycoprotein of SARS-CoV-2 is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18,354 mutations in S protein were analyzed and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3,705 mutations in SARS-CoV-2 RBD and 11,324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.
Sequence and Expression of mRNAs Encoding the α 1 and α 2 Subunits of a DHP-Sensitive Calcium Channel (1988)

Complementary DNAs were isolated and used to deduce the primary structures of the alpha 1 and alpha 2 subunits of the dihydropyridine-sensitive, voltage-dependent calcium channel from rabbit skeletal muscle. The alpha 1 subunit, which contains putative binding sites for calcium antagonists, is a hydrophobic protein with a sequence that is consistent with multiple transmembrane domains and shows structural and sequence homology with other voltage-dependent ion channels. In contrast, the alpha 2 subunit is a hydrophilic protein without homology to other known protein sequences. Nucleic acid hybridization studies suggest that the alpha 1 and alpha 2 subunit mRNAs are expressed differentially in a tissue-specific manner and that there is a family of genes encoding additional calcium channel subtypes.
Metformin pathways (2012)

Gong, Li; Goswami, Srijib; Giacomini, Kathleen M.; Altman, Russ B.; Klein, Teri E. Author Information
Selection of Novel Exon Recognition Elements from a Pool of Random Sequences (1995)

A 20-nucleotide sequence close to the 3' end of the internal exon of a model two-intron, three-exon pre-mRNA (DUP184 [Z. Dominski and R. Kole, J. Biol. Chem. 269:23590-23596, 1994]) was replaced by a random 20-mer, resulting in a pool of pre-mRNAs which, like the initial DUP184 construct, were spliced in vitro by a pathway leading to predominant skipping of the internal exon. The randomized pre-mRNAs were subjected to a selection protocol, resulting in a pool enriched in pre-mRNAs that efficiently included the internal exon. Isolation and sequencing of a number of clones corresponding to the selected pre-mRNAs showed that two classes of sequences were selected from the initial pool. Most abundant among these were sequences with purine tracts similar to those in the recently identified exon-splicing enhancers while a smaller class included sequences lacking discernible purine tracts within the 20-nucleotide region. Splicing of selected pre-mRNAs showed that the purine tracts vary in their ability to promote exon inclusion and, more important, that sequences lacking purine tracts stimulate inclusion of the internal exon as efficiently as their purine-rich counterparts. The latter result indicates the existence of a novel class of exon recognition sequences or splicing enhancers.
The role of T-cell subsets and cytokines in the regulation of infection (1991)

The study of immunity to infectious agents has proved valuable for analysing the role of T-cell subsets. This was true when Zinkernagel and Doherty demonstrated MHC restriction using viral and bacterial systems, and was re-emphasized at a recent meeting, where data were presented on the role of T cells and cytokines in viral, bacterial, protozoan and helminth infections. This report summarizes some of the highlights.
An improved method for estimating epicardial potentials from the body surface (1998)

We present a new method for regularizing the illposed problem of computing epicardial potentials from body surface potentials. The method simultaneously regularizes the equations associated with all time points, and relies on a new theorem which states that a solution based on optimal regularization of each integral equation associated with each principal component of the data will be more accurate than a solution based on optimal regularization of each integral equation associated with each time point. The theorem is illustrated with simulations mimicking the complexity of the inverse electrocardiography problem. As must be expected from a method which imposes no additional a priori constraints, the new approach addresses uncorrelated noise only, and in the presence of dominating correlated noise it is only successful in producing a "cleaner" version of a necessarily compromised solution. Nevertheless, in principle, the new method is always preferred to the standard approach, since it (without penalty) eliminates pure noise that would otherwise be present in the solution estimate.
Graft-versus-Leukemia Reactions in Clinical Bone Marrow Transplantation (1993)

Immunologie reactions occurring after allogeneic bone marrow transplantation, known as graft-versus-leukemia effect, contribute significantly to the control of minimal residual disease and decreased risk of relapse post-transplant. Graft-versus-leukemia reactions occur with or without graft-versus-host disease and are either mediated through T-cells or are independent of T-cells. The contribution made by graft-versus-leukemia reactions to improvement in overall survival depends upon the underlying type of leukemia, the nature of the marrow graft and the morbidity of any associated graft-versus-host disease. This article reviews the evidence demonstrating graft-versus-leukemia effect in clinical bone marrow transplantation, some approaches to dissociate graft-versus-leukemia from graft-versus-host disease, and attempts to induce graft-versus-leukemia recations in the setting of autologous bone marrow transplantation by immunotherapy.
Tunable semiconductor laser withliquid crystal pixel mirror in grating-loaded external cavity (1999)

The wavelength of a commercial red pointer laser diode has been tuned over 4 nm digitally in 0.2 nm steps with a folded telescopic grating loaded external cavity incorporating a liquid crystal pixel mirror. The sidemode-suppression ratio of the laser was better than 20 dB throughout this range.
Induction of nasal turbinate atrophy in germ-free pigs, using Pasteurella multocida as well as bacterium-free crude and purified dermonecrotic toxin of P multocida (1988)

SUMMARY To establish the role of the dermonecrotic toxin ( dnt ) of Pasteurella multocida in the cause and pathogenesis of atrophic rhinitis, germ-free pigs were inoculated with several strains of P multocida , crude dnt , or purified dnt . In some experiments, the aforementioned inocula were combined with Bordetella bronchiseptica . All dnt -producing P multocida strains induced severe turbinate atrophy. Histologic examination of the remnants of the nasal turbinates revealed intact, but undulated, ciliated epithelium and numerous osteoclasts. Inflammation was minimal or absent. A dnt -producing B bronchiseptica strain induced only mild turbinate atrophy. The lesions were characterized histologically by loss of cilia and ciliated cells and by an infiltration of predominantly mononuclear cells. Bone formation seemed impaired. Turbinate lesions were most severe in pigs infected with a combination of B bronchiseptica and a dnt -producing P multocida strain. Intranasal administration of sterile dnt -containing culture filtrate of P multocida or purified dnt of P multocida did not result in turbinate atrophy. In contrast, turbinate atrophy developed when these preparations were injected im or when intranasal administration of dnt was preceded by inoculation of B bronchiseptica .
A Study in Human Nature Entitled The Varieties of Religious Experience (2003)

Shortly after the appearance of William James's volume, The Varieties of Religious Experience, in June 1902, Josiah Royce commented on contemporary religious life at a meeting of the American Philosophical Association. Royce noted that, on the one hand, "Religion, in its higher sense, constitutes the most important business of the human being. . . ." By this he was referring to his conviction that
Impedance Control: An Approach to Manipulation: Part II—Implementation (1985)

This three-part paper presents an approach to the control of dynamic interaction between a manipulator and its environment. Part I presented the theoretical reasoning behind impedance control. In Part II the implementation of impedance control is considered. A feedback control algorithm for imposing a desired cartesian impedance on the end-point of a nonlinear manipulator is presented. This algorithm completely eliminates the need to solve the “inverse kinematics problem” in robot motion control. The modulation of end-point impedance without using feedback control is also considered, and it is shown that apparently “redundant” actuators and degrees of freedom such as exist in the primate musculoskeletal system may be used to modulate end-point impedance and may play an essential functional role in the control of dynamic interaction.
Differential Sensitivities of Malignant and Normal Skin Cells to Nanosecond Pulsed Electric Fields (2011)

Pulsed electric fields with nanosecond duration and high amplitude have effects on biological subjects and bring new venue in disease diagnosis and therapy. To address this respect, we investigated the responses of paired tumor and normal human skin cells - a basal cell carcinoma (BCC) cell line, and its sister normal cell line (TE) - to nanosecond, megavolt-per-meter pulses. When BCC (TE 354.T) and TE (TE 353.SK) cells, cultured under standard conditions, were exposed to 30 ns, 3 MV/m, 50 Hz pulses and tested for membrane permeabilization, viability, morphology, and caspase activation, we found that nanoelectropulse exposure: 1) increased cell membrane permeability in both cell lines but to a greater extent in BCC cells than in normal cells; 2) decreased cell viabilities with BCC cells affected more than normal cells; 3) induced morphological changes in both cell lines including condensed and fragmented chromatin with enlarged nuclei; 4) induced about twice as much caspase activation in BCC cells compared to normal cells. We concluded that in paired tumor and normal skin cell lines, the response of the tumor cells to nanoelectropulse exposure is stronger than the response of normal cells, indicating the potential for selectivity in therapeutic applications.
Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis (1999)

The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.
Reduction of experimental myocardial infarct size by oral administration of tocopherol (1991)

High dose dietary supplementation with vitamin E can improve myocardial tolerance to ischaemia and reperfusion, significantly reducing myocardial infarct size.
CD33/Siglec-3 Binding Specificity, Expression Pattern, and Consequences of Gene Deletion in Mice (2003)

Mouse CD33/Siglec-3 (mCD33) is the apparent ortholog of human CD33/Siglec-3 (hCD33), a member of the Siglec (sialic acid-binding Ig superfamily lectin) family of sialic acid-recognizing cell-surface lectins. We examined the binding specificity and expression pattern of mCD33 and explored its functions by generating mice deficient in this molecule. Like hCD33, mCD33 is expressed on myeloid precursors in the bone marrow, albeit mostly in the more mature stages of the granulocytic lineage. Moreover, unlike hCD33, mCD33 in peripheral blood is primarily expressed on granulocytes. Also, unlike hCD33, mCD33 did not bind to alpha2-3- or alpha2-6-linked sialic acids on lactosamine units. Instead, it showed distinctive sialic acid-dependent binding only to the short O-linked glycans of certain mucins and weak binding to the sialyl-Tn epitope. Binding was enhanced by removal of 9-O-acetyl groups and attenuated by truncation of the glycerol-like side chain of sialic acids. Mice deficient in CD33 were viable and fertile in a controlled-access specific-pathogen-free vivarium, showed no major morphological or histological abnormalities, had no changes in bone marrow or peripheral leukocyte subpopulations, and had very minor differences in biochemical and erythrocyte parameters. Cellular responses to intraperitoneally injected proinflammatory stimulants, as well as subsequent interleukin-6 secretion, were also apparently unaffected. These results indicate substantial species differences in CD33 expression patterns and ligand recognition and suggest functional degeneracy between mCD33 and the other CD33-related Siglec proteins expressed on cells of the myeloid lineage.
On the power of chemical synthesis: Immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines (2002)

Synthetic carbohydrate cancer vaccines have been shown to stimulate antibody-based immune responses in both preclinical and clinical settings. The antibodies have been observed to react in vitro with the corresponding natural carbohydrate antigens expressed on the surface of tumor cells, and are able to mediate complement-dependent and/or antibody-dependent cell-mediated cytotoxicity. Furthermore, these vaccines have proven to be safe when administered to cancer patients. Until recently, only monovalent antigen constructs had been prepared and evaluated. Advances in total synthesis have now enabled the preparation of multivalent vaccine constructs, which contain several different tumor-associated carbohydrate antigens. Such constructs could, in principle, serve as superior mimics of cell surface antigens and, hence, as potent cancer vaccines. Here we report preclinical ELISA-based evaluation of a TF-Le(y)-Tn bearing construct (compound 3) with native mucin glycopeptide architecture and a Globo-H-Le(y)-Tn glycopeptide (compound 4) with a nonnative structure. Mice were immunized with one or the other of these constructs as free glycopeptides or as keyhole lymphet hemocyanin conjugates. Either QS-21 or the related GPI-0100 were coadministered as adjuvants. Both keyhole lymphet hemocyanin conjugates induced IgM and IgG antibodies against each carbohydrate antigen, however, the mucin-based TF-Le(y)-Tn construct was shown to be less antigenic than the unnatural Globo-H-Le(y)-Tn construct. The adjuvants, although related, proved significantly different, in that GPI-0100 consistently induced higher titers of antibodies than QS-21. The presence of multiple glycans in these constructs did not appear to suppress the response against any of the constituent antigens. Compound 4, the more antigenic of the two constructs, was also examined by fluorescence activated cell sorter analysis. Significantly, from these studies it was shown that antibodies stimulated in response to compound 4 reacted with tumor cells known to selectively express the individual antigens. The results demonstrate that single vaccine constructs bearing several different carbohydrate antigens have the potential to stimulate a multifaceted immune response.
Neuraminidase Inhibitor-Resistant and -Sensitive Influenza B Viruses Isolated from an Untreated Human Patient (2006)

An influenza B virus from an infant with no history of treatment or contact with neuraminidase inhibitors demonstrated a significant reduction in sensitivity to these drugs. Here, we describe the analysis of a mixed viral population that contained a novel D197E amino acid substitution that was responsible for this reduction.
Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas (2013)

SOX10 expression in ACC and BBC appears to be a part of a highly coordinated transcriptional programme characteristic for cancers with basal/myoepithelial features. Comparison between ACC/BBC and other cancers, such as neuroblastomaand MEL, reveals potential molecular markers specific for these cancers that are likely linked to their cell identity. SOX10 as a novel diagnostic marker for ACC and BBC provides important molecular insight into their molecular aetiology and cell origin. Given that SOX10 was recently described as a principal driver of MEL, identification of conserved elements of the SOX10 signatures may help in better understanding of SOX10-related signalling and development of novel diagnostic and therapeutic tools.
Intravenous iron sucrose for children with iron deficiency failing to respond to oral iron therapy (2010)

Parenteral iron is a safe and effective means to treat iron deficiency in children who cannot receive or do not respond to oral iron due to intolerance, poor adherence, or iron malabsorption.
The interleukin-13 receptor α2 chain: an essential component for binding and internalization but not for interleukin-13–induced signal transduction through the STAT6 pathway (2001)

The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL-13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a productive complex with the primary IL-4 binding protein (IL-4Ralpha also known as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Ralpha2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 chain; (2) a recombinant chimeric fusion protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Ralpha2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Ralpha2-transfected cells. IL-13 efficiently caused activation of STAT6 protein in cells transfected with the IL-13Ralpha1 and IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Ralpha2 is signal independent and that this property of IL-13Ralpha2 can be exploited for receptor-directed cancer therapy.
Novel GmFAD2-1b mutant alleles created by reverse genetics induce marked elevation of oleic acid content in soybean seeds in combination with GmFAD2-1a mutant alleles (2010)

The generation of useful mutant alleles of specific genes would accelerate conventional breeding programs in various commercially important crops. Common soybean oil is easily oxidized because it is rich in polyunsaturated fatty acids (PUFAs). Microsomal omega-6 fatty acid desaturase (FAD2), which introduces a second unsaturated bond into oleic acid, is a primary target for elevating oleic acid levels and reducing PUFA levels. The paleopolyploid soybean genome contains five FAD2 gene homologues, at least three of which (GmFAD2-1a, 2-1b, and 2-2a) are functional. In spite of their importance, very little genetic variation has been identified in these genes except in GmFAD2-1a, because fatty acid content is easily affected by environmental conditions such as temperature. Here we isolated novel mutant alleles of GmFAD2-1b from ethyl methanesulfonate-treated soybean mutant populations through Targeting Induced Local Lesions In Genomes (TILLING), a reverse genetic method. Evaluation of enzyme activity in a yeast heterologous expression system suggested that two mutant lines, ‘B12’ and ‘E11’, contain near-null and null alleles, respectively, of GmFAD2-1b. Furthermore, by combining GmFAD2-1a and GmFAD2-1b mutant alleles, we successfully generated soybean lines with >80% oleic acid content. TILLING could provide a practical method for expanding the genetic diversity of polyploid crops.