gebhart/patrepeval huggingface dataset:
Identification of a novel deletion mutant strain in Saccharomyces cerevisiae that results in a microsatellite instability phenotype (2012)

The DNA mismatch repair (MMR) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity. The genes of the MMR pathway are highly conserved across different organisms. Likewise, defective MMR function universally results in microsatellite instability (MSI) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer. (Lynch syndrome). To identify previously unrecognized deleted genes or loci that can lead to MSI, we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae. This pool represents a collection of non-essential homozygous yeast diploid (2N) mutants in which there are deletions for over four thousand yeast open reading frames (ORFs). From this screen, we identified a deletion mutant strain of the &amp;lt;i&amp;gt;PAU24&amp;lt;/i&amp;gt; gene that leads to MSI. In a series of validation experiments, we determined that this &amp;lt;i&amp;gt;PAU24&amp;lt;/i&amp;gt; mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain, other deletion mutants and comparable to a MMR mutant involving the MLH1 gene. Likewise, in yeast strains with a deletion of &amp;lt;i&amp;gt;PAU24&amp;lt;/i&amp;gt;, we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen.
The Correlation of Cytokine Levels With Body Weight After Megestrol Acetate Treatment in Geriatric Patients (2001)

Although there was no significant change in cytokine levels between the two groups, the reduction in cytokine levels after MA treatment correlated with improvement in weight, fat mass, and FFM at 12 weeks.
Construction, expression, and purification of recombinant kringle 1 of human plasminogen and analysis of its interaction with .omega.-amino acids (1991)

An Escherichia coli expression vector, containing the alkaline phosphatase promoter and the stII heat-stable enterotoxin signal sequence, along with the cDNA of the kringle 1 (K1) region of human plasminogen (HPg), has been employed to express into the periplasmic space amino acid residues 82-163 (E163----D) of HPg. This region of the molecule contains the entire K1 domain (residues C84-C162) of HPg, as well as two non-kringle amino-terminal amino acids (S82-E83) that are present in their normal locations in HPg and a carboxyl-terminal amino acid, D163, that results from mutation of the E163, normally present at this location in the HPg amino acid sequence. After purification of r-K1 by chromatographic techniques, we have investigated its omega-amino acid binding properties by titration calorimetry, intrinsic fluorescence, and differential scanning microcalorimetry (DSC). The antifibrinolytic agent, epsilon-aminocaproic acid (EACA), possesses a single binding site for r-K1. The thermodynamic properties of this interaction, studied by calorimetric titrations of the heats of binding with this ligand, reveal a Kd of 12 +/- 2 microM at 25 degrees C and pH 7.4, a corresponding delta G of -6.7 +/- 0.1 kcal/mol, a delta H of -3.6 +/- 0.1 kcal/mol, and a delta S of 10.5 +/- 0.8 eu. The intrinsic fluorescence of r-K1 decreases by approximately 44% when its binding site is saturated with EACA, and titrations of this perturbation with EACA lead to calculation of a Kd of approximately 13 microM, a value in good agreement with that obtained from titration calorimetric analysis. EACA represents the strongest binding ligand of a variety of simple aliphatic omega-amino acids examined. A cyclic analogue of EACA, trans-4-(aminomethyl)cyclohexanecarboxylic acid, interacts with r-K1 with an approximate 12-fold tighter Kd (1.0 +/- 0.2 microM). Investigations by DSC, at pH 7.4, demonstrate that a significant stabilization of the r-K1 structure occurs when EACA binds to this domain. The temperature of maximum heat capacity change (Tm) in the thermal denaturation of r-K1 increases from approximately 340.8 to 359.1 K as a consequence of EACA binding. These studies demonstrate that a fully functional EACA-binding kringle from HPg can be expressed and secreted in E. coli, purified by techniques that do not require refolding, and investigated as an independent structural unit.
Electron microscopy shows periodic structure in collagen fibril cross sections. (1981)

X-ray diffraction was used to monitor the effects of electron microscope fixation, staining, and embedding procedures on the preservation of the three-dimensional crystalline order in collagen fibrils of rat tail tendon. A procedure is described in which the characteristic 3.8-nm lateral spacing is preserved, with increased contrast, in the diffraction pattern of the embedded fiber. This spacing is correlated with the separation between the tangentially oriented equally spaced lines of density observed in electron microscope ultrathin fibril cross sections of the same material. Optical diffraction of electron micrographs gives an objective measure of the periodicity and suggests that the fibril is composed of concentrically oriented crystalline domains. These observations, when combined with a recent interpretation of the native x-ray diffraction data [Hulmes, D. J. S. & Miller, A. (1979) Nature (London) 282, 878-880] suggest a tentative model for the three-dimensional structure of collagen fibrils.
Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study (2011)

MAP about 72 to 82 mmHg could be necessary to avoid acute kidney insufficiency in patients with septic shock and initial renal function impairment.
Ribosomal RNA cleavage, nuclease activation and 2-5A (ppp(A2′p)nA) in interferon-treated cells (1981)

Ribosomal RNA (rRNA) in intact ribosomes is cleaved into discrete products on incubation of reticulocyte lysates or L-cell extracts with ppp(A2'p)3A. Cleavage of rRNA may, therefore, provide a useful assay for 2-5A (ppp)A2'p)nA; n = 2 to 4) or for the presence of a 2-5A-dependent nuclease. The results with reticulocyte lysates differed from those obtained in the L-cell-free system in that (a) a different RNA cleavage pattern was produced (with added L-cell ribosomes) and (b) cleavage was fully activated by the analogue ppp(A2'p)3A3'pCp. As might be expected from the relatively high levels of 2-5A present in interferon-treated, encephalomyocarditis virus (EMC)-infected L-cells, rRNA extracted from these cells was also cleaved. The cleavage pattern observed overlapped with that obtained on incubation of an L-cell-free system with 2-5A. Thus, not only is 2-5A present, but the 2-5A-dependent nuclease also appears to be active, in interferon-treated, EMC-infected L-cells.
Strategies for improving nitrogen use efficiency: A review (2017)

Nitrogen (N) is the most critical externally added input for any crop production system. The half of the global population directly or indirectly depends on nitrogenous fertilizers for food supply. Today, Rice, wheat, and maize are consuming more than 90% of total nitrogenous fertilizer used in cereals. Underuse of nitrogen is associated with lower crop production while overuse leads to several soil and environmental related consequences. Therefore, response to applied nitrogen and its use efficiency have to be monitored properly for obtaining the maximum potential and sustainable yield. Efficiency of applied nitrogenous fertilizers is very low due to its various losses i.e. volatilization, leaching, surface runoff and denitrification from soil-plant system. Therefore, the proper understanding of advanced soil and plant management practices which helps in enhancement of nitrogen recovery efficiency is one of the key factors to enhance crop output, decreasing cost of cultivation, and to maintain environmental quality which ultimately adds towards the goal of achieving long term sustainable production system. In this review, an attempt has been made summarize the locally as well as scientific soil and crop management technologies used for improving use efficiency of applied N. This paper also discusses nitrogen cycling in soil-plant systems, various N losses pathways, present status and most possible management options at the farm level for enhancing nitrogen use in crop production system.
Orientation Dependence of Grain-Boundary Critical Currents inYBa2Cu3O7−δBicrystals (1988)

The critical current densities across grain boundaries have been measured as a function of misorientation angle in the basal plane of bicrystals of $\mathrm{Y}{\mathrm{Ba}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{7\ensuremath{-}\ensuremath{\delta}}$. For small misorientation angles, the ratio of the grain-boundary critical current density to the bulk critical current density is roughly proportional to the inverse of the misorientation angle; for large angles, this ratio saturates to a value of about $\frac{1}{50}$. These results imply that achieving a high degree of texture both normal to and within the basal plane is important for the obtaining of very high critical currents in pure polycrystalline samples.
Probabilistic databases and decision problems: results and a conjecture (1993)

An algebra applicable to recently introduced probabilistic models of data and which resembles the relational algebra is presented.It is shown to support various strategies for decision-making with information in the form of a probabilistic database.A conjecture is stated which, if true, could be exploited to reduce, without loss of information, the cost ol solving decision problems involving databases with large numbers of attributes.*A(P>) = *A(PJ), for all AC s(pt)r\s(pj).Definition.A model X is a refinement of model Y (and Y is an aggregate or coarsening of X), denoted X < Y, iff for each Vx X there exists a Vy Y such that Vm C Vv [5,9].
Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK) (2018)

We present the development of the first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB) cell lines. These degraders were developed through conjugation of known pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand pomalidomide. We demonstrate that in some cell types degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).
ACE Inhibitor Improves Insulin Resistance in Diabetic Mouse Via Bradykinin and NO (2002)

Improvement of insulin resistance by ACE inhibitors has been suggested; however, this mechanism has not been proved. We postulated that activation of the bradykinin-nitric oxide (NO) system by an ACE inhibitor enhances glucose uptake in peripheral tissues by means of an increase in translocation of glucose transporter 4 (GLUT4), resulting in improvement of insulin resistance. Administration of an ACE inhibitor, temocapril, significantly decreased plasma glucose and insulin concentrations in type 2 diabetic mouse KK-Ay. Mice treated with temocapril showed a smaller plasma glucose increase after glucose load. We demonstrated that temocapril treatment significantly enhanced 2-[3H]-deoxy-D-glucose (2-DG) uptake in skeletal muscle but not in white adipose tissue. Administration of a bradykinin B2 receptor antagonist, Hoe140, or an NO synthase inhibitor, L-NAME, attenuated the enhanced glucose uptake by temocapril. Moreover, we observed that translocation of GLUT4 to the plasma membrane was significantly enhanced by temocapril treatment without influencing insulin receptor substrate-1 phosphorylation. In L6 skeletal muscle cells, 2-DG uptake was increased by temocaprilat, and Hoe140 inhibited this effect of temocaprilat but not that of insulin. These results suggest that temocapril would improve insulin resistance and glucose intolerance through increasing glucose uptake, especially in skeletal muscle at least in part through enhancement of the bradykinin-NO system and consequently GLUT4 translocation.
Antimicrobial factors in whole saliva of human infants (1986)

Antimicrobial factors were analyzed in samples of whole saliva from 31 children, aged 0.8 to 3.8 years. When compared with the adult reference group, the children displayed similar levels of lysozyme, salivary peroxidase, and hypothiocyanite (OSCN-), whereas the amounts of immunoglobulins (isotypes A, G, and M), lactoferrin, myeloperoxidase, thiocyanate (SCN-), amylase, and protein were significantly lower than the adult values. The child's behavior during the collection period noticeably influenced the composition of the saliva. Children who were restless and crying during the collection had significantly more immunoglobulins, lysozyme, lactoferrin, salivary peroxidase, myeloperoxidase, and protein in their saliva samples, obviously due to the contamination of saliva mixed with nasal or lacrimal secretions. Therefore, the normal values for saliva could be determined for the noncrying children only. These salivary defense systems did not show any relation to the length of breast-feeding or to the previous history of antibiotic treatment. Thus, with the exception of lactoferrin and myeloperoxidase, the nonimmunoglobulin antimicrobial saliva systems studied here seem to be already at the adult level during early childhood, when the protective antibody systems are still immature.
Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics (2008)

Scaffold proteins link signaling molecules into linear pathways by physically assembling them into complexes. Scaffolds may also have a higher-order role as signal-processing hubs, serving as the target of feedback loops that optimize signaling amplitude and timing. We demonstrate that the Ste5 scaffold protein can be used as a platform to systematically reshape output of the yeast mating MAP kinase pathway. We constructed synthetic positive- and negative-feedback loops by dynamically regulating recruitment of pathway modulators to an artificial binding site on Ste5. These engineered circuits yielded diverse behaviors: ultrasensitive dose response, accelerated or delayed response times, and tunable adaptation. Protein scaffolds provide a flexible platform for reprogramming cellular responses and could be exploited to engineer cells with novel therapeutic and biotechnological functions.
Combinatory effects of siRNA-induced myostatin inhibition and exercise on skeletal muscle homeostasis and body composition (2014)

Abstract Inhibition of myostatin (Mstn) stimulates skeletal muscle growth, reduces body fat, and induces a number of metabolic changes. However, it remains unexplored how exercise training modulates the response to Mstn inhibition. The aim of this study was to investigate how siRNA-mediated Mstn inhibition alone but also in combination with physical activity affects body composition and skeletal muscle homeostasis. Adult mice were treated with Mstn-targeting siRNA and subjected to a treadmill-based exercise protocol for 4 weeks. Effects on skeletal muscle and fat tissue, expression of genes, and serum concentration of proteins involved in myostatin signaling, skeletal muscle homeostasis, and lipid metabolism were investigated and compared with Mstn(-/-) mice. The combination of siRNA-mediated Mstn knockdown and exercise induced skeletal muscle hypertrophy, which was associated with an upregulation of markers for satellite cell activity. SiRNA-mediated Mstn knockdown decreased visceral fat and modulated lipid metabolism similar to effects observed in Mstn(-/-) mice. Myostatin did not regulate its own expression via an autoregulatory loop, however, Mstn knockdown resulted in a decrease in the serum concentrations of myostatin propeptide, leptin, and follistatin. The ratio of these three parameters was distinct between Mstn knockdown, exercise, and their combination. Taken together, siRNA-mediated Mstn knockdown in combination with exercise stimulated skeletal muscle hypertrophy. Each intervention or their combination induced a specific set of adaptive responses in the skeletal muscle and fat metabolism which could be identified by marker proteins in serum.
Clinical Perspectives on Ototoxic Drugs (1990)

Ototoxic drugs such as salicylates, the aminoglycoside antibiotics, loop diuretics, cisplatin, erythromycin, and vancomycin are widely used in clinical practice. The most commonly used are aspirin and the aminoglycoside antibiotics. This chapter briefly discusses the pharmacology of the commonly prescribed ototoxic drugs and the doses that may result in ototoxicity. An outline for the monitoring of ototoxic drugs is presented. The role of topical ear drops as a possible cause of ototoxicity is reviewed.
ChemInform Abstract: HETEROCYCLIC FUSED NAPHTHALENE SYSTEMS FROM THEBAINE. 1 (1983)

Abstract (Id) sowie einiger Reaktionsprodukte werden, u.a. zur Klärung von Bildungsmechanismen, untersucht.
Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. (1985)

In order to obtain information about the nature of the local inflammatory process during late asthmatic reactions after house dust mite inhalation, bronchoalveolar lavage (BAL) was performed in 19 asthmatic patients and in 5 control subjects. In 16 of the patients and in all of the control subjects, BAL was performed 6 to 7 h after allergen inhalation. Six of the patients showed early and late asthmatic reactions (LAR), 5 showed early reactions, and 5 showed no reactions. Bronchoalveolar lavage was also performed shortly after the early reaction in 5 patients with documented combined early and late reactions. In the BAL fluid of the patients with LAR, a significant eosinophilia (0.01 less than p less than 0.05) was found compared with that in all other patient groups and with that in the control subjects. This bronchoalveolar eosinophilia was accompanied by elevated eosinophil cationic protein/albumin ratio in the BAL fluid (0.01 less than p less than 0.05). These observations suggest that eosinophils and their mediators might be involved in the development of LAR after allergen inhalation.
Sequence requirements of the hammerhead RNA self-cleavage reaction (1990)

A previously well-characterized hammerhead catalytic RNA consisting of a 24-nucleotide substrate and a 19-nucleotide ribozyme was used to perform an extensive mutagenesis study. The cleavage rates of 21 different substrate mutations and 24 different ribozyme mutations were determined. Only one of the three phylogenetically conserved base pairs but all nine of the conserved single-stranded residues in the central core are needed for self cleavage. In most cases the mutations did not alter the ability of the hammerhead to assemble into a bimolecular complex. In the few cases where mutant hammerheads did not assemble, it appeared to be the result of the mutation stabilizing an alternate substrate or ribozyme secondary structure. All combinations of mutant substrate and mutant ribozyme were less active than the corresponding single mutations, suggesting that the hammerhead contains few, if any, replaceable tertiary interactions as are found in tRNA. The refined consensus hammerhead resulting from this work was used to identify potential hammerheads present in a variety of Escherichia coli gene sequences.
Assessment of disease activity and impending flare in patients with systemic lupus erythematosus. Comparison of the use of complement split products and conventional measurements of complement (1992)

These data suggest that elevated levels of complement split products, particularly products of alternative and terminal pathway activation, more accurately reflect disease activity than do conventional measurements of complement in SLE and may be useful in the prediction of impending disease flares.
Deciphering and Reversing Immunosuppressive Cells in the Treatment of Hepatocellular Carcinoma (2020)

Use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) has been partially successful. However, most HCC patients do not respond to immunotherapy. HCC has been shown to induce several immune suppressor mechanisms in patients. These suppressor mechanisms include involvement of myeloid-derived suppressor cells, regulatory T-cells, functionally impaired dendritic cells (DCs), neutrophils, monocytes, and tumor associated macrophages. The accumulation of immunosuppressive cells may lead to an immunosuppressive tumor microenvironment as well as the dense fibrotic stroma which may contribute to immune tolerance. Our laboratory has been investigating different cellular mechanisms of immune suppression in HCC patients. <i>In vitro</i> as well as <i>in vivo</i> studies have demonstrated that abrogation of the suppressor cells enhances or unmasks tumor-specific antitumor immune responses. Two or three effective systemic therapies including ICIs and/or molecular targeted therapies and the addition of innovative combination therapies targeting immune suppressor cells may lead to increased immune recognition with a greater tumor response. We reviewed the literature for the latest research on immune suppressor cells in HCC, and here we provide a comprehensive summary of the recent studies in this field.
HyperCBR: Large-Scale Content-Based Routing in a Multidimensional Space (2008)

Content-based routing (CBR) is becoming increasingly popular as a building block for distributed applications. CBR differs from classical routing paradigms as messages are routed based on their content rather than their destination address, which fosters decoupling and flexibility in the application's distributed architecture. However, most available systems realize CBR by relying on a tree-shaped overlay network and adopt a routing strategy based on broadcasting subscription requests, thus hampering applicability in very large-scale networks. We observe that a fundamental underpinning of any CBR protocol is for messages and subscriptions to "meet" at some points in the network. In the approach we propose here, called HyperCBR <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> , we enforce this topological property in a multidimensional space, by routing messages and subscriptions on different, albeit intersecting, partitions. We derive an analytical model of HyperCBR, validated through simulation, and use it to evaluate our approach in two relevant CBR contexts - content-based searches in peer-to-peer networks, and content- based publish-subscribe. The results show that our protocol achieves efficient CBR even in very large scale settings (e.g., millions of nodes) while at the same time opening up intriguing opportunities for deployment-time tuning based on the expected traffic profiles. The analytical evaluation is complemented by simulation results relying on a CAN-based implementation, showing that HyperCBR generates a small forwarding and matching load, and that it is able to tolerate high churn with low overhead.