gebhart/patrepeval huggingface dataset:
Stem cells in gastrointestinal epithelium: numbers, characteristics and death (1998)

The mammalian intestinal mucosa, with its distinctive polarity, high rate of proliferation and rapid cell migration, is an excellent model system to study proliferative hierarchies and the regulation of cell division, differentiation and cell death. Each crypt contains a few lineage ancestral stem cells (the 'ultimate stem cells'). However, there are other potential stem cells within the early lineage, and many rapidly proliferating transit cells with no stem cell capabilities. Apoptosis under two circumstances has a specificity for the ultimate stem cells in the small intestine and this represents, in one case, part of the stem cell homeostatic process and, in another case, a protective mechanism against DNA damage. Apoptosis occurs with a lower frequency in the large intestine owing to the expression of the bcl-2 gene in this region, and this probably contributes to the causes for the low cancer risk in the small bowel and the high risk in the large bowel. Current studies are beginning to unravel the complex interaction of growth factors and regulatory genes that determine whether a cell divides, differentiates or dies.
A semidiscrete matrix decomposition for latent semantic indexing information retrieval (1998)

The vast amount of textual information available today is useless unless it can be effectively and efficiently searched. The goal in information retrieval is to find documents that are relevant to a given user query. We can represent and document collection by a matrix whose ( i, j) entry is nonzero only if the i th term appears in the j th document; thus each document corresponds to a columm vector. The query is also represented as a column vector whose i th term is nonzero only if the i th term appears in the query. We score each document for relevancy by taking its inner product with the query. The highest-scoring documents are considered the most relevant. Unfortunately, this method does not necessarily retrieve all relevant documents because it is based on literal term matching. Latent semantic indexing (LSI) replaces the document matrix with an approximation generated by the truncated singular-value decomposition (SVD). This method has been shown to overcome many difficulties associated with literal term matching. In this article we propose replacing the SVD with the semidiscrete decomposition (SDD). We will describe the SDD approximation, show how to compute it, and compare the SDD-based LSI method to the SVD-based LSI methods. We will show that SDD-based LSI does as well as SVD-based LSI in terms of document retrieval while requiring only one-twentieth the storage and one-half the time to compute each query. We will also show how to update the SDD approximation when documents are added or deleted from the document collection.
Synthesis and Characterization of Insulin−Transferrin Conjugates (2006)

Receptor-mediated endocytosis can be exploited for improving the transcellular delivery of therapeutic proteins. Insulin conjugated to transferrin by forming disulfide bonds has been shown to improve insulin oral bioavailability in diabetic rats. We are developing a combination strategy involving complexation hydrogels as delivery vehicles for insulin-transferrin conjugates. The complexation hydrogels developed in our laboratory have been shown to be promising carriers for oral delivery of proteins and peptides. Integrating the strategies based on the complexation hydrogels and insulin-transferrin conjugates may prove to be a novel approach for oral delivery of insulin and other therapeutic proteins. In this work, electrospray ionization mass spectrometry (ESI-MS) was used to study the modification of insulin during its reaction with transferrin. The stability of the conjugated insulin to enzymatic degradation was also studied. ESI-MS studies confirmed the site-specific modifications of insulin. The transferrin conjugation of insulin was also shown to increase the stability of insulin to enzymatic degradation.
Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion (2009)

Despite the success of passive immunotherapy with monoclonal antibodies (mAbs), many lymphoma patients eventually relapse. Induction of an adaptive immune response may elicit active and long-lasting antitumor immunity, thereby preventing or delaying recurrence. Immunomodulating mAbs directed against immune cell targets can be used to enhance the immune response to achieve efficient antitumor immunity. Anti-CD137 agonistic mAb has demonstrated antitumor efficacy in various tumor models and has now entered clinical trials for the treatment of solid tumors. Here, we investigate the therapeutic potential of anti-CD137 mAb in lymphoma. We found that human primary lymphoma tumors are infiltrated with CD137+ T cells. We therefore hypothesized that lymphoma would be susceptible to treatment with anti-CD137 agonistic mAb. Using a mouse model, we demonstrate that anti-CD137 therapy has potent antilymphoma activity in vivo. The antitumor effect of anti-CD137 therapy was mediated by both natural killer (NK) and CD8 T cells and induced long-lasting immunity. Moreover, the antitumor activity of anti-CD137 mAb could be further enhanced by depletion of regulatory T cell (T(regs)). These results support the evaluation of anti-CD137 therapy in clinical trials for patients with lymphoma.
CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivo (2013)

Novel combinations targeting new molecular vulnerabilities are needed to improve the outcome of patients with acute myeloid leukemia. We recently identified WEE1 kinase as a novel target in leukemias. To identify genes that are synthetically lethal with WEE1 inhibition, we performed a short interfering RNA screen directed against cell cycle and DNA repair genes during concurrent treatment with the WEE1 inhibitor MK1775. CHK1 and ATR, genes encoding two replication checkpoint kinases, were among the genes whose silencing enhanced the effects of WEE1 inhibition most, whereas CDK2 short interfering RNA antagonized MK1775 effects. Building on this observation, we examined the impact of combining MK1775 with selective small molecule inhibitors of CHK1, ATR and cyclin-dependent kinases. The CHK1 inhibitor MK8776 sensitized acute myeloid leukemia cell lines and primary leukemia specimens to MK1775 ex vivo, whereas smaller effects were observed with the MK1775/MK8776 combination in normal myeloid progenitors. The ATR inhibitor VE-821 likewise enhanced the antiproliferative effects of MK1775, whereas the cyclin-dependent kinase inhibitor roscovitine antagonized MK1775. Further studies showed that MK8776 enhanced MK1775-mediated activation of the ATR/CHK1 pathway in acute leukemia cell lines and ex vivo. These results indicate that combined cell cycle checkpoint interference with MK1775/MK8776 warrants further investigation as a potential treatment for acute myeloid leukemia.
Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients (2006)

We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion. Kaplan-Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation.
Relation of Body Mass Index and Insulin Resistance to Cardiovascular Risk Factors, Inflammatory Factors, and Oxidative Stress During Adolescence (2005)

These results show the significant association of both fatness and insulin resistance and their significant interaction with cardiovascular risk factors in adolescence. The finding that insulin resistance may be acting interactively with fatness suggests that interventions directed at insulin resistance in addition to weight loss may be required to alter early development of cardiovascular risk.
Motility Potential of Macaque Epididymal Sperm: The Role of Protein Phosphatase and Glycogen Synthase Kinase‐3 Activities (1999)

Human and monkey ejaculated sperm contain protein phosphatase-1 (PP1), PP1 inhibitor 2 (12), and glycogen synthase kinase-3 (GSK-3). Inhibition of ejaculated human sperm protein phosphatase (PP) activity with calyculin-a (CL-A) significantly stimulates motility, implicating protein dephosphorylation in motility regulation. The present experiments were conducted to characterize and compare PP and GSK-3 activity in monkey caput and caudal epididymal sperm, to determine the cellular distribution of these enzymes, and to test the thesis that epididymal sperm PP activity is inversely related to motility. Caput epididymal sperm populations, (8.8% motile) contained levels of PP activity that were >3 times as high as those of caudal spermatozoa. This PP activity was further identified by inhibitor response profiles as PP1. In both caput and caudal sperm, the majority of this PP1 activity was localized in 100,000 x g soluble fractions. Western blot analysis indicated that a portion of this difference was the result of elevated amounts of PP1 in caput compared with caudal epididymal sperm. The presence of GSK-3 activity was undetectable in 100,000 x g insoluble fractions of epididymal sperm, whereas both caput and caudal sperm soluble fractions contained GSK-3 activity, which was approximately threefold higher in caput sperm compared with caudal populations. Treatment of caput epididymal sperm from the rhesus macaque with the PP inhibitor CL-A resulted in a significant, dose-dependent increase from 8 to 38% motile cells (without any effect on their path velocity). In contrast, CL-A had no significant influence on either percent motility or path velocity of caudal epididymal sperm. Cytosolic PP1 and GSK-3 activities appear to be inversely related to the motility of monkey epididymal sperm and may have a regulatory role in the development of the potential for motility in epididymal sperm.
Ceramic microstructures : property control by processing (1994)

Ceramic processing. General influence of microstructure on ceramic properties. Techniques for characterizing ceramic microstructures. Preparation of ceramic samples for microscopy. Structural oxides I: Al2O3 and mullite. Structural oxides II: ZrO2. Synthetic structural non-oxides. Refractories. Ceramic matrix composites. Index.
Two Heteromeric Kinesin Complexes in Chemosensory Neurons and Sensory Cilia ofCaenorhabditis elegans (1999)

Chemosensation in the nervous system of the nematode Caenorhabditis elegans depends on sensory cilia, whose assembly and maintenance requires the transport of components such as axonemal proteins and signal transduction machinery to their site of incorporation into ciliary structures. Members of the heteromeric kinesin family of microtubule motors are prime candidates for playing key roles in these transport events. Here we describe the molecular characterization and partial purification of two heteromeric kinesin complexes from C. elegans, heterotrimeric CeKinesin-II and dimeric CeOsm-3. Transgenic worms expressing green fluorescent protein driven by endogenous heteromeric kinesin promoters reveal that both CeKinesin-II and CeOsm-3 are expressed in amphid, inner labial, and phasmid chemosensory neurons. Additionally, immunolocalization experiments on fixed worms show an intense concentration of CeKinesin-II and CeOsm-3 polypeptides in the ciliated endings of these chemosensory neurons and a punctate localization pattern in the corresponding cell bodies and dendrites. These results, together with the phenotypes of known mutants in the pathway of sensory ciliary assembly, suggest that CeKinesin-II and CeOsm-3 drive the transport of ciliary components required for sequential steps in the assembly of chemosensory cilia.
Bacteriophage Lambda Vector for Transducing a cDNA Clone Library into Mammalian Cells (1985)

We have developed a bacteriophage lambda vector (lambda NMT) that permits efficient transduction of mammalian cells with a cDNA clone library constructed with the pcD expression vector (H. Okayama and P. Berg, Mol. Cell. Biol. 3:280-289, 1983). The phage vector contains a bacterial gene (neo) fused to the simian virus 40 early-region promoter and RNA processing signals, providing a dominant-acting selectable marker for mammalian transformation. The phage DNA can accommodate pcD-cDNA recombinants with cDNA of up to about 9 kilobases without impairing the ability of the phage DNA to be packaged in vitro and propagated in vivo. Transfecting cells with the lambda NMT-pcD-cDNA recombinant phage yielded G418-resistant clones at high frequency (approximately 10(-2]. Cells that also acquired a particular cDNA segment could be detected among the G418-resistant transformants by a second selection or by a variety of screening protocols. Reconstitution experiments indicated that the vector could transduce 1 in 10(6) cells for a particular phenotype if the corresponding cDNA was present as 1 functional cDNA clone per 10(5) clones in the cDNA library. This expectation was confirmed by obtaining two hypoxanthine-guanine phosphoribosyltransferase (HPRT)-positive transductants after transfecting 10(7) HPRT-deficient mouse L cells with a simian virus 40-transformed human fibroblast cDNA library incorporated into the lambda NMT phage vector. These transductants contained the human HPRT cDNA sequences and expressed active human HPRT.
A reinforcement learning based robotic navigation system (2014)

It is a challenging task for an autonomous robot to navigate in an unknown environment. Machine learning could be useful to support the robot to adapt to the environment and learn the correct navigation skills quickly. In this paper, a reinforcement learning (Q-learning) based approach is proposed to help a robot to move out of an unknown maze. The definitions of the world states, actions and rewards of the algorithm are presented and some experiments are completed to validate the approach. The experimental results show that the proposed approach does have a good performance on mobile robot navigation.
An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene (2005)

We have investigated a herpes simplex virus mutant that expresses low levels of thymidine kinase (TK), a phenotype associated with drug resistance and pathogenicity, despite a single-base deletion in the gene. Using a dual-reporter system, a 39-nt sequence including the mutation was shown to direct expression of the downstream reporter gene in reticulocyte lysate. Translation of the downstream reporter was not impaired when the mRNA lacked a 5' cap or had a stable stem loop 5' of the upstream reporter and was relatively resistant to edeine, an antibiotic that prevents AUG codon recognition by the 40S-eIF2-GTP/Met-tRNAi complex. Twelve nucleotides were as active as the original sequence for translation of the downstream reporter. Surprisingly, this sequence lacks an AUG codon. Analysis of point mutations showed that a CUG codon in the sequence was important. However, many single-base changes had only limited effects, and introduction of AUG codons did not increase translation. A mutant virus containing both the single-base deletion and a mutation that reduced downstream translation in vitro had significantly less TK activity than a virus with the single-base deletion alone. Thus, a remarkably short internal ribosome entry site (IRES) that lacks an AUG codon resides in the viral tk gene. The IRES appears to be responsible for TK expression from a drug-resistant mutant that would otherwise express no TK, which may contribute to pathogenicity. Because we found numerous short sequences with IRES activity, there might be many hitherto unrecognized polypeptides expressed at low levels from eukaryotic mRNAs.
Deformation Potentials in Silicon. I. Uniaxial Strain (1962)

The rate of splitting with uniaxial strain of the fourfold degenerate ($J=\frac{3}{2}$) valence-band edge of silicon is computed by applying perturbation theory to the Si wave functions calculated previously by Kleinman and Phillips. Based on a "self-consistent" model the calculated values for strain along the [100] and [111] directions are 40% larger than Hensel's experimental values. A primary objective of this calculation was to test the rigid-ion and deformable-ion models often used in the theory of electron-phonon coupling. The rigid-ion model agrees with experiment to within the accuracy of the calculation while the deformable-ion model disagrees with experiment by 300%. For [111] strain the crystal symmetry is so reduced that the separation of the two atoms in each unit cell is not uniquely determined from the macroscopic strain. We have used a model in which the atoms locate themselves in such a way that nearest-neighbor covalent bonds are unchanged in length by shearing strains. This "bond-bending" model is contrasted with a model in which the atomic separation changes with strain like a macroscopic vector. The latter model yields a deformation potential of opposite sign to the experimental one.
Boundary Element Analysis of the Stress Distribution Around Multiple Fractures: Implications for the Spacing of Perforation Clusters of Hydraulically Fractured Horizontal Wells (2009)

Abstract For multi-stage hydraulic fracturing of horizontal wells with casing hole completion, multiple cluster perforations are typically used to create multiple fractures in any single stage. How to place these perforations is a critical issue because the number of perforation clusters to be used and the space between them significantly impact how effective the fractures can be created in the formation. To optimize the spacing of perforation clusters, stress distributions and fracture mechanics need to be well understood. In this study, the displacement discontinuity method is used to construct a boundary element model, which is able to analyze the stress distributions around multiple transverse fractures and the geometries of these fractures. With the boundary element model, multiple cases are investigated for different number of fractures and fracture spacing. Changes of both minimum and maximum stresses, as well as shear stress around these fractures are first illustrated. It is found that for the cases with more than two parallel fractures, there is a strong stress concentration around the center fractures. The calculated displacements indicate that the created fractures are no longer elliptic-like, and the widths of the center fractures are significantly reduced compared with that of a single fracture. For the case of two parallel fractures, the stress concentration between two fractures also results in the asymmetrical shape of fractures, but the fracture widths are not reduced significantly. The study indicates that the number and spacing of the fractures need to be carefully selected in order to create effective fractures with appropriate fracture geometries. The boundary element model provides a useful tool to relate rock geomechanic properties to stress distribution and fracture geometries for multiple fractures in hydraulic fracturing of horizontal wells, which can be served as a guidance to space the perforation clusters.
Natriuretic peptides and their therapeutic potential. (2001)

Natriuretic peptides are a group of naturally occurring substances that act in the body to oppose the activity of the renin-angiotensin system. There are three major natriuretic peptides: atrial natriuretic peptide (ANP), which is synthesized in the atria; brain natriuretic peptide (BNP), which is synthesized in the ventricles; and C-type natriuretic peptide (CNP), which is synthesized in the brain. Both ANP and BNP are released in response to atrial and ventricular stretch, respectively, and will cause vasorelaxation, inhibition of aldosterone secretion in the adrenal cortex, and inhibition of renin secretion in the kidney. Both ANP and BNP will cause natriuresis and a reduction in intravascular volume, effects amplified by antagonism of antidiuretic hormone (ADH). The physiologic effects of CNP are different from those of ANP and BNP. CNP has a hypotensive effect, but no significant diuretic or natriuretic actions. Three natriuretic peptide receptors (NPRs) have been described that have different binding capacities for ANP, BNP, and CNP. Removal of the natriuretic peptides from the circulation is affected mainly by binding to clearance receptors and enzymatic degradation in the circulation. Increased blood levels of natriuretic peptides have been found in certain disease states, suggesting a role in the pathophysiology of those diseases, including congestive heart failure (CHF), systemic hypertension, and acute myocardial infarction. The natriuretic peptides also serve as disease markers and indicators of prognosis in various cardiovascular conditions. The natriuretic peptides have been used in the treatment of disease, with the most experience with intravenous BNP in the treatment of CHF. Another pharmacologic approach being used is the inhibition of natriuretic peptide metabolism by neutral endopeptidase (NEP) inhibitor drugs. The NEP inhibitors are currently being investigated as treatments for CHF and systemic hypertension.