gebhart/patrepeval huggingface dataset:
Ribozymes as therapeutic tools for genetic disease (1998)

The discovery that RNA can act as a biological catalyst, as well as a genetic molecule, indicated that there was a time when biological reactions were catalysed in the absence of protein-based enzymes. It also provided the platform to develop those catalytic RNA molecules, called ribozymes, as trans -acting tools for RNA manipulation. Viral diseases or diseases due to genetic lesions could be targeted therapeutically through ribozymes, provided that the sequence of the genetic information involved in the disease is known. The hammerhead ribozyme, one of the smallest ribozymes identified, is able to induce site-specific cleavage of RNA, with ribozyme and substrate being two different oligoribonucleotides with regions of complementarity. Its ability to down-regulate gene expression through RNA cleavage makes the hammerhead ribozyme a candidate for genetic therapy. This could be particularly useful for dominant genetic diseases by down-regulating the expression of mutant alleles. The group I intron ribozyme, on the other hand, is capable of site-specific RNA trans -splicing. It can be engineered to replace part of an RNA with sequence attached to its 3' end. Such application may have importance in the repair of mutant mRNA molecules giving rise to genetic diseases. However, to achieve successful ribozyme-mediated RNA-directed therapy, several parameters including ribozyme stability, activity and efficient delivery must be considered. Ribozymes are promising genetic therapy agents and should, in the future, play an important role in designing strategies for the therapy of genetic diseases.
Mexican marital endogamy and educational homogamy in the USA, 1980-2000: a case of social closure? (2009)

The high rates of Mexican immigration into the United States in recent decades raises questions about marital assimilation and social closure. We use data for approximately two million couples aged 30-39 from the 1980, 1990 and 2000 IPUMS census samples for the USA to analyze the demographic and social dynamics of ethnic endogamy and educational homogamy (N = 2,019,754). Log-linear models leave no doubt that endogamy remains the rule among the Mexican-born, Mexican-origin and Non-Hispanic Whites—both at the national and local levels (~2,000 PUMAS). The increase in endogamy among the Mexican-born, while significant, does not portend the emergence of social closure, perhaps not even a trend. Post-secondary education substantially weakens the endogamy rule for all three groups. The gender squeeze (more Mexican born males than females) forces the ruleto be broken in a large fraction of cases. 2010 census microdata will provide an important test of these findings.
Differential Reactivity of Maleimide and Bromoacetyl Functions with Thiols: Application to the Preparation of Liposomal Diepitope Constructs (1999)

The comparative reactivity of maleimide and bromoacetyl groups with thiols (2-mercaptoethanol, free cysteine, and cysteine residues present at the N-terminus of peptides) was investigated in aqueous media. These studies were performed (i) with water-soluble functionalized model molecules, i.e., polyoxyethylene-based spacer arms that could also be coupled to lipophilic anchors destined to be incorporated into liposomes, and (ii) with small unilamellar liposomes carrying at their surface these thiol-reactive functions. Our results indicate that an important kinetic discrimination (2-3 orders of magnitude in terms of rate constants) can be achieved between the maleimide and bromoacetyl functions when the reactions with thiols are performed at pH 6.5. The bromoacetyl function which reacts at higher pH values (e.g., pH 9.0) retained a high chemoselectivity; i.e., under conditions where it reacted appreciably with the thiols of, e.g., HS-peptides, it did react with other nucleophilic functions such as alpha- and epsilon-amino groups or imidazole, which could also be present in peptides. This differential reactivity was applied to design chemically defined and highly immunogenic liposomal diepitope constructs as synthetic vaccines, i.e., vesicles carrying at their surface two different peptides conjugated each to a specific amphiphilic anchor. This was realized by coupling sequentially at pH 6.5 and 9.0 two HS-peptides to preformed vesicles containing lipophilic anchors functionalized with maleimide and bromoacetyl groups [Boeckler, C., et al. (1999) Eur. J. Immunol. 29, 2297-2308].
Difference in the induction of macrophage interleukin-1 production between viable and killed cells of Listeria monocytogenes (1990)

T-cell-mediated immunity to Listeria monocytogenes in mice, as determined by delayed-type hypersensitivity and acquired resistance, was induced by immunization with viable bacteria but not with killed bacteria, even when killed cells were injected in a high dose or repeatedly. T cells obtained from mice immunized with viable L. monocytogenes were readily stimulated with killed-bacterial antigens, resulting in T-cell proliferation in vitro and expression of a delayed footpad reaction in vivo. After immunization with killed-bacterial vaccine, T-cell responsiveness to interleukin 2 (IL-2) never developed but a lower level of responsiveness to IL-1 appeared later than with T cells from mice immunized with viable bacteria. When IL-1 production by macrophages was examined in vitro, viable L. monocytogenes stimulated a high level of IL-1 release while killed bacteria did not. Avirulent strains which were ineffective in the induction of T-cell mediated immunity were incapable of inducing IL-1 production as well. The impaired ability of killed bacteria to stimulate IL-1 production was confirmed by the level of IL-1 mRNA expression. These results suggested that the ineffectiveness of killed L. monocytogenes vaccine is not due to loss or lack of antigenic epitopes but may be ascribed to insufficient induction of IL-1 production in the initial stage of the immune response in vivo.
Calmodulin Trapping by Calcium-Calmodulin-Dependent Protein Kinase (1992)

Multifunctional calcium-calmodulin-dependent protein kinase (CaM kinase) transduces transient elevations in intracellular calcium into changes in the phosphorylation state and activity of target proteins. By fluorescence emission anisotropy, the affinity of CaM kinase for dansylated calmodulin was measured and found to increase 1000 times after autophosphorylation of the threonine at position 286 of the protein. Autophosphorylation markedly slowed the release of bound calcium-calmodulin; the release time increased from less than a second to several hundred seconds. In essence, calmodulin is trapped by autophosphorylation. The shift in affinity does not occur in a site-directed mutant in which threonine at position 286 has been replaced by a non-phosphorylatable amino acid. These experiments demonstrate the existence of a new state in which calmodulin is bound to CaM kinase even though the concentration of calcium is basal. Calmodulin trapping provides for molecular potentiation of calcium transients and may enable detection of their frequency.
Pharmacology of Valproate (2015)

Valproate has been in clinical use for nearly 40 years for the treatment of a variety of neuropsychiatric illnesses, including bipolar disorder and epilepsy. Early reports linked its biochemical mechanism of action to alterations in gamma-aminobutyric acid (GABA)-ergic function. The definitive mechanism(s) mediating the clinical efficacy of this relatively simple molecule remain obscure. Although valproate does not directly interact with postsynaptic GABA receptors, it does increase regional neuronal concentrations of GABA by both inhibiting its metabolism and increasing its synthesis. The relevance of these effects to the clinical efficacy of valproate is unclear. Results of preclinical research, largely in rodents, have implicated ion channels, monoamines, corticotropin-releasing factor, and intracellular signaling proteins in the mechanism of action of valproate. This relative dearth of data in the area of valproate neuropharmacology is also evident when discussing the mechanism( s) of action of other mood stabilizers and anticonvulsants. Modern tools of basic and clinical neuroscience (eg, genomics, proteomics, functional brain imaging) will rapidly provide valuable insights into the precise mechanism(s) of action of valproate.
DC-field-driven combustion waves for one-step fabrication of reduced manganese oxide/multi-walled carbon nanotube hybrid nanostructures as high-performance supercapacitor electrodes (2017)

DC field-driven combustion waves enable one-step fabrication of heterogeneously reduced, nanostructured electrodes for high-performance supercapacitors.
Solution Conformation of an Intramolecular DNA Triplex Containing a Nonnucleotide Linker:  Comparison with the DNA Duplex (1997)

The solution properties of the parallel intramolecular DNA triplex d(GAGAGA-oct-TCTCTC-oct-CTCTCT) (oct = -O-(CH2)8-O-PO2-O-(CH2)8-O-PO2-) and the duplex d(GAGAGA-oct-TCTCTC) have been examined by UV melting and high-resolution nuclear magnetic resonance spectroscopy (NMR). All nucleotides were primarily in the S conformation (i.e. near C2'-endo) in both the duplex and the triplex. However, the sugars of the Hoogsteen pyrimidine strand had a lower fraction of the S state than the Watson-Crick strands. Glycosidic torsion angles derived from nuclear Overhauser effect (NOE) build-up curves were found in the range -103 degrees to -133 degrees, with a clear alternation in magnitude along the GAGAGA strand in the triplex, whereas the glycosidic torsion angles were more similar in the duplex. Internucleotide NOEs were also consistent with an overall B-like geometry, rather than the A family. However, particularly in the Hoogsteen strand, some sequential NOE intensities were intermediate between those of the B and A forms. Distance and torsion constraints derived from NMR experiments were used to generate structures and were refined by restrained molecular dynamics. Extensive chemical shift differences between residues in the triplex and duplex were found for the purine strand, and there were remarkable differences in the pattern of shift differences for the A and G residues that correlated with differences in glycosidic torsion angles. Although there are differences in structure between the free duplex and that in the triplex, they are in important respects similar, indicating that only small conformational adjustments are needed to make parallel triple helices.
LightWave (2011)

In this paper, we describe LightWave, a sensing approach that turns ordinary compact fluorescent light (CFL) bulbs into sensors of human proximity. Unmodified CFL bulbs are shown to be sensitive proximity transducers when they are illuminated. This approach utilizes predictable variations in electromagnetic noise resulting from the change in impedance due to the proximity of a human body to the bulb. The electromagnetic noise can be sensed from any point along a home's electrical wiring. This allows users to perform gestures near any CFL lighting fixture, even when multiple lamps are operational. Gestures can be sensed using a single interface device plugged into any electrical outlet. We experimentally show that we can reliably detect hover gestures (waving a hand close to a lamp), touches on lampshades, and touches on the glass part of the bulb itself. Additionally, we show that touches anywhere along the body of a metal lamp can be detected. These basic detectable signals can then be combined to form complex gesture sequences for a variety of applications. We also show that CFLs can function as more general-purpose sensors for distributed human motion detection and ambient temperature sensing.
Phantom evaluation of an image-guided navigation system based on electromagnetic tracking and open source software (2008)

We have developed an image-guided navigation system using electromagnetically-tracked tools, with potential applications for abdominal procedures such as biopsies, radiofrequency ablations, and radioactive seed placements. We present the results of two phantom studies using our navigation system in a clinical environment. In the first study, a physician and medical resident performed a total of 18 targeting passes in the abdomen of an anthropomorphic phantom based solely upon image guidance. The distance between the target and needle tip location was measured based on confirmatory scans which gave an average of 3.56 mm. In the second study, three foam nodules were placed at different depths in a gelatin phantom. Ten targeting passes were attempted in each of the three depths. Final distances between the target and needle tip were measured which gave an average of 3.00 mm. In addition to these targeting studies, we discuss our refinement to the standard four-quadrant image-guided navigation user interface, based on clinician preferences. We believe these refinements increase the usability of our system while decreasing targeting error.
Industrial MEMS on SOI (2000)

The industrial use of silicon on insulator (SOI) substrates is quickly spreading. For microelectronics applications, this material brings new functionality, such as radiation-hard, high-voltage or low-voltage and low-consumption integrated circuits. Industrial wafers are now commercially available and new technologies, such as Smart Cut® from SOITEC company, will provide low prices in high-volume production. SOI also provides very important features for microelectromechanical systems (MEMS) and new industrial products, such as high-temperature and low-noise piezoresistive pressure sensors or miniature high-performance capacitive pressure and acceleration sensors, are now proposed. These new generic technologies will provide various industrial products in the near future.
Hydrocortisone Dosing during Puberty in Patients with Classical Congenital Adrenal Hyperplasia: An Evidence-Based Recommendation (2009)

With conventional hydrocortisone treatment, pubertal growth is significantly reduced in both sexes, resulting in a FH at the lower limit of genetic potential. These deleterious effects on pubertal growth can be reduced if hydrocortisone does not exceed 17 mg/m(2).
MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25) (1999)

MLL (ALL1, Htrx, HRX), which is located on chromosome band 11q23, frequently is rearranged in patients with therapy-related acute myeloid leukemia who previously were treated with DNA topoisomerase II inhibitors. In this study, we have identified a fusion partner of MLL in a 10-year-old female who developed therapy-related acute myeloid leukemia 17 months after treatment for Hodgkin's disease. Leukemia cells of this patient had a t(11;17)(q23;q25), which involved MLL as demonstrated by Southern blot analysis. The partner gene was cloned from cDNA of the leukemia cells by use of a combination of adapter reverse transcriptase-PCR, rapid amplification of 5' cDNA ends, and BLAST database analysis to identify expressed sequence tags. The full-length cDNA of 2.8 kb was found to be an additional member of the septin family, therefore it was named MSF (MLL septin-like fusion). Members of the septin family conserve the GTP binding domain, localize in the cytoplasm, and interact with cytoskeletal filaments. A major 4-kb transcript of MSF was expressed ubiquitously; a 1.7-kb transcript was found in most tissues. An additional 3-kb transcript was found only in hematopoietic tissues. By amplification with MLL exon 5 forward primer and reverse primers in MSF, the appropriately sized products were obtained. MSF is highly homologous to hCDCrel-1, which is a partner gene of MLL in leukemias with a t(11;22)(q23;q11.2). Further analysis of MSF may help to delineate the function of MLL partner genes in leukemia, particularly in therapy-related leukemia.
Novel fibre amplifier configuration suitable for bidirectional system (1992)

A novel configuration of erbium-doped fibre amplifier, in which an optical circulator is used as the wavelength multiplexing device, is proposed and tested experimentally. The experimental results show that the proposed configuration is insensitive to reflections, and suitable for both bidirectional amplification and OTDR fault location.
Use of Cortical Surface Vessel Registration for Image-guided Neurosurgery (1997)

Video registration using cortical surface vessels is practical and improves two-dimensional projection accuracy significantly, compared with skin registration.
Electrical Impedance Tomography (2004)

Objective: The distribution of ventilation within the lung is inhomogeneous.We hypothesized that the degree of inhomogeneity in patients with cystic fibrosis (CF) differs from that in healthy subjects.Method: Three adult patients with cystic fibrosis (CF) and two healthy subjects were recruited for this preliminary study.Subjects were asked to breathe in as deep and exhale as hard as possible three times.Electrical impedance tomography (EIT) measurements were performed during spirometry tests.The global inhomogeneity index(GI) was applied to assess the degree of ventilation homogeneity at 25%, 50%, 75% and 100% of maximum inspiratory volume.Results: Airway obstruction was detected in CF patients but not in healthy volunteers during spirometry tests.GI decreased as inspiratory volume increased in CF patients (0.59±0.20 at 25% and 0.39±0.09at 100%, p<0.01, mean±SD) while GI remained unchanged in healthy subjects (0.40±0.05 at 25% and 0.37±0.03at 100%, p=0.31).Conclusion: Degree of ventilation homogeneity appears to vary during forced respiration in CF patients, but not in healthy volunteers.EIT is a practical method to measure the inhomogeneity of ventilation distribution.
Ten Strategies for Getting Students to Take Responsibility for Their Learning (2003)

Abstract This article presents ten strategies instructors can use to get their students to take more responsibility for their learning. Suggestions are given about the importance of getting students to verbalize why they are taking the course, helping students get into the proper mindset for each class, and structuring assignments so students will be more likely to come to class prepared. Other suggestions include teaching students to look out for each other, behave responsibly when working in groups, and analyze their learning experiences. By teaching responsibility, as well as content, in our classrooms, we can enhance learning, raise the level of our classrooms, and produce more responsible members of society.
Label-free cell nuclear imaging by Grüneisen relaxation photoacoustic microscopy (2018)

Photoacoustic microscopy (PAM) with ultraviolet (UV) laser illumination has recently been demonstrated as a promising tool that provides fast, label-free, and multilayered histologic imaging of human breast tissue. Thus far, the axial resolution has been determined ultrasonically. To enable optically defined axial resolution, we exploit the Grüneisen relaxation (GR) effect. By imaging mouse brain slices, we show that GRUV-PAM reveals detailed information about three-dimensional cell nuclear distributions and internal structures, which are important diagnostic features for cancers. Due to the nonlinear effect, GRUV-PAM also provides better contrast in images of cell nuclei.
Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood (2002)

CD4(+) CD25(+) regulatory T cells prevent organ-specific autoimmune diseases in various animal models. We analysed human lymphoid tissues to identify similar CD25(+) regulatory T cells. Adult peripheral blood contained two populations of CD4(+) T cells that expressed CD25 at different densities. The larger population (approximately 40%) expressed intermediate levels of CD25 (CD25(+)) and displayed a memory T-cell phenotype (CD45RA-/RO(+), CD45RB(low), CD95(+), CD62L(low), CD38(low)). The smaller population of cells (approximately 2%) expressed very high levels of CD25 (CD25(++)). In addition to the activation/memory T-cell antigens mentioned above they also expressed intracellular CD152 (CTLA-4) as well as enhanced levels of cell-surface CD122, similar to the murine CD4(+) CD25(+) regulatory counterpart. To exclude that the CD25(++) cells had not been recently primed by external antigen we analysed cord blood and thymus. CD25(++), CD152(+) and CD122(++) cells were present in paediatric thymus (10% of CD4(+) CD8(-) thymocytes) expressing signs of recent selection (CD69+) and in cord blood (5% of CD4(+) cells) where they showed a naive phenotype. In addition, cord blood contained a small population of CD25(+) cells (approximately 2% of CD4 T cells) that were CD152(-) and CD122(low) and displayed signs of activation. Together with published data that CD25(+) CD25(++) cells from the thymus and peripheral blood are regulatory, our results suggest that regulatory CD25(+) T cells leave the thymus in a naïve state and become activated in the periphery.
Effect of sodium butyrate on the antiviral and anticellular action of interferon in normal and MSV‐transformed cells (1979)

Sodium butyrate enhances the antiviral and anticellular action of interferon in MSV-transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate-induced elaboration of the microtubule and microfilament network.
Identification of Novel Brain Biomarkers (2006)

The use of relative mRNA production appears to be a valid method of identifying possible biomarkers of tissue injury. The tissue specificity suggested by gene expression was confirmed by Western blot. One of the biomarkers identified, VLP-1, was increased in a rat model of stroke and in plasma of patients after stroke. More extensive, prospective studies of the candidate biomarkers identified appear warranted.
AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer (2020)

Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate that constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis in Trp53ΔIEC mice (Trp53ΔIECAktE17K) upon challenge with the carcinogen azoxymethane. Gene-expression profiling indicates that Trp53ΔIECAktE17K tumors resemble the human mesenchymal colorectal cancer subtype (CMS4), which is characterized by the poorest survival rate among the four CMSs. Trp53ΔIECAktE17K tumor cells are characterized by Notch3 up-regulation, and treatment of Trp53ΔIECAktE17K mice with a NOTCH3-inhibiting antibody reduces invasion and metastasis. In CRC patients, NOTCH3 expression correlates positively with tumor grading and the presence of lymph node as well as distant metastases and is specifically up-regulated in CMS4 tumors. Therefore, we suggest NOTCH3 as a putative target for advanced CMS4 CRC patients.
Proapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α (2006)

Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response-termed the unfolded protein response (UPR)-mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme-1alpha (IRE1alpha). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1alpha signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1alpha that was essential for IRE1alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR.