gebhart/patrepeval huggingface dataset:
Transcription-dependent redistribution of the large subunit of RNA polymerase II to discrete nuclear domains. (1995)

A subpopulation of the largest subunit of RNA polymerase II (Pol II LS) is located in 20-50 discrete subnuclear domains that are closely linked to speckle domains, which store splicing proteins. The speckle-associated fraction of Pol II LS is hyperphosphorylated on the COOH-terminal domain (CTD), and it is highly resistant to extraction by detergents. A diffuse nucleoplasmic fraction of Pol II LS is relatively hypophosphorylated on the CTD, and it is easily extracted by detergents. In transcriptionally active nuclei, speckle bound hyperphosphorylated Pol II LS molecules are distributed in irregularly shaped speckle domains, which appear to be interconnected via a reticular network. When transcription is inhibited, hyperphosphorylated Pol II LS and splicing protein SC35 accumulate in speckle domains, which are transformed into enlarged, dot-like structures lacking interconnections. When cells are released from transcriptional inhibition, Pol IIO and SC35 redistribute back to the interconnected speckle pattern of transcriptionally active cells. The redistribution of Pol II and SC35 is synchronous, reversible, and temperature dependent. It is concluded that: (a) hyperphosphorylation of Pol II LS's CTD is a better indicator of its tight association to discrete subnuclear domains than its transcriptional activity; (b) during states of transcriptional inhibition, hyperphosphorylated Pol II LS can be stored in enlarged speckle domains, which under the light microscope appear to coincide with the storage sites for splicing proteins; and (c) Pol II and splicing proteins redistribute simultaneously according to the overall transcriptional activity of the nucleus.
Identification of an RNA-Protein Bridge Spanning the Ribosomal Subunit Interface (1999)

The 7.8 angstrom crystal structure of the 70S ribosome reveals a discrete double-helical bridge (B4) that projects from the 50S subunit, making contact with the 30S subunit. Preliminary modeling studies localized its contact site, near the bottom of the platform, to the binding site for ribosomal protein S15. Directed hydroxyl radical probing from iron(II) tethered to S15 specifically cleaved nucleotides in the 715 loop of domain II of 23S ribosomal RNA, one of the known sites in 23S ribosomal RNA that are footprinted by the 30S subunit. Reconstitution studies show that protection of the 715 loop, but none of the other 30S-dependent protections, is correlated with the presence of S15 in the 30S subunit. The 715 loop is specifically protected by binding free S15 to 50S subunits. Moreover, the previously determined structure of a homologous stem-loop from U2 small nuclear RNA fits closely to the electron density of the bridge.
A Functional Hybrid Memristor Crossbar-Array/CMOS System for Data Storage and Neuromorphic Applications (2011)

Crossbar arrays based on two-terminal resistive switches have been proposed as a leading candidate for future memory and logic applications. Here we demonstrate a high-density, fully operational hybrid crossbar/CMOS system composed of a transistor- and diode-less memristor crossbar array vertically integrated on top of a CMOS chip by taking advantage of the intrinsic nonlinear characteristics of the memristor element. The hybrid crossbar/CMOS system can reliably store complex binary and multilevel 1600 pixel bitmap images using a new programming scheme.
Using Similarity Metrics For Terminology Recognition (2008)

In this paper we present an approach to terminology recognition whereby a sublanguage term (e.g. an aircraft engine component term extracted from a maintenance log) is matched to its corresponding term from a pre-defined list (such as a taxonomy representing the official break-down of the engine). Terminology recognition is addressed as a classification task whereby the extracted term is associated to one or more potential terms in the official description list via the application of string similarity metrics. The solution described in the paper uses dynamically computed similarity cut-off thresholds calculated on the basis of modeling a noise curve. Dissimilar string matches form a Gaussian distributed noise curve that can be identified and extracted leaving only mostly similar string matches. Dynamically calculated thresholds are preferable over fixed similarity thresholds as fixed thresholds are inherently imprecise, that is, there is no similarity boundary beyond which any two strings always describe the same concept. 1.
ChemInform Abstract: Epothilones: Microtubule Stabilizing Agents with Enhanced Activity Against Multidrug‐Resistant Cell Lines and Tumors (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Scale‐up process for expression and renaturation of recombinant human epidermal growth factor from Escherichia coli inclusion bodies (2000)

A cDNA encoding mature epidermal growth factor (EGF) was isolated and cloned into a pQE30 vector in which the His(6)-tagged EGF was expressed. pH-stat feeding of concentrated medium at the time of isopropyl beta-D-thiogalactoside induction and slug-feedings of the enriched medium during the induction resulted in a higher cell density and specific expression. Using a simple refolding protocol that consisted of 1 mM L-cysteine addition for a 1-h reduction followed by 5 mM L-cystine addition for oxidative refolding, we were able to convert nearly all EGF monomers into the oxidized form. Also, there folding aggregate was converted into the monomeric form. Approx. 50% overall yield was obtained from the dissolved inclusion bodies to a single peak under FPLC. We hope that the result of this study may provide information that is useful for the scale-up of the recombinant human EGF production process.
Murine and humanized constructs of monoclonal antibody m195 (anti-cd33) for the therapy of acute myelogenous leukemia (1994)

Long-term survival rates of patients with acute myelogenous leukemia treated with intensive chemotherapy are 15–20%, despite efforts to develop new treatment strategies. Murine M195 (131I-M195), an anti-CD33, immunoglobulin (Ig) G2a monoclonal antibody has reactivity restricted to early myeloid cells and myeloid leukemic blasts but not hematopoietic progenitors. Previous trials in patients with relapsed or refractory myeloid leukemia showed that 131I-M195 rapidly targeted to the bone marrow and internalized into target cells. This article describes a therapeutic dose escalation study in which 24 patients received from 50 mCi/m2 to 210 mCi/m2 of 131I-M195 in divided doses. Cytoreduction of peripheral cell counts and bone marrow blasts occurred without nonhematopoietic toxicity. Doses of 131I-M195 greater than 135 mCi/m2 were associated with marrow cytoreduction sufficient to necessitate bone marrow transplant. However, 37% of the patients developed human anti-mouse antibody, preventing retreatment. To decrease immunogenicity and improve effector function, chimeric IgG1 and IgG3, and complementarity-determining region-grafted, humanized IgG1 and IgG3 versions of mouse M195 were developed by genetic engineering techniques. The new versions maintained specificity and biologic function, and they were superior to the mouse M195 in their ability to perform antibody-dependent cellular cytotoxicity against leukemia cells. Humanized M195, but not chimeric M195, showed a 4–8.6 times higher avidity than its mouse counterpart. Because effector function of IgG depends to a large extent on Fc clustering, a homodimeric HuG1 also was developed. Homodimeric HuG1 showed an ability to cause additional dramatic improvements in effector functions, as well as an ability to internalize and retain radioisotope in target leukemia cells. Monomeric and dimeric forms of humanized M195 may be advantageous in the therapy of acute myelogenous leukemia. Cancer 1994; 73:1049–56.
Design of Biocompatible Chitosan Microgels for Targeted pH-Mediated Intracellular Release of Cancer Therapeutics (2006)

We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.
Native cartilage matrix protein (CMP). A compact trimer of subunits assembled via a coiled-coil alpha-helix. (1994)

Cartilage matrix protein (CMP), a major component of many types of cartilage, is a noncollagenous glycoprotein with a molecular mass of 148 kDa consisting of three identical subunits. With the aim of performing a more comprehensive characterization, we purified CMP in a native conformation from fetal bovine rib cartilage avoiding the denaturing solvents previously used. CMP could be selectively extracted with EDTA-containing buffer which indicates a divalent cation-dependent anchorage in the cartilage matrix. Determination of the amino-terminal sequence of the bovine protein confirmed its identity when compared with published cDNA sequences of chicken and human CMP. Electron microscopy revealed the presence of three ellipsoid subunits which are connected at one end. Sequence analysis indicated the presence of a coiled-coil alpha-helical assembly domain formed by the COOH-terminal end of the subunits. The trimeric structure was retained after complete reduction under native conditions which shows that the coiled-coil domain is stable also in the absence of interchain disulfide bonds.
Co-fermentation withPichia kluyveriincreases varietal thiol concentrations in Sauvignon Blanc (2008)

Background and Aims: Volatile varietal thiols are one class of yeast metabolite that add aroma/flavour to Sauvignon Blanc, particularly to the Marlborough style from New Zealand. While various strains of Saccharomyces cerevisiae are known to liberate such thiols, there are no data examining whether non-Saccharomyces species effect concentrations of these thiols in wine. Methods and Results: We screened a variety of New Zealand wine yeast isolates and found some that were able to liberate either 3-mercaptohexan-1-ol (3MH) or 3-mercaptohexyl acetate (3MHA). We show that co-fermentation with specific commercial strains and an isolate of Pichia kluyveri from New Zealand, at a 1:9 starting ratio, significantly enhances the 3MHA concentrations in Sauvignon Blanc compared with single species ferments. Conclusions: Co-fermentation with this isolate of P. kluyveri may provide a means to elevate 3MHA concentrations in Sauvignon Blanc; the mechanism behind this increase is unknown. Significance of the Study: Techniques that allow the predictable manipulation of varietal thiols potentially provide tools for winemakers to alter wine style without the use of genetically modified organisms.
DNA bending by the bulge defect (1989)

Comparative gel electrophoresis measurements were used to characterize DNA bending in molecules containing an extra adenosine on one strand, the so-called bulge defect. We used oligomers containing A6 tracts separated from the bulged base by varying numbers of nucleotides to determine the direction and magnitude of the bulge bend. Helix unwinding by the bulge was determined from the electrophoretic anomaly as a function of the size of the repeated monomers. We conclude that the bulge bend is 21 degrees +/- 3 degrees, primarily in the direction of tilt away from the bulged base. The total helical advance of the DNA at the bulge site is smaller than would be the case if the complementary T were present, corresponding to an unwinding by 25 degrees +/- 6 degrees. These values are in good agreement with the results of NMR and energy minimization studies of the bulged base in double-helical deoxyoligonucleotides [Woodson, S. A., & Crothers, D.M. (1988) Biochemistry 27, 3130-3141]
The adult hair follicle: Cradle for pluripotent neural crest stem cells (2004)

This review focuses on the recent identification of two novel neural crest-derived cells in the adult mammalian hair follicle, pluripotent stem cells, and Merkel cells. Wnt1-cre/R26R compound transgenic mice, which in the periphery express beta-galactosidase in a neural crest-specific manner, were used to trace neural crest cells. Neural crest cells invade the facial epidermis as early as embryonic day 9.5. Neural crest-derived cells are present along the entire extent of the whisker follicle. This includes the bulge area, an epidermal niche for keratinocyte stem cells, as well as the matrix at the base of the hair follicle. We have determined by in vitro clonal analysis that the bulge area of the adult whisker follicle contains pluripotent neural crest stem cells. In culture, beta-galactosidase-positive cells emigrate from bulge explants, identifying them as neural crest-derived cells. When these cells are resuspended and grown in clonal culture, they give rise to colonies that contain multiple differentiated cell types, including neurons, Schwann cells, smooth muscle cells, pigment cells, chondrocytes, and possibly other types of cells. This result provides evidence for the pluripotentiality of the clone-forming cell. Serial cloning showed that bulge-derived neural crest cells undergo self-renewal, which identifies them as stem cells. Pluripotent neural crest cells are also localized in the back skin hair of adult mice. The bulge area of the whisker follicle is surrounded by numerous Merkel cells, which together with innervating nerve endings form slowly adapting mechanoreceptors that transduce steady skin indentation. Merkel cells express beta-galactosidase in double transgenic mice, which confirms their neural crest origin. Taken together, our data indicate that the epidermis of the adult hair follicle contains pluripotent neural crest stem cells, termed epidermal neural crest stem cells (eNCSCs), and one newly identified neural crest derivative, the Merkel cell. The intrinsic high degree of plasticity of eNCSCs and the fact that they are easily accessible in the skin make them attractive candidates for diverse autologous cell therapy strategies.
Expression Vector for Zymomonas mobilis (1987)

This study describes the construction of several useful cloning vectors which can be conjugated from Escherichia coli into Zymomonas mobilis at high frequency, approaching 10 per donor or recipient. These vectors contain a broad-host-range replicon and mob site from RSF1010, a chloramphenicol acyltransferase gene under the control of an enteric consensus promoter, and a second mob site (originally derived from RP4). The addition of this second mob site appears to be responsible for a 2-order-of-magnitude increase in the efficiency of transfer into Z. mobilis. Such vectors may be useful for other gram-negative bacteria in which conjugation efficiencies are low. These vectors are stably maintained in Z. mobilis with no detectable loss of plasmid after 50 generations in the absence of selective pressure. One of these, pLOI193, contains the tetracycline gene from pBR322 and associated cloning sites for insertional inactivation. Another, pLOI204, contains a Z. mobilis promoter immediately upstream from a BamHI site which can be used for cloning. This promoter has been shown to efficiently drive the expression of beta-galactosidase in both Z. mobilis and E. coli. This promoter fragment from Z. mobilis has been sequenced, and the site for transcriptional initiation in E. coli and Z. mobilis has been identified.
The Effect of Chondrocyte Growth Factor on Membrane Transport by Articular Chondrocytes in Monolayer Culture (1978)

Chondrocyte growth factor (CGF), a contaminant of pituitary glycoprotein hormones, stimulates growth of cultured lapine articular chondrocytes while depressing SO4-proteoglycan synthesis. To study its effect on membrane transport, NIH-bTSH and two other preparations with comparable CGF activity were employed. In early log phase (36 hr) cultures CGF (64 microgram/ml) did not alter thymidine (dThd) uptake during the first 5 min. By 15 min however, TCA-precipitable dThd was 4-fold greater than in controls while the TCA-soluble fraction remained the same. CGF increased deoxy-glucose (DG) uptake in 36-hr old cultures. At 66 hr, CGF reduced DG transport. The transport of cycloleucine (CL) and aminoisobutyric acid (AIB) was reduced by CGF in 36 and 66-hr old cultures. There was a dose dependency between CGF concentration, the lowered uptake of DG, CL and AIB, and cell protein content. The effect of CGF on DG transport and dThd incorporation into DNA was not immediate but required prior exposure of the cells to CGF. CGF did not alter DG transport in rabbit or mouse fibrocytes or Chang liver cells. This and the reported finding that pituitary fibroblast growth factor (FGF), increases amino acid transport in other cells suggests that the biological specificity of CGF may not be identical to that of FGF.
From steam engine to solar cells: can thermodynamics guide the development of future generations of photovoltaics? (2016)

Thermodynamics has played a singular role in the development of virtually all energy technologies to‐date. This review argues that it also has a role to play in the understanding and design of solar cell operation, particularly looking toward the future, high‐efficiency solar cells. After a historical overview of the key developments in the ‘thermodynamics of light,’ the conversion of a monochromatic light beam is used as a starting point to analyze the conversion process, examine the fundamental losses in terms of irreversible entropy generation, and consider in detail one of the key applications: the Shockley–Queisser detailed balance. We review and compare the principal suggestions for the highest theoretical efficiency of solar energy conversion, and analyze one possible embodiment of such a third‐generation structure: the hot‐carrier solar cell. A somewhat different application of the statistical approach—light trapping—is reviewed at a fundamental level, and the future potential is considered for devices which combine such a ‘thermodynamic squeezing’ of light with latest developments in photonics, leading to a photonic bandgap solar cell. We argue that the widespread use of thermodynamic tools in the current photovoltaics research, especially when combined with the potential benefits to future devices, already indicates that our thinking should not be about if but how thermodynamics can guide us to make better solar cells. WIREs Energy Environ 2016, 5:543–569. doi: 10.1002/wene.204 This article is categorized under: Photovoltaics &gt; Science and Materials Solar Heating and Cooling &gt; Science and Materials
A Heterodimeric Fc-Based Bispecific Antibody Simultaneously Targeting VEGFR-2 and Met Exhibits Potent Antitumor Activity (2013)

Heterodimeric Fc designed by engineering the CH3 homodimeric interface of immunoglobulin G1 serves as an attractive scaffold for the generation of bispecific antibodies (bsAb) due to the favorable properties of the Fc region. In this study, we describe a heterodimeric Fc generated by substituting the conserved electrostatic interactions at the CH3 core interface with asymmetric hydrophobic interactions and introducing asymmetric, long-range electrostatic interactions at the rim of the CH3 interface. Coexpression of Fc proteins carrying the combined CH3 variant pairs in HEK293F cells produced the heterodimer, which was purified with more than 90% yield, and retained wild-type Fc biophysical properties. The heterodimeric Fc was exploited to generate a bsAb simultaneously targeting both the Met receptor tyrosine kinase and the VEGF receptor 2 (VEGFR-2), with two respective antigen-specific, single-chain variable fragments (scFv) into the N-terminus. The Met × VEGFR-2 bsAb bound concurrently to the two target antigens, efficiently inhibited the downstream signaling and tube formation stimulated by the two receptors in human endothelial cells, and exhibited more potent antitumor efficacy in MKN45 human gastric cancer xenograft models than both the parent monospecific antibody alone. Collectively, based on the newly designed heterodimeric Fc-based bsAb, our results provide the therapeutic potential of bsAb targeting both Met and VEGFR-2 simultaneously for the treatment of human cancers.
"Misfits" and the Celebration of Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Youth At a High School in the United States (2018)

As part of a six-month case study, this article delineated the relationship between homonormativity and the victimization of students in a high school in the United States by investigating the strategies of policing, resistance, and queering. Not only do these strategies reappropriate practices inherent in homonormative practices, these strategies reconfigure practices associated with heteronormativity and homophobia. The undercurrent of this research highlights how schools marginalize identities in some spaces and elevate identities in other spaces, the socio-political readings of that positioning, and what educators can do to promote an inclusive environment for all students.
Immunosuppressive Strategies that are Mediated by Tumor Cells (2006)

Despite major advances in understanding the mechanisms leading to tumor immunity, a number of obstacles hinder the successful translation of mechanistic insights into effective tumor immunotherapy. Such obstacles include the ability of tumors to foster a tolerant microenvironment and the activation of a plethora of immunosuppressive mechanisms, which may act in concert to counteract effective immune responses. Here we discuss different strategies employed by tumors to thwart immune responses, including tumor-induced impairment of antigen presentation, the activation of negative costimulatory signals, and the elaboration of immunosuppressive factors. In addition, we underscore the influence of regulatory cell populations that may contribute to this immunosuppressive network; these include regulatory T cells, natural killer T cells, and distinct subsets of immature and mature dendritic cells. The current wealth of preclinical information promises a future scenario in which the synchronized blockade of immunosuppressive mechanisms may be effective in combination with other conventional strategies to overcome immunological tolerance and promote tumor regression.
Evolving Strategies for Protein Synthesis Converge on Native Chemical Ligation (2006)

Build a bridge: Although used widely, certain limitations of popular protein assembly strategies such as native chemical ligation (NCL) have persisted. This highlight presents the results of recent reports that tackle these limitations (see picture). Aux=auxiliary.