gebhart/patrepeval huggingface dataset:
Structural Properties of Dibenzosuberanylpiperazine Derivatives for Efficient Reversal of Chloroquine Resistance in Plasmodium chabaudi (2003)

For the purpose of developing chemosensitizers to reverse chloroquine (CQ) resistance in Plasmodium chabaudi in vivo, dibenzosuberanylpiperazine (1-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)piperazine) (DSP) and its piperazin-1-yl derivatives were synthesized systematically. DSP hydrochloride (3) was obtained from the reaction of dibenzosuberanyl chloride with piperazine in the presence of 1,8-diazabicyclo[5,4,0]-7-undecene (DBU). To understand the relationship between the substituent patterns of DSP derivatives and their biological activities, 13 hydroxyalkyl or hydroxyalkenyl derivatives were synthesized by an attack of the piperazine secondary amine of 3 on commercially available epoxides in the presence of triethylamine or DBU, and three alkyl or alkynyl derivatives were synthesized by the reactions of 3 with the corresponding organic chlorides in the presence of DBU. In both reactions, the yield was a maximum of 90%. The biological activities of the synthesized compounds were evaluated on the basis of two values: antimalarial activity and reversal activity. The values of antimalarial activities by single administration of 17 test compounds were not effective, being in the range 67-152% on day 4 after infection of Plasmodium chabaudi to mice except for the administration of 3-(dibenzosuberanylpiperazin-1-yl)-1-butene (29, 22%). On the other hand, administration of the seven test compounds (50 mg/kg dose) combined with CQ (3-4 mg/kg) gave high reversal activities, namely, low values (0% on day 4). The effective test compounds were those obtained by introducing the following substituents: 2-hydroxybutyl (24), 2-hydroxyhexen-5-yl (27), 2-hydroxybuten-3-yl (28a), 2-substituted 1-hydroxybuten-3-yl (28b), 4-acetoxybutyn-2-yl (30), 4-hydroxybutyn-2-yl (31), and 3-substituted buten-1-yl (29), which correspond to the nonbulky groups of hydroxyalkyl (C4), hydroxyalkenyl (C4-C6), hydroxyalkynyl (C4), or alkenyl (C4). These results may lead to the development of an approach to developing clinically applicable chemosensitizers for drug-resistant malaria.
First Principles Optimization of Opto-Electronic Communication Links (2017)

We introduce a first principles, end-to-end analysis of opto-electronic communication links which incorporates a thorough model of the receiver circuitry, in addition to the more familiar laser transmitter optimization. In particular, we optimize receiver sensitivity and power by studying their dependence on front-end design as well as follow-on digital sampler requirements. We find that the photo-receiver sensitivity is the most important factor in controlling the overall link power consumption. Our physical model and circuit optimization principles are applied to a heterogenous-integrated photonic+CMOS platform, where we show state-of-the-art performance through this physics-based rapid-design protocol. Incidentally this greatly simplifies the design process. Lastly, we apply this approach to extrapolate future performance trends, platform bottlenecks, and fundamental limits in optical link design while showcasing the potential for sub-1fJ/bit system efficiency at high speeds.
High-field transport of inversion-layer electrons and holes including velocity overshoot (1997)

In this paper, we experimentally address the effect of a wide range of parameters on the high-field transport of inversion-layer electrons and holes. The studied parameters include substrate doping level, surface micro-roughness, vertical field strength, nitridation of the gate oxide, and device channel length. We employ special test structures built on Silicon-On-Insulator (SOI) and bulk wafers to accurately measure the high-field drift velocity of inversion-layer carriers. Our findings point to electron velocity overshoot at room temperature, dependence of electron and hole saturation velocities on nitridation of the gate oxide, dependence of the high-field drift velocity on the effective vertical field, and relative insensitivity of electron and hole mobility and saturation velocity to moderate surface roughness.
A Ca2(+)-activated K+ current in ras-transformed fibroblasts is absent from nontransformed cells (1991)

Biochemical similarities between ras proteins and the GTP-binding proteins and correlation of ras-induced cell transformation with altered transmembrane cation fluxes indicate that ras proteins may act to modulate ion channel activity. To test this idea, whole cell, tight-seal, patch-clamp recording was used to compare macroscopic currents of ras-transformed fibroblasts with currents of their nontransformed counterparts. A prominent calcium-activated, voltage-independent potassium current was observed in 83-100% of cells from three separate fibroblast lines transformed by two different oncogenic ras alleles, whereas the same current was present at much smaller amplitudes in only 0-15% of nontransformed cells. The calcium-activated potassium current is blocked by charybdotoxin and by concentrations of tetraethylammonium above 1 mM, but it is insensitive to apamin. Both normal and ras-transformed cells have another calcium-activated current that is not potassium selective, and, consistent with other studies, normal cells display a voltage-activated calcium conductance. These results suggest that the mechanisms by which ras triggers or maintains cell transformation may involve alterations in the number or activity of certain ion channels, in particular, a type of calcium-activated potassium channel.
Human erythropoietin dimers with markedly enhancedin vivo activity (1998)

Human erythropoietin, a widely used and important therapeutic glycoprotein, has a relatively short plasma half-life due to clearance by glomerular filtration as well as by other mechanisms. We hypothesized that an erythropoietin species with a larger molecular size would exhibit an increased plasma half-life and, potentially, an enhanced biological activity. We now report the production of biologically active erythropoietin dimers and trimers by chemical crosslinking of the conventional monomeric form. We imparted free sulfhydryl residues to a pool of erythropoietin monomer by chemical modification. A second pool was reacted with another modifying reagent to yield monomer with maleimido groups. Upon mixing these two pools, covalently linked dimers and trimers were formed that were biologically active in vitro. The plasma half-life of erythropoietin dimers in rabbits was >24 h compared with 4 h for the monomers. Importantly, erythropoietin dimers were biologically active in vivo as shown by their ability to increase the hematocrits of mice when injected subcutaneously. In addition, the dimers exhibited >26-fold higher activity in vivo than did the monomers and were very effective after only one dose. Dimeric and other oligomeric forms of Epo may have an important role in therapy.
Over-expression of 14-3-3zeta is an early event in oral cancer (2007)

Our findings suggest that over-expression of 14-3-3zeta is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3zeta may serve as an important molecular target for designing novel therapy for oral cancer.
Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis (2005)

Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae. These factors induce the expression of iron regulon genes in iron-deficient yeast but are inactivated in iron-replete cells. Iron inhibition of Aft1/Aft2 is abrogated in cells defective for Fe-S cluster biogenesis within the mitochondrial matrix (Chen, O. S., Crisp, R. J., Valachovic, M., Bard, M., Winge, D. R., and Kaplan, J. (2004) J. Biol. Chem. 279, 29513-29518). To determine whether iron sensing by Aft1/Aft2 requires the function of the mitochondrial Fe-S export and cytosolic Fe-S protein assembly systems, we evaluated the expression of the iron regulon in cells depleted of glutathione and in cells depleted of Atm1, Nar1, Cfd1, and Nbp35. The iron regulon is induced in cells depleted of Atm1 with Aft1 largely responsible for the induced gene expression. Aft2 is activated at a later time in Atm1-depleted cells. Likewise, the iron regulon is induced in cells depleted of glutathione. In contrast, repression of NAR1, CFD1, or NBP35 fails to induce the iron regulon despite strong inhibition of cytosolic/nuclear Fe-S protein assembly. Thus, iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins, but the mitochondrial inner membrane transporter Atm1 is important to transport the inhibitory signal. Although Aft1 and Aft2 sense a signal emanating from the Fe-S cluster biogenesis pathway, there is no indication that the proteins are inhibited by direct binding of an Fe-S cluster.
Successful treatment of human Waldenström's macroglobulinemia with combination biological and chemotherapy agents. (1994)

The immunomodulating effects and antitumor activity of two biological agents, bryostatin 1 (Bryo1) and alpha-interferon, were tested in vitro and in vivo either alone or prior to chemotherapy agents, against a Waldenström's macroglobulinemia tumor line (WSU-WM). Bryol caused a decrease in the expression of CD10, CD19, IgM, Leu10, and CD22 and a temporary growth inhibition as measured by cell cycle analysis. alpha-Interferon did not show any major effects. In vivo, severe combined immunodeficient mice were used to test the activity of the agents against WSU-WM. Bryo1 (i.p.) was given either alone or sequentially with doxorubicin (i.v.), vincristine (i.v.), melphalan (i.v.), and alpha-interferon (i.v.). Bryo1 given 24 h before vincristine or melphalan resulted in the highest tumor growth inhibition, tumor growth delay, and tumor cell kill. Two of five mice receiving Bryo1/vincristine combination were free of tumors > 200 days after treatment and were considered cured. In light of our findings, we recommend that Bryo1 be considered for clinical investigation in human B-cell tumors and might best be given combined with other chemotherapy agents used in the treatment of that disease. Whether Bryo1 is acting as a differentiating agent or as a direct anti-Waldenström's macroglobulinemia tumor agent, remains unclear.
Characterization of a murine tumor of spontaneous origin with selective hepatic metastasis. (1987)

The primary objective of this study was to establish the identity and characteristics of a murine uterine tumor of spontaneous origin in a C57Bl/6 Ros mouse that selectively metastasized to the liver. The primary tumor contained a minimum of two different cell types. One cell type was elongated and spindly and readily adhered to a plastic coated surface. From it, a permanent cell line, termed RCS-1 was established. The RCS-1 cell line was poorly tumorigenic in normal C57Bl/6 Ros mice. The other cell type, designated RCS-2, was more rounded in structure. It was maintained in vivo, enzymatically dissociated and used after short-term in vitro cell culture. The RCS-2 cells had phagocytic vacuoles, Fc, and C3 receptors. These cells phagocytosed antibody coated SRBCs and opsonized zymosan. Furthermore, these cells generated the superoxide anion. Thus, the RCS-2 cells are of macrophage origin. The spontaneous and experimental pattern of metastasis of the RCS-2 tumor cells was established. The RCS-2 tumor cells selectively metastasized to the liver by the hematogenous route. Metastatic RCS-2 tumor cells obtained from the liver (RCS-2M) retained their macrophage characteristics. These studies indicate that this murine uterine tumor of spontaneous origin consists of two cell types. One cell type is a reticulum cell sarcoma.
NEPAL-an N/sup 1.5/ algorithm for solving the volume integral equation (1992)

The authors present an algorithm called the nested equivalence principle algorithm (NEPAL) to solve volume integral equations with computational complexity of N/sup 1.5/ in two dimensions and N/sup 2/ in three dimensions. The principal idea of this approach is to nest one algorithm within another so that a smaller problem is solved before a larger one. The size of the problem increases by a factor of 2/sup n/ at each stage where n is the dimension of the problem. In this manner, an N unknown problem is solved in log/sub n/ N steps. The authors have implemented NEPAL to solve volume integral equations and compared the results with the direct solution of the volume integral equations by the method of moments. The results are in good agreement for both E/sub z/ and H/sub z/ polarized waves. The authors have also studied the growth of computer time with the number of unknowns in the problem and found that NEPAL is very competitive with RATMA.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glycosylation-inhibiting factor from human T cell hybridomas constructed from peripheral blood lymphocytes of a bee venom-sensitive allergic patient (1992)

Human T cell hybridomas, which constitutively secrete glycosylation inhibiting factor (GIF), were constructed from PBL of an allergic individual who was sensitive to honey bee venom. PBMC of the patient were stimulated with either denatured or cyanogen bromide-treated bee venom phospholipase A2 (PLA2), and Ag-activated cells were propagated by IL-2 in the presence of human recombinant lipocortin I. T cells obtained in the cultures were fused with a HAT-sensitive mutant of the human lymphoblastoid cell line CEM. Approximately one-third of hybridoma clones constitutively secreted GIF. The GIF-producing hybridomas were CD3+ and bore TCR-alpha beta. GIF formed by unstimulated hybridomas lacked affinity for bee venom PLA2. Upon cross-linking of CD3, however, a majority of the GIF-producing hybridomas formed IgE-binding factors and GIF, the latter of which had affinity for bee venom PLA2. Both nonspecific GIF and Ag-binding GIF from the hybridomas bound to an immunosorbent coupled with the anti-lipomodulin mAb 141-B9. Using an affinity-purified GIF as an immunogen, we established mouse B cell hybridomas that secreted monoclonal anti-human GIF. In order to characterize human nonspecific GIF, one of the GIF-producing hybridomas was adapted to a serum-free medium, and culture supernatant was fractionated by DEAE-Sepharose column chromatography and by gel filtration. The majority of nonspecific GIF in the culture supernatant was recovered from DEAE-Sepharose by elution of the column with 10 mM Tris-HCl buffer, pH 8.0, containing 50 mM NaCl. Affinity-purification of GIF in the DEAE Sepharose fraction by using anti-GIF-coupled Affigel, and analysis of the purified GIF by SDS-PAGE revealed that human GIF is a single polypeptide chain of 14 to 15 kDa. Gel filtration of both crude and affinity-purified GIF preparations confirmed the molecular size of the cytokine.
Immunization of sheep against GnRH early in life: effects on reproductive function and hormones in rams (1994)

Groups of Merino ram lambs were immunized against GnRH either soon after birth (prepubertal) or around puberty (peripubertal) with a prototype commercial preparation and studied over the following 2 years to determine the long-term effects of such immunization on reproductive development, function and hormone concentrations. The treatment was equally effective in suppressing reproductive function and hormones when given at either time. Growth rates of immunized and controls rams were similar throughout the study. Prepubertal immunization delayed testicular growth until the rams were at least 27 weeks of age and some rams had subnormally sized testes even at 115 weeks of age. After peripubertal immunization, the mass of the testes declined and remained regressed until the rams were from 51 to 90 weeks old. There was a significant correlation between total testicular mass at 115 weeks of age and duration (weeks) of suppression of testicular growth (prepubertal, r = -0.7375; peripubertal, r = -0.7132, P < 0.001). Prepubertal immunization markedly delayed separation of the penis from the prepuce. The immunized rams did not display sexual activity until their total testicular mass reached at least 70 g. In control and immunized rams with testicular mass > 100 g, the semen did not differ in the percentage of spermatozoa that were unstained (live), of normal morphology, or showed progressive movement. Compared with the increase in plasma LH and FSH concentrations with age in control rams, the concentrations of these hormones in the immunized animals were lower and remained relatively constant from 46 to 90 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Sequence-specific cross-linking of deoxyoligonucleotides via hybridization-triggered alkylation (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSequence-specific cross-linking of deoxyoligonucleotides via hybridization-triggered alkylationThomas R. Webb and Mark D. MatteucciCite this: J. Am. Chem. Soc. 1986, 108, 10, 2764–2765Publication Date (Print):May 1, 1986Publication History Published online1 May 2002Published inissue 1 May 1986https://pubs.acs.org/doi/10.1021/ja00270a051https://doi.org/10.1021/ja00270a051research-articleACS PublicationsRequest reuse permissionsArticle Views175Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Alpha-crystallin can function as a molecular chaperone. (1992)

The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha-crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-crystallin may have other functions in addition to its capacity to suppress aggregation of proteins.
Properties of an epithelial cell type in culture: the epidermal keratinocyte and its dependence on products of the fibroblast. (1977)

Keratinocytes of stratified squamous epithelium can be grown serially in culture and retain the various markers typical of their form of differentiation. In order to form colonies at each transfer, the keratinocytes must be suitably supported by fibroblasts. Established keratinocyte lines of teratomal origin show this dependence, as do diploid strains of finite culture life derived from human skin. For at least some keratinocyte lines, this requirement can be satisfied by soluble products elaborated by the fibroblasts. It is suggested that epithelial cells in general may not be independent cell types and that their poor cultivability may be due to failure to provide suitable fibroblast support. The existence of a number of established lines of epithelial origin that can grow without such support and of lines of fibroblastic origin which cannot support keratinocytes suggests that both epithelial dependence and the fibroblast supporting function can sometimes be lost in established cell lines.
3D human airway segmentation for virtual bronchoscopy (2002)

This paper describes a new airway segmentation algorithm that improves the speed of morphological-based segmentation approaches. Airway segmentation methods based on morphological operators suffer from the indiscriminant application of all operators to a large area. Using the results of three-dimensional (3D) region growing, the discrete application of larger operators is possible. This change can greatly decrease the execution time of the algorithm. This hybrid approach typically runs 5 to 10 times faster than the original algorithm. 3D adaptive region growing, morphological segmentation, and the hybrid approach are then compared via data obtained from human volunteers using a Marconi MX8000 scanner with the lungs held at 85% TLC. Results show that filtering improves robustness of these techniques. The hybrid approach allows for the practical use of morphological operators to create a clinically useful segmentation. We also demonstrate the method's utility for peripheral nodule analysis in a human case.
Controlled Amine Functionality in Self-Assembled Monolayers via the Hidden Amine Route:  Chemical and Electronic Tunability (2006)

A synthetic strategy for fabricating a dense amine functionalized self-assembled monolayer (SAM) on hydroxylated surfaces is presented. The assembly steps are monitored by X-ray photoelectron spectroscopy, Fourier transform infrared- attenuated total reflection, atomic force microscopy, variable angle spectroscopic ellipsometry, UV-vis surface spectroscopy, contact angle wettability, and contact potential difference measurements. The method applies alkylbromide-trichlorosilane for the fabrication of the SAM followed by surface transformation of the bromine moiety to amine by a two-step procedure: S(N)2 reaction that introduces the hidden amine, phthalimide, followed by the removal of the protecting group and exposing the free amine. The use of phthalimide moiety in the process enabled monitoring the substitution reaction rate on the surface (by absorption spectroscopy) and showed first-order kinetics. The simplicity of the process, nonharsh reagents, and short reaction time allow the use of such SAMs in molecular nanoelectronics applications, where complete control of the used SAM is needed. The different molecular dipole of each step of the process, which is verified by DFT calculations, supports the use of these SAMs as means to tune the electronic properties of semiconductors and for better synergism between SAMs and standard microelectronics processes and devices.