gebhart/patrepeval huggingface dataset:
Growth and adipose differentiation of sheep preadipocyte fibroblasts in serum‐free medium (1983)

Fibroblasts from ovine skin, and from the perirenal and subcutaneous adipose tissues of sheep were grown at clonal densities in medium MCDB 202 supplemented with 1 microgram/ml bovine insulin, 1 microM dexamethasone, 100 ng/ml fibroblast growth factor and 20 micrograms/ml of the lipid preparation described by Bettger, W. J., Boyce, S. T., Walthall, B. J. and Ham, R. G. [(1981) Proc. Natl Acad. Sci, USA, 78, 5588-5592]. When maintained as a confluent monolayer in this medium, the fibroblasts from the adipose tissues spontaneously underwent an adipose differentiation. This was accelerated by substituting medium F12 for medium MCDB 202, and by raising the CO2 tension from 2% to 7.5% in air over the cultures. The differentiation was inhibited by deleting FGF from the growth medium, or by coating the culture surface with fibronectin or poly-D-lysine. Differentiation also failed to occur when the defined supplements were replaced with fetal bovine serum. The synthesis of triacylglycerol by the cells, as seen by the increased specific activity of [14C]acetate incorporated into this lipid class, was accompanied by an increase in the specific activity of glycerol-3-phosphate dehydrogenase.
Temporal and Spatial Clustering for a Parking Prediction Service (2014)

It has been estimated that in urban scenarios up to 30% of the traffic is due to vehicles looking for a free parking space. Thanks to recent technological evolutions, it is now possible to have at least a partial coverage of real-time data of parking space availability, and some preliminary mobile services are able to guide drivers towards free parking spaces. Nevertheless, the integration of this data within car navigators is challenging, mainly because (I) current In-Vehicle Telematic systems are not connected, and (II) they have strong limitations in terms of storage capabilities. To overcome these issues, in this paper we present a back-end based approach to learn historical models of parking availability per street. These compact models can then be easily stored on the map in the vehicle. In particular, we investigate the trade-off between the granularity level of the detailed spatial and temporal representation of parking space availability vs. The achievable prediction accuracy, using different spatio-temporal clustering strategies. The proposed solution is evaluated using five months of parking availability data, publicly available from the project Spark, based in San Francisco. Results show that clustering can reduce the needed storage up to 99%, still having an accuracy of around 70% in the predictions.
CHEMISTRY OF THE METAL CARBONYLS. VII. PERFLUOROALKYL IRON COMPOUNDS1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCHEMISTRY OF THE METAL CARBONYLS. VII. PERFLUOROALKYL IRON COMPOUNDS1T. A. Manuel, S. L. Stafford, and F. G. A. StoneCite this: J. Am. Chem. Soc. 1961, 83, 1, 249–250Publication Date (Print):January 1, 1961Publication History Published online1 May 2002Published inissue 1 January 1961https://pubs.acs.org/doi/10.1021/ja01462a052https://doi.org/10.1021/ja01462a052research-articleACS PublicationsRequest reuse permissionsArticle Views188Altmetric-Citations60LEARN 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
Gene Therapy, Early Promises, Subsequent Problems, and Recent Breakthroughs (2013)

Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist's ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, to date gene therapy is considered for many non-life-threatening conditions including those adversely influence on a patient's quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years.
Proglucagon-Derived Peptides: Mechanisms of Action and Therapeutic Potential (2005)

Glucagon is used for the treatment of hypoglycemia, and glucagon receptor antagonists are under development for the treatment of type 2 diabetes. Moreover, glucagon-like peptide (GLP)-1 and GLP-2 receptor agonists appear to be promising therapies for the treatment of type 2 diabetes and intestinal disorders, respectively. This review discusses the physiological, pharmacological, and therapeutic actions of the proglucagon-derived peptides, with an emphasis on clinical relevance of the peptides for the treatment of human disease.
A Scanline Data Structure Processor for VLSI Geometry Checking (1987)

This paper proposes an architecture to support VLSI geometry checking tasks based on scanline algorithms. Rather than recast the entire verification task in hardware, we identify primitives around which geometry checking tools can be built, and examine the feasibility of accelerating two of these critical primitives. We focus on the operations of Boolean combinations of mask layers, and region numbering within a mask layer. Unlike previous proposals for special hardware (e.g., bit map processors), this architecture operates on a more realistic representation of masks: a sorted stream of possibly oblique edges. The architecture can be viewed as directly interpreting the operators that manipulate the relevant scanline data structures. We show how the edge computations in these two algorithms can be restructured into the form of a single, shared hardware pipeline. Data from a simulation of this processor suggests that, relative to the specific software functions it is intended to replace, the scanline processor can reduce computation time significantly. In particular, simulations of one possible implementation for this processor yield speedups of three orders of magnitude for Manhattan mask data, degrading gracefully to speedups of two orders of magnitude for highly oblique mask data.
Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors (1998)

The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM-CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S-phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findings suggest that transduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site.
The Novel, Irreversible Proteasome Inhibitor PR-171 Demonstrates Potent Anti-Tumor Activity in Pre-Clinical Models of Multiple Myeloma, and Overcomes Bortezomib Resistance. (2006)

Abstract Introduction: The ubiquitin-proteasome pathway has been validated as a therapeutic target with the approval of the small molecule proteasome inhibitor, bortezomib (VELCADE®), in multiple myeloma and non-Hodgkin lymphoma. However, the overall response rate of patients with multiple myeloma in phase III clinical trials was 43%, underscoring the need for a next generation of inhibitors with the potential for greater efficacy. Methods: PR-171 is a novel, tetrapeptide epoxomicin-related inhibitor that binds the proteasome irreversibly, and our objectives were to evaluate its activity and mechanism of action in pre-clinical models of multiple myeloma. Results: PR-171 potently bound and inhibited the chymotrypsin-like subunit of the proteasome in vitro, in cellulo, and in vivo at low concentrations. At higher concentrations, however, unlike bortezomib, which targeted the chymotrypsin-like and peptidyl-glutamyl peptide hydrolyzing activities in vivo, PR-171 also displayed significant inhibition of the trypsin-like and the peptidyl-glutamyl peptide hydrolyzing activities. PR-171-induced proteasome inhibition was associated with accumulation of polyubiquitinated substrates and pro-apoptotic Bax. Brief pulse PR-171 exposure, which simulates the in vivo pharmacokinetics of bortezomib, led to PR-171-mediated inhibition of cellular proliferation linked to induction of caspase-3-dependent apoptosis through both intrinsic (caspase-9) and extrinsic (caspase-8-dependent) pathways. Pretreatment with caspase-3, -8, and -9 inhibitors rescued the anti-proliferative effect of PR-171. Furthermore, pulse PR-171 treatment activated c-Jun-N-terminal kinase, a key-signaling molecule in proteasome inhibitor-induced apoptosis, and cleavage of poly-ADP-ribose polymerase, while abrogation of c-Jun-N-terminal kinase signaling with a dominant-negative c-Jun inhibited PR-171-induced effects. PR-171 displayed enhanced anti-proliferative activity compared to bortezomib in multiple myeloma cell lines and freshly isolated patient-derived CD138+ plasma cells, associated with enhanced phosphorylation of c-Jun-N-terminal kinase and capase-3, -8, and -9 activation. Lastly, PR-171 was a potent inhibitor of proliferation in a multiple myeloma cell line model resistant to bortezomib and in isolates from two patients, one with primary and the other with acquired bortezomib-resistance. Conclusions: These data indicate that PR-171 has enhanced activity against preclinical models of multiple myeloma, perhaps owing to its irreversible binding and subunit specificity, and provide a rationale for its translation into the clinic.
Cloning and Expression of Human Carboxypeptidase Z, a Novel Metallocarboxypeptidase (1997)

A novel cDNA, designated carboxypeptidase Z (CPZ), was identified based on its homology to known metallocarboxypeptidases. Northern blot analysis shows bands of 2.1 and/or 2.6 kilobases in all tissues examined. The major form of CPZ mRNA in human salivary gland encodes a protein with an open reading frame of 641 amino acids. In addition, three variants were found that presumably arise due to alternative intron splicing. The 641-amino acid protein contains an 18-residue signal peptide-like sequence, a 120-residue region that shows 23-29% amino acid identity with a Cys-rich domain found in frizzled proteins and in type XVIII collagen, and then a 390-residue carboxypeptidase domain with 49% amino acid identity to carboxypeptidases E and N. The 641-amino acid form of CPZ expressed in the baculovirus system cleaves 5-dimethylaminonaphthalene-1-sulfonyl (dansyl)-Phe-Ala-Arg, although the level of enzyme activity was approximately 10-fold lower than either carboxypeptidase E or D expressed using the same viral system. The CPZ activity is more active at neutral pH than at pH 5.5 and is inhibited by active site-directed inhibitors of metallocarboxypeptidases. In summary, CPZ is a novel metallocarboxypeptidase that is active toward substrates with C-terminal basic amino acids.
Solvent-Resistant Photocurable “Liquid Teflon” for Microfluidic Device Fabrication (2004)

We report the first fabrication of a solvent-compatible microfluidic device based on photocurable "Liquid Teflon" materials. The materials are highly fluorinated functionalized perfluoropolyethers (PFPEs) that have liquidlike viscosities that can be cured into tough, highly durable elastomers that exhibit the remarkable chemical resistance of fluoropolymers such as Teflon. Poly(dimethylsiloxane) (PDMS) elastomers have rapidly become the material of choice for many recent microfluidic device applications. Despite the advantages of PDMS in relation to microfluidics technology, the material suffers from a serious drawback in that it swells in most organic solvents. The swelling of PDMS-based devices in organic solvents greatly disrupts the micrometer-sized features and makes it impossible for fluids to flow inside the channels. Our approach to this problem has been to replace PDMS with photocurable perfluoropolyethers. Device fabrication and valve actuation were accomplished using established procedures for PDMS devices. The additional advantage of photocuring allows fabrication time to be decreased from several hours to a matter of minutes. The PFPE-based device exhibited mechanical properties similar to those of Sylgard 184 before and after curing as well as remarkable resistance to organic solvents. This work has the potential to expand the field of microfluidics to many novel applications.
Wavelength-encoding/temporal-spreading optical code division multiple-access system with in-fiber chirped moiré gratings (1999)

We propose an optical code division multiple-access (OCDMA) system that uses in-fiber chirped moiré gratings (CMG's) for encoding and decoding of broadband pulses. In reflection the wavelength-selective and dispersive nature of CMG's can be used to implement wavelength-encoding/temporal-spreading OCDMA. We give examples of codes designed around the constraints imposed by the encoding devices and present numerical simulations that demonstrate the proposed concept.
Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae. (1994)

Laboratory strains of Saccharomyces cerevisiae are dimorphic; in response to nitrogen starvation they switch from a yeast form (YF) to a filamentous pseudohyphal (PH) form. Time-lapse video microscopy of dividing cells reveals that YF and PH cells differ in their cell cycles and budding polarity. The YF cell cycle is controlled at the G1/S transition by the cell-size checkpoint Start. YF cells divide asymmetrically, producing small daughters from full-sized mothers. As a result, mothers and daughters bud asynchronously. Mothers bud immediately but daughters grow in G1 until they achieve a critical cell size. By contrast, PH cells divide symmetrically, restricting mitosis until the bud grows to the size of the mother. Thus, mother and daughter bud synchronously in the next cycle, without a G1 delay before Start. YF and PH cells also exhibit distinct bud-site selection patterns. YF cells are bipolar, producing their second and subsequent buds at either pole. PH cells are unipolar, producing their second and subsequent buds only from the end opposite the junction with their mother. We propose that in PH cells a G2 cell-size checkpoint delays mitosis until bud size reaches that of the mother cell. We conclude that yeast and PH forms are distinct cell types each with a unique cell cycle, budding pattern, and cell shape.
[Flow cytometric analysis of helper T cell subsets (Th1 and Th2) in healthy adults]. (1998)

To estimate frequency of T helper (Th) 1, Th2, and other related subsets in T cells among healthy Japanese, we determined the frequencies of interferon (IFN)-gamma- and/or interleukin (IL)-4-producing cells in stimulated peripheral blood lymphocytes (PBL) from 51 healthy adults of various ages by three-color flow cytometry using FITC-labeled anti-IFN-gamma, PE-conjugated anti-IL-4, and peridinin chlorophyll protein (PerCP)-labeled anti-CD4 or anti-CD3 antibody. As a result, proportions (mean +/- SD) of IFN-gamma-single positive (conveniently called Th1), IL-4-single positive (Th2), and double-positive cells (Th0) in CD4+ PBL, and homologous cell populations in CD3+ PBL (Th1 type, Th2 type, and Th0 type cells) were 21.3 +/- 8.2%, 2.7 +/- 1.1%, 1.9 +/- 1.0%, 39.5 +/- 13.5%, 1.7 +/- 0.8%, and 1.8 +/- 1.0%, respectively. Percentages of Th1 and Th2 were roughly consistent with those reported previously. Proportions of Th1, Th2, Th1 type, and Th2 type cells were found to increase with the age, whereas there were no significant difference in sex at least in 20s. Furthermore, positive correlation was seen between Th1 and Th1 type (r = 0.79), Th2 and Th2 type (r = 0.87), and Th0 and Th0 type (r = 0.86). Frequencies of these subsets in each donor were maintained at substantially the same levels for at least 3 months, suggesting existence of particular and stable Th1/Th2 balance among healthy individuals. As reported, 6 patients with atopic dermatitis examined in this study showed significantly lower frequencies of Th1 (11.0 +/- 2.5%) as compared with healthy donors (p < 0.01), implying usefulness of the immune test.
Amphipathic domains in the C terminus of the transmembrane protein (gp41) permeabilize HIV-1 virions: a molecular mechanism underlying natural endogenous reverse transcription. (1996)

Reverse transcription of HIV-1, without detergent or amphipathic peptide-induced permeability of the viral envelope, has been demonstrated to occur in the intact HIV-1 virion. In this report, we demonstrate that the amphipathic domains in the C terminus of the transmembrane glycoprotein (gp41) account for the natural permeability of the HIV-1 envelope to deoxyribonucleoside triphosphates, the substrates for DNA polymerization. In addition, nonphysiological deoxyribonucleoside triphosphates, such as 3'-azido-3'-deoxythymidine 5'-triphosphate and 3'-deoxythymidine 5'-triphosphate, can also penetrate the viral envelope, incorporate into, and irreversibly terminate reverse transcripts. As a result, viral infectivity is potently inhibited. Since the lentiviral envelope with these newly demonstrated characteristics can serve as a delivery pathway for anti-reverse transcription agents, we propose a unique strategy to prevent HIV-1 interand, possibly, intrahost transmission.
A technique for software module specification with examples (1972)

This paper presents an approach to writing specifications for parts of software systems. The main goal is to provide specifications sufficiently precise and complete that other pieces of software can be written to interact with the piece specified without additional information. The secondary goal is to include in the specification no more information than necessary to meet the first goal. The technique is illustrated by means of a variety of examples from a tutorial system.
Variability of Neutral-Position Casting of the Foot (2003)

Neutral-position casting of the foot is used for the manufacture of functional foot orthoses, and an accurate cast is widely assumed to be a prerequisite for a good orthotic device. The primary aim of this study was to determine the variability of casting between inexperienced and experienced clinicians and the variability of one experienced clinician taking multiple casts. Ten inexperienced and ten experienced clinicians took a cast of the right foot of a single subject, and a single experienced clinician took ten casts of the same foot. The frontal plane forefoot-to-rearfoot relationship of each cast was determined, and no difference was found in the mean and variances among the three groups. The range of the forefoot-to-rearfoot relationship across all groups was from 10.0 degrees everted to 6.5 degrees inverted, indicating that there is a wide range in neutral-position casting of the foot. As outcome studies have reported the successful outcomes of functional foot orthoses, this wide variability may not necessarily be a problem.
Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism. (1992)

The cleavage of C3 is a critical step for complement (C) activation in the classical and alternative pathways. This reaction is controlled by the regulators of C activation protein family. Membrane cofactor protein (MCP) is a cofactor for the factor I-mediated inactivation of C3b and C4b. As a widely distributed membrane protein, MCP may protect host cells from inadvertent C activation. Human MCP has recently been shown to protect transfected rodent cells from human C-mediated lysis. In this report the relationship of MCP expression to C3b deposition and cytoprotection was examined using NIH/3T3 cells transfected with human MCP and exposed to human serum as a source of C and naturally occurring anti-mouse antibody. MCP inhibited C3b deposition in a dose-dependent fashion and inhibited lysis of the mouse cells expressing it. MCP did not inhibit lysis on bystander cells. These results demonstrate the protective role of MCP, at the cellular level, by an intrinsic mechanism.
Oncogenic Mutations of PIK3CA in Human Cancers (2004)

Phosphatidylinositol 3-kinases (PI3Ks) are important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in human cancers, we recently analyzed the sequences of the PI3K gene family and discovered that one member, the PIK3CA gene encoding the p110alpha catalytic subunit, was frequently mutated in cancers of the colon, breast, brain and lung. The majority of mutations clustered near two positions within the PI3K helical or catalytic domains and at least one hotspot mutation appeared to increase kinase activity. PIK3CA represents one of the most highly mutated oncogenes identified in human cancers and may be a useful diagnostic and therapeutic target.
FcRn, a critical regulator of antibody pharmacokinetics (2010)

腫瘍や自己免疫疾患等の治療を目的とした分子標的薬として，抗体医薬品の研究開発が国内外で活発に行われている．抗体医薬品の特徴は標的分子に高い親和性をもって極めて特異的に結合することであるが，他のバイオ医薬品と比較して血中半減期が長いことも特筆すべき点である．ペプチドあるいはタンパク質を医薬品として応用する場合には血中半減期が実用化のためのハードルとなることが少なくない．しかし，多くの抗体医薬品は，生体内IgGの分解抑制に関わるneonatal Fc receptor（FcRn）を介したリサイクリング機構を利用することができるため，数日～数週間という長い血中半減期を有している．FcRnは齧歯類の新生児小腸に高発現し，乳汁に含まれる母親由来IgGの吸収に関与する受容体として同定された．その後の研究により，FcRnが成体においても種々の組織に発現し，IgGのリサイクリングやトランスサイトーシス等に関与していることが報告され，母子免疫以外にも様々な側面でIgGの体内動態制御に関わっていることが明らかにされている．我々は，既承認抗体医薬品のFcRn結合親和性を解析し，ヒトでの血中半減期とFcRn結合親和性の相関，および抗体医薬品のFcRn結合親和性を規定する構造特性の一端を明らかにした．近年の創薬研究では，FcRn結合親和性を改変した抗体医薬品等の開発が進んでいる他，FcRnのもう1つのリガンドであるアルブミンを利用することにより体内動態特性を改変したタンパク質医薬品の開発も進んでいる．FcRnは，抗体医薬品をはじめとするバイオ医薬品の体内動態制御に関わる鍵分子の1つと言えるであろう．