gebhart/patrepeval huggingface dataset:
Signal transduction mediated by growth hormone receptor and its chimeric molecules with the granulocyte colony-stimulating factor receptor. (1993)

The granulocyte colony-stimulating factor receptor (G-CSF-R) and growth hormone receptor (GH-R) belong to the cytokine receptor family and have some similarity in the cytokine receptor-homologous (CRH) domain of the extracellular region. Among members of this family, the G-CSF-R and GH-R seem to function as homodimers. Previously, we showed that mouse myeloid precursor FDC-P1 cells expressing the G-CSF-R can respond to G-CSF for growth. Here we show that the GH-R can also transduce the growth signal in FDC-P1 cells in the range 10 pM-100 nM GH. At a higher concentration of GH, GH did not promote the growth of the transformant cells. A series of chimeric receptor cDNAs between the G-CSF-R and GH-R cDNAs was constructed by exon swapping and was expressed in FDC-P1 cells. A ligand-binding assay with transformants expressing chimeric receptors indicated that the entire CRH domain is necessary for specific binding of the ligand. Although the transmembrane and cytoplasmic regions of the G-CSF-R and GH-R have no apparent similarity, these regions were interchangeable, resulting in growth-signal transduction in FDC-P1 cells.
Design, synthesis and crystallization of a novel glucagon analog as a therapeutic agent (2007)

Glucagon and glucagon-like peptide 1 (GLP-1) are drugs or drug candidates for the treatment of metabolic diseases such as diabetes and obesity. The native hormones have pharmacological deficiencies such as short half-life and poor solubility. A novel glucagon receptor agonist named glucagon-Cex has been designed, synthesized and crystallized. This peptide was highly soluble under physiological conditions and crystallized readily. The crystal diffracted X-rays to 2.2 A resolution and the diffraction was consistent with space group P23, with unit-cell parameters a = b = c = 48.20 A, alpha = beta = gamma = 90.0 degrees. The crystals were suitable for a full structural determination to reveal the conformational differences between glucagon-Cex and the native hormone.
Regenerative medicine: using liver to generate pancreas for treating diabetes. (2006)

Recent advances in pancreatic islet transplantation emphasize the potential of this approach for the long-term control of blood glucose levels as treatment of diabetes. To overcome the organ shortage for cell replacement therapy, efforts are being invested in generating new and abundant sources of insulin-producing cells from embryonic or adult stem cells. We review recent evidence documenting the surprising capacity of the mature liver to serve as a potential source of tissue for generating functional endocrine pancreas. The process of liver-to-pancreas developmental redirection is induced by ectopic expression of pancreatic transcription and differentiation factors. This approach may allow the diabetic patient to be the donor of his or her own therapeutic tissue, thus alleviating both the need for allotransplantations and the subsequent immune suppression.
Production of Human Monoclonal Antibodies against FcεRIα by a Method Combiningin VitroImmunization with Phage Display (2009)

An in vitro immunization protocol using human peripheral blood mononuclear cells (PBMC) was developed to generate human antigen-specific antibodies. Monoclonal antibodies have great potential, and in particular, efficient acquirement of monoclonal antibodies against membrane proteins provides advantages. In this study, we tried to generate a human monoclonal antibody against the high affinity IgE receptor, Fc(epsilon)RI(alpha), using a method combining in vitro immunization and phage display. Heavy and light chain variable region genes were obtained from PBMC immunized in vitro with Fc(epsilon)RI(alpha)-expressed KU812F cells. Subsequently a combined phage antibody library 6 x 10(3) in the size was generated. Antigen-specific phage antibody clones were selected by panning with recombinant Fc(epsilon)RI(alpha) and recombined to produce human IgG format antibodies using CHO cells. The antibodies exhibited specific binding against Fc(epsilon)RI(alpha). These results suggest that one can obtain membrane protein-specific human monoclonal antibodies from a relatively small phage antibody library using in vitro immunized PBMCs.
Effect of Introns and AT-Rich Sequences on Expression of the Bacterial Hygromycin B Resistance Gene in the Basidiomycete Schizophyllum commune (2001)

Previously, it was shown that introns are required for efficient mRNA accumulation in Schizophyllum commune and that the presence of AT-rich sequences in the coding region of genes can result in truncation of transcripts in this homobasidiomycete. Here we show that intron-dependent mRNA accumulation and truncation of transcripts are two independent events that both affect expression of the bacterial hygromycin B resistance gene in S. commune.
Combination of a selective cyclooxygenase-2 inhibitor with epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 and protein kinase A antisense causes cooperative antitumor and antiangiogenic effect. (2003)

This is the first demonstration that three novel agents blocking multiple signaling pathways, in absence of cytotoxic drugs, may have a potent antitumor and antiangiogenic activity after oral administration. Because all agents are under clinical evaluation, our results provide a rationale to translate this feasible therapeutic strategy into a clinical setting.
Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis. (2002)

Clinical and prognostic significance of differential gene expression should be studied with a larger series of patients by using other techniques, such as quantitative real-time PCR.
SPIRIT: Sequential Pattern Mining with Regular Expression Constraints (1999)

Discovering sequential patterns is an important problem in data mining with a host of application domains including medicine, telecommunications, and the World Wide Web. Conventional
A biotech route to polyphenylene (1983)

Starting from benzene and oxygen and using the genetically modified bacteria Pseudominium putida as an oxidation catalyst compound (6) is readily obtained; derivative of the latter are soluble in organic solvents and polymerise to give a soluble precursor (5) which can be used to make fibres and films which on heating are converted into polyphenylene fibres and films.
Xylitol production byCyberlindnera(Williopsis) saturnus, a tropical mangrove yeast from xylose and corn cob hydrolysate (2013)

Microbes offer an economically viable and green approach for production of xylitol, an industrially important compound. A mangrove ecosystem with its battery of lignocellulolytic enzymes is an ideal location for isolating fungi capable of producing xylitol from agroindustrial waste such as CCH.
Low Dose Nesiritide and the Preservation of Renal Function in Patients With Renal Dysfunction Undergoing Cardiopulmonary-Bypass Surgery (2007)

This proof of concept pilot study supports the conclusion that perioperative administration of low dose nesiritide is biologically active and decreases plasma cystatin in patients with renal insufficiency undergoing cardiopulmonary bypass cardiac surgery. Further studies are warranted to determine whether these physiological observations can be translated into improved clinical outcomes.
Die Konstitution des Alkaloids Cryptolepin (1951)

Abstract Es wurde die Konstitution des Alkaloids Cryptolepin aufgeklärt und im Zusammenhang damit bewiesen, dass das zuerst von Fichter synthetisierte Chindolinsystem [Indolo‐3′,2′:2,3‐chinolin] auch in Naturprodukten vorkommen kann.
Peptide-mediated delivery of green fluorescent protein into yeasts and bacteria (2002)

Stringent microbial cell barriers limit the application of many substances in research and therapeutics. Carrier peptides that penetrate or translocate across cell membranes may help overcome this problem. To assess peptide-mediated delivery into two yeast and three bacterial species, a range of cell penetrating and signal peptide sequences were fused to green fluorescent protein (GFP), expressed in Escherichia coli, partially purified and incubated with growing cells. Fluorescence microscopy indicated several peptides that mediated delivery. In particular, VLTNENPFSDP efficiently delivered GFP into Candida albicans and Staphylococcus aureus, while YKKSNNPFSD was most efficient for Bacillus subtilis and CFFKDEL for Escherichia coli. Carrier peptides may improve delivery of certain large molecular mass molecules into microorganisms for research and therapeutic applications.
Medical management of Cushing’s disease: what is the future? (2012)

Cushing's disease (CD) is caused by a corticotroph, adrenocorticotropic-hormone (ACTH)-secreting pituitary adenoma resulting in significant morbidity and mortality. Transsphenoidal surgery is the initial treatment of choice in almost all cases. Remission rates for microadenomas are good at 65-90 % (with an experienced neurosurgeon) but remission rates are much lower for macroadenomas. However, even after postoperative remission, recurrence rates are high and can be seen up to decades after an initial diagnosis. Repeat surgery or radiation can be useful in these cases, although both have clear limitations with respect to efficacy and/or side effects. Hence, there is a clear unmet need for an effective medical treatment. Currently, most drugs act by inhibiting steroidogenesis in the adrenal glands. Most is known about the effects of ketoconazole and metyrapone. While effective, access to ketoconazole and metyrapone is limited in many countries, experience with long-term use is limited, and side effects can be significant. Recent studies have suggested a role for a pituitary-directed therapy with new multireceptor ligand somatostatin analogs (e.g., pasireotide, recently approved in Europe for treatment of CD), second-generation dopamine agonists, or a combination of both. Mifepristone (a glucocorticoid receptor antagonist) is another promising drug, recently approved by the FDA for treatment of hyperglycemia associated with Cushing's syndrome. We review available medical treatments for CD with a focus on the two most recent compounds referenced above. Our aim is to expand awareness of current research, and the possibilities afforded by available medical treatments for this mesmerizing, but often frightful disease.
Salt-Induced Cardiac Hypertrophy Is Independent of Blood Pressure and Endothelin in Obese, Heart Failure-Prone SHHF Rats (2008)

The interaction of salt sensitivity and obesity in development of cardiac hypertrophy is incompletely understood. The SHHF/Mcc-fa(cp) (SHHF) rat model was used to examine the effect of high salt on cardiac hypertrophy and expression of endothelin (ET) and nitric oxide synthase (NOS) isoforms. Homozygous lean (+/+) and obese (fa(cp)/fa(cp)) SHHF were fed a low-salt diet (0.3% NaCl) for seven days followed by a high-salt diet (8.0% NaCl) for seven days. To assess the role of ET in mediating cardiac hypertrophy and gene expression with high salt, additional groups were treated with an ET(A)/ET(B) receptor antagonist (bosentan) while on high salt. Obese SHHF showed an increase in systolic blood pressure and cardiac hypertrophy in response to the high-salt diet. High salt resulted in decreased expression of preproET as well as all three NOS isoforms in the Obese, while cytokine induced NOS (iNOS) and neuronal NOS (nNOS) increased in Leans. Though the salt-sensitive component of the hypertension observed in the Obese was prevented by bosentan, cardiac hypertrophy still occurred and expression of all NOS isoforms remained lower in Obese compared to Lean. Endothelial NOS (eNOS) expression increased in the Lean with bosentan. These studies suggest that cardiac hypertrophy is independent of the level of hypertension and may be mediated by altered production of NOS isoforms in salt-sensitive, obese SHHF.
Viscoelastic Surfactant Solutions (1994)

A review is given on rheological data of viscoelastic surfactant solutions. The viscoelastic properties in the discussed systems are due to entangled threadlike micelles. In such solutions that have this microstructure the zero shear viscosities depend strongly on conditions like the charge density of the micelles, the salt and cosurfactant concentration, and the chainlength of the surfactant. For a 1% solution the viscosity can vary between one and 106 mPas. Over extended concentration ranges the viscosities show simple power law behaviour (η° = (c/c*)x with x = 1.5 - 8.5). The largest values for x are observed for systems with charged unshielded micelles and the smallest values for shielded or neutral systems which are close to the L1/Lα-phase boundary. The various exponents are explained on the basis or different scission mechanisms as proposed by M. Cates. Many viscoelastic surfactant solutions show simple Maxwell behaviour.
Serverless network file systems (1995)

In this paper, we propose a new paradigm for network file system design, serverless network ,file systems. While traditional netwc~rk file systems rely on a central server machine, a serverless system utilizes workstations cooperating as peers to provide all file system services. Any machine in the system can store, cache, or control any block of' data. Our approach uses this location illdepelldeIICe, in combination with fast local area networks, to proviclc better performance and scalability than traditional file systems. Further, because any machine in the system can assume the responsibilities of a failed component, our serverless clesign also provides high availability via redundant data storage. To demonstrate our approach, we have implemented a prototype serverless network file system called xFS. Preliminary performance measurements suggest that our architecture achieves its goal of scalability. For instance, in a 32-node xI% system with 32 active clients, each client receives nearly as much read or write throughput as it would see if it were the only active client.
Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation (2017)

Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21). We developed fluorescent, morphology-based seeding assays that allow the formation of pathological tau aggregates to be measured in situ within 24 h in the presence of picomolar concentrations of tau seeds. We found that anti-tau antibodies accompany tau seeds into the cell, where they recruit TRIM21 shortly after entry. After binding, TRIM21 neutralizes tau seeds through the activity of the proteasome and the AAA ATPase p97/VCP in a similar manner to infectious viruses. These results establish that intracellular antiviral immunity can be redirected against host-origin endopathogens involved in neurodegeneration.
Total synthesis of onnamide A (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of onnamide AChang Yong Hong and Yoshito KishiCite this: J. Am. Chem. Soc. 1991, 113, 25, 9693–9694Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://doi.org/10.1021/ja00025a056RIGHTS & PERMISSIONSArticle Views1010Altmetric-Citations68LEARN 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 InReddit PDF (288 KB) Get e-Alerts Get e-Alerts
Recovery of inter-block information when block sizes are unequal (1971)

A method is proposed for estimating intra-block and inter-blook weights in the analysis of incomplete block designs with block sizes not necessarily equal. The method consists of maximizing the likelihood, not of all the data, but of a set of selected error contrasts. When block sizes are equal results are identical with those obtained by the method of Nelder (1968) for generally balanced designs. Although mainly concerned with incomplete block designs the paper also gives in outline an extension of the modified maximum likelihood procedure to designs with a more complicated block structure.
Internet protocols for multimedia communications. II. Resource reservation, transport, and application protocols (1997)

Part I (ibid., July-Oct. 1997) surveyed the evolution of Internet protocols and applications and described the Internet protocol IPv6 in detail. This part discusses new developments at the upper layers that support real-time Internet multimedia, such as audio and video conferencing and shared whiteboard applications. Application-level framing (ALF), proposed in 1990 for protocol and application design, now forms the basis for many new Internet protocols and applications, including Real-time Transport Protocol (RTP) and Mbone multimedia applications. RTP supports real-time applications that adapt to changing network situations to maintain the quality of service (QoS). The Resource Reservation Protocol (RSVP) provides new Internet services with higher quality than best-effort by means of resource reservations.
CRISPR/Cas9 for genome editing: progress, implications and challenges (2014)

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system provides a robust and multiplexable genome editing tool, enabling researchers to precisely manipulate specific genomic elements, and facilitating the elucidation of target gene function in biology and diseases. CRISPR/Cas9 comprises of a nonspecific Cas9 nuclease and a set of programmable sequence-specific CRISPR RNA (crRNA), which can guide Cas9 to cleave DNA and generate double-strand breaks at target sites. Subsequent cellular DNA repair process leads to desired insertions, deletions or substitutions at target sites. The specificity of CRISPR/Cas9-mediated DNA cleavage requires target sequences matching crRNA and a protospacer adjacent motif locating at downstream of target sequences. Here, we review the molecular mechanism, applications and challenges of CRISPR/Cas9-mediated genome editing and clinical therapeutic potential of CRISPR/Cas9 in future.
Optimizing 10-Gigabit Ethernet for Networks of Workstations, Clusters, and Grids: A Case Study (2003)

This paper presents a case study of the 10-Gigabit Ethernet (10GbE) adapter from Intel(reg sign). Specifically, with appropriate optimizations to the configurations of the 10GbE adapter and TCP, we demonstrate that the 10GbE adapter can perform well in local-area, storage-area, system-area, and wide-area networks. For local-area, storage-area, and system-area networks in support of networks of workstations, network-attached storage, and clusters, respectively, we can achieve over 7-Gb/s end-to-end throughput and 12-{micro}s end-to-end latency between applications running on Linux-based PCs. For the wide-area network in support of grids, we broke the recently-set Internet2 Land Speed Record by 2.5 times by sustaining an end-to-end TCP/IP throughput of 2.38 Gb/s between Sunnyvale, California and Geneva, Switzerland (i.e., 10,037 kilometers) to move over a terabyte of data in less than an hour. Thus, the above results indicate that 10GbE may be a cost-effective solution across a multitude of computing environments.
Candela-class high-brightness InGaN/AlGaN double-heterostructure blue-light-emitting diodes (1994)

Candela-class high-brightness InGaN/AlGaN double-heterostructure (DH) blue-light-emitting diodes (LEDs) with the luminous intensity over 1 cd were fabricated. As an active layer, a Zn-doped InGaN layer was used for the DH LEDs. The typical output power was 1500 μW and the external quantum efficiency was as high as 2.7% at a forward current of 20 mA at room temperature. The peak wavelength and the full width at half-maximum of the electroluminescence were 450 and 70 nm, respectively. This value of luminous intensity was the highest ever reported for blue LEDs.
Selective delivery of CB300638, a cyclopenta[g]quinazoline-based thymidylate synthase inhibitor into human tumor cell lines overexpressing the alpha-isoform of the folate receptor. (2003)

The alpha-isoform of the glycosylphosphatidylinositol cell membrane tethered folate receptor (alpha-FR) is overexpressed in some carcinomas (notably ovarian carcinomas) relative to normal tissues. The nonpolyglutamatable folate-based thymidylate synthase (TS) inhibitor, CB300638 (TS K(i) = 0.24 nM) displayed an IC(50) of 0.0028 microM for the inhibition of the growth of human A431-FBP cells transfected with the alpha-FR. In contrast, the IC(50) for the neotransfected A431 cells was 0.81 microM (300-fold higher). Similarly, this compound inhibited the growth of human KB cells that constitutively overexpress the alpha-FR with an IC(50) of 0.0036 microM. These data were derived from cells grown in a physiological concentration of folate (20 nM R,S-leucovorin). Incubation of KB cells with a 1 microM excess of folic acid (FA), to selectively block uptake via the alpha-FR, increased the CB300638 IC(50) to 0.39 microM. The relatively low potency of CB300638 under these conditions, or in cell lines not expressing the alpha-FR, is ascribed to its low affinity for the ubiquitously expressed folate transporter, the reduced-folate carrier (K(i) for inhibition of [(3)H]methotrexate transport >100 microM). The high potency of CB300638 in alpha-FR-overexpressing cell lines is attributable to high affinity of the alpha-FR (53% of FA) and efficient endosomal trafficking mediated by the alpha-FR. Sixteen-h exposure to CB300638 inhibited the rate of (3)H(2)O release from 5-[(3)H]dUrd (in situ TS assay) in A431, A431-FBP, and KB cells with IC(50) values of 0.1 microM, 0.005 microM, and 0.002 microM, respectively. The coaddition of 1 micro M FA increased the IC(50)s for A431-FBP and KB cells to approximately 0.1 microM consistent with alpha-FR-mediated transport of CB300638. In conclusion, alpha-FR-mediated uptake of CB300638 leads to TS and growth inhibition that is highly selective for alpha-FR overexpressing tumor cell lines. The low expression of the alpha-FR in normal tissues, particularly those sensitive to TS inhibitors, together with the low affinity of CB300638 for the reduced-folate carrier, suggests that the compound may have potential as an antitumor agent with a high therapeutic index.