gebhart/patrepeval huggingface dataset:
Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. (1995)

Despite molecular biological advances in understanding human cancers, translation into therapy has been less forthcoming; targeting neoplastic cells still requires that tumor-specific markers, preferably those on the cell surface, be identified. The epidermal growth factor receptor (EGFR) exists in a deletion-mutant form, EGFRvIII, which has been identified by genetic and immunological means in a subset of gliomas and non-small cell lung carcinomas. Specific polyvalent antisera to the extracellular portion of the variant were readily induced, but immunization using a synthetic linear peptide representing the unique EGFRvIII primary sequence has been unsuccessful in mice or macaques. We report here five specific monoclonal antibodies (mAbs) developed through long-term immunization protocols using the EGFRvIII-specific synthetic peptide and the intact variant in different formats that maintained secondary and tertiary conformation. These mAbs identify the EGFRvIII on the cell surface with relatively high affinity (KA range, 0.13 to 2.5 x 10(9) M-1) by live cell Scatchard analysis. These mAbs are specific for EGFRvIII as determined by RIA, ELISA, Western blot, analytical flow cytometry, autophosphorylation, and immunohistochemistry. Isolating specific mAbs enabled us to analyze normal and neoplastic human tissue and establish that EGFRvIII is truly tumor specific for subsets of breast carcinomas and for previously reported non-small cell lung carcinomas and gliomas. Also, this receptor is not expressed by any normal human tissues thus far examined, including elements of the peripheral, central nervous, and lymphoid systems. With mAbs, we identified a higher incidence of EGFRvIII positivity in gliomas than previously described and identified an EGFRvIII-positive subset of breast tumors; also, we observed that the EGFRvIII epitope is not expressed in normal tissues, and we demonstrated the localizing and therapeutic potential of the mAbs for tumors expressing this epitope. Our observations strongly warrant development of this mAb-antigen system as therapy for breast, lung, and central nervous system tumors.
Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. (1994)

The effects of somatostatin analogues RC-160 and SMS-201-995 on tyrosine phosphatase and cell proliferation were investigated in COS-7 and NIH 3T3 cells expressing human somatostatin receptor subtype 1 or 2 (SSTR1 or SSTR2). Binding experiments were performed on membranes from COS-7 cells expressing human SSTR1 or SSTR2 using 125I-labeled [Tyr11]S-14 or [Tyr3]SMS-201-995, respectively. The somatostatin analogues RC-160 and SMS-201-995 exhibited low affinity for SSTR1 (IC50 of 0.43 and 1.5 microM, respectively) and high affinity for SSTR2 (IC50 of 0.27 and 0.19 nM). Addition of these analogues to cells expressing either SSTR1 or SSTR2 did not result in an inhibition of adenylate cyclase activity. In SSTR2-expressing cells, both analogues induced a rapid stimulation of a tyrosine phosphatase activity (EC50: RC-160, 2 pM; SMS-201-995, 6 pM) and an inhibition of serum-stimulated proliferation (EC50: RC-160, 6.3 pM; SMS-201-995, 12 pM). In SSTR1-expressing cells, only RC-160 induced stimulation of a tyrosine phosphatase activity. Both analogues caused an inhibition of cell proliferation at a concentration higher than 10 nM in accordance with their affinities for the SSTR1 receptor subtype. A good correlation between the affinities of RC-160 and SMS-201-995 for each receptor subtype and their potencies to inhibit cell proliferation suggests the involvement of these receptors in cell growth regulation. Tyrosine phosphatase was stimulated by both these analogues in SSTR2 and by RC-160 in SSTR1 at affinities similar to their ability to inhibit growth and bind to receptors, implicating tyrosine phosphatase as a transducer of the growth inhibition signal. We also found that mRNAs of receptor subtypes were variably expressed in different pancreatic and colon cancer cell lines, indicating the necessity of a precise analysis of receptor subtypes in target tissues before therapy with analogues.
Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: A phase I/II clinical trial (1999)

To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 receptor mAb (Daclizumab) therapy in the treatment of patients with severe, sight-threatening, intermediate and posterior noninfectious uveitis, a nonrandomized, open-label, pilot study was performed. Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. All patients were able to tolerate the study medications without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2 receptor therapy may be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile.
A Single-Amino-Acid Change of the Gustatory Receptor Gene, Gr5a, Has a Major Effect on Trehalose Sensitivity in a Natural Population of Drosophila melanogaster (2004)

Variation in trehalose sensitivity and nucleotide sequence polymorphism of the Gr5a gene encoding the gustatory receptor to sugar trehalose were investigated in 152 male lines of Drosophila melanogaster collected from a natural population. Among the observed 59 segregating sites, some pairs of sites showed significant linkage disequilibrium. A single SNP, which results in the Ala218Thr amino acid change, was significantly associated with trehalose sensitivity, as previously suggested. Threonine at amino acid position 218 was found to be the ancestral form in D. melanogaster, suggesting that low trehalose sensitivity was an ancestral form with respect to the receptor function. There was large genetic variation in trehalose sensitivity. It was continuously distributed, indicating that trehalose sensitivity measured by the behavioral assay is a quantitative trait. These results suggest that apart from the Gr5a gene, other genetic factors contribute to variation in trehalose sensitivity. Nucleotide diversity (pi) and nucleotide variation (theta) per site were 0.00874 and 0.00590, respectively. Fu and Li's test and the MK test showed no significant departure from the expectation of selective neutrality in the Gr5a gene. However, we rejected selective neutrality by Tajima's test and Fay and Wu's test with the observed level of recombination. We discuss possible causes of the observed pattern of nucleotide variation in the gustatory receptor Gr5a gene.
Digitally tunable channel dropping filter/equalizer based on waveguide grating router and optical amplifier integration (1994)

We demonstrate a novel and powerful device that permits individual and simultaneous control of all the wavelength channels in a WDM system. The device is based on the monolithic integration of two identical waveguide grating routers with semiconductor optical amplifiers. By biasing appropriately the individual amplifier, each WDM channel can be amplified, detected or modulated. The device exhibits a channel bandwidth of 60 GHz, a channel spacing of 195 GHz and a crosstalk of /spl minus/19 dB.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
O-GLYCBASE: a revised database of O-glycosylated proteins (1996)

O-GLYCBASE is a comprehensive database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the SWISS-PROT and PIR databases as well as directly from recently published reports. Nineteen percent of the entries extracted from the databases needed revision with respect to O-linked glycosylation. Entries include information about species, sequence, glycosylation site and glycan type, and are fully referenced. Sequence logos displaying the acceptor specificity for the GaINAc transferase are shown. A neural network method for prediction of mucin type O-glycosylation sites in mammalian glycoproteins exclusively from the primary sequence is made available by E-mail or WWW. The O-GLYCBASE database is also available electronically through our WWW server or by anonymous FTP.
A Database and Evaluation Methodology for Optical Flow (2010)

The quantitative evaluation of optical flow algorithms by Barron et al. (1994) led to significant advances in performance. The challenges for optical flow algorithms today go beyond the datasets and evaluation methods proposed in that paper. Instead, they center on problems associated with complex natural scenes, including nonrigid motion, real sensor noise, and motion discontinuities. We propose a new set of benchmarks and evaluation methods for the next generation of optical flow algorithms. To that end, we contribute four types of data to test different aspects of optical flow algorithms: (1) sequences with nonrigid motion where the ground-truth flow is determined by tracking hidden fluorescent texture, (2) realistic synthetic sequences, (3) high frame-rate video used to study interpolation error, and (4) modified stereo sequences of static scenes. In addition to the average angular error used by Barron et al., we compute the absolute flow endpoint error, measures for frame interpolation error, improved statistics, and results at motion discontinuities and in textureless regions. In October 2007, we published the performance of several well-known methods on a preliminary version of our data to establish the current state of the art. We also made the data freely available on the web at http://vision.middlebury.edu/flow/ . Subsequently a number of researchers have uploaded their results to our website and published papers using the data. A significant improvement in performance has already been achieved. In this paper we analyze the results obtained to date and draw a large number of conclusions from them.
Metabolic engineering of Pseudomonas putida for the utilization of parathion as a carbon and energy source (2002)

Pseudomonas putida KT2442 was engineered to use the organophosphate pesticide parathion, a compound similar to other organophosphate pesticides and chemical warfare agents, as a source of carbon and energy. The initial step in the engineered degradation pathway was parathion hydrolysis by organophosphate hydrolase (OPH) to p-nitrophenol (PNP) and diethyl thiophosphate, compounds that cannot be metabolized by P. putida KT2442. The gene encoding the native OPH (opd), with and without the secretory leader sequence, was cloned into broad-host-range plasmids under the control of tac and taclac promoters. Expression of opd from the tac promoter resulted in high OPH activity, whereas expression from the taclac promoter resulted in low activity. A plasmid-harboring operons encoding enzymes for p-nitrophenol transformation to beta-ketoadipate was transformed into P. putida allowing the organism to use 0.5 mM PNP as a carbon and energy source. Transformation of P. putida with the plasmids harboring opd and the PNP operons allowed the organism to utilize 0.8 mM parathion as a source of carbon and energy. Degradation studies showed that parathion formed a separate dense, non-aqueous phase liquid phase but was still bioavailable.
THE CELLULAR AND MOLECULAR RESPONSE OF CARDIAC MYOCYTES TO MECHANICAL STRESS (1997)

External load plays a critical role in determining muscle mass and its phenotype in cardiac myocytes. Cardiac myocytes have the ability to sense mechanical stretch and convert it into intracellular growth signals, which lead to hypertrophy. Mechanical stretch of cardiac myocytes in vitro causes activation of multiple second messenger systems that are very similar to growth factor-induced cell signaling systems. Stretch of neonatal rat cardiac myocytes stimulates a rapid secretion of angiotensin II which, together with other growth factors, mediates stretch-induced hypertrophic responses in vitro. In this review, various cell signaling mechanisms initiated by mechanical stress on cardiac myocytes are summarized with emphasis on potential mechanosensing mechanisms and the relationship between mechanical loading and the cardiac renin-angiotensin system.
Nurse executives: new roles, new opportunities. (1999)

As women have been nursing since the earliest days of recorded civilization, so nurses have been associated with health care since the earliest days of recorded medical history. Gender and function have been inextricably woven in ways that created a struggle for success within a male-dominated industry. Nurses, as women, have been undervalued as, until recently, their role in health care has been similarly undervalued. Changing realities in the health care environment have created an opportunity for women's unique skills and talents to be revalued in a way that offers new opportunities for nurses. Teamwork, global thinking, multitasking, creativity, and flexibility are characteristics that have assumed new importance in the marketplace. Nursing leaders possess these attributes, along with a strong clinical foundation that is integrated with knowledge of sound business principles. This combination now positions nurse executives to reach the highest levels of heath care administration. Critical to this achievement is the professional credibility obtained through education at the master's degree level in health care and nursing administration programs that provide the essential tools for professional success. New opportunities for nurse executives afford educators in health care and nursing administration similar opportunities to develop and market programs to this large group of health care professionals who are seeking graduate education in increasing numbers.
Pure Red-Cell Aplasia and Antierythropoietin Antibodies in Patients Treated with Recombinant Erythropoietin (2002)

Neutralizing antierythropoietin antibodies and pure red-cell aplasia can develop in patients with the anemia of chronic renal failure during treatment with epoetin.
Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer. (1994)

A large group of transcription factors regulating cell growth and differentiation share a dimeric alpha-helical DNA-binding domain termed the basic region helix-loop-helix (bHLH). bHLH proteins associate as homodimers and heterodimers having distinctive DNA-binding activities and transcriptional activities that are central to the regulated differentiation of a number of tissues. Some of the bHLH residues specifying these activities have been identified, but a full understanding of their function has awaited further structural information. We report here the crystal structure of the transcription factor E47 bHLH domain bound to DNA. The bHLH of E47 is a parallel, four-helix bundle with structural features that distinguish it from the bHLH-zipper protein Max. The E47 dimer makes nonequivalent contacts to each half of the -CACCTG- binding site. Sequence discrimination at the center of the E box may result from interaction with both the DNA bases and the phosphodiester backbone.
Solvent Evaporation Processes for the Production of Controlled Release Biodegradable Microsphere Formulations for Therapeutics and Vaccines (1998)

Novel drug delivery technologies have now evolved to allow the clinical production of new dosage forms. One new form, biodegradable microspheres, may have utility as a second-generation formulation for parenterally administered proteins and peptides or may be required for the success of some new chemical entities. Here, we have focused on the use of poly(lactic-co-glycolic acid) (PLGA) microspheres to provide a continuous delivery of therapeutic proteins or a pulsatile delivery of protein-based vaccines. To date, our success with solvent evaporation processes has been primarily in the production of microspheres with a triphasic protein release pattern instead of a continuous release. However, with continued development efforts, this method may be used to produce continuous release protein formulations. While this review draws from our own work, there is a great deal of excellent research in this area at both universities and industrial laboratories. This work combined with our studies indicates that this technology holds much promise for new protein formulations that will provide improvements in patient care and, perhaps, increased efficacy.
Amyloid A4 Protein and Its Precursor in Down's Syndrome and Alzheimer's Disease (1989)

In patients with Alzheimer's disease, amyloid fibrils that are aggregates of A4 protein subunits are deposited in the brain. A similar process occurs at an earlier age in persons with Down's syndrome. To investigate the deposition of amyloid in these diseases, we used a radioimmunoassay to measure levels of the amyloid precursor (PreA4) in the serum of 17 patients with Down's syndrome, 15 patients with Alzheimer's disease, and 33 normal elderly controls. The mean (+/- SD) concentration of serum PreA4 was increased 1.5-fold in patients with Down's syndrome (2.49 +/- 1.13 nmol per liter) as compared with that in controls (1.68 +/- 0.49 nmol per liter; P less than 0.007); the levels in patients with Alzheimer's disease were similar to those in controls (1.83 +/- 0.78; P less than 0.98). We also found that the concentration of PreA4 in the brain tissue of two adults with Down's syndrome (100 and 190 pmol per gram) was higher than that in the brain tissue of either 26 patients with Alzheimer's disease (64.4 +/- 17.3 pmol per gram) or 17 elderly controls with neurologic disease (68.5 +/- 26.3 pmol per gram). Immunocytochemical studies of brain tissue from 26 patients with Down's syndrome showed that the deposition of A4 protein amyloid began in these patients approximately 50 years earlier than it began in 127 normal aging subjects studied previously, although the rate of deposition was the same. We conclude that, since the gene for PreA4 is on the long arm of chromosome 21, which is present in triplicate in Down's syndrome, overexpression of this gene may lead to increased levels of PreA4 and amyloid deposition in Down's syndrome. However, since increased levels of PreA4 are not present in Alzheimer's disease, additional factors must account for the amyloid deposition in that disorder.
Nuclear and Nucleolar Localization of 18-kDa Fibroblast Growth Factor-2 Is Controlled by C-terminal Signals (2004)

Members of high (22-, 22.5-, 24-, and 34-kDa) and low (18-kDa) molecular mass forms of fibroblast growth factor-2 (FGF-2) regulate cell proliferation, differentiation, and migration. FGF-2s have been previously shown to accumulate in the nucleus and nucleolus. Although high molecular weight forms of FGF-2 contain at least one nuclear localization signal (NLS) in their N-terminal extension, the 18-kDa FGF-2 does not contain a standard NLS. To determine signals controlling the nuclear and subnuclear localization of the 18-kDa FGF-2, its full-length cDNA was fused to that of green fluorescent protein (GFP). The fusion protein was primarily localized to the nucleus of COS-7 and HeLa cells and accumulated in the nucleolus. The subcellular distribution was confirmed using wild type FGF-2 and FGF-2 tagged with a FLAG epitope. A 17-amino acid sequence containing two groups of basic amino acid residues separated by eight amino acid residues directed GFP and a GFP dimer into the nucleus. We systematically mutated the basic amino acid residues in this nonclassical NLS and determined the effect on nuclear and nucleolar accumulation of 18-kDa FGF-2. Lys(119) and Arg(129) are the key amino acid residues in both nuclear and nucleolar localization, whereas Lys(128) regulates only nucleolar localization of 18-kDa FGF-2. Together, these results demonstrate that the 18-kDa FGF-2 harbors a C-terminal nonclassical bipartite NLS, a portion of which also regulates its nucleolar localization.
Targeting Natural Killer Cells to Acute Myeloid LeukemiaIn Vitrowith a CD16 × 33 Bispecific Killer Cell Engager and ADAM17 Inhibition (2013)

CD16 × 33 BiKE can overcome self-inhibitory signals and effectively elicit NK cell effector activity against AML. These in vitro studies highlight the potential of CD16 × 33 BiKE ± ADAM17 inhibition to enhance NK cell activation and specificity against CD33(+) AML, which optimally could be applied in patients with relapsed AML or for adjuvant antileukemic therapy posttransplantation.
Taxol (1992)

Taxol has been demonstrated in numerous laboratories worldwide to have broad-spectrum antitumor activity against many tumor models. The susceptible tumors include murine leukemias and solid tumors, and human solid tumor xenografts. The initial findings of taxol's ineffectiveness against most distal site tumor models was probably a consequence of the insolubility of taxol in nearly all the vehicles used in those early studies. On the occasions when an ethanol-based vehicle was used to dissolve taxol, substantial distal site antitumor activity was observed. Although no definitive schedule dependency data have evolved, once-a-day or every-other-day i.v. injections for several treatments have proved to be reproducibly effective in stringent s.c. tumor models. Attempts to discern a therapeutically synergistic cytotoxic drug combination was made on two occasions without success. In the manner evaluated, taxol plus either adriamycin, cisplatin, cyclophosphamide or etoposide (VP-16) were not meaningfully more efficacious than the more effective drug in each of those combination settings.