gebhart/patrepeval huggingface dataset:
Rational Design and Engineered Biosynthesis of a Novel 18-Carbon Aromatic Polyketide (1997)

Heuristics for the rational design of aromatic polyketides were recently proposed and tested via the engineered biosynthesis of two novel products. Here we have applied these rules to a previously untested subclass of aromatic polyketides, the unreduced molecules. A recombinant strain of Streptomyces coelicolor expressing the genes for the frenolicin (fren) minimal polyketide synthase (PKS) and the TcmN subunit (a putative aromatase/cyclase) from the tetracenomycin PKS was constructed, and its principal product, the nonaketide PK8, was characterized by spectroscopic and isotope labeling methods. The structure of PK8 was exactly as predicted by the design rules. Surprisingly however, no major octaketide product was isolated from this strain. In contrast, a strain expressing the fren minimal PKS genes alone produced octaketides to the exclusion of nonaketides. These results differ from earlier reports of both octaketide and nonaketide products from strains containing the fren minimal PKS and a regiospecific ketoreductase. We therefore propose a model for bacterial aromatic polyketide biosynthesis in which auxiliary PKS subunits such as ketoreductases, aromatases, and cyclases can modulate the intrinsic specificity of the minimal PKS with respect to both the folding pattern and the chain length of the final product.
Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells (2005)

Lymphocyte activation gene 3 (LAG-3/CD223) is a CD4 homolog known to be selectively expressed in activated T and NK cells. It is thought to have a negative regulatory function in T cells. With the help of new monoclonal antibodies against mouse LAG-3, we show that LAG-3 surface expression is not limited to activated T and NK cells but is also found on activated B cells. Induction of B cell surface expression is T cell dependent and mediated by a soluble factor. The majority of LAG-3 on B cell surface is endogenously produced, even though soluble LAG-3 is present in the culture supernatants and can be passively absorbed. As B cells express LAG-3 in a T cell dependent manner and not when activated by Toll-like-receptor agonists alone, we propose LAG-3 as a new marker of T cell induced B cell activation.
Microbial–Host Interactions: Selecting the Right Probiotics and Prebiotics for Infants (2009)

Probiotics were originally used to influence human health through intestinal microbiota alterations. At present, probiotics and their effects on human health have been demonstrated both within different food matrices and as single or mixed culture preparations. The health-promoting properties are known to be strain-dependent. Thus, strain identification and characterization are important: only well-characterized strains identified with modern techniques are acceptable, especially if health claims are desired. Linking the strain to a specific health effect as well as to enable accurate surveillance and epidemiological studies are important targets. Currently there are specific strains which have demonstrated beneficial in vitro properties and clinically proven health benefits. Such specific probiotics have been included in recommendations on pediatric nutrition. The model is the microbiota of the healthy breastfed infant. Molecular methods in microbiota assessment enable more specific probiotics and prebiotics to be identified for infants with aberrancies in intestinal microbiota. Probiotic products require information on the concentration and viability of the strain(s) in the product as well as data on required dosages. Continuous control of probiotic strains or strain combinations is a must as small changes in production process or growth media may significantly affect the properties of a strain or strain combination.
The International HapMap Project (2003)

The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.
Lemur tyrosine kinase-3 (LMTK3) in cancer and evolution (2011)

Justin Stebbing, Aleksandra Filipović and Georgios Giamas 1 Department of Oncology and Surgery, Imperial College, Hammersmith Campus, London Received: June 8, 2011; Accepted: June 9, 2011; Published: June 16, 2011; Correspondence: Justin Stebbing, email: // // Abstract
Immunomagnetic Techniques for the Enrichment and Detection of Isolated Breast Carcinoma Cells in Bone Marrow and Peripheral Blood (1997)

Detection of isolated tumor cells (TC) in bone marrow (BM) from patients with breast cancer is usually accomplished by immunocytochemical (ICC) analysis of up to 2 X 10(6) mononuclear cells (MNC). However, this method is cumbersome if large numbers of BM cells (i.e. > 1 X 10(7) cells) are to be analyzed. This emphasizes the need for TC enrichment strategies. This report describes immunomagnetic separation (IMS) techniques for enrichment and detection of viable breast carcinoma cells in BM and peripheral blood (PB). The positive IMS technique was performed by incubation of MNC with 2.8 microns magnetic particles (rat antimouse IgG1 M280-Dynabeads) coated with monoclonal antibody (mAb) against epithelial surface antigens. The rosetted tumor cells were then visualized by ICC staining using alkaline phosphatase-conjugated A45-B/B3 anticytokeratin mAb (Fab). The negative IMS technique was performed by incubation of MNC with anti-CD45-coated M450-Dynabeads (4.5 microns), followed by ICC staining of the nonrosetted cells. When 1000, 100, and 10 breast carcinoma cells were mixed with 1 X 10(7) MNC, an average of 748 (n = 9), 70 (n = 10), and 7.8 TC (n = 8), respectively, were detected with the positive IMS technique. With the negative IMS technique, 648 (n = 8), 57.8 (n = 6), and 7.3 TC (n = 6), respectively, were detected. The analysis of 1 X 10(7) MNC with the IMS techniques was compared with the ICC analysis of 2 X 10(6) unseparated MNC. A mean 3.7-fold (range 1.5-6.4) to 4.2-fold (2.5-8.2) (positive IMS) and 3.1-fold (range 2.0-5.0) to 3.8-fold (2.0-6.0) (negative IMS) higher TC detection frequency was achieved after enrichment by IMS in experiments with 100 and 1000 TC/10(7) MNC. The IMS techniques were used for examination of BM samples from locally advanced breast cancer patients. A 5.3-fold mean increase (range 2.1-13.3) in the number of TC detected was obtained when the use of positive and negative IMS together was compared with the direct ICC analysis of unseparated MNC (n = 11). Enrichment of TC by IMS techniques enables us to examine large numbers of MNC from BM or PB, which can result in the detection and characterization of minimal residual disease with increased sensitivity and specificity.
Association of Sorcin With the Cardiac Ryanodine Receptor (1995)

Sorcin is a 22-kDa calcium-binding protein initially identified in multidrug-resistant cells; however, its patterns of expression and function in normal tissues are unknown. Here we demonstrate that sorcin is widely distributed in rodent tissues, including the heart, where it was localized by immunoelectron microscopy to the sarcoplasmic reticulum. A > 500-kDa protein band immunoprecipitated from cardiac myocytes by sorcin antiserum was indistinguishable in size on gels from the 565-kDa ryanodine receptor/calcium release channel recognized by ryanodine receptor-specific antibody. Association of sorcin with a ryanodine receptor complex was confirmed by complementary co-immunoprecipitations of sorcin with the receptor antibody. Forced expression of sorcin in ryanodine receptor-negative Chinese hamster lung fibroblasts resulted in accumulation of the predicted 22-kDa protein as well as the unexpected appearance of ryanodine receptor protein. In contrast to the parental host fibroblasts, sorcin transfectants displayed a rapid and transient rise in intracellular calcium in response to caffeine, suggesting organization of the accumulated ryanodine receptor protein into functional calcium release channels. These data demonstrate an interaction between sorcin and the ryanodine receptor and suggest a role for sorcin in modulation of calcium release channel activity, perhaps by stabilizing the channel protein.
Chromium Oligopeptide Activates Insulin Receptor Tyrosine Kinase Activity (1997)

A possible new mechanism for the amplification of insulin receptor tyrosine kinase activity in response to insulin has been identified. The chromium-containing oligopeptide low molecular weight chromium-binding substance (LMWCr) does not effect the tyrosine protein kinase activity of rat adipocytic membrane fragments in the absence of insulin; however, insulin-stimulated kinase activity in the membrane fragments is increased up to 8-fold by the oligopeptide. Using isolated rat insulin receptor, LMWCr has been shown to bind to insulin-activated insulin receptor with a dissociation constant of circa 250 pM, resulting in the increase of its tyrosine protein kinase activity. The ability of LMWCr to stimulate insulin receptor tyrosine kinase activity is dependent on its chromium content. The results appear to explain the previously poorly understood relationship between chromium and adult-onset diabetes and cardiovascular disease.
Femtosecond optical transfection of cells:viability and efficiency (2006)

Photoporation is a rapidly expanding technique for the introduction of macromolecules into single cells. However, there remains no study into the true efficiency of this procedure. Here, we present a detailed analysis of transfection efficiency and cell viability for femtosecond optical transfection using a titanium sapphire laser at 800 nm. Photoporation of 4000 Chinese Hamster ovary cells was performed, representing the largest optical transfection study reported to date. We have investigated a range of laser fluences at the cell membrane and, at 1.2 microJ/cm(2), have found an average transfection efficiency of 50 +/- 10%. Contrary to recent literature, in which 100% efficiency is claimed, our measure of efficiency accounts for all irradiated cells, including those lost as a result of laser treatment, thereby providing a true biological measure of the technique.
Dynamic Server Selection In The Internet (2005)

Abstract As distributed information services like the World Wide Web become increasingly popular on the Internet, problems of scale are clearly evident. A promising technique that addresses many of these problems is service (or document) replication. However, when a service is replicated, clients then need the additional ability to find a ``good'''' provider of that service. In this paper we report on techniques for finding good service providers without a priori knowledge of server location or network topology. We consider the use of two principal metrics for measuring distance in the Internet: hops, and round-trip latency. We show that these two metrics yield very different results in practice. Surprisingly, we show data indicating that the number of hops between two hosts in the Internet is {\em not\/} strongly correlated to round-trip latency. Thus, the distance in hops between two hosts is not necessarily a good predictor of the expected latency of a document transfer. Instead of using known or measured distances in hops, we show that the extra cost at runtime incurred by dynamic latency measurement is well justified based on the resulting improved performance. In addition we show that selection based on dynamic latency measurement performs much better in practice that any static selection scheme. Finally, the difference between the distribution of hops and latencies is fundamental enough to suggest differences in algorithms for server replication. We show that conclusions drawn about service replication based on the distribution of hops need to be revised when the distribution of latencies is considered instead.
Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection (1991)

After the onset of parasite egg deposition, mice infected with the helminth Schistosoma mansoni mount strong Th2 cytokine responses in the absence of significant Th1 cytokine synthesis. To examine the basis of this immunoregulatory state, spleen or lymph node cells from schistosome-infected mice were stimulated with parasite-specific Ag and the supernatants tested for their capacity to suppress IFN-gamma synthesis by a Th1 cell line. Strong inhibition was observed that was neutralized by a mAb against IL-10, a cytokine previously shown to down-regulate Th1 cytokine synthesis. By means of ELISA measurements the production of IL-10 in schistosome infection was confirmed and shown to depend on CD4+ T cells. IL-10 synthesis stimulated by either mitogen or Ag was observed only at those stages of infection when Th2 response induction and Th1 cytokine down-regulation also occurred and was not detected in mice vaccinated with attenuated parasites. Moreover, the addition of the neutralizing anti-IL-10 mAb to Ag-stimulated spleen cell cultures from infected mice caused a dramatic augmentation in IFN-gamma synthesis. These findings suggest that IL-10 is responsible for the down-regulation of Th1 responses observed in schistosome infections, a phenomenon that may enable the parasite to escape potentially harmful cell-mediated responses.
Parathyroid Hormone Messenger Ribonucleic Acid: Effects of Calcium on Cellular Regulation in Vitro* (1983)

The effects of changes in the concentration of extracellular calcium the principal regulatory of PTH secretion, on the cellular levels of the mRNA encoding prepro-PTH, a precursor of PTH, were studied in bovine parathyroid slices in vitro using a sensitive radiodensitometric cDNA hybridization assay and mRNA translation in a wheat germ cell-free system. Although lowering the calcium from 5 to 0.5 mM during 5- to 70-h incubations stimulated the secretion of PTH 4- to 8-fold and pro-PTH synthesis 1.4-fold, the cellular levels of total hybridizable PTH mRNA did not change. However, a 2- to 3-fold increase in PTH mRNA, which could be hybridized to oligo-dT-cellulose [poly(A)-rich], was observed in the slices incubated in 5 mM calcium (suppressed slices). The poly(A)-rich PTH mRNA constituted 30% of the total PTH mRNA in suppressed gland slices and 10% of the total PTH mRNA in stimulated gland slices. PTH mRNA did not decay measurably when RNA synthesis in the gland slices was inhibited with actinomycin D and alpha-amanitin for 6 h. Both the stability and the lack of perturbation of the cellular levels of total of total hybridizable PTH mRNA by changes in the concentration of extracellular calcium suggest that the short term regulation of PTH biosynthesis involves posttranscriptional mechanisms.
Bacterial Programmed Cell Death and Multicellular Behavior in Bacteria (2006)

Traditionally, programmed cell death (PCD) is associated with eukaryotic multicellular organisms. However, recently, PCD systems have also been observed in bacteria. Here we review recent research on two kinds of genetic programs that promote bacterial cell death. The first is mediated by mazEF, a toxin-antitoxin module found in the chromosomes of many kinds of bacteria, and mainly studied in Escherichia coli. The second program is found in Bacillus subtilis, in which the skf and sdp operons mediate the death of a subpopulation of sporulating bacterial cells. We relate these two bacterial PCD systems to the ways in which bacterial populations resemble multicellular organisms.
Clonality and field cancerization in intraductal papillary-mucinous tumors of the pancreas (2001)

The current results suggest that multiple, distinct K-ras mutations of different ductal hyperplasias in a given pancreas are due to a field (multicentric) cancerization effect in IPMTs. Thus, most of IPMTs are polyclonal and/or oligoclonal in origin, i.e., IPMTs may originate from multiple (molecularly distinct) precursor lesions.
Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment (2005)

The new england journal of medicine * CI denotes confidence interval. P values were not adjusted for multiple comparisons. In the donepezil group, when corrected for multiple comparisons, the P value at 24 months for all subjects became nonsignificant (P=0.052), and the P value at 36 months for APOE e 4 carriers also became nonsignificant (P=0.078).
Prognostic Significance of Activated Akt Expression in Pancreatic Ductal Adenocarcinoma (2004)

p-Akt expression is a significant prognostic indicator for PDAC. Inhibition of Akt is a possible molecular approach for treatment of PDAC.
Performance of Selected Chemical Compounds in Eliciting Feeding of Asian Buffalo Leech, Hirudinaria manillensis (2011)

The understanding of appetitive and foraging behavior of medicinal leeches is important for successful breeding and culture of healthy leeches. This study was conducted to determine the response of Asian buffalo leech, Hirudinaria manillensis for combinations of selected chemical compounds. Five solutions with different combinations of sodium chloride, arginine, glycine and glucose were filled into rubber sacs and fed to the leeches in 3 replicates each. Heparinized cattle blood was used as the control. The percentages of leech that approached the sacs and the average volume consumed per individual were estimated. After feeding, the survival of leeches in each treatment was monitored daily for seven days. The results showed that a solution containing 150 mM sodium chloride, 1 mM L-arginine, 50 mM glycine and 1 mg mL-1 glucose gave significantly higher (p<0.05) approach percentage and feed consumption than other solutions. Its performance was equivalent to the cattle blood. Poor feeding consumption was observed when only L-arginine or glycine were added to the saline solution. Nevertheless, mortality up to 40% was observed among the feeding leeches while the survival of non-feeding leeches was nearing or at 100%.
The Rana catesbeiana rcr Gene Encoding a Cytotoxic Ribonuclease (1998)

Rana catesbeiana ribonuclease (RC-RNase) is a pyrimidine-guanine sequence-specific ribonuclease found in R. catesbeiana (bullfrog) oocytes. It possesses both ribonuclease activity and cytotoxicity against tumor cells. We report here for the first time the cloning of RC-RNase cDNA from liver rather than from oocytes where RC-RNase is stored. An internal fragment of cDNA was obtained by reverse transcription-PCR using deduced oligonucleotides as primers. Full-length cDNA was obtained by 5'- and 3'-RACE technique. The cDNA clone, named rcr gene, contained a 5'-untranslated region, a putative signal peptide (22 amino acids), a mature protein (111 amino acids), a 3'-untranslated region, and a polyadenylation site. The cDNA which encoded the mature protein was fused upstream with a modified pelB signal peptide DNA and inserted into pET11d for expression in Escherichia coli strain BL21(DE3). The secretory RC-RNase in the culture medium was enzymatically active and was purified to homogeneity. The recombinant RC-RNase had the same amino acid sequence, specific activity, substrate specificity, antigenicity, and cytotoxicity as that of native RC-RNase from frog oocytes. Amino acid residues His-10, Lys-35, and His-103 are involved in RC-RNase catalytic activity. Ribonucleolytic activity was involved in and may be essential for RC-RNase cytotoxicity. DNA sequence analysis showed that RC-RNase had approximately 45% identity to that of RNase superfamily genes. This indicates that RC-RNase is a distinct ribonuclease gene in the RNase superfamily.
The myogenic transcriptional network (2011)

Myogenesis has been a leading model for elucidating the molecular mechanisms that underlie tissue differentiation and development since the discovery of MyoD. During myogenesis, the fate of myogenic precursor cells is first determined by Pax3/Pax7. This is followed by regulation of the myogenic differentiation program by muscle regulatory factors (Myf5, MyoD, Myog, and Mrf4) to form muscle tissues. Recent studies have uncovered a detailed myogenic program that involves the RP58 (Zfp238)-dependent regulatory network, which is critical for repressing the expression of inhibitor of DNA binding (Id) proteins. These novel findings contribute to a comprehensive understanding of the muscle differentiation transcriptional program.
Effects of Beta-Carotene, Vitamin A, and Glucocorticoids on Collagen Synthesis in Wounds (1971)

Beta-Carotene, a precursor of vitamin A, was as effective as vitamin A itself in reversing the retarding effects of glucocorticoids on the tensile strength of incised wounds and on the accumulation of collagen in sponge granulomas.
1.5 µm Semiconductor Wavelength Tunable Optical Filter Using a λ/4-Shifted Passive Waveguide Grating Resonator (1991)

A 1.5 µm semiconductor wavelength tunable optical filter using a λ/4-shifted passive waveguide grating resonator has been developed. Both wavelength channel number and transmissivity are analyzed with respect to grating coupling coefficient, filter length, and waveguide loss. The influence of facet reflectivity and phase-shift value on transmissivity and wavelength channel number are also investigated. A wavelength shift as wide as 42 Å is able to be obtained by carrier injection with the fabricated filter.
AIDS caregiving crisis (1989)

Within the next few years, it is very likely that AIDS will personally affect almost everyone in the United States in some manner. A relative, neighbor, friend, acquaintance, or coworker may develop AIDS. It is estimated that 1 to 1.5 million people in the United States are presently infected with the human immunodeficiency virus and may develop AIDS. AIDS is, indeed, a major public health problem. With the high cost of hospital care, home care is an effective health care alternative for people with AIDS. Obviously, people feel more comfortable in their own homes. Professional home care services are available for many people with AIDS but cannot always meet their needs 24 hours a day. The Home Nursing Course for Caregivers of Persons With AIDS is an example of an effective way to begin to deal with the present and future caregiving crisis. Nurses serve as both teachers and role models while presenting the course. This type of course presents a challenge for nurses to use their knowledge, experiences, and creativity to continue to address AIDS and other health care crises in similar ways.
Parallel language constructs for tensor product computations on loosely coupled architectures (1989)

Distributed memory architectures offer high levels of performance and flexibility, but have proven awkward to program. Current languages for nonshared memory architectures provide a relatively low-level programming environment, and are poorly suited to modular programming, and to the construction of libraries. This paper describes a set of language primitives designed to allow the specification of parallel numerical algorithms at a higher level. We focus here on tensor product array computations, a simple but important class of numerical algorithms. We consider first the problem of programming one dimensional “kernel” routines, such as parallel tridiagonal solvers, and after that look at how such parallel kernels can be combined to form parallel tensor product algorithms.