gebhart/patrepeval huggingface dataset:
Production of a polyketide natural product in nonpolyketide-producing prokaryotic and eukaryotic hosts (1998)

The polyketides are a diverse group of natural products with great significance as human and veterinary pharmaceuticals. A significant barrier to the production of novel genetically engineered polyketides has been the lack of available heterologous expression systems for functional polyketide synthases (PKSs). Herein, we report the expression of an intact functional PKS in Escherichia coli and Saccharomyces cerevisiae. The fungal gene encoding 6-methylsalicylic acid synthase from Penicillium patulum was expressed in E. coli and S. cerevisiae and the polyketide 6-methylsalicylic acid (6-MSA) was produced. In both bacterial and yeast hosts, polyketide production required coexpression of 6-methylsalicylic acid synthase and a heterologous phosphopantetheinyl transferase that was required to convert the expressed apo-PKS to its holo form. Production of 6-MSA in E. coli was both temperature- and glycerol-dependent and levels of production were lower than those of P. patulum, the native host. In yeast, however, 6-MSA levels greater than 2-fold higher than the native host were observed. The heterologous expression systems described will facilitate the manipulation of PKS genes and consequent production of novel engineered polyketides and polyketide libraries.
High-Speed Programmable Logic Array Adders (1979)

Programmable Logic Array (PLA) adders are described which perform an addition in one cycle with a single pass through a PLA and require a reasonable number of product terms for an 8-, 16-, or even a 32-bit adder. The PLA features two- bit input decoders feeding an AND array followed by an OR array whose outputs are pairwise EXCLUSIVE-ORed. Carry-look-ahead adder equations, adapted to the PLA to require relatively few product terms, are adjusted for maximum sharing of product terms. The number of unique product terms is a relative measure of one of the physical dimensions of the PLA. Equations for contiguous sum bits are grouped into strings, each using a common input carry. A procedure optimally assigns sum bits to strings to further minimize the total number of unique product terms. The methods are extended to PLAs with decoders of increased inputs and substantially reduced product terms. They can serve as dedicated macro functions on a chip, using special decoders relevant to adders. As a result, the other PLA dimension comprising the number of outputs from all input decoders increases only moderately, and can even decrease, with larger decoders. Finally, the PLA adder can be further substantially compressed by splitting the OR array into two parts such that a row of the AND array is shared between two product terms, and an OR array column is shared between two sums of product terms.
Combining Morphology and DNA Barcoding Resolves the Taxonomy of Western MalagasyLiotrigonaMoure, 1961 (Hymenoptera: Apidae: Meliponini) (2010)

The taxonomy of the western Malagasy stingless bees (Liotrigona spp.) has been complicated by the high degree of morphological similarity between the described species. This group includes one of the smallest bee species of the world, Liotrigona bitika (Brooks & Michener, 1988). However, the description of this species is solely based on size differences, and observation of individuals intermediate in size between Liotrigona bitika and Liotrigona madecassa (Saussure, 1890) have cast doubt on the distinctness of the former taxon. I examined specimens, collected in the dry deciduous forest of Kirindy, representing all three of the described Liotrigona species of western Madagascar using a combined approach of size measures and DNA sequence analysis of the cytochrome oxidase I barcoding region. The analysis revealed all described taxa to be valid and furthermore uncovered the existence of a fourth taxon, described as Liotrigona kinzelbachi sp. n. The sympatric species exhibit non-overlapping body size ranges, indicating a strong influence of body size in niche differentiation of this otherwise morphological highly similar clade.
Cloning and Sequence Analysis ofczcGenes inAlcaligenessp. Strain CT14 (1996)

We have isolated 14 cadmium (Cd)-resistant, soil-borne bacteria. Among those, strain CT14, which was identified as an Alcaligenes sp., has a czc (cadmium, zinc, and cobalt divalent cation resistant determinant) system. Here we report the nucleotide sequence of 4 genes (czcCBAD) of the system. CzcCBA showed over 98% identity with those of A. eutrophus CH34, however, CzcD, the distal gene product, was 117 amino acids longer than that (199 amino acids) of A. eutrophus CH34, and had considerable similarity to the members of the CDF (cation diffusion facilitator) family proteins all over the region.
Expression of a novel high-affinity purine nucleobase transport function in mutant mammalian T lymphoblasts. (1986)

The single nucleoside transport function of mouse S49 lymphoblasts also transports purine bases (B. Aronow and B. Ullman, J. Biol. Chem. 261:2014-2019, 1986). This transport of purine bases by S49 cells is sensitive to inhibition by dipyridamole (DPA) and 4-nitrobenzylthioinosine, two potent inhibitors of nucleoside transport. Therefore, wild-type S49 cells cannot salvage low hypoxanthine concentrations in the presence of 10 microM DPA and 11 microM azaserine; the latter is a potent inhibitor of purine biosynthesis. Among a mutagenized wild-type population, a cell line, JPA2, was isolated which could proliferate in 50 microM hypoxanthine-11 microM azaserine-10 microM DPA. The basis for the survival of JPA2 cells under these selective conditions was expression of a unique, high-affinity purine nucleobase transport function not present in wild-type cells. JPA2 cells could transport 5 microM concentrations of hypoxanthine, guanine, and adenine 15- to 30-fold more efficiently than parental cells did. Kinetic analyses revealed that the affinity of the JPA2 transporter for all three purine bases was much greater than that of the wild-type nucleobase transport system. Moreover, nucleobase transport in JPA2 cells, unlike that in parental cells, was insensitive to inhibition by DPA, 4-nitrobenzylthioinosine, sulfhydryl reagents, and nucleosides. No alterations in nucleoside transport capability, phosphoribosylpyrophosphate levels, or purine phosphoribosyltransferase enzymes were detected in JPA2 cells. Thus, JPA2 cells express a novel nucleobase transport capability which can be distinguished from the nucleoside transport function by multiple biochemical parameters.
Frataxin knockin mouse (2002)

Friedreich ataxia is the consequence of frataxin deficiency, most often caused by a GAA repeat expansion in intron 1 of the corresponding gene. Frataxin is a mitochondrial protein involved in iron homeostasis. As an attempt to generate a mouse model of the disease, we introduced a (GAA)(230) repeat within the mouse frataxin gene by homologous recombination. GAA repeat knockin mice were crossed with frataxin knockout mice to obtain double heterozygous mice expressing 25-36% of wild-type frataxin levels. These mice were viable and did not develop anomalies of motor coordination, iron metabolism or response to iron loading. Repeats were meiotically and mitotically stable.
Feature-based survey of model transformation approaches (2006)

Model transformations are touted to play a key role in Model Driven Development™. Although well-established standards for creating metamodels such as the Meta-Object Facility exist, there is currently no mature foundation for specifying transformations among models. We propose a framework for the classification of several existing and proposed model transformation approaches. The classification framework is given as a feature model that makes explicit the different design choices for model transformations. Based on our analysis of model transformation approaches, we propose a few major categories in which most approaches fit.
Fluctuations and Supercoiling of DNA (1994)

Frequently, DNA in vivo is organized into loops that are partially underwound and consequently form interwound helical supercoils. Methods from polymer statistical mechanics are used to show how the competition between entropy (thermal fluctuations) and elastic energy determines supercoil radius and pitch, in good agreement with recent experiments and simulations. Supercoil reorganization by means of slithering (reptation) of the DNA along the supercoil is argued to be a slow process. Extension of supercoiled DNA by an applied force shows a number of unexpected features, including coexistence of interwound and helical states.
Review of the efficacy and safety of antidepressants in youth depression (2005)

With the variability in trial methodology and the variation in the drug/placebo response rates within a single trial, clinicians need to be judicious in their interpretation of research data on pediatric antidepressant trials. Significant methodological issues may also have affected the efficacy and safety results from these clinical trials.
Trilinearity of three perspective views and its associated tensor (2002)

It has been established that certain trilinear forms of three perspective views give rise to a tensor of 27 intrinsic coefficients. We show in this paper that a permutation of the the trilinear coefficients produces three homography matrices (projective transformations of planes) of three distinct intrinsic planes, respectively. This, in turn, yields the result that 3D invariants are recovered directly-simply by appropriate arrangement of the tensor's coefficients. On a secondary level, we show new relations between fundamental matrix, epipoles, Euclidean structure and the trilinear tensor. On the practical side, the new results extend the existing envelope of methods of 3D recovery from 2D views-for example, new linear methods that cut through the epipolar geometry, and new methods for computing epipolar geometry using redundancy available across many views.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Activation of Transforming Growth Factor-β by the Integrin αvβ8 Delays Epithelial Wound Closure (2006)

Transforming growth factor (TGF)-beta family members regulate multiple aspects of wound repair through effects on cell proliferation, matrix production, and tissue inflammation, but the effects of TGF-beta on wound closure itself have been controversial. We found that blocking antibodies to TGF-beta enhanced the degree of closure of scratch wounds in primary airway epithelial monolayers, while addition of exogenous TGF-beta1 inhibited the degree of closure, suggesting that endogenous activation of TGF-beta normally serves as a brake on the degree of wound closure. Although these cells secreted large amounts of TGF-beta2 and small amounts of TGF-beta1, blockade of TGF-beta1 enhanced the degree of wound closure, whereas blockade of TGF-beta2 had no effect. TGF-beta1 (but not TGF-beta2) can be activated by two members of the integrin family, alphavbeta6 and alphavbeta8, which are both expressed on airway epithelial cells. Wounding induced activation of TGF-beta through effects of both integrins, but antibodies against alphavbeta8 enhanced the degree of wound closure, whereas antibodies against alphavbeta6 did not.
Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma. (1991)

We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma.
Powering the dream [power over Ethernet] (2006)

Power over Ethernet (PoE) brings a host of benefits to the design, implementation and long-term usability of wired Ethernet local area networks (LANs). Cost, flexibility and even safety are all enhanced. It overcomes the major limitation that system designers often encounter whereby they must locate powered network devices within close proximity to AC power outlets. With PoE, both data and power at a safe nominal 48VDC are carried over the same Ethernet cable. To take full advantage of PoE, the network devices will also be required to handle the hand-shaking process that allows the network hub to recognise a device as being PoE enabled and understand and manage its specific power needs.
Fatty Acid Synthesis of an Eicosapentaenoic Acid-Producing Bacterium: De Novo Synthesis, Chain Elongation, and Desaturation Systems (1997)

The fatty acid synthesis systems of a Shewanella sp., strain SCRC-2738, that produces a large amount of eicosapentaenoic acid were investigated. Two kinds of fatty acid synthesis system, de novo synthesis and chain elongation ones, were detected in the cytosol. The de novo synthesis system required an acyl carrier protein, and produced palmitoyl- and palmitoleoyl-acyl carrier proteins as final products. The chain elongation system also required an acyl carrier protein, and produced an acyl-acyl carrier protein as a product, using palmitoyl-, palmitoleoyl-, stearoyl-, and oleoyl-CoAs as primers but not eicosanoyl- or eicosenoyl-CoA. There were an anaerobic pathway and an aerobic desaturation one for the production of unsaturated fatty acids. Eicosapentaenoic acid seemed to be produced through the aerobic desaturation pathway and not through the anaerobic one, since the latter pathway produced n-7 type monoenoic fatty acids, which are different from eicosapentaenoic acid in the position of the double bond. The desaturase utilized an acyl-acyl carrier protein as a substrate, and this activity increased in the presence of ferredoxin and ferredoxin NADP+ reductase. Thus, Shewanella sp., strain SCRC-2738, has novel characteristics as to both fatty acid chain elongation and desaturation systems.
Mechanism of p53 Dependent Apoptosis and its Role in Breast Cancer Therapy (2000)

Abstract : The ability of pS3 to induce apoptosis requires its sequence-specific DNA binding activity; however, the transactivation deficient p53(gln22-ser23) can still induce apoptosis. Previously, we have shown that the region between residues 22 and 97 in p53 is necessary for such activity. In an effort to more precisely map adomain necessary for apoptosis within the N-terminus, we found that deletion of the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of apoptosis. Surprisingly, p53(Delta1-42), which lacks the N-terminal 42 amino acids and the previously defined activation domain, retains the ability to induce apoptosis to an even higher level than wild-type p53. A more extensive deletion, which eliminates the N-terminal 63 amino acids, renders p53 completely inert in mediating apoptosis. In addition, we found that both p53(Delta1-42) and p53(gln22-ser23) can activate a subset of cellular pS3 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Al- 42) and p53(gln22-ser23). Taken together, these data suggest that within residues 43 to 63 lies an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(g1n22-ser23) and p53(Deltal-42) is still transcription-dependent.
Renal fibrosis and the renin-angiotensin system. (2001)

These data demonstrate that regression of biopsy-proven glomerulosclerosis can be achieved in various experimental settings. The potential importance of the RAS in renal fibrosis is underscored by the effectiveness of therapies that aim to inhibit its manifold actions, including induction of PAI-1. An understanding of the interactions of the RAS with the immune response, aldosterone, and PAI-1, as well as the dynamic control of cell proliferation, apoptosis, and regeneration, is now evolving. Ongoing studies will establish which of these recent provocative findings from animal models are relevant to human diseases, and may lead to optimal therapies to fore-stall progression and perhaps even induce regression of sclerosis.
Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester‐urethane)ureas based on poly(caprolactone) and putrescine (2002)

The engineering of tissue for mechanically demanding applications in the cardiovascular system is likely to require mechanical conditioning of cell-scaffold constructs prior to their implantation. Scaffold properties amenable to such an application include high elasticity and strength coupled with controllable biodegradative and cell-adhesive properties. To fulfill such design criteria, we have synthesized a family of poly(ester-urethane)ureas (PEUUs) from polycaprolactone and 1,4-diisocyanatobutane. Lysine ethyl ester (Lys) or putrescine was used as chain extenders. To encourage cell adhesion, PEUUs were surface modified with radio-frequency glow discharge followed by coupling of Arg-Gly-Asp-Ser (RGDS). The synthesized PEUUs were highly flexible, with breaking strains of 660-895% and tensile strengths from 9.2-29 MPa. Incubation in aqueous buffer for 8 weeks resulted in mass loss, from >50% (Lys chain extender) to 10% (putrescine chain extender). Human endothelial cells cultured for 4 days with medium containing the degradation products from PEUUs with either the Lys or putrescine chain extender showed no toxic effects. Cell adhesion was 85% of that measured on tissue-culture polystyrene for unmodified PEUU surfaces (p < 0.01) and >160% (p < 0.001) of polystyrene on RGDS-modified PEUUs. These biodegradable PEUUs demonstrate potential for future application as cell scaffolds in cardiovascular tissue-engineering or other soft-tissue applications.
Noise robust speech recognition using feature compensation based on polynomial regression of utterance SNR (2005)

A feature compensation (FC) algorithm based on polynomial regression of utterance signal-to-noise ratio (SNR) for noise robust automatic speech recognition (ASR) is proposed. In this algorithm, the bias between clean and noisy speech features is approximated by a set of polynomials which are estimated from adaptation data from the new environment by the expectation-maximization (EM) algorithm under the maximum likelihood (ML) criterion. In ASR, the utterance SNR for the speech signal is first estimated and noisy speech features are then compensated for by regression polynomials. The compensated speech features are decoded via acoustic HMMs trained with clean data. Comparative experiments on the Aurora 2 (English) and the German part of the Aurora 3 databases are performed between FC and maximum likelihood linear regression (MLLR). With the Aurora2 experiments, there are two MLLR implementations: pooling adaptation data across all SNRs, and using three distinct SNR clusters. For each type of noise, FC achieves, on average, a word error rate reduction of 16.7% and 16.5% for Set A, and 20.5% and 14.6% for Set B compared to the first and second MLLR implementations, respectively. For each SNR condition, FC achieves, on average, a word error rate reduction of 33.1% and 34.5% for Set A, and 23.6% and 21.4% for Set B. Results using the Aurora3 database show that, the best FC performance outperforms MLLR by 15.9%, 3.0% and 14.6% for well-matched, medium-mismatched and high-mismatched conditions, respectively.
Genetics of Sensory Thresholds: Taste for Phenyl Thio Carbamide (1932)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Developing a learing culture (2001)

A KEY ELEMENT to retaining and recruiting a nursing workforce is making sure that nurses are empowered to develop their practice and that they know their managers and other health professionals value their work. Although patients and relatives may well be effusive in their thanks to nurses, which in itself is an important aspect for job satisfaction, it is not enough.
Phase 1 multicenter study of vincristine sulfate liposomes injection and dexamethasone in adults with relapsed or refractory acute lymphoblastic leukemia (2009)

In this study, VSLI plus dexamethasone appeared to be an effective salvage therapy option for relapsed/refractory ALL. A phase 2, international, multicenter clinical trial assessing the efficacy of single-agent VSLI as second salvage therapy for patients with previously treated ALL is underway.
Heparin inhibition of insulin-like growth factor-binding protein-3 binding to human fibroblasts and rat glioma cells: role of heparan sulfate proteoglycans (1996)

The mitogenic action of insulin-like growth factors (IGFs) on target cells is determined by interaction with signaling IGF-I receptors and modulated by interactions with IGF-binding proteins (IGFBPs). IGFBP-3, an abundant IGFBP that binds IGF-I and IGF-II with high affinity, can form soluble inhibitory complexes with the IGFs that prevent them from binding to IGF-I receptors. Alternatively, IGFBP-3 can bind to the cell surface and possibly potentiate IGF action or act independently of the IGFs. Previous studies showed that heparin inhibited IGFBP-3 binding to the cell surface and increased its accumulation in the medium, suggesting that it might act as a competitive inhibitor of IGFBP-3 binding to structurally similar heparan sulfate proteoglycans on the cell surface. We evaluated this hypothesis by binding 125I-labeled recombinant glycosylated human IGFBP-3 to human fetal skin fibroblasts (GM-10) and to C6 rat glioma cells at 12 C. Heparin inhibited [125I]IGFBP-3 binding more effectively than chondroitin sulfate and dextran sulfate. Complete digestion of cell surface heparan sulfate and chondroitin sulfate glycosaminoglycans using heparitinase and chondroitinase ABC, however, did not significantly decrease IGFBP-3 binding. Quantitative removal was demonstrated by analysis of parallel cultures of cells whose glycosaminoglycans had been biosynthetically labeled using Na2 35SO4. These results suggested that IGFBP-3 did not bind to heparan sulfate glycosaminoglycans on the cell surface, and that the inhibition of IGFBP-3 binding by heparin most likely resulted from its direct interaction with the heparin-binding domains of IGFBP-3. When [125I]IGFBP-3 was incubated with GM-10 fibroblasts or C6 glioma cells at 37 C for 4 h, only 10% of the bound ligand remained associated with the cell surface; approximately 90% of the cell-associated radio-activity was internalized and could be recovered in lysates of acid-washed cells. Incubation with IGF-I or heparin decreased the total cell-associated radioactivity, but did not affect internalization. These results suggest that direct interaction of heparin or IGF-I with IGFBP-3 inhibits its ability to bind to the surface of GM-10 fibroblasts and C6 glioma cells.