gebhart/patrepeval huggingface dataset:
Filamentous Fusion Phage: Novel Expression Vectors That Display Cloned Antigens on the Virion Surface (1985)

Foreign DNA fragments can be inserted into filamentous phage gene III to create a fusion protein with the foreign sequence in the middle. The fusion protein is incorporated into the virion, which retains infectivity and displays the foreign amino acids in immunologically accessible form. These "fusion phage" can be enriched more than 1000-fold over ordinary phage by affinity for antibody directed against the foreign sequence. Fusion phage may provide a simple way of cloning a gene when an antibody against the product of that gene is available.
Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. (1995)

In this study we examine the molecular basis for the synergistic regulation of the minimal TCR alpha enhancer by multiple proteins. We find that reconstitution of TCR alpha enhancer function in nonlymphoid cells requires expression of the lymphoid-specific proteins LEF-1, Ets-1 and PEBP2 alpha (CBF alpha), and a specific arrangement of their binding sites in the enhancer. We show that Ets-1 cooperates with PEBP2 alpha to bind adjacent sites at one end of the enhancer, forming a ternary complex that is unstable by itself. Stable occupancy of the Ets-1- and PEBP2 alpha-binding sites in a DNase I protection assay was found to depend on both a specific helical phasing relationship with a nonadjacent ATF/CREB-binding site at the other end of the enhancer and on LEF-1. The HMG domain of LEF-1 was found previously to bend the DNA helix in the center of the TCR alpha enhancer. We now show that the HMG domain of the distantly related SRY protein, which also bends DNA, can partially replace LEF-1 in stimulating enhancer function in transfection assays. Taken together with the observation that Ets-1 and members of the ATF/CREB family have the potential to associate in vitro, these data suggest that LEF-1 can coordinate the assembly of a specific higher-order enhancer complex by facilitating interactions between proteins bound at nonadjacent sites.
Stereochemical influences upon the opioid ligand activities of 4‐alkyl‐4‐arylpiperidine derivatives (1989)

The synthesis and stereochemistry (configuration and preferred solute conformation) of some 4-alkyl (methyl, n-propyl, isobutyl)-4-(3-hydroxy-phenyl)-1-methylpiperidines and corresponding 3-methyl diastereoisomeric pairs are reported, together with their in vivo and in vitro activities as opioid ligands. All potent agonists exhibit a preference for axial 4-aryl chair conformations when protonated, and stereochemical analogies with rigid opioids of the benzomorphan class are discussed. Antagonist properties are found in compounds with preference for equatorial 4-aryl chairs, notably the cis 3,4-dimethyl derivative.
Anti‐inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL‐12 and up‐regulation of IL‐10 production (2000)

Cytokines are critical in regulating unresponsiveness versus immunity towards enteric antigens derived from the intestinal flora and ingested food. There is increasing evidence that butyrate, a major metabolite of intestinal bacteria and crucial energy source for gut epithelial cells, also possesses anti-inflammatory properties. Its influence on cytokine production, however, is not established. Here, we report that butyrate strongly inhibits interleukin-12 (IL-12) production by suppression of both IL-12p35 and IL-12p40 mRNA accumulation, but massively enhances IL-10 secretion in Staphylococcus aureus cell-stimulated human monocytes. The effect of butyrate on IL-12 production was irreversible upon the addition of neutralizing antibodies to IL-10 or transforming growth factor b1 and of indomethacin. In anti-CD3-stimulated peripheral blood mononuclear cells, butyrate enhanced IL-10 and IL-4 secretion but reduced the release of IL-2 and interferon-g. The latter effect was in part a result of suppressed IL-12 production but also a result of inhibition of IL-12 receptor expression on T cells. These data demonstrate a novel anti-inflammatory property of butyrate that may have broad implications for the regulation of immune responses in vivo and could be exploited as new therapeutic approach in inflammatory conditions.
The role of integrins in the maintenance of endothelial monolayer integrity. (1991)

This paper shows that, in confluent human umbilical vein endothelial cell (EC) monolayers, the integrin heterodimers alpha 2 beta 1 and alpha 5 beta 1, but not other members of the beta 1 subfamily, are located at cell-cell contact borders and not at cellular free edges. Also the alpha v chain, but not its most common partner beta 3, that is widely expressed in EC cell-matrix junctions, is found at cell-cell borders. In EC monolayers, the putative ligands of alpha 2 beta 1 and alpha 5 beta 1 receptors, i.e., laminin, collagen type IV, and fibronectin, are also organized in strands corresponding to cell-cell borders. The location of the above integrin receptors is not an artifact of in vitro culture since it has been noted also in explanted islets of the native umbilical vein endothelium. The integrins alpha 2 beta 1 and alpha 5 beta 1 play a role in the maintenance of endothelial monolayer continuity in vitro. Indeed, specific antibodies to alpha 2 beta 1, alpha 5 beta 1, and the synthetic peptide GRGDSP alter its continuity without any initial cell detachment. Moreover, antibodies to alpha 5 beta 1 increase the permeation of macromolecules across confluent EC monolayers. In contrast beta 3 antibodies were ineffective. It is suggested that the relocation of integrins to cell-cell borders is a feature of cells programmed to form polarized monolayers since integrins have a different distribution in nonpolar confluent dermal fibroblasts. The conclusion is that some members of the integrin superfamily collaborate with other intercellular molecules to form lateral junctions and to control both the monolayer integrity and the permeability properties of the vascular endothelial lining. This also suggest that integrins are adhesion molecules provided with a unique biochemical adaptability to different biological functions.
Sheared flow stabilization experiments in the ZaP flow Z pinch (2003)

The stabilizing effect of a sheared axial flow on the m=1 kink instability in Z pinches has been studied numerically with a linearized ideal magnetohydrodynamic model to reveal that a sheared axial flow stabilizes the kink mode when the shear exceeds a threshold. The sheared flow stabilizing effect is investigated with the ZaP (Z-Pinch) Flow Z-pinch experiment at the University of Washington. An axially flowing Z pinch is generated with a 1 m coaxial accelerator coupled to a pinch assembly chamber. The plasma assembles into a pinch 50 cm long with a radius of approximately 1 cm. An azimuthal array of surface mounted magnetic probes located at the midplane of the pinch measures the fluctuation levels of the azimuthal modes m=1, 2, and 3. After the pinch assembles a quiescent period is found where the mode activity is significantly reduced. Optical images from a fast framing camera and a ruby holographic interferometer indicate a stable, discrete pinch plasma during this time. Multichord Doppler shift measurements of impurity lines show a large, sheared flow during the quiescent period and low, uniform flow profiles during periods of high mode activity. Z-pinch plasmas have been produced that are globally stable for over 700 times the theoretically predicted growth time for the kink mode of a static Z pinch. The plasma has a sheared axial flow that exceeds the theoretical threshold for stability during the quiescent period and is lower than the threshold during periods of high mode activity.
Rapid Detection of Methicillin Resistance in Staphylococcus aureus Isolates by the MRSA-Screen Latex Agglutination Test (1999)

The slide agglutination test MRSA-Screen (Denka Seiken Co., Niigata, Japan) was compared with the mecA PCR ("gold standard") for the detection of methicillin resistance in Staphylococcus aureus. The MRSA-Screen test detected the penicillin-binding protein 2a (PBP2a) antigen in 87 of 90 genetically diverse methicillin-resistant S. aureus (MRSA) stock culture strains, leading to a sensitivity of 97%. The three discrepant MRSA strains displayed positive results only after induction of the mecA gene by exposure to methicillin. Both mecA PCR and MRSA-Screen displayed negative results among the methicillin-susceptible S. aureus strains (n = 106), as well as for Micrococcus spp. (n = 10), members of the family Enterobacteriaceae (n = 10), Streptococcus pneumoniae (n = 10), and Enterococcus spp. (n = 10) (specificity = 100%). Producing the same PBP2a antigen, all 10 methicillin-resistant Staphylococcus epidermidis strains score positived in both the latex test and the mecA PCR. Consequently, the MRSA-Screen test should be applied only after identification of the MRSA strain to the species level to rule out coagulase-negative staphylococci. In conclusion, due to excellent specificity and sensitivity the MRSA-Screen latex test has the potential to be successfully used for routine applications in the microbiology laboratory.
Isolation and molecular characterization of high-performance cellobiose-fermenting spontaneous mutants of ethanologenic Escherichia coli KO11 containing the Klebsiella oxytoca casAB operon (1997)

Escherichia coli KO11 was previously constructed to produce ethanol from acid hydrolysates of hemicellulose (pentoses and hexoses) by the chromosomal integration of Zymomonas mobilis genes encoding pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adhB). Klebsiella oxytoca P2 was constructed in an analogous fashion for the simultaneous saccharification and fermentation of cellulose and contains PTS enzymes for cellobiose. In this study, KO11 was further engineered for the fermentation of cellulose by adding the K. oxytoca casAB genes encoding Enzyme IIcellobiose and phospho-beta-glucosidase. Although the two K. oxytoca genes were well expressed in cloning hosts such as DH5 alpha, both were expressed poorly in E. coli KO11, a derivative of E. coli B. Spontaneous mutants which exhibited more than 15-fold-higher specific activities for cellobiose metabolism were isolated. The mutations of these mutants resided in the plasmid rather than the host. Three mutants were characterized by sequence analysis. All contained similar internal deletions which eliminated the casAB promoter and operator regions and placed the lacZ Shine-Dalgarno region immediately upstream from the casA Shine-Dalgarno region. KO11 harboring mutant plasmids (pLOI1908, pLOI1909, or pLOI1910) rapidly fermented cellobiose to ethanol, and the yield was more than 90% of the theoretical yield. Two of these strains were used with commercial cellulase to ferment mixed-waste office paper to ethanol.
Protein engineering of alcohol dehydrogenases; effects of amino acid changes at positions 93 and 48 of yeast ADH1 (1990)

By protein engineering we have investigated changes to two amino acid residues (Trp93 and Ser48) in the substrate pocket of yeast alcohol dehydrogenase 1. Upon changing Thr48 to serine we produced an enzyme which has markedly greater activity towards aliphatic alcohols with chain length up to 8, together with a general increase in catalytic activity (V/K). Changes at position 93 were less pronounced, with the Phe enzyme being more active than the parent towards the range of alcohols but with the alanine enzyme showing very little difference from the wild-type. Enzymes with the double changes at 48 and 93 showed increased activity towards alcohols with 3-8 carbons but the increases were not additive over the single changes. The enzymes with changes at the two positions would metabolize both stereoisomers of 2-octanol whereas the parent ADH would attack only one of them. None of the engineered enzymes would attack cyclohexanol or aromatic alcohols. The results are in general agreement with the prediction that reducing the size of amino acids in the substrate pocket would enhance the ability to oxidize alcohols larger than ethanol.
Mutations in XRS2 and RAD50 Delay but Do Not Prevent Mating-Type Switching in Saccharomyces cerevisiae (1994)

In Saccharomyces cerevisiae, a large number of genes in the RAD52 epistasis group has been implicated in the repair of chromosomal double-strand breaks and in both mitotic and meiotic homologous recombination. While most of these genes are essential for yeast mating-type (MAT) gene switching, neither RAD50 nor XRS2 is required to complete this specialized mitotic gene conversion process. Using a galactose-inducible HO endonuclease gene to initiate MAT switching, we have examined the effect of null mutations of RAD50 and of XRS2 on intermediate steps of this recombination event. Both rad50 and xrs2 mutants exhibit a marked delay in the completion of switching. Both mutations reduce the extent of 5'-to-3' degradation from the end of the HO-created double-strand break. The steps of initial strand invasion and new DNA synthesis are delayed by approximately 30 min in mutant cells. However, later events are still further delayed, suggesting that XRS2 and RAD50 affect more than one step in the process. In the rad50 xrs2 double mutant, the completion of MAT switching is delayed more than in either single mutant, without reducing the overall efficiency of the process. The XRS2 gene encodes an 854-amino-acid protein with no obvious similarity to the Rad50 protein or to any other protein in the database. Overexpression of RAD50 does not complement the defects in xrs2 or vice versa.
Low-nonlinearity single-transverse-mode ytterbium-doped photonic crystal fiber amplifier (2004)

We report on an air-clad large-core single-transverse-mode ytterbium-doped photonic crystal fiber with a mode-field-diameter of 35 microm, corresponding to a mode-field-area of ~1000 microm(2). In a first experiment this fiber is used to amplify 10-ps pulses to a peak power of 60 kW without significant spectral broadening due to self-phase modulation allowing for the frequency up-conversion of these pulses using narrow-bandwidth phase matched nonlinear crystals.
Exosomes as miRNA Carriers: Formation–Function–Future (2016)

Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes' formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine.
MS 미생물복합군에 의한 음식폐기물의 양돈사료화를 위한 적정처리공정 (2000)

토양미생물군인 Miraculous soil-Microorganisms (MS균) 제제를 음식폐기물에 처리 후 발효공정에 따른 아플라톡신의 잔존 유무 분석, 열량 아미노산 및 지방산 조성분석을 통해 양돈사료화를 위한 효율적 처리방법에 대한 자료를 얻고자 실시하였다. 음식폐기물의 MS균 발효 후 calorimeter를 이용한 열량측정 결과 건물 1g당 평균 7.599 Kcal D.M 정도의 높은 열량을 가지는 것으로 나타났으며, MS균 첨가 후 각 발효공정의 모든 시료에서 아플라톡신은 검출되지 않았다. 음식폐기물내 총 아미노산의 함량은 쌀겨 (10%) 및 어분 (5%) 첨가 후 MS균에 의한 3주간 혐기발효 하였을 때 92.99 ㎎·g^(-1)으로 저온 발효 후 보다 약 18.5%의 아미노산 함량이 증가되었다. MS균에 의한 최종 발효 후 필수아미노산 함량은 34.43 ㎎·g^(-1) D.M 이었으며, leucine, phenylalanine, isoleucine 및 thereonine이 높은 구성비율을 보였다. 비필수아미노산 함량은 58.66 ㎎·g^(-1) D.M이었고 proline과 glutamic acid의 함량이 상대적으로 높았다. 지방산 조성에 있어서는 palmitic acid, oleic acid 및 palmitoleic acid의 함량이 상대적으로 높았으며, 지방산 함량 역시 혐기숙성 발효에 의해 증가되었다. 이상의 결과들은 음식폐기물을 MS균에 의해 발효처리하였을때 양돈사료로서의 충분한 열량을 함유하고 있으며, 아플라톡신으로부터 안전함을 보여주며, MS균에 의한 혐기발효를 통해 음식폐기물내 단백질 및 지방의 가수분해를 촉진시킬 수 있음을 잘 보여주었다.
Gene therapy for lysosomal storage disorders (2001)

The lysosomal storage disorders (LSD) are monogenic inborn errors of metabolism with heterogeneous pathophysiology and clinical manifestations. In the last decades, these disorders have been models for the development of molecular and cellular therapies for inherited metabolic diseases. Studies in preclinical in vitro systems and animal models have allowed the successful development of bone marrow transplantation (BMT) and enzyme replacement therapy (ERT) as therapeutic options for several LSDs. However, BMT is limited by poor donor availability and high morbidity and mortality, and ERT is not a life-long cure. Moreover, the neuropathology present in many LSDs responded poorly, if at all, to these treatments. Therefore, gene therapy is an attractive therapeutic alternative. Gene therapy strategies for LSDs have employed ex vivo gene transduction of cellular targets with subsequent transplantation of the enzymatically corrected cells, or direct in vivo delivery of the viral vectors. Oncoretroviral vectors and more recently adeno associated vectors (AAV) and lentiviral vectors have been extensively tested, with some success. This review summarises the main gene therapy strategies which have been employed or are under development for both non-neurological and neuronopathic LSDs. Some of the in vitro and in vivo preclinical studies presented herein have provided the rationale for a gene therapy clinical trial for Gaucher disease Type I.
Forecasting Cancer Trends to Optimize Control Strategies (1984)

Population projections and age-stratified cancer rates were used to forecast the trends for cancer occurrence for the United States during the coming decades: A progressive increase in the number of new cases is already predetermined by the high birth rate that occurred during the middle part of the century, and it will lead to nearly a doubling in the number of cases in about 4 decades. The demographic circumstances that determine the per capita costs of cancer are likely to worsen, because expected population trends will produce a deteriorating per capita economic base. Furthermore, the high costs of emerging treatment technologies are likely to magnify the deterioration ever further. Development of methods for cancer trend forecasting can provide a sound and accurate foundation for planning a comprehensive national strategy for optimal partitioning of research resources between the need for development of new treatments and the need for new research directed toward primary preventive measures.
IL-33 Expands Suppressive CD11b+ Gr-1int and Regulatory T Cells, including ST2L+ Foxp3+ Cells, and Mediates Regulatory T Cell-Dependent Promotion of Cardiac Allograft Survival (2011)

IL-33 administration is associated with facilitation of Th2 responses and cardioprotective properties in rodent models. However, in heart transplantation, the mechanism by which IL-33, signaling through ST2L (the membrane-bound form of ST2), promotes transplant survival is unclear. We report that IL-33 administration, while facilitating Th2 responses, also increases immunoregulatory myeloid cells and CD4(+) Foxp3(+) regulatory T cells (Tregs) in mice. IL-33 expands functional myeloid-derived suppressor cells, CD11b(+) cells that exhibit intermediate (int) levels of Gr-1 and potent T cell suppressive function. Furthermore, IL-33 administration causes an St2-dependent expansion of suppressive CD4(+) Foxp3(+) Tregs, including an ST2L(+) population. IL-33 monotherapy after fully allogeneic mouse heart transplantation resulted in significant graft prolongation associated with increased Th2-type responses and decreased systemic CD8(+) IFN-γ(+) cells. Also, despite reducing overall CD3(+) cell infiltration of the graft, IL-33 administration markedly increased intragraft Foxp3(+) cells. Whereas control graft recipients displayed increases in systemic CD11b(+) Gr-1(hi) cells, IL-33-treated recipients exhibited increased CD11b(+) Gr-1(int) cells. Enhanced ST2 expression was observed in the myocardium and endothelium of rejecting allografts, however the therapeutic effect of IL-33 required recipient St2 expression and was dependent on Tregs. These findings reveal a new immunoregulatory property of IL-33. Specifically, in addition to supporting Th2 responses, IL-33 facilitates regulatory cells, particularly functional CD4(+) Foxp3(+) Tregs that underlie IL-33-mediated cardiac allograft survival.
The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. (1985)

We showed previously that adoptive immunotherapy with the combination of LAK cells and recombinant IL 2 (RIL 2) can markedly reduce pulmonary micrometastases from multiple sarcomas established 3 days after the i.v. injection of syngeneic tumor cells in C57BL/6 mice. In this report, we analyzed the factors required for successful therapy. Titration analysis in vivo revealed an inverse relationship between the number of pulmonary metastases remaining after treatment and both the number of LAK cells and the amount of RIL 2 administered. Fresh or unstimulated splenocytes had no anti-tumor effect; a 2- to 3-day incubation of splenocytes in RIL 2 was required. LAK cells generated from allogeneic DBA (H-2d) splenocytes were as effective in vivo as syngeneic, C57BL/6 (H-2b) LAK cells. The anti-metastatic capacity of LAK cells was significantly reduced or eliminated when irradiated with 3000 rad before adoptive transfer. The combined therapy of LAK cells plus RIL 2 was shown to be highly effective in mice immunosuppressed by 500 rad total body irradiation and in treating macrometastases established in the lung 10 days after the i.v. injection of sarcoma cells. Further, reduction of both micrometastases and macrometastases could also be achieved by RIL 2 alone when administered at higher levels than were required with LAK cells. The value of LAK cell transfer and of IL 2 administration for the treatment of tumors established at other sites is currently under investigation.
Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. (1995)

The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of numerous suppurative diseases of human skin. The M protein of S. pyogenes mediates the adherence of the bacterium to keratinocytes, the most numerous cell type in the epidermis. In this study, we have constructed and analyzed a series of mutant M proteins and have shown that the C repeat domain of the M molecule is responsible for cell recognition. The binding of factor H, a serum regulator of complement activation, to the C repeat region of M protein blocked bacterial adherence. Factor H is a member of a large family of complement regulatory proteins that share a homologous structural motif termed the short consensus repeat. Membrane cofactor protein (MCP), or CD46, is a short consensus repeat-containing protein found on the surface of keratinocytes, and purified MCP could competitively inhibit the adherence of S. pyogenes to these cells. Furthermore, the M protein was found to bind directly to MCP, whereas mutant M proteins that lacked the C repeat domain did not bind MCP, suggesting that recognition of MCP plays an important role in the ability of the streptococcus to adhere to keratinocytes.
Performance of 3GPP high speed downlink packet access (HSDPA) (2005)

High speed downlink packet access (HSDPA) technology was standardized for 3GPP W-CDMA release-5. HSDPA includes advanced techniques such as adaptive modulation and coding (AMC), hybrid ARQ (HARQ), and fast scheduling. HSDPA can deliver a 3/spl times/ increase in sector and a 6/spl times/ increase in user throughput for some traffic models. Additionally HSDPA can support almost a 4/spl times/ increase in the number of users compared to UMTS release-99 for the same service. With advanced receivers, HSDPA can support broadband quality service with 60 users per site. This paper provides an overview of the physical layer aspects of HSDPA and discusses the improvements in sector and user throughput (with respect to release-99 UMTS) resulting from HSDPA with joint scheduling and resource allocation.