gebhart/patrepeval huggingface dataset:
Engineering metabolic systems for production of advanced fuels (2009)

The depleting petroleum storage and increasing environmental deterioration are threatening the sustainable development of human societies. As such, biofuels and chemical feedstocks generated from renewable sources are becoming increasingly important. Although previous efforts led to great success in bio-ethanol production, higher alcohols, fatty acid derivatives including biodiesels, alkanes, and alkenes offer additional advantages because of their compatibility with existing infrastructure. In addition, some of these compounds are useful chemical feedstocks. Since native organisms do not naturally produce these compounds in high quantities, metabolic engineering becomes essential in constructing producing organisms. In this article, we briefly review the four major metabolic systems, the coenzyme-A mediated pathways, the keto acid pathways, the fatty acid pathway, and the isoprenoid pathways, that allow production of these fuel-grade chemicals.
Orientation‐Controlled Growth of Single‐Crystal Silicon‐Nanowire Arrays (2005)

Silicon nanowire arrays on silicon substrates can be synthesized with precise orientation depending on the crystal orientation of the substrate using a vapor–liquid–solid epitaxial growth mechanism. The projections of the as-grown arrays form rectangular networks on silicon (100) substrates (see Figure), parallel straight lines on silicon (110) substrates, and triangular networks on silicon (111) substrates. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2005/c0474_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Amantadine and Rimantadine Have No Direct Inhibitory Effects against Hepatitis C Viral Protease, Helicase, ATPase, Polymerase, and Internal Ribosomal Entry Site–Mediated Translation (2000)

Amantadine, a drug known to inhibit influenza A viral matrix (M2) protein function, was reported to be an effective treatment in some patients with chronic hepatitis C virus (HCV) infection. Sequence comparison shows no homology between M2 and any of the HCV proteins. The effects of amantadine and a related analogue, rimantadine, on viral protease, helicase, ATPase, RNA-dependent RNA polymerase, and HCV internal ribosomal entry site (IRES) translation were tested by established in vitro biochemical assays. No inhibition (>15%) of HCV protease, helicase, ATPase, and polymerase was observed with concentrations up to 400 microgram/mL. IRES-specific inhibition was not observed at clinically relevant concentrations, but both cap and IRES reporter genes were suppressed at higher levels, suggesting nonspecific translation inhibition. In conclusion, amantadine and rimantadine have no direct and specific inhibitory effects against HCV protease, helicase, ATPase, polymerase, and IRES in vitro.
The nucleotide sequence and comparative analysis of the H-2Dp class I H-2 gene. (1986)

We present the complete nucleotide sequence and the deduced amino acid sequence of the H-2Dp class I gene. This gene, which was cloned from a B10.P genomic DNA library, encodes and intact, functional H-2Dp molecule. Comparative analysis of the Dp sequence with other class I sequences reveals both similarities and differences. This analysis also shows that these genes exhibit D region-specific, locus-specific, as well as allele-specific sequences. The H-2Dp nucleotide sequence is greater than 90% homologous to the H-2Ld and H-2Db genes and only approximately 85% homologous to the H-2Dd gene. The K region and Qa region genes are less homologous. The 3' noncoding sequences appear to be region-specific. All of the previously described D region genes, Db, Ld, and Dd, possess the B2-SINE Alu-like repetitive sequence, as does Dp. Thus, this B2 repeat is a region-specific marker present in all D region genes studied so far. The additional polyadenylation site found in the H-2Dp gene starting at nucleotide 4671, which is homologous to non-D region sequences, as well as unique protein Dp coding sequences, make this gene an interesting model for studying the evolution of polymorphism and structure/function relationships in the class I gene family.
Primase-based whole genome amplification (2008)

In vitro DNA amplification methods, such as polymerase chain reaction (PCR), rely on synthetic oligonucleotide primers for initiation of the reaction. In vivo, primers are synthesized on-template by DNA primase. The bacteriophage T7 gene 4 protein (gp4) has both primase and helicase activities. In this study, we report the development of a primase-based Whole Genome Amplification (pWGA) method, which utilizes gp4 primase to synthesize primers, eliminating the requirement of adding synthetic primers. Typical yield of pWGA from 1 ng to 10 ng of human genomic DNA input is in the microgram range, reaching over a thousand-fold amplification after 1 h of incubation at 37 degrees C. The amplification bias on human genomic DNA is 6.3-fold among 20 loci on different chromosomes. In addition to amplifying total genomic DNA, pWGA can also be used for detection and quantification of contaminant DNA in a sample when combined with a fluorescent reporter dye. When circular DNA is used as template in pWGA, 10(8)-fold of amplification is observed from as low as 100 copies of input. The high efficiency of pWGA in amplifying circular DNA makes it a potential tool in diagnosis and genotyping of circular human DNA viruses such as human papillomavirus (HPV).
The role of the diphtheria toxin receptor in cytosol translocation. (1988)

The role of the receptor in the transport of diphtheria toxin (DT) to the cytosol was examined. A point-mutant form of DT, CRM 107 (CRM represents cross-reacting material), that has an 8,000-fold lower affinity for the DT receptor than native toxin was conjugated to transferrin and monoclonal antibodies specific for the cell-surface receptors T3 and Thy1. Conjugating the binding site-inactivated CRM 107 to new binding moieties reconstituted full toxicity, indistinguishable from native DT linked to the same ligand, indicating that the entry activity of the DT B chain can be fully separated from the receptor binding function. Like DT, the toxin conjugates exhibited a dose-dependent lag period before first-order inactivation of protein synthesis. Inactivation of the binding site of the toxin portion of the conjugate was found to have no effect on the kinetics of protein synthesis inactivation. The receptor used by the toxin determined the length of the lag period relative to the killing rate. Comparing the potency of CRM 107 conjugates with native DT, standardized for receptor occupancy, shows that new receptors can be as or more efficient than the DT receptor in transporting DT to the cytosol. The transferrin-CRM 107 conjugate, unlike native DT, was highly toxic to murine cells. All the data presented are consistent with a model that the DT receptor, other than initiating rapid internalization of the toxin to low pH compartments, is unnecessary for transport of the toxin to the cytosol and that membrane translocation activity is expressed by the DT B subunit independent of the receptor-binding site.
Adipogenesis inhibitory factor A novel inhibitory regulator of adipose conversion in bone marrow (1991)

Recombinant adipogenesis inhibitory factor (AGIF) was purified to homogeneity from the conditioned medium of COS-1 cells transfected with human AGIF cDNA. The amino-terminal sequence analysis of the mature AGIF revealed that AGIF was produced as a precursor consisting of 199 amino acids and processed into a mature form of 178 amino acids by a cleavage between Ala(-1) and Pro(+1). The purified AGIF inhibited the process of adipogenesis in mouse 3T3-L1 preadipocytes, indicating that AGIF directly acts on the cells. AGIF acted as an adipogenic antagonist not only on the extramedullary cell line 3T3-L1 but also on the mouse bone marrow stroma-derived cell line H-1/A, suggesting that this cytokine may regulate adipogenesis in bone marrow.
Nonlinear Interferometric Vibrational Imaging (2004)

Coherent anti-Stokes Raman scattering (CARS) processes are "coherent," but the phase of the anti-Stokes radiation is lost by most incoherent spectroscopic CARS measurements. We propose a Raman microscopy imaging method called nonlinear interferometric vibrational imaging, which measures Raman spectra by obtaining the temporal anti-Stokes signal through nonlinear interferometry. With a more complete knowledge of the anti-Stokes signal, we show through simulations that a high-resolution Raman spectrum can be obtained of a molecule in a single pulse using broad band radiation. This could be useful for identifying the three-dimensional spatial distribution of molecular species in tissue.
Dai Wangshu: The Life and Poetry of a Chinese Modernist (1991)

Dai Wangshu as a poet and a personality made a controversial and lasting impact on the Chinese literary world of the 1930s and 1940s. Since the 1950s, however, many literary figures of the time have suffered neglect because they are not easily categorized as belonging to the orthodoxies of Left or Right. This has been so in Dai Wangshu's case. Moreover, there is also genuine confusion about Dai's political and literary beliefs. This thesis aims to revaluate Dai's position in the canon of modern Chinese literature and, by chronicling his literary, political and personal life, to present a comprehensive picture and correct current misconceptions. There is a biographical emphasis as a result of much new information uncovered in the course of the author's research. The approach is chronological and covers Dai's early involvement in poetry and politics in late 1920s Shanghai, the process of intellectual sophistication and expansion in Europe, his anti-Japanese stance during the war period in Hong Kong and the final years of poetic silence leading up to his premature death in Peking, in 1950. Dai's poetry is treated in terms of theme, language and form to reveal the poet's growth and progression of style. The extent of the poet's retention of classical Chinese poetic elements and the assimilation of Western post-Symbolist and other poetic influences are assessed in order to arrive at the essence of the poet's style, to examine its effectiveness as a modern medium for the expression of poetic thought and to decide the appropriateness of the label 'Modernist'. The definition of Modernism is thus broached and discussed. Previously unconsulted material such as letters, diary fragments and manuscripts have been exploited and in the discussion of Dai's poetry and the literary and political questions of his day, extensive use has been made of correspondence and interviews conducted in China.
Herpes simplex virus immune evasion from antibody and complement (2006)

Herpes simplex virus type 1 (HSV-1) evades immunity mediated by antibody and complement. HSV-1 glycoproteins E (gE) and I (gI) encode a viral IgG Fc receptor (vFcγR) that blocks functions mediated by IgG. HSV-1 glycoprotein C (gC1) binds complement component C3b and inhibits the interaction of C5 and properdin (P) with Cab, blocking activation of both the classical and alternative complement pathways. Herpes simplex virus type 2 (HSV-2) encodes homologues of gE, gI, and gC, yet despite the significance of HSV-2 in human disease, relatively few studies address the complement evasion strategies used by this virus. In this dissertation, I examined the significance of HSV-2 gC (gC2) in immune evasion. Three independently derived wild type (WT) and gC2null virus pairs were compared to evaluate the mechanisms by which gC2 protects cell-free virus from complement-mediated neutralization; to determine whether gC2 protects infected cells from complement-mediated cell lysis; and to examine whether gC2 contributes to viral pathogenesis in vivo. Additional studies were performed to evaluate whether blocking immune evasion has potential therapeutic value in human immunodeficiency virus (HIV) patients. gC2 prevents complement-mediated neutralization induced by natural IgM antibody and the classical complement pathway. Natural IgM antibody in nonimmune human serum bound to HSV-2 gCnull virus and neutralized through a mechanism that required C1q and involved both C3 and C5, but not the formation of the membrane attack complex. Interestingly, HSV antibody-negative sera obtained from four individuals differed in potency of complement-mediated virus neutralization, indicating that innate immunity offers variable protection against HSV. gC2 contributes to viral pathogenesis. All gC2null viruses examined were significantly attenuated in the murine flank model of infection compared with WT strains. In C3 knockout mice, disease severity increased to levels comparable with WT virus for two HSV-2 strains, indicating that the virulence conferred by gC2 was through interaction with complement. Finally, studies examining complement and HSV antibody neutralization in HIV infected subjects support a significant contribution for gC and gE in preventing antibody and complement mediated neutralization, and indicate that gC and gE immune evasion domains shield critical neutralizing epitopes on viral glycoproteins involved in entry.
Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response (2010)

The serine proteinase inhibitor α-1 antitrypsin (AAT) is produced principally by the liver at the rate of 2 g/d. It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung, where it can neutralise the activity of the serine protease neutrophil elastase. Mutations leading to deficiency in AAT are associated with liver and lung disease. The most notable is the Z AAT mutation, which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine. More than 95% of all individuals with AAT deficiency carry at least one Z allele. ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum (ER) of hepatocytes and other AAT-producing cells. This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT. However, the misfolded protein acquires a toxic gain of function that impacts on the ER. A major function of the ER is to ensure correct protein folding. ZAAT interferes with this function and promotes ER stress responses and inflammation. Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.
The Function of Tocopherols and Tocotrienols in Plants (2002)

Referee: Dr. Kozi Asada, Department of Biotechnology, Faculty of Engineering, Fukuyama University, Gakuencho 1, Fukuyama 729-0292, Japan Tocopherols and tocotrienols, which differ only in the degree of saturation of their hydrophobic prenyl side chains, are lipid-soluble molecules that have a number of functions in plants. Synthesized from homogentisic acid and isopentenyl diphosphate in the plastid envelope, tocopherols and tocotrienols are essential to maintain membrane integrity. α-Tocopherol is the major form found in green parts of plants, while tocotrienols are mostly found in seeds. These compounds are antioxidants, thus they protect the plant from oxygen toxicity. Tocopherols and tocotrienols scavenge lipid peroxy radicals, thereby preventing the propagation of lipid peroxidation in membranes, and the ensuing products tocopheroxyl and tocotrienoxyl radicals, respectively, are recycled back to tocopherols and tocotrienols by the concerted action of other antioxidants. Furthermore, tocopherols and tocotrienols protect lipids and other membrane components by physically quenching and reacting chemically with singlet oxygen. The scavenging of singlet oxygen by α-tocopherol in chloroplasts results in the formation of, among other products, α -tocopherol quinone, a known contributor to cyclic electron transport in thylakoid membranes, therefore providing photoprotection for chloroplasts. Moreover, given that α-tocopherol increases membrane rigidity, its concentration, together with that of the other membrane components, might be regulated to afford adequate fluidity for membrane function. Furthermore, α-tocopherol may affect intracellular signaling in plant cells. The effects of this compound in intracellular signaling may be either direct, by interacting with key components of the signaling cascade, or indirect, through the prevention of lipid peroxidation or the scavenging of singlet oxygen. In the latter case, α-tocopherol may regulate the concentration of reactive oxygen species and plant hormones, such as jasmonic acid, within the cell, which control both the growth and development of plants, and also plant response to stress.
A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy (2021)

Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of "off-the-shelf" T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce "off-the-shelf" and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology.
The Human Genome Sequence Expedition: Views from the “Base Camp” (2001)

The past year has brought unprecedented public attention to biomedical research, with a particularly intense focus on the Human Genome Project and the completion of a first-generation ∼3-billion-basepair human genome sequence. Much of this attention related to the competition between the two parallel, yet separate, efforts of the publicly-funded International Human Genome Sequencing Consortium and the private company Celera Genomics. Despite the apparent rancor between the groups, two celebratory events notably punctuate the past year: the joint media announcement in late June 2000 that both groups had generated a “working draft” sequence of the human genome and the two landmark scientific publications in February 2001 that describe the efforts of each project (International Human Genome Sequencing Consortium 2001; Venter et al. 2001). Numerous grandiose cliches and metaphors have been used to convey the magnitude of these accomplishments and their associated implications for biomedical research and clinical medicine. Here we add one more to this list. Our choice for capturing the essence of contemporary human genome analysis is an analogy to a mountain climbing expedition, one where significant progress has been made to provide a spectacular view of the genetic landscape. But this is not an expedition that is complete, with uncertain— yet exciting—genomic terrain ahead. Indeed, the Human Genome Project is now firmly at the “base camp” of the expedition to elucidate the human genetic blueprint and to begin to understand its content. Nevertheless, this is a milestone of tremendous significance and excitement. Here we outline some of the key lessons learned during the initial analysis of the human genome sequence. We highlight a few of the many remaining questions in understanding the genome’s structure and function, with most answers likely becoming available later in the expedition. Finally, we preview the anticipated climb to the final summit and the ascent to a complete and finished sequence.
A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth through Hypoxia-inducible Factor (HIF)-1/2α (2014)

The calcium-permeable ion channel TRPM2 is highly expressed in a number of cancers. In neuroblastoma, full-length TRPM2 (TRPM2-L) protected cells from moderate oxidative stress through increased levels of forkhead box transcription factor 3a (FOXO3a) and superoxide dismutase 2. Cells expressing the dominant negative short isoform (TRPM2-S) had reduced FOXO3a and superoxide dismutase 2 levels, reduced calcium influx in response to oxidative stress, and enhanced reactive oxygen species, leading to decreased cell viability. Here, in xenografts generated with SH-SY5Y neuroblastoma cells stably expressing TRPM2 isoforms, growth of tumors expressing TRPM2-S was significantly reduced compared with tumors expressing TRPM2-L. Expression of hypoxia-inducible factor (HIF)-1/2α was significantly reduced in TRPM2-S-expressing tumor cells as was expression of target proteins regulated by HIF-1/2α including those involved in glycolysis (lactate dehydrogenase A and enolase 2), oxidant stress (FOXO3a), angiogenesis (VEGF), mitophagy and mitochondrial function (BNIP3 and NDUFA4L2), and mitochondrial electron transport chain activity (cytochrome oxidase 4.1/4.2 in complex IV). The reduction in HIF-1/2α was mediated through both significantly reduced HIF-1/2α mRNA levels and increased levels of von Hippel-Lindau E3 ligase in TRPM2-S-expressing cells. Inhibition of TRPM2-L by pretreatment with clotrimazole or expression of TRPM2-S significantly increased sensitivity of cells to doxorubicin. Reduced survival of TRPM2-S-expressing cells after doxorubicin treatment was rescued by gain of HIF-1 or -2α function. These data suggest that TRPM2 activity is important for tumor growth and for cell viability and survival following doxorubicin treatment and that interference with TRPM2-L function may be a novel approach to reduce tumor growth through modulation of HIF-1/2α, mitochondrial function, and mitophagy.
Near-infared hyperspectral imaging of teeth for dental caries detection (2009)

Near-infrared (NIR) is preferred for caries detection compared to visible light imaging because it exhibits low absorption by stain and deeper penetration into teeth. Hyperspectral images from 1000 to 2500 nm have been obtained for a total of 12 extracted teeth (premolars and molars) with different degrees of natural lesion. Analysis of the reflectance spectra suggests that light scattering by porous enamel and absorption by water in dentin can be used to quantify the lesion severity and generate a NIR caries score. Teeth were ground for histological examination after the measurements. The NIR caries score obtained correlates significantly (Spearman's correlation of 0.89, p<0.01) with the corresponding histological score. Results yield a sensitivity of >99% and a specificity of 87.5% for enamel lesions and a sensitivity of 80% and a specificity >99% for dentine lesions. The nature of the technique offers significant advantages, including the ability to map the lesion distribution rather than obtaining single-point measurements, it is also noninvasive, noncontact, and stain insensitive. These results suggest that NIR spectral imaging is a potential clinical technique for quantitative caries diagnosis and can determine the presence of occlusal enamel and dentin lesions.