gebhart/patrepeval huggingface dataset:
Opportunities with Wood Dissolved in Ionic Liquids (2010)

Biomass represents an abundant carbon-neutral renewable resource for the production of bioenergy and biomaterials. Shifting society’s dependence away from petroleum to renewable biomass resources is generally regarded as an important contributor to building up a sustainable society and effective management of greenhouse gas emissions. An ionic liquids-based processing platform for the efficient transformation of lignocellulosic materials into new materials and value-added chemicals has been developed. We have demonstrated that woody lignocellulosic materials are soluble in certain ionic liquids. The first preparation of homogenous wood solutions not only extends the utilization of lignocellulosic materials from heterogenous to homogenous processing conditions, but also creates a variety of new strategies for converting our abundant lignocellulosic biomass to novel value-added bioproducts. This chapter describes some applications under development, aimed at converting woody lignocellulose into new materials, chemicals and energy using ionic liquids as a processing platform.
Three Members of the 6-cys Protein Family of Plasmodium Play a Role in Gamete Fertility (2010)

The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of additional members of this family in Plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of P. berghei. This analysis revealed that in addition to P48/45, two members (P230 and P47) also play an essential role in the process of parasite fertilization. Mating studies between parasites lacking P230, P48/45 or P47 demonstrate that P230, like P48/45, is a male fertility factor, consistent with the previous demonstration of a protein complex containing both P48/45 and P230. In contrast, disruption of P47 results in a strong reduction of female fertility, while males remain unaffected. Further analysis revealed that gametes of mutants lacking expression of p48/45 or p230 or p47 are unable to either recognise or attach to each other. Disruption of the paralog of p230, p230p, also specifically expressed in gametocytes, had no observable effect on fertilization. These results indicate that the P. berghei 6-cys family contains a number of proteins that are either male or female specific ligands that play an important role in gamete recognition and/or attachment. The implications of low levels of fertilisation that exist even in the absence of these proteins, indicating alternative pathways of fertilisation, as well as positive selection acting on these proteins, are discussed in the context of targeting these proteins as transmission blocking vaccine candidates.
Cloning of CviPII nicking and modification system from chlorella virus NYs-1 and application of Nt.CviPII in random DNA amplification (2004)

The cloning and expression of the CviPII DNA nicking and modification system encoded by chlorella virus NYs-1 is described. The system consists of a co-linear MTase encoding gene (cviPIIM) and a nicking endonuclease encoding gene (cviPIINt) separated by 12 nt. M.CviPII possesses eight conserved amino acid motifs (I to VIII) typical of C5 MTases, but, like another chlorella virus MTase M.CviJI, lacks conserved motifs IX and X. In addition to modification of the first cytosine in CCD (D = A, G or T) sequences, M.CviPII modifies both the first two cytosines in CCAA and CCCG sites as well. Nt.CviPII has significant amino acid sequence similarity to Type II restriction endonuclease CviJI that recognizes an overlapping sequence (RG--CY). Nt.CviPII was expressed in Escherichia coli with or without a His-tag in a host pre-modified by M.CviPII. Recombinant Nt.CviPII recognizes the DNA sequence CCD and cleaves the phosphodiester bond 5' of the first cytosine while the other strand of DNA at this site is not affected. Nt.CviPII displays site preferences with CCR (R = A or G) sites preferred over CCT sites. Nt.CviPII is active from 16 to 65 degrees C with a temperature optimum of 30-45 degrees C. Nt.CviPII can be used to generate single-stranded DNAs (ssDNAs) for isothermal strand-displacement amplification. Nt.CviPII was used in combination with Bst DNA polymerase I large fragment to rapidly amplify anonymous DNA from genomic DNA or from a single bacterial colony.
Evaluation of sodium polyanethanol sulfonate as a blood culture additive for recovery of Salmonella typhi and Salmonella paratyphi A (1983)

A total of 640 blood specimens from patients in an area endemic for enteric fever were cultured in parallel in tryptic soy broth with and without sodium polyanethanol sulfonate (SPS). A total of 95 specimens were positive for Salmonella spp., 54 for Salmonella typhi, and 41 for Salmonella paratyphi A in one or both bottles of a set. Significantly higher rates of recovery were obtained from the SPS-containing medium (P less than 0.01) upon subculturing blindly at 24 h and 3 days of incubation. Subcultures performed at 7, 14, and 21 days also yielded a greater number of positive cultures with SPS than without it, although the differences between the two media were not significant (P greater than 0.05). Neither of the media yielded 100% of the positive cultures. Moreover, even if the results of the two media were combined, 34 and 19% of the isolates would have been missed if the specimens had not been incubated to 14 and 21 days, respectively. The data indicate that SPS aids in early recovery of S. typhi and S. paratyphi A from blood cultures, and additionally, that under the conditions used in the study, incubation beyond a 1-week period is required for efficient isolation of these organisms from blood.
Warfarin (1984)

ON the basis of two facts — that bishydroxycoumarin produced a bleeding disease in cattle and that it retarded blood clotting — coumarin compounds were hailed in 1941 as likely antithrombotic agents, a rather debatable prediction on the basis of the facts then available.With the development of the prothrombin-time assay to monitor the drug-induced defect in plasma,1 the stage was set, after a few studies in animals, for the first clinical trials. These studies were reported in 1941, one fifth of a century after "sweet clover disease" was first recognized by Schofield.2 Since World War II, information has accumulated . . .
Nonallelic homologous recombination events responsible for copy number variation within an RNA silencing locus (2019)

The structure of chalcone synthase (<i>CHS</i>) gene repeats in different alleles of the <i>I</i> (inhibitor) locus in soybean spawns endogenous RNA interference (RNAi) that leads to phenotypic change in seed coat color of this major agronomic crop. Here, we examined <i>CHS</i> gene copy number by digital PCR and single nucleotide polymorphisms (SNPs) through whole genome resequencing of 15 cultivars that varied in alleles of the <i>I</i> locus (<i>I</i>, <i>i<sup>i</sup></i> , <i>i<sup>k</sup></i> , and <i>i</i>) that control the pattern distribution of pigments in the seed coats. Lines homozygous for the <i>i<sup>i</sup></i> allele had the highest copy number followed by the <i>I</i> and <i>i<sup>k</sup></i> cultivars which were more related to each other than to the lines with <i>i<sup>i</sup></i> alleles. Some of the recessive <i>i</i> alleles were spontaneous mutations, and each revealed a loss of copy number by digital PCR relative to the parent varieties. Amplicon sequencing and whole genome resequencing determined that the breakpoints of several <i>i<sup>i</sup></i> to <i>i</i> mutations resulted from nonallelic homologous recombination (NAHR) events between <i>CHS</i> genes located in segmental duplications leading to large 138-kilobase deletions that erase the structure generating the <i>CHS</i> siRNAs along with eight other non-<i>CHS</i> genes. Functional hybrid <i>CHS</i> genes (designated <i>CHS5:1</i>) were formed in the process and represent rare examples of NAHR in higher plants that have been captured by examining spontaneous mutational events in isogenic mutant lines.
Planar waveguide Mach-Zender bandpass filter fabricated with single exposure UV-induced gratings (1996)

Summary form only given. Future optical fiber communication systems employing wavelength-division multiplexing will require narrow bandwidth multiplexing and demultiplexing components with good isolation and cross talk performance and minimal insertion loss. Mach-Zehnder interferometers containing UV-induced Bragg gratings have previously been demonstrated for use as a wavelength-multiplexing /demultiplexing device in planar waveguides. Bandpass filters are presented here which exhibit good performance without requiring any interferometer balancing after writing the gratings.
In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras–effector interaction (2013)

Mutational activation of the Ras oncogene products (H-Ras, K-Ras, and N-Ras) is frequently observed in human cancers, making them promising anticancer drug targets. Nonetheless, no effective strategy has been available for the development of Ras inhibitors, partly owing to the absence of well-defined surface pockets suitable for drug binding. Only recently, such pockets have been found in the crystal structures of a unique conformation of Ras⋅GTP. Here we report the successful development of small-molecule Ras inhibitors by an in silico screen targeting a pocket found in the crystal structure of M-Ras⋅GTP carrying an H-Ras-type substitution P40D. The selected compound Kobe0065 and its analog Kobe2602 exhibit inhibitory activity toward H-Ras⋅GTP-c-Raf-1 binding both in vivo and in vitro. They effectively inhibit both anchorage-dependent and -independent growth and induce apoptosis of H-ras(G12V)-transformed NIH 3T3 cells, which is accompanied by down-regulation of downstream molecules such as MEK/ERK, Akt, and RalA as well as an upstream molecule, Son of sevenless. Moreover, they exhibit antitumor activity on a xenograft of human colon carcinoma SW480 cells carrying the K-ras(G12V) gene by oral administration. The NMR structure of a complex of the compound with H-Ras⋅GTP(T35S), exclusively adopting the unique conformation, confirms its insertion into one of the surface pockets and provides a molecular basis for binding inhibition toward multiple Ras⋅GTP-interacting molecules. This study proves the effectiveness of our strategy for structure-based drug design to target Ras⋅GTP, and the resulting Kobe0065-family compounds may serve as a scaffold for the development of Ras inhibitors with higher potency and specificity.
Dasatinib in Imatinib-Resistant Philadelphia Chromosome–Positive Leukemias (2006)

Dasatinib induces hematologic and cytogenetic responses in patients with CML or Ph-positive ALL who cannot tolerate or are resistant to imatinib. (ClinicalTrials.gov number, NCT00064233 [ClinicalTrials.gov].).
Des-γ-carboxy Prothrombin Is a Potential Autologous Growth Factor for Hepatocellular Carcinoma (2004)

Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.
Memory Access Scheduling Schemes for Systems with Multi-Core Processors (2008)

On systems with multi-core processors, the memory access scheduling scheme plays an important role not only in utilizing the limited memory bandwidth but also in balancing the program execution on all cores. In this study, we propose a scheme, called ME-LREQ, which considers the utilization of both processor cores and memory subsystem. It takes into consideration both the long-term and short-term gains of serving a memory request by prioritizing requests hitting on the row buffers and from the cores that can utilize memory more efficiently and have fewer pending requests. We have also thoroughly evaluated a set of memory scheduling schemes that differentiate and prioritize requests from different cores. Our simulation results show that for memory-intensive, multiprogramming workloads, the new policy improves the overall performance by 10.7% on average and up to 17.7% on a four-core processor, when compared with scheme that serves row buffers hit memory requests first and allows memory reads bypassing writes; and by up to 9.2% (6.4% on average) when compared with the scheme that serves requests from the core with the fewest pending requests first.
CD137 and CD137L signals are main drivers of type 1, cell-mediated immune responses (2015)

CD137 is expressed on activated T cells and NK cells, among others, and is a potent co-stimulator of antitumor immune responses. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC), and CD137L reverse signaling into APC enhances their activity. CD137-CD137L interactions as main driver of type 1, cell-mediated immune responses explains the puzzling observation that CD137 agonists which enhance antitumor immune responses also ameliorate autoimmune diseases. Upon co-stimulation by CD137, Th1 CD4<sup>+</sup> T cells together with Tc1 CD8<sup>+</sup> T cells and NK cells inhibit other T cell subsets, thereby promoting antitumor responses and mitigating non-type 1 auto-immune diseases.
The kinase Mirk is a potential therapeutic target in osteosarcoma (2009)

Osteosarcoma is the most common primary malignant bone tumor affecting children and adolescents. The majority of patients are treated by surgery and chemotherapy but have limited alternative therapeutic options. Kinases play an important role in the growth and survival of tumor cells. We aim to identify specific kinases to be vital in the survival of osteosarcoma cells and thus may be a key target in creating novel anticancer therapies. A lentiviral short hairpin RNA kinase library, screened osteosarcoma cells, identified kinase minibrain-related kinase (Mirk) (Dyrk1B) as a potential target. Knockdown Mirk expression could inhibit cell growth and induce apoptosis. Chemically synthetic small interfering RNA knockdown and complementary DNA rescue assay further confirmed the results from the decrease of Mirk gene expression. The relationship between Mirk gene expression and the clinical characteristics of patients with osteosarcoma was investigated using tissue microarray and immunohistochemistry analysis. The data indicate that the overall survival rate of patients with Mirk high staining (high levels of Mirk protein expression) is significantly shorter than those with Mirk low staining and moderate staining. This highlights Mirk's potential to serve as a promising target for molecular therapy in the treatment of osteosarcoma.
Genetic and DNA sequence analysis of the kanamycin resistance transposon Tn903. (1980)

The kanamycin resistance transposon Tn903 consists of a unique region of about 1000 base pairs bounded by a pair of 1050-base-pair inverted repeat sequences. Each repeat contains two Pvu II endonuclease cleavage sites separated by 520 base pairs. We have constructed derivatives of Tn903 in which this 520-base-pair fragment is deleted from one or both repeats. Those derivatives that lack both 520-base-pair fragments cannot transpose, whereas those that lack just one remain transposition proficient. One such transposable derivative, Tn903 delta I, has been selected for further study. We have determined the sequence of the intact inverted repeat. The 18 base pairs at each end are identical and inverted relative to one another, a structure characteristic of insertion sequences. Additional experiments indicate that a single inverted repeat from Tn903 can, in fact, transpose; we propose that this element be called IS903. To correlate the DNA sequence with genetic activities, we have created mutations by inserting a 10-base-pair DNA fragment at several sites within the intact repeat of Tn903 delta 1, and we have examined the effect of such insertions on transposability. The results suggest that IS903 encodes a 307-amino-acid polypeptide (a "transposase") that is absolutely required for transposition of IS903 or Tn903.
A New Approach to Search for the Bioactive Conformation of Glucagon:  Positional Cyclization Scanning (2001)

In search for the bioactive conformation of glucagon, "positional cyclization scanning" was used to determine secondary structures of glucagon required for maximal interaction with the glucagon receptor. Because glucagon is flexible in nature, its bioactive conformation is not known except for an amphiphilic helical conformation at the C-terminal region. To understand the conformational requirement for the N-terminal region that appears to be essential for signal transduction, a series of glucagon analogues conformationally constrained by disulfide or lactam bridges have been designed and synthesized. The conformational restrictions via disulfide bridges between cysteine i and cysteine i + 5, or lactam bridges between lysine i and glutamic acid i + 4, were applied to induce and stabilize certain corresponding secondary structures. The results from the binding assays showed that all the cyclic analogues with disulfide bridges bound to the receptor with significantly reduced binding affinities compared to their linear counterparts. On the contrary, glucagon analogues containing lactam bridges, in particular, c[Lys(5), Glu(9)]glucagon amide (10) and c[Lys(17), Glu(21)]glucagon amide (14), demonstrated more than 7-fold increased receptor binding affinities than native glucagon. These results suggest that the bioactive conformation of glucagon may adopt a helical conformation at the N-terminal region as well as the C-terminal region, which was not evident from earlier biophysical studies of glucagon.
Homogenization of tissues via picosecond-infrared laser (PIRL) ablation: Giving a closer view on the in-vivo composition of protein species as compared to mechanical homogenization (2016)

Enzymatic protein modifications during tissue homogenization are responsible for changes of the in-vivo protein species composition. Cold vaporization of tissues by PIRL-DIVE is comparable with taking a snapshot at the time of the laser irradiation of the dynamic changes that occur continuously under in-vivo conditions. At that time point all biomolecules are transferred into an aerosol, which is immediately frozen.
Design and Testing of an Advanced Implantable Neuroprosthesis With Myoelectric Control (2010)

An implantable stimulator-telemeter (IST-12) was developed for applications in neuroprosthetic restoration of limb function in paralyzed individuals. The IST-12 provides 12 stimulation channels and two myoelectric signal (MES) channels. The MES circuitry includes a two-channel multiplexer, preamplifier, variable gain amplifier/bandpass filter, full-wave rectifier, and bin integrator. Power and control signals are transmitted from an external control unit to the IST-12 through an inductive link. Recorded MES signals are telemetered back to the external control unit through the same inductive link. Following bench testing, one device was implanted chronically in a dog for 15 months and evaluated. Conditions were identified in which MES could be recorded with minimal stimulus artifact. The ability to record MES in the presence of stimulation was verified, confirming the potential of the IST-12 to be used as a myoelectric controlled neuroprosthesis.
Thermostable Ligase-Mediated Incorporation of Mutagenic Oligonucleotides During PCR Amplification (2003)

PCR amplification has become an extremely powerful and universally used technique for cloning and manipulating DNA segments. It is especially useful for the ability to alter the terminal sequences of an amplified product simply by using primers containing the desired changes. However, the inability to alter easily regions of a product between the amplification primers has limited the use of PCR for more general mutagenesis. The protocol presented in this chapter employs a sample method that removes this limitation.
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies (2013)

Fc γ receptor (FcγR) coengagement can facilitate antibody-mediated receptor activation in target cells. In particular, agonistic antibodies that target tumor necrosis factor receptor (TNFR) family members have shown dependence on expression of the inhibitory FcγR, FcγRIIB. It remains unclear if engagement of FcγRIIB also extends to the activities of antibodies targeting immunoregulatory TNFRs expressed by T cells. We have explored the requirement for activating and inhibitory FcγRs for the antitumor effects of antibodies targeting the TNFR glucocorticoid-induced TNFR-related protein (GITR; TNFRSF18; CD357) expressed on activated and regulatory T cells (T reg cells). We found that although FcγRIIB was dispensable for the in vivo efficacy of anti-GITR antibodies, in contrast, activating FcγRs were essential. Surprisingly, the dependence on activating FcγRs extended to an antibody targeting the non-TNFR receptor CTLA-4 (CD152) that acts as a negative regulator of T cell immunity. We define a common mechanism that correlated with tumor efficacy, whereby antibodies that coengaged activating FcγRs expressed by tumor-associated leukocytes facilitated the selective elimination of intratumoral T cell populations, particularly T reg cells. These findings may have broad implications for antibody engineering efforts aimed at enhancing the therapeutic activity of immunomodulatory antibodies.
Substrate and size effects on the coalescence of small particles (1991)

Here we present experimental results, using high-resolution electron microscopy and real time video recording, on the liquid-like coalescence of small gold particles supported on silica. We report that particles that are few nanometers in size, and decoupled from substrate interactions, coalesce extremely fast, in fractions of a second. When the particles are properly supported on a substrate, coalescence is orders of magnitude slower, depending on the particle size, and influenced by the diffusion of atoms on the substrate surface. Necks are seen to develop distinctly during coalescence only for particles above certain size.