gebhart/patrepeval huggingface dataset:
Cloning and DNA sequence of the gene coding for Bacillus stearothermophilus T-6 xylanase (1994)

Bacillus stearothermophilus T-6 produces an extracellular thermostable xylanase. Affinity-purified polyclonal serum raised against the enzyme was used to screen a genomic library of B. stearothermophilus T-6 constructed in lambda-EMBL3. Two positive phages were isolated, both containing similar 13-kb inserts, and their lysates exhibited xylanase activity. A 3,696-bp SalI-BamHI fragment containing the xylanase gene was subcloned in Escherichia coli and subsequently sequenced. The open reading frame of xylanase T-6 consists of 1,236 bp. On the basis of sequence similarity, two possible -10 and -35 regions, a ribosome-binding site at the 5' end of the gene and a potential transcriptional termination motif at the 3' end of the gene, were identified. From the previously known N-terminal amino acid sequence of xylanase T-6 and the possible ribosome-binding site, a putative 28-amino-acid signal peptide was deduced. The mature xylanase T-6 consists of 379 amino acids with a calculated molecular weight and pI of 43,808 and 6.88, respectively. Multiple alignment of beta-glycanase amino acid sequences revealed highly conserved regions. Northern (RNA) blot analysis indicated that the xylanase T-6 transcript is about 1.4 kb and that the induction of this enzyme synthesis by xylose is on the transcriptional level.
Lipoteichoic Acid Is a Potent Inducer of Cytokine Production in Rat and Human Kupffer Cells In Vitro (2003)

Our results support the contention that gram-positive bacteria may activate cytokine production in Kupffer cells during bacteremia and suggest that LTA is important in this interaction.
MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma (2015)

Genomic analyses of squamous cell carcinoma (SCC) have yet to yield significant strategies against pathway activation to improve treatment. Platinum-based chemotherapy remains the mainstay of treatment for SCC of different histotypes either as a single-agent or alongside other chemotherapeutic drugs or radiotherapy; however, resistance inevitably emerges, which limits the duration of treatment response. To elucidate mechanisms that mediate resistance to cisplatin, we compared drug-induced perturbations to gene and protein expression between cisplatin-sensitive and -resistant SCC cells, and identified MAPK-ERK pathway upregulation and activation in drug-resistant cells. ERK-induced resistance appeared to be activated by Son of Sevenless (SOS) upstream, and mediated through Bim degradation downstream. Clinically, elevated p-ERK expression was associated with shorter disease-free survival in patients with locally advanced head and neck SCC treated with concurrent chemoradiation. Inhibition of MEK/ERK, but not that of EGFR or RAF, augmented cisplatin sensitivity in vitro and demonstrated efficacy and tolerability in vivo. Collectively, these findings suggest that inhibition of the activated SOS-MAPK-ERK pathway may augment patient responses to cisplatin treatment.
OLAP and Statistical Databases: Similarities and Differences. (1996)

During the 1980&amp;apos;s there was a lot of activity in the area of Statistical Databases, focusing mostly on socio-economic type applications, such as census data, national production and consumption patterns, etc. In the 1990&amp;apos;s the area of On-Line-Analytic Processing (OLAP) was introduced for the analysis of transaction based business data, such as retail stores transactions. Both areas deal with the representation and support of data in a multi-dimensional space. Much of the OLAP literature does not refer to the Statistical Database literature, perhaps because the connection between analyzing business data and socio-economic data is not obvious. Furthermore, there are papers published in one area or the other whose results can be applied in both application areas. In this paper, we compare the work done in these two areas. We discuss concepts used in the conceptual modeling of the data and operations over them, efficient physical organization and access methods, as well as privaccy issues. We point out the terminology used and the correspondence between terms. We identify which research aspects are emphasized in each of these areas and the reasons for that. We conclude by arguing for the support of a Statistical Object data type as one of the fundamental structures that object-oriented data models and systems should support.
Solution-Phase Parallel Synthesis of Novel Membrane-Targeted Antibiotics (2009)

The increase in the incidence of antibiotic-resistant infections is a major concern to healthcare workers and requires the development of novel antibacterial agents. Recently, we described a series of benzophenone-containing antibiotics which displayed activity against antibiotic-resistant bacteria. We have shown that these agents function by disrupting the bacterial membrane. To further explore these compounds, a practical and efficient solution-phase parallel synthesis method was developed which allowed us to prepare combinatorial libraries of these agents. Using this method, we prepared 218 compounds in 58 reactions. All of the compounds were characterized by HPLC and MALDI-TOF mass spectrometry. Analysis of this library for antibacterial activity identified six compounds which displayed MIC values of 2.0 mg/L against Staphylococcus aureus. Examination of the structure-function relationships of these agents revealed that cationic groups were required and that cyclic, aliphatic amines were crucial for activity. Using the information generated here, we speculate on how the various structural features of the molecule are necessary for the interaction with the bacterial membrane.
Conformational constraints in nuclear dna (1976)

We have investigated DNA superstructure in a wide range of nuclei of higher cells by gently lysing cells to release structures that resemble nuclei but are depleted of nuclear proteins. The sedimentation properties of these structures, which we call nucleoids, have been examined in sucrose gradients containing the intercalating agent, ethidium. The sedimentation rate of nucleoids derived from the growing cells of mammals, birds, amphibians and insects varies in the manner characteristic of circular and superhelical molecules of DNA. These characteristic changes in sedimentation rate are abolished by irradiating the nucleoids with low doses of gamma-rays, a procedure known to introduce single-strand scissions into DNA. We have also investigated by similar means DNA superstructure in nucleoids derived from a variety of different chick cells. Nucleoids derived from adult hen erythrocytes differ from the other nucleoids studied in that their sedimentation rate does not vary in the manner characteristic of supercoiled DNA.
Effective Reduction of Critical Current for Current-Induced Magnetization Switching by a Ru Layer Insertion in an Exchange-Biased Spin Valve (2004)

Recently, it has been predicted that a spin-polarized electrical current perpendicular to plane directly flowing through a magnetic element can induce magnetization switching through spin-momentum transfer. In this Letter, the first observation of current-induced magnetization switching (CIMS) in exchange-biased spin valves (ESPVs) at room temperature is reported. The ESPVs show the CIMS behavior under a sweeping dc current with a very high critical current density. It is demonstrated that a thin ruthenium (Ru) layer inserted between a free layer and a top electrode effectively reduces the critical current densities for the CIMS. An "inverse" CIMS behavior is also observed when the thickness of the free layer increases.
The Biology of CD20 and Its Potential as a Target for mAb Therapy (2004)

CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of almost all normal and malignant B cells. It is also the target for rituximab, the most effective anti-cancer monoclonal antibody developed to date. Rituximab has now been given to over 300,000 lymphoma patients in the last decade and interestingly is now being explored for use in other disorders, such as autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus. Despite the success in immunotherapy, knowledge about the biology of CD20 is still relatively scarce, partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype. However, interesting insight has come from work showing that CD20 is resident in lipid raft domains of the plasma membrane where it probably functions as a store-operated calcium channel following ligation of the B cell receptor for antigen. In the current review, these and data relating to its activity as a therapeutic target will be discussed in depth. It is clear that a greater understanding of CD20 biology and the effector mechanisms, such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and growth regulation, which operate with anti-CD20 mAb in vivo will allow more efficient exploitation of CD20 as a therapeutic target.
Applicability of classical optical fiber theories to holey fibers (2004)

We discuss the applicability of well-established classical optical fiber theories to holey fibers. By appropriately defining the V parameter, we can easily estimate the fundamental properties of holey fibers, such as effective index, group-velocity dispersion, mode field diameter, beam divergence, and splice loss, through simple empirical expressions without the need for heavy numerical computations. We confirm the validity of the V parameter defined here by comparing the calculated results with the earlier experimental and numerical results.
Reactivity and Derivatization of Five-Coordinate, Chelated Aluminum (2001)

The convenient five-coordinate starting materials, Salen(tBu)AlCl (Salen(tBu) = N,N‘-alkylene (or arylene) bis (3,5-di-tert-butyl-2-hydroxybenzylideneamine) (1−4) can be used in a wide range of reactions to form five-coordinate aluminum compounds. Herein, these reagents were used to produce new five-coordinate azides, LAlN3 (L = Salen(tBu) (5), Salpen(tBu) (6), and Salomphen(tBu) (7)) through trimethylsilylhalide elimination. The decomposition of the azides produce first hydroxide (LAlOH (L = Salen(tBu) (8)) and, subsequently in the presence of chlorotrimethylsilane, the siloxide compounds, LAlOSiMe3 (L = Salen(tBu) (9), Salpen(tBu) (10), and Salomphen(tBu) (11)). Alkane elimination reactions may also be used to access this type of compound as evidenced by the formation of Salomphen(tBu)AlOSiPh3 (12). Additionally, the first structurally characterized five-coordinate monomeric amide, Salcen(tBu)AlN(SiMe3)2 (13), can prepared by a salt elimination utilizing Salcen(tBu)AlCl (4). The compounds were characterized by spectroscopic methods (1H and 27Al NMR, MS, and IR) and, in the case of 2 (Salpen(tBu)AlCl), 3 (Salomphen(tBu)AlCl) 9, 11, 12, and 13, by X-ray analysis. Several of the compounds were explored as potential catalysts for the living polymerization of propylene oxide.
Serum and CSF immunological findings in ALS (1991)

Serum and CSF immunological findings were analysed in 37 patients with amyotrophic lateral sclerosis (ALS). ALS patients had significantly higher mean values of serum IgG and complement component C4 and significantly lower mean value of total haemolytic titre of complement (THC) compared with normal controls. Incidence of immune complexes (ICs) was significantly higher in sera of ALS patients than in normal controls. There was no significant difference regarding mean serum levels of IgM, IgA, and complement components C3 and Factor B between patients and controls. The blood-brain barrier (BBB) damage was found in 46% of patients. Intrathecal IgG synthesis was detected in six patients (16%). These results support the hypothesis of immune system involvement in ALS.
Crystal Structure of Red Sea Bream Transglutaminase (2001)

The crystal structure of the tissue-type transglutaminase from red sea bream liver (fish-derived transglutaminase, FTG) has been determined at 2.5-A resolution using the molecular replacement method, based on the crystal structure of human blood coagulation factor XIII, which is a transglutaminase zymogen. The model contains 666 residues of a total of 695 residues, 382 water molecules, and 1 sulfate ion. FTG consists of four domains, and its overall and active site structures are similar to those of human factor XIII. However, significant structural differences are observed in both the acyl donor and acyl acceptor binding sites, which account for the difference in substrate preferences. The active site of the enzyme is inaccessible to the solvent, because the catalytic Cys-272 hydrogen-bonds to Tyr-515, which is thought to be displaced upon acyl donor binding to FTG. It is postulated that the binding of an inappropriate substrate to FTG would lead to inactivation of the enzyme because of the formation of a new disulfide bridge between Cys-272 and the adjacent Cys-333 immediately after the displacement of Tyr-515. Considering the mutational studies previously reported on the tissue-type transglutaminases, we propose that Cys-333 and Tyr-515 are important in strictly controlling the enzymatic activity of FTG.
A rapid and sensitive bioassay to measure bone morphogenetic protein activity (2007)

The assay is rapid (less than 24 hours) and can be used, as described in this paper, to measure BMP activity in complex solutions and in cell culture in a simple and efficient way.
Large‐scale production of endotoxin‐free plasmids for transient expression in mammalian cell culture (2007)

Transient expression of recombinant proteins in mammalian cell culture in a 100-L scale requires a large quantity of plasmid that is very labour intensive to achieve with shake flask cultures and commercially available plasmid purification kits. In this paper we describe a process for plasmid production in 100-mg scale. The fermentation is carried out in a 4-L fed-batch culture with a minimal medium. The detection of the end of batch and triggering the exponential (0.1 h(-1)) feed profile was unattended and controlled by Multi-fermenter Control System. A restricted specific growth rate in fed-batch culture increased the specific plasmid yield compared to batch cultures with minimal and rich media. This together with high biomass concentration (68-107 g L(-1) wet weight) achieves high volumetric yields of plasmid (95-277 mg L(-1) depending on the construct). The purification process consisted of alkaline lysis, lysate clarification and ultrafiltration, two-phase extraction with Triton X-114 for endotoxin removal, anion-exchange chromatography as a polishing step, ultrafiltration and sterile filtration. Both fermentation and purification processes were used without optimisation for production of four plasmids yielding from 39 to 163 mg of plasmids with endotoxin content of 2.5 EU mg(-1) or less.
Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data (1983)

A theoretical model of blood-brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and determining whether a unidirectional transfer process was dominant during part or all of the experimental period. If the graph indicates unidirectionality of uptake, then an influx constant (Ki) can be calculated. The model is general, assumes linear transfer kinetics, and consists of a blood-plasma compartment, a reversible tissue region with an arbitrary number of compartments, and one or more irreversible tissue regions. The solution of the equations for this model shows that a graph of the ratio of the total tissue solute concentration at the times of sampling to the plasma concentration at the respective times (Cp) versus the ratio of the arterial plasma concentration-time integral to Cp should be drawn. If the data are consistent with this model, then this graph will yield a curve that eventually becomes linear, with a slope of Ki and an ordinate intercept less than or equal to the vascular plus steady-state space of the reversible tissue region.
Lipid rafts: heterogeneity on the high seas (2004)

Lipid rafts are membrane microdomains that are enriched in cholesterol and glycosphingolipids. They have been implicated in processes as diverse as signal transduction, endocytosis and cholesterol trafficking. Recent evidence suggests that this diversity of function is accompanied by a diversity in the composition of lipid rafts. The rafts in cells appear to be heterogeneous both in terms of their protein and their lipid content, and can be localized to different regions of the cell. This review summarizes the data supporting the concept of heterogeneity among lipid rafts and outlines the evidence for cross-talk between raft components. Based on differences in the ways in which proteins interact with rafts, the Induced-Fit Model of Raft Heterogeneity is proposed to explain the establishment and maintenance of heterogeneity within raft populations.
IL-4 plus CD40 monoclonal antibody induces human B cells γ subclass-specific isotype switch: switching to γ 1, γ 3, and γ 4, but not γ 2 (1995)

Stimulation with IL-4 plus CD40 mAb is known to induce production of IgE and IgG4. In this study, we determined the IgG subclass specificity of IL-4 plus CD40 mAb stimulation for human purified B cells. We determined true in vitro switching by the generation of switch circular DNA (S gamma/S mu) representing primary S mu/S gamma events and production of gamma subclass-specific germ-line transcripts by a combination of reverse transcription-PCR and restriction endonuclease digestion. We simultaneously measured changes in the levels of IgG subclass proteins produced. Forty-two clones of circular switch DNA were identified and sequenced. The IgG subclass of S gamma fragment in the S gamma/S mu chimeric PCR products was determined by analyzing key S gamma nucleotides. The switch-deleted clones were found to consist of S gamma 1/S mu, S gamma 3/S mu, and S gamma 4/S mu chimeric switch sequences, showing that such switching had occurred. No S gamma 2/S mu chimeric switch sequences were found. While a consensus sequence was not identified at the S gamma/S mu breakpoints, four contiguous guanines (GGGG) were noticeably present in the S gamma region near the breakpoint. The induction of gamma 1, gamma 3, and gamma 4 switch circles in human purified B cells was accompanied by enhanced production of IgG1, IgG3, and IgG4 but not IgG2. Similarly, stimulation with IL-4 alone induced gamma 1, gamma 3, and gamma 4 but not gamma 2 germ-line transcripts. These results demonstrate that IL-4 plus CD40 mAb induces Ig isotype switch from mu to gamma 1, gamma 3, and gamma 4 but not to gamma 2.
Finite precision error analysis of neural network hardware implementations (1993)

Through parallel processing, low precision fixed point hardware can be used to build a very high speed neural network computing engine where the low precision results in a drastic reduction in system cost. The reduced silicon area required to implement a single processing unit is taken advantage of by implementing multiple processing units on a single piece of silicon and operating them in parallel. The important question which arises is how much precision is required to implement neural network algorithms on this low precision hardware. A theoretical analysis of error due to finite precision computation was undertaken to determine the necessary precision for successful forward retrieving and back-propagation learning in a multilayer perceptron. This analysis can easily be further extended to provide a general finite precision analysis technique by which most neural network algorithms under any set of hardware constraints may be evaluated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
How to generate cryptographically strong sequences of pseudo random bits (1982)

We give a set of conditions that allow one to generate 50–50 unpredictable bits.Based on those conditions, we present a general algorithmic scheme for constructing polynomial-time deterministic algorithms that stretch a short secret random input into a long sequence of unpredictable pseudo-random bits.We give an implementation of our scheme and exhibit a pseudo-random bit generator for which any efficient strategy for predicting the next output bit with better than 50–50 chance is easily transformable to an “equally efficient” algorithm for solving the discrete logarithm problem. In particular: if the discrete logarithm problem cannot be solved in probabilistic polynomial time, no probabilistic polynomial-time algorithm can guess the next output bit better than by flipping a coin: if “head” guess “0”, if “tail” guess “1”
Micromachined low-loss microwave switches (1999)

The design and fabrication of a micromechanical capacitive membrane microwave switching device is described. The switching element consists of a thin metallic membrane, which has two states, actuated or unactuated, depending on the applied bias. A microwave signal is switched on and off when the membrane is switched between the two states. These switches have a switching on speed of less than 6 /spl mu/s and a switching off speed of less than 4 /spl mu/s. The switching voltage is about 50 V. The switches have a bowtie shape and showed low insertion loss of 0.14 dB at 20 GHz and 0.25 dB at 35 GHz, and isolation of 24 dB at 20 GHz and 35 dB at 35 GHz. These devices offer the potential for building a new generation of low-loss high-linearity microwave circuits for a variety of phased antenna arrays for radar and communications applications.
High‐yield expression of a viral peptide animal vaccine in transgenic tobacco chloroplasts (2004)

The 2L21 peptide, which confers protection to dogs against challenge with virulent canine parvovirus (CPV), was expressed in tobacco chloroplasts as a C-terminal translational fusion with the cholera toxin B subunit (CTB) or the green fluorescent protein (GFP). Expression of recombinant proteins was dependent on plant age. A very high-yield production was achieved in mature plants at the time of full flowering (310 mg CTB-2L21 protein per plant). Both young and senescent plants accumulated lower amounts of recombinant proteins than mature plants. This shows the importance of the time of harvest when scaling up the process. The maximum level of CTB-2L21 was 7.49 mg/g fresh weight (equivalent to 31.1% of total soluble protein, TSP) and that of GFP-2L21 was 5.96 mg/g fresh weight (equivalent to 22.6% of TSP). The 2L21 inserted epitope could be detected with a CPV-neutralizing monoclonal antibody, indicating that the epitope is correctly presented at the C-terminus of the fusion proteins. The resulting chimera CTB-2L21 protein retained pentamerization and G(M1)-ganglioside binding characteristics of the native CTB and induced antibodies able to recognize VP2 protein from CPV. To our knowledge, this is the first report of an animal vaccine epitope expression in transgenic chloroplasts. The high expression of antigens in chloroplasts would reduce the amount of plant material required for vaccination (approximately 100 mg for a dose of 500 microg antigen) and would permit encapsulation of freeze-dried material or pill formation.