gebhart/patrepeval huggingface dataset:
Effect of Codon Optimization on Expression Levels of a Functionally Folded Malaria Vaccine Candidate in Prokaryotic and Eukaryotic Expression Systems (2003)

We have produced two synthetic genes that code for the F2 domain located within region II of the 175-kDa Plasmodium falciparum erythrocyte binding antigen (EBA-175) to determine the effects of codon alteration on protein expression in homologous and heterologous host systems. EBA-175 plays a key role in the process of merozoite invasion into erythrocytes through a specific receptor-ligand interaction. The F2 domain of EBA-175 is the ligand that binds to the glycophorin A receptor on human erythrocytes and is therefore a target of vaccine development efforts. We designed synthetic genes based on P. falciparum, Escherichia coli, and Pichia codon usage and expressed recombinant F2 in E. coli and Pichia pastoris. Compared to the expression of the native F2 sequence, conversion to prokaryote (E. coli)- or eukaryote (Pichia)-based codon usage dramatically improved the levels of recombinant protein expression in both E. coli and P. pastoris. The majority of the protein expressed in E. coli, however, was produced as inclusion bodies. The protein expressed in P. pastoris, on the other hand, was expressed as a secreted, soluble protein. The P. pastoris-produced protein was superior to that produced in E. coli based on its ability to bind to red blood cells. Consistent with these observations, the antibodies generated against the Pichia-produced protein prevented the binding of recombinant EBA to red blood cells. These antibodies recognize EBA-175 present on merozoites as well as in sporozoites by immunofluorescence. Our results suggest that the Pichia-based EBA-F2 vaccine construct has further potential to be developed for clinical use.
FT-NFS: an efficient fault-tolerant NFS server designed for off-the-shelf workstations (2002)

In most modern local area network environments, NFS is used to provide remote file storage on a particular server machine. A consequence of this distributed architecture is that the failure of the server results in paralysis or a loss of work for users. The paper presents the design of a low cost fault tolerant NFS server which can be installed on most Unix networking environments. FT-NFS runs as a user process and does not necessitate any underlying specific operating system functionality. The originality of our approach relies on the use of a stable cache which provides data availability and resiliency to a single failure. The main benefits of the stable cache are first to allow disk write operations to be safely performed in the back ground and second to permit the gathering of small files in large containers. The latter technique permits disk I/Os to be improved by reducing their number and increasing their length. Under the nhf-stone benchmark, FT-NFS outperforms the in kernel Sun NFS implementation both in terms of latency and throughput.
Simulation optimization: A comprehensive review on theory and applications (2004)

For several decades, simulation has been used as a descriptive tool by the operations research community in the modeling and analysis of a wide variety of complex real systems. With recent developments in simulation optimization and advances in computing technology, it now becomes feasible to use simulation as a prescriptive tool in decision support systems. In this paper, we present a comprehensive survey on techniques for simulation optimization with emphasis given on recent developments. We classify the existing techniques according to problem characteristics such as shape of the response surface (global as compared to local optimization), objective functions (single or multiple objectives) and parameter spaces (discrete or continuous parameters). We discuss the major advantages and possible drawbacks of the different techniques. A comprehensive bibliography and future research directions are also provided in the paper.
Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation. (1992)

Although the immunologic basis of protective immunity in human immunodeficiency virus type 1 (HIV-1) infection has not yet been defined, virus-specific cytotoxic T lymphocytes (CTL) are likely to be an important host defense and may be a critical feature of an effective vaccine. These observations, along with the inclusion of the HIV-1 envelope in the majority of vaccine candidates presently in clinical trials, underscore the importance of the precise characterization of the cellular immune responses to this protein. Although humoral immune responses to the envelope protein have been extensively characterized, relatively little information is available regarding the envelope epitopes recognized by virus-specific CTL and the effects of sequence variation within these epitopes. Here we report the identification of two overlapping CTL epitopes in a highly conserved region of the HIV-1 transmembrane envelope protein, gp41, using CTL clones derived from two seropositive subjects. An eight-amino acid peptide was defined as the minimum epitope recognized by HLA-B8-restricted CTL derived from one subject, and in a second subject, an overlapping nine-amino acid peptide was identified as the minimal epitope for HLA-B14-restricted CTL clones. Selected single amino acid substitutions representing those found in naturally occurring HIV-1 isolates resulted in partial to complete loss of recognition of these epitopes. These data indicate the presence of a highly conserved region in the HIV-1 envelope glycoprotein that is immunogenic for CTL responses. In addition, they suggest that natural sequence variation may lead to escape from immune detection by HIV-1-specific CTL. Since the region containing these epitopes has been previously shown to contain an immunodominant B cell epitope and also overlaps with a major histocompatibility complex class II T cell epitope recognized by CD4+ CTL from HIV-1 rgp160 vaccine recipients, it may be particularly important for HIV-1 vaccine development. Finally, the identification of minimal CTL epitopes presented by class I HLA molecules should facilitate the definition of allele-specific motifs.
Genomic organization and expression of the human alpha 1B-adrenergic receptor. (1992)

alpha 1-Adrenergic receptors (ARs) are members of the guanine nucleotide-binding protein-coupled receptor superfamily. The genes for all ARs described thus far are intronless. We report here the cloning and the nucleotide sequence of the gene for the human alpha 1B-AR. It consists of two exons and a single large intron of at least 20 kilobases which interrupts the coding region at the end of the putative sixth transmembrane domain. The deduced amino acid sequence of the encoded receptor has a high degree of homology to the cloned hamster, rat, and dog alpha 1B-ARs. To characterize the encoded protein, a fusion gene constructed by splicing together exon 1 and exon 2 was expressed transiently in COS-1 cells. The transfected gene fusion product resulted in the production of an alpha 1B-AR with ligand binding characteristics indistinguishable from those of the expressed hamster alpha 1B cDNA. Evidence that the human alpha 1B-AR gene we have isolated is indeed transcribed is the finding of similar sized (2.8-kilobase) transcripts in human heart and other tissues by Northern blot analysis when either exon 1 or exon 2 is used as a probe. Moreover, using primers designed to span the exon 1/exon 2 boundary, a polymerase chain reaction product generated from single-stranded DNA prepared from human heart mRNA had the exact size and nucleotide sequence predicted for a transcript in which exon 1 is spliced to exon 2. The 5'-flanking region (924 base pairs (bp)) of exon 1 contains neither a TATA box nor a CAAT box but is high in GC content (70%) and contains several Sp1 binding sites (GC boxes), consistent with promoters described for housekeeping genes. The 5'-untranslated region also contains a putative cyclic AMP response element. Primer extension studies and RNase protection assays suggested that there are several potential transcription start sites in most tissues with a predominant site located 173 bp upstream from the translation start site. The 3'-flanking region contains a putative polyadenylation signal (ATTAAA) 492 bp downstream from the stop codon. The genomic organization of the human alpha 1B-AR with a single large intron interrupting its coding region differs from those of other ARs as well as muscarinic and 5-hydroxy-tryptamine receptors, which are intronless. The location of the intron in the human alpha 1B-AR gene is also unique among those members of the G-protein-coupled receptor family that do possess introns.(ABSTRACT TRUNCATED AT 400 WORDS)
Determination of the nucleotide sequence for the exonuclease I structural gene (sbcB) of Escherichia coli K12. (1987)

The complete nucleotide sequence of the structural gene for Escherichia coli exonuclease I has been determined. The coding region corresponds to a 465-amino acid protein with molecular weight of 53,174. The partial amino acid sequence of purified exonuclease I agrees with that predicted by the DNA sequence. Two putative weak promoters have been localized by S1 nuclease analysis. The sbcB coding sequence contains many non-optimal codons, characteristic of many poorly expressed E. coli genes.
Synthesis and Biological Activity of Aromatic Amino Acid Phosphoramidates of 5-Fluoro-2‘-deoxyuridine and 1-β-Arabinofuranosylcytosine:  Evidence of Phosphoramidase Activity (1996)

The amino acid phosphoramidate diesters of FUdR (2) and Ara-C (6), 5-fluoro-2'-deoxy-5'-uridyl N-(1-carbomethoxy-2-phenylethyl)phosphoramidate (5a), 5-fluoro-2'-deoxy-5'- uridyl N-(1-carbomethoxy-2-indolylethyl)phosphoramidate (5b), 1-beta-arabinofuranosylcytosine 5'-N-(1-carbomethoxy-2-phenylethyl) phosphoramidate (8a), and 1-beta-arabinofuranosylcytosine 5'-N-(1-carbomethoxy-2-indolylethyl)phosphoramidate (8b), were synthesized and tested for their antitumor activity against L1210 mouse lymphocytic leukemia cells and CCRF-CEM human T-cell lymphoblastic leukemia cells. Ara-C phosphoramidates 8a,b were found to be inactive at a concentration of 100 microM, while the FUdR conjugates 5a,b exhibited IC50 values within a range of 0.30-0.40 microM. Stability studies revealed that > 99% of the phosphoramidates remained intact after incubation for > 2 days in 20% calf or 20% human serum. Intracellular thymidylate synthase (TS) inhibition studies revealed that treatment of L1210 and CCRF-CEM cells with 5a or 5b resulted in significant inhibition of TS in intact and permeabilized cells, while treatment of L929 TK- cells with these compounds did not result in inhibition of TS activity in intact cells. However, permeabilization of L929 TK- cells enhanced the activity of 5a,b toward intracellular TS by 900- and 1500-fold, respectively. In addition, incubation of cell-free extracts of CEM cells with radiolabeled 5b resulted in the rapid production of FUdR 5'-monophosphate and a lag in the generation of FUdR. Consequently, it is proposed that the metabolism of the phosphoramidate diesters of FUdR in proliferating tissue proceeds through two separate enzymatic steps involving P-N bond cleavage by an unknown phosphoramidase followed by P-O bond cleavage by phosphatases such as 5'-nucleotidase.
Striped Smith–Waterman speeds database searches six times over other SIMD implementations (2006)

http://farrar.michael.googlepages.com/Smith-waterman
Activation of the STAT Pathway by Angiotensin II in T3CHO/AT1A Cells (1995)

We recently reported that angiotensin II (AII), acting through the STAT (Signal Transducers and Activators of Transcription) pathway, stimulated a delayed SIF (sis-inducing factor)-like DNA binding activity (maximal at 2-3 h) (Bhat, G.J., Thekkumkara, T.J., Thomas, W.G., Conrad, K.M., and Baker, K.M. (1994) J. Biol. Chem. 269, 31443-31449). Using a cell line transfected with the AT1A receptor (T3CHO/AT1A), we further characterized the AII-induced SIF response and explored the possible reasons for the delay in stimulated SIF activity. In cells transfected with a chloramphenicol acetyltransferase reporter plasmid, under the control of a SIE (sis-inducing element), AII markedly stimulated chloramphenicol acetyltransferase activity. The delayed SIF activation by AII was not due to a requirement for the release of other SIF inducing factors into the medium and contrasts with the rapid (5 min) induction elicited by the cytokine, interleukin-6 (IL-6). Interestingly, both agents stimulated tyrosine phosphorylation of Stat92 and predominantly the formation of SIF complex A. We tested the hypothesis that AII initially activated an inhibitory pathway, which was responsible for delaying the maximal SIF stimulation until 2 h. Pretreatment of cells for 15 min with AII resulted in significant inhibition of the IL-6 induced nuclear SIF response (10 min) and Stat92 tyrosine phosphorylation, which was blocked by EXP3174, an AT1 receptor antagonist. This inhibition was transient with return of the IL-6-induced SIF response at 2 h, suggesting that the delayed maximal activation of SIF by AII occurs following an initial transient inhibitory phase. Pretreatment of cells with phorbol 12-myristate 13-acetate for 15 min, to activate protein kinase C, resulted in inhibition of the IL-6-induced SIF response (10 min). However, down-regulation of protein kinase C activity prevented phorbol 12-myristate 13-acetate, but not AII mediated inhibition of the IL-6-induced SIF response. Although the mechanism is not clear, the results presented in this paper raise the interesting possibility that the activation of SIF/Stat92 by AII is characterized by an initial inhibitory phase, followed by the induction process. The observation that AII and IL-6 utilize similar components of the STAT pathway and that AII can cross-talk with IL-6 signaling through inhibition of IL-6-induced SIF/Stat92, implies a modulatory role for AII in cellular responses to cytokines.
Addiction to Oncogenes--the Achilles Heal of Cancer (2002)

Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer,
Atrial Electroanatomic Remodeling After Circumferential Radiofrequency Pulmonary Vein Ablation (2001)

Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.
ChemInform Abstract: Metal Deposition from Aromatic Solvents. (1989)

Abstract It is demonstrated that Cu and Pd can be successfully deposited from a phenanthrene/anisole mixed solvent using the amine complexes PdCl 2 ·2 (n‐octylamine) and CuCl·n‐pentylamine.
Mutant rhodopsin transgene expression on a null background. (2001)

GHL-rhodopsin dimerizes, localizes to the ER, and fails to transport and support outer segment formation. Additionally, the mutant protein does not support a scotopic ERG a-wave and accelerates photoreceptor degeneration over that occurring with the rhodopsin knockout alone. These findings indicate a cytotoxic effect of the mutant protein, probably elicited by an unfolded protein response.
Use of Animal Models of Human Disease for Nonclinical Safety Assessment of Novel Pharmaceuticals (2012)

Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode of action of novel pharmaceuticals. However, conventional (healthy) rodent and nonrodent models are generally utilized in nonclinical safety testing. Animal models of human disease may be helpful in understanding safety risks of compounds in nonclinical or clinical development, with their greatest value being in targeted or hypothesis-driven studies to help understand the mechanism of a particular toxicity. Limitations of animal models of disease in nonclinical safety testing include a lack of historical control, heterogeneity in disease expression, a limited life span, and confounding effects of the disease. In most instances, animal models of human disease should not be utilized to supplant testing in conventional animal models. While of potential benefit, testing in an animal model of human disease should only be taken after adequate consideration of relevance along with benefits and limitations of the proposed model.
Outbreak of Pseudomonas fluorescens Bacteremia among Oncology Patients (1998)

From 7 to 24 March 1997, four patients developed Pseudomonas fluorescens bacteremia at the hospital; one on the oncology ward and the other three in the chemotherapy room. These patients all had underlying malignancies and had the Port-A-Cath (Smiths Industries Medical Systems, Deltec, Inc., St. Paul, Minn.) implants. Three patients had primary bacteremia, and one had Port-A-Cath-related infection. None of these patients had received a blood transfusion before the episodes of bacteremia. All patients recovered: two received antimicrobial agents with in vitro activity against the isolates, and the other two did not have any antibiotic treatment. A total of eight blood isolates were recovered from these patients during the febrile episodes that occurred several minutes after the infusion of chemotherapeutic agents via the Port-A-Cath. These isolates were initially identified as P. fluorescens or Pseudomonas putida (four), Burkholderia (Ralstonia) pickettii (three), and a non-glucose-fermenting gram-negative bacillus (one) by routine biochemical methods and the Vitek GNI card. These isolates were later identified as P. fluorescens on the basis of the characteristic cellular fatty acid chromatogram and the results of supplemental biochemical tests. The identification of identical antibiotypes by the E test and the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR of the isolates showed that the outbreak was caused by a single clone of P. fluorescens. Surveillance cultures of the possibly contaminated infusion fluids and disinfectants, which were performed 7 days after recognition of the last infected patient, failed to isolate P. fluorescens. This report of a small outbreak caused by P. fluorescens suggests that timely, accurate identification of unusual nosocomial pathogens is crucial for early initiation of an epidemiological investigation and timely control of an outbreak.
A New Function of Human HtrA2 as an Amyloid-β Oligomerization Inhibitor (2009)

Human HtrA2 is part of the HtrA family of ATP-independent serine proteases that are conserved in both prokaryotes and eukaryotes and localizes to the intermembrane space of the mitochondria. Several recent reports have suggested that HtrA2 is important for maintaining proper mitochondrial homeostasis and may play a role in Alzheimer's disease (AD), which is characterized by the presence of aggregates of the amyloid-beta peptide 1-42 (Abeta1-42). In this study, we analyzed the ability of HtrA2 to delay the aggregation of the model substrate citrate synthase (CS) and of the toxic Abeta1-42 peptide. We found that HtrA2 had a moderate ability to delay the aggregation of CS in vitro, and this activity was significantly enhanced when the PDZ domain was removed suggesting an inhibitory role for this domain on the activity. Additionally, using electron microscopy and nuclear magnetic resonance analyses, we observed that HtrA2 significantly delayed the aggregation of the Abeta1-42 peptide. Interestingly, the protease activity of HtrA2 and its PDZ domain were not essential for the delay of Abeta1-42 peptide aggregation. These results indicate that besides its protease activity, HtrA2 also performs a chaperone function and suggest a role for HtrA2 in the metabolism of intracellular Abeta and in AD.
A technique of catheter insertion for uncomplicated peritoneal dialysis. (1983)

Malfunction of a peritoneal dialysis catheter usually results from its incorrect placement, either in the mesentery or anterior to the intestine or omentum. A technique for catheter insertion has been used successfully in 22 patients.
NUPACK: Analysis and design of nucleic acid systems (2010)

sequence design for complexes of nucleic acid strands intended to adopt a target secondary structure at equilibrium.Utilities: evaluation, display, and annotation of equilibrium properties of a complex of nucleic acid strands. NUPACK algorithms are formulated in terms of nucleic acid secondary structure. In most cases, pseudoknots are excluded from the structural ensemble.
Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells (2012)

Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer.
Authoring of physical models using mobile computers (2002)

Context-aware computers rely on user and physical models to describe the context of a user. In this paper, we focus on the problem of developing and maintaining a physical model of the environment using a mobile computer. We describe a set of tools for automatically creating and modifying three-dimensional contextual information. The tools can be utilized across multiple hardware platforms, with different capabilities, and operating in collaboration with one another. We demonstrate the capabilities of the tools using two mobile platforms. One of them, a mobile augmented reality system is used to construct a geometric model of an indoor environment which is then visualized on the same platform.
Iron-Catalyzed Imination of Sulfoxides and Sulfides (2006)

The Fe(III)-catalyzed imination of sulfoxides and sulfides with sulfonylamides in the presence of iodinanes has been investigated. The best results were obtained when Fe(acac)3 was used as a catalyst in combination with iodosylbenzene, providing an effective alternative (stereospecific) access to sulfoximines and sulfilimines.
Low voltage electron beam lithography in self-assembled ultrathin films with the scanning tunneling microscope (1994)

With a scanning tunneling microscope (STM) operating in vacuum, we have studied the lithographic patterning of self-assembling organosilane monolayer resist films. Where the organic group is benzyl chloride, the resist layer can be patterned with electrons down to 4 eV in energy. The patterned films have been used as templates for the electroless plating of thin Ni films. Linewidths down to ∼20 nm have been observed in scanning electron micrographs of the plated films. Still smaller features are observed in STM images of the exposed organosilane films.