gebhart/patrepeval huggingface dataset:
Development of a Lyophilized Parenteral Pharmaceutical Formulation of the Investigational Polypeptide Marine Anticancer Agent Kahalalide F (2001)

Kahalalide F is a novel antitumor agent isolated from the marine mollusk Elysia rufescens; it has shown highly selective in vitro activity against androgen-independent prostate tumors. The purpose of this study was to develop a stable parenteral formulation of kahalalide F to be used in early clinical trials. Solubility and stability of kahalalide F were studied as a function of polysorbate 80 (0.1%-0.5% w/v) and citric acid monohydrate (15-15 mM) concentrations using an experimental design approach. Stabilities of kahalalide F lyophilized products containing crystalline (mannitol) or amorphous (sucrose) bulking agents were studied at +5 degrees C and +30 degrees C +/- 60% relative humidity (RH) in the dark. Lyophilized products were characterized by infrared (IR) spectroscopy and differential scanning calorimetry (DSC). Recovery studies after reconstitution of kahalalide F lyophilized product and further dilution in infusion fluid were carried out to select an optimal reconstitution vehicle. It was found that a combination of polysorbate 80 and citric acid monohydrate is necessary to solubilize kahalalide F. Lyophilized products were considerably less stable with increasing polysorbate 80 and citric acid monohydrate concentrations, with polysorbate 80 being the major effector. A combination of 0.1% w/v polysorbate 80 and 5 mM citric acid monohydrate was selected for further investigation. Lyophilized products containing sucrose as a hulking agent were more stable compared to the products containing mannitol. The glass transition temperature of the sucrose-based product was determined to be + 46 degrees C. The amorphous state of the product was confirmed by IR analysis. A solution composed of Cremophor EL, ethanol, and water for injection (5%/5%/90% v/v/v CEW, kept kahalalide F in solution after reconstitution andfurther dilution with 0.9% w/v sodium chloride (normal saline) to 1.5 microg/m. A stable lyophilized formulation was presented containing 100 microg of kahalalide F, 100 mg sucrose, 2.1 mg citric acid monohydrate, and 2mg polysorbate 80 to be reconstituted with a vehicle composed of 5%/5%/90% v/v/v CEW and to be diluted further using normal saline.
Genome editing in plants via designed zinc finger nucleases (2015)

The ability to create DNA double-strand breaks (DSBs) at specified genomic locations, which then stimulate the cell's naturally occurring DNA repair processes, has introduced intriguing possibilities for genetic modification. Zinc finger nucleases (ZFNs) are designed restriction enzymes consisting of a nonspecific cleavage domain fused to sequence-specific DNA binding domains. ZFN-mediated DSB formation at endogenous genomic loci followed by error-prone non-homologous end joining (NHEJ) repair can result in gene-specific mutations <i>via</i> nucleotide base pair insertions or deletions. Similarly, specific DNA sequence modifications can be made by providing donor DNA templates homologous to sequences flanking the cleavage site <i>via</i> homology-directed repair (HDR). Targeted deletions of intervening DNA sequence can be obtained by ZFNs used to create concurrent DSBs. Site-specific transgene integration into ZFN-induced DSBs is possible <i>via</i> either NHEJ or HDR. Genome editing can be used to enhance our basic understanding of plant gene function as well as modify and improve crop plants. As with conventional plant transformation technology, the efficiency of genome editing is absolutely dependent on the ability to initiate, maintain, and regenerate plant cell and tissue cultures.
Level conversion for dual-supply systems (2003)

Dual-supply voltage design using a clustered voltage scaling (CVS) scheme is an effective approach to reduce chip power. The optimal CVS design relies on a level converter (LC) implemented in a flip-flop to minimize energy, delay, and area penalties due to level conversion. Novel flip-flops presented in this paper incorporate a half-latch LC and a precharged LC. These flip-flops are optimized in the energy-delay design space to achieve over 30% reduction of energy-delay product and about 10% savings of total power in a CVS design as compared to the conventional flip-flop. These benefits are accompanied by 24% robustness improvement and 18% layout area reduction.
Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion (2011)

Tumors are often heterogeneous, being composed of multiple cell types with different phenotypic and molecular properties. Cancer stem-like cells (CSCs) are a highly tumorigenic cell type found in developmentally diverse tumors or cancer cell lines, and they are often resistant to standard chemotherapeutic drugs. The origins of CSCs and their relationships to nonstem cancer cells (NSCCs) are poorly understood. In an inducible breast oncogenesis model, CSCs are generated from nontransformed cells at a specific time during the transformation process, but CSC formation is not required for transformation. MicroRNA profiles indicate that CSCs and NSCCs are related, but different cell types arising from a common nontransformed population. Interestingly, medium from the transformed population stimulates NSCCs to become CSCs, and conversion of NSCCs to CSCs occurs in mouse xenografts. Furthermore, IL6 is sufficient to convert NSCCs to CSCs in genetically different breast cell lines, human breast tumors, and a prostate cell line. Thus, breast and prostate CSCs and NSCCs do not represent distinct epigenetic states, and these CSCs do not behave as or arise from classic stem cells. Instead, tumor heterogeneity involves a dynamic equilibrium between CSCs and NSCCs mediated by IL6 and activation of the inflammatory feedback loop required for oncogenesis. This dynamic equilibrium provides an additional rationale for combining conventional chemotherapy with metformin, which selectively inhibits CSCs.
The plasmids of Chlamydia trachomatis and Chlamydophila pneumoniae (N16): accurate determination of copy number and the paradoxical effect of plasmid-curing agents (2005)

A 7.5 kbp cryptic plasmid is found in almost all isolates of Chlamydia trachomatis. Real-time PCR assays, using TaqMan chemistry, were set up to quantify accurately both the chlamydial plasmid and the single copy, chromosomal omcB gene in the infectious, elementary bodies (EBs) of C. trachomatis L1 440. Plasmid copy number was also determined in the EBs of six other lymphogranuloma venereum (LGV) isolates (serovars L1-L3), ten trachoma isolates (serovars A-C) and nine urogenital isolates (serovars D-J). The results indicated an average plasmid copy number of 4.0+/-0.8 (mean+/-95 % confidence interval) plasmids per chromosome. During the chlamydial developmental cycle, up to 7.6 plasmids per chromosome were detected, indicating an increased plasmid copy number in the actively replicating reticulate bodies. Attempts to eliminate the plasmid from strain L1 440 using the plasmid-curing agents ethidium bromide, acridine orange or imipramine/novobiocin led to a paradoxical increase in plasmid copy number. It is speculated that the stress induced by chemical curing agents may stimulate the activity of plasmid-encoded replication (Rep) proteins. In contrast to C. trachomatis, only a single isolate of Chlamydophila pneumoniae bears a plasmid. C. pneumoniae strain N16 supports a 7.4 kbp plasmid in which ORF1, encoding one of the putative Rep proteins, is disrupted by a deletion and split into two smaller ORFs. Similar assay techniques revealed 1.3+/-0.2 plasmids per chromosome (mean+/-95 % confidence interval) in EBs of this strain. These findings are in agreement with the hypothesis that the ORF1-encoded protein is involved in, but not essential for, plasmid replication and control of copy number.
Systemic use of the endolysin Cpl-1 rescues mice with fatal pneumococcal pneumonia* (2009)

Cpl-1 may provide a new therapeutic option in the treatment of pneumococcal pneumonia.
Anatomical and Physiological Plasticity of Dendritic Spines (2007)

In excitatory neurons, most glutamatergic synapses are made on the heads of dendritic spines, each of which houses the postsynaptic terminal of a single glutamatergic synapse. We review recent studies demonstrating in vivo that spines are motile and plastic structures whose morphology and lifespan are influenced, even in adult animals, by changes in sensory input. However, most spines that appear in adult animals are transient, and the addition of stable spines and synapses is rare. In vitro studies have shown that patterns of neuronal activity known to induce synaptic plasticity can also trigger changes in spine morphology. Therefore, it is tempting to speculate that the plastic changes of spine morphology reflect the dynamic state of its associated synapse and are responsible to some extent for neuronal circuitry remodeling. Nevertheless, morphological changes are not required for all forms of synaptic plasticity, and whether changes in the spine shape and size significantly impact synaptic signals is unclear.
Mechanistic studies on depurination and apurinic site chain breakage in oligodeoxyribonucleotides (1994)

Products formed from defined oligodeoxyribonucleotide tetramers (oligonucleotides) by depurination at pH 5.0 and 90 degrees C followed by chain breakage at the resulting apurinic sites (AP sites) were assigned by reversed phase HPLC. Through kinetic analysis, rate constants of depurination and subsequent chain breakage reactions were measured. Depurination of the oligonucleotides with purine bases locating at the terminal positions was several times faster than those with purines at the internal ones. The pKa values for the N7 of the G residues and the activation energies of the depurination were essentially independent of the position of the bases. The frequency factor was found to be responsible for the observed difference of the depurination rates. In contrast, the chain breakage by beta-elimination was several times faster for the AP sites formed at the internal positions than those at the 5'-terminal positions. It is suggested that an electron withdrawing phosphate group attached to the 5'-side of an AP site facilitates the chain cleavage.
Strong password-only authenticated key exchange (1996)

A new simple password exponential key exchange method (SPEKE) is described. It belongs to an exclusive class of methods which provide authentication and key establishment over an insecure channel using only a small password, without risk of offline dictionary attack. SPEKE and the closely-related Diffie-Hellman Encrypted Key Exchange (DH-EKE) are examined in light of both known and new attacks, along with sufficient preventive constraints. Although SPEKE and DH-EKE are similar, the constraints are different. The class of strong password-only methods is compared to other authentication schemes. Benefits, limitations, and tradeoffs between efficiency and security are discussed. These methods are important for several uses, including replacement of obsolete systems, and building hybrid two-factor systems where independent password-only and key-based methods can survive a single event of either key theft or password compromise.
Pre-Targeting and Direct Immunotargeting of Liposomal Drug Carriers to Ovarian Carcinoma (2012)

Intraperitoneal administration of liposomes may be a beneficial approach to treat the tumors in the abdominal cavity. The i.p. pre-targeting method warrants further studies as a potential approach in cancer therapy.
Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1. (1997)

The mCAT-1 gene encodes a basic amino acid transporter that also acts as the receptor for murine ecotropic leukemia viruses. Targeted mutagenesis in embryonic stem cells has been used to introduce a germ-line null mutation into this gene. This mutation removes a domain critical for virus binding and inactivates amino acid transport activity. Homozygous mutant pups generated from these cells were approximately 25% smaller than normal littermates, very anemic, and died on the day of birth. Peripheral blood from homozygotes contained 50% fewer red blood cells, reduced hemoglobin levels, and showed a pronounced normoblastosis. Histological analyses of bone marrow, spleen, and liver showed a decrease in both erythroid progenitors and mature red blood cells. Mutant fetal liver cells behaved normally in in vitro hematopoietic colony-forming assays but generated an anemia when transplanted into irradiated C.B.-17 SCID mice. Furthermore, reconstitution of the white cell compartment of SCID mice by mutant fetal liver cells was less complete than that observed with a mixed population of wild-type and heterozygous fetal liver cells. Primary embryo fibroblasts from mutant mice were completely resistant to ecotropic retrovirus infection. Thus, mCAT-1 not only appears to be the sole receptor for a group of murine ecotropic retroviruses associated with hematological disease but also plays a critical role in both hematopoiesis and growth control during mouse development.
Establishing a framework for comparative analysis of genome sequences (2002)

This paper describes a framework and a high level language tool for comparative analysis of genome sequence alignment. The framework integrates the information derived from multiple sequence alignment and phylogeny to derive new properties about homologous sequences. Multiple sequence alignments are treated as an abstract data type. Abstract operations have been described to manipulate a multiple sequence alignment, and to derive mutation related information from a phylogenetic tree by superimposing parsimony. The framework has been applied to derive constrained columns which exhibit evolutionary pressure to preserve a common property in a column despite mutation. A Prolog tool based on the the framework has been implemented and demonstrated on alignments containing 3000 sequences and 3904 columns.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glucuronidation of opioids, carboxylic acid-containing drugs, and hydroxylated xenobiotics catalyzed by expressed monkey UDP-glucuronosyltransferase 2B9 protein. (1997)

UDP-glucuronosyltransferase (UGT) 2B9, isolated from a cynomolgus monkey liver cDNA library, is 89% identical to human UGT2B7 in primary amino acid sequence, and the two expressed enzymes were previously shown to catalyze the glucuronidation of many common endogenous substrates. The purpose of the present study was to characterize the reactivity of expressed UGT2B9 with important therapeutic agents and other xenobiotics. UGT2B9, stably expressed in human embryonic kidney 293 cells, catalyzes the 3-O- and 6-O-glucuronidation of morphine and the 6-O-glucuronidation of codeine. A number of other morphinan (e.g. naloxone, naltrexone, and nalorphine) and oripavine (e.g. buprenorphine) derivatives are substrates for this enzyme. In general, morphinan derivatives are glucuronidated at higher rates, compared with oripavines; however, glucuronidation efficiency values (Vmax/KM) for the compounds are similar. Stably expressed UGT2B9 also catalyzes the glucuronidation of profen nonsteroidal anti-inflammatory drugs, fibrate hypolipidemic agents, and straight-chain fatty acids at the carboxylic acid moiety. Monoterpenoid alcohols and propanolol are glucuronidated at aliphatic hydroxyl positions. Expressed UGT2B9 exhibits enantioselective glucuronidation for (R/S)-ibuprofen, (R/S)-propanolol, and (+)/(-)-menthol. The data suggest that monkey UGT2B9 and human UGT2B7 are functionally similar.
Direct visualization of distinct T cell epitopes derived from a melanoma tumor-associated antigen by using human recombinant antibodies with MHC- restricted T cell receptor-like specificity (2002)

Specificity in the cellular immune system is controlled and regulated by the T cell antigen receptor (TCR), which specifically recognizes peptide/major histocompatibility complex (MHC) molecules. In recent years many cancer-associated MHC-restricted peptides have been isolated and because of their highly restricted fine specificity, they are desirable targets for novel approaches in immunotherapy. Antibodies that would recognize tumor-associated MHC-peptide complexes with the same specificity as the TCR would be valuable reagents for studying antigen presentation by tumor cells, for visualizing MHC-peptide complexes on cells, and eventually for monitoring the expression of specific complexes during immunotherapy. To generate molecules with such a unique fine specificity, we selected a large nonimmune repertoire of phage Fab antibodies on recombinant HLA-A2 complexed with three common antigenic T cell, HLA-A2-restricted epitopes derived from the melanoma differentiation antigen gp100. We were able to isolate a surprisingly large panel of human recombinant Fab antibodies that exhibit a characteristic TCR-like binding specificity to each of the three gp100-derived epitopes, yet unlike TCRs, they did so with an affinity in the nanomolar range. These TCR-like antibodies recognize the native MHC-peptide complex expressed on the surface of antigen-presenting cells. Moreover, they can detect the specific MHC-peptide complexes on the surface of melanoma tumor cells. These results demonstrate the ability to isolate high-affinity human recombinant antibodies with the antigen-specific, MHC-restricted specificity of T cells, and this ability was demonstrated for three different epitopes of the same melanoma-derived antigen.
Injury-induced upregulation of bFGF and CNTF mRNAS in the rat retina (1995)

Focal mechanical injury to the retina has been shown to slow or prevent photoreceptor degeneration near the lesion site in two animal models of retinal degeneration, inherited retinal dystrophy in the Royal College of Surgeons (RCS) and light damage in albino rats. Thus, when injured, the rat retina activates a self-protective mechanism to minimize damage. To identify injury responsive factors and cells, we examined the mRNAs for the following factors and some of their receptors: basic and acidic fibroblast growth factors (bFGF, aFGF) and FGF receptor-1 (FGFR1); ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFR alpha); brain-derived neurotrophic factor (BDNF) and its receptor trkB; and insulin-like growth factor-1 (IGF-1) and IGFR-1 receptor (IGF-1R). After a single mechanical lesion to the subretinal space and retina, there was a substantial increase in bFGF and CNTF expression that persisted for the entire 10 d period of study. The increase in bFGF mRNA after injury was prompt and great in amplitude, while the elevation of CNTF mRNA was relatively slower. In addition, there was a transient increase in FGFR1 mRNA. In situ hybridizations showed that the elevation of bFGF and CNTF was localized to the vicinity of the lesion. The expression of GFAP (glial fibrillary acidic protein) mRNA also increased in response to injury. These findings strongly suggest that increases in endogenous bFGF and/or CNTF play key roles in injury-induced photoreceptor rescue.
Airport surface surveillance based on video images (2005)

In this correspondence the design of an airport surface surveillance system based on TV cameras and low-cost processing hardware is described. The work presented here focuses on the single-sensor multiple-target tracking part of the system, giving a description of a prototype of this key system component and some quantitative and qualitative assessments of tracking reliability and accuracy.
A model-driven approach to broaden the detection of software performance antipatterns at runtime (2014)

Performance antipatterns document bad design patterns that have negative influence on system performance. In our previous work we formalized such antipatterns as logical predicates that predicate on four views: (i) the static view that captures the software elements (e.g. classes, components) and the static relationships among them; (ii) the dynamic view that represents the interaction (e.g. messages) that occurs between the software entities elements to provide the system functionalities; (iii) the deployment view that describes the hardware elements (e.g. processing nodes) and the mapping of the software entities onto the hardware platform; (iv) the performance view that collects specific performance indices. In this paper we present a lightweight infrastructure that is able to detect performance antipatterns at runtime through monitoring. The proposed approach precalculates such predicates and identifies antipatterns whose static, dynamic and deployment sub-predicates are validated by the current system configuration and brings at runtime the verification of performance sub-predicates. The proposed infrastructure leverages model-driven techniques to generate probes for monitoring the performance sub-predicates and detecting antipatterns at runtime.
Construction of an in vivo-regulated U6 snRNA transcription unit as a tool to study U6 function. (1998)

U6 snRNA is the only spliceosomal snRNA transcribed by RNA polymerase III in yeast. We have constructed a regulated U6 snRNA transcription unit by introducing the binding site for the Escherichia coli lacI repressor protein in the U6 snRNA promoter. GAL-induced expression of lacI protein led to a decrease in U6 snRNA levels and blocked cell growth. lacI dissociation from the promoter, and consequent U6 snRNA transcription, could be induced by addition of IPTG and repression of lacI transcription. To test the usefulness of this system in studying spliceosomal U6 snRNA function, we conditionally expressed U6 snRNAs with a single base substitution in position A51. We demonstrate that expression of the U6-A51 mutations confers a strong dominant negative phenotype as shown by severe reductions in growth rate. In these strains, splicing of endogenous pre-mRNAs was blocked before the second step.
Purification, Characterization, and Cloning of a Eubacterial 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase, a Key Enzyme Involved in Biosynthesis of Terpenoids (1999)

The eubacterial 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) was purified 3,000-fold from Streptomyces sp. strain CL190 to apparent homogeneity with an overall yield of 2.1%. The purification procedure consisted of (NH4)2SO4 precipitation, heat treatment and anion exchange, hydrophobic interaction, and affinity chromatographies. The molecular mass of the enzyme was estimated to be 41 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 100 to 105 kDa by gel filtration chromatography, suggesting that the enzyme is most likely to be a dimer. The enzyme showed a pH optimum of around 7.2, with apparent Km values of 62 microM for NADPH and 7.7 microM for HMG-CoA. A gene from CL190 responsible for HMG-CoA reductase was cloned by the colony hybridization method with an oligonucleotide probe synthesized on the basis of the N-terminal sequence of the purified enzyme. The amino acid sequence of the CL190 HMG-CoA reductase revealed several limited motifs which were highly conserved and common to the eucaryotic and archaebacterial enzymes. These sequence conservations suggest a strong evolutionary pressure to maintain amino acid residues at specific positions, indicating that the conserved motifs might play important roles in the structural conformation and/or catalytic properties of the enzyme.
Cancer stem cells and radioresistance (2014)

We focus our discussions on breast cancer and glioblastoma multiforme (GBM) and conclude that both CSC-intrinsic and CSC-extrinsic factors as well as adaptive responses in CSC caused by irradiation and microenvironmental changes all make contributions to CSC-mediated radioresistance. Our discussions emphasize CSC as novel therapeutic targets in order to potentiate radiotherapy efficacy.