gebhart/patrepeval huggingface dataset:
Mouse Models of Prostate Adenocarcinoma with the Capacity to Monitor Spontaneous Carcinogenesis by Bioluminescence or Fluorescence (2007)

The application of Cre/loxP technology has resulted in a new generation of conditional mouse models of prostate cancer. Here, we describe the improvement of the conditional Pten deletion model of prostate adenocarcinoma by combining it with either a conditional luciferase or enhanced green fluorescent protein reporter line. In these models, the recombination mechanism that inactivates the Pten alleles also activates the reporter gene. In the luciferase reporter model, the growth of the primary cancer can be followed noninvasively by bioluminescence imaging (BLI). Surgical castration of tumor-bearing animals leads to a reduced bioluminescence signal corresponding to tumor regression that is verified at necropsy. When castrated animals are maintained, the emergence of androgen depletion-independent cancer is detected using BLI at times varying from 7 to 28 weeks postcastration. The ability to monitor growth, regression, or relapse of the tumor with the use of BLI lead to the collection of tumors at different stages of development. By comparing the distribution of phenotypically distinct populations of epithelial cells in cancer tissues, we noted that the degree of hyperplasia of cells with neuroendocrine differentiation significantly increases in the recurrent cancer relative to the primary cancer, a characteristic which may parallel the appearance of a neuroendocrine phenotype in human androgen depletion-independent cancer. The enhanced green fluorescent protein model, at necropsy, can provide an opportunity to locate or assess tumor volume or to isolate enriched populations of cancer cells from tumor tissues via fluorescence-based technologies. These refined models should be useful in the elucidation of mechanisms of prostate cancer progression, and for the development of approaches to preclinical intervention.
Characterization of fHbp , nhba ( gna2132 ), nadA , porA , Sequence Type (ST), and Genomic Presence of IS 1301 in Group B Meningococcal ST269 Clonal Complex Isolates from England and Wales (2009)

Highly effective glycoconjugate vaccines exist against four of the five major pathogenic groups of meningococci: A, C, W-135, and Y. An equivalent vaccine against group B meningococci (menB) has remained elusive due to the poorly immunogenic capsular polysaccharide. A promising alternative, the investigational recombinant menB (rMenB)- outer membrane vesicle (OMV) vaccine, contains fHBP, NHBA (previously GNA2132), NadA, and outer membrane vesicles (OMVs) from the New Zealand MeNZB vaccine. MenB currently accounts for 90% of meningococcal disease in England and Wales, where the multilocus sequence type (ST) 269 (ST269) clonal complex (cc269) has recently expanded to account for a third of menB cases. To assess the potential cc269 coverage of the rMenB-OMV vaccine, English and Welsh cc269 isolates from the past decade were genetically characterized with respect to fHBP, NHBA, and NadA. All of the isolates harbored fHbp and nhba alleles, while 98% of the cc269 isolates were devoid of nadA. Subvariant profiling of fHbp, nhba, and porA against STs revealed the presence of two broadly distinct and well-defined clusters of isolates, centered around ST269 and ST275, respectively. An additional molecular marker, insertion sequence IS1301, was found to be present in 100% and <2% of isolates of the respective clusters. On the basis of the genetic data, the potential rMenB-OMV coverage of cc269 in England and Wales is high (up to 100%) within both clusters. Expression studies and serum bactericidal antibody assays will serve to enhance predictions of coverage and will augment ongoing studies regarding the significance of IS1301 within the ST269 cluster.
The delivery of therapeutic oligonucleotides (2016)

The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology.
Stimuli-responsive opals: colloidal crystals and colloidal amorphous arrays for use in functional structurally colored materials (2013)

Two distinct types of colloidal particle aggregated states exist in opal, namely, the colloidal crystal and the colloidal amorphous array. Today, these aggregates can be artificially prepared and are now studied as non-fading structurally colored materials as a result of our better understanding of their optical properties. Additionally, by applying the aggregates as stimuli-responsive materials, we can fabricate stimuli-responsive structurally colored systems that change their hue and saturation in response to external stimuli. In this review, the conditions necessary for fabricating stimuli-responsive structurally colored systems using the two types of aggregates present in opal are explained.
Wide-scale botnet detection and characterization (2007)

Malicious botnets are networks of compromised computers that are controlled remotely to perform large-scale distributed denial-of-service (DDoS) attacks, send spam, trojan and phishing emails, distribute pirated media or conduct other usually illegitimate activities.

This paper describes a methodology to detect, track and characterize botnets on a large Tier-1 ISP network. The approach presented here differs from previous attempts to detect botnets by employing scalable non-intrusive algorithms that analyze vast amounts of summary traffic data collected on selected network links. Our botnet analysis is performed mostly on transport layer data and thus does not depend on particular application layer information. Our algorithms produce alerts with information about controllers. Alerts are followed up with analysis of application layer data, that indicates less than 2% false positive rates.
ChemInform Abstract: Substituted 4‐Benzylfuro(3,2‐b)pyrroles. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A Family-Genetic Study of Dementia of Alzheimer Type (1988)

A family study of 22 rigorously diagnosed subjects with dementia of Alzheimer type (DAT) and 24 nondemented controls revealed a morbid risk of DAT to first-degree relatives of probands of 41% by age 83 years compared with a risk of 23% by age 85 years in control relatives. Senescent forgetfulness, defined as consistent but not incapacitating memory deficit, may have represented early DAT in some instances. When such cases were included as secondary cases, the morbid risk to first-degree relatives of probands was 67% by age 86 years while risk to comparable control relatives remained 23%. No cases of Down's syndrome were observed. A significant excess of hematologic malignant neoplasms was found among first-degree relatives of probands, supporting an association with DAT. Overall, the findings add further evidence of the action of familial-genetic factors in the etiology of DAT. The magnitude of the effect is consistent with an autosomal dominant mode of inheritance, with penetrance nearly complete by age 85 years. The probands were not selected on the basis of factors posited by some to indicate a familial form of DAT, suggesting that such a genetic mechanism may be involved in the occurrence of DAT in general.
Metalorganic chemical vapor deposition of TiO2:N anatase thin film on Si substrate (1995)

Titanium dioxide thin film doped with nitrogen was deposited at 420 °C on p-type silicon substrate by metalorganic chemical vapor deposition using titanium tetra-isopropoxide and nitrous oxide. From an x-ray diffraction result, when deposited at 420 °C, only the anatase (101) peak and (200) peak were observed. Raman spectroscopy confirmed the presence of anatase phase without any rutile or TiN phase. X-ray photoelectron spectrum revealed that nitrogen was doped into the lattice of TiO2 anatase. In the bulk of the film nitrogen peak was observed, and the spectrum of Ti 2p core level confirmed titanium–nitrogen bonding due to nitrogen incorporation into the anatase lattice.
Controlled Release of Proteins from Their Poly(Ethylene Glycol) Conjugates:  Drug Delivery Systems Employing 1,6-Elimination (2003)

Several tripartate releasable PEG linkers (rPEG) that can provide anchimeric assistance to hydrolysis (cyclization prodrugs) were prepared and, after conjugation to lysozyme demonstrated rapid cleavage in rat plasma compared to nonassisted, permanently bound PEG. By varying the chemical structure and adding steric hindrance, the half-life of the protein conjugates can be adjusted from slow to very fast. The pharmacokinetics (PK) of regeneration of native protein, from various rPEG conjugates can, for the first time, be easily followed in the rat using green fluorescent protein. The PK in mice was also determined for rPEG-Interleukin 2 (rPEG-IL-2) conjugates in vivo using an ELISA assay. Thus, a systematic study of rPEGylated proteins, either in vivo or in vitro during processing, has been investigated based on regeneration of native protein. The employment of releasable PEG polymers substantially broadens the applications of PEGylation drug delivery technology by introducing the benefits of controlled release of native protein therapeutics.
Targeted gene repair – in the arena (2003)

The development of targeted gene repair is under way and, despite some setbacks, shows promise as an alternative form of gene therapy. This approach uses synthetic DNA molecules to activate and direct the cell’s inherent DNA repair systems to correct inborn errors. The progress of this technique and its therapeutic potential are discussed in relation to the treatment of genetic diseases.
Adjunctive Cabergoline Therapy of Parkinson's Disease: Comparison with Placebo and Assessment of Dose Responses and Duration of Effect (1996)

Adjunctive cabergoline or placebo, in doses up to 5 mg daily, were administered to Parkinson's disease patients with short-duration levodopa responses in a 6-month double-blind trial. The 13 patients randomized to cabergoline and completing the study had significantly improved Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and timed hand-tapping test scores. Serial measurements on test days documented improved scores: (a) before the first levodopa (and cabergoline) dose of the day, (b) at the time of the peak levodopa effect, and (c) at the end of the levodopa response cycle, 5 h after test doses. Continued testing verified that these therapeutic responses were sustained for at least 48 h after the last cabergoline dose. Patients randomized to placebo failed to improve on any of these measures. In a subsequent open-label dose-escalation phase, further improvement was documented as the dosage was gradually raised to 10 mg daily. As in the double-blind phase, levodopa reduction allowed the improvement to occur in the absence of significantly increased dyskinesias. Other side effects were more substantial with higher doses, however, including two of 11 patients with hallucinations and confusion. In summary, adjunctive single-daily-dose cabergoline therapy resulted in long-lasting, dose-related improvement in parkinsonism not seen in patients receiving placebo.
Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the road ahead (2015)

At its height, the Clostridium difficile infection epidemic caused approximately 7000 infections and 300 deaths per day in the USA. Fecal microbiota transplantation (FMT) has demonstrated extraordinary clinical resolution, C. difficile infection cure rates of over 90%, and low recurrence. In tandem with the rise of FMT, the gastrointestinal microbiome has emerged as a 'vital' organ armed with a wealth of microbe 'soldiers' more powerful than known antibiotics. FMTs' reputation has diffused into many new 'indications' yet these appear to be merely the tip of the iceberg when considering its potential applications. FMT as a therapeutic tool has evolved from the original format of blended donor stool and moved towards a refined product comprising a myriad of microbial components, presented aesthetically as encapsulated lyophilized powder.
Movable Aperture Lensless Transmission Microscopy: A Novel Phase Retrieval Algorithm (2004)

We propose an iterative phase retrieval method that uses a series of diffraction patterns, measured only in intensity, to solve for both amplitude and phase of the image wave function over a wide field of view and at wavelength-limited resolution. The new technique requires an aperture that is scanned to two or more positions over the object wave function. A simple implementation of the method is modeled and demonstrated, showing how the algorithm uses overlapping data in real space to resolve ambiguities in the solution. The technique opens up the possibility of practical transmission lensless microscopy at subatomic resolution using electrons, x rays, or nuclear particles.
Spider silks: recombinant synthesis, assembly, spinning, and engineering of synthetic proteins (2004)

Since thousands of years humans have utilized insect silks for their own benefit and comfort. The most famous example is the use of reeled silkworm silk from Bombyx mori to produce textiles. In contrast, despite the more promising properties of their silk, spiders have not been domesticated for large-scale or even industrial applications, since farming the spiders is not commercially viable due to their highly territorial and cannibalistic nature. Before spider silks can be copied or mimicked, not only the sequence of the underlying proteins but also their functions have to be resolved. Several attempts to recombinantly produce spider silks or spider silk mimics in various expression hosts have been reported previously. A new protein engineering approach, which combines synthetic repetitive silk sequences with authentic silk domains, reveals proteins that closely resemble silk proteins and that can be produced at high yields, which provides a basis for cost-efficient large scale production of spider silk-like proteins.
Structural characterization of self-assemblies of new omega-3 lipids: docosahexaenoic acid and docosapentaenoic acid monoglycerides (2018)

The attractiveness of new omega-3 (ω-3) polyunsaturated fatty acid (PUFA) monoglycerides (MAGs) lies in the amphiphilic nature and the beneficial health effects as PUFA precursors in various disorders including cancer, pulmonary hypertension, and inflammatory diseases. For exploring the potential therapeutic applications of these new amphiphilic lipids, particularly as main lipid constituents in the development of nanocarriers for delivery of drugs and PUFAs, it is of paramount importance to gain insight into their self-assembly behavior on exposure to excess water. This work describes the structural characteristics of self-assemblies based on two newly synthesized MAGs, namely docosahexaenoic acid (MAG-DHA) and docosapentaenoic acid (MAG-DPA) monoglycerides, on exposure to excess water. We found that both lipids tend to form a dominant inverse hexagonal (H<sub>2</sub>) phase in excess water at 25 °C and a temperature-triggered structural transition to an inverse micellar solution (L<sub>2</sub> phase) is detected similar to that recently reported (A. Yaghmur et al., Langmuir, 2017, 33, 14045-14057) for eicosapentaenoic acid monoglyceride (MAG-EPA). An experimental SAXS structural evaluation study on the temperature-dependent behavior of these new monoglycerides is provided, and the effects of unsaturation degree and fatty acyl chain length on the self-assembled structural features in excess water and on the H<sub>2</sub>-L<sub>2</sub> phase transition temperature are discussed. In addition, hexosomes stabilized by using the triblock copolymer F127 and the food-grade emulsifier citrem were investigated to gain insights into the effects of stabilizer and temperature on the internal nanostructure. These nanoparticles are attractive for use in the development of nanocarriers for delivering drugs and/or nutritional compounds as the beneficial health effects of ω-3 PUFA monoglycerides can be combined with those of loaded therapeutic agents or nutraceuticals.
CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions (2005)

Rats and mice exhibit a spontaneous attraction for lipids. Such a behavior raises the possibility that an orosensory system is responsible for the detection of dietary lipids. The fatty acid transporter CD36 appears to be a plausible candidate for this function since it has a high affinity for long-chain fatty acids (LCFAs) and is found in lingual papillae in the rat. To explore this hypothesis further, experiments were conducted in rats and in wild-type and CD36-null mice. In mice, RT-PCR experiments with primers specific for candidate lipid-binding proteins revealed that only CD36 expression was restricted to lingual papillae although absent from the palatal papillae. Immunostaining studies showed a distribution of CD36 along the apical side of circumvallate taste bud cells. CD36 gene inactivation fully abolished the preference for LCFA-enriched solutions and solid diet observed in wild-type mice. Furthermore, in rats and wild-type mice with an esophageal ligation, deposition of unsaturated LCFAs onto the tongue led to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions. These findings demonstrate that CD36 is involved in oral LCFA detection and raise the possibility that an alteration in the lingual fat perception may be linked to feeding dysregulation.
Gene Knockout Using Transcription Activator-like Effector Nucleases (TALENs) Reveals That Human NDUFA9 Protein Is Essential for Stabilizing the Junction between Membrane and Matrix Arms of Complex I (2012)

Transcription activator-like effector nucleases (TALENs) represent a promising approach for targeted knock-out of genes in cultured human cells. We used TALEN-technology to knock out the nuclear gene encoding NDUFA9, a subunit of mitochondrial respiratory chain complex I in HEK293T cells. Screening for the knock-out revealed a mixture of NDUFA9 cell clones that harbored partial deletions of the mitochondrial N-terminal targeting signal but were still capable of import. A cell line lacking functional copies of both NDUFA9 alleles resulted in a loss of NDUFA9 protein expression, impaired assembly of complex I, and cells incapable of growth in galactose medium. Cells lacking NDUFA9 contained a complex I subcomplex consisting of membrane arm subunits but not marker subunits of the matrix arm. Re-expression of NDUFA9 restored the defects in complex I assembly. We conclude that NDUFA9 is involved in stabilizing the junction between membrane and matrix arms of complex I, a late assembly step critical for complex I biogenesis and activity.
How To Make Ohmic Contacts to Organic Semiconductors (2004)

The process of charge injection plays an important role in organic semiconductor devices. We review various experimental techniques that allow injection to be separated from other competing processes, and quantify the injection efficiency of a contact. We discuss the dependence of the injection efficiency on parameters such as the energy barrier at the interface, the carrier mobility of the organic semiconductor, its carrier density (doping level), the presence of mobile ions, and the sample geometry. Based on these findings, we outline guidelines for forming ohmic contacts and present examples of contact engineering in organic semiconductor devices.
Peptoid Oligomers with α-Chiral, Aromatic Side Chains:  Effects of Chain Length on Secondary Structure (2001)

Oligomeric N-substituted glycines or "peptoids" with alpha-chiral, aromatic side chains can adopt stable helices in organic or aqueous solution, despite their lack of backbone chirality and their inability to form intrachain hydrogen bonds. Helical ordering appears to be stabilized by avoidance of steric clash as well as by electrostatic repulsion between backbone carbonyls and pi clouds of aromatic rings in the side chains. Interestingly, these peptoid helices exhibit intense circular dichroism (CD) spectra that closely resemble those of peptide alpha-helices. Here, we have utilized CD to systematically study the effects of oligomer length, concentration, and temperature on the chiral secondary structure of organosoluble peptoid homooligomers ranging from 3 to 20 (R)-N-(1-phenylethyl)glycine (Nrpe) monomers in length. We find that a striking evolution in CD spectral features occurs for Nrpe oligomers between 4 and 12 residues in length, which we attribute to a chain length-dependent population of alternate structured conformers having cis versus trans amide bonds. No significant changes are observed in CD spectra of oligomers between 13 and 20 monomers in length, suggesting a minimal chain length of about 13 residues for the formation of stable poly(Nrpe) helices. Moreover, no dependence of circular dichroism on concentration is observed for an Nrpe hexamer, providing evidence that these helices remain monomeric in solution. In light of these new data, we discuss chain length-related factors that stabilize organosoluble peptoid helices of this class, which are important for the design of helical, biomimetic peptoids sharing this structural motif.
Proteolytic Processing Patterns of Prosaposin in Insect and Mammalian Cells (1996)

Prosaposin is a multifunctional protein encoded at a single locus in humans and mice. The precursor contains, in tandem, four glycoprotein activators or saposins, termed A, B, C, and D, that are essential for specific glycosphingolipid hydrolase activities. Prosaposin appears to be a potent neurotrophic factor. To explore the proteolytic processing from prosaposin to mature activator proteins, metabolic labeling was done with human prosaposin expressed in insect cells, human fibroblasts, neuronal stem cells (NT2) and retinoic acid-differentiated NT2 neurons. In all cell types, the major processing pathway was through a tetrasaposin, A-B-C-D, from which saposin A was then removed. In mammalian cells monosaposins were derived from the trisaposin B-C-D by cleavage to the disaposins, B-C and C-D, that were processed to monosaposins. In insect cells the major end products were the disaposins, with A-B and C-D derived from the tetrasaposin, A-B-C-D, or with B-C and C-D derived from the trisaposin, B-C-D. In insect and mammalian cells, the nonsignal NH2-terminal peptide preceding saposin A (termed Nter) was usually removed prior to saposin A cleavage. In NT2-derived differentiated neurons, precursor tetrasaposins containing A-B-C-D were secreted with and without Nter. Immunofluorescence studies using prosaposin-specific antisera showed large steady state amounts of uncleaved prosaposin in Purkinje cells, cortical neurons, and other specific cell types in adult mice. These studies indicate that prosaposin processing is highly regulated at a proteolytic level to produce prosaposin, tetrasaposins, or mature monosaposins in specific mammalian cells.