gebhart/patrepeval huggingface dataset:
Progress towards gene therapy for Duchenne muscular dystrophy (1996)

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by defects in the dystrophin gene. Patients exhibit progressive muscle degeneration, generally begin using a wheelchair before 11 years of age, and die from respiratory or cardiac failure by their early to mid-twenties. Currently no treatment is available for this disease that affects 1 in 3500 newborn males worldwide. As a result, intensive efforts are under way to develop methods to treat DMD by gene therapy. This Commentary will present some of the successes of this research and identify a few of the most challenging obstacles to be overcome before effective treatment is available. Success in treating any disorder by gene therapy hinges on a thorough understanding of the biological parameters of the disease process and the tissues involved. Much of this groundwork has been laid for DMD, and this research effort can serve as a paradigm for the assault
An α- l -Arabinofuranosidase from Trichoderma reesei Containing a Noncatalytic Xylan-Binding Domain (1999)

L-Sorbose, an excellent cellulase and xylanase inducer from Trichoderma reesei PC-3-7, also induced alpha-L-arabinofuranosidase (alpha-AF) activity. An alpha-AF induced by L-sorbose was purified to homogeneity, and its molecular mass was revealed to be 35 kDa (AF35), which was not consistent with that of the previously reported alpha-AF. Another species, with a molecular mass of 53 kDa (AF53), which is identical to that of the reported alpha-AF, was obtained by a different purification procedure. Acid treatment of the ammonium sulfate-precipitated fraction at pH 3.0 in the purification steps or pepsin treatment of the purified AF53 reduced the molecular mass to 35 kDa. Both purified enzymes have the same enzymological properties, such as pH and temperature effects on activity and kinetic parameters for p-nitrophenyl-alpha-L-arabinofuranoside (pNPA). Moreover, the N-terminal amino acid sequences of these enzymes were identical with that of the reported alpha-AF. Therefore, it is obvious that AF35 results from the proteolytic cleavage of the C-terminal region of AF53. Although AF35 and AF53 showed the same catalytic constant with pNPA, the former showed drastically reduced specific activity against oat spelt xylan compared to the latter. Furthermore, AF53 was bound to xylan rather than to crystalline cellulose (Avicel), but AF35 could not be bound to any of the glycans. These results suggest that AF53 is a modular glycanase, which consists of an N-terminal catalytic domain and a C-terminal noncatalytic xylan-binding domain.
Neuropathologic effects of phenylmethylsulfonyl fluoride (PMSF)-induced promotion and protection in organophosphorus ester-induced delayed neuropathy (OPIDN) in hens. (1999)

The serine/cysteine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) has been used both to promote and to protect against neuropathic events of organophosphorus-induced delayed neuropathy (OPIDN) in hens (Veronesi and Padilla, 1985; Pope and Padilla, 1990; Lotti et al., 1991; Pope et al., 1993; Randall et al., 1997). This study is the first to expand upon this work by using high resolution microscopy provided by epoxy resin embedding and thin sectioning to evaluate neuropathological manifestations of promotion and protection, and to correlate them with associated clinical modifications. To evaluate dose-related effects of OPIDN, single phenyl saligenin phosphate (PSP) dosages of 0.5, 1.0, or 2.5 mg/kg were administered to adult hens. PMSF (90 mg/kg) was given either 4 hours after (for promotion) or 12 hours prior to (for protection) PSP administration. Clinical signs and pathologic changes in the biventer cervicis nerve, which is uniquely sensitive to OPIDN (El-Fawal et al., 1988), were monitored. PSP alone, 2.5 mg/kg, caused severe OPIDN (terminal clinical score 7.5 +/- 1.0 [0-8 scale]; neuropathology score 2.7 +/- 0.3 [0-4 scale, based on myelinated fiber degeneration]). PMSF given 12 hours prior to PSP gave complete protection (clinical and neuropathology scores of 0; p<0.0001 compared to PSP alone). Signs and lesions of OPIDN were absent following 0.5 mg/kg PSP alone, but PMSF given 4 hours after PSP potentiated its neurotoxic effects (all hens had clinical scores of 4.0 and the average neuropathology score was 3.5 +/- 0.3; p<0.0001 compared to PSP alone). Although quantitative differences were noted, qualitative differences among nerves from hens with OPIDN were not evident, either with light or electron microscopy. At the time of sacrifice, there was a statistically linear relationship (r2 = 0.76) between the clinical scores on the last day of observation and the neuropathology scores (p<0.0001). This study demonstrates that the degree of peripheral nerve myelinated fiber degeneration correlates with clinical deficits in PMSF-induced potentiation of and protection against OPIDN.
QSAR: Hansch Analysis and Related Approaches (1993)

Biological data - the additivity of group contributions parameters quantitative models statistical methods design of test series in QSAR applications of Hansch analysis applications of Free Wilson analysis and related models.
Effects of Subantimicrobial-Dose Doxycycline in the Treatment of Moderate Acne (2003)

Twice-daily SD doxycycline treatment significantly reduced the number of inflammatory and noninflammatory lesions in patients with moderate facial acne, was well tolerated, had no detectable antimicrobial effect on the skin flora, and did not result in any increase in the number or severity of resistant organisms.
Targeted vectors for gene therapy (1995)

Successful gene therapy requires not only the identification of an appropriate therapeutic gene for treatment of the disease, but also a delivery system by which that gene can be delivered to the desired cell type both efficiently and accurately. Reductions in accuracy will inevitably also reduce efficiency since fewer particles will be available for delivery to the correct cells if many are sequestered into nontarget cells. In addition, the therapy will have net benefit to the patient only if gene delivery is sufficiently restricted such that normal cells are left unaffected by any detrimental affects of bystander cell transduction. Here we review how currently available delivery systems, both plasmid and viral, can be manipulated to improve their targeting to specific cell types. Currently, targeting is achieved by engineering of the surface components of viruses and liposomes to achieve discrimination at the level of target cell recognition and/or by incorporating transcriptional elements into plasmid or viral genomes such that the therapeutic gene is expressed only in certain target cell types. In addition, we discuss emerging vectors and suggest how gene therapy delivery systems of the future will be composites of the best features of diverse vectors already in use.
Multicontrast delayed enhancement provides improved contrast between myocardial infarction and blood pool (2005)

The MCODE method provides a significant improvement in the ability to easily discriminate subendocardial MI by providing a T(2)-weighted image with high contrast between blood and MI. MCODE should improve both the detection and accurate sizing of MI.
Theory of Propagation of Elastic Waves in a Fluid-Saturated Porous Solid. I. Low-Frequency Range (1956)

A theory is developed for the propagation of stress waves in a porous elastic solid containing compressible viscous fluid. The emphasis of the present treatment is on materials where fluid and solid are of comparable densities as for instance in the case of water-saturated rock. The paper denoted here as Part I is restricted to the lower frequency range where the assumption of Poiseuille flow is valid. The extension to the higher frequencies will be treated in Part II. It is found that the material may be described by four nondimensional parameters and a characteristic frequency. There are two dilatational waves and one rotational wave. The physical interpretation of the result is clarified by treating first the case where the fluid is frictionless. The case of a material containing viscous fluid is then developed and discussed numerically. Phase velocity dispersion curves and attenuation coefficients for the three types of waves are plotted as a function of the frequency for various combinations of the characteristic parameters.
[Diaphragm pacing for the ventilatory support of the quadriplegic patients with respiratory paralysis]. (1992)

Electrical stimulation of the phrenic nerve to pace the diaphragm in patients with chronic ventilatory insufficiency has been an established therapeutic modality since William W.L. Glenn first described using radiofrequency signals in 1978 to stimulate the phrenic nerves. Before this event, patients who were ventilator-dependent and thus bedridden because of respiratory paralysis associated with quadriplegia usually anticipated little chance for physical or psychosocial rehabilitation. Two cases of C1-C2 subluxtion with cord injury and chronic ventilatory insufficiency were implanted at VGH-Taipei with diaphragm pacemaker in 1988. Postoperative phrenic nerve stimulation was given according to individual training schedule. One case with total phrenic paralysis received bilateral phrenic nerve stimulation and became weaned from the ventilator 6 months later. The other case with partially active ventilatory function received unilateral phrenic nerve stimulation to compensate the ventilation. However, its final outcome still showed the necessity of a bilateral mode to achieve adequate ventilation irrespective of strenuous training for 2 years.
Down-Regulation of Endometrial Matrix Metalloproteinase-3 and -7 Expressionin Vitroand Therapeutic Regression of Experimental Endometriosisin Vivoby a Novel Nonsteroidal Progesterone Receptor Agonist, Tanaproget (2006)

Given the positive preclinical pharmacological profile of TNPR that has recently been reported, additional development of this compound for the treatment of endometriosis is warranted.
Multifeature audio segmentation for browsing and annotation (2003)

Indexing and content-based retrieval are necessary to handle the large amounts of audio and multimedia data that is becoming available on the Web and elsewhere. Since manual indexing using existing audio editors is extremely time consuming a number of automatic content analysis systems have been proposed. Most of these systems rely on speech recognition techniques to create text indices. On the other hand, very few systems have been proposed for automatic indexing of music and general audio. Typically these systems rely on classification and similarity-retrieval techniques and work in restricted audio domains. A somewhat different, more general approach for fast indexing of arbitrary audio data is the use of segmentation based on multiple temporal features combined with automatic or semi-automatic annotation. In this paper, a general methodology for audio segmentation is proposed. A number of experiments were performed to evaluate the proposed methodology and compare different segmentation schemes. Finally, a prototype audio browsing and annotation tool based on segmentation combined with existing classification techniques was implemented.
Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis (2000)

Clinical abnormalities in multiple sclerosis (MS) have classically been considered to be caused by demyelination and/or axonal degeneration; the possibility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properties, has not been considered. Sensory Neuron-Specific sodium channel SNS displays a depolarized voltage dependence, slower activation and inactivation kinetics, and more rapid recovery from inactivation than classical "fast" sodium channels. SNS is selectively expressed in spinal sensory and trigeminal ganglion neurons within the peripheral nervous system and is not expressed within the normal brain. Here we show that sodium channel SNS mRNA and protein, which are not present within the cerebellum of control mice, are expressed within cerebellar Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. We also demonstrate SNS mRNA and protein expression within Purkinje cells from tissue obtained postmortem from patients with MS, but not in control subjects with no neurological disease. These results demonstrate a change in sodium channel expression in neurons within the brain in an animal model of MS and in humans with MS and suggest that abnormal patterns of neuronal ion channel expression may contribute to clinical abnormalities such as ataxia in these disorders.
A Seven-Segmented Influenza A Virus Expressing the Influenza C Virus Glycoprotein HEF (2008)

Influenza viruses are classified into three types: A, B, and C. The genomes of A- and B-type influenza viruses consist of eight RNA segments, whereas influenza C viruses only have seven RNAs. Both A and B influenza viruses contain two major surface glycoproteins: the hemagglutinin (HA) and the neuraminidase (NA). Influenza C viruses have only one major surface glycoprotein, HEF (hemagglutinin-esterase fusion). By using reverse genetics, we generated two seven-segmented chimeric influenza viruses. Each possesses six RNA segments from influenza virus A/Puerto Rico/8/34 (PB2, PB1, PA, NP, M, and NS); the seventh RNA segment encodes either the influenza virus C/Johannesburg/1/66 HEF full-length protein or a chimeric protein HEF-Ecto, which consists of the HEF ectodomain and the HA transmembrane and cytoplasmic regions. To facilitate packaging of the heterologous segment, both the HEF and HEF-Ecto coding regions are flanked by HA packaging sequences. When introduced as an eighth segment with the NA packaging sequences, both viruses are able to stably express a green fluorescent protein (GFP) gene, indicating a potential use for these viruses as vaccine vectors to carry foreign antigens. Finally, we show that incorporation of a GFP RNA segment enhances the growth of seven-segmented viruses, indicating that efficient influenza A viral RNA packaging requires the presence of eight RNA segments. These results support a selective mechanism of viral RNA recruitment to the budding site.
A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293 (2002)

A two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy acid amides under smooth conditions. Successful application of this methodology to the open-chain transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide 18 with unprotected N-terminus in 70−75% yield. This result demonstrates that the protocol developed even works in the presence of an ester and several methylated and unmethylated amide bonds. Finally, a sequence of ligation of methyl d-dehydroglutaminate (20) to the C-terminus of the saponification product 21, followed by the degradation protocol and ring closure, allowed chemical “point mutation” at the DGCN site affording the aza analogue of HUN-7293 (24) in 15% overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of 2-hydroxy acid amides.
Heterogeneous Organocatalysis for the Asymmetric Desymmetrization of meso‐Cyclic Anhydrides Using Silica Gel‐Supported Bis‐cinchona Alkaloids. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
An Efficient FPGA Implementation of Principle Component Analysis based Network Intrusion Detection System (2008)

Modern network intrusion detection systems (NIDSs) use anomaly detection to capture malicious attacks. Since such connections are described by large set of dimensions, processing these huge amounts of network data becomes extremely slow. To solve this time-efficiency problem, statistical methods like principal component analysis (PCA) can be used to reduce the dimensionality of the network data. In this paper, we design and implement an efficient FPGA architecture for Principal Component Analysis to be used in NIDSs. Moreover, using representative network intrusion traces, we show that our architecture correctly classifies attacks with detection rates exceeding 99.9% and false alarm rates as low as 1.95%. Our implementation on a Xilinx Virtex-II Pro FPGA platform provides a core throughput of up to 24.72 Gbps, clocking at a frequency of 96.56 MHz.
Effect of sulfasalazine on B cells. (1991)

We studied the in vitro immunomodulatory effect of sulfasalazine on purified human B cells, using a reversed plaque forming cell (PFC) assay and a proliferation assay. Sulfasalazine inhibited the PFC response of B cells in a dose-dependent manner. Sulfasalazine was added to PFC culture systems at several time points after the cultures were started. A marked reduction in B cell response was seen in the early phases (0-48 hours). Staphylococcus Aureus Cowan I (SAC) induced maximal B cell proliferation at day 3. Sulfasalazine at 5 micrograms/ml depressed that maximal proliferation on day 3. This indicates that sulfasalazine inhibited an early-phase event in the proliferation and differentiation of B cells. Sulfapyridine also inhibited the PFC response, but 5-aminosalicylic acid and N-acetyl sulfapyridine had no significant effect. These findings are significant since sulfapyridine is an active moiety of sulfasalazine, which is responsible for the second line of defense in the treatment of rheumatoid arthritis (RA). Adding T cells or macrophages to the PFC culture system had no significant effect. Furthermore, medium containing indomethacin was used to study the effect of prostaglandin released by residual macrophages. The results indicate that sulfasalazine inhibited the PFC response without affecting T cells, macrophages or prostaglandin. Sulfasalazine apparently has a direct immunosuppressive effect on B cells.
TCDD and a Putative Endogenous AhR Ligand, ITE, Elicit the Same Immediate Changes in Gene Expression in Mouse Lung Fibroblasts (2009)

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1'H-indolo-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5muM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible.
The Spasmodic Peptide Defines a New Conotoxin Superfamily (2000)

We purified and characterized a peptide from the venom of Conus textile that makes normal mice assume the phenotype of a well-known mutant, the spasmodic mouse. This "spasmodic" peptide has 27 amino acids, including two gamma-carboxyglutamate (Gla) residues. A cDNA clone encoding the precursor for the peptide was identified; a gamma-carboxylation recognition signal sequence (gamma-CRS) is present in the -1 --> -20 region of the peptide precursor. Both the gamma-CRS and the position of the Gla residues in the mature toxin are notably different from other Gla-containing conopeptides. The spasmodic peptide has a novel disulfide framework and distinct signal sequence which together define a new P-superfamily of conopeptides. A cDNA encoding another member of the P-superfamily was identified from a different species, Conus gloriamaris.
Pay-As-You-Go (2011)

Phase Change Memory (PCM) suffers from the problem of limited write endurance. This problem is exacerbated because of the high variability in lifetime across PCM cells, resulting in weaker cells failing much earlier than nominal cells. Ensuring long lifetimes under high variability requires that the design can correct a large number of errors for any given memory line. Unfortunately, supporting high levels of error correction for all lines incurs significantly high overhead, often exceeding 10% of overall memory capacity. Such an overhead may be too high for wide-scale adoption of PCM, given that memory market is typically very cost-sensitive.
Sustained Antigen-Specific Antitumor Recall Response Mediated by Gene-Modified CD4+ T Helper-1 and CD8+ T Cells (2007)

Given that specific subsets of T helper 1 (Th1) and T helper 2 (Th2) CD4(+) T cells have been shown to play key roles in tumor rejection models, we wanted to assess the contribution of either Th1 or Th2 CD4(+) cell subtypes for redirected T-cell immunotherapy. In this study, we have developed a novel method involving retroviral transduction and in vitro T-cell polarization to generate gene-engineered mouse CD4(+) Th1 and Th2 cells or T helper intermediate (Thi) cells expressing an anti-erbB2-CD28-zeta chimeric receptor. Gene-modified Th1 and Th2 polarized CD4(+) cells were characterized by the preferential secretion of IFN-gamma and interleukin-4, respectively, whereas Thi cells secreted both cytokines following receptor ligation. In adoptive transfer studies using an erbB2(+) lung metastasis model, complete survival of mice was observed when transduced Th1, Th2, or Thi CD4(+) cells were transferred in combination with an equivalent number of transduced CD8(+) T cells. Tumor rejection was consistently associated with transduced T cells at the tumor site and interleukin-2 secretion. However, the surviving mice treated with gene-modified Th1 CD4(+) cells were significantly more resistant to a subsequent challenge with a different erbB2(+) tumor (4T1.2) implanted s.c. This result correlated with both increased expansion of Th1 CD4(+) and CD8(+) T cells in the blood and a greater number of these cells localizing to the tumor site following rechallenge. These data support the use of gene-modified CD4(+) Th1 and CD8(+) T cells for mediating a sustained antitumor response.