gebhart/patrepeval huggingface dataset:
Molecular and cellular approaches to the treatment of neurological disease (1993)

Introduction: molecular and cellular organization of the central nervous system - implications for new therapeutics. Part 1 Mechanisms of neuronal injury and death: calcium and glutamate-induced cortical neuronal death glutamate receptors and excitotoxicity cellular physiology of hypoxia of the mammalian central nervous system metrochondrial dysfunction as a mechanism of CNS injury free radicals in CNS injury. Part 2 Neuronal injury in specific disease states: strokes involving gray matter - studies on in situ models of cerebral anoxia anoxic injury of central myelinated axons - ionic mechanisms and pharmacology the ischemic penumbra in stroke - prospects for analysis by nuclear magnetic resonance spectroscopy role of excitotoxins in heredito-degenerative neurologic diseases the therapeutic window for methylprednisolone treatment of acute spinal cord injury - implications for cell injury mechanisms. Part 3 Therapeutic strategies: emerging strategies for the treatment of ischemic brain injury the design and appraisal of randomized clinical trials in cerebrovascular disease and CNS trauma pharmacological modification of axon membrane molecules and cell transplantation as approaches to the restoration of conduction in demyelinated axons current anti-sense nucleic acid strategies for manipulating neuronal and glial cells. Part 4 Cellular and molecular replacement: factors affecting proviral expression in primary cells grafted into the CNS cellular replacement of dopamine deficit in Parkinson's disease using human foetal mesencephalic tissue - preliminary results in four patients intracerebral transplantation - prospects for neuronal replacement in neurodegenerative diseases.
DSP architectures (2003)

As far as the future of communication is concerned, we have seen that there is great demand for audio and video data to complement text. Digital signal processing (DSP) is the science that enables traditionally analog audio and video signals to be processed digitally for transmission, storage, reproduction and manipulation. In this paper, we will explain the various DSP architectures and its silicon implementation. We will also discuss the state-of-the art and examine the issues pertaining to performance.
Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels (2017)

Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.
Effect of drug loading on the pharmacology, pharmacokinetics, and toxicity of an anti-CD30 antibody-drug conjugate (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

624 

Antibodies that target tumor-associated antigens are currently used in the clinic to treat cancer, in some cases as front-line therapy. Even with these successes there is a need to improve the therapeutic activity of antibody-based therapies. We have recently shown that an antibody-drug conjugate (ADC) targeted to CD30 has potent and selective activity against CD30+ malignancies such as Hodgkin’s disease (HD) and anaplastic large cell lymphoma (ALCL) (Blood 102: 1458-1465, 2003). This ADC, cAC10-vcMMAE, consists of a chimeric anti-CD30 antibody, cAC10, conjugated with 8 molecules of the cytotoxic drug monomethyl auristatin E (MMAE). The drug moieties were attached via a Val-Cit peptide linker to the 8 cysteine residues that comprise the 4 inter-chain disulfide bonds of the cAC10 antibody. cAC10-vcMMAE first binds to CD30 expressed on the surface of CD30+ cells and, upon internalization, drug moieties are enzymatically released and inhibit tubulin polymerization. In the present work, we sought to optimize the therapeutic potential of cAC10-vcMMAE conjugates by assessing the impact of drug loading. ADCs with 2 and 4 drugs per mAb, cAC10-vcMMAE2 and cAC10-vcMMAE4, respectively, were constructed and compared to cAC10-vcMMAE8. Cytotoxicity of the ADCs against CD30+ cell lines in vitro was found to be dependent on drug loading; as drug loading increased ADC cytotoxicity was enhanced. Karpas-299, an ALCL line, and L540cy, a HD cell line, were implanted into SCID mice to compare the efficacy of the ADCs. Unlike the in vitro findings, decreasing drug loading did not necessarily reduce potency in vivo . Complete regressions were achieved with cAC10-vc-MMAE8 and cAC10-vcMMAE4 at the same dose of antibody even though the latter contained half the amount of cytotoxic drug. The difference between cAC10-vcMMAE2 and cAC10-vcMMAE4 was dependent on drug load in that twice the dose was required to achieve complete regressions with cAC10-vcMMAE2. The clearance of the cAC10-ADCs was directly related to the drug loading as cAC10-vcMMAE8 cleared faster than cAC10-vcMMAE4. Similarly, cAC10-vcMMAE2 cleared the slowest of any ADC tested, and was comparable in clearance with the naked cAC10 antibody. In contrast to the in vivo efficacy, there was evidence of a correlation between drug loading and the maximum tolerated dose (MTD). The MTDs of cAC10-vc-MMAE2 and cAC10-vc-MMAE4 in mice were at least four-fold and two-fold higher, respectively, than cAC10-vc-MMAE8. Our data indicates that decreasing the drug loading from eight to four drugs per antibody doubles the therapeutic window of the cAC10-vcMMAE. These results demonstrate that drug loading is a key design parameter in optimizing the therapeutic window of ADCs.
Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. (1993)

The calicheamicin family of antitumor antibiotics are capable of producing double-stranded DNA breaks at sub-picomolar concentrations. Their potency suggested that the calicheamicins would be excellent candidates for targeted delivery and a hydrazide prepared from the most potent and abundant of the naturally occurring derivative, gamma 1I, was linked to oxidized sugars on CT-M-01, an internalizing anti-polyepithelial mucin antibody. The conjugates retained the immunoreactivity of the unmodified antibody and were specifically cytotoxic toward antigen positive tumor cells in vitro and in vivo. Hydrazide analogues of less potent calicheamicin derivatives were also prepared and conjugated to CT-M-01. Comparison of the therapeutic efficacy of the conjugates against the MX-1 xenograft tumor implanted s.c. in nude mice showed that conjugates of derivatives missing the rhamnose, a sugar residue that is part of the DNA binding region of the drug, were not as promising as antitumor therapies. However, conjugates of two derivatives, alpha 3I and N-acetyl-gamma 1I, in which the rhamnose residue is present but the amino sugar residue of the parent drug is either missing or modified, significantly inhibited tumor growth over a 4-fold dose range and produced long-term tumor-free survivors. Sterically hindering methyl groups adjacent to the disulfide in the linker further increased the therapeutic window of these potent conjugates.
Parallel Information Processing in the Dorsal Striatum: Relation to Hippocampal Function (1999)

We investigated the effects of localized medial and lateral CPu lesions and fornix/fimbria lesions on responses to a local cue and to behavior based on cognitive-spatial information in the water maze. Rats were trained concurrently on the cue (visible platform) and spatial (submerged platform) components of the task, followed by a test in which responses to the two types of information were dissociated by a measure of competing response tendencies. Bilateral lesions of lateral CPu did not affect acquisition of either cue or spatial responding but produced a preference for the spatial response on the competition test. Bilateral lesions of the medial CPu retarded but did not prevent learning both components and produced a preference for the cue response on the competition test. The latter effect was accompanied by increased thigmotaxis (swimming in the periphery of the pool), primarily during the early acquisition trials, which was attributed to an impaired ability to respond to learned spatial information. Fornix/fimbria lesions prevented spatial but not cue learning and produced a preference for the cue response on the competition test. Asymmetric lesions (unilateral hippocampus and contralateral medial CPu) produced mild retardation of acquisition of both the cue and spatial tasks and a preference for the cue response on the competition test. These findings dissociate the functions of the lateral and medial CPu and suggest that the hippocampus and medial CPu may be parts of a system that promotes responding based on learned cognitive-spatial information, particularly in competitive cue-place response situations.
The Proteasome Is Involved in the First Metaphase-to-Anaphase Transition of Meiosis in Rat Oocytes1 (2000)

The proteasome engages in protein degradation as a regulatory process in biological transactions. Among other cellular processes, the proteasome participates in degradation of ubiquinated cyclins in mitosis. However, its role in meiosis has not been established. Resumption of meiosis in the oocyte involves the activation of maturation promoting factor (MPF), a complex of p34cdc2 and cyclin B. Inactivation of this factor, occurring between the two meiotic divisions, is associated with degradation of cyclin B. In this study, we examined the possible involvement of the proteasome in regulation of the exit from metaphase I in spontaneously maturing rat oocytes. We found that upon resumption of meiosis, proteasomes translocate to the spindle apparatus. We further demonstrated that specific inhibitors of proteasome catalytic activity, MG132 and lactacystin, blocked polar body extrusion. Chromosome and microtubule fluorescent staining verified that MG132-treated oocytes were arrested at metaphase I. Intervention of proteasomal action with this inhibitor also resulted in accumulation of cyclin B and elevated activity of MPF. These data demonstrate that proteasomal catalytic activity is absolutely essential for the decrease in MPF activity and completion of the first meiotic division. Its translocation to the spindle apparatus may facilitate the timely degradation of cyclin B.
Facile Synthesis of a High-Affinity Ligand for Mammalian Hepatic Lectin Containing Three Terminal N-Acetylgalactosamine Residues (1997)

A simple cluster glycoside containing three residues of N-acetylgalactosamine with proper inter-residual distances can be a high-affinity ligand for asialoglycoprotein receptor of mammalian liver. YEE(ah-GalNAc)3 [Lee, R. T., and Lee, Y. C. (1987) Glycoconjugate J, 4, 317-328] is such a ligand having a Kd in the subnanomolar range, and this high-affinity ligand has been successfully utilized in the delivery of gene to the parenchymal cells of the liver [Merwin, J. R., Noell, G. S., Thomas, W. L., Chiou, H. C., DeRome, M. E., McKee, T. D., Spitalny, G. L., and Findeis, M. A. (1994) Bioconjugate Chem. 5, 612-620; Hangeland, J. J., Levis, J. T., Lee, Y. C., and Ts'o, P. O. P. (1995) Bioconjugate Chem. 6, 695-701]. Reported here is a synthetic procedure for an equally effective, homologous trivalent ligand, YDD(G-ah-GalNAc)3. The advantage offered by this new cluster glycoside is that the synthetic scheme accomplishes purification of reaction intermediates and the product without chromatographic separations. This greatly simplifies the procedure and allows scale-up of the operation at reduced cost of production.
Relationship between EGFR overexpression and gene amplification status in central nervous system gliomas. (2005)

EGFR protein overexpression is closely associated with gene amplification. Seventy-eight percent of cases showing protein overexpression demonstrated gene amplification. All cases of central nervous system neoplasms showing protein overexpression but lacking gene amplification were associated with only 2+ protein overexpression. All central nervous system neoplasms demonstrating gene amplification and/or overexpression were high grade neoplasms.
Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: An open‐label extension analysis (2007)

These findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events.
Sporadic Occurrence of Parthenogenesis In Poultry (1970)

Journal Article Sporadic Occurrence of Parthenogenesis In Poultry Get access PATRICIA SARVELLA PATRICIA SARVELLA Research-genticist Poultry Research Branch, Animal Husbandry Research Division, Agricultural Research Service, United States Department of AgricultureBeltsville, Maryland 20705 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 61, Issue 5, September 1970, Pages 215–219, https://doi.org/10.1093/oxfordjournals.jhered.a108087 Published: 01 September 1970
Clinical Evaluation of Azelastine Nasal Spray versus Terfenadine in the Treatment of Allergic Rhinitis (1999)

BACKGROUND: Anitihistamines are primarile used for the therapy of allergic rhinitis. Azelastine tablet is very effective and well tolerated. The newly developed Azelastine nasal spray has the advantage of acting more rapidly and in lower doses because of the local administration in the affected area. 
METHODS: This study was designed as double-blind, randomized, active controlled with parallel group to compare the therapeutic efficacy and tolerance of intranasal Azelastine with that of Terfenadine tablet in relieving both the nasal and eye symptoms in allergic rhinitis patients. 
RESULTS: The results showed that after 2 weeks of treatment, 79% of patients in Azelastine group (n=19) and 59% of patients in Terfenadine group (n=23) had improvement in the symptom assessment. The percentage was not statistically different between treatments (p＞0.20). Except for the event of bitter taste when significant difference was found in Azelastine group, other adverse experiences were compatible between treatments.
CONCLUSIONS: This clinical study demonstrates the efficacy and safety of a twice daily dosage of Azelastine nasal spray, 0.14 mg per nostril (0.56mg Azelastine/day), in the treatment of allergic rhinitis. The efficacy of Azelastine nasal spray is at least as good as that of Terfenadine, 60 mg tablets b.i.d. The safety outcomes show that Azelastine nasal spray is safe in the treatment of allergic rhinitis. (J Taiwan Otolaryngol Head Neck Surg 1999;34:471-478)
TERRITORIAL DISCREPANCIES IN THE RURAL-URBAN FRINGE ZONE OF BUCHAREST (2015)

The rural-urban fringe area of Bucharest is the most economically dynamic region of Romania, and, at the same time, is the one, which suffered the most from the recent economic decline. The article is focused on the analysis of inequalities of social-economic variables, including differences in their spatial patterns, before and after the 2008 economic crisis. We involved two methods of inequality analysis. Gini coefficient was used to determine the overall level of inequalities in the region. Comparison with the region’s mean value was used for identification of spatial patterns of these inequalities. Our results highlight four trends in the overall level of inequality dynamics, while all the studied variables follow more or less accurately the same pattern of spatial dynamics. Our findings provide new arguments in support of the idea that the new processes in the Bucharest fringe zone follow the circular pattern, which privileges the northern part of the area, while south is the last to benefit from any new development.
Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation (2005)

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-alpha- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-alpha, macrophages, in response to TNF-alpha and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases.
Long-term control of renal blood flow: what is the role of the renal nerves? (2001)

We have developed a system for long-term continuous monitoring of cardiovascular parameters in rabbits living in their home cage to assess what role renal sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were recorded continuously for 4 wk. Beginning 4-5 days after surgery a circadian rhythm, dependent on feeding time, was observed. When averaged over all days RBF to the innervated and denervated kidneys was not significantly different. However, control of RBF around these mean levels was dependent on the presence of the renal sympathetic nerves. In particular we observed episodic elevations in heart rate and other parameters associated with activity. In the denervated kidney, during these episodic elevations, the increase in renal resistance was closely related to the increase in arterial pressure. In the innervated kidney the renal resistance response was significantly more variable, indicating an interaction of the sympathetic nervous system. These results indicate that whereas overall levels of RSNA do not set the mean level of RBF the renal vasculature is sensitive to episodic increases in sympathetic nerve activity.
Wafer and reticle positioning system for the Extreme Ultraviolet Lithography Engineering Test Stand (2000)

This paper is an overview of the wafer and reticle positioning system of the Extreme Ultraviolet Lithography (EUVL) Engineering Test Stand (ETS). EUVL represents one of the most promising technologies for supporting the integrated circuit (IC) industry's lithography needs for critical features below 100nm. EUVL research and development includes development of capabilities for demonstrating key EUV technologies. The ETS is under development at the EUV Virtual National Laboratory, to demonstrate EUV full-field imaging and provide data that supports production-tool development. The stages and their associated metrology operated in a vacuum environment and must meet stringent outgassing specifications. A tight tolerance is placed on the stage tracking performance to minimize image distortion and provide high position repeatability. The wafer must track the reticle with less than {+-}3nm of position error and jitter must not exceed 10nm rms. To meet these performance requirements, magnetically levitated positioning stages utilizing a system of sophisticated control electronics will be used. System modeling and experimentation have contributed to the development of the positioning system and results indicate that desired ETS performance is achievable.
2'-Deoxy-2'-fluoro- -D-arabinonucleic acid (2'F-ANA) modified oligonucleotides (ON) effect highly efficient, and persistent, gene silencing (2006)

To be effective in vivo, antisense oligonucleotides (AS ON) should be nuclease resistant, form stable ON/RNA duplexes and support ribonuclease H mediated heteroduplex cleavage, all with negligible non-specific effects on cell function. We report herein that AS ONs containing a 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (2'F-ANA) sugar modification not only meet these criteria, but have the added advantage of maintaining high intracellular concentrations for prolonged periods of time which appears to promote longer term gene silencing. To demonstrate this, we targeted the c-MYB protooncogene's mRNA in human leukemia cells with fully phosphorothioated 2'F-ANA-DNA chimeras (PS-2'FANA-DNA) and compared their gene silencing efficiency with AS ON containing unmodified nucleosides (PS-DNA). When delivered by nucleofection, chemically modified ON of both types effected a >90% knockdown of c-MYB mRNA and protein expression, but the PS-2'F-ANA-DNA were able to accomplish this at 20% of the dose of the PS-DNA, and in contrast to the PS-AS DNA, their silencing effect was still present after 4 days after a single administration. Therefore, our data demonstrate that PS-2'F-ANA-DNA chimeras are efficient gene silencing molecules, and suggest that they could have significant therapeutic potential.
Targeting Sh2 Domains in Breast Cancer (2014)

Breast cancer is among the most commonly diagnosed cancer types in women worldwide and is the second leading cause of cancer-related disease in the USA. SH2 domains recruit signaling proteins to phosphotyrosine residues on aberrantly activated growth factor and cytokine receptors and contribute to cancer cell cycling, metastasis, angiogenesis and so on. Herein we review phosphopeptide mimetic and small-molecule approaches targeting the SH2 domains of Grb2, Grb7 and STAT3 that inhibit their targets and reduce proliferation in in vitro breast cancer models. Only STAT3 inhibitors have been evaluated in in vivo models and have led to tumor reduction. Taken together, these studies suggest that targeting SH2 domains is an important approach to the treatment of breast cancer.