gebhart/patrepeval huggingface dataset:
Pharmacological Treatment of Mild Cognitive Impairment as a Prodromal Syndrome of Alzheimer´s Disease (2013)

Mild cognitive impairment (MCI) is a syndrome which, depending on various neurobiological, psychological and social factors, carries a high risk of developing into dementia. As far as diagnostic uncertainty and the heterogeneous underlying pathophysiological mechanisms are concerned, only limited therapeutic options are currently available. Clinical trials involving a wide range of substances have failed to show efficacy on primary and secondary outcome parameters. Most results reflect not only a lack of effectiveness of drug therapy but also methodological constraints in true prodromal Alzheimer´s disease (AD) based on clinical criteria. Biomarkers may help to identify MCI as a prodromal phase of dementia, so it is important to use them to improve specificity of case selection in future studies. For MCI as a prodromal syndrome of AD, clinical trials with disease modifying drugs that target underlying pathological mechanisms such as amyloid-beta accumulation and neurofibrillary tangle formation may help develop effective treatment options in the future. Alternative pharmacological approaches are currently being evaluated in ongoing phase 1 and phase 2 studies. Nevertheless, a lack of approved pharmacotherapeutic options has led to specific interventions that focus on patient education and life-style related factors receiving increasing attention. Keywords: Mild cognitive impairment, Alzheimer’s Dementia, Clinical Trials, Treatment
Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior (1998)

Reverse genetics, in which detailed knowledge of a gene of interest permits in vivo modification of its expression or function, provides a powerful method for examining the physiological relevance of any protein. Transgenic and knockout mouse models are particularly useful for studies of complex neurobiological problems. The primary aims of this review are to familiarize the nonspecialist with the techniques and limitations of mouse mutagenesis, to describe new technologies that may overcome these limitations, and to illustrate, using representative examples from the literature, some of the ways in which genetically altered mice have been used to analyze central nervous system function. The goal is to provide the information necessary to evaluate critically studies in which mutant mice have been used to study neurobiological problems.
Sonochemical Hydrolysis of Ga3+ Ions:  Synthesis of Scroll-like Cylindrical Nanoparticles of Gallium Oxide Hydroxide (1999)

The sonochemical reaction of an aqueous solution of GaCl3 led to the formation of gallium oxide hydroxide rolled up in a scroll-like layered structure to give cylinders 80−120 nm in diameter and 500−600 nm in length. Small amounts of metallic Ga were incorporated with these tubes. A mechanism for this reaction has been suggested where the reaction takes place in a shell surrounding the collapsing bubble.
High-power planar dielectric waveguide lasers (2001)

The advantages and potential hazards of using a planar waveguide as the host in a high-power diode-pumped laser system are described. The techniques discussed include the use of proximity-coupled diodes, double-clad waveguides, unstable resonators, tapers, and integrated passive Q switches. Laser devices are described based on Yb&lt;sup&gt;3+&lt;/sup&gt;-, Nd&lt;sup&gt;3+&lt;/sup&gt;-, and Tm&lt;sup&gt;3+&lt;/sup&gt;-doped YAG, and monolithic and highly compact waveguide lasers with outputs greater than 10 W are demonstrated. The prospects for scaling to the 100 W level and for further integration of devices for added functionality in a monolithic laser system are discussed.
Pairwise comparisons of mitochondrial DNA sequences in subdivided populations and implications for early human evolution. (1994)

We consider the effect on the distribution of pairwise differences between mitochondrial DNA sequences of the incorporation into the underlying population genetics model of two particular effects that seem realistic for human populations. The first is that the population size was roughly constant before growing to its current level. The second is that the population is geographically subdivided rather than panmictic. In each case these features tend to encourage multimodal distributions of pairwise differences, in contrast to existing, unimodal datasets. We argue that population genetics models currently used to analyze such data may thus fail to reflect important features of human mitochondrial DNA evolution. These may include selection on the mitochondrial genome, more realistic mutation mechanisms, or special population or migration dynamics. Particularly in view of the variability inherent in the single available human mitochondrial genealogy, it is argued that until these effects are better understood, inferences from such data should be rather cautious.
Serum lectin with known structure activates complement through the classical pathway. (1987)

Serum mannan-binding protein (MBP), a lectin specific for mannose and N-acetylglucosamine, was revealed to activate the complement system as measured by passive hemolysis using sheep erythrocytes coated with yeast mannan. In contrast, rat liver MBP, which shares many properties in common with serum MBP, could not activate complement at all. The activation by serum MBP was inhibited effectively by the presence of haptenic sugars and dependent absolutely upon the presence of C4, indicating that the activation is initiated by the sugar binding activity of MBP and proceeds through the classical pathway. The 25 NH2-terminal amino acid sequence of rat serum MBP determined in this study was completely matched with that of MBP-A deduced from cDNA sequence by Drickamer et al. (Drickamer, K., Dordal, M. S., and Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887), revealing that MBP-A is in fact identical with serum MBP. On the basis of the knowledge of primary structures and physicochemical properties of rat serum and liver MBPs, a possible mechanism of the complement activation by serum MBP is discussed with reference to close similarity in the gross structures of serum MBP and C1q.
PTK/ZK (Novartis). (2003)

PTK/ZK, a VEGF receptor tyrosine kinase inhibitor, is under development by Novartis AG and Schering AG as an inhibitor of angiogenesis for the potential treatment of various cancers.
Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness (2013)

Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of complex muscle diseases of unknown etiology. These diseases are characterized by progressive muscle weakness and damage, together with involvement of other organ systems. It is generally believed that the autoimmune response (autoreactive lymphocytes and autoantibodies) to skeletal muscle-derived antigens is responsible for the muscle fiber damage and muscle weakness in this group of disorders. Therefore, most of the current therapeutic strategies are directed at either suppressing or modifying immune cell activity. Recent studies have indicated that the underlying mechanisms that mediate muscle damage and dysfunction are multiple and complex. Emerging evidence indicates that not only autoimmune responses but also innate immune and non-immune metabolic pathways contribute to disease pathogenesis. However, the relative contributions of each of these mechanisms to disease pathogenesis are currently unknown. Here we discuss some of these complex pathways, their inter-relationships and their relation to muscle damage in myositis. Understanding the relative contributions of each of these pathways to disease pathogenesis would help us to identify suitable drug targets to alleviate muscle damage and also improve muscle weakness and quality of life for patients suffering from these debilitating muscle diseases.
Thermal Ablation of Canine Prostate Using Interstitial Temperature Self-Regulating Seeds: New Treatment for Prostate Cancer (1997)

An interstitial temperature self-regulating implantable thermal seed for ablation of the prostate was investigated for the treatment of cancer. The technique is analogous to brachytherapy implants with three important advantages: highly localized temperatures may reduce complications, the thermal seed can be activated for retreatment at any point in time, and the seeds pose no radiation hazard to the clinical staff. Thermal seeds were implanted in the left lobe of the prostates in four dogs; the right lobe was a control to evaluate undesired heating outside the seed array. Linear-array thermometry probes were placed in both lobes, and the induction field for heating the implants was activated for 1 hour. After treatment, biopsies were taken from both lobes at 4-hour intervals up to 28 hours to evaluate thermal damage and thermotolerance as measured by expression of heat shock protein (hsp) 70. Only 5 minutes was required to heat the left lobe to 45 degrees to 55 degrees C. The maximum and minimum cumulative equivalent minutes at 43 degrees C (CEM43) thermal doses in the treated lobe were 174 and 4.4 hours, respectively; less than a 1-minute CEM43 was observed in the control lobe. Elevated hsp70 expression was detected in tissue of the treated lobe between 12 and 24 hours after treatment; minimal increases occurred in the control lobe. The thermal seed system was effective at heating the prostatic volume without damage to normal tissues outside the implant array, and subsequent treatments were simplified in comparison with other hyperthermia devices. Expression of hsp70 implies that retreatment of the prostate at intervals as short as 48 to 72 hours may avoid thermotolerance making weekly treatment an appropriate regimen.
Cold Fusion Believer Turned Skeptic Crusades For More Rigorous Research (1995)

RETURN TO ISSUEPREVNewsNEXTCold Fusion Believer Turned Skeptic Crusades For More Rigorous ResearchPhysicist Steven Jones, one originator of cold fusion, retracted previous claims and is pushing others to be as diligentRON DAGANIView Author Information C&EN WashingtonCite this: Chem. Eng. News 1995, 73, 23, 34–40Publication Date (Print):June 5, 1995Publication History Published online12 November 2010Published inissue 5 June 1995https://pubs.acs.org/doi/10.1021/cen-v073n023.p034https://doi.org/10.1021/cen-v073n023.p034newsACS PublicationsCopyright © 1995 AMERICAN CHEMICAL SOCIETYArticle Views7Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Electrolysis,Explosives,Nuclear fusion,Physical chemistry Get e-Alerts
Role of endothelium-derived nitric oxide in the regulation of blood pressure. (1989)

The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg.kg-1) also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg.kg-1), but not by D-arginine (300 mg.kg-1), indomethacin (1 mg.kg-1), prazosin (0.3 mg.kg-1), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.
DNA sequencing using capillary array electrophoresis (1992)

A DNA sequencing method is presented that utilizes capillary array electrophoresis, two-color fluorescence detection, and a two-dye labeling protocol. Sanger DNA sequencing fragments are separated on an array of capillaries and detected on-column using a two-color, laser-excited, confocal-fluorescence scanner. The four sets of DNA sequencing fragments are separated in a single capillary and then distinguished by using a binary coding scheme where each fragment set is labeled with a characteristic ratio of two dye-labeled primers. Since only two dye-labeled primers are required, it is possible to select dyes that have identical mobility shifts. It is also shown that the ratio of the signal in the two detection channels provides a reliable identification of the sequencing fragment. DNA sequencing results on a 25-capillary array are presented.
Intracranial Neurostimulation for Pain Control:A Review (2010)

Intracranial neurostimulation for pain relief is most frequently delivered by stimulating the motor cortex, the sensory thalamus, or the periaqueductal and periventricular gray matter. The stimulation of these sites through MCS (motor cortex stimulation) and DBS (deep brain stimulation) has proven effective for treating a number of neuropathic and nociceptive pain states that are not responsive or amenable to other therapies or types of neurostimulation. Prospective randomized clinical trials to confirm the efficacy of these intracranial therapies have not been published. Intracranial neurostimulation is somewhat different than other forms of neurostimulation in that its current primary application is for the treatment of medically intractable movement disorders. However, the increasing use of intracranial neurostimulation for the treatment of chronic pain, especially for pain not responsive to other neuromodulation techniques, reflects the efficacy and relative safety of these intracranial procedures. First employed in 1954, intracranial neurostimulation represents one of the earliest uses of neurostimulation to treat chronic pain that is refractory to medical therapy. Currently, 2 kinds of intracranial neurostimulation are commonly used to control pain: motor cortex stimulation and deep brain stimulation. MCS has shown particular promise in the treatment of trigeminal neuropathic pain and central pain syndromes such as thalamic pain syndrome. DBS may be employed for a number of nociceptive and neuropathic pain states, including cluster headaches, chronic low back pain, failed back surgery syndrome, peripheral neuropathic pain, facial deafferentation pain, and pain that is secondary to brachial plexus avulsion. The unique lack of stimulation-induced perceptual experience with MCS makes MCS uniquely suited for blinded studies of its effectiveness. This article will review the scientific rationale, indications, surgical techniques, and outcomes of intracranial neuromodulation procedures for the treatment of chronic pain. Key words: Motor cortex stimulation, deep brain stimulation, pain, neurostimulation
Waldenstrom's macroglobulinemia: Recent advances in biology and therapy. (2009)

Waldenstrom's macroglobulinemia (WM) is a B-cell disorder characterized by bone marrow infiltration with clonal lymphoplasmacytic cells (LPCs), along with an immunoglobulin M monoclonal gammopathy. Recent studies have led to several insights into disease biology as well as the development of an international staging system. Patients with asymptomatic macroglobulinemia should be observed without therapy. Options for frontline therapy include alkylating agents, nucleoside analogs, and rituximab, either as monotherapy or in combination. Although objective responses are common, complete remissions are infrequent. Several novel agents including proteasome inhibitors and thalidomide, as well as high-dose chemotherapy and stem cell transplantation are being incorporated into the therapeutic armamentarium in WM and show promising activity. This report provides an update on recent advances in biology and treatment of this disease.
Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish (2018)

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and <i>Cas9</i> mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the <i>tyr</i> gene and two sites in the <i>gol</i> gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites (<i>tyr1</i> > 66%, <i>tyr2</i> > 73%, <i>gol1</i> > 50%, and <i>gol2</i> > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and <i>Cas9</i> mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system.
Green Gasoline by Catalytic Fast Pyrolysis of Solid Biomass Derived Compounds (2008)

A fuelling success: High-quality aromatic fuel additives can be produced directly from solid biomass feedstocks by catalytic fast pyrolysis in a single catalytic reactor at short residence times. High heating rates and catalyst-to-feed ratios are needed to ensure that pyrolized biomass compounds enter the pores of the ZSM5 catalyst and that thermal decomposition is avoided. Product selectivity is a function of the active site and pore structure of the catalyst. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2476/2008/z800018_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. (1994)

Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intra-arterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.
Safety and Efficacy of Dispase and Plasmin in Pharmacologic Vitreolysis (2004)

Intravitreal injection of dispase at 0.025 U or more can induce PVD, but it is not safe. Plasmin (1-4 U) is safer, except for the potential risk of inducing intraocular inflammation.
Abstract 2145: PSMA-specific anti-tumor activity of the targeted-tubulysin conjugate, EC1169. (2013)

Abstract Prostate-specific membrane antigen (PSMA) is a biomarker that is overexpressed on prostate cancer, and it's also present on the neovasculature within many non-prostate solid tumors. We previously reported on EC0652, a 99mTc-labeled small molecule that specifically binds to PSMA-positive tumors and is currently being clinically evaluated for diagnostic imaging applications. Herein, we report on the construction and biological testing of novel tubulysin B-containing, companion therapeutic agents for the treatment of PSMA-expressing cancer. One of these compounds, EC1169, recently emerged as a lead candidate for preclinical development. This water-soluble conjugate was shown to have high affinity for PSMA-positive cells. When tested in vitro, EC1169 was found to inhibit the growth of PSMA-positive cells, but it displayed no activity against PSMA-negative cells. Brief treatment of nude mice bearing PSMA-positive LNCaP human xenografts with EC1169 led to complete remissions in 5/7 mice, and cures (i.e. tumor free &amp;gt;90 days post implantation) in 2/7 mice. Furthermore, this activity occurred in the absence of weight loss or major organ tissue degeneration. In contrast, the non-targeted tubulysin B drug proved to be inactive against the LNCaP tumor model when administered at doses near to or greater than the maximum tolerated level. PSMA-negative KB tumors did not appreciably respond to EC1169 therapy, thereby confirming this compound's targeted specificity for PSMA-expressing cells. Finally, treatment of LNCaP-bearing mice with docetaxel (the most active chemotherapeutic agent approved for prostate cancer), was found to produce only modest anti-tumor activity (2/4 partial responses, 1/4 cures), and this outcome was also associated with severe weight loss (18%). Taken together, these results strongly indicate that PSMA-positive tumors may be more effectively treated using highly potent, PSMA-targeted small-molecule drug conjugates using regimens that do not cause unwanted toxicity. Citation Format: Joseph A. Reddy, Alicia Bloomfield, Ryan Dorton, Melissa Nelson, Marilynn Vetzel, Spencer Hahn, Iontcho Vlahov, Christopher Leamon. PSMA-specific anti-tumor activity of the targeted-tubulysin conjugate, EC1169. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2145. doi:10.1158/1538-7445.AM2013-2145