gebhart/patrepeval huggingface dataset:
Bench to bedside advances in the 21st century for primary headache disorders: migraine treatments for migraine patients: Table 1 (2016)

Primary headache disorders represent a remarkable opportunity for clinical neuroscience to improve patients’ lives in substantial numbers and reduce societal economic burden (Olesen et al. , 2012). Of the neurological maladies (Goadsby et al. , 2002; Akerman et al. , 2011) one could never be accused of bloviating when presenting the impact or opining on the need for investment in research in headache disorders, particularly migraine (Shapiro and Goadsby, 2007). Migraine alone is the sixth leading cause of disability of any condition, and was the leading cause of neurological disability, globally in 1990; it is exactly sixth again in 2013 (Global Burden of Disease Study, 2015). It seems a scandal that major funders have not addressed the issue. As an example, the US National Institutes of Health – NIH-Wide Strategic Plan (https://www.nih.gov/about-nih/nih-wide-strategic-plan) identifies headache disorders and migraine as the most underfunded of all conditions when the burden of the disorder is considered; yet we await any serious attempt to resolve this conundrum. However, as we move into the 21st century there is much to be excited about as we strive to treat migraine patients with migraine medicines, as opposed, particularly in preventive management, to the rag-tag collection of hand-me-downs currently available (Goadsby and Sprenger, 2010).

Of the strategies outlined in Table 1, those targeted at calcitonin gene-related peptide (CGRP)-based mechanisms are clearly front-running in terms of both excitement and likely impact. The CGRP story is set out elsewhere in detail (Ho et al. , 2010). In brief, studies in the 1980s (Goadsby et al. , 1983; McCulloch et al. , 1986) led the authors to be interested in the question of whether neuropeptides, such as CGRP or substance P, could be used to track trigeminovascular activation in experimental animals in a manner that could be translated …
Development of Novel Aminoglycoside (NB54) with Reduced Toxicity and Enhanced Suppression of Disease-Causing Premature Stop Mutations (2009)

Nonsense mutations promote premature translational termination and represent the underlying cause of a large number of human genetic diseases. The aminoglycoside antibiotic gentamicin has the ability to allow the mammalian ribosome to read past a false-stop signal and generate full-length functional proteins. However, severe toxic side effects along with the reduced suppression efficiency at subtoxic doses limit the use of gentamicin for suppression therapy. We describe here the first systematic development of the novel aminoglycoside 2 (NB54) exhibiting superior in vitro readthrough efficiency to that of gentamicin in seven different DNA fragments derived from mutant genes carrying nonsense mutations representing the genetic diseases Usher syndrome, cystic fibrosis, Duchenne muscular dystrophy, and Hurler syndrome. Comparative acute lethal toxicity in mice, cell toxicity, and the assessment of hair cell toxicity in cochlear explants further indicated that 2 exhibits far lower toxicity than that of gentamicin.
The terahertz frontier (2011)

If we credit the integrated circuit with one thing, it should be the taming of the electromagnetic spectrum. If you want to create or capture visible photons, there are plenty of compact devices to choose from, incorporating everything from miniature photodiodes and lasers to LEDs and slim charge-coupled devices. And if you want to pick up or send a radio signal, there are a staggering number of receivers, transmitters, and antennas to suit your needs. But the IC hasn't conquered every bit of the spectrum, and one region stands out: the terahertz frontier, a range that extends from the highest frequency radio waves to the lowest frequency infrared light. Over the decades, engineers have made many attempts to create compact, solidstate devices that can harness it, but terahertz radiation has proven particularly tricky to use.
Thermoactivation of a periplasmic heat-stable enterotoxin of Escherichia coli (1983)

Strains of Escherichia coli that host a plasmid that codes for the heat-stable (ST) enterotoxin showed 160 times more extracellular enterotoxin than intracellular activity. However, when washed bacteria were sonicated and incubated at between 50 and 85 degrees C, an activity similar to that of the ST enterotoxin was detected. No such effect was present in strains lacking the plasmid, in a plasmid ST- mutant, or in chromosomal mutants that lack a cyclic AMP-linked positive regulatory system which previously were shown to yield an ST- phenotype. The thermoactivation was inhibited by iodoacetamide and N-ethylmaleimide; chloramphenicol did not affect the phenomenon. The heat-activated ST-like enterotoxin was localized in the periplasmic space. The results are discussed in relation to the export of the toxin from the periplasm to the outside of the cell.
Aspirin Use and Reduced Risk of Fatal Colon Cancer (1991)

Experiments in animals and two epidemiologic studies in humans suggest that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) may be protective against colon cancer. We tested this hypothesis in a prospective mortality study of 662,424 adults who provided information in 1982 on the frequency and duration of their aspirin use. Death rates from colon cancer were measured through 1988. The possible influence of other risk factors for colon cancer was examined in multivariate analyses for 598 case patients and 3058 matched control subjects drawn from the cohort.Death rates from colon cancer decreased with more frequent aspirin use in both men and women. The relative risk among persons who used aspirin 16 or more times per month for at least one year was 0.60 in men (95 percent confidence interval, 0.40 to 0.89) and 0.58 in women (95 percent confidence interval, 0.37 to 0.90). The risk estimates were unaffected when we excluded persons who reported at entry into the study that they had cancer, heart disease, stroke, or another condition that might influence both their aspirin use and their mortality. Adjustment for dietary factors, obesity, physical activity, and family history did not alter the findings significantly. No association was found between the use of acetaminophen and the risk of colon cancer.Regular aspirin use at low doses may reduce the risk of fatal colon cancer. Whether this is due to a direct effect of aspirin, perhaps mediated by the inhibition of prostaglandin synthesis, or to other factors indirectly associated with aspirin use is unclear.
A new high resolution color flow system using an eigendecomposition-based adaptive filter for clutter rejection (2002)

We present a new signal processing strategy for high frequency color flow mapping in moving tissue environments. A new application of an eigendecomposition-based clutter rejection filter is presented with modifications to deal with high blood-to-clutter ratio's (BCR). Additionally, a new method for correcting blood velocity estimates with an estimated tissue motion profile is detailed. The performance of the clutter filter and velocity estimation strategies are quantified using a new swept-scan signal model. In vivo color flow images are presented to illustrate the potential of the system for mapping blood flow in the microcirculation with external tissue motion.
Repetitive Transcranial Magnetic Stimulation Effects on Language Function Depend on the Stimulation Parameters (2001)

In previous studies it has been shown that picture-naming latencies can be facilitated with both suprathreshold single and repetitive transcranial magnetic stimulation (TMS/rTMS) over Wernicke's area. The aim of this study was to investigate whether low-frequency rTMS (1 Hz) or high-frequency rTMS (20 Hz) at subthreshold intensities is also capable of influencing picture naming. In 16 healthy right-hand male subjects, trains of 1 Hz or 20 Hz were applied over either Wernicke's area, Broca's area, or the primary visual cortex. The subjects had to name 20 black-and-white line drawings, which were shown immediately after rTMS and again 2 minutes later. Naming latency could be facilitated only immediately after Wernicke's area stimulation at a frequency of 20 Hz and at an intensity of 55% of the maximal stimulator output, which was more than the motor threshold. All other stimulation procedures failed to influence naming latencies. These results indicate that language functions can be facilitated in healthy subjects only by high-frequency rTMS with intensities at or above the motor threshold.
Low Molecular Weight Amidoximes that Act as Potent Inhibitors of Lysine-Specific Demethylase 1 (2012)

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides and their urea- and thiourea isosteres are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1, but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD) and transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents.
Is Random Close Packing of Spheres Well Defined? (2000)

Despite its long history, there are many fundamental issues concerning random packings of spheres that remain elusive, including a precise definition of random close packing (RCP). We argue that the current picture of RCP cannot be made mathematically precise and support this conclusion via a molecular dynamics study of hard spheres using the Lubachevsky-Stillinger compression algorithm. We suggest that this impasse can be broken by introducing the new concept of a maximally random jammed state, which can be made precise.
Monocyclic Phenolic Acids; Hydroxy- and Polyhydroxybenzoic Acids: Occurrence and Recent Bioactivity Studies (2010)

Among the wide diversity of naturally occurring phenolic acids, at least 30 hydroxy- and polyhydroxybenzoic acids have been reported in the last 10 years to have biological activities. The chemical structures, natural occurrence throughout the plant, algal, bacterial, fungal and animal kingdoms, and recently described bioactivities of these phenolic and polyphenolic acids are reviewed to illustrate their wide distribution, biological and ecological importance, and potential as new leads for the development of pharmaceutical and agricultural products to improve human health and nutrition.
Chiral Auxiliary Mediated Conjugate Reduction and Asymmetric Protonation: Synthesis of High Affinity Ligands for HIV Protease Inhibitors (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral Auxiliary Mediated Conjugate Reduction and Asymmetric Protonation: Synthesis of High Affinity Ligands for HIV Protease InhibitorsArun K. Ghosh and Wenming LiuCite this: J. Org. Chem. 1995, 60, 19, 6198–6201Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/jo00124a042https://doi.org/10.1021/jo00124a042research-articleACS PublicationsRequest reuse permissionsArticle Views480Altmetric-Citations17LEARN 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 optionsGet e-Alertsclose Get e-Alerts
A Domain and Type Enforcement UNIX Prototype. (1995)

UNIX system security today often relies on correct operation of numerous privileged subsystems and careful attention by expert system administrators. In the context of global and possibly hostile networks, these traditional UNIX weaknesses raise a legitimate question about whether UNIX systems are appropriate platforms for processing and safeguarding important information resources. Domain and Type Enforcement (DTE) is an access control technology for partitioning host operating systems such as UNIX into access control domains. Such partitioning has promise both to enforce organizational security policies that protect special classes of information and to generically strengthen operating systems against penetration attacks. This paper reviews the primary DTE concepts, discusses their application to IP networks and NFS, and then describes the design and implementation of a DTE UNIX prototype system.
Treatment of opioid-induced gut dysfunction (2007)

Opioid analgesics are the mainstay in the treatment of moderate-to-severe pain, yet their use is frequently associated with adverse effects, the most common and debilitating being constipation. Opioid-induced motor stasis results from blockade of gastrointestinal peristalsis and fluid secretion, and reflects the action of the endogenous opioid system in the gut. Methylnaltrexone and alvimopan are new investigational drugs that selectively target peripheral mu-opioid receptors because they are poorly absorbed in the intestine and do not enter the brain. Clinical studies have proved the concept that these drugs prevent opioid-induced bowel dysfunction without interfering with analgesia. As reviewed in this article, opioid receptor antagonists with a peripherally restricted site of action also hold therapeutic promise in postoperative ileus and chronic constipation due to the fact that they have been found to stimulate intestinal transit.
The ependyma: A protective barrier between brain and cerebrospinal fluid (1995)

This review summarizes the current scientific literature concerning the ependymal lining of the cerebral ventricles of the brain with an emphasis on selective barrier function and protective roles for the common ependymal cell. Topics covered include the development, morphology, protein and enzyme expression including reactive changes, and pathology. Some cells lining the neural tube are committed at an early stage to becoming ependymal cells. They serve a secretory function and perhaps act as a cellular/axonal guidance system, particularly during fetal development. In the mature mammalian brain ependymal cells possess the structural and enzymatic characteristics necessary for scavenging and detoxifying a wide variety of substances in the CSF, thus forming a metabolic barrier at the brain-CSF interface.
A comparative synthesis of the [DTrp6] LH-RH analog by the UNCA method in solution and by solid phase. (1993)

[DTrp6] LH-RH was prepared using urethane-protected alpha-amino and N-carboxyanhydrides (UNCAs) both in solution and by solid-phase methodologies. The yields and purities of the crude materials in both cases were high, as indicated by HPLC. The structures were confirmed by 1H NMR, FAB mass spectrometry and found to be identical to an authentic sample. Both synthetic samples were analytically pure by capillary zone electrophoresis.
The Mechanics of Airway Narrowing in Asthma (1989)

This study was designed to determine the potential importance of airway wall thickening in the pathogenesis of the excess airways narrowing of asthma. The airways in postmortem specimens of lung obtained from 18 patients who suffered from asthma were compared to similar airways from 23 patients without asthma. Each airway was projected onto a digitizing board of a microcomputer to trace the internal and external perimeter of the airway and to calculate the submucosal and mucosal thicknesses. The relaxed length of the airway smooth muscle and the shortening required to occlude the airway lumen were calculated. These data show that the wall area was greater (p less than 0.001) in the membranous and cartilaginous airways of asthmatic patients and the airway smooth muscle shortening required to occlude the lumen was less in asthmatic than nonasthmatic airways (p less than 0.001). The increased wall area was due to increased areas of epithelium, muscle, and submucosa. We conclude that the walls of the airways of patients with asthma are thickened by chronic inflammation and that this thickening could be as important as smooth muscle shortening in determining the airway responsiveness of these patients.
Enabling a continuum of virtual environment experiences (2003)

We define a virtual environment as a set of surroundings that appear to a user through computer-generated sensory stimuli. The level of immersion-or sense of being in another world-that a user experiences within a VE relates to how much stimuli the computer delivers to the user. Thus, one can classify VEs along a virtuality continuum, which ranges from the real world to an entirely computer-generated environment. We present a technology that allows seamless transitions between levels of immersion in VEs. Milgram and Kishino (1994) first proposed the concept of a virtuality continuum in the context of visual displays. The concept of a virtuality continuum extends to multimodal VEs, which combine multiple sensory stimuli, including 3D sound and haptic capability, leading to a multidimensional virtuality continuum. Emerging applications will benefit from multiple levels of immersion, requiring innovative multimodal technologies and the ability to traverse the multidimensional virtuality continuum.
An Efficient Fmoc‐SPPS Approach for the Generation of Thioester Peptide Precursors for Use in Native Chemical Ligation (2008)

Intramolecular activation of C-terminal peptides: Mildly activated N-acylurea peptides are readily formed on the solid support following chain assembly, avoiding over-activation of the C-terminus. The utility of these peptides is demonstrated by the native chemical ligation of unprotected peptides (see scheme; R=amino acid side chain).
Enhanced electro-optical properties in gold nanoparticles doped ferroelectric liquid crystals (2007)

Influential electro-optical and textural properties in the smectic C* phase have been observed using gold nanoparticles (Au NPs) in ferroelectric liquid crystals (FLCs). An application of mere 0.1V brings fivefold increase in optical tilt and doping creates a strong intrinsic field inside the sample generating high tilt and a reproducible observation of memory effect. The lowering of threshold voltage and the enhanced optical contrast is probably due to the interaction of electron wave oscillation in Au NPs with the incident light traversing through the FLC molecules.
Multiphoton intrapulse interference 6; binary phase shaping (2004)

We demonstrate a new approach to laser control using binary phase shaping. We apply this method to the problem of spectrally narrowing multiphoton excitation using shaped laser pulses as required for selectivity in two-photon microscopy. The symmetry of the problem is analyzed from first principles and a rational solution is proposed. Successful experimental implementation and simulations are presented using 10 fs ultrashort pulses. The proposed solution is a factor of 6 better than the sinusoidal phase used previously by our group. An evolutionary learning algorithm was used to efficiently improve the solution by a further factor of 2.5 because of the greatly reduced search space afforded by binary phase shaping.
An architecture for the Internet Key Exchange Protocol (2001)

In this paper we present the design, rationale, and implementation of the Internet Key Exchange (IKE) Protocol. This protocol is used to create and maintain Internet Protocol Security (IPSec) associations and secure tunnels in the IP layer. Secure tunnels are used to construct virtual private networks (VPNs) over the Internet. The implementation is done in the application layer. The design includes four components: (1) an IKE protocol engine to execute the IKE protocol, (2) a tunnel manager to create and manage secure tunnels—it generates requests to the IKE protocol engine to establish security associations, (3) VPN policy administration tools to manage VPN policies that guide the actions of the IKE protocol engine and the tunnel manager, and (4) a certificate proxy server to acquire and verify public key certificates that are used for authentication of messages and identities in the IKE protocol. The implementation was done on the Advanced Interactive Executive® (AIX®) operating system at IBM Research and has been transferred to IBM's AIX, Application System/400®, and System/390® products.
An in vitro Pathway from Embryonic Stem Cells to Neurons and Glia (1999)

Mouse embryonic stem (ES) cells can be induced to differentiate into neurons and glia in vitro. Induction protocols are straightforward and involve culture in the presence of retinoic acid. They result in an efficient conversion of undifferentiated ES cells to neural cells. Mature neurons produced have the key physiological, morphological and molecular properties of primary cultured neurons derived from the central nervous system. Most significantly, they form functional chemical synapses that utilize either glutamate, GABA or glycine as neurotransmitters. ES cell-derived glial cells also correspond well with their normal counterparts. During induction, ES cells undergo a series of developmental steps that resemble key stages in the early mouse embryo. This supports the hypothesis that the in vitro pathway is a valid model of the normal developmental pathway leading to neurons and glia. The in vitro system combines three experimental strengths. It is suitable for genetic manipulation, affords large numbers of cells and allows precise manipulation of the culture environment. It is thus suitable for a wide variety of mechanistic studies in the areas of neural development and cell biology.