gebhart/patrepeval huggingface dataset:
The pain of “chronic Lyme disease”: moving the discourse in a different direction (2011)

About 30% of the population of the United States suffers from acute or chronic pain, often of unknown cause. Among this group might be included patients with symptoms claimed to be caused by a poorly defined condition called "chronic Lyme disease" in which chronic pain is a major contributor. Since there is no evidence to indicate that chronic Lyme disease is due to a persistent infection and that extended antibiotic therapy is beneficial and safe, this condition should not be viewed solely as an infectious disease problem. Rather, it should be considered within the context of a broad-based, multidisciplinary approach to determining the cause of chronic pain per se and developing more effective strategies for its treatment as outlined in a recent report on pain issued by the Institute of Medicine.
Characterization of printable cellular micro-fluidic channels for tissue engineering (2013)

Tissue engineering has been a promising field of research, offering hope of bridging the gap between organ shortage and transplantation needs. However, building three-dimensional (3D) vascularized organs remains the main technological barrier to be overcome. One of the major challenges is the inclusion of a vascular network to support cell viability in terms of nutrients and oxygen perfusion. This paper introduces a new approach to the fabrication of vessel-like microfluidic channels that has the potential to be used in thick tissue or organ fabrication in the future. In this research, we investigate the manufacturability of printable micro-fluidic channels, where micro-fluidic channels support mechanical integrity as well as enable fluid transport in 3D. A pressure-assisted solid freeform fabrication platform is developed with a coaxial needle dispenser unit to print hollow hydrogel filaments. The dispensing rheology is studied, and effects of material properties on structural formation of hollow filaments are analyzed. Sample structures are printed through the developed computer-controlled system. In addition, cell viability and gene expression studies are presented in this paper. Cell viability shows that cartilage progenitor cells (CPCs) maintained their viability right after bioprinting and during prolonged in vitro culture. Real-time PCR analysis yielded a relatively higher expression of cartilage-specific genes in alginate hollow filament encapsulating CPCs, compared with monolayer cultured CPCs, which revealed that printable semi-permeable micro-fluidic channels provided an ideal environment for cell growth and function.
Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial. (2002)

Once-daily applications of 0.1% tazarotene cream significantly reduced multiple signs of photodamage. Plasma levels of tazarotenic acid remained below those of endogenous retinoids.
A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R (2002)

IL-23 is a heterodimeric cytokine composed of the IL-12p40 "soluble receptor" subunit and a novel cytokine-like subunit related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells. Like IL-12, IL-23 binds to the IL-12R subunit IL-12Rbeta1. However, it does not use IL-12Rbeta2. In this study, we identify a novel member of the hemopoietin receptor family as a subunit of the receptor for IL-23, "IL-23R." IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3. The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2.
The chemoattractant Trp-Lys-Tyr-Met-Val-D-Met activates eosinophils through the formyl peptide receptor and one of its homologues, formyl peptide receptor-like 1 (2002)

Whereas prokaryotes use L- and D-isomers of amino acids in their protein synthesis, eukaryotic proteins as a rule incorporate only L-isomers. Hence, D-isomers may constitute danger signals to the innate immune system. A D-methionine-containing peptide, Trp-Lys-Tyr-Met-Val-D-Met-NH(2) (WKYMVm), has been shown to be a stronger activator of neutrophils than f-Met-Leu-Phe. The aim of this study was to compare the responsiveness of eosinophils to WKYMVm with that of neutrophils. The peptide was found to induce chemotaxis and respiratory burst in eosinophils. However, it did not mobilize granule constituents, as evidenced by a lack of eosinophil cationic protein, eosinophil peroxidase, and interleukin-5 in the supernatants of stimulated eosinophils. In contrast, WKYMVm caused the release of complement receptor 3 from secretory vesicles in neutrophils. Different members of the formyl peptide receptor family were preferentially engaged by the peptide in the two classes of granulocytes: the formyl peptide receptor itself in eosinophils and formyl peptide receptor-like 1 in neutrophils.
NMR techniques for quantum control and computation (2005)

Fifty years of developments in nuclear magnetic resonance (NMR) have resulted in an unrivaled degree of control of the dynamics of coupled two-level quantum systems. This coherent control of nuclear spin dynamics has recently been taken to a new level, motivated by the interest in quantum information processing. NMR has been the workhorse for the experimental implementation of quantum protocols, allowing exquisite control of systems up to seven qubits in size. This article surveys and summarizes a broad variety of pulse control and tomographic techniques which have been developed for, and used in, NMR quantum computation. Many of these will be useful in other quantum systems now being considered for the implementation of quantum information processing tasks.
Remember that? A comparison of real-time versus retrospective recall of smoking lapses. (1997)

Research and treatment assessments often rely on retrospective recall of events. The accuracy of recall was tested using accounts of smoking lapse episodes from 127 participants who had quit smoking, and lapses and temptations were recorded in near-real time using a hand-held computer. These computer records were compared with retrospective accounts elicited 12 weeks later, with a focus on recall of lapses in 4 content domains: mood, activity, episode Triggers, and abstinence violation effects. Recall of lapses was quite poor: Average kappas for items ranged from 0.18 to 0.27. Mean profile rs assessing recall for the overall pattern of behavior were .36, .30, .33, and .44 for these domains, respectively. In recall, participants overestimated their negative affect and the number of cigarettes they had smoked during the lapse, and their recall was influenced by current smoking status. The findings suggest caution in the use of recall in research and intervention.
THE CHEMICAL STABILITY OFS-(2-ACYLTHIOETHYL) ANDS-ACYLOXYMETHYL PROTECTED THYMIDYLYL-3′,5′-THYMIDINE PHOSPHOROMONOTHIOLATES AND THEIR DEACYLATION PRODUCTS IN AQUEOUS SOLUTION (2001)

The hydrolytic stability of the S-(2-acetylthioethyl) (1a,b), S-(2-pivaloylthioethyl) (2a,b), and S-acetyloxymethyl (3a,b) protected Rp and Sp phosphoromonothiolates of 3',5'-TpT has been studied. Rather unexpectedly, an intramolecular hydroxide ion catalyzed acetyl migration from the protecting group to the nucleoside 3'- and 5'-hydroxy functions was found to compete with the intermolecular displacement of the AcSCH2CH2S- or AcOCH2S-ligand from the phosphorus atom of 1a,b and 3a,b, respectively. With the S-pivaloylthioethyl derivative 2a,b no such reaction took place. Additionally, the kinetics of the cleavage of the S-(2-mercaptoethyl) group from 4a,b, the products of enzymatic deacylation of 1a,b and 2a,b, were studied as a function of pH.
Reflection vector shading hardware (1994)

Surface reflections of an environment can be rendered in real time if hardware calculates an unnormalized reflection vector at each pixel. Conventional perspective-correct texture hardware can then be leveraged to draw high-quality reflections of an environment or specular highlights in real time. This fully accommodates area light sources, allows a local viewer to move interactively, and is especially well suited to the inspection of surface orientation and curvature. By emphasizing the richness of the incoming illumination rather than physical surface properties, it represents a new direction for real-time shading hardware.
Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin (2003)

This case adds to the limited data regarding dexmedetomidine in pediatric critical care and suggests that caution should be used when considering sedation with dexmedetomidine in patients also receiving digoxin.
The Hydrophobic Core of the Sec61 Translocon Defines the Hydrophobicity Threshold for Membrane Integration (2010)

The Sec61 translocon mediates the translocation of proteins across the endoplasmic reticulum membrane and the lateral integration of transmembrane segments into the lipid bilayer. The structure of the idle translocon is closed by a lumenal plug domain and a hydrophobic constriction ring. To test the function of the apolar constriction, we have mutated all six ring residues of yeast Sec61p to more hydrophilic, bulky, or even charged amino acids (alanines, glycines, serines, tryptophans, lysines, or aspartates). The translocon was found to be surprisingly tolerant even to the charge mutations in the constriction ring, because growth and translocation efficiency were not drastically affected. Most interestingly, ring mutants were found to affect the integration of hydrophobic sequences into the lipid bilayer, indicating that the translocon does not simply catalyze the partitioning of potential transmembrane segments between an aqueous environment and the lipid bilayer but that it also plays an active role in setting the hydrophobicity threshold for membrane integration.
Interstitial chemotherapy of the 9L gliosarcoma: controlled release polymers for drug delivery in the brain. (1993)

The administration of drugs directly into the central nervous system using polymers as drug carriers may improve the treatment of malignant brain tumors. In this study, the effect of the interstitial, localized delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) incorporated into controlled release polymers implanted adjacent to the 9L gliosarcoma was assessed in s.c. and intracranial (i.c.) models. In the s.c. experiment, the 9L gliosarcoma was implanted in the flank of rats and subsequently treated with BCNU either (a) delivered in controlled release polymers inserted adjacent to the tumor or (b) administered systemically by i.p. injections or by controlled release polymers inserted at a site distant from the tumor. The interstitial release of BCNU adjacent to the tumor in the flank resulted in a significant tumor growth delay of 16.3 days, as compared to a growth delay of 9.3 and 11.2 days obtained with the systemic administration of BCNU. In the i.c. experiment, the 9L gliosarcoma was implanted in the brain of Fischer 344 rats and treated either (a) with controlled release polymers containing BCNU inserted into the brain or (b) with the systemic i.p. administration of BCNU. The interstitial release of BCNU in the brain resulted in a significant 5.4- to 7.3-fold increased survival, compared with a 2.4-fold increased survival after the systemic administration of the same dose of BCNU. The two groups with i.c. tumors treated interstitially had 17 and 42% cures, but no long-term cures were obtained in the group treated with systemic therapy. The localized, controlled delivery of chemotherapeutic agents in the s.c. tissues and in the brain via polymeric carriers may be more effective than standard systemic chemotherapy. This approach could be used to deliver a wide variety of agents into the central nervous system to treat diverse neuropathological conditions which remain refractory to systemic therapy.
Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. (1989)

Insulin and insulin-like growth factors (IGFs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR), expressed in these cells, may mediate the mitogenic effects of these peptides. We have examined the effect of type I SR blockade on human breast cancer growth with a monoclonal antibody (alpha-IR3) that blocks the receptor binding domain. alpha-IR3 inhibited binding of 125I-IGF-I in all breast cancer cell lines tested. Binding affinity of alpha-IR3 was 2 to 5 times higher than that of IGF-I in MDA-231 (Kd 2.1 nM) and MCF-7 cells (Kd 0.6 nM), respectively. In the presence of 10% calf serum, the antibody inhibited anchorage-independent growth of six of seven breast cancer cell lines. This inhibition was reversible with excess IGF-I. In serum-free medium, alpha-IR3 blocked IGF-I-stimulated DNA synthesis in four of four breast cancer cell lines (MCF-7, ZR75-1, MDA-231, and HS578T). However, the antibody did not inhibit basal growth of any of the breast cancer cell lines in serum-free conditions. In three estrogen receptor-positive, estrogen-responsive breast cancer cell lines (MCF-7, ZR75-1, and T47D), type I SR blockade with alpha-IR3 failed to block estrogen-stimulated DNA synthesis or cell proliferation, indicating that secreted IGF activity is not the sole mediator of the growth effects of estrogen. In conclusion, antibody-mediated type I SR blockade does not inhibit basal growth of breast cancer cells under serum-free conditions, arguing against a critical autocrine role of endogenously secreted IGF activity in vitro. However, type I SR blockade inhibits breast cancer cell growth in the presence of serum, suggesting that serum IGFs might be critical endocrine or paracrine regulators of human breast cancer.
Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus (2013)

Even though highly active anti-retroviral therapy is able to keep HIV-1 replication under control, the virus can lie in a dormant state within the host genome, known as a latent reservoir, and poses a threat to re-emerge at any time. However, novel technologies aimed at disrupting HIV-1 provirus may be capable of eradicating viral genomes from infected individuals. In this study, we showed the potential of the CRISPR/Cas9 system to edit the HIV-1 genome and block its expression. When LTR-targeting CRISPR/Cas9 components were transfected into HIV-1 LTR expression-dormant and -inducible T cells, a significant loss of LTR-driven expression was observed after stimulation. Sequence analysis confirmed that this CRISPR/Cas9 system efficiently cleaved and mutated LTR target sites. More importantly, this system was also able to remove internal viral genes from the host cell chromosome. Our results suggest that the CRISPR/Cas9 system may be a useful tool for curing HIV-1 infection.
Synthesis of glycopyranosylphosphonate analogs of certain natural nucleoside diphosphate sugars as potential inhibitors of glycosyltransferases (1987)

The synthesis of alpha-D-glucopyranosyl-, alpha-D-galactopyranosyl-, and alpha-D-mannopyranosylphosphonate is described. Condensation of tris(trimethylsilyl) phosphite with 2,3,4,6-tetrakis-O-(phenylmethyl)-1-O-acetyl-alpha-D-glucopyranose generated 2,3,4,6-tetrakis-O-(phenylmethyl)-alpha-D-glucopyranosylphosphonic acetic anhydride (13). The benzyl blocking groups were removed by catalytic hydrogenation, and the anhydride bond was cleaved by alkaline hydrolysis to obtain alpha-D-glucopyranosylphosphonate (15). alpha-D-Galactopyranosylphosphonate (17) and alpha-D-mannopyranosylphosphonate (19) were also similarly synthesized. The anomeric configuration of 15 was assigned by single-crystal X-ray analysis, and the structural assignments of 17 and 19 were made on the basis of comparative NMR spectral studies. Compound 15 was then coupled with adenosine 5'-phosphoric di-n-butylphosphinothioic anhydride in dry pyridine to give adenosine 5'-phosphoric alpha-D-glucopyranosylphosphonic anhydride (23). Similarly, uridine 5'-phosphoric alpha-D-galactopyranosylphosphonic anhydride (24) and guanosine 5'-phosphoric alpha-D-mannopyranosylphosphonic anhydride (25) were synthesized from 17 and 19, respectively. With ovalbumin as an acceptor for [3H]galactose, provided by UDP-[3H]galactose, only uridine 5'-phosphoric alpha-D-galactopyranosylphosphonic anhydride (24) was shown to inhibit glycoprotein beta-D-galactosyltransferase (EC 2.4.1.38), with an apparent Ki equal to 165 microM. Even though these ionic compounds hardly penetrate the cell membrane, preliminary in vitro antitumor screening shows that compounds 23 and 25 are slightly active against human B-lymphoblastic leukemia and human T-lymphoblastic leukemia. None of these compounds show any antiviral activity.
Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals (2006)

Transient receptor potential melastatin 8 (TRPM8) is the best molecular candidate for innocuous cold detection by peripheral thermoreceptor terminals. To dissect out the contribution of this cold- and menthol-gated, nonselective cation channel to cold transduction, we identified BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide] as a potent and full blocker of recombinant TRPM8 channels. In cold-sensitive trigeminal ganglion neurons of mice and guinea pig, responses to menthol were abolished by BCTC. In contrast, the effect of BCTC on cold-evoked responses was variable but showed a good correlation with the presence or lack of menthol sensitivity in the same neuron, suggesting a specific blocking action of BCTC on TRPM8 channels. The biophysical properties of native cold-gated currents (I(cold)), and the currents blocked by BCTC were nearly identical, consistent with a role of this channel in cold sensing at the soma. The temperature activation threshold of native TRPM8 channels was significantly warmer than those reported in previous expression studies. The effect of BCTC on native I(cold) was characterized by a dose-dependent shift in the temperature threshold of activation. The role of TRPM8 in transduction was further investigated in the guinea pig cornea, a peripheral territory densely innervated with cold thermoreceptors. All cold-sensitive terminals were activated by menthol, suggesting the functional expression of TRPM8 channels in their membrane. However, the spontaneous activity and firing pattern characteristic of cold thermoreceptors was totally immune to TRPM8 channel blockade with BCTC or SKF96365 (1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride). Cold-evoked responses in corneal terminals were also essentially unaffected by these drugs, whereas responses to menthol were completely abolished. The minor impairment in the ability to transduce cold stimuli by peripheral corneal thermoreceptors during TRPM8 blockade unveils an overlapping functional role for various thermosensitive mechanisms in these nerve terminals.
Specificity Determinants in MAPK Signaling to Transcription Factors (2002)

One critical component in determining the specificity, fidelity, and efficiency of MAPK substrate phosphorylation is the presence of distinct docking domains in the substrate proteins. These docking domains are found in a range of substrates, including the transcription factors myocyte enhancer factor-2A and SAP-1. However, the sequences of these motifs differ, as does their targeting preferences by MAPKs, with SAP-1 being targeted by both the ERK and p38 isoforms, whereas myocyte enhancer factor-2A is targeted only by certain members of the p38 subfamily. Here, we have investigated the specificity determinants within these motifs and generated a model for how specificity is generated. We demonstrate that residues throughout the docking domains play important roles in the recognition process. However, residues located at different positions are important for discriminating between ERK and p38 MAPKs. Furthermore, the docking domains can be further subdivided into submotifs, which are differentially required for phosphorylation by ERK or p38 MAPKs. We have used loss- and gain-of-function mutagenesis to identify residues that discriminate between ERK and p38 MAPKs, residues that act to promote suboptimal interactions, and regions that are differentially required depending on the kinase involved. A model is proposed to explain how specificity is generated within these short docking domains.
Gilles de la Tourette's Syndrome and Obsessive-Compulsive Disorder (1986)

Previous studies have suggested that obsessive-compulsive symptoms frequently occur among patients with Gilles de la Tourette's syndrome (TS). To examine the relationship between TS and obsessive-compulsive disorder (OCD), data from all first-degree relatives of TS probands were obtained with a semistructured interview designed to collect information on the presence of TS, other tic disorders, and neuropsychiatric illnesses during the lifetime of the individual. The rate of OCD among first-degree relatives was significantly increased over estimates from the general population and a control sample of adoptive relatives. The rates of TS, OCD, and chronic multiple tics (CMT) were virtually the same in families of probands with OCD (TS +/- OCD) when compared with families of probands without OCD (TS - OCD). Finally, the frequency of OCD without TS or CMT among first-degree relatives was significantly elevated in families of both TS + OCD and TS - OCD probands, suggesting that some forms of OCD may represent an alternative expression of the factors responsible for TS and/or CMT.
Photo-displacement imaging (1981)

A modulated laser beam, incident on a surface, gives rise to a time-varying surface displacement. This displacement can be detected by means of a laser interferometer, thereby forming the basis for a novel imaging system. Preliminary results to demonstrate the viability of such a technique are presented.