gebhart/patrepeval huggingface dataset:
Visual pigment composition in zebrafish: Evidence for a rhodopsin–porphyropsin interchange system (2004)

Numerous reports have concluded that zebrafish (Danio rerio) possesses A1-based visual pigments in their rod and cone photoreceptors. In the present study, we investigated the possibility that zebrafish have a paired visual pigment system. We measured the spectral absorption characteristics of photoreceptors from zebrafish maintained in different temperature regimes and those treated with exogenous thyroid hormone using CCD-based microspectrophotometry. Rods from fish housed at 15 degrees C and 28 degrees C were not significantly different, having lambda max values of 503 +/- 5 nm (n = 106) and 504 +/- 6 nm (n = 88), respectively. Thyroid hormone treatment (held at 28 degrees C), however, significantly shifted the lambda max of rods from 503 +/- 5 nm (n = 194) to 527 +/- 8 nm (n = 212). Cone photoreceptors in fish housed at 28 degrees C (without thyroid hormone treatment) had lambda max values of 361 +/- 3 nm (n = 2) for ultraviolet-, 411 +/- 5 nm (n = 18) for short-, 482 +/- 6 nm (n = 9) for medium-, and 565 +/- 10 nm (n = 14) for long-wavelength sensitive cones. Thyroid hormone treatment of fish held at 28 degrees C significantly shifted the lambda max of long-wavelength sensitive cones to 613 +/- 11 nm (n = 20), substantially beyond that of the lambda max of the longest possible A1-based visual pigment (approximately 580 nm). Thyroid hormone treatment produced smaller shifts of lambda max in other cone types and increased the half-band width. All shifts in photoreceptor lambda max values resulting from thyroid hormone treatment matched predictions for an A1- to A2-based visual pigment system. We therefore conclude that zebrafish possess a rhodopsin-porphyropsin interchange system that functions to spectrally tune rod and cone photoreceptors. We believe that these observations should be carefully considered during analysis of zebrafish spectral sensitivity.
Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua (2019)

These findings support that prior DENV infection may protect individuals from symptomatic Zika. More research is needed to address the possible immunological mechanism(s) of cross-protection between ZIKV and DENV and whether DENV immunity also modulates other ZIKV infection outcomes such as neurological or congenital syndromes.
Imaging of Melanoma Using 64Cu− and 86Y−DOTA−ReCCMSH(Arg11), a Cyclized Peptide Analogue of α-MSH (2005)

Early detection of melanoma is essential, since a patient's prognosis with metastatic melanoma is poor. Previous studies showed that (111)In-DOTA-ReCCMSH(Arg(11)), a cyclic analogue of alpha-melanocyte stimulating hormone (alpha-MSH), exhibited high tumor concentration and rapid clearance from nontarget tissue. The goal of this current study was to label DOTA-ReCCMSH(Arg(11)) with beta(+)-emitting radionuclides, to determine if the high sensitivity of positron emission tomography (PET) imaging would aid in the detection of malignant melanoma. DOTA-ReCCMSH(Arg(11)) was labeled with (64)Cu and (86)Y. Biodistribution and small animal PET imaging were carried out in mice implanted with B16/F1 murine melanoma tumor and compared with data obtained in the same animal model with [(18)F]FDG. In both cases a subset of animals were co-injected with 20 microg of DOTA-ReCCMSH(Arg(11)) to determine if tumor concentration was receptor mediated. Tumor concentration for both the (86)Y- and (64)Cu-complexes reached a maximum at 30 min, while coadministering 20 microg of unlabeled complex reduced tumor uptake significantly. Nontarget organ concentration was considerably lower with (86)Y-DOTA-ReCCMSH(Arg(11)) than its (64)Cu analogue, except in the kidneys, where the (64)Cu complex had lower accumulation at all time points. Small animal PET images for both complexes showed the tumor could be visualized after 30 min, with the standardized uptake value (SUV) analysis following a similar trend as the biodistribution data. The data obtained suggests that DOTA-ReCCMSH(Arg(11)), when labeled with beta(+)-emitting radionuclides, has the potential for early detection of malignant melanoma by exploiting the sensitivity and high resolution of PET.
Use of Oxirane Ring-Opening Reactions for Synthesis of Ethylene-bis(indenyl) Ligands Containing Alkene Tethers (2005)

An efficient strategy is presented for the synthesis of novel bis-indenyl ligands containing alkene tethers for their further immobilization. The tether was attached to a bridge or aromatic ring of the ligand. The ligands were prepared using oxirane ring-opening reaction.
RET Is Constitutively Activated by Novel Tandem Mutations that Alter the Active Site Resulting in Multiple Endocrine Neoplasia Type 2B (2006)

Constitutive activation of the RET receptor tyrosine kinase underlies the genesis and progression of multiple endocrine neoplasia type 2 (MEN 2), a dominantly inherited cancer predisposition. Importantly, although kinase activation represents a common theme in neoplasias, not all activating mutations are functionally equivalent. Consistent with this, we ascertained a patient with classical features of MEN 2B, but lacking either of the classical mutations in RET (M918T or A883F). Instead, the patient harbors a novel pair of germ line missense mutations in cis at codons 804 and 805. We evaluated the potential physiochemical effects of these substitutions in silico, predicting both to be moderately deleterious in isolation, but severely deleterious in combination. Consistent with this postulate, we show that the identified tandem mutations (V804M/E805K) are biologically active, transforming cells in culture and that their transforming capacity in combination is distinctly synergistic. Furthermore, the V804M/E805K tandem lesion confers resistance to the small molecule receptor tyrosine kinase inhibitor, PP1, suggesting a mode of action distinct from that known for classical MEN 2B mutations. To address this question, we used homology molecular modeling in silico to model the active site of RET. We predict that RET804 constitutes a critical gatekeeper residue that, when mutated in combination with RET805, induces a conformational change in the hinge region that locks the active site in a position permissive for ATP hydrolysis. Our findings have implications both in the clinic and in the successful development of novel kinase-targeted anticancer drugs.
Analysis of multilayer semiconductor rib waveguides with high refractive index substrates (1993)

The waveguiding properties of semiconductor rib waveguides with high refractive index substates are studied using the spectral index method. The propagation constants of leaky modes in such two-dimensional structures are calculated for the first time. The method is applied to the design of high wall GaAs/AlGaAs rib waveguides. Results indicate that the number of low-loss modes can be controlled by careful positioning of the substrate relative to the guiding region.
Effects of Enactment of Legislative (Public) Smoking Bans on Voluntary Home Smoking Restrictions: A Review (2016)

Findings converge in dispelling notions of displacement of smoking into the home as a consequence of legislative bans that prohibit smoking in public spaces. Evidence from the studies reviewed suggests that through their influence on social norms, legislative bans on smoking in public places may encourage citizens to establish voluntary home smoking restrictions, thus decreasing harm related to secondhand smoke.
Server-side object recognition and client-side object tracking for mobile augmented reality (2010)

In this paper we present a system for mobile augmented reality (AR) based on visual recognition. We split the tasks of recognizing an object and tracking it on the user's screen into a server-side and a client-side task, respectively. The capabilities of this hybrid client-server approach are demonstrated with a prototype application on the Android platform, which is able to augment both stationary (landmarks) and non stationary (media covers) objects. The database on the server side consists of hundreds of thousands of landmarks, which is crawled using a state of the art mining method for community photo collections. In addition to the landmark images, we also integrate a database of media covers with millions of items. Retrieval from these databases is done using vocabularies of local visual features. In order to fulfill the real-time constraints for AR applications, we introduce a method to speed-up geometric verification of feature matches. The client-side tracking of recognized objects builds on a multi-modal combination of visual features and sensor measurements. Here, we also introduce a motion estimation method, which is more efficient and precise than similar approaches. To the best of our knowledge this is the first system, which demonstrates a complete pipeline for augmented reality on mobile devices with visual object recognition scaled to millions of objects combined with real-time object tracking.
Positive pressure therapy for Ménière's disease or syndrome (2015)

There is no evidence, from five included studies, to show that positive pressure therapy is effective for the symptoms of Ménière's disease. There is some moderate quality evidence, from two studies, that hearing levels are worse in patients who use this therapy. The positive pressure therapy device itself is minimally invasive. However, in order to use it, a tympanostomy tube (grommet) needs to be inserted, with the associated risks. These include the risks of anaesthesia, the general risks of any surgery and the specific risks of otorrhoea and tympanosclerosis associated with the insertion of a tympanostomy tube. Notwithstanding these comments, no complications or adverse effects were noted in any of the included studies.
Cyclic Tensile Culture Promotes Fibroblastic Differentiation of Marrow Stromal Cells Encapsulated in Poly(Ethylene Glycol)-Based Hydrogels (2010)

To inform future efforts in tendon/ligament tissue engineering, our laboratory has developed a well-controlled model system with the ability to alter both external tensile loading parameters and local biochemical cues to better understand marrow stromal cell differentiation in response to both stimuli concurrently. In particular, the synthetic, poly(ethylene glycol)-based hydrogel material oligo(poly(ethylene glycol) fumarate) (OPF) has been explored as a cell carrier for this system. This biomaterial can be tailored to present covalently incorporated bioactive moieties and can be loaded in our custom cyclic tensile bioreactor for up to 28 days with no loss of material integrity. Human marrow stromal cells encapsulated in these OPF hydrogels were cultured (21 days) under cyclic tensile strain (10%, 1 Hz, 3 h of strain followed by 3 h without) or at 0% strain. No difference was observed in cell number due to mechanical stimulation or across time (n = 4), with cells remaining viable (n = 4) through 21 days. Cyclic strain significantly upregulated all tendon/ligament fibroblastic genes examined (collagen I, collagen III, and tenascin-C) by day 21 (n ≥ 6), whereas genes for other pathways (osteogenic, chondrogenic, and adipogenic) did not increase. After 21 days, the presence of collagen I and tenascin-C was observed via immunostaining (n = 2). This study demonstrates the utility of this hydrogel/bioreactor system as a versatile, yet well-controlled, model environment to study marrow stromal cell differentiation toward the tendon/ligament phenotype under a variety of conditions.
Introduction of Recombinant DNA into Clostridium spp. (2003)

The importance of the Clostridia both in terms of their pathogenicity toward humans and their potential role in biotechnological processes has prompted many studies of the genetic manipulation of these organisms. Obviously, a prerequisite for such studies is a means of introducing recombinant DNA into individual viable cells, and the first reports of successful plasmid transformation involved use of protoplasts or L-forms (1–4), or conjugal cointegrate transfer techniques (5,6). However, these methods proved tedious or time-consuming to perform, and sometimes gave inconsistent results. Some workers suggested that it was the presence of DNases produced by many species of Clostridium that contributed to the low or inconsistent transformation efficiencies obtained by these methods (7,8). Even so, protoplast transformation is still used routinely and successfully for the introduction of shuttle plasmids into Clostridium acetobutylicum (e.g., 9).
Zolpidem-induced Psychiatric Symptoms (2006)

Objective: Zolpidem is considered a safe and effective hypnotic agent for the short-term treatment of insomnia. Sporadic cases of zolpidem-induced psychiatric symptoms, however, such as somnambulism, delirium or psychotic symptoms have been reported. We report 10 additional cases with zolpidem-induced psychiatric symptoms in patients from a single psychiatric clinic. These cases illustrate the need for clinicians to carefully monitor patients for adverse events associated with zolpidem. Case reports: We identified 10 patients with zolpidem-induced psychiatric symptoms from a review of medical records between June 2002 and February 2003. Among these patients, three had amnesia, three had somnambulism, three had symptoms of delirium and one had psychotic symptoms. Two of these patients had exhibited dangerous behaviors towards their family members. All of these patients denied any history of above psychiatric problems before the use of zolpidem as well as any recurrence after discontinuation. Conclusion: Zolpidem may induce amnesia, somnambulism, delirium or psychotic symptoms in a small percentage of patients. Careful monitoring of these potential adverse events and alerting of patients to their possible occurrence is warranted.
Preclinical Pharmacology of Albumin-Free B-Domain Deleted Recombinant Factor VIII (2002)

A second-generation recombinant factor VIII molecule was developed with an albumin-free formulation. In this modified form of factor VIII, the N- and C-terminal sections of the B-domain are retained and fused at serine 743 and glutamine 1638, resulting in a B-domain deleted factor VIII protein known as ReFacto (Genetics Institute, Andover, MA). Preclinical studies of ReFacto have focused on efficacy of the product for the hemophilia A patient population. The efficacy and pharmacokinetic profiles of ReFacto were similar to plasma-derived factor VIII in correcting the hemostatic defect of hemophilia A dogs. Both ReFacto and plasma-derived human factor VIII (Octonativ-M7, Pharmacia, Stockholm, Sweden) were found to associate with von Willebrand factor (vWF) after infusion into hemophilia A dogs as demonstrated by size exclusion chromatography. Infusion of either ReFacto or Octonativ-M7 quickly corrected factor VIII coagulant activity (FVIIIc), whole blood clotting time (WBCT), and activated partial thromboplastin time (aPTT). No obvious differences were seen between ReFacto and Octonativ-M7. Both ReFacto and Octonativ-M7 treatment reduced secondary bleeding time to less than 6 minutes. The clearance was faster and the volume of distribution at steady state was larger for plasma-derived factor VIII compared with ReFacto. The half-life was similar between Octonativ-M7 and ReFacto. These data predict that ReFacto will be effective in correcting human factor VIII deficiency states.
Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. (1989)

Denaturing gradient gel electrophoresis (DGGE) can be used to distinguish two DNA molecules that differ by as little as a single-base substitution. This method detects approximately 50% of all possible single-base changes in DNA fragments ranging from 50 to approximately 1000 base pairs. To increase the number of single-base changes that can be distinguished by DGGE, we used the polymerase chain reaction to attach a 40-base-pair G + C-rich sequence, designated a GC-clamp, to one end of amplified DNA fragments that encompass regions of the mouse and human beta-globin genes. We show that this GC-clamp allows the detection of mutations, including the hemoglobin sickle (HbS) and hemoglobin C (HbC) mutations within the human beta-globin gene, that were previously indistinguishable by DGGE. In addition to providing an easy way to attach a GC-clamp to genomic DNA fragments, the polymerase chain reaction technique greatly increases the sensitivity of DGGE. With this approach, DNA fragments derived from less than 5 ng of human genomic DNA can be detected by ethidium bromide staining of the gel, obviating the need for radioactive probes. These improvements extend the applicability of DGGE for the detection of polymorphisms and mutations in genomic and cloned DNA.
Cell-Mediated Immunity and Antibody Responses Elicited by Attenuated Salmonella enterica Serovar Typhi Strains Used as Live Oral Vaccines in Humans (2007)

The development of improved typhoid vaccines is a high global public health priority. However, their development has been hampered by a lack of information regarding the specific determinants of protective immunity to Salmonella enterica serovar Typhi (S. Typhi) infection in humans. Although antibodies to S. Typhi O, H, and Vi appear to be involved in protection against S. Typhi infection, it is unknown whether such antibodies mediate protection, act in conjunction with other adaptive responses, or serve as a surrogate for the presence of other, more dominant protective immune responses (e.g., cell-mediated immunity [CMI]). CMI responses elicited by immunization of subjects with attenuated S. Typhi oral vaccines include lymphoproliferation; production of type 1 cytokines (e.g., interferon- gamma and tumor necrosis factor- alpha ); and classical major histocompatibility complex (MHC) class Ia-restricted and novel, nonclassical MHC class Ib (human leukocyte antigen [HLA]-E)-restricted CD8(+) cytotoxic T cell responses. In sum, human immunity to S. Typhi elicited by immunization is unexpectedly broad and complex. However, the immunologic correlates of protection remain largely undefined.
Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by oxysterol by-products of cholesterol biosynthesis. Possible mediators of low density lipoprotein action. (1984)

Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34, reductase) activity was studied in cultured rat intestinal epithelial cells using 3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one ( U18666A ), an inhibitor of 2,3- oxidosqualene cyclase (EC 5.4.99.7, cyclase) that causes cellular accumulation of squalene 2,3:22,23-dioxide ( Sexton , R. C., Panini , S.R., Azran , F., and Rudney , H. (1983) Biochemistry 22, 5687-5692). Treatment of cells with U18666A (5-50 ng/ml) caused a progressive inhibition of reductase activity. Further increases in the level of the drug paradoxically lessened the inhibition such that at a level of 1 microgram/ml, no inhibition of enzyme activity was observed. Cellular metabolism of squalene 2,3:22,23-dioxide to compounds with the chromatographic properties of polar sterols led to an inhibition of reductase activity that could be prevented by U18666A (1 microgram/ml). The drug was unable to prevent the inhibition of enzyme activity by 25-hydroxycholesterol or mevalonolactone, but totally abolished the inhibitory action of low density lipoproteins. Pretreatment with U18666A did not affect the ability of cells to degrade either the apoprotein or the cholesteryl ester component of low density lipoproteins. These results suggest that oxysterols derived from squalene 2,3:22,23-dioxide may act as physiological regulators of reductase and raise the possibility that the suppressive action of low density lipoproteins on reductase may be partially or wholly mediated by such endogenous oxysterols generated through incomplete inhibition of the cyclase.
CcpA-Dependent Carbon Catabolite Repression in Bacteria (2003)

Carbon catabolite repression (CCR) by transcriptional regulators follows different mechanisms in gram-positive and gram-negative bacteria. In gram-positive bacteria, CcpA-dependent CCR is mediated by phosphorylation of the phosphoenolpyruvate:sugar phosphotransferase system intermediate HPr at a serine residue at the expense of ATP. The reaction is catalyzed by HPr kinase, which is activated by glycolytic intermediates. In this review, the distribution of CcpA-dependent CCR among bacteria is investigated by searching the public databases for homologues of HPr kinase and HPr-like proteins throughout the bacterial kingdom and by analyzing their properties. Homologues of HPr kinase are commonly observed in the phylum Firmicutes but are also found in the phyla Proteobacteria, Fusobacteria, Spirochaetes, and Chlorobi, suggesting that CcpA-dependent CCR is not restricted to gram-positive bacteria. In the alpha and beta subdivisions of the Proteobacteria, the presence of HPr kinase appears to be common, while in the gamma subdivision it is more of an exception. The genes coding for the HPr kinase homologues of the Proteobacteria are in a gene cluster together with an HPr-like protein, termed XPr, suggesting a functional relationship. Moreover, the XPr proteins contain the serine phosphorylation sequence motif. Remarkably, the analysis suggests a possible relation between CcpA-dependent gene regulation and the nitrogen regulation system (Ntr) found in the gamma subdivision of the Proteobacteria. The relation is suggested by the clustering of CCR and Ntr components on the genome of members of the Proteobacteria and by the close phylogenetic relationship between XPr and NPr, the HPr-like protein in the Ntr system. In bacteria in the phylum Proteobacteria that contain HPr kinase and XPr, the latter may be at the center of a complex regulatory network involving both CCR and the Ntr system.
Structural Basis for the Potent Antisickling Effect of a Novel Class of Five-Membered Heterocyclic Aldehydic Compounds (2004)

Naturally occurring five-membered heterocyclic aldehydes, including 5-hydroxymethyl-2-furfural, increase the oxygen affinity of hemoglobin (Hb) and strongly inhibit the sickling of homozygous sickle red blood (SS) cells. X-ray studies of Hb complexed with these compounds indicate that they form Schiff base adducts in a symmetrical fashion with the N-terminal alphaVal1 nitrogens of Hb. Interestingly, two cocrystal types were isolated during crystallization experiments with deoxygenated Hb (deoxyHb): one crystal type was composed of the low-affinity or tense (T) state Hb quaternary structure; the other crystal type was composed of high-affinity or relaxed state Hb (with a R2 quaternary structure). The R2 crystal appears to be formed as a result of the aldehydes binding to fully or partially ligated Hb in the deoxyHb solution. Repeated attempts to crystallize the compounds with liganded Hb failed, except on rare occasions when very few R state crystals were obtained. Oxygen equilibrium, high performance liquid chromatography (HPLC), antisickling, and X-ray studies suggest that the examined heterocyclic aldehydes may be acting to prevent polymerization of sickle hemoglobin (HbS) by binding to and stabilizing liganded Hb in the form of R2 and/or various relaxed state Hbs, as well as binding to and destabilizing unliganded T state Hb. The proposed mechanism may provide a general model for the antisickling effects of aldehyde containing small molecules that bind to N-terminal alphaVal1 nitrogens of Hb. The examined compounds also represent a new class of potentially therapeutic agents for treating sickle cell disease (SCD).