gebhart/patrepeval huggingface dataset:
Compact holographic beam expander (1993)

A compact planar beam expander, composed of two holographic lenses that are recorded on a signal holographic plate, is presented. The smaller lens converts a narrow input beam into a diverging spherical wave at a high offaxis angle. This wave propagates toward the second lens, undergoing total internal reflections within the plate, and emerges from the larger lens as a magnified plane wave. One such expander, having a magnification of 3.5, was designed and recorded. The design and the recording procedure, along with the experimental results, are given.
Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers (2005)

The present study suggests that the NMDA antagonist model of psychosis is not overall superior to the serotonin 5-HT2A agonist model. Rather, the two classes of drugs tend to model different aspects or types of schizophrenia. The NMDA antagonist state may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5-HT2A agonist state may be a better model for psychoses of the paranoid type.
Structure of the Antimicrobial Peptide Tachystatin A (2002)

The solution structure of antimicrobial peptide tachystatin A from the Japanese horseshoe crab (Tachypleus tridentatus) was determined by two-dimensional nuclear magnetic resonance measurements and distance-restrained simulated annealing calculations. The correct pairs of disulfide bonds were also confirmed in this study. The obtained structure has a cysteine-stabilized triple-stranded beta-sheet as a dominant secondary structure and shows an amphiphilic folding observed in many membrane-interactive peptides. Interestingly, tachystatin A shares structural similarities with the calcium channel antagonist omega-agatoxin IVA isolated from spider toxin and mammalian defensins, and we predicted that omega-agatoxin IVA also have the antifungal activity. These structural comparisons and functional correspondences suggest that tachystatin A and omega-agatoxin IVA may exert the antimicrobial activity in a manner similar to defensins, and we have confirmed such activity using fungal culture assays. Furthermore, tachystatin A is a chitin-binding peptide, and omega-agatoxin IVA also showed chitin-binding activities in this study. Tachystatin A and omega-agatoxin IVA showed no structural homology with well known chitin-binding motifs, suggesting that their structures belong to a novel family of chitin-binding peptides. Comparison of their structures with those of cellulose-binding proteins indicated that Phe(9) of tachystatin A might be an essential residue for binding to chitin.
FRAG1, a gene that potently activates fibroblast growth factor receptor by C-terminal fusion through chromosomal rearrangement. (1996)

A constitutively active form of fibroblast growth factor 2 (FGFR2) was identified in rat osteosarcoma (ROS) cells by an expression cloning strategy. Unlike other tyrosine kinase receptors activated by N-terminal truncation in tumors, this receptor, FGFR2-ROS, contains an altered C terminus generated from chromosomal rearrangement with a novel gene, designated FGFR activating gene 1 (FRAG1). While the removal of the C terminus slightly activates FGFR2, the presence of the FRAG1 sequence drastically stimulates the transforming activity and autophosphorylation of the receptor. FGFR2-ROS is expressed as a unusually large protein and is highly phosphorylated in NIH 3T3 transfectants. FRAG1 is ubiquitously expressed and encodes a predicted protein of 28 kDa lacking significant structural similarity to known proteins. Epitope-tagged FRAG1 protein showed a perinuclear localization by immunofluorescence staining. The highly activated state of FGFR2-ROS appears to be attributed to constitutive dimer formation and higher phosphorylation level as well as possibly altered subcellular localization. These results indicate a unique mechanism of receptor activation by a C terminus alteration through a chromosomal fusion with FRAG1.
A blue light emitting polymer with phenylenevinylene segments in the side‐chains (1995)

Polymer‐based light emitting diodes constructed from amorphous materials with well‐defined conjugated segments and high glass transition temperatures are reproted. It is shown that grafting 4‐vinyl‐ trans ‐stilbene onto polystyrene results in side‐chain polymers with conjugated segments in the side chains which have amorphous morphologies whereas blends between a conjugated unit and a matrix polymer exhibit unwanted crystallizaion.
Gene expression of natriuretic peptide receptors in rats with DOCA-salt hypertension (1997)

In our previous studies, we found that the atrial natriuretic peptide (ANP) binding and guanylyl cyclase activity of A-type natriuretic peptide receptors (NPR-A) were upregulated in renal papillae but downregulated in vascular tissues and glomeruli of rats with deoxycorticosterone acetate (DOCA)-salt hypertension [E. Nuglozeh, G. Gauquelin, R. Garcia, J. Tremblay, and E. L. Schiffrin. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F130-F137, 1990]. To further understand the molecular significance of these regulations, we measured the relative abundance of the transcripts of NPR-A and NPR-B by Northern blot in the aorta, mesenteric arteries, adrenal cortex, renal papillae, and lungs in DOCA-salt hypertensive and control rats. In renal papillae we also examined the translation and transcription of NPR-A by ribosome loading and run-on assay. Compared with controls, the steady-state levels of mRNA for NPR-A were increased in the aorta and mesenteric arteries but were decreased in the adrenal cortex and renal papillae in DOCA-salt-treated rats. NPR-B mRNA was decreased in the aorta, mesenteric arteries, and adrenal cortex in hypertensive rats. In lungs the mRNA for both receptors was unchanged. Translation of NPR-A mRNA, as assessed by ribosome loading, was reduced in renal papillae. Transcriptional activity of its gene was not detectable in these tissues. Guanosine 3',5'-cyclic monophosphate levels generated by NPR-A in renal papillae and by NPR-A and NPR-B in the adrenal cortex, aorta, and mesenteric arteries of DOCA-salt-treated rats remained increased in hypertension. The higher NPR-A activity in the presence of a lower level of its mRNA in renal papillae and the higher NPR-B activity in the presence of a lower level of its mRNA in the vasculature, adrenal cortex, and lungs can alternatively be explained by receptor stabilization or increased receptor recycling.
Novel pharmacological activity of a vitamin (Novel pharmacological action of vitamin D) (1997)

The endocrine system to maintain calcium homeostasis involves the active vitamin D, as well as parathyloid hormone (PTH). Based on this 'classical' calcium-regulatory function, 1,25-(OH)2D3 and 1 alpha OHD3 was developed as the drug for vitamin D resistant rickets, renal dystrophy, and osteoporosis. Psoriasis is a chronic skin disease which is characterized by hyperproliferation and abnormal differentiation of epidermis. As an anti-psoriatic drug, 1,24R-(OH)2D3 has been on clinical use. The efficacy for psoriasis is explainable by the differentiation-inducing activity of this compound. 1,25-(OH)2D3 was also reported to suppress proliferation and induce differentiation of tumor cells including breast cancer, colon cancer and so forth, suggesting the possible therapy of malignant tumors. In immune system, active vitamin D3 exerts various effects; 1,25-(OH)2D3 suppresses proliferation and cytokine production in T cells and antibody production in B cells. Animal models of autoimmune diseases and skin-graft suggest active vitamin D becomes a novel immuno suppressant. Since 1,25-(OH)2D3 induces the synthesis of nerve growth factor (NGF), it will be a new therapy for the treatment of neuronal degenerative diseases.
Sketching in Air: A Single Stroke Classification Framework (2014)

We describe a trainable, hand drawn, single stroke 3D sketch–based classification system, using a motion detecting depth sense camera. Our system captures data from a user, who is free to sketch any desired shape in a 3D environment. The overall system is based on a set of previously defined and well developed classifiers, which are, the Rubine Classifier, $1 recognizer and the Image based classifier. The novelty of this paper comes from 1) the classification of sketches drawn in a 3D environment; 2) extending the pixel based image representation to a voxel–based scheme; and 3) combining the results from individual classifiers using a sensitivity matrix. To evaluate the performance of the system, user studies were performed. To validate the significance of results obtained from the user studies, we performed a t–test. Our system outperforms the individual classifiers and is able to achieve an average overall accuracy of 93+%.
Molecular Cloning of NKp46: A Novel Member of the Immunoglobulin Superfamily Involved in Triggering of Natural Cytotoxicity (1998)

NKp46 has been shown to represent a novel, natural killer (NK) cell-specific surface molecule, involved in human NK cell activation. In this study, we further analyzed the role of NKp46 in natural cytotoxicity against different tumor target cells. We provide direct evidence that NKp46 represents a major activating receptor involved in the recognition and lysis of both human and murine tumor cells. Although NKp46 may cooperate with other activating receptors (including the recently identified NKp44 molecule) in the induction of NK-mediated lysis of human tumor cells, it may represent the only human NK receptor involved in recognition of murine target cells. Molecular cloning of the cDNA encoding the NKp46 molecule revealed a novel member of the immunoglobulin (Ig) superfamily, characterized by two C2-type Ig-like domains in the extracellular portion. The transmembrane region contains the positively charged amino acid Arg, which is possibly involved in stabilizing the association with CD3zeta chain. The cytoplasmic portion, spanning 30 amino acids, does not contain immunoreceptor tyrosine-based activating motifs. Analysis of a panel of human/hamster somatic cell hybrids revealed segregation of the NKp46 gene on human chromosome 19. Assessment of the NKp46 mRNA expression in different tissues and cell types unambiguously confirmed the strict NK cell specificity of the NKp46 molecule. Remarkably, in line with the ability of NKp46 to recognize ligand(s) on murine target cells, the cDNA encoding NKp46 was found to be homologous to a cDNA expressed in murine spleen. In conclusion, this study reports the first characterization of the molecular structure of a NK-specific receptor involved in the mechanism of NK cell activation during natural cytotoxicity.
The enzymatic epimerization of deoxynivalenol by Devosia mutans proceeds through the formation of 3-keto-DON intermediate (2017)

The enzymatic detoxification of deoxynivalenol (DON) is a promising mitigation strategy for addressing this mycotoxin contamination of cereal grains. A recently described bacterium, Devosia mutans 17-2-E-8, capable of transforming DON into its non-toxic stereoisomer 3-epi-DON, holds promise for the development of such applications. Earlier observations suggested that DON epimerization proceeds via a two-step catalysis with 3-keto-DON as an intermediate. The results of this study indicate that NADPH is required for DON epimerization by cell-free protein extracts of D. mutans, while high concentrations of glucose and sucrose have a suppressive effect. Chemically synthesized 3-keto-DON incubated with D. mutans protein fractions enriched by ammonium sulfate precipitation at 35-55% saturation selectively reduced 3-keto-DON to 3-epi-DON, but fell short of supporting the complete epimerization of DON. In addition, seven Devosia species investigated for DON epimerization were all able to reduce 3-keto-DON to 3-epi-DON, but only a few were capable of epimerizing DON. The above observations collectively confirm that the enzymes responsible for the oxidation of DON to 3-keto-DON are physically separate from those involved in 3-keto-DON reduction to 3-epi-DON. The enzymatic nature of DON epimerization suggests that the process could be used to develop genetically engineered crops or microorganisms, ultimately reducing foodborne exposure of consumers and farm animals to DON.
Partial methylation of two adjacent adenosines in ribosomes fromEuglena gracilischloroplasts suggests evolutionary loss of an intermediate stage in the methyl-transfer reaction (1984)

Bacterial, cytoplasmic and organellar ribosomes from a wide phylogenetic spectrum of organisms have a characteristic m6(2)Am6(2)A structure near the 3' end of the RNA of the small ribosomal subunit (SSU). We have studied one of the few exceptions to this extremely conserved post-transcriptionally modified sequence, i.e. dimethylation of only one of the two A's in chloroplasts from Euglena gracilis. It was established that only the A closest to the 5' end is dimethylated, the other one being unmodified. The methylation reaction was studied in vitro using ribosomes from a kasugamycin resistant mutant (ksgA) of Escherichia coli and purified methyl-transferase. Using limited amounts of the methyl donor S-adenosylmethionine (SAM) a partial level of methylation (50% of control) was attained. It is shown that in this case the 3' proximal A is dimethylated while the other is not. This suggests that dimethylation takes place in two successive stages. Apparently in E. gracilis chloroplasts the first stage of methylation does not occur.
A general method for the preparation of internally quenched fluorogenic protease substrates using solid-phase peptide synthesis (1992)

A general scheme for obtaining a fluorescent donor/acceptor peptide substrate via solid-phase synthesis methodology is presented. The key feature of this method is the design of a glutamic acid derivative that has been modified on the carboxyl side chain with a 5-[(2'-aminoethyl)-amino]naphthelenesulfonic acid (EDANS) to create a fluorescent donor moiety that can be incorporated near the C-terminus of the peptide substrate. The corresponding fluorescent acceptor group containing a 4-[[4-(dimethylamino)phenyl]azo]benzoic acid (DABCYL) can then be attached to the resin-bound peptide at the N-terminus while all side-chain groups are still fully protected. Substrates for renin and HIV proteinase are synthesized as examples.
A Review and Adaptation of Methods of Object Tracking to Telemetry Capsules (2007)

Abstract This review considers techniques employing radio frequency (RF) as well as ultrasound signals for tracking. Medical capsules have been employed since the SOs to measure various physiological parameters in the human body. Examples are temperature, pH, or pressure inside the gastrointestinal (GI) tract. The development and subsequent incorporation of new technology into reasonably priced, commercially available devices have made ultrasound and RF devices readily accessible for medical diagnosis. Some applications for telemetry capsules are drug delivery, and collection of tissue/fluid samples. Samples are taken from the GI to understand or treat diseases where diagnosis can only be made by taking a biopsy from the intestinal walls. Such biopsies have traditionally been performed using customized endoscopes. In order for a telemetry capsule to be effective in the above named tasks, accurate knowledge of the location of the capsule within the body during tests is necessary. As such, methods for calculating the position of an object based on geometry, i.e. triangulation, time of flight, time difference of arrival and angle of arrival, etc, are presented in detail.
Clinical and Biological Effects of Recombinant Human Interleukin-18 Administered by Intravenous Infusion to Patients with Advanced Cancer (2006)

rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. A maximum tolerated dose of rhIL-18 was not determined. Further clinical studies of rhIL-18 are warranted.
The mechanism of U insertion/deletion RNA editing in kinetoplastid mitochondria (1997)

Recent advances in in vitrosystems and identification of putative enzymatic activities have led to the acceptance of a modified 'enzyme cascade' model for U insertion/deletion RNA editing in kinetoplastid mitochondria. Models involving the transfer of uridines (Us) from the 3'-end of gRNA to the editing site appear to be untenable. Two types of in vitrosystems have been reported: (i) a gRNA-independent U insertion activity that is dependent on the secondary structure of the mRNA; (ii) a gRNA-dependent U insertion activity that requires addition of a gRNA that can form an anchor duplex with the pre-edited mRNA and which contains guiding A and G nucleotides to base pair with the added Us. In the case of the gRNA-mediated reaction, the precise site of cleavage is at the end of the gRNA-mRNA anchor duplex, as predicted by the original model. The model has been modified to include the addition of multiple Us to the 3'-end of the 5'-cleavage fragment, followed by the formation of base pairs with the guiding nucleotides and trimming back of the single-stranded oligo(U) 3'-overhang. The two fragments, which are held together by the gRNA 'splint', are then ligated. Circumstantial in vitroevidence for involvement of an RNA ligase and an endoribonuclease, which are components of a 20S complex, was obtained. Efforts are underway in several laboratories to isolate and characterize specific components of the editing machinery.
Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD (2000)

It is unclear how cellular and soluble inflammatory markers in induced sputum relate to markers in lavage fluid and biopsies in chronic obstructive pulmonary disease (COPD). This was investigated and also the possible differences between subjects with COPD and healthy controls assessed. Eighteen nonatopic subjects with COPD and 11 healthy controls were studied. Sputum was induced by inhalation of hypertonic saline. The airways were lavaged, using the first 50 mL for bronchial wash (BW) and the subsequent 150 mL for bronchoalveolar lavage (BAL), and biopsies were taken from subsegmental carinae. Neutrophils were the predominant cell type in sputum in COPD (median 77.3%) but not in BW (5.5%) and BAL fluid (1.7%). Differential cell counts in sputum did not correlate with the counts in BW or BAL fluid or biopsies, whereas sputum eosinophil cationic protein (ECP) levels correlated with BW fluid ECP levels (p=0.66, p=0.007) and sputum interleukin-8 (IL-8) concentration with BAL fluid IL-8 concentration (p= 0.52, p=0.026). Subjects with COPD had a higher percentage of sputum neutrophils and eosinophils and higher concentrations of ECP and IL-8 than healthy controls. The higher percentages of eosinophils and concentrations of ECP were also seen in BW and BAL fluid. Finally, higher numbers of macrophages and eosinophils were found in biopsies. In conclusion, induced sputum is derived from a different compartment from BW and BAL fluid and biopsies. Induced sputum may be useful for studying the contribution of luminal neutrophils and eosinophils in chronic obstructive pulmonary disease.
Accelerated bottom-up drug design platform enables the discovery of novel stearoyl-CoA desaturase 1 inhibitors for cancer therapy (2017)

Here we present an innovative computational-based drug discovery strategy, coupled with machine-based learning and functional assessment, for the rational design of novel small molecule inhibitors of the lipogenic enzyme stearoyl-CoA desaturase 1 (SCD1). Our methods resulted in the discovery of several unique molecules, of which our lead compound SSI-4 demonstrates potent anti-tumor activity, with an excellent pharmacokinetic and toxicology profile. We improve upon key characteristics, including chemoinformatics and absorption/distribution/metabolism/excretion (ADME) toxicity, while driving the IC50 to 0.6 nM in some instances. This approach to drug design can be executed in smaller research settings, applied to a wealth of other targets, and paves a path forward for bringing small-batch based drug programs into the Clinic.
Kinetic control of Ca(II) signaling: tuning the ion dissociation rates of EF-hand Ca(II) binding sites. (1993)

EF-hand Ca(II) binding sites share a conserved architecture and are prevalent in Ca(II) signaling pathways. The ion binding kinetics of these sites are carefully tuned to provide the physiologically appropriate activation and inactivation time scales. Here we examine kinetic tuning by the side chain at the ninth position of the EF-loop. A model is proposed in which both the size and charge of the side chain contribute to kinetic tuning. To test this model, the ninth loop position of the EF-hand-like site in the Escherichia coli D-galactose binding protein has been engineered and the Tb(III) dissociation kinetics of the resulting sites have been analyzed. Substitutions at this position are observed to generate up to 10(4)-fold changes in Tb(III) dissociation rates, with little effect on Tb(III) affinity. Furthermore, the observed pattern of rate changes confirm the model's predictions; long side chains at the ninth loop position yield slow dissociation kinetics as predicted for a steric block, whereas acidic side chains yield slow dissociation kinetics as expected for an electrostatic barrier.
Tissue-Engineered Rotator Cuff Tendon Using Porcine Small Intestine Submucosa (2001)

To determine its efficacy in stimulating the regeneration of a rotator cuff tendon, an implant of 10-ply porcine small intestinal submucosa was used to replace a completely resected infraspinatus tendon in 21 adult mongrel dogs. The contralateral infraspinatus tendon was elevated and then reattached to the greater tubercle with sutures to mimic conventional repair (sham operation). Mechanical evaluations were performed at 0, 3, and 6 months (five specimens at each time period). Histologic comparisons were made at 3 and 6 months (three specimens). At both times, the gross appearance, histologic continuity, and failure mode of the constructs mimicked those of sham-operated and native infraspinatus tendons, thus suggesting host tissue ingrowth and implant remodeling with solid integration of the regenerated tissue to muscular and bony interfaces. Tissue ingrowth occurred without histologic evidence of foreign body or immune-mediated reactions or adhesions to peripheral tissues. Sham operations simulated tendon mobilization and reimplantation procedures routinely performed to treat chronic rotator cuff tendon injuries. Although the ultimate strength of small intestinal submucosa-regenerated tendons was significantly less than that of native infraspinatus tendons (P < 0.001), it was similar to that of reimplanted tendons at 3 (P > 0.05) and 6 months (P > 0.05).