gebhart/patrepeval huggingface dataset:
Bicyclic Tripeptide Mimetics with Reverse Turn Inducing Properties (1999)

Analogues of the hypertensive octapeptide angiotensin II, comprising novel constrained 5,8-bicyclic and 5,9-bicyclic tripeptide units adopting nonclassical beta-turn geometries, as deduced from theoretical conformational analysis, have been synthesized. Spontanous bicyclization upon acid-catalyzed deprotection of a model peptide, encompassing a protected omega-formyl alpha-amino acid in position 5 and cysteine residues in positions 3 and 7, revealed a strong preference for bicyclization toward the C-terminus. The bicyclic thiazolidine related angiotensin II analogues synthesized exhibited no affinity for the angiotensin II AT1 receptor.
Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent Phosphorylation of Chk1 on Ser-317 in Response to Ionizing Radiation (2003)

In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2. In mammalian cells, evidence has been presented that Chk1 is devoted to the ATR signaling pathway and is modified by ATR in response to replication inhibition and UV-induced damage, whereas Chk2 functions primarily through ATM in response to ionizing radiation (IR), suggesting that Chk2 and Chk1 might have evolved to channel the DNA damage signal from ATM and ATR, respectively. We demonstrate here that the ATR-Chk1 and ATM-Chk2 pathways are not parallel branches of the DNA damage response pathway but instead show a high degree of cross-talk and connectivity. ATM does in fact signal to Chk1 in response to IR. Phosphorylation of Chk1 on Ser-317 in response to IR is ATM-dependent. We also show that functional NBS1 is required for phosphorylation of Chk1, indicating that NBS1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. Abrogation of Chk1 expression by RNA interference resulted in defects in IR-induced S and G(2)/M phase checkpoints; however, the overexpression of phosphorylation site mutant (S317A, S345A or S317A/S345A double mutant) Chk1 failed to interfere with these checkpoints. Surprisingly, the kinase-dead Chk1 (D130A) also failed to abrogate the S and G(2) checkpoint through any obvious dominant negative effect toward endogenous Chk1. Therefore, further studies will be required to assess the contribution made by phosphorylation events to Chk1 regulation. Overall, the data presented in the study challenge the model in which Chk1 only functions downstream from ATR and indicate that ATM does signal to Chk1. In addition, this study also demonstrates that Chk1 is essential for IR-induced inhibition of DNA synthesis and the G(2)/M checkpoint.
A self-migration method for preparation of sperm for in-vitro fertilization (1987)

Human sperm samples (n = 211) were prepared for in-vitro fertilization (IVF) and embryo transfer by a self-migration procedure in Earle's medium containing highly purified hyaluronic acid (Hya) (MW 3,000,000) included to increase the viscosity of the medium. The method resulted in the recovery of a significantly higher percentage of motile spermatozoa compared with the traditional centrifugation method, 87.5 +/- 0.9% versus 76.1 +/- 1.3% (P less than 0.001). When comparing media with and without Hya in the self-migration method for preparation of normal sperm samples, the media containing Hya resulted in the recovery of a significantly higher percentage of motile spermatozoa, 89.0 +/- 0.8% versus 73.8 +/- 2.0% (P less than 0.001). In a group of 80 consecutive couples entering our IVF programme, sperm samples from 44 of the men were allocated at random for the self migration method in medium containing Hya and sperm samples from 36 men for preparation by centrifugation and swim-up. Significantly more pregnancies were achieved in the group prepared in medium containing Hya. It is concluded that self-migration of sperm in a medium containing Hya is simple and rapid, and results in a high recovery of motile spermatozoa which can be used for in-vitro insemination of human oocytes with favourable results.
Studying copy number variations using a nanofluidic platform (2008)

Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). All these approaches are limited in resolution and can at best distinguish a twofold (or 50%) difference in copy number. We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. We have evaluated the digital array's performance using a model system, to show that this technology is exquisitely sensitive, capable of differentiating as little as a 15% difference in gene copy number (or between 6 and 7 copies of a target gene). We have also analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were consistent with those obtained independently using conventional techniques. In a screening experiment with breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in about 35% of breast cancer samples. The use of the digital array enables accurate measurement of gene copy numbers and is of significant value in CNV studies.
IonCCD™ for Direct Position-Sensitive Charged-Particle Detection: from Electrons and keV Ions to Hyperthermal Biomolecular Ions (2011)

A novel, low-cost, pixel-based detector array (described elsewhere Sinha and Wadsworth (76(2), 1) is examined using different charged particles, from electrons to hyperthermal (<100 eV) large biomolecular positive and negative ions, including keV small atomic and molecular ions. With this in mind, it is used in instrumentation design (beam profiling), mass spectrometry, and electron spectroscopy. The array detector is a modified light-sensitive charge-coupled device (CCD) that was engineered for direct charged-particle detection by replacing the semiconductor part of the CCD pixel with a conductor Sinha and Wadsworth (76(2), 1). The device is referred to as the IonCCD. For the first time, we show the direct detection of 250-eV electrons, providing linearity response of the IonCCD to the electron beam current. We demonstrate that the IonCCD detection efficiency is virtually independent from the particle energy (250 eV, 1250 eV), impact angle (45(o), 90(o)) and flux. By combining the IonCCD with a double-focusing sector field mass spectrometer (MS) of Mattauch-Herzog geometry (MH-MS), we demonstrate fast data acquisition. Detection of hyperthermal biomolecular ions produced using an electrospray ionization source (ESI) is also presented. In addition, the IonCCD was used as a beam profiler to characterize the beam shape and intensity of 15 eV protonated and deprotonated biomolecular ions at the exit of an rf-only collisional quadrupole. This demonstrates an ion-beam profiling application for instrument design. Finally, we present simultaneous detection of 140 eV doubly protonated biomolecular ions when the IonCCD is combined with the MH-MS. This demonstrates the possibility of simultaneous separation and micro-array deposition of biological material using a miniature MH-MS.
Monitoring Structural Changes of Proteins in an Ion Trap over ∼10−200 ms:  Unfolding Transitions in Cytochrome c Ions (2001)

A new technique for studying the time dependence of conformational changes of gas-phase protein ions is described. In this approach, a short pulse of electrosprayed protein ions is introduced into an ion trap and stored. After a defined time period, the distribution of ions is ejected from the trap into an ion mobility/time-of-flight mass spectrometer. Combined measurements of mobilities and flight times in the mass spectrometer provide information about the abundances of different conformer types and charge-state distributions. By varying the storage time in the trap, it is possible to monitor changes in ion conformation that occur over extended time periods (approximately 10-200 ms). The method is demonstrated by examining changes in cytochrome c ion conformations for the +7 to +10 charge states.
Palladium‐Catalyzed Substitution of Allylic Fluorides (2009)

As unusual substrates for the Tsuji-Trost allylation reaction, allylic fluorides are responsive to palladium-catalyzed substitution. Their activity towards this reaction fits in the series OCO(2)Me>OBz>>F>>OAc. The classic stereoretention mechanism that involves sequential inversions does not operate in this case. Several distinct cases are considered.
Stabilizing PdII on hollow magnetic mesoporous spheres: a highly active and recyclable catalyst for carbonylative cross-coupling and Suzuki coupling reactions (2013)

A hollow magnetic mesoporous silica sphere (HMMS) catalyst has been synthesized using polystyrene microspheres as a chemical template. The catalyst was characterized by TEM, XRD, XPS and vibrating sample magnetometry (VSM). The catalyst shows high activity for the carbonylative cross-coupling reaction of aryl iodides with arylboronic acids and Suzuki coupling reactions. The newly developed catalyst is easy to recover by magnetic separation from the liquid phase of the reaction and can be recycled. Importantly, the catalyst revealed high efficiency and high stability under the reaction conditions and during recycling stages.
Application, Predictive Test, and Strategy Implications for a Dynamic Model of Consumer Response (1982)

This paper describes and evaluates the application of a dynamic stochastic model of consumer response. The model describes, then forecasts, how consumers respond to a new transportation service and to the marketing strategies used during its introduction. The model is estimated on survey data during the first 11 weeks of service. Forecasts over the next 19 weeks are then compared to actual ridership as measured by dispatch records. The model is simple. At any point in time, consumers are described by a set of “behavioral states”, indicating (1) whether they are aware of the new service (DART) and (2) what mode of transportation was used for their last trip. Behavior is described by movement among behavioral states. E.G., If a car user tries DART, he makes a transition from ‘car used for last trip’ to ‘DART used for last trip’. The transition probabilities and the rate of transition are dependent on marketing strategies (direct mail, publicity), word of mouth, consumer perceptions, availability of a mode, and budget allocation to transportation. The advantages and disadvantages of the model and the measurements are discussed with respect to predictive ability and managerial utility.
Automating the design of graphical presentations of relational information (1986)

The goal of the research described in this paper is to develop an application-independent presentation tool that automatically designs effective graphical presentations (such as bar charts, scatter plots, and connected graphs) of relational information. Two problems are raised by this goal: The codification of graphic design criteria in a form that can be used by the presentation tool, and the generation of a wide variety of designs so that the presentation tool can accommodate a wide variety of information. The approach described in this paper is based on the view that graphical presentations are sentences of graphical languages. The graphic design issues are codified as expressiveness and effectiveness criteria for graphical languages. Expressiveness criteria determine whether a graphical language can express the desired information. Effectiveness criteria determine whether a graphical language exploits the capabilities of the output medium and the human visual system. A wide variety of designs can be systematically generated by using a composition algebra that composes a small set of primitive graphical languages. Artificial intelligence techniques are used to implement a prototype presentation tool called APT (A Presentation Tool), which is based on the composition algebra and the graphic design criteria.
Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies. (1991)

The use of 188Re from an alumina-based 188W/188Re generator has been investigated for antibody radiolabeling. It was found that, with simple labeling techniques, 188Re can be used immediately after elution. The direct radiolabeling of intact antibodies with 188Re is described. Lyophilized antibody preparations have been reconstituted with 188Re taken directly from the generator at specific activities of up to 15 mCi of 188Re per mg of antibody. Radiolabeling yields of 90 to 98% have been obtained, with the incorporation rate being dependent upon time and the relative concentrations of the reagents. It was determined that the conjugates were immunoreactive and stable when challenged by serum in vitro, with 188Re-immunoglobulin G showing adequate resistance to reoxidation with no transfer of 188Re to serum protein. 188Re-antibody conjugates were shown to clear from the blood faster than the corresponding 131I-labeled antibody, giving rise to good tumor/nontumor ratios at 24 to 72 h postinjection, while serum samples taken from the animals have shown that the circulating 188Re remained bound to immunoglobulin G. The combination of the technologies of the 188W/188Re generator, the direct labeling methodology, and the use of single-vial lyophilized antibody makes the use of 188Re-radiolabeled monoclonal antibodies a simple and convenient method of cancer radioimmunotherapy with a beta-emitting radionuclide.
The Amino Acid Sequence of Peptide (1–24) of Rat and Human Serum Albumins (1969)

The amino-terminal fragment, comprising the tist 24 residues, has been isolated from rat and human serum albumins after limited peptic digestion.The complete sequence of each fragment has been deduced from the tryptic peptides alone by taking advantage of overlapping peptides resulting from incomplete cleavage.A comparison of the structure of the (l-24) peptides of rat and human albumins with that obtained from bovine serum albumin (J.Biol.Chem., 242, 5451 (1967)) indicates a high degree of shnilarity.The rat fragment difIers from the bovine at three sites, whereas the human fragment differs at four sites.There is a single replacement at Residue 2 common to the rat and human peptides.Because production of this fragment by limited proteolysis must be indicative of certain conformational parameters in the region of Residue 24, it may be concluded that the rat, human, and bovine serum albumin molecules are closely homologous in primary and three-dimensional structure in the amino-terminal region.
Numerical Taxonomy of Mycobactin-Dependent Mycobacteria, Emended Description of Mycobacterium avium, and Description of Mycobacterium avium subsp. avium subsp. nov., Mycobacterium avium subsp. paratuberculosis subsp. nov., and Mycobacterium avium subsp. silvaticum subsp. nov. (1990)

We performed a numerical taxonomy analysis of 38 Mycobacterium paratuberculosis and related mycobacterial strains, including wood pigeon mycobacteria; this analysis was based on 22 tests, which were selected for their potential discriminative value from a total of 51 tests studied and produced four well-defined clusters. Cluster 1 contained the M. paratuberculosis strains, including two strains isolated from Crohn's disease patients; cluster 2 contained Mycobacterium avium and Mycobacterium intracellulare reference strains; cluster 3 consisted of the wood pigeon mycobacteria; and the only strain in cluster 4 was M. paratuberculosis 316F, which is used for antigen and vaccine production. Strains in cluster 1 were mycobactin dependent even when they were subcultured, whereas strains in cluster 3 were unable to grow on egg medium and their growth was stimulated by pH 5.5. Growth stimulation by pyruvate, resistance to D-cycloserine (50 micrograms/ml), and alkaline phosphatase activity also were characteristics that were useful for discriminating between clusters 1 and 3. The results of previous DNA-DNA hybridization studies have demonstrated that M. avium Chester 1901, M. paratuberculosis Bergey et al. 1923, and the wood pigeon mycobacteria belong to a single genomic species, and we propose that the name of this species should be M. avium. On the basis of the results of previous genomic analyses based on restriction fragment length, the results of polymorphism studies, and DNA patterns determined by field inversion gel electrophoresis as well as the results of our phenotypic study, we propose that the species should be divided into subspecies which correspond to pathogenicity and host range characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthesis of tunichromes mm-l and mm-2, blood pigments of the iron.Assimilating tunicate, molgula manhattensis (1990)

Unstable poly-phenolic pigments, tunichromes Mm-1 and Mm-2, blood pigments of the iron-assimilating tunicate, Molgula manhattensis, have been synthesized by a modified versatile route.
Lasing at three-dimensionally quantum-confined sublevel of self-organized In/sub 0.5/Ga/sub 0.5/As quantum dots by current injection (1995)

A laser oscillation from self-organized In/sub 0.5/Ga/sub 0.5/As quantum dots is achieved at 80 K by current injection. Lasing at a three-dimensionally quantum confined sublevel of the In/sub 0.5/Ga/sub 0.5/As quantum dots is clearly demonstrated for the first time by electroluminescence and diamagnetic energy shift measurement. The results predict the possibility of ultra-low threshold current operation of quantum dot lasers.
Correlation Between Wound Temperature Obtained With an Infrared Camera and Clinical Wound Bed Score in Venous Leg Ulcers. (2015)

The results obtained in this preliminary research suggest that this correlation is worth being further investigated with a larger dataset.
Tardive dyskinesia and phenylalanine metabolism: risk-factor studies (1996)

Continuing research on tardive dyskinesia has considerably broadened the classic hypothesis of dopamine-receptor supersensitivity, proposed more than 20 years ago (Klawans, 1973). Roles for other neurotransmitter systems (GABA and norepinephrine) have been postulated (Tamminga, Crayton, & Chase, 1979; Wagner et al., 1982; Fibiger & Lloyd, 1984; Gunne, Haggstrom, & Sjoquist, 1984; Jeste, Doongaji, & Linnoila, 1984; Stahl et al., 1985; Kaufman et al., 1986; Thaker et al., 1987; Andersson et al., 1989; Thaker, Nguyen, & Tamminga, 1989), and there is a newer hypothesis suggesting that cellular damage mediated by free radicals underlies tardive dyskinesia (Lohr et al., 1988, 1990; Cadet & Lohr, 1989). Demographic and psychiatric variables, such as gender, age, and concomitant affective disorder, have also been identified as risk factors (Smith & Baldessarini, 1980; Jeste & Wyatt, 1982; Kane & Smith, 1982; Richardson et al., 1985; Kane et al., 1986; Weiner & Lang, 1989). Increasingly, these disparate variables support the concept that tardive dyskinesia, like most brain dysfunctions, may involve multiple abnormalities and that vulnerability to it may be multifactorial. In this chapter we summarize our findings concerning risk factors for tardive dyskinesia that suggest that amino acid metabolism – particularly that of the large neutral amino acid phenylalanine (Phe) – may play a role in vulnerability to tardive dyskinesia.
Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers (2009)

Tumor development is a complex and dynamic process that involves malignant, vascular, and stromal cells. Endosialin is a tumor endothelial marker (TEM) present in the microvasculature and stroma of human tumors. Cancer-associated fibroblasts (CAF) have been implicated in promoting tumor development and have been associated with mesenchymal stem cells (MSC). Since stem/progenitor cells recruited either from bone marrow or residing in nearby tissues can contribute to pathological processes we investigated endosialin in MSC using a novel monoclonal antibody. Endosialin is highly expressed by CAF and human bone marrow-derived MSC. MSC can form networks in a tube formation assay that is inhibited by an anti-endosialin antibody. Immunohistochemistry for human endosialin in xenograft tumors following co-injection of MSC and cancer cells identified MSC in tumor stroma. MSC are a potential target for anticancer therapeutic intervention and endosialin expression offers a new tool for the identification of MSC. Endosialin expression by both CAF and MSC further implies the potential contribution of MSC to tumor stroma via differentiation into tumor stromal fibroblasts.
Comparative analysis of chimeric ZFP-, TALE- and Cas9-piggyBac transposases for integration into a single locus in human cells (2017)

Integrating DNA delivery systems hold promise for many applications including treatment of diseases; however, targeted integration is needed for improved safety. The piggyBac (PB) transposon system is a highly active non-viral gene delivery system capable of integrating defined DNA segments into host chromosomes without requiring homologous recombination. We systematically compared four different engineered zinc finger proteins (ZFP), four transcription activator-like effector proteins (TALE), CRISPR associated protein 9 (SpCas9) and the catalytically inactive dSpCas9 protein fused to the amino-terminus of the transposase enzyme designed to target the hypoxanthine phosphoribosyltransferase (HPRT) gene located on human chromosome X. Chimeric transposases were evaluated for expression, transposition activity, chromatin immunoprecipitation at the target loci, and targeted knockout of the HPRT gene in human cells. One ZFP-PB and one TALE-PB chimera demonstrated notable HPRT gene targeting. In contrast, Cas9/dCas9-PB chimeras did not result in gene targeting. Instead, the HPRT locus appeared to be protected from transposon integration. Supplied separately, PB permitted highly efficient isolation of Cas9-mediated knockout of HPRT, with zero transposon integrations in HPRT by deep sequencing. In summary, these tools may allow isolation of 'targeted-only' cells, be utilized to protect a genomic locus from transposon integration, and enrich for Cas9-mutated cells.