gebhart/patrepeval huggingface dataset:
Microfluidic chamber arrays for whole-organism behavior-based chemical screening (2011)

The nematode Caenorhabditis elegans is an important model organism in genetic research and drug screening because of its relative simplicity, ease of maintenance, amenability to simple genetic manipulation, and relevance to human biology. However, their small size and mobility make nematodes difficult to physically manipulate, particularly with spatial and temporal precision. We have developed a microfluidic device to overcome these challenges and enable fast behavior-based chemical screening in C. elegans. The key components of this easy-to-use device allow rapid loading and housing of C. elegans in a chamber array for chemical screening. A simple two-step loading process enables simultaneous loading of a large number of animals within a few minutes without using any expensive/active off-chip components. In addition, chemicals can be precisely delivered to the worms and exchanged with high temporal precision. To demonstrate this feature and the ability to measure time dependent responses to chemicals, we characterize the transient response of worms exposed to different concentrations of anesthetics. We then use the device to study the effect of chemical signals from hermaphrodite worms on male behavior. The ability of the device to maintain a large number of free moving animals in one field of view over a long period of time permits us to demonstrate an increase in the incidence of a specific behavior in males subjected to worm-conditioned medium. Because our device allows monitoring of a large number of worms with single-animal resolution, we envision that this platform will greatly expedite chemical screening in C. elegans.
Model-Driven Constraint Engineering (2024)

Precise specification of meta-models is an important rerequisite for the successful application of a model-driven engineering (MDE) process. One means of precise specification are textual constraints. However, the task of constraint development is time-consuming and error-prone if done manually. In this paper, we present both a methodology and a tool for developing constraints in a systematic way that can be integrated into a CASE tool. Thus, we provide a semi-automated means for integrating constraints into the MDE process. Our approach is based on an extensible library of generic constraint patterns. Constraint patterns can be combined to create complex constraints and easily parameterized in a CASE tool. Moreover, we show how these parameterized patterns are transformed into platform-independent or platform- specific constraints by a model transformation.
Heterogeneous Nuclear Ribonucleoprotein K (hnRNP-K) Promotes Tumor Metastasis by Induction of Genes Involved in Extracellular Matrix, Cell Movement, and Angiogenesis (2013)

Cancer is a leading cause of death and still awaits effective therapies. Rapid industrialization has contributed to increase in incidence of cancer. One of the reasons why most of the cancers fail therapy is due to their metastatic property. Hence identification of factors leading to metastasis is highly important to design effective and novel anti-cancer therapeutics. In our earlier study (Inoue, A., Sawata, S. Y., Taira, K., and Wadhwa, R. (2007) Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. Proc. Natl. Acad. Sci. U.S.A. 104, 8983-8988), we had reported that the involvement of heterogeneous nuclear ribonucleoprotein K (hnRNP-K) in metastasis. Here, we established hnRNP-K-overexpressing and -underexpressing derivative cell lines and examined their proliferation and metastatic properties in vitro and in vivo. Whereas hnRNP-K compromised cells showed delayed tumor growth, its overexpression resulted in enhanced malignancy and metastasis. Molecular basis of the hnRNP-K induced malignant and metastatic phenotypes was dissected by cDNA microarray and pathway analyses. We found that the hnRNP-K regulates extracellular matrix, cell motility, and angiogenesis pathways. Involvement of the selected genes (Cck, Mmp-3, Ptgs2, and Ctgf) and pathways was validated by gene-specific expression analysis. Our results demonstrated that the hnRNP-K is a potential target for metastasis therapy.
The real-frequency technique applied to a narrow band MMIC active filter with transmission zero at finite frequencies (2002)

This paper reports on a narrow band MMIC active filter designed by the real-frequency technique (RFT). RFT provides several advantages over most of the usual techniques : it does not require any active component model and no predetermined matching network topology is necessary. The CAD procedure based on the RFT is introduced to resolve the input and output matching problems. A practical design is proposed for a 7.7-8.1 GHz active filter with two transmission zeroes at 6.8 GHz and 9.2 GHz.
Crystal structure of ab -Bis(3-methylpyridine)- dc,fe -bis(pentane-2,3,4-trione 3-oximato)iron(II) (1978)

The crystal structure of the title compound has been determined at 295 K by single-crystal X-ray diffraction and refined by least squares to a residual of 0.062. Crystals are monoclinic, P2/c, a 19.102(8), b 8.117(4), c 16.610(8) ?, ß 111.90(3)°, Z. Unlike the tris(a-oxyimino ketonato)iron(II) complexes which are fac, the present derivative is based upon substitution of the two picoline moieties into a mer derivative, trans to the nitrogen atoms of the chelate ligands. &amp;lt;Fe- N(picoline)&amp;gt; is 2.020; &amp;lt;Fe-N, O(chelate)&amp;gt; 1.880, 1.952 ?.
Indications for a second prostate biopsy in patients suspected with prostate cancer after an initial negative prostate biopsy (2016)

The indications for a second prostate biopsy are a low prostate volume and a high number of increases in the PSA level among patients with a PSA decrease at the first follow-up and a low prostate volume and a high number of biopsy cores among patients with a PSA increase at the first follow-up.
Investigation of bias-free positioning estimators for the scintillation cameras (2001)

Bias-free positioning estimators for scintillation cameras are investigated. A linear correlation coefficient (LCC) and Chi square error (CSE) method are evaluated with respect to linearity and spatial resolution performance. The LCC method uses correlation information between the true function (i.e., light response function) and measured data in mapping an event characterization vector to the associated position. The CSE method estimates the position where the Chi square error between two functions becomes minimized. In order to determine true statistics as a function of position, the light response function (LRF) was estimated based on sample measurements by using a cubic spline interpolation technique which provides smooth first-order and continuous second-order derivative of the LRF. Both methods have superior linearity properties compared to the weighted centroid. Each method call be considered as a bias-free positioning estimator within the effective field of view of the detector. The spatial resolution performance of the CSE method is /spl sim/7% and /spl sim/16% better than the weighted centroid method for a 16- and 25-mm-thick crystal, respectively. The spatial resolution performance of the LCC method is comparable to that of the weighted centroid method.
Synthesis and Isolation of 5,6-Dihydro-4H-1,3-Oxazine Hydrobromides by Autocyclization of N-(3-Bromopropyl)amides (2010)

5,6-Dihydro-4H-1,3-oxazine hydrobromides have been synthesized by the nucleophilic autocyclo-O-alkylation of N-(3-bromopropyl)amides under neutral conditions in chloroform. It is found that electron-donating amide α-substituents influence the autocyclization efficiency.
FRaeppli: a multispectral imaging toolbox for cell tracing and dense tissue analysis in zebrafish (2022)

Visualizing cell shapes and interactions of differentiating cells is instrumental for understanding organ development and repair. Across species, strategies for stochastic multicolour labelling have greatly facilitated in vivo cell tracking and mapping neuronal connectivity. Yet integrating multi-fluorophore information into the context of developing zebrafish tissues is challenging given their cytoplasmic localization and spectral incompatibility with common fluorescent markers. Inspired by Drosophila Raeppli, we developed FRaeppli (Fish-Raeppli) by expressing bright membrane- or nuclear-targeted fluorescent proteins for efficient cell shape analysis and tracking. High spatiotemporal activation flexibility is provided by the Gal4/UAS system together with Cre/lox and/or PhiC31 integrase. The distinct spectra of the FRaeppli fluorescent proteins allow simultaneous imaging with GFP and infrared subcellular reporters or tissue landmarks. We demonstrate the suitability of FRaeppli for live imaging of complex internal organs, such as the liver, and have tailored hyperspectral protocols for time-efficient acquisition. Combining FRaeppli with polarity markers revealed previously unknown canalicular topologies between differentiating hepatocytes, reminiscent of the mammalian liver, suggesting common developmental mechanisms. The multispectral FRaeppli toolbox thus enables the comprehensive analysis of intricate cellular morphologies, topologies and lineages at single-cell resolution in zebrafish.
Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax (2016)

Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB) containing 3 distinct mutations in the major histocompatibility complex class II binding site was combined with an alum adjuvant (Alhydrogel) and used as a potential parenteral vaccine named STEBVax. Consenting healthy adult volunteers (age range, 23 to 38 years) participated in a first-in-human open-label dose escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg. Safety was assessed by determination of the frequency of adverse events and reactogenicity. Immune responses to the vaccination were determined by measurement of anti-staphylococcal enterotoxin B (anti-SEB) IgG by enzyme-linked immunosorbent assay and a toxin neutralization assay (TNA). Twenty-eight participants were enrolled in 7 dosing cohorts. All doses were well tolerated. The participants exhibited heterogeneous baseline antibody titers. More seroconversions and a faster onset of serum anti-SEB IgG toxin-neutralizing antibodies were observed by TNA with increasing doses of STEBVax. There was a trend for a plateau in antibody responses with doses of STEBVax of between 2.5 and 20 μg. Among the participants vaccinated with 2.5 μg to 20 μg of STEBVax, ∼93% seroconverted for SEB toxin-neutralizing antibody. A strong correlation between individual SEB-specific serum IgG antibody titers and the neutralization of gamma interferon production was found in vitro STEBvax appeared to be safe and immunogenic, inducing functional toxin-neutralizing antibodies. These data support its continued clinical development. (This study has been registered at ClinicalTrials.gov under registration no. NCT00974935.).
Self-Assembled Out-of-Plane High Q Inductors (2002)

We report for the first time self-assembled out-of-plane micro inductors. The resulting Q values are among the highest reported to date.
Micro-Retroreflectors in Immunoassays and Biosensors (2008)

Many current bioanalytical and diagnostic methods rely on labeling the species of interest and the use of specialized detection equipment to monitor the label. Incorporation of retroreflectors into immunoassays and biosensors offers a novel and economical solution to problems associated with these methods and provides a detection assay useful in clinical and defense applications. Spotting of various detection antibodies on various test surfaces was done to test the viability of a “syndrome chip” for use in clinical diagnostics. Magnetic particles were used to incorporate magnetic stringency into the assay, which when combined with microfluidics will increase the specificity of the system. Such a chip would be activated with capture antibodies for several common disease vectors as well as some that are less common and may have bioterrorism applications.
Subcell Segmentation for Current Matching and Design Flexibility in Multijunction Solar Cells (2020)

Subcell segmentation is a method to obtain nearly ideal current-matching while employing nonideal bandgap combinations in high-efficiency multijunction solar cells. By splitting each subcell into multiple semitransparent pn junctions, called segments, current-matching can be satisfied by layer design rather than material selection. This architecture replaces the standard requirement for an optimal combination of bandgaps with a simpler requirement for optimal layer thicknesses in each series-connected segment. The total device current is divided across all segments, reducing the resistive power loss especially under nonuniform illumination or high to extreme concentration. Detailed balance-based analysis of three- and four-subcell devices in both terrestrial concentrator and one-sun space applications demonstrates that the segmented architecture can approach the theoretical efficiency peak using a broad range of physically realizable bandgap combinations. For example, detailed-balance analysis reveals a 7.5%-8.1% absolute efficiency improvement for 1-cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> segmented cells compared with standard InGaP/InGaAs/Ge designs under 1000-suns AM1.5D illumination. Higher-order segmentation multiplies the number of segments in all subcells by a common multiple, which further reduces the device current, resistive power loss, and segment thicknesses.
Interferometric modulator with phase-modulating and cavity-modulating components (IMPACC) for high linearity microwave applications: technology review (2013)

In this invited paper, we review the theoretical model and performance of an Interferometric Modulator with Phase modulating And Cavity-modulating Components (IMPACC). IMPACC has the highest reported SFDR (e.g., 132 dB-Hz) and offers additional advantages compared to other Mach-Zehnder Interferometer (MZI) based electro-optic modulators (e.g., MZI, ring-assisted MZI or RAMZI). The modulator is based on a unique combination of a RF driven phase-modulator (PM) and a ring resonator (RR) within a MZI interferometer. Both the PM and RR in the IMPACC are simultaneously driven by a RF signal of the same frequency, but not necessarily the same amplitude and phase. Here, we summarize the non-ideal and oftentimes detrimental effects such as: (1) RF bandwidth limitation due to free spectral range (FSR) of the RR, (2) RR waveguide loss, (3) deviation of RR coupling ratio from the ideal value, and (4) unbalanced MZ splitter/coupler on the performance of both IMPACC and RAMZI. We show that proper choice of RF power split ratio and RF phase for IMPACC compensate these negative effects and recover IMPACC’s ideal performance. Unlike RAMZI, this translates to higher device tolerance, added manufacturing flexibility, and superior modulator performance.
Chiral recognition by 1H‐NMR, EPR, and ENDOR spectroscopy (1993)

Abstract Chiral recognition with magnetic methods requires the formation of diastereomers. Due to the variety of appropriate reactions, hydrogen bond formation, esterification, and acetalization as well as host–guest interactions were chosen for basic investigations. The results obtained indicate that in the case of diamagnetic compounds the chemical shifts and for paramagnetic compounds the β‐proton coupling constants are the most useful parameters. By combination of both pieces of information, assignment of the absolute configuration was achieved. © 1993 Wiley‐Liss, Inc.
Author Correction: The repertoire of mutational signatures in human cancer (2023)

In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional minor corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper.
Multi‐input CRISPR / C as genetic circuits that interface host regulatory networks (2014)

Genetic circuits require many regulatory parts in order to implement signal processing or execute algorithms in cells. A potentially scalable approach is to use dCas9, which employs small guide RNAs (sgRNAs) to repress genetic loci via the programmability of RNA:DNA base pairing. To this end, we use dCas9 and designed sgRNAs to build transcriptional logic gates and connect them to perform computation in living cells. We constructed a set of NOT gates by designing five synthetic Escherichia coli σ70 promoters that are repressed by corresponding sgRNAs, and these interactions do not exhibit crosstalk between each other. These sgRNAs exhibit high on-target repression (56- to 440-fold) and negligible off-target interactions (< 1.3-fold). These gates were connected to build larger circuits, including the Boolean-complete NOR gate and a 3-gate circuit consisting of four layered sgRNAs. The synthetic circuits were connected to the native E. coli regulatory network by designing output sgRNAs to target an E. coli transcription factor (malT). This converts the output of a synthetic circuit to a switch in cellular phenotype (sugar utilization, chemotaxis, phage resistance).
Generation of Mice with Either Ubiquitous or Corpus Luteum-Specific Expression of the Long Form of the Prolactin Receptor Reveals That Both Isoforms of the Receptor Are Required for Normal Female Fertility. (2009)

We have previously established that PRL does not rescue the corpus luteum (CL) and causes premature ovarian failure in mice expressing only the short form of the PRL receptor (PRLRS). In this investigation, we examined whether PRL signaling solely through the long form of the receptor (PRLRL) can sustain fertility. Using PRLR null mice, we generated transgenic mice expressing PRLRL alone and discovered that the females are sterile, but the males are fertile and become obese with age due to severe accumulation of epididymal fat. Female PRLRL mice have normal estrus cycles, mating behavior, and ovulate normally. PRLRL embryos transplanted to wild type mothers are born, indicating that the infertility defect in PRLRL female mice is maternal. We found no difference in LH or FSH levels in PRLRL mice, yet estradiol levels are dramatically elevated. Although CLs are found through day 5 of pregnancy and PRL can induce Stat5 phosphorylation in ovaries of PRLRL mice, implantation does not occur. Daily administration of progesterone could not totally rescue pregnancy and only few embryos are found alive by C-section. A severe defect in decidualization is observed despite progesterone treatment through day 9 of pregnancy. To determine whether the infertility defect in PRLRL mice is a result of ubiquitous expression of this receptor, we generated transgenic mice expressing PRLRL specifically in the CL (CL-PRLRL) using the PRAP-17BHSD7 promoter. To our surprise, these mice are also infertile and, similarly to the PRLRL mice, have normal estrus cycle, mating behaviors, ovulation rate, and CL formation, yet implantation does not occur. Transplantation of CL-PRLRL embryos to wild type mothers led to normal birth of pups and progesterone treatment of CL-PRLRL mice could rescue pregnancy. In summary, we have succeeded at generating transgenic mice expressing PRLRL either in the whole animal or specifically in the CL and demonstrated that although PRL can activate the Stat pathway through PRLRL, it is unable to sustain progesterone production, but rather induces high levels of estradiol and causes a decidualization defect. Moreover, we have found that while female mice are sterile, male mice are fertile and PRL signaling exclusively through PRLRL can induce fat deposition in males. The results of this investigation clearly indicate that PRLRL alone is unable to support normal ovarian function and that both isoforms of the receptor are required for normal female fertility. Our finding that PRLRL transgenic mice on the wild type background are fertile further indicates that both PRLRS and PRLRL are required for maintenance of pregnancy. Supported by NIH HD12356 and HD11119 (GG), T32 HL007692 (JL & AS) and APS fellowship (JH).
Electrooxidation of Alcohols Catalyzed by Amino Alcohol Ligated Ruthenium Complexes (2013)

Ruthenium transfer hydrogenation catalysts physisorbed onto edge-plane graphite electrodes are active electrocatalysts for the oxidation of alcohols. Electrooxidation of CH3OH (1.23 M) in a buffered aqueous solution at pH 11.5 with [(η(6)-p-cymene)(η(2)-N,O-(1R,2S)-cis-1-amino-2-indanol)]Ru(II)Cl (2) on edge-plane graphite exhibits an onset current at 560 mV vs NHE. Koutecky-Levich analysis at 750 mV reveals a four-electron oxidation of methanol with a rate of 1.35 M(-1) s(-1). Mechanistic investigations by (1)H NMR, cyclic voltammetry, and desorption electrospray ionization mass spectrometry indicate that the electroxidation of methanol to generate formate is mediated by surface-supported Ru-oxo complexes.
Taxonogenomic Analysis of Marine-Derived Streptomyces sp. N11-50 and the Profile of NRPS and PKS Gene Clusters (2023)

Streptomyces sp. N11-50 was isolated from deep-sea water and found to produce diketopiperazine (DKP) compounds such as albonoursin and cyclo(Phe-Leu). This study aimed to reveal the potential to synthesize diverse nonribosomal peptide and polyketide compounds as the other secondary metabolites different from DKP after clarifying the taxonomic position. Strain N11-50 was identified as Streptomyces albus, as it showed 100% 16S rRNA gene sequence similarities and 95.5% DNA–DNA relatedness to S. albus NBRC 13014T. We annotated the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene clusters in the genome. Consequently, five NRPS, one hybrid PKS/NRPS, five type-I PKS and one type-II PKS gene clusters were observed, of which we predicted the products through bioinformatic analysis. These gene clusters were well conserved in already whole-genome sequence (WGS)-published strains belonging to S. albus. On the other hand, our taxonogenomic analysis revealed that three WGS-published S. albus strains were not S. albus. Two of the three should be classified as Streptomyces albidoflavus, and the remaining one was likely a new genomospecies. After reclassifying these appropriately, we demonstrated species-specific profiles of the NRPS and PKS gene clusters with little strain-level diversities.