gebhart/patrepeval huggingface dataset:
Specific in vivo localization of monoclonal antibodies directed against the Thy 1.1 antigen. (1980)

Abstract The ability of a homogeneous IgG2a monoclonal antibody against Thy 1.1 antigen to selectively bind to Thy 1-containing tissues in congenic AKR mice was tested as a function of time. The rapid clearance from blood of [125I]-labeled 19-F12(M) antibody from AKR/J (Thy 1.1) mice, compared to that of AKR/Cu (Thy 1.2) mice, was consistent with the specificity of the antibody and its homing into target tissues. The selective localization of this antibody into lymphatic tissues was time dependent. At optimal times (20 hr post-injection) the lymph nodes of AKR/J mice contained 9-fold more antibody than the lymph nodes of AKR/Cu mice. Localization of the F(ab′)2 fragment of 19-F12(M) antibody into lymphatic tissues was even more striking. Clearance of the F(ab′)2 from blood was extremely rapid, and at 16 hr after injection, the lymph nodes of AKR/J mice contained 144-fold more F(ab’)2 than did the lymph nodes of AKR/Cu mice. When localization within specific organs was determined relative to nonimmune IgG2a the F(ab′)2 concentrated into lymph nodes and spleen of AKR/J mice by factors in excess of 475 and 250, respectively. In contrast, neither intact 19-F12(M) antibody or its F(ab′)2 fragment were concentrated in the lymphatic tissues of AKR/Cu mice. These studies demonstrate that monoclonal antibodies against Thy 1.1 antigen possess sufficient specificity, homogeneity, and avidity to selectively localize in appropriate target tissues in vivo.
New sutureless ‘atrial- mitral-valve prosthesis’ for minimally invasive mitral valve therapy (2010)

Incompetence is the most relevant dysfunction of the mitral valve. Surgical replacement and reconstruction is the treatment of choice whereas trans-catheter replacement or repair of mitral valve regurgitation proved demanding. We aimed for a new sutureless approach to anchor a biological heart valve in the mitral position without major surgery by inserting a valve-carrying hollow body into the left atrium. A mould representing the porcine left atrium from the pulmonary veins as far as the mitral valve was created. A superelastic Nitinol-skeleton was sutured onto a warp knitted tubular bifurcation of polyvinylidene fluoride (PVDF) multifilaments fitting the mould. This new self-expandable composite-material hollow body customized to the porcine anatomy was equipped with a commercially available biological heart valve. The functionality of this prosthesis was investigated in a circulatory mock loop simulator and the overall properties were examined in an open animal operation. The left atrium was incised and the prosthesis was placed in eight female pigs of 70 kg, under extracorporeal circulation. Prior to implantation, an artificial valve incompetence was created. Hemodynamic, echocardiographic, and radiological examinations were performed. A post mortem examination of the entire heart was performed. In the simulator we could demonstrate that the composite-material hollow body exhibited enough self-expansion to anchor onto the surrounding structures and that the function of the expanded valve was not compromised. In the animal, the prostheses walls almost completely adapted to surrounding structures leading to an exclusion of the left atrium. Sufficient treatment of mitral regurgitation was displayed hemodynamically and by echocardiography, although overall visualization was difficult. Therefore, in the last four animals a CT scan was performed demonstrating full expansion. Autopsy revealed an excellent anchorage of the prostheses. The relevant intracavitary injury and thrombotic formation were not seen. By the use of a composite-material self-expanding hollow body it is possible exclude a complete heart chamber and thereby to anchor a biological heart valve without sutures.
Robotic systems in surgery. (1993)

Computer-driven robots and medical imaging technology may soon enable surgeons to plan and execute intricate procedures with unprecedented precision. Our experience in introducing a robotic system for use in an active role in cementless total hip replacement surgery has convinced us that the marriage of these two technologies-robotics and medical imaging-is likely to change the way many types of surgical procedures are performed. The ability to link an image-based preoperative plan with its surgical execution by a robot may be the key to improved outcomes. Research and development of robotic systems for a wide variety of medical applications is underway at a number of prestigious institutions. Grenoble University has developed the IGOR (Imaged Guided Operating Robot) system. This six-axis robot has performed more than 400 interventions, acting as a positioner for brain surgery in both biopsy and therapeutic procedures. AlephMed and Digital are currently assisting the developers in integrating image analysis into the system. Future development plans include an application for spinal surgery.
A murine model to evaluate the ability of in vitro clonogenic assays to predict the response to tumors in vivo. (1988)

The use of the human tumor cloning assay as a predictor of clinical response of human tumors to drugs is predicated on the hypothesis that the in vivo response of a tumor to a drug can be correlated with the in vitro response of cells derived from the tumor. To test this hypothesis, we utilized a murine tumor model in which the in vivo and in vitro responses of a tumor can be accurately and reproducibly compared. Drug activity was assessed in P388 leukemia with the standard in vivo antitumor assay (i.p. tumor/i.p. drug administration) and an in vitro assay wherein the ascites tumor cells are removed from mice, treated with a drug, and directly cloned in soft agar to measure clonogenic capacity. The response of P388 cells to analogues within four separate classes of antitumor agents, anthracyclines, anthraquinones, platinum(II) coordination complexes, and phosphinogold(I) complexes was evaluated. The clonogenic assay failed to discriminate between highly active in vivo antitumor agents and analogues with only marginal in vivo efficacy (i.e., doxorubicin and daunorubicin versus rhodomycins A and B, ametantrone versus NSC 276740, cisplatin versus transplatin, [Au(dppe)2]Cl versus [Au(depe)2]PF6. Furthermore, the in vitro clonogenic assay failed to detect carboplatin which was a highly active agent in vivo. The basis for these discrepancies was explored by a more detailed comparison of doxorubicin and rhodomycin B. In vivo or in vitro drug exposure with subsequent measurement of cell kill by the in vitro clonogenic and in vivo tumorigenic assay demonstrated that the in vitro assay overestimated the cytotoxic potency of the drugs relative to the tumorigenic assay. Treatment of tumors in vivo with doxorubicin at doses below the maximally tolerated dose in mice resulted in multiple log cell kill as measured in vitro or in vivo, whereas rhodomycin B was cytotoxic only at dose levels exceeding its maximally tolerated dose. The results indicate that a subset of tumor stem cells capable of forming colonies in soft agar are significantly more sensitive to the cytotoxic effects of anthracyclines than are in vivo tumorigenic stem cells. Cytotoxic potency as measured by an in vitro soft agar clonogenic assay is not an accurate predictor of in vivo antitumor efficacy even in a model in which ascites tumor cells are directly exposed to i.p. drug. The in vitro cytotoxicity assay is useful only as a nonselective prescreen and must be used in combination with other indicators of tumor cell selectivity and dose-limiting organ toxicity.
Mild, selective, general method of ketone synthesis from acid chlorides and organotin compounds catalyzed by palladium (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMild, selective, general method of ketone synthesis from acid chlorides and organotin compounds catalyzed by palladiumD. Milstein and J. K. StilleCite this: J. Org. Chem. 1979, 44, 10, 1613–1618Publication Date (Print):May 1, 1979Publication History Published online1 May 2002Published inissue 1 May 1979https://pubs.acs.org/doi/10.1021/jo01324a006https://doi.org/10.1021/jo01324a006research-articleACS PublicationsRequest reuse permissionsArticle Views1290Altmetric-Citations170LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Architecture of the human regulatory network derived from ENCODE data (2012)

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.
Inoculation of silicon nanoparticles with silver atoms (2013)

Silicon (Si) nanoparticles were coated inflight with silver (Ag) atoms using a novel method to prepare multicomponent heterostructured metal-semiconductor nanoparticles. Molecular dynamics (MD) computer simulations were employed, supported by high-resolution bright field (BF) transmission electron microscopy (HRTEM) and aberration-corrected scanning transmission electron microscopy (STEM) with a resolution ≤0.1 nm in high angle annular dark field (HAADF) mode. These studies revealed that the alloying behavior and phase dynamics during the coating process are more complex than when attaching hetero-atoms to preformed nanoparticles. According to the MD simulations, Ag atoms condense, nucleate and diffuse into the liquid Si nanoparticles in a process that we term "inoculation", and a phase transition begins. Subsequent solidification involves an intermediate alloying stage that enabled us to control the microstructure and crystallinity of the solidified hybrid heterostructured nanoparticles.
Metabolites in safety testing: metabolite identification strategies in discovery and development (2009)

The publication of the FDA MIST guidelines in 2008, together with the acknowledged importance of metabolism data for the progression of novel compounds through drug discovery and drug development, has resulted in a renewed focus on the metabolite identification strategies utilised throughout the pharmaceutical industry. With the plethora of existing and emerging technologies available to the metabolite identification scientist, it is argued that increased diligence should be applied to metabolism studies in the early stages of both drug discovery and drug development, in order to more routinely impact chemical design and to comply with the concepts of the MIST guidance without re-positioning the definitive radiolabelled studies from there typical place in late development.Furthermore, these strategic elements should be augmented by a broad and thorough understanding of the impact of the derived metabolism data, most notably considerations of absolute abundance, structure and pharmacological activity, such that they can be put into proper context as part of a holistic safety strategy.The combination of these approaches should ensure a metabolite identification strategy that successfully applies the principles of the MIST guidance throughout the discovery/development continuum and thereby provides appropriate confidence in support of human safety.
Dominant lethal mutations in a conserved loop in 16S rRNA. (1990)

The 530 stem-loop region in 16S rRNA is among the most phylogenetically conserved structural elements in all rRNAs, yet its role in protein synthesis remains mysterious. G-530 is protected from kethoxal attack when tRNA, or its 15-nucleotide anticodon stem-loop fragment, is bound to the ribosomal A site. Based on presently available evidence, however, this region is believed to be too remote from the decoding site for this protection to be the result of direct contact. In this study, we use a conditional rRNA expression system to demonstrate that plasmid-encoded 16S rRNA genes carrying A, C, and T point mutations at position G-530 confer a dominant lethal phenotype when expressed in Escherichia coli. Analysis of the distribution of plasmid-encoded 16S rRNA in ribosomal particles, following induction of the A-530 mutation, shows that mutant rRNA is present both in 30S subunits and in 70S ribosomes. Little mutant rRNA is found in polyribosomes, however, indicating that the mutant ribosomes are severely impaired at the stage of polysome formation and/or stability. Detailed chemical probing of mutant ribosomal particles reveals no evidence of structural perturbation within the 16S rRNA. Taken together, these results argue for the direct participation of G-530 in ribosomal function and, furthermore, suggest that the dominant lethal phenotype caused by these mutations is due primarily to the mutant ribosomes blocking a crucial step in protein synthesis after translational initiation.
Pollen development and multi-nucleate microspores of Populus bolleana Lauche (2008)

Populus bolleana 是许多 P。白长袍的一，通常在在中国引起节目的白杨使用。包含 P 的雄花，微孢子和 microgametogenesis 的发展生物学。bolleana 为在在有性生殖的为更好的特征的生气繁殖的 Populus 改进是必要的。花形态学和花粉开发被描述并且说明了使用解剖， sectioning 和污点空地技术。结果证明 microsporocytes 经历一个常规 meiotic 过程，但是一些多核的小孢子发生在小孢子阶段。让 microsporocytes 由在温室条件下面强迫花树枝发展到成熟花粉花五天。另外，一种重要关系在成熟分裂和花药颜色的阶段之间被发现。当花药颜色变得黄时，形成的小孢子四个，当花粉成熟时，花药是红的，磁带弦音器完全堕落了。当成熟花粉粒被形成时，花芽发展成男柳絮。最后，细丝伸长了，花粉粒被免除张口的花药。
Molecular analysis of reverse mutations from nonagouti (a) to black-and-tan (a(t)) and white-bellied agouti (Aw) reveals alternative forms of agouti transcripts. (1994)

The agouti gene regulates the differential production of eumelanin (black or brown) and phaeomelanin (yellow) pigment granules by melanocytes in the hair follicles of mice. The original nonagouti (a) allele, which confers a predominantly black coat color, has been shown to revert to two other more dominant agouti alleles, black-and-tan (a(t)) and white-bellied agouti (Aw), with an exceptionally high frequency. The a(t) and Aw alleles confer phenotypes in which the pigmentation is not uniformly distributed over the dorsal and ventral surfaces of the animal; in both cases the ventral surface of the animal is markedly lighter than the dorsal surface due to an increase in phaeomelanin production. To understand the unusually high reversion rate of a to a(t) or Aw, and to decipher the molecular events associated with the different pigmentation patterns associated with these three agouti alleles, we have characterized a, a(t) and Aw at the molecular level. Here, we report that insertions of 11, 6, and 0.6 kb are present at precisely the same position in the first intron of the agouti gene in a, a(t), and Aw, respectively. The a insertion consists of a 5.5-kb VL30 element that has incorporated 5.5 kb of additional sequence internally; this internal sequence is flanked by 526-bp direct repeats. The a(t) allele contains only the VL30 element and a single, internal 526-bp repeat. The Aw allele has only a solo VL30 LTR. Based on the comparison of the structure of the a(t) and Aw insertions, we propose that reverse mutations occur by excision of inserted sequences in a through homologous recombination, utilizing either the 526-bp direct repeats to generate a(t) or the VL30 LTRs to generate Aw. Moreover, the analysis of these three alleles has allowed us to identify additional exons of the agouti gene that give rise to alternatively processed forms of agouti mRNA. We demonstrate that the distinct insertions in a, a(t) and Aw cause pigmentation differences by selectively inactivating the expression of different forms of agouti transcripts.
Characterization of Randomly Time-Variant Linear Channels (1963)

This paper is concerned with various aspects of the characterization of randomly time-variant linear channels. At the outset it is demonstrated that time-varying linear channels (or filters) may be characterized in an interesting symmetrical manner in time and frequency variables by arranging system functions in (timefrequency) dual pairs. Following this a statistical characterization of randomly time-variant linear channels is carried out in terms of correlation functions for the various system functions. These results are specialized by considering three classes of practically interesting channels. These are the wide-sense stationary (WSS) channel, the uncorrelated scattering (US) channel, and the wide-sense stationary uncorrelated scattering (WSSUS) channel. The WSS and US channels are shown to be (time-frequency) duals. Previous discussions of channel correlation functions and their relationships have dealt exclusively with the WSSUS channel. The point of view presented here of dealing with the dually related system functions and starting with the unrestricted linear channels is considerably more general and places in proper perspective previous results on the WSSUS channel. Some attention is given to the problem of characterizing radio channels. A model called the Quasi-WSSUS channel is presented to model the behavior of such channels. All real-life channels and signals have an essentially finite number of degrees of freedom due to restrictions on time duration and bandwidth. This fact may be used to derive useful canonical channel models with the aid of sampling theorems and power series expansions. Several new canonical channel models are derived in this paper, some of which are dual to those of Kailath.
Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins (2005)

Quantitative LC-MS/MS assays were designed for tryptic peptides representing 53 high and medium abundance proteins in human plasma using a multiplexed multiple reaction monitoring (MRM) approach. Of these, 47 produced acceptable quantitative data, demonstrating within-run coefficients of variation (CVs) (n = 10) of 2-22% (78% of assays had CV <10%). A number of peptides gave CVs in the range 2-7% in five experiments (10 replicate runs each) continuously measuring 137 MRMs, demonstrating the precision achievable in complex digests. Depletion of six high abundance proteins by immunosubtraction significantly improved CVs compared with whole plasma, but analytes could be detected in both sample types. Replicate digest and depletion/digest runs yielded correlation coefficients (R(2)) of 0.995 and 0.989, respectively. Absolute analyte specificity for each peptide was demonstrated using MRM-triggered MS/MS scans. Reliable detection of L-selectin (measured at 0.67 microg/ml) indicates that proteins down to the microg/ml level can be quantitated in plasma with minimal sample preparation, yielding a dynamic range of 4.5 orders of magnitude in a single experiment. Peptide MRM measurements in plasma digests thus provide a rapid and specific assay platform for biomarker validation, one that can be extended to lower abundance proteins by enrichment of specific target peptides (stable isotope standards and capture by anti-peptide antibodies (SISCAPA)).
Single-User Beamforming in Large-Scale MISO Systems with Per-Antenna Constant-Envelope Constraints: The Doughnut Channel (2012)

Large antenna arrays at the transmitter (TX) have recently been shown to achieve remarkable intra-cell interference suppression at low complexity. However, building large arrays in practice, would require the use of power-efficient RF amplifiers, which generally have poor linearity characteristics and hence would require the use of input signals with a very small peak-to-average power ratio (PAPR). In this paper, we consider the single-user Multiple-Input Single-Output (MISO) channel for the case where the TX antennas are constrained to transmit signals having constant envelope (CE). We show that, with per-antenna CE transmission the effective channel seen by the receiver is a SISO AWGN channel with its input constrained to lie in a doughnut-shaped region. For a broad class of fading channels, analysis of the effective doughnut channel shows that under a per-antenna CE input constraint, i) compared to an average-only total TX power constrained MISO channel, the extra total TX power required to achieve a desired information rate is small and bounded, ii) with N TX antennas an O(N) array power gain is achievable, and iii) for a desired information rate, using power-efficient amplifiers with CE inputs would require significantly less total TX power when compared to using highly linear (power-inefficient) amplifiers with high PAPR inputs.
Measurements and modeling of two-phase flow in microchannels with nearly constant heat flux boundary conditions (2002)

Two-phase forced convective flow in microchannels is promising for the cooling of integrated circuits. There has been limited research on boiling flow in channels with dimensions below 100 /spl mu/m, in which bubble formation and flow regimes can differ from those in larger channels. This work develops single and multi-channel experimental structures using plasma-etched silicon with pyrex glass cover, which allow uniform heating and spatially-resolved thermometry and provide optical access for visualization of boiling regimes. Boiling was observed with less than 5/spl deg/C of super-heating in rectangular channels with hydraulic diameters between 25 and 60 /spl mu/m. The channel wall widths are below 350 /spl mu/m, which minimizes solid conduction and reduces variations in the heat flux boundary condition. Pressure drop and wall temperature distribution data are consistent with predictions accounting for solid conduction and homogeneous two-phase convection.