gebhart/patrepeval huggingface dataset:
Encapsulating particles with coatings that conform to size and shape of the particles (2023)

Particles such as islet cells are encapsulated by a method that forms a coating of uniform thickness that conforms to the size and shape of the particles. Two substantially immiscible liquids of different densities are provided in a container as upper and lower liquids such that an interface exists between the liquids. The upper liquid is less dense and has a greater viscosity than the lower liquid which is a coating liquid containing particles to be encapsulated. A tube is positioned in the upper liquid such that an orifice of the tube is above the interface. A pump connected to the tube sucks liquid through the tube at a rate sufficient to form a spout containing substantially the lower liquid extending between the interface and the tube orifice. The spout has maximum diameter at the interface and decreases in diameter as the spout approaches the tube orifice. Particles in the lower liquid are drawn up through the spout as liquid is withdrawn, and coated particles are released from the spout at a point where the diameter of the spout is less than the diameter of the particles, and the coated particles flow through the tube. The coating liquid may be a pre-polymer that can be polymerized and crosslinked after coating. The coated particles have therapeutic applications such as administering coated islet cells to treat diabetes.
Data from Altered Microenvironment Promotes Progression of Preinvasive Breast Cancer: Myoepithelial Expression of αvβ6 Integrin in DCIS Identifies High-risk Patients and Predicts Recurrence (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; This study investigated the functional and clinical significance of integrin αvβ6 upregulation in myoepithelial cells of ductal carcinoma &lt;i&gt;in situ&lt;/i&gt; (DCIS).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Archival samples of DCIS and DCIS with associated invasion (&lt;i&gt;n&lt;/i&gt; = 532) were analyzed for expression of αvβ6 by immunohistochemistry and ability to predict recurrence and progression assessed in an independent, unique cohort of DCIS cases with long-term follow-up. Primary myoepithelial cells and myoepithelial cell lines, with and without αvβ6 expression, were used to measure the effect of αvβ6 on growth and invasion of tumor cell lines &lt;i&gt;in vitro&lt;/i&gt; and in a xenograft mouse model. Involvement of TGFβ signaling was established using mink lung epithelial cell (MLEC) assay and antibody inhibition, and expression and activation of matrix metalloproteinase (MMP)-9 established by Real Time-PCR and zymography.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Expression of αvβ6 is significantly associated with progression to invasive cancer (&lt;i&gt;P&lt;/i&gt; &lt; 0.006) and with recurrence over a median follow-up of 114 months in a series of matched DCIS cases treated with local excision. We show that expression of αvβ6 drives myoepithelial cells to promote tumor cell invasion &lt;i&gt;in vitro&lt;/i&gt; and enhances mammary tumor growth &lt;i&gt;in vivo&lt;/i&gt;. The tumor-promoting effect of αvβ6-positive myoepithelial cells is dependent on TGFβ-driven upregulation of MMP9 and can be abrogated by inhibiting this pathway.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; These findings indicate that altered myoepithelial cells in DCIS predict disease progression and recurrence and show that upregulation of αvβ6 on myoepithelial cells generates a tumor promoter function through TGFβ upregulation of MMP-9. These data suggest that expression of αvβ6 may be used to stratify patients with DCIS. &lt;i&gt;Clin Cancer Res; 20(2); 344–57. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Celebrating 20 Years of IGHV Mutation Analysis in CLL (2020)

The division of CLL into 2 broad subsets with highly significant differences in clinical behavior was reported in 2 landmark papers in Blood in 1999.<sup>1,2</sup> The simple analysis of the mutational status of the IGV regions provided both a prognostic indicator and an insight into the cellular origins. Derivation from B cells with very low or no IGV mutations generally leads to a more aggressive disease course than derivation from B cells with higher levels. This finding focused attention on surface Ig (sIg), the major B-cell receptor, and revealed dynamic antigen engagement in vivo as a tumor driver. It has also led to new drugs aimed at components of the intracellular activation cascades. After 20 years, the 2 senior authors of those papers have looked at the history of the observations and at the increasing understanding of the role of sIg in CLL that have emanated from them. As in the past, studies of CLL have provided a link between biology and the clinic, enabling more precise targeting which attacks critical pathways but minimizes side effects.
High-precision measurements of the diamond Hugoniot in and above the melt region (2008)

High-precision measurements of the diamond principal Hugoniot have been made at pressures between 6 and 19 Mbar. Shock velocities were determined with 0.3%--1.1% precision using a velocity interferometer. Impedance-matching analysis, incorporating systematic uncertainties in the equation of state of the quartz standard, was used to determine the Hugoniot with 1.2%--2.7% precision in density. The results are in good agreement with published ab initio calculations, which predict a small negative melt slope along the Hugoniot, but disagree with previous laser-driven shock wave experiments, which had observed a large density increase in the melt region. In the extensive solid-liquid coexistence regime between 6 and 10 Mbar, the present measurements indicate that the mixed phase is a few percent more dense than what would be expected from a simple interpolation between liquid and solid Hugoniots.
Structure–Activity Relationships of Bis-Intercalating Peptides and Their Application as Antibody–Drug Conjugate Payloads (2023)

Synthetic analogs based on the DNA bis-intercalating natural product peptides sandramycin and quinaldopeptin were investigated as antibody drug conjugate (ADC) payloads. Synthesis, biophysical characterization, and <i>in vitro</i> potency of 34 new analogs are described. Conjugation of an initial drug-linker derived from a novel bis-intercalating peptide produced an ADC that was hydrophobic and prone to aggregation. Two strategies were employed to improve ADC physiochemical properties: addition of a solubilizing group in the linker and the use of an enzymatically cleavable hydrophilic mask on the payload itself. All ADCs showed potent <i>in vitro</i> cytotoxicity in high antigen expressing cells; however, masked ADCs were less potent than payload matched unmasked ADCs in lower antigen expressing cell lines. Two pilot <i>in vivo</i> studies were conducted using stochastically conjugated DAR4 anti-FRα ADCs, which showed toxicity even at low doses, and site-specific conjugated (THIOMAB) DAR2 anti-cMet ADCs that were well tolerated and highly efficacious.
College Announcements (1978)

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ChemInform Abstract: N‐Methyl Lithiation of N‐Methylindoles Directed by α‐Amino Alkoxides. (1990)

Abstract N‐Methylindole‐2‐carboxaldehyde (I) is consecutively treated with the lithium piperazide (II) and n‐butyllithium (III) to form the dilithium salt (IV) which is silylated to give a moderate yield of the 3‐silyl derivative (VI).
Influence of the crystallite size of BaTiO₃ on the dielectric properties of polyester reactive resin composite materials (2008)

Commercially available barium titanate powder was temperature treated to induce grain growth at temperatures between 500 � C and 1200 � C. The permittivities of polyester reactive resin composite materials with a filler load of 60m% where examined in dependence of the heat treatment. A permittivity of 25 at 150Hz was achieved using a treatment temperature of about 1000 � C while a composite containing the original powder exhibits a permittivity of 11. Temperature treatment of commercial BaTiO 3 powder is one crucial step in optimizing high dk composite materials without having direct influence over the powder production process.
Computer-aided detection of breast masses on mammograms: bilateral analysis for false positive reduction (2006)

In this study, our purpose was to develop a false positive (FP) reduction method for computerized mass detection systems based on the analysis of bilateral mammograms. We first detect the mass candidates on each view by utilizing our unilateral computer-aided detection (CAD) system. For each detected object, the regional registration technique is used to define a region of interest (ROI) that is "symmetrical" to the object location on the contralateral mammogram. Spatial gray level dependence matrices (SGLD) texture features and morphological features are extracted from both the ROI containing the detected object on a mammogram and its corresponding ROI on the contralateral mammogram. Bilateral features are then generated from the extracted unilateral features and a final bilateral score is formed as a new feature to differentiate symmetric from asymmetric ROIs. By incorporating the unilateral features of the mass candidates and their bilateral scores, a bilateral classifier was trained to reduce the FPs. It was found that our bilateral CAD system achieved a case-based sensitivity of 70%, 80%, and 85% at 0.52, 0.83, and 1.05 FPs/image on the test data set. In comparison to the FP rates for the unilateral CAD system of 0.67, 1.11, and 1.69, respectively, at the corresponding sensitivities, the FP rates were reduced by 22%, 25%, and 37% with the bilateral symmetry information.
Adaptive Penalty Methods for Genetic Optimization of Constrained Combinatorial Problems (1996)

The application of genetic algorithms (GA) to constrained optimization problems has been hindered by the inefficiencies of reproduction and mutation when feasibility of generated solutions is impossible to guarantee and feasible solutions are very difficult to find. Although several authors have suggested the use of both static and dynamic penalty functions for genetic search, this paper presents a general adaptive penalty technique which makes use of feedback obtained during the search along with a dynamic distance metric. The effectiveness of this method is illustrated on two diverse combinatorial applications: (1) the unequal-area, shape-constrained facility layout problem and (2) the series-parallel redundancy allocation problem to maximize system reliability given cost and weight constraints. The adaptive penalty function is shown to be robust with regard to random number seed, parameter settings, number and degree of constraints, and problem instance.
Autologous Platelet-Rich Plasma Administration on the Intervertebral Disc in Low Back Pain Patients with Modic Type 1 Change: Report of Two Cases (2023)

<i>Background and Objectives</i>: Modic type 1 is known to be associated with lower back pain (LBP), but at present, a treatment has not been fully established. Meanwhile, platelet-rich plasma (PRP) has been used for tissue regeneration and repair in the clinical setting. There is no clinical PRP injection trial for the intervertebral disc of LBP patients with Modic type 1. Thus, this study aimed to verify PRP injection safety and efficacy in LBP patients with Modic type 1. As a preliminary experiment, two LBP cases with Modic type 1 are presented. <i>Materials and Methods</i>: PRP was administered intradiscally to two LBP patients with Modic type 1. PRP was obtained from the patients' anticoagulated blood. Primary endpoints were physical condition, laboratory data, and X-ray for safety evaluation. Secondary endpoints were pain scores using the visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) to evaluate PRP efficacy. The observation period was 24 weeks after the PRP injection. In addition, changes in Modic type 1 using MRI were evaluated. <i>Results</i>: This study assessed two LBP patients with Modic type 1. There were no adverse events in physical condition, laboratory data, or lumbar X-rays after injection. Follow-up MRI showed a decrease of high signal intensity on T2WI compared to before PRP administration. The pain scores tended to improve after the injection. <i>Conclusions</i>: PRP injection into the intervertebral disc of LBP patients with Modic type 1 might be safe and effective. This analysis will be continued as a prospective study to establish the efficacy.
Progress in polydopamine-based melanin mimetic materials for structural color generation (2020)

Structural color is a color derived from optical interaction between light and a microstructure and is often seen in nature. Natural melanin plays an important role in bright structural coloration. For example, the vivid colors of peacock feathers are due to structural colors. The periodic arrangement of melanin granules inside the feathers leads to light interference, and the black granules absorb scattered light well, resulting in bright structural color. In recent years, polydopamine (PDA) has attracted attention as a melanin mimetic material. This review article summarizes recent research on structural coloration using PDA-based artificial melanin materials. It also outlines possible applications using bright structural colors realized by artificial melanin materials and future perspectives.
Quantitative cross-linking/mass spectrometry reveals subtle protein conformational changes (2016)

Quantitative cross-linking/mass spectrometry (QCLMS) probes protein structural dynamics in solution by quantitatively comparing the yields of cross-links between different conformational statuses. We have used QCLMS to understand the final maturation step of the proteasome lid and also to elucidate the structure of complement C3(H2O). Here we benchmark our workflow using a structurally well-described reference system, the human complement protein C3 and its activated cleavage product C3b. We found that small local conformational changes affect the yields of cross-linking residues that are near in space while larger conformational changes affect the detectability of cross-links. Distinguishing between minor and major changes required robust analysis based on replica analysis and a label-swapping procedure. By providing workflow, code of practice and a framework for semi-automated data processing, we lay the foundation for QCLMS as a tool to monitor the domain choreography that drives binary switching in many protein-protein interaction networks.
SymNet (2013)

Today's networks deploy many stateful procesing boxes ranging from NATs to firewalls and application optimizers: these boxes operate on packet flows, rather than individual packets. As more and more middleboxes are deployed, understanding their composition is becoming increasingly difficult. Static checking of network configurations is a promising approach to help understand whether a network is configured properly, but existing tools are limited as they only support stateless processing.
Potential effect of vitamin K on microgravity-induced bone loss. (1996)

The role of vitamin K in microgravity related bone loss is explored. Previous research has suggested a role for vitamin K in increasing bone formation and decreasing bone resorption in postmenapausal women. This paper describes an experiment performed during the EUROMIR-95 spaceflight involving vitamin K supplements. Experimental design and methods are discussed, along with the rationale for conducting the experiment. No results are given.
Homeobox 1.3 Expression: Induction by Retinoic Acid in Human Bronchial Fibroblasts (1992)

Homeobox (Hox) genes code for transcriptional factors and are expressed during many developmental and differentiative processes. In this study, we describe the induction of Hox 1.3 expression by retinoic acid (RA) in human bronchial fibroblasts (HBF) derived from explants of bronchial tissue. Using Northern blot analysis, we show that RA induces Hox 1.3 mRNA 3- to 10-fold over steady-state levels within 2 h after addition of RA to HBF culture medium. The induction was dose dependent, reaching a half-maximal level at approximately 10(-8) M RA. This induction was not seen in human dermal fibroblasts. Immunofluorescent staining of HBF showed a corresponding increase in Hox 1.3 protein levels in the nuclei. The increase in Hox 1.3 transcript levels in HBF was not abolished by cycloheximide treatment, suggesting that synthesis of a protein intermediate is not required for the induction. RA did not significantly alter the rate of degradation of the Hox 1.3 mRNA as determined by actinomycin D treatment, suggesting that the increase in Hox 1.3 mRNA may be due to an increase in the rate of transcription. This study provides further evidence that bronchial fibroblasts are targets for RA. Although downstream target genes for Hox 1.3 have not yet been identified, it is likely that the induction of Hox 1.3 by RA is an early step in a cascade of RA-induced changes in gene expression in bronchial fibroblasts.
Synergistic effect of trichostatin A and 5‐aza‐2′‐deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: A proteomic study (2009)

Our research group recently reported that pancreatic endocrine cancer cell lines are sensitive to the HDAC inhibitor trichostatin A (TSA). In the present paper, we show that the combined treatment of pancreatic endocrine tumour cell lines with TSA and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) determines a strong synergistic inhibition of proliferation mainly due to apoptotic cell death. Proteomic analysis demonstrates that the modulation of specific proteins correlates with the antiproliferative effect of the drugs. A schematic network clarifies the most important targets or pathways involved in pancreatic endocrine cancer growth inhibition by single or combined drug treatments, which include proteasome, mitochondrial apoptotic pathway and caspase related proteins, p53 and Ras related proteins. A comparison between the patterns of proteins regulated by TSA or DAC in endocrine and ductal pancreatic cancer cell lines is also presented.
Fine-grained lesion annotation in CT images with knowledge mined from radiology reports (2019)

In radiologists' routine work, one major task is to read a medical image, e.g., a CT scan, find significant lesions, and write sentences in the radiology report to describe them. In this paper, we study the lesion description or annotation problem as an important step of computer-aided diagnosis (CAD). Given a lesion image, our aim is to predict multiple relevant labels, such as the lesion's body part, type, and attributes. To address this problem, we define a set of 145 labels based on RadLex to describe a large variety of lesions in the DeepLesion dataset. We directly mine training labels from the lesion's corresponding sentence in the radiology report, which requires minimal manual effort and is easily generalizable to large data and label sets. A multi-label convolutional neural network is then proposed for images with multi-scale structure and a noise-robust loss. Quantitative and qualitative experiments demonstrate the effectiveness of the framework. The average area under ROC curve on 1,872 test lesions is 0.9083.
Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke (2017)

Soluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.
Hallmarks of HIV-1 pathogenesis are modulated by NefÃ¢ÂÂs Secretion Modification Region (2015)

CD4<sup>+</sup> T cell depletion and immune activation are hallmarks of HIV infection. Despite extensive studies, the mechanisms underlying immune modulation remain elusive. HIV-1 Nef protein is secreted in exosomes from infected cells and is abundant in the plasma of HIV+ individuals. Exosomal Nef (exNef) was also shown to induce apoptosis in bystander CD4<sup>+</sup> T cells. We hypothesized that exNef contributes to HIV pathogenesis. A HIV-1 NL4-3 virus containing alanine substitutions in the secretion modification region (SMR; amino acids 66 to 70; HIVNefsmr5a) was developed. Nef protein containing this modified SMR was shown to be deficient in exNef secretion in <i>nef</i>-transfected cells. Using both HIV-1 NL4-3 wild type (HIVwt) and HIVNefsmr5a, correlates of pathogenesis were evaluated in cell-lines, human peripheral blood mononuclear cells, and humanized NOD-RAG1<sup>-/-</sup> IL2r<sup>-/-</sup> double mutant (NRG) mice. Disruption of the SMR did not affect viral replication or exNef secretion from infected cell cultures as compared with <i>nef</i>-transfected cells. However, T cell apoptosis was reduced in HIVNefsmr5a infected cell cultures and CD4<sup>+</sup> T cell depletion was reduced in the spleen and peripheral blood of similarly infected NRG mice. Inflammatory cytokine release was also decreased in the sera of HIVNefsmr5a infected mice relative to HIVwt infected controls. These findings demonstrate the importance of Nef and the SMR motif in HIV pathogenesis and suggest a potential role for exNef in HIV-driven immune modulation.
Efficient folding of proteins with multiple disulfide bonds in the <i>Escherichia coli</i> cytoplasm (1999)

Under physiological conditions, the Escherichia coli cytoplasm is maintained in a reduced state that strongly disfavors the formation of stable disulfide bonds in proteins. However, mutants in which the reduction of both thioredoxins and glutathione is impaired (trxB gor mutants) accumulate oxidized, enzymatically active alkaline phosphatase in the cytoplasm. These mutants grow very poorly in the absence of an exogenous reductant and accumulate extragenic suppressors at a high frequency. One such suppressor strain, FA113, grows almost as rapidly as the wild type in the absence of reductant, exhibits slightly faster kinetics of disulfide bond formation, and has fully induced activity of the transcriptional activator, OxyR. FA113 gave substantially higher yields of properly oxidized proteins compared with wild-type or trxB mutant strains. For polypeptides with very complex patterns of disulfide bonds, such as vtPA and the full-length tPA, the amount of active protein was further enhanced up to 15-fold by co-expression of TrxA (thioredoxin 1) mutants with different redox potentials, or 20-fold by the protein disulfide isomerase, DsbC. Remarkably, higher yields of oxidized, biologically active proteins were obtained by expression in the cytoplasm of E. coli FA113 compared with what could be achieved via secretion into the periplasm of a wild-type strain, even under optimized conditions. These results demonstrate that the cytoplasm can be rendered sufficiently oxidizing to allow efficient formation of native disulfide bonds without compromising cell viability.