gebhart/patrepeval huggingface dataset:
The state of the field: from inception to commercialization of metal–organic frameworks (2020)

As chemists and materials scientists, it is our duty to synthesize and utilize materials for a multitude of applications that promote the development of society and the well-being of its citizens. Since the inception of metal-organic frameworks (MOFs), researchers have proposed a variety of design strategies to rationally synthesize new MOF materials, studied their porosity and gas sorption performances, and integrated MOFs onto supports and into devices. Efforts have explored the relevance of MOFs for applications including, but not limited to, heterogeneous catalysis, guest delivery, water capture, destruction of nerve agents, gas storage, and separation. Recently, several start-up companies have undertaken MOF commercialization within industrial sectors. Herein, we provide a brief overview of the state of the MOF field from their design and synthesis to their potential applications, and finally, to their commercialization.
Baculovirus Vector for Gene Delivery and Vaccine Development (2007)

The baculovirus Autographa californica multiple nucleopolyhedrovirus has been widely used not only to acheive a high level of foreign gene expression in insect cells, but also for efficient gene transduction into mammalian cells. Recombinant and pseudotyped baculoviruses possessing chimeric or foreign ligands have been constructed to improve the efficiency of gene transduction and to confer specificity for gene delivery into mammalian cells, respectively. Baculoviral DNA CpG motifs induce proinflammatory cytokines through a Toll-like receptor (TLR9)/MyD88-dependent signaling pathway. Other baculovirus components produce type I interferons via a TLR-independent pathway. Baculovirus exhibits a strong adjuvant property and recombinant baculoviruses encoding microbial antigens elicit antibodies to the antigens and provide protective immunity in mice. This review deals with recent progress in the application of baculovirus vectors to gene delivery and vaccine development, and discusses the future prospects of baculovirus vectors.
High-Permeability Core Coils for Transcranial Magnetic Stimulation of Deep Brain Regions (2007)

Stimulation of deep brain regions with Transcranial Magnetic Stimulation (TMS) may have an important role as a therapy to treat chemical dependency and depression. The coils traditionally used in TMS, however, have a poor performance in stimulating deep neurons. In this work we study the usage of high permeability cores combined with coils specifically designed to induce fields that decay slowly with depth. By using the finite elements method we show that the use of such cores increases the field's magnitude, decreases its decay rate and improves its focality. Such improvements make these high permeability core coils more suited to stimulate deep brain regions.
Characterization of a recombinant pneumolysin and its use as a protein carrier for pneumococcal type 18C conjugate vaccines (1995)

Pneumolysin from Streptococcus pneumoniae was expressed in Escherichia coli as a glutathione S-transferase fusion protein and purified by affinity and hydroxylapatite chromatography. The purified recombinant pneumolysin (rPL), with a molecular mass of 53 kDa, had a specific activity of 3 x 10(5) hemolytic units per mg of protein on rabbit erythrocytes and reacted identically in immunodiffusion with the antisera against native pneumolysin. The rPL was used as a protein carrier to prepare conjugate vaccine with pneumococcal type 18C polysaccharide (PS18C). The PS18C was directly coupled to rPL by reductive animation or was indirectly coupled to rPL via a spacer molecule, adipic acid dihydrazide. The conjugates were nontoxic for mice and guinea pigs at 100 micrograms per dose. The immunogenicity and protective efficacy of both conjugates were tested in mice. A single dose of either of the vaccines elicited a rise in immunoglobulin G antibody production; after two booster injections of the vaccines, statistically significant booster responses (P < 0.001) to both rPL and PS18C were produced. The sera containing the antibodies to rPL were capable of neutralizing the hemolytic activity of rPL to rabbit erythrocytes and the cytotoxicity of rPL to bovine pulmonary endothelial cells. Immunization with the conjugate vaccines conferred statistically significant protection in mice against lethal challenge with type 18C pneumococci.
Molecular Engineering of Ion-Conducting Polymers for Fuel Cell Membrane Applications (2015)

Aromatic polymers functionalized with various sulfonate groups and ammonium cations were synthesized for use in proton exchange membranes (PEMs) and anion exchange membranes (AEMs), respectively. The effect of these different ionic side groups of polymers on membrane transport properties will be discussed. On second part, high-molecular-weight quaternary ammonium (QA)-tethered aromatic polymers that are void of alkaline labile C–O bonds were prepared to achieve improved stability of AEM fuel cells. This new class of hydrocarbon polymers showed high hydroxide ion conductivity and excellent alkaline stability at 80 °C. Overall, this work provides a new synthetic strategy for preparation of AEMs with good fuel cell performance and excellent stability.
Rapid changes in chromatin structure during dedifferentiation of primary hepatocyte <i>s in vitro</i> (2020)

Abstract Primary hepatocytes are widely used in the pharmaceutical industry to screen drug candidates for hepatotoxicity, but isolated hepatocytes quickly dedifferentiate and lose their mature metabolic function in culture. Attempts have been made to better recapitulate the in vivo liver environment in culture, but the full spectrum of signals required to maintain hepatocyte function in vitro remains elusive. Here we studied the dedifferentiation process in detail through RNA-sequencing of hepatocytes cultured over eight days. We identified three distinct phases of dedifferentiation. An early phase, where mature hepatocyte genes are rapidly downregulated in a matter of hours. A middle phase, where fetal genes are activated, leading to hepatocytes with a fetal phenotype. A late phase, where initially rare contaminating non-parenchymal cells over-grow the culture as the hepatocytes gradually die. Using genetically tagged hepatocytes, we demonstrate that the cells reactivating fetal marker alpha-fetoprotein arise from cells previously expressing the mature hepatocyte marker albumin, and not from albumin negative precursor cells, proving that hepatocytes undergo true dedifferentiation. To better understand the signaling events that result in the rapid down-regulation of mature hepatocyte genes, we examined changes in chromatin accessibility of hepatocytes during the first 24h of culture using ATAC-seq. We find that drastic and rapid changes in chromatin accessibility occurs immediately upon start of culture. Using binding motif analysis of the areas of open chromatin sharing similar temporal profiles, we identify several candidate transcription factors potentially involved in the dedifferentiation of primary hepatocytes in culture.
Establishment of a Serum Tumor Marker for Preclinical Trials of Mouse Prostate Cancer Models (2005)

Current prostate cancer research in both basic and preclinical trial studies employ genetically engineered mouse models. However, unlike in human prostate cancer patients, rodents have no counterpart of prostatic-specific antigen (PSA) for monitoring prostate cancer initiation and progression. In this study, we established a mouse serum tumor marker from a mouse homologue of human prostate secretory protein of 94 amino acids (PSP94). Immunohistochemistry studies on different histologic grades from both transgenic and knock-in mouse prostate cancer models showed the down-regulation of tissue PSP94 expression (P < 0.001), the same as for PSA and PSP94 in humans. The presence of mouse serum PSP94 was shown by affinity column and immunoprecipitation purification using a polyclonal mouse PSP94 antibody. A competitive ELISA protocol was established to quantify serum PSP94 levels with a sensitivity of 1 ng/mL. Quantified serum levels of mouse PSP94 ranged from 49.84 ng/mL in wild-type mice to 113.86, 400.45, and 930.90 ng/mL in mouse prostatic intraepithelial neoplasia with microinvasion, well differentiated, moderately differentiated, and poorly differentiated prostate cancer genetically engineered prostate cancer mice, respectively (P < 0.01, n = 68). This increase in serum PSP94 is also well correlated with age and tumor weight. Through longitudinal monitoring of serum PSP94 levels of castrated mice (androgen ablation therapy), we found a correlation between responsiveness/refractory prostate tissues and serum PSP94 levels. The utility of mouse serum PSP94 as a marker in hormone therapy was further confirmed by three-dimensional ultrasound imaging. The establishment of the first rodent prostate cancer serum biomarker will greatly facilitate both basic and preclinical research on human prostate cancer.
Going beyond the beam quality limit of spectral beam combining of diode lasers in a V-shaped external cavity (2018)

A novel spectral beam combining (SBC) approach based on off-axis feedback in a V-shaped external cavity (VSBC) was proposed and demonstrated. A highly reflecting mirror was used to supply the optical feedback by partial overlapping the beam. The advantages of simple setup, output coupler free, tunable beam quality and emission power over traditional SBC were presented. The beam quality exceeds single emitter with the similar energy conversion efficiency to the traditional SBC. The M<sup>2</sup> factors of 2.31 × 3.76 in fast and slow axes and a brightness of 122 MWcm<sup>-2</sup>sr<sup>-1</sup> were realized at 30 A based on a commercial broad-area diode laser array.
Development and Use of Monoclonal Antibodies Against an Oncofetal Protein Associated with Carcinogenesis and Tumorigenesis (1991)

An oncofetal protein (OFP) studied in our laboratory associated with embryogenesis, carcinogenesis and tumorigenesis has as its known biological function the modification of RNA release from isolated nuclei. In the present study, we have developed and investigated the use of monoclonal antibodies against OFP. Six hybridoma cell lines (A-F) were isolated by screening the hybridoma culture media for anti-OFP antibodies (MOFP) with an indirect ELISA and by testing the ability of these antibodies complexed with anti-mouse IgG-agarose to bind to rat OFP and remove its associated RNA transport activity from solution (Immunobioassay). An inhibition ELISA developed to measure OFP gave a linear response up to 20 ng of plasma protein from a tumor-bearing rat. Western blot analysis using these monoclonals showed that OFP from a rat tumor (H7777) cytosol that shed to the blood consisted of two species exhibiting molecular weights of 50 and 55 kD respectively. In order to show the usefulness of our assays, a preliminary study showing the ability of the immunobioassay to detect the expression of OFP in the plasma of carcinogen treated rats in a dosage dependent manner has been presented. Since OFP is produced in the target organ of rats shortly after treatment with carcinogens and persists in the preneoplastic foci and subsequent tumors, these monoclonal antibodies will be valuable in studying its involvement in chemical carcinogenesis and tumorigenesis.
CMS-PDX: A 20-gene genomic panel to predict consensus molecular subtypes in patient-derived xenografts (PDX) of colorectal cancer. (2019)

598 Background: The consensus molecular subtypes (CMS1-4) partition colorectal cancer (CRC) into subgroups with varying prognoses and treatment responses. We previously reported the ColotypeR-CMS genomic scores (4 scores defined with 5 genes each) that accurately define the CMS subtypes of primary CRC tumors. There is also a critical need to develop an epithelial cell based algorithm for CMS subtyping of PDX models. Methods: To define scores predicting CMS subtypes for PDX models, genes that both predict CMS subtypes in primary CRC tissue and that have linearly correlated expression in primary tumor and tissue-matched PDX models, were identified in GSE35144 (N = 64, Affymetrix microarray). Using the identified genes, a 20-gene CMS-PDX score was developed using multistate gene methodology. ROC curve (AUC) analysis was used to measure the ability of CMS-PDX scores to predict subtypes obtained with CMScaller (473 genes), a preclinical CMS classifier. The ability of CMS subtypes to determine cetuximab response in PDX cohorts was analyzed in GSE78806 (N = 121, Affymetrix microarray) and GSE76402 (N = 529, Illumina beadarray). Results: In GSE78806 (N = 121), CMS1-4 subtypes obtained with CMScaller were predicted by CMS-PDX scores with AUC 0.88, 0.94, 0.81, 0.86, respectively; in GSE78806 CMScaller failed to classify 32% of samples. In CRC-derived PDX models, higher values of the CMS-PDX CMS2 score were predictive of reduced tumor volume following cetuximab treatment (p = 1.7 x 10 -5 in GSE78806, p < 2.2 x 10 -16 in GSE76402, by linear regression.) In contrast, higher values of the CMS1 score were predictive of increased tumor volume (p = 3.8 x 10 -5 in GSE78806, p = 2.9 x 10 -10 in GSE76402.) Change in tumor volume was independent of the CMS-PDX CMS4 score in both PDX cohorts. Conclusions: We showed that the 20-genes CMS-PDX scores are predictive of CMS subtypes obtained with CMScaller. Moreover, CMS2, by CMS-PDX scores, was highly predictive of sensitivity to cetuximab treatment in CRC PDX models.
Optical and Acoustic Monitoring of Bubble Dynamics at a Tissue-fluid Interface in Ultrasound Tissue Erosion (2006)

High intensity pulsed ultrasound can achieve tissue erosion at a tissue‐fluid interface. The mechanism for erosion is believed to be cavitation, as evidenced by a temporally changing acoustic backscatter. To understand the erosion mechanism, optical and acoustic observations are employed to monitor dynamics of the ultrasound generated bubble cloud at a tissue‐fluid interface. The results show that the initiation of variable acoustic backscatter occurs due to formation of a bubble cloud. Pulses of several μsec in duration result in bubble cloud lasting hundreds of μsec, with cavitation nuclei persisting tens of msec. The dynamics of the bubble cloud highly depend on therapy pulse parameters. For example, the life‐time and the size of the bubble cloud are greater with longer pulse duration, higher pulse intensity, and higher PRF.
The structural basis of the inhibition of human <i>α</i>-mannosidases by azafuranose analogues of mannose (1993)

Eight pyrrolidine, five pyrrolizidine and one indolizidine analogue(s) of the known alpha-mannosidase inhibitor, the azafuranose, 1,4-dideoxy-1,4-imino-D-mannitol (DIM), have been tested for inhibition of the multiple forms of alpha-mannosidase in human liver in vitro. Substitution of the ring nitrogen markedly decreased or abolished inhibition, but loss of the C-6 hydroxy group, as in 6-deoxy-DIM and 6-deoxy-6-fluoro-DIM, enhanced inhibition, particularly of the lysosomal alpha-mannosidase. Addition of the anomeric substituent-CH2OH decreased inhibition. To be a potent inhibitor of the lysosomal, Golgi II and neutral alpha-mannosidases, a polyhydroxylated pyrrolidine must have the same substituents and chirality as mannofuranose at C-2, C-3, C-4 and C-5. These four chiral centres can also be part of a polyhydroxylated indolizidine, e.g. swainsonine, but not of a pyrrolizidine, e.g. cyclized DIM, ring-contracted swainsonine or 1,7-diepi-australine. DIM did not inhibit lysosomal alpha-mannosidase intracellularly, but both 6-deoxy-DIM and 6-deoxy-6-fluoro-DIM caused accumulation of partially catabolized glycans in normal human fibroblasts. Analysis of these induced storage products by h.p.l.c. showed that both compounds also inhibited Golgi alpha-mannosidase II and that 6-deoxy-6-fluoro-DIM was also a good inhibitor of the endoplasmic reticulum alpha-mannosidase and specific lysosomal alpha (1-6)-mannosidase. None of the mannofuranose analogues appeared to inhibit Golgi alpha-mannosidase I.
Greedy sparse signal reconstruction from sign measurements (2009)

This paper presents Matched Sign Pursuit (MSP), a new greedy algorithm to perform sparse signal reconstruction from signs of signal measurements, i.e., measurements quantized to 1-bit. The algorithm combines the principle of consistent reconstruction with greedy sparse reconstruction. The resulting MSP algorithm has several advantages, both theoretical and practical, over previous approaches. Although the problem is not convex, the experimental performance of the algorithm is significantly better compared to reconstructing the signal by treating the quantized measurement as values. Our results demonstrate that combining the principle of consistency with a sparsity prior outperforms approaches that use only consistency or only sparsity priors.
Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele (2011)

Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P< 5.0 × 10(-8)): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P= 1.0 × 10(-9)), and two loci previously identified in EA participants, SLC2A9 (P= 3.8 × 10(-32)) and SLC22A12 (P= 2.1 × 10(-10)). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta -1.19 mg/dl, P= 2.7 × 10(-16)). (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants.
The radio-frequency quadrupole (2013)

Radio-frequency quadrupole (RFQ) linear accelerators appeared on the accelerator scene in the late 1970s and have since revolutionized the domain of low-energy proton and ion acceleration. The RFQ makes the reliable production of unprecedented ion beam intensities possible within a compact radio-frequency (RF) resonator which concentrates the three main functions of the low-energy linac section: focusing, bunching and accelerating. Its sophisticated electrode structure and strict beam dynamics and RF requirements, however, impose severe constraints on the mechanical and RF layout, making the construction of RFQs particularly challenging. This lecture will introduce the main beam optics, RF and mechanical features of a RFQ emphasizing how these three aspects are interrelated and how they contribute to the final performance of the RFQ.
Nanoparticle and Gelation Stabilized Functional Composites of an Ionic Salt in a Hydrophobic Polymer Matrix (2014)

Polymer composites consisted of small hydrophilic pockets homogeneously dispersed in a hydrophobic polymer matrix are important in many applications where controlled release of the functional agent from the hydrophilic phase is needed. As an example, a release of biomolecules or drugs from therapeutic formulations or release of salt in anti-icing application can be mentioned. Here, we report a method for preparation of such a composite material consisted of small KCOOH salt pockets distributed in the styrene-butadiene-styrene (SBS) polymer matrix and demonstrate its effectiveness in anti-icing coatings. The mixtures of the aqueous KCOOH and SBS-cyclohexane solutions were firstly stabilized by adding silica nanoparticles to the emulsions and, even more, by gelation of the aqueous phase by agarose. The emulsions were observed in optical microscope to check its stability in time and characterized by rheological measurements. The dry composite materials were obtained via casting the emulsions onto the glass substrates and evaporations of the organic solvent. Composite polymer films were characterized by water contact angle (WCA) measurements. The release of KCOOH salt into water and the freezing delay experiments of water droplets on dry composite films demonstrated their anti-icing properties. It has been concluded that hydrophobic and thermoplastic SBS polymer allows incorporation of the hydrophilic pockets/phases through our technique that opens the possibility for controlled delivering of anti-icing agents from the composite.
Antigen Presentation to Celiac Lesion-Derived T Cells of a 33-Mer Gliadin Peptide Naturally Formed by Gastrointestinal Digestion (2004)

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gluten proteins. A peptide fragment of 33 residues (alpha(2)-gliadin 56-88) produced by normal gastrointestinal proteolysis contains six partly overlapping copies of three T cell epitopes and is a remarkably potent T cell stimulator after deamidation by tissue transglutaminase (TG2). This 33-mer is rich in proline residues and adopts the type II polyproline helical conformation in solution. In this study we report that after deamidation, the 33-mer bound with higher affinity to DQ2 compared with other monovalent peptides harboring gliadin epitopes. We found that the TG2-treated 33-mer was presented equally effectively by live and glutaraldehyde-fixed, EBV-transformed B cells. The TG2-treated 33-mer was also effectively presented by glutaraldehyde-fixed dendritic cells, albeit live dendritic cells were the most effective APCs. A strikingly increased T cell stimulatory potency of the 33-mer compared with a 12-mer peptide was also seen with fixed APCs. The 33-mer showed binding maximum to DQ2 at pH 6.3, higher than maxima found for other high affinity DQ2 binders. The 33-mer is thus a potent T cell stimulator that does not require further processing within APC for T cell presentation and that binds to DQ2 with a pH profile that promotes extracellular binding.
A Novel Connexin 26 Mutation Associated with Autosomal Recessive Sensorineural Deafness (2003)

Mutations in the connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary hearing impairment which affects approximately 1 in 2000 newborn children. We report the identification of a novel Cx26 point mutation (439 G-->A) linked to familial, autosomal recessive, sensorineural hearing loss. This missense mutation (E147K) is located in the highly conserved, putative K(+) channel lining sequence of the third transmembrane domain (TM3) of Cx26. Hearing impairment associated with this mutation was congenital, moderate to profound and showed no signs of progressive deterioration.