gebhart/patrepeval huggingface dataset:
Highly porous, emulsion-templated, zwitterionic hydrogels: amplified and accelerated uptakes with enhanced environmental sensitivity (2018)

Highly porous, emulsion-templated, zwitterionic hydrogels exhibited amplified and accelerated uptakes, enhanced environmental sensitivity, anti-polyelectrolyte behavior, and dual-pH sensitive uptakes.
Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma (2004)

Using Affymetrix oligonucleotide microarrays, we analyzed mRNA gene expression patterns of 12 primary pediatric rhabdomyosarcomas (RMS) and 11 Ewing's sarcomas (EWS), which belong to the small round blue cell tumors (SRBCTs). Diagnostic classification of these cancers is frequently complicated by the highly similar appearance in routine histology, and additional molecular markers could significantly improve tumor classification. A combination of three independent statistical approaches (t-test, SAM, k-nearest neighborhood analysis) resulted in 101 highly significant probe sets that clearly discriminate between EWS and RMS. We identified novel marker transcripts that have not been previously associated with either RMS or EWS yet, including CITED2, glypican 3 (GPC3), and cyclin D1 (CCND1). Expression levels for selected candidate genes were validated by quantitative real-time reverse-transcription PCR. Furthermore, to identify biologically meaningful trends, functional annotations were assigned to 946 genes differentially expressed between EWS and RMS (t-test). Genes involved in protein biosynthesis (n = 28) and complex assembly (n = 9), lipid metabolism (n = 23), energy generation (n = 22), and mRNA processing (n = 11) were expressed significantly higher in EWS. Thus, functional annotation of tumor-specific genes reveals detailed insights into tumor biology and differentiation-specific expression patterns and gives important clues related to the possible cellular origin of these pediatric tumors. Supplementary material for this article is available at the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.
Survival of Frozen Mycoplasmas (1975)

Cooling to -70 C killed a higher percentage of Acholeplasma laidlawii and Mycoplasma mycoides var. capri cells than cooling to -20 C. However, to preserve cell viability for prolonged periods storage at -70 C was much more preferable. The percentage of cells surviving freezing could be increased by increasing the initial cell concentration or by the addition of dimethyl sulfoxide or glycerol as cryoprotective agents. In the presence of 1.5 M of any one of these agents survival rates of up to 100% could be obtained. The optimal cooling rates for maximal survival of A. laidlawii under the experimental conditions tested were 11 C/min for cooling to -20 C and about 15 C/min for cooling to -70 C. Increasing the warming rate during thawing from 0.6 to 67 C/min increased survival by 3 log. Oleic acid enrichment of A. laidlawii membrane lipids, or reduction in the cholesterol content of M. mycoides var. capri membranes, increased the percentage of organisms surviving freezing. Hence, the composition of membrane lipids appears to have a marked influence on the susceptibility of mycoplasmas to freezing injury.
Demonstration of an Electrochemical Liquid Cell for Operando Transmission Electron Microscopy Observation of the Lithiation/Delithiation Behavior of Si Nanowire Battery Anodes (2013)

Over the past few years, in situ transmission electron microscopy (TEM) studies of lithium ion batteries using an open-cell configuration have helped us to gain fundamental insights into the structural and chemical evolution of the electrode materials in real time. In the standard open-cell configuration, the electrolyte is either solid lithium oxide or an ionic liquid, which is point-contacted with the electrode. This cell design is inherently different from a real battery, where liquid electrolyte forms conformal contact with electrode materials. The knowledge learnt from open cells can deviate significantly from the real battery, calling for operando TEM technique with conformal liquid electrolyte contact. In this paper, we developed an operando TEM electrochemical liquid cell to meet this need, providing the configuration of a real battery and in a relevant liquid electrolyte. To demonstrate this novel technique, we studied the lithiation/delithiation behavior of single Si nanowires. Some of lithiation/delithation behaviors of Si obtained using the liquid cell are consistent with the results from the open-cell studies. However, we also discovered new insights different from the open cell configuration-the dynamics of the electrolyte and, potentially, a future quantitative characterization of the solid electrolyte interphase layer formation and structural and chemical evolution.
Efficient and Rapid Induction of Human iPSCs/ESCs into Nephrogenic Intermediate Mesoderm Using Small Molecule-Based Differentiation Methods (2014)

The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an embryonic germ layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.
A Genome-Wide Association Study of Optic Disc Parameters (2010)

The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72x10(-19)) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67x10(-33)) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15x10(-11)) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10)) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.
Molecular Imaging of Biological Samples:  Localization of Peptides and Proteins Using MALDI-TOF MS (1997)

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been used to generate ion images of samples in one or more mass-to-charge (m/z) values, providing the capability of mapping specific molecules to two-dimensional coordinates of the original sample. The high sensitivity of the technique (low-femtomole to attomole levels for proteins and peptides) allows the study of organized biochemical processes occurring in, for example, mammalian tissue sections. The mass spectrometer is used to determine the molecular weights of the molecular in the surface layers of the tissue. Molecules desorbed from the sample typically are singly protonated, giving an ion at (M + H)+, where M is the molecular mass. The procedure involves coating the tissue section, or a blotted imprint of the section, with a thin layer of energy-absorbing matrix and then analyzing the sample to produce an ordered array of mass spectra, each containing nominal m/z values typically covering a range of over 50,000 Da. Images can be displayed in individual m/z values as a selected ion image, which would localize individual compounds in the tissue, or as summed ion images. MALDI ion images of tissue sections can be obtained directly from tissue slices following preparative steps, and this is demonstrated for the mapping of insulin contained in an islet in a section of rat pancreas, hormone peptides in a small area of a section of rat pituitary, and a small protein bound to the membrane of human mucosa cells. Alternatively, imprints of the tissue can be analyzed by blotting the tissue sections on specially prepared targets containing an adsorbent material, e.g., C-18 coated resin beads. Peptides and small proteins bind to the C-18 and create a positive imprint of the tissue which can then be imaged by the mass spectrometer. This is demonstrated for the MALDI ion image analysis of regions of rat splenic pancreas and for an area of rat pituitary traversing the anterior, intermediate, and posterior regions where localized peptides were mapped. In a single spectrum from the anterior/intermediate lobe of a rat pituitary print, over 50 ions corresponding to the peptides present in this tissue were observed as well as precursors, isoforms, and metabolic fragments.
Identification and purification of a protein that induces production of the Lactobacillus acidophilus bacteriocin lactacin B (1994)

Lactacin B is a heat-stable bacteriocin produced by Lactobacillus acidophilus N2 that is active against closely related lactobacilli, including Lactobacillus delbrueckii subsp. lactis (formerly Lactobacillus leichmannii) ATCC 4797. Pure producer cultures propagated in MRS broth (initial pH 6.5) contain no lactacin B; it is detected only in cultures maintained at pH 5.0 to 6.0 and produced optimally at pH 6.0 S. F. Barefoot and T. R. Klaenhammer, Antimicrob. Agents Chemother. 26:328-334, 1984). Associative growth of producer and indicator, L. delbrueckii subsp. lactis ATCC 4797, resulted in production of an inhibitor identical to lactacin B. Associative growth increased lactacin B production from nondetectable levels (< 100 activity units [AU]/ml) to between 3,200 and 6,400 AU/ml in MRS broth (initial pH 6.5) and resulted in early but equal production of lactacin B (approximately 25,600 AU/ml) in broth maintained at pH 6.0. Indicator cells, but not spent culture filtrates, induced lactacin B production. Indicator cells disrupted by a French pressure cell yielded cell-free filtrates containing inducing activity. Chromatofocusing and gel filtration high-performance liquid chromatography of cell-free filtrates yielded a protein with a pI of 4.1 and a molecular size of approximately 58 kDa that induced lactacin B production. Analytical isoelectric focusing yielded a single protein band. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels contained a 28-kDa protein suggesting a two-subunit structure. Protein sequencing identified an N-terminal serine and 18 additional amino acids. To our knowledge, there are not previous descriptions of proteins that induce bacteriocin production in lactic acid bacteria.
Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles (2001)

Dopamine (DA) is a key hormone in mammalian sodium homeostasis. DA induces natriuresis via acute inhibition of the renal proximal tubule apical membrane Na(+)/H(+) exchanger NHE3. We examined the mechanism by which DA inhibits NHE3 in a renal cell line. DA acutely decreases surface NHE3 antigen in dose- and time-dependent fashion without altering total cellular NHE3. Although DA(1) receptor agonist alone decreases surface NHE3, simultaneous DA(2) agonist synergistically enhances the effect of DA(1). Decreased surface NHE3 antigen, caused by stimulation of NHE3 endocytosis, is dependent on intact functioning of the GTPase dynamin and involves increased binding of NHE3 to the adaptor protein AP2. DA-stimulated NHE3 endocytosis can be blocked by pharmacologic or genetic protein kinase A inhibition or by mutation of two protein kinase A target serines (Ser-560 and Ser-613) on NHE3. We conclude that one mechanism by which DA induces natriuresis is via protein kinase A-mediated phosphorylation of proximal tubule NHE3 leading to endocytosis of NHE3 via clathrin-coated vesicles.
A Contemporary Prognostic Nomogram for Men with Hormone-Refractory Metastatic Prostate Cancer: A TAX327 Study Analysis (2007)

This multivariate model identified several new independent prognostic factors in men with metastatic HRPC, including PSA doubling time, and led to the successful development of a clinically applicable nomogram. External prospective validation may support the wider use of this prognostic baseline model for men with HRPC treated with chemotherapy.
The Relationship Between Lupus Anticoagulants and Antibodies to Phospholipid (1988)

The relationship between lupus anticoagulants and antibodies directed against negatively charged phospholipids, as measured by an enzyme-linked immunosorbent assay, was explored in a series of plasma samples from 100 patients with well-characterized lupus anticoagulants. Only 73% of the patients had detectable IgG, IgM antibodies, or both, to one or more of four phospholipids. Of these patients, 29% had IgG-type antibodies only, 56% had both IgG and IgM antibodies, and 15% had IgM antibodies only. Of the 100 patients, 19% had a history of thrombosis, 8% had a history of spontaneous abortion, and 6% had a history of seizure disorder. These complications occurred in the presence (80%) and absence (20%) of detectable antiphospholipid antibodies. Drug-related antibodies were observed in 34 patients; of these, 71% had detectable anti-phospholipid antibodies and 24% had a history of thrombosis. There were ten patients with lupus anticoagulants associated with infections; none of these patients had a history of thrombosis. The results indicate that antiphospholipid antibodies are not present in all patients with lupus anticoagulants, that the presence of antiphospholipid antibodies in patients with lupus anticoagulants does not increase the risk of thrombosis in these patients, and that drug-related antibodies are associated with an increased risk of thrombosis. Lupus anticoagulants and antiphospholipid antibodies seem to define two distinct but related patient populations, each associated with an increased risk of thrombosis.
Development of a force sensor for atomic force microscopy using piezoelectric thin films (1993)

A piezoelectric force sensor has been developed to overcome the complexity of the force detector of the conventional non contact atomic force microscope (AFM). The sensor consists of a cantilever with a piezoelectric thin film deposited on one side. The layer is formed on a thermal SiO2 microbeam and is then encapsulated by a thin passivation film. The piezoelectric film is c-axis oriented ZnO deposited by RF magnetron sputtering, or lead-zirconate-titanate (PZT) prepared by the sol-gel method. The cantilever is excited near its first natural resonance and forces are monitored by detecting the change in the admittance of the layer induced by the piezoelectric effect. The gradient of the force between the tip of the vibrating cantilever and the sample when in close proximity modifies the vibration amplitude, hence inducing a change in the admittance of the layer. A typical sensor with a length of 200 mu m and a width of 50 mu m had a calculated spring constant of 8.7 N m-1 and a first resonance frequency of 72.5 kHz. We have measured a sensor signal as a function of the tip-sample spacing and verified the feasibility of the sensor for a non contact AFM.
Treatment of Heliocobacter pylori: future therapeutic and prophylactic perspectives (1998)

Helicobacter is one of the most widespread, chronic infections in the world and causes a serious disease with a significant mortality. The organism is difficult to eradicate using antibiotic therapy and to date no vaccine is available for use in humans. The most successful treatments comprise acid suppression in combination with two antibiotics and a series of seven day courses will reliably cure around 85% of infected individuals. Further modifications of these regimens via the introduction of newer and more effective antibiotics and acid suppressants may enable the treatment to be simplified, made more effective and cause fewer side effects. However, the major challenge is to develop a specific monotherapy targeted against Helicobacter pylori. The H pylori genome has now been sequenced and this provides an opportunity both to identify specific targets for drug therapy, and to facilitate the identification and production of antigens that may be helpful in manufacturing a vaccine. This paper discusses the future of helicobacter therapy and vaccination.
Microscopy beyond the diffraction limit using actively controlled single molecules (2012)

In this short review, the general principles are described for obtaining microscopic images with resolution beyond the optical diffraction limit with single molecules. Although it has been known for several decades that single-molecule emitters can blink or turn on and off, in recent work the addition of on/off control of molecular emission to maintain concentrations at very low levels in each imaging frame combined with sequential imaging of sparse subsets has enabled the reconstruction of images with resolution far below the optical diffraction limit. Single-molecule active control microscopy provides a powerful window into information about nanoscale structures that was previously unavailable.
Synthetic Approaches to Taxodione. Synthesis of Methyl 12-Oxopodocarpa-5,9(11)-diene-8β-Carboxylate (1978)

Abstract In connection with studies leading to the total synthesis of taxodione1 (1), we required the tricyclic enone 3. We have previously described2 an AB→ABC approach to this intermediate which was flawed by a low yield in the penultimate closure of the C ring (2→3). We now wish to report an alternate synthesis of 3 which involves a BC→ABC approach for the construction of this tricyclic system.
Analysis of the kinetics of isomerization of spiro oxindole alkaloids (1996)

The isomerization of the spiro oxindole alkaloids mitraphylline, isomitraphylline, pteropodine, isopteropodine, speciophylline and uncarine F in water has been studied at several temperatures and the rate coefficients have been determined. The effect of pH on the rate of reaction and the equilibrium composition has been investigated. The rate coefficients in water and in organic solvents correlate satisfactorily with the Dimroth–Reichardt solvent polarity parameter. The present results support the existence of a zwitterionic intermediate stabilized by polar solvents and show that protonation of the alkaloids inhibits the isomerization. The crystal structure of pteropodine has been determined.
Cell-cycle–dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling (2001)

Disruption of the RAS-to-mitogen-activated protein kinase (MAPK/ERK) signaling pathway, either directly through activating RAS gene mutations or indirectly through other genetic aberrations, plays an important role in the molecular pathogenesis of myeloid leukemias. Constitutive activation of ERK-1/2 and MEK-1/2, which elicit oncogenic transformation in fibroblasts, has recently been observed in acute myeloid leukemias (AML). In this study, the activation of the RAS-to-MAPK cascade in 14 AML and 5 chronic myeloid leukemia (CML) cell lines is examined and correlated with the effects of a panel of 9 RAS signaling inhibitors on cell viability, colony formation, cell-cycle progression, and induction of apoptosis. Activation of MEK, ERK, and the transcription factors CREB-1, ATF-1, and c-Myc is demonstrated in the majority of the cell lines (9 of 14 AML and 2 of 5 CML cell lines). Although activation of the ERK cascade did not always correlate with the presence of activating RAS mutations or BCR-Abl, it is linked to the G0/G1 and the G2/M phase of the cell cycle. In contrast to most inhibitors (eg, B581, Cys-4-Abs-Met, FPT-2, FTI-276, and FTS), a significant growth inhibition was only observed for FTI-277 (19 of 19), FPT-3 (10 of 19), and the MEK inhibitors U0126 (19 of 19) and PD098059 (8 of 19). Treatment of NB-4 cells with FTI-277 primarily resulted in a G2/M block, whereas treatment with FPT-3 and U0126 led to induction of apoptosis. FTI-277 revealed strong toxicity toward normal purified CD34+ cells. The results suggest differences in the mechanisms of action and support a potential therapeutic usefulness of these inhibitors in the treatment of myeloid leukemias.
Diffusion-limited aggregation (1983)

Diffusion-limited aggregation (DLA) is an idealization of the process by which matter irreversibly combines to form dust, soot, dendrites, and other random objects in the case where the rate-limiting step is diffusion of matter to the aggregate. We study the process from several points of view stressing the fact that it apparently gives rise to scale-invariant objects whose Hausdorff dimension is independent of short-range details. We show that DLA has no upper critical dimension. We apply scale invariance to study growth, gelation, and the structure factor of aggregates.
One- and two-electron pathways in the electrocatalytic reduction of CO2by fac-Re(bpy)(CO)3Cl (bpy = 2,2′-bipyridine) (1985)

The cyclic voltammetry of fac-Re(bpy)(CO)3Cl (bpy = 2,2′-bipyridine) and of the intermediate complexes formed by bulk electrolysis in MeCN solution in the presence and absence of CO2 has been interpreted in terms of two different electrocatalytic pathways for the reduction of CO2 to Co, one involving an initial one-electron reduction and the other an initial two-electron reduction.
Graph-grammar productions for the modeling of medical dilemmas. (1992)

We introduce graph-grammar production rules, which can guide physicians to construct models for normative decision making. A physician describes a medical decision problem using standard terminology, and the graph-grammar system matches a graph-manipulation rule to each of the standard terms. With minimal help from the physician, these graph-manipulation rules can construct an appropriate Bayesian probabilistic network. The physician can then assess the necessary probabilities and utilities to arrive at a rational decision. The grammar relies on prototypical forms that we have observed in models of medical dilemmas. We have found graph grammars to be a concise and expressive formalism for describing prototypical forms, and we believe such grammars can greatly facilitate the modeling of medical dilemmas and medical plans.