gebhart/patrepeval huggingface dataset:
Wnt and Notch Signals Guide Embryonic Stem Cell Differentiation into the Intestinal Lineages (2013)

The studies of differentiation of mouse or human embryonic stem cells (hESCs) into specific cell types of the intestinal cells would provide insights to the understanding of intestinal development and ultimately yield cells for the use in future regenerative medicine. Here, using an in vitro differentiation procedure of pluripotent stem cells into definitive endoderm (DE), inductive signal pathways' guiding differentiation into intestinal cells was investigated. We found that activation of Wnt/β-catenin and inhibition of Notch signaling pathways, by simultaneous application of 6-bromoindirubin-3'-oxime (BIO), a glycogen synthase kinase-3β inhibitor, and N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester (DAPT), a known γ-secretase inhibitor, efficiently induced intestinal differentiation of ESCs cultured on feeder cell. BIO and DAPT patterned the DE at graded concentrations. Upon prolonged culture on feeder cells, all four intestinal differentiated cell types, the absorptive enterocytes and three types of secretory cells (goblet cells, enteroendocrine cells, and Paneth cells), were efficiently differentiated from mouse and hESC-derived intestinal epithelium cells. Further investigation revealed that in the mouse ESCs, fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signaling act synergistically with BIO and DAPT to potentiate differentiation into the intestinal epithelium. However, in hESCs, FGF signaling inhibited, and BMP signaling did not affect differentiation into the intestinal epithelium. We concluded that Wnt and Notch signaling function to pattern the anterior-posterior axis of the DE and control intestinal differentiation.
Amino Acid Analysis of the Isolated and Purified Components from Crystalline Toxin of Clostridium botulinum Type A (1970)

The toxic and hemagglutinating components of the crystalline toxin of Clostridium botulinum were analyzed for their amino acid content and were proven to be completely different proteins.
T Cell Proliferation in Response to Interleukins 2 and 7 Requires p38MAP Kinase Activation (1997)

Interleukin-2 (IL-2) is a potent T cell mitogen. However, the signaling pathways by which IL-2 mediates its mitogenic effect are not fully understood. One of the members of the mitogen-activated protein kinase (MAPK) family, p42/44MAPK (ERK2/1), is known to be activated by IL-2. We have now investigated the response to IL-2 of two other members of the MAP kinase family, p54MAP kinase (stress-activated protein kinase (SAPK)/Jun-N-terminal kinase (JNK)) and p38MAP kinase (p38/Mpk2/CSBP/RK), which respond primarily to stressful and inflammatory stimuli (e.g. tumor necrosis factor-alpha, IL-1, and lipopolysaccharide). Here we show that IL-2, and another T cell growth factor, IL-7, activate both SAPK/JNK and p38MAP kinase. Furthermore, inhibition of p38MAP kinase activity with a specific pyrinidyl imidazole inhibitor SB203580 that prevents activation of its downstream effector, MAPK-activating protein kinase-2, correlated with suppression of IL-2- and IL-7-driven T cell proliferation. These data indicate that in T cells p38MAP kinase has a role in transducing the mitogenic signal.
Cholesterol as Modulator of Receptor Function (1997)

The modulatory effect of cholesterol on the function of two structurally related peptide receptors, the oxytocin receptor and the brain cholecystokinin receptor in plasma membranes as well as in intact cells, was analyzed. Different approaches for cholesterol modification were applied: (i) depletion and reloading of cholesterol mediated by methyl-beta-cyclodextrin and cholesterol-methyl-beta-cyclodextrin, respectively, in a reversible manner; (ii) mild treatment of the plasma membranes with cholesterol oxidase under control of the membrane fluidity as measured by fluorescence anisotropy of diphenylhexatriene; and (iii) filipin pretreatment of membranes. The results allowed us to distinguish two mechanisms of cholesterol affecting the ligand-binding function of receptors: changes of the membrane fluidity as demonstrated for the cholecystokinin receptor, or a putatively specific cholesterol-receptor interaction as shown for the oxytocin receptor. This was confirmed in a structure-activity analysis with a variety of sterol analogues substituting for cholesterol in the membranes. While the agonist binding of the cholecystokinin receptor was supported by each of the tested steroids and was well correlated with the corresponding fluorescence anisotropy values, a stringent and unique requirement of the oxytocin receptor's affinity state for structural features of the sterol molecule was found. The molecular requirements differ both from those postulated for sterol-phospholipid interactions and from those known to be necessary for the functional activity of other proteins. The different behavior of both peptide receptors concerning the cholesterol dependence of their ligand binding was also present in vivo at the level of signal transduction. The results suggest that cholesterol can modulate receptor function by two distinct mechanisms, by changes of the membrane fluidity, and/or by a highly specific molecular interaction.
Integrin regulation of leukocyte inflammatory functions. CD11b/CD18 enhancement of the tumor necrosis factor-alpha responses of monocytes (1993)

Engagement of the integrin CD11b/CD18 (alpha M beta 2, Mac-1, CR3) on cells of monocyte (Mo) lineage has recently been demonstrated to enhance synthesis and surface expression of the integral plasmalemma receptor tissue factor. The role of cognate interactions between integrin and its ligands in the regulation of cellular responses important to inflammation can be extended to the effect on the enhancement of TNF-alpha mRNA accumulation and protein secretion by Mo once stimulated by an initial signal such as LPS. At a concentration optimal for inducing TNF-alpha responses, LPS was observed to rapidly increase by two- to threefold the surface expression on Mo of CD11b but not CD11a or CD11c. In the absence of initial signal, engagement of CD11/CD18 integrins per se failed to elicit a TNF-alpha response. In the presence of the initial transcriptional agonist LPS, both TNF-alpha mRNA expression and protein secretion were enhanced several-fold by cells adherent to a CD11b/CD18 ligand, to endothelial cells as well as engagement of CD11b/CD18 integrin by specific antibodies. This enhancement appears to be CD11b/CD18 specific and not from mere attachment or spreading. The enhancement effect after HUVEC binding was inhibited 75% by anti-CD11b mAb M1/70. These studies lead to the hypothesis that engagement of the CD11b/CD18 integrin results in the transduction of cellular signals that quantitatively enhance the expression of inflammatory mediators of Mo-mediated responses.
Molecular beacon probes combined with amplification by NASBA enable homogeneous, real-time detection of RNA (1998)

Molecular beacon probes can be employed in a NASBA amplicon detection system to generate a specific fluorescent signal concomitantly with amplification. A molecular beacon, designed to hybridize within the target sequence, was introduced into NASBA reactions that amplify the genomic RNA of potato leafroll virus (PLRV). During amplification, the probe anneals to the antisense RNA amplicon generated by NASBA, producing a specific fluorescent signal that can be monitored in real-time. The assay is rapid, sensitive and specific. As RNA amplification and detection can be carried out in unopened vessels, it minimizes the risk of carry-over contaminations. Robustness has been verified on real-world samples. This homogeneous assay, called AmpliDet RNA, is a significant improvement over current detection methods for NASBA amplicons and is suitable for one-tube applications ranging from high-throughput diagnostics to in vivo studies of biological activities.
A Low-Spin d5 Iron Imide:  Nitrene Capture by Low-Coordinate Iron(I) Provides the 4-Coordinate Fe(III) Complex [PhB(CH2PPh2)3]Fe⋮N-p-tolyl (2002)

Entry into "[PhBP3]Fe" chemistry affords a rare, pseudotetrahedral iron(I) complex, [PhBP3]Fe(PPh3), with an S = 3/2 ground state. This precursor undergoes rapid oxidation by aryl azide to produce the d5 imide [PhBP3]FeNAr (Ar = p-tolyl). The Fe(III) imide is significant in that it is low-spin and represents the first mononuclear imide of iron. Doublet [PhBP3]FeNAr reacts rapidly and quantitatively with CO at room temperature to release isocyanate and [PhBP3]Fe(CO)2. The [PhBP3]Fe(CO)2 byproduct is also a precursor to [PhBP3]FeNAr upon addition of aryl azide.
A Hybrid System Based on Neural Network and Immune Co-Evolutionary Algorithm for Garment Pattern Design Optimization (2009)

The purpose of this study is to develop a system to utilize the successful experiences and help the beginners of garment pattern design (GPD) by optimization methods. A hybrid algorithm (NN-ICEA) based on Neural Network (NN) and immune co-evolutionary algorithm (ICEA) to predict the fit of the garments and search optimal sizes. ICEA takes NN as fitness function and procedures including clonal proliferation, hyper-mutation and co-evolution search the optimal size values. Then, a series of experiments with a dataset of 450 pieces of garments are conducted to demonstrate the prediction and optimization capabilities of NN-ICEA. In the comparative studies, NN-ICEA is compared with NN-GA to show the value of immune inspired operators. Four types of GPD methods are summarized and compared. Moreover, the hybrid system for general features of garment is discussed. The fit prediction based on NN can achieve the high accuracy with the error rate less than 0.2. The size optimization based on ICEA works well when number of the missing sizes is less than 1/3 of the total size number. The research is a feasible and effective attempt aiming at a valuable problem and provides key algorithms for fit prediction and size optimization. The algorithms can be incorporated into garment CAD system.
Genetic Variations in Calpain-10 Gene Are Not a Major Factor in the Occurrence of Type 2 Diabetes in Japanese (2003)

The 112/121 haplotype combination defined by the UCSNP-43, -19, and -63 alleles in the calpain-10 gene is associated with type 2 diabetes in Mexican Americans. To determine whether this genetic variation constitutes risk of type 2 diabetes in Japanese, we investigated its frequency in 177 patients with type 2 diabetes and 172 controls. Though this variation occurs in Japanese more frequently than in Mexican Americans, there is no significant difference in frequency between diabetic (29.9%) and control (31.9%) subjects. We also screened all exons and the putative promoter of the calpain-10 gene for mutations in 96 of the genotyped patients, resulting in the identification of 7 coding variants, including 3 missense mutations and 5 nucleotide alterations in the promoter. However, their frequencies all are similar in patients and controls, suggesting that these genetic variations are not a major factor in the occurrence of type 2 diabetes in Japanese, although they could yet be associated with various phenotypes of the disease.
A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β3-galactosyltransferase (2002)

Human core 1 beta3-galactosyltransferase (C1beta3Gal-T) generates the core 1 O-glycan Galbeta1-3GalNAcalpha1-SerThr (T antigen), which is a precursor for many extended O-glycans in animal glycoproteins. We report here that C1beta3Gal-T activity requires expression of a molecular chaperone designated Cosmc (core 1 beta3-Gal-T-specific molecular chaperone). The human Cosmc gene is X-linked (Xq23), and its cDNA predicts a 318-aa transmembrane protein ( approximately 36.4 kDa) with type II membrane topology. The human lymphoblastoid T cell line Jurkat, which lacks C1beta3Gal-T activity and expresses the Tn antigen GalNAcalpha1-SerThr, contains a normal gene and mRNA encoding C1beta3Gal-T, but contains a mutated Cosmc with a deletion introducing a premature stop codon. Expression of Cosmc cDNA in Jurkat cells restored C1beta3Gal-T activity and T antigen expression. Without Cosmc, the C1beta3Gal-T is targeted to proteasomes. Expression of active C1beta3Gal-T in Hi-5 insect cells requires coexpression of Cosmc. Overexpression of active C1beta3Gal-T in mammalian cell lines also requires coexpression of Cosmc, indicating that endogenous Cosmc may be limiting. A small portion of C1beta3Gal-T copurifies with Cosmc from cell extracts, demonstrating physical association of the proteins. These results indicate that Cosmc acts as a specific molecular chaperone in assisting the foldingstability of C1beta3Gal-T. The identification of Cosmc, a uniquely specific molecular chaperone required for a glycosyltransferase expression in mammalian cells, may shed light on the molecular basis of acquired human diseases involving altered O-glycosylation, such as IgA nephropathy, Tn syndrome, Henoch-Schönlein purpura, and malignant transformation, all of which are associated with a deficiency of C1beta3Gal-T activity.
Passive Perchorionic Carcinogen Bioassay Using Rainbow Trout (Salmo gairdneri) Embryos (1986)

A noninvasive method for exposing eyed-stage rainbow trout (Salmo gairdneri) embryos to chemicals in a bioassay for toxicity and carcinogenicity was tested with four known mammalian carcinogens. Aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), dimethylnitrosamine (DMN), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were applied topically in dimethyl sulfoxide (DMSO) to the chorion of developing rainbow trout embryos. All chemicals were toxic and decreased viability of fry after hatching. In addition, AFB1 (90 ng/egg) increased mortality in the egg stage and was the most toxic chemical tested. After a latent period of eight months, all chemicals had induced liver neoplasms in surviving fingerlings. The incidence of liver neoplasia ranged from 4.8% for DMN at 170.7 µg/egg to 76.9% for MNNG at 20.5 µg/egg and generally was in the form of basophilic foci of altered hepatocytes. Eleven months post exposure, all treatment groups had individuals with well-differentiated hepatocellular carcinomas. The data suggest that the method has the potential to be a useful bioassay for chemical carcinogenicity.
Microfluidic plug steering using surface acoustic waves (2015)

Digital microfluidic systems, in which isolated droplets are dispersed in a carrier medium, offer a method to study biological assays and chemical reactions highly efficiently. However, it's challenging to manipulate these droplets in closed microchannel devices. Here, we present a method to selectively steer plugs (droplets with diameters larger than the channel's width) at a specially designed Y-junction within a microfluidic chip. The method makes use of surface acoustic waves (SAWs) impinging on a multiphase interface in which an acoustic contrast is present. As a result, the liquid-liquid interface is subjected to acoustic radiation forces. These forces are exploited to steer plugs into selected branches of the Y-junction. Furthermore, the input power can be finely tuned to split a plug into two uneven plugs. The steering of plugs as a whole, based on plug volume and velocity is thoroughly characterized. The results indicate that there is a threshold plug volume after which the steering requires elevated electrical energy input. This plug steering method can easily be integrated to existing lab-on-a-chip devices and it offers a robust and active plug manipulation technique in closed microchannels.
Recognizing scene viewpoint using panoramic place representation (2012)

We introduce the problem of scene viewpoint recognition, the goal of which is to classify the type of place shown in a photo, and also recognize the observer's viewpoint within that category of place. We construct a database of 360° panoramic images organized into 26 place categories. For each category, our algorithm automatically aligns the panoramas to build a full-view representation of the surrounding place. We also study the symmetry properties and canonical viewpoint of each place category. At test time, given a photo of a scene, the model can recognize the place category, produce a compass-like indication of the observer's most likely viewpoint within that place, and use this information to extrapolate beyond the available view, filling in the probable visual layout that would appear beyond the boundary of the photo.
Deep learning-based assessment of tumor-associated stroma for diagnosing breast cancer in histopathology images (2017)

Diagnosis of breast carcinomas has so far been limited to the morphological interpretation of epithelial cells and the assessment of epithelial tissue architecture. Consequently, most of the automated systems have focused on characterizing the epithelial regions of the breast to detect cancer. In this paper, we propose a system for classification of hematoxylin and eosin (H&E) stained breast specimens based on convolutional neural networks that primarily targets the assessment of tumor-associated stroma to diagnose breast cancer patients. We evaluate the performance of our proposed system using a large cohort containing 646 breast tissue biopsies. Our evaluations show that the proposed system achieves an area under ROC of 0.92, demonstrating the discriminative power of previously neglected tumor associated stroma as a diagnostic biomarker.
Controlled Release Carbamazepine: Cognitive Side Effects in Patients with Epilepsy (1987)

The treatment of epilepsy with carbamazepine (CBZ) may be hampered by cognitive side effects. These side effects are thought to be related to pharmacokinetic properties of the drug. The serum concentration of CBZ is characterized by rapid absorption and a short half-life, which may lead to a considerable fluctuation of the level between doses. Cognitive defects may result from peak levels: short periods with high serum concentration. In a single-blind crossover design, cognitive performance was compared in three conditions. All patients were first tested in the steady state of conventional CBZ. The patients were then assigned randomly to either CBZ-controlled release (CR) or a condition in which conventional CBZ was administered in the same tablet form and dose frequency as CR. Psychological tests were administered four times daily, immediately after the serum samples were taken. A nonmedication control group was tested following the same test scheme to obtain standards for the evaluation of changes in performance during the day. A systematic tendency was found toward higher test performance in the CR condition. This is especially evident for tests of memory and accuracy of visual information processing. The results of the repeated test procedure show that the smoothing effect of the CR condition on serum concentration fluctuations results in a more stable pattern of cognitive functioning during the day.
Passive music listening spontaneously engages limbic and paralimbic systems (2004)

In this PET study, non-musicians passively listened to unfamiliar instrumental music revealed afterward to elicit strongly pleasant feelings. Activations were observed in the subcallosal cingulate gyrus, prefrontal anterior cingulate, retrosplenial cortex, hippocampus, anterior insula, and nucleus accumbens. This is the first observation of spontaneous responses in such limbic and paralimbic areas during passive listening to unfamiliar although liked music. Activations were also seen in primary auditory, secondary auditory, and temporal polar areas known to respond to music. Our findings complement neuroimaging studies of aesthetic responses to music that have used stimuli selected by subjects or designed by experimenters. The observed pattern of activity is discussed in terms of a model synthesizing emotional and cognitive responses to music.
Mesenchymal Stem Cells (2009)

In the summer of 1964, I took a graduate pathology course for non-MDs given by Professor Guido Mino at Harvard Medical School. Dr Jerry Gross gave a 2-hour lecture in that course which went from the chemistry and structure of collagen up through the collagenase-mediated destruction of collagen during tadpole tail resorption and metamorphosis. This lecture changed my life forever and set the tone of my thinking and research by demonstrating the continuum of molecules through the control of biological phenomena as seen through the eyes of a biochemist and developmental biologist. In 1967, I started a postdoctoral fellowship with Nathan O. Kaplan, PhD, at Brandeis University where I met and joined the lab of Edgar Zwilling, PhD. Professor Zwilling was a renowned embryologist and developmental biologist1,2 who taught me about these subjects as I started studying the differentiation capacity of undifferentiated embryonic chick limb mesodermal cells in culture.3 These cells were mesenchymal stem cells (MSCs) that have the capabilities to differentiate in vitro into a number of mesodermal phenotypes by controlling the initial seeding density in culture and the medium additives and conditions.4-6 Thus, I was able to study the molecular control of embryonic chick limb cell differentiation and limb development7 in ways complementary to those described by Dr Gross 5 years earlier. This was the start of my MSC journey and experimental exploits.
In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand (TPO) on purified murine hematopoietic stem cells (1994)

Recently, the ligand for c-mpl has been identified and cloned. Initial studies of this molecule indicate that it is the platelet regulatory factor, thrombopoietin (TPO). Previous work has indicated that c-mpl is expressed in very immature hematopoietic precursors and thus raised the possibility that TPO may act directly on the hematopoietic stem cell. Therefore, in these studies, we investigate the effects of TPO on hematopoietic stem cell populations isolated from the murine fetal liver and bone marrow. Cocultivation of stem cells with fetal liver stroma give rise to multilineage expansion of the stem cells but with little or no megakaryocytopoiesis. Addition of TPO to these cocultures gives significant megakaryocyte production. This production is enhanced in combination with Kit ligand or interleukin-3. The addition of TPO to stem cell suspension cultures produces a dynamic thrombopoietic system in which stem cells undergo differentiation to produce megakaryocytes and proplatelets. These experiments show that the megakaryocytopoietic and thrombopoietic activities of TPO are initiated at the level of an early progenitor cell or upon the hematopoietic stem cell.
Hemodynamics of the splanchnic and systemic circulation after hypotonic water load-comparison between normal subjects and patients with congestive heart failure. (1983)

The authors investigated the changes in cardiovascular and splanchnic hemodynamic, diuresis and urinary and hepatic veins osmolarity induced by hypotonic water load in five normal subjects and in five patients with congestive heart failure (CHF). Pulmonary wedge pressure increased significantly only in CHF patients while cardiac index, total pulmonary resistances and peripheral vascular resistances remained unchanged in both groups. Hepatic blood flow increased significantly in control group while in CHF showed a significant reduction 15 and 30 minutes after water load. Hepatic veins osmolarity decreased significantly in control group only at the 45th minute. Diuresis was significantly higher in normals which eliminated water load with a lower urinary osmolarity. The authors conclude that: water loading is particularly interesting in so much it resembles the physiological conditions of the absorption of the alimentary hypotonic bolus; the failing heart responds to the water load on a depressed function curve; the hepatic blood flow is reduced in CHF patients and is probably responsible for some humoral abnormalities found in these subjects; CHF patients eliminate a water load slower than a normal subject and with a higher osmolarity.