gebhart/patrepeval huggingface dataset:
Energy Balance in Rhesus Monkeys (Macaca mulatta) Subjected to Long-term Dietary Restriction (1995)

Male rhesus monkeys of various age groups representative of the species life span were fed ad libitum amounts (controls) or 30% less food than control monkeys of comparable age and body weight. Despite significantly lowered energy intake and body weight, the amount of energy lost in the feces, and fecal energy density (concentration) were not altered in diet-restricted (DR) monkeys, compared to age- and weight-matched controls. Absolute energy expenditure (EE; 24-hr) was consistently lower in DR monkeys, but this trend was not statistically significant. Expressed as a function of metabolic mass (body weight, metabolic body size, lean mass), 24-hr EE was not different in monkeys subjected to long-term DR, compared to controls. Calculations of net energy (intake-loss), as an index of energy balance, revealed that energy expenditure generally exceeded energy intake in all juvenile and adult group monkeys. However, this discrepancy was not statistically different from zero, suggesting that most animals were in energy balance. Also, there was no difference between control and DR animals with respect to energy balance. Diet restriction induced significant reductions in the absolute amount of lean body mass; however, percent (of total weight) lean and fat mass did not differ from controls.
Math Operation Embeddings for Open-ended Solution Analysis and Feedback (2021)

Feedback on student answers and even during intermediate steps in their solutions to open-ended questions is an important element in math education. Such feedback can help students correct their errors and ultimately lead to improved learning outcomes. Most existing approaches for automated student solution analysis and feedback require manually constructing cognitive models and anticipating student errors for each question. This process requires significant human effort and does not scale to most questions used in homework and practices that do not come with this information. In this paper, we analyze students' step-by-step solution processes to equation solving questions in an attempt to scale up error diagnostics and feedback mechanisms developed for a small number of questions to a much larger number of questions. Leveraging a recent math expression encoding method, we represent each math operation applied in solution steps as a transition in the math embedding vector space. We use a dataset that contains student solution steps in the Cognitive Tutor system to learn implicit and explicit representations of math operations. We explore whether these representations can i) identify math operations a student intends to perform in each solution step, regardless of whether they did it correctly or not, and ii) select the appropriate feedback type for incorrect steps. Experimental results show that our learned math operation representations generalize well across different data distributions.
Porcine valves: Hancock and Carpentier-Edwards aortic prostheses. (1996)

Hancock and Carpentier-Edwards porcine bioprostheses are the two most widely implanted biological valves and have become the standard by which the performance of newer tissue valves are measured. New guidelines for reporting valve-related complications have provided more comprehensive evaluations and meaningful comparison of the long-term results of valve substitutes. Clinical investigations directly comparing the Hancock and Carpentier-Edwards bioprostheses have shown no significant differences in the long-term performance of these two valves. The incidence of structural valve deterioration for porcine bioprostheses begins to increase 5 to 6 years after implantation. For patients undergoing aortic valve replacement, estimates of freedom from structural valve deterioration at 10 and 15 years range from 76% to 91% and 37% to 63%, respectively. The incidence of structural valve deterioration may be offset by the limited survival of older patients; thus, the durability of a bioprosthesis may be sufficient for the majority of these patients. The long-term results of the porcine bioprosthesis have been satisfactory, particularly in older patients and those undergoing aortic valve replacement. The performance of the Hancock modified orifice (MO) bioprosthesis is comparable with that of other bioprostheses despite its more complex fabrication process. Although it does not offer any distinct advantages in terms of durability, the Hancock MO valve is associated with lower pressure gradients and larger calculated valve areas compared with other porcine valves in the smaller sizes. Based on currently available data, there are no distinct differences in the performance of the second-generation porcine bioprostheses compared with the first-generation valves, and any purported advantages need to be confirmed with long-term evaluations.
Human ClC‐6 is a lipid raft associated glycoprotein that resides in late endosomes in neuronal cells but not upon overexpression in COS and HeLa cells (2007)

The mammalian CLC family comprises 9 proteins (ClC‐1 to ‐7 and ClC‐Ka, ‐Kb) that function either as plasma membrane chloride channels or as intracellular chloride/proton antiporters. Recently, ClC‐6 has been described as a late endosomal/lysosomal protein in neuronal cells and a lysosomal storage disease is associated with abolition of its function. We have developed a polyclonal antibody that recognizes human ClC‐6 (hClC‐6) both upon overexpression (COS and Hela cells) and endogenous in a human neuronal cell line (SH‐SY5Y). Confocal immunofluorescence experiments showed that endogenous hClC‐6 in SH‐SY5Y cells resides in a late endosomal compartment. However, upon overexpression in COS and HeLa cells, hClC‐6 colocalized with early endosomal markers but not with different markers for late endosomes/lysosomes. This suggests that ClC‐6 is sorted to late endosomes via an intermediary early endosomal compartment and that this sorting step is rate‐limiting in COS and HeLa cells. Furthermore, hClC‐6 copurifies with detergent resistant membrane fractions suggesting partitioning in lipid rafts. Finally, hClC‐6 is N‐glycosylated upon overexpression. Three asparagines residues have been identified as acceptor sites for N‐glycosylation, but only two of three are simultaneously N‐glycosylated in the wild type protein. We therefore conclude that hClC‐6 is a lipid‐raft associated endosomal glycoprotein.
Cover Picture: Kinetically Controlled, Shape‐Directed Assembly of Nanorods (Small 2/2008) (2008)

The cover picture shows various superstructures generated using kinetically controlled assembly. These scanning electron microscopy images are overlaid on an image of the building blocks—two part gold/polypyrrole nanorods—that constitute each structure. Templating orients and spaces the nanorods such that they form discrete structures. Photolithography preselects rods to assemble into a given structure, thereby dictating the resulting shape. This kinetic control allows for designer assemblies that incorporate more than 106 building blocks. For more information, please read the Communication by C. Mirkin et al., beginning on page 206.
Evidence for structured variation in self-renewal capacity within long-term bone marrow cultures. (1980)

Bone marrow pluripotent stem cells (CFUs) demonstrate capacity for both proliferation and differentiation. The proliferative capacity of CFUs has been measured by serial transplantability and by the Rs, a measurement of CFU production in a single 14-day transfer. In the present study, the self-renewal capacity fo both adherent and nonadherent CFUs from long-term bone marrow cultures was measured. Culture conditions were established such that nonadherent cells were derived from the adherent cell layer. Both adherent and non-adherent cells produced spleen colonies, demonstrating that significant proliferative potential was present in both locations; however, at all times in culture, the CFUs within the adherent stromal cell layer had a significantly greater self-renewal capacity than did the nonadherent CFUs. During the initial establishment of the cultures, the self-renewal capacity of the adherent CFUs decreased as the total number of CFUs per flask increased. After 3 weeks in culture, the self-renewal potential of the adherent CFUs stabilized and was maintained. These results suggest two different mechanisms of stem cell proliferation. In order to increase the most primitive stem cell pool size, there was initial proliferation of early stem cells with a concomitant decrease in self renewal capacity. Once this pool was established, the self-renewal capacity of the adherent CFUs maintained for 13 weeks in culture suggests that CFU production and cell maintenance were achieved by clonal succession.
GATA-4 Activates Transcription Via Two Novel Domains That Are Conserved within the GATA-4/5/6 Subfamily (1997)

GATA-4 is one of the earliest developmental markers of the precardiac mesoderm, heart, and gut and has been shown to activate regulatory elements controlling transcription of genes encoding cardiac-specific proteins. To elucidate the molecular mechanisms underlying the transcriptional activity of the GATA-4 protein, structure-function analyses were performed. These analyses revealed that the C-terminal zinc finger and adjacent basic domain of GATA-4 is bifunctional, modulating both DNA-binding and nuclear localization activities. The N terminus of the protein encodes two independent transcriptional Activation Domains (amino acids 1-74 and amino acids 130-177). Amino acid residues were identified within each domain that are required for transcriptional activation. Finally, we have shown that regions of Xenopus GATA-5 and -6 corresponding to Activation Domains I and II, respectively, function as potent transcriptional activators. The identification and functional characterization of two evolutionarily conserved transcriptional Activation Domains within the GATA-4/5/6 subfamily suggests that each of these domains modulates critical functions in the transcriptional regulatory program(s) encoded by GATA-4, -5, and -6 during vertebrate development. As such these data provide novel insights into the molecular mechanisms that control development of the heart.
Efficient production of membrane‐integrated and detergent‐soluble G protein‐coupled receptors inEscherichia coli (2008)

G protein-coupled receptors (GPCRs) are notoriously difficult to express, particularly in microbial systems. Using GPCR fusions with the green fluorescent protein (GFP), we conducted studies to identify bacterial host effector genes that result in a general and significant enhancement in the amount of membrane-integrated human GPCRs that can be produced in Escherichia coli. We show that coexpression of the membrane-bound AAA+ protease FtsH greatly enhances the expression yield of four different class I GPCRs, irrespective of the presence of GFP. Using this new expression system, we produced 0.5 and 2 mg/L of detergent-solubilized and purified full-length central cannabinoid receptor (CB1) and bradykinin receptor 2 (BR2) in shake flask cultures, respectively, two proteins that had previously eluded expression in microbial systems.
Image representation by blob and its application in CT reconstruction from few projections (2011)

The localized radial symmetric function, or blob, is an ideal alternative to the pixel basis for X-ray computed tomography (CT) image reconstruction. In this paper we develop image representation models using blob, and propose reconstruction methods for few projections data. The image is represented in a shift invariant space generated by a Gaussian blob or a multiscale blob system of different frequency selectivity, and the reconstruction is done through minimizing the Total Variation or the 1 norm of blob coefficients. Some 2D numerical results are presented, where we use GPU platform for accelerating the X-ray projection and back-projection, the interpolation and the gradient computations.
Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists. (2012)

New derivatives of 2-[2-(2-Chlorophenoxy)phenyl]-1,3,4-oxadiazole as candidates for agonistic effect on benzodiazepine receptors were synthesized. Conformational analysis and superimposition of energy minima conformers of the novel compounds on estazolam, a known benzodiazepine agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. In pharmacological evaluation, anticonvulsant activity of the compounds determined by pentylenetetrazole-induced lethal convulsion and maximal electroshock tests. The results showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 6 that has a considerable effect. Compound 8 with a hydroxyl substituent on position 5 of 1,3,4- oxadiazole ring showed a relatively mild anticonvulsant activity, which was significantly weaker than that of diazepam and compound 6. Anticonvulsant effects of active compounds were antagonized by flumazenil, an antagonist of benzodiazepine receptors, indicating the involvement of benzodiazepine receptors in these effects.
Selective and Potent Raf Inhibitors Paradoxically Stimulate Normal Cell Proliferation and Tumor Growth (2010)

Raf inhibitors are under clinical investigation, specifically in patients with tumor types harboring frequent activating mutations in B-Raf. Here, we show that cell lines and tumors harboring mutant B-Raf were sensitive to a novel series of Raf inhibitors (e.g., (V600E)B-Raf A375, IC(50) on cells = 2 nmol/L; ED(50) on tumor xenografts = 1.3 mg/kg). However, in cells and tumors with wild-type B-Raf, exposure to Raf inhibitors resulted in a dose-dependent and sustained activation of mitogen-activated protein kinase signaling. In some of these cell lines, Raf inhibition led to entry into the cell cycle, enhanced proliferation, and significantly stimulated tumor growth in vivo. Inhibition with structurally distinct Raf inhibitors or isoform-specific small interfering RNA knockdown of Raf showed that these effects were mediated directly through Raf. Either A-Raf or C-Raf mediated the Raf inhibitor-induced mitogen-activated protein kinase pathway activation in an inhibitor-specific manner. These paradoxical effects of Raf inhibition were seen in malignant and normal cells in vitro and in vivo. Hyperplasia of normal epithelial cells in the esophagus and the stomach was evident in mice with all efficacious Raf inhibitors (n = 8) tested. An implication of these results is that Raf inhibitors may induce unexpected normal cell and tumor tissue proliferation in patients.
Unnatural helical peptidic foldamers as protein segment mimics (2023)

Unnatural helical peptidic foldamers have attracted considerable attention owing to their unique folding behaviours, diverse artificial protein binding mechanisms, and promising applications in chemical, biological, medical, and material fields. Unlike the conventional α-helix consisting of molecular entities of native α-amino acids, unnatural helical peptidic foldamers are generally comprised of well-defined backbone conformers with unique and unnatural structural parameters. Their folded structures usually arise from unnatural amino acids such as <i>N</i>-substituted glycine, <i>N</i>-substituted-β-alanine, β-amino acid, urea, thiourea, α-aminoxy acid, α-aminoisobutyric acid, aza-amino acid, aromatic amide, γ-amino acid, as well as sulfono-γ-AA amino acid. They can exhibit intriguing and predictable three-dimensional helical structures, generally featuring superior resistance to proteolytic degradation, enhanced bioavailability, and improved chemodiversity, and are promising in mimicking helical segments of various proteins. Although it is impossible to include every piece of research work, we attempt to highlight the research progress in the past 10 years in exploring unnatural peptidic foldamers as protein helical segment mimics, by giving some representative examples and discussing the current challenges and future perspectives. We expect that this review will help elucidate the principles of structural design and applications of existing unnatural helical peptidic foldamers in protein segment mimicry, thereby attracting more researchers to explore and generate novel unnatural peptidic foldamers with unique structural and functional properties, leading to more unprecedented and practical applications.
Construction and characterization of a selectable multidrug resistance-glucocerebrosidase fusion gene. (1996)

Gene fusions can be employed to ensure concomitant expression of two different proteins under the same transcriptional control elements. We have synthesized a retroviral expression vector (pHaMG1) containing a human multidrug resistance (MDR1)-glucocerebrosidase (GC) chimeric gene inserted between the long terminal repeats of the Harvey murine sarcoma virus. When introduced into psi-CRE mouse fibroblasts, pHaMG1 conferred the drug-selectable multidrug resistance phenotype, and drug-resistant clones produced active human GC of about 60 kDa. Percoll gradient fractionation of homogenates prepared from transfectants confirmed correct targeting of P-glycoprotein to the plasma membrane and of GC to lysosomes. Although this construction was designed as a translational fusion of the MDR1 gene product, P-glycoprotein, and human GC, no evidence for a fusion protein was found in transfected cells, and an analysis of the RNAs transcribed from the integrated pHaMG1 retroviral vector suggests that either P-glycoprotein and GC are translated from one mRNA and rapidly processed into two proteins or they are translated separately from different mRNAs. These results reveal the feasibility of using fusion genes, which are smaller than alternative constructions with two promoters or with an internal ribosome entry site, for coexpression of selectable and nonselectable cDNAs in retroviral vectors.
Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice (2005)

Although blood cell-endothelial cell adhesion and oxidative stress have been implicated in the pathogenesis of sickle cell disease (SCD), the nature of the linkage between these vascular responses in SCD remains unclear. The objective of this study was to determine whether superoxide derived from endothelial cell-associated NADPH oxidase mediates the leukocyte-endothelial (L/E) and platelet-endothelial cell (P/E) adhesion that is observed in the cerebral microvasculature of sickle cell transgenic (betaS) mice. Intravital fluorescence microscopy was used to monitor L/E and P/E adhesion in brain postcapillary venules of wild-type (WT), SOD1 transgenic (SOD1-TgN), and gp91phox (NADPH oxidase)-deficient mice that were transplanted with bone marrow from betaS mice. Hypoxia/reoxygenation (H/R) yielded intense P/E and L/E adhesion responses in cerebral venules of betaS/WT chimeras that were significantly attenuated in both betaS/SOD1-TgN, and betaS/gp91phox-/- chimeras. Pretreatment of betaS/WT chimeras with the iron-chelator desferroxamine blunted the blood cell-endothelial cell adhesion responses to H/R, whereas pretreatment with the xanthine oxidase inhibitor allopurinol had no effect. These findings suggest that superoxide derived from endothelial cell NADPH-oxidase and catalytically active iron contribute to the proinflammatory and prothrombogenic responses associated with sickle cell disease.
Growth and characterization of Fe0.82Ni0.18/V(001) superlattices (2003)

Epitaxial Fe0.82Ni0.18/V(001) superlattices grown by dc magnetron sputtering on MgO(001) substrate were investigated structurally by means of x-ray diffraction, Rutherford backscattering spectrometry and transmission electron microscopy. The results show that samples grown around 150°C have high interface sharpness with low interdiffusion and good crystallographic quality.
Multi-Task Attention-Based Semi-Supervised Learning for Medical Image Segmentation (2019)

We propose a novel semi-supervised image segmentation method that simultaneously optimizes a supervised segmentation and an unsupervised reconstruction objectives. The reconstruction objective uses an attention mechanism that separates the reconstruction of image areas corresponding to different classes. The proposed approach was evaluated on two applications: brain tumor and white matter hyperintensities segmentation. Our method, trained on unlabeled and a small number of labeled images, outperformed supervised CNNs trained with the same number of images and CNNs pre-trained on unlabeled data. In ablation experiments, we observed that the proposed attention mechanism substantially improves segmentation performance. We explore two multi-task training strategies: joint training and alternating training. Alternating training requires fewer hyperparameters and achieves a better, more stable performance than joint training. Finally, we analyze the features learned by different methods and find that the attention mechanism helps to learn more discriminative features in the deeper layers of encoders.
Abstract 2215: Detection of novel markers of transitional cell carcinoma of the ovary, the TCC-like variant of high grade serous carcinoma, using proteomics and immunohistochemistry (2017)

Abstract Background: The current WHO classification does not separate transitional carcinoma of the ovary (TCCO) from conventional high grade serous carcinoma of the ovary (HGSC). TCCO has a better prognosis, possibly due to better chemosensitivity or less infiltrative growth pattern. The available immunohistochemical (IHC) markers do not differentiate between the two subtypes. Therefore, we sought to compare the proteomic profiles of conventional HGSC and TCCO to identify surrogate biomarkers of good prognosis from TCCO that could identify conventional HGSC tumors with a better prognosis. Design: Full proteome analysis of 12 cases of TCCO and 12 cases of HGSC was performed using SP3-clinical proteomics, run on an ThermoFisher Orbitrap Fusion. For validation, tissue microarrays of TCCO (n=89) and HGSC (n=237) were immunostained with antibodies against proteins found to be enriched in TCCO. All cases and immunostains were scored by a gynecologic pathologist. Univariate analysis was performed comparing IHC expression in TCCO vs. HGSC. Results: We identified 1220 proteins that were significantly enriched in TCCO over HGSC. Claudin 4 and Ubiquitin carboxyl-terminal esterase L1 (UCHL1) were selected as potential markers of TCCO-like biology (p=0.0017, 0.0322). By IHC, Claudin 4 (95% confidence interval (CI) 0.171, 0.430) and UCHL1 (95% CI 0.291, 0.550) showed a significantly higher expression in TCCO as compared to HGSC (see table). % of tumors with high immunoreactivity scoresClaudin 4UCHL1Pure TCCO34/59 (58%)26/59 (44%)Mixed TCCO-HGSC, TCCO component14/29 (48%)8/29 (28%)Mixed TCCO-HGSC, HGSC component19/28 (68%)6/28 (21%)Conventional HGSC33/235 (14%)32/237 (14%) Legend: Mixed TCCO: TCCO with minor component of conventional HGSC Conclusion: Proteomic analysis showed differing protein profiles for TCCO and HGSC. By IHC, Claudin 4 and UCHL1 were identified as potential markers for TCC-like differentiation of high-grade serous carcinomas. Further studies will focus on the prognostic significance of these and other markers in larger cohorts of HGSC. This study presents a novel approach at identifying potential diagnostic and prognostic biomarkers as well as therapeutic targets. Citation Format: Basile Tessier-Cloutier, Jamie Magrill, Stefan Kommoss, Blake C. Gilks, David G. Huntsman, Dawn R. Cochrane, Aline Talhouk, Robert Soslow, Gregg B. Morin, Chris J. Hughes, Anthony N. Karnezis, Christine Chow, Angela S. Cheng, Andreas du Bois, Jacobus Pfisterer, Friedrich Kommoss. Detection of novel markers of transitional cell carcinoma of the ovary, the TCC-like variant of high grade serous carcinoma, using proteomics and immunohistochemistry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2215. doi:10.1158/1538-7445.AM2017-2215