gebhart/patrepeval huggingface dataset:
Immunolocalization and expression of bone morphogenetic proteins 2 and 4 in fracture healing (1995)

Recently, it has become increasingly evident that fracture healing involves a complex interaction of many local and systemic regulatory factors. The roles of some of these growth factors have been described; however, little is understood about the presence of the bone morphogenetic proteins in fracture repair, despite the fact that they are the most potent osteoinductive proteins known. This study defines and characterizes the physiologic presence, localization, and chronology of the bone morphogenetic proteins in fracture healing with an established rat fracture healing model. With use of a recently developed monoclonal antibody against bone morphogenetic proteins 2 and 4 developed with standard avidin-biotin complex/immunoperoxidase protocols, frozen undecalcified fracture calluses were analyzed semiquantitatively for the percentage of various types of fracture cells staining positively. During the early stages of fracture healing, only a minimum number of primitive cells stained positively in the fracture callus. As the process of endochondral ossification proceeded, the presence of bone morphogenetic proteins 2 and 4 increased dramatically, especially in the primitive mesenchymal and chondrocytic cells. While the cartilaginous component of the callus matured with a concomitant decrease in the number of primitive cells, there was a concomitant decrease in both the intensity and the number of positively staining cells. As osteoblasts started to lay down woven bone on the chondroid matrix, these osteoblastic cells exhibited strong positive staining. The intensity of this staining decreased, however, as lamellar bone replaced the primitive woven bone. A similar observation was noted for the areas of the callus undergoing intramembranous ossification. Initially, within several days after the fracture, periosteal cells and osteoblasts exhibited intense staining for bone morphogenetic proteins 2 and 4. As the woven bone was replaced with mature lamellar bone, this staining decreased. These data, and the awareness of the strong osteoinductive capacities of bone morphogenetic protein, suggest that bone morphogenetic proteins 2 and 4 are important regulators of cell differentiation during fracture repair.
Surface-Enhanced Raman Spectroscopy of Lipids on Silver Microprobes (1998)

The surface-enhanced Raman scattering (SERS) spectra of model sebaceous gland secretions and their bacterially generated fatty acids are described. Long-chain fatty acids, their parent triglycerides, and long-chain hydrocarbons have characteristic SERS signatures that make them readily resolvable in heterogeneous mixtures. Silicon-substrate silver microprobes are shown to be useful for studying the spatial distribution of lipids and their corresponding fatty acids in nanoflow rate systems.
Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody. (1994)

The antiviral characteristics of monoclonal antibody IAM-41-2F5 (2F5) were determined in cell culture. The antibody had been previously shown to bind a specific sequence, ELDKWA, within the external domain of the gp41 envelope glycoprotein human immunodeficiency virus type 1 (HIV-1). Selection by 2F5 of recombinant phage from an epitope library confirmed the identification of the antibody's binding determinant. The antibody was found to be capable of neutralizing a broad range of lymphoid cell culture-adapted HIV-1 variants as well as HIV-1 primary isolates. Sequence analysis of the latter showed that neutralization was related to the presence of the antibody binding site. From kinetic measurements using an epitope-containing peptide or gp41, the half-time of dissociation for 2F5 was determined to be 122 min for the peptide and 156 min for gp41. The region of gp41 expressing this sequence exhibits greater conservation among HIV-1 isolates than do the variable domains of gp120.
Inhibition of plasma kallikrein by C1-inhibitor: role of endothelial cells and the amino-terminal domain of C1-inhibitor (2004)

Activation of plasma prekallikein and generation of bradykinin are responsible for the angioedema attacks observed with C1-inhibitor deficiency. Heterozygous individuals with <50% levels of active C1-inhibitor are susceptible to angioedema attacks indicating a critical need for C1-inhibitor to be present at maximum levels to prevent unwanted prekallikrein activation. Studies with purified proteins do not adequately explain this observation. Therefore to investigate why reduction of C1-inhibitor to levels seen in angioedema patients results in excessive kallikrein generation we examined the effect of endothelial cells on the inhibition of kallikrein by C1-inhibitor. Surprisingly, it was found that a C1-inhibitor concentration of greater than 1 microM was needed to inhibit 3 nM kallikrein. We propose that this apparent protection from inhibition was mediated by kallikrein binding to the cells via the heavy chain in a high molecular weight kininogen and zinc independent manner. Protection of kallikrein from inhibition was not observed when C1-inhibitor truncated in the amino-terminal domain by the StcE metalloproteinase was used, which suggests a novel function for this unique domain. The requirement for high concentrations of C1-inhibitor to fully inhibit kallikrein is consistent with the fact that reduced levels of C1-inhibitor result in the kallikrein activation seen in angioedema.
Rapid evolution of the neutralizing antibody response to HIV type 1 infection (2003)

A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0-39 months) autologous viruses, whereas responses to laboratory and heterologous primary strains were often lower and delayed. Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.
Prostate cancer in a transgenic mouse. (1995)

Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.
Nucleic acid-binding specificity of human FUS protein (2015)

FUS, a nuclear RNA-binding protein, plays multiple roles in RNA processing. Five specific FUS-binding RNA sequence/structure motifs have been proposed, but their affinities for FUS have not been directly compared. Here we find that human FUS binds all these sequences with Kd (app) values spanning a 10-fold range. Furthermore, some RNAs that do not contain any of these motifs bind FUS with similar affinity. FUS binds RNA in a length-dependent manner, consistent with a substantial non-specific component to binding. Finally, investigation of FUS binding to different nucleic acids shows that it binds single-stranded DNA with three-fold lower affinity than ssRNA of the same length and sequence, while binding to double-stranded nucleic acids is weaker. We conclude that FUS has quite general nucleic acid-binding activity, with the various proposed RNA motifs being neither necessary for FUS binding nor sufficient to explain its diverse binding partners.
Cloning and Expression of the β- N-Acetylglucosaminidase Gene from Streptococcus pneumoniae (1995)

The gene encoding a beta-N-acetylglucosaminidase from Streptococcus pneumoniae has been obtained by screening an expression library for beta-N-acetylglucosaminidase activity. Clones of different nucleotide sizes each having arylglycoside activity were obtained, and DNA sequencing revealed a gene of 3933 base pairs possessing typical bacterial transcription initiation and termination sequences and terminating in an ochre stop codon. Computer analysis of the translated protein of 1311 amino acids (144,210 Da) identified a tandem repeat within which lies a sequence homologous with six other hexosaminidase gene products from a wide variety of species ranging from bacteria to humans. Also found were an amino-terminal putative secretion signal peptide and a carboxyl-terminal cell sorting/anchorage motif typically found in over 20 other Gram-positive surface proteins. The expression of an almost complete DNA clone in Escherichia coli produced a functional and authentic beta-N-acetylglucosaminidase with aglycon specificity identical to the wild-type enzyme. However, enzymes produced from truncated DNA clones show more restricted aglycon specificity and are unable to hydrolyze terminal beta 1-2GlcNAc residues from N-glycans containing a bisecting N-acetylglucosamine. The availability of these clones allows structural analyses to be made of catalytic and oligosaccharide recognition protein domains that enhance functional activity.
Regulation of the Epithelial Na+ Channel by the Protein Kinase CK2 (2008)

CK2 is a ubiquitous, pleiotropic, and constitutively active Ser/Thr protein kinase that controls protein expression, cell signaling, and ion channel activity. Phosphorylation sites for CK2 are located in the C terminus of both beta- and gamma-subunits of the epithelial Na(+) channel (ENaC). We examined the role of CK2 on the regulation of both endogenous ENaC in native murine epithelia and in Xenopus oocytes expressing rENaC. In Ussing chamber experiments with mouse airways, colon, and cultured M1-collecting duct cells, amiloride-sensitive Na(+) transport was inhibited dose-dependently by the selective CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB). In oocytes, ENaC currents were also inhibited by TBB and by the structurally unrelated inhibitors heparin and poly(E:Y). Expression of a trimeric channel lacking both CK2 sites (alphabeta(S631A)gamma(T599A)) produced a largely attenuated amiloride-sensitive whole cell conductance and rendered the mutant channel insensitive to CK2. In Xenopus oocytes, CK2 was translocated to the cell membrane upon expression of wt-ENaC but not of alphabeta(S631A)gamma(T599A)-ENaC. Phosphorylation by CK2 is essential for ENaC activation, and to a lesser degree, it also controls membrane expression of alphabetagamma-ENaC. Channels lacking the Nedd4-2 binding motif in beta-ENaC (R561X, Y618A) no longer required the CK2 site for channel activity and siRNA-knockdown of Nedd4-2 eliminated the effects of TBB. This implies a role for CK2 in inhibiting the Nedd4-2 pathway. We propose that the C terminus of beta-ENaC is targeted by this essential, conserved pleiotropic kinase that directs its constitutive activity toward many cellular protein complexes.
Immunological Prevention of a Multigene Cancer Syndrome (2004)

Vaccines effectively prevent the onset of tumors in transgenic mice carrying activated oncogenes; however, human tumors are caused by combined alterations in oncogenes and oncosuppressor genes. We evaluated the impact of prophylactic vaccines in HER-2/neu transgenic, p53 wild-type/null mice that succumb to an aggressive cancer syndrome comprising mammary and salivary gland carcinomas and rhabdomyosarcoma. A vaccine made of allogeneic mammary carcinoma cells expressing HER-2/neu and interleukin 12 afforded long-term protection from tumor onset. Tumor prevention was mediated by T cell-derived cytokines, in particular gamma-interferon, and by anti-HER-2/neu antibodies. HER-2/neu expression was inhibited in target tissues of vaccinated mice, and somatic loss of the wild-type p53 allele did not occur. A highly effective vaccine against a single oncoprotein induced a powerful immune response that arrested multistep carcinogenesis in distinct target tissues.
Cell lineage in the developing neural tube (1998)

Acquisition of cell type specific properties in the spinal cord is a process of sequential restriction in developmental potential. A multipotent stem cell of the nervous system, the neuroepithelial cell, generates central nervous system and peripheral nervous system derivatives via the generation of intermediate lineage restricted precursors that differ from each other and from neuroepithelial cells. Intermediate lineage restricted neuronal and glial precursors termed neuronal restricted precursors and glial restricted precursors, respectively, have been identified. Differentiation is influenced by extrinsic environmental signals that are stage and cell type specific. Analysis in multiple species illustrates similarities between chick, rat, mouse, and human cell differentiation. The utility of obtaining these precursor cell types for gene discovery, drug screening, and therapeutic applications is discussed.Key words: stem cells, oligodendrocytes, astrocytes, neurons, spinal cord.
Cardiac preconditioning for ischaemia: lost in translation (2010)

Coronary heart disease (CHD) is the leading cause of death worldwide. The development of novel treatment strategies for protecting the myocardium against the detrimental effects of acute ischaemia-reperfusion injury, termed cardioprotection, and for improving clinical outcomes in patients with CHD requires the use of appropriate animal disease models. The concept of cardioprotection was first conceived in the late 1960s and has evolved to include the endogenous cardioprotective phenomenon of ischaemic conditioning, a concept in which the heart can be protected from an episode of acute lethal ischaemia-reperfusion injury by applying brief non-lethal episodes of ischaemia and reperfusion either to the heart itself or to an organ or tissue that is remote from the heart. The brief conditioning episodes of ischaemia and reperfusion can be applied prior to the index ischaemic episode (ischaemic preconditioning), after the onset of the index ischaemic episode (ischaemic perconditioning), or at the onset of reperfusion (ischaemic postconditioning). Elucidation of the signal transduction pathways underlying ischaemic conditioning has identified a variety of pharmacological agents that are capable of reproducing its cardioprotective actions. Despite a wealth of preclinical, experimental animal data demonstrating clear cardioprotective benefits with these treatment strategies, their translation into clinical therapy has been hugely disappointing. This review explores the potential reasons behind this failure; it will focus primarily on the inadequacy of the experimental animal disease models that are currently being used to investigate novel cardioprotective strategies, which on the whole are not adequately representative of the clinical scenario, and finally, we will discuss potential solutions to remedy this problem.
Synthesis and Inhibitory Activities of Isochromophilone Analogues against gp120-CD4 Binding. (1996)

Several isochromophilone analogues were synthesized from sclerotiorin (1) by Wittig reactions and aldol condensation reaction. The structures of the products were elucidated from MS, elemental analysis, 1H NMR and 13C NMR spectra, and their inhibitory activities against gp120-CD4 binding were determined.
Inhibition of apoptosis by the expression of antisense Nedd2 (1995)

Nedd2 belongs to a family of mammalian cysteine proteases which share similarity with the Caenorhabditis elegans cell death protein, Ced-3. Overexpression of Nedd2 has been shown to induce apoptosis in mammalian cells but in the absence of a specific known inhibitor, it remains to be seen whether this represents cytotoxic effects of the Nedd2 protease or the specific activation of an apoptotic pathway. The present work shows that the factor-dependent cell line FDC-P1 expressing mouse antisense Nedd2 mRNA, exhibits significant inhibition of cell death upon removal of the cytokines, thus providing evidence for a direct role of Nedd2 in mediating apoptosis.
Transforming growth factor--alpha stimulates chemotaxis of osteoblasts and osteoblast-like cells in vitro. (1994)

Homeostatic turnover of bone is believed to be regulated in part by growth factors present in the surrounding environment. The first step during the bone formation process is the recruitment of osteoblasts from the surrounding intact bone to the resorption site. In this study, the effects of TGF-alpha on osteoblast chemotaxis was investigated. Cultures of rat osteoblasts and human osteoblast-like cells were examined for chemotaxis in response to increasing concentrations of TGF-alpha utilizing a modified Boyden Chamber technique. TGF-alpha stimulated a dose-dependent increase in chemotaxis by both cell populations. These results indicate that TGF-alpha may be playing an important role in the early stages of bone matrix regeneration by stimulating osteoblast chemotaxis.
Learning Real-World Robot Policies by Dreaming (2019)

Learning to control robots directly based on images is a primary challenge in robotics. However, many existing reinforcement learning approaches require iteratively obtaining millions of robot samples to learn a policy, which can take significant time. In this paper, we focus on learning a realistic world model capturing the dynamics of scene changes conditioned on robot actions. Our dreaming model can emulate samples equivalent to a sequence of images from the actual environment, technically by learning an action-conditioned future representation/scene regressor. This allows the agent to learn action policies (i.e., visuomotor policies) by interacting with the dreaming model rather than the real-world. We experimentally confirm that our dreaming model enables robot learning of policies that transfer to the real-world.
The Ubiquitin-Proteasome Pathway Mediates Gelsolin Protein Downregulation in Pancreatic Cancer (2008)

A well-known observation with respect to cancer biology is that transformed cells display a disturbed cytoskeleton. The underlying mechanisms, however, remain only partly understood. In an effort to identify possible mechanisms, we compared the proteome of pancreatic cancer with matched normal pancreas and observed diminished protein levels of gelsolin--an actin filament severing and capping protein of crucial importance for maintaining cytoskeletal integrity--in pancreatic cancer. Additionally, pancreatic ductal adenocarcinomas displayed substantially decreased levels of gelsolin as judged by Western blot and immunohistochemical analyses of tissue micoarrays, when compared with cancerous and untransformed tissue from the same patients (P < 0.05). Importantly, no marked downregulation of gelsolin mRNA was observed (P > 0.05), suggesting that post-transcriptional mechanisms mediate low gelsolin protein levels. In apparent agreement, high activity ubiquitin-proteasome pathway in both patient samples and the BxPC-3 pancreatic cancer cell line was detected, and inhibition of the 26s proteasome system quickly restored gelsolin protein levels in the latter cell line. The status of ubiquitinated gelsolin is related to lymph node metastasis of pancreatic cancer. In conclusion, gelsolin levels are actively downregulated in pancreatic cancer and enhanced targeting of gelsolin to the ubiquitin-proteasome pathway is an important contributing factor for this effect.
Novel techniques for multichannel wavelength division multiplexing (1986)

Wavelength division multiplexing (WDM) is a technology which enables greater exploitation of the available optical bandwidth of the fiber and as such is becoming increasingly important not only for wide-bandwidth trunk transmission but also for wideband local area networks. In the latter WDM not only increases bandwidth but also makes available another dimension to further enhance system architecture.
Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP (2015)

The Hippo signaling pathway converges on YAP to regulate growth, differentiation, and regeneration. Previous studies with overexpressed proteins have shown that YAP is phosphorylated by its upstream kinase, Lats1/2, on multiple sites, including an evolutionarily conserved 14-3-3-binding site whose phosphorylation is believed to inhibit YAP by excluding it from the nucleus. Indeed, nuclear localization of YAP or decreased YAP phosphorylation at this site (S168 in Drosophila, S127 in humans, and S112 in mice) is widely used in current literature as a surrogate of YAP activation even though the physiological importance of this phosphorylation event in regulating endogenous YAP activity has not been defined. Here we address this question by introducing a Yap(S112A) knock-in mutation in the endogenous Yap locus. The Yap(S112A) mice are surprisingly normal despite nuclear localization of the mutant YAP protein in vivo and profound defects in cytoplasmic translocation in vitro. Interestingly, the mutant Yap(S112A) mice show a compensatory decrease in YAP protein levels due to increased phosphorylation at a mammalian-specific phosphodegron site on YAP. These findings reveal a robust homeostatic mechanism that maintains physiological levels of YAP activity and caution against the assumptive use of YAP localization alone as a surrogate of YAP activity.
Java Software Solutions: Foundations of Program Design (1997)

Intended for use in the Java programming course Java Software Solutions teaches a foundation of programming techniques to foster well-designed object-oriented software. Heralded for its integration of small and large realistic examples, this worldwide best-selling text emphasizes building solid problem-solving and design skills to write high-quality programs. Teaching and Learning ExperienceTo provide a better teaching and learning experience, for both instructors and students, this program will: Personalize Learning: Through the power of practice and immediate personalized feedback, MyProgrammingLab helps students fully grasp the logic, semantics, and syntax of programming. Help Students Build Sound Program-Development Skills: A software methodology is introduced early and revisited throughout the text to ensure that students build sound program-development skills. Enhance Learning with In-text Features: A variety of features in each chapter help motivate learning. Provide Opportunities to Practice Design Skills and Implement Java Programs: A wealth of end-of-chapter programming projects and chapter review features help reinforce key concepts. Support Instructors and Students: Resources to support learning are available on the Companion website and Instructor Resource Center.