gebhart/patrepeval huggingface dataset:
Hippocampal Dysfunction and Cognitive Impairments Provoked by Chronic Early-Life Stress Involve Excessive Activation of CRH Receptors (2010)

Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF(1)) located on pyramidal cell dendrites. Additionally, chronic CRF(1) occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH expression is augmented in hippocampus of middle-aged CES rats, and then tested whether the morphological defects and poor memory performance in these animals involve excessive activation of CRF(1) receptors. Central or peripheral administration of a CRF(1) blocker following the stress period improved memory performance of CES rats in novel-object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH-CRF(1) interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF(1) occupancy post hoc normalized hippocampal function during middle age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress.
Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin-interacting protein 1-related-deficient mice (2010)

Huntingtin-interacting protein 1-related (Hip1r) is highly expressed in gastric parietal cells, where it participates in vesicular trafficking associated with acid secretion. Hip1r-deficient mice have a progressive remodeling of the mucosa, including apoptotic loss of parietal cells, glandular hypertrophy, mucous cell metaplasia, and reduced numbers of zymogenic cells. In this study, we characterized gastric gland development in wild-type and Hip1r-deficient mice to define normal development, as well as the timing and sequence of the cellular transformation events in the mutant stomach. Postnatal (newborn to 8-wk-old) stomachs were examined by histological and gene expression analysis. At birth, gastric glands in wild-type and mutant mice were rudimentary and mature gastric epithelial cells were not apparent, although marker expression was detected for most cell lineages. Interestingly, newborns exhibited unusual cell types, including a novel surface cell filled with lipid and cells that coexpressed markers of mature mucous neck and zymogenic cells. Glandular morphogenesis proceeded rapidly in both genotypes, with gastric glands formed by weaning at 3 wk of age. In the Hip1r-deficient stomach, epithelial cell remodeling developed in a progressive manner. Initially, in the perinatal stomach, cellular changes were limited to parietal cell apoptosis. Other epithelial cell changes, including apoptotic loss of zymogenic cells and expansion of metaplastic mucous cells, emerged several weeks later when the glands were morphologically mature. Thus, parietal cell loss appeared to be the initiating event in Hip1r-deficient mice, with secondary remodeling of the other gastric epithelial cells.
THE MAMMALIAN CELL-VIRUS RELATIONSHIP (1959)

Primary or established strain cultures of a variety of primate cells that were susceptible to cytopathic infection strongly adsorbed poliovirus. Insusceptible non-primate cells in primary or established-strain culture did not so adsorb virus (or propagate it), with exception of the ERK-1 embryo rabbit kidney strain. All tested cells, regardless of type or susceptibility, adsorbed about 1 per cent of input virus, which became cell-associated (CAV) without loss of infectivity. In combination with susceptible or insusceptible cells, CAV was only about 90 per cent neutralized by homotypic antiserum. CAV eluted continuously from non-susceptible cells with continued incubation; eluted virus gave rise to infection and new CAV to the same degree in susceptible cells as did original virus.
The Development of Prosthetic Heart Valves — Lessons in Form and Function (2007)

Interview with Albert Starr on the invention of the first successful artificial heart valve. (10:34)Download The 2007 Lasker Award for Clinical Medical Research, granted in mid-September to Albert Starr and Alain Carpentier, recognizes their extraordinary contributions to the development of the prosthetic heart valve, which represents a milestone in the journey toward the fabrication of synthetic living tissues and organ systems. The prosthetic heart valve was built on a foundation laid down during the first half of the 20th century with the introduction of cardiac catheterization by André Cournand and Dickinson Richards, the development of innovative surgical techniques by Alfred Blalock, the invention of the heart–lung machine by John Gibbon, and the discovery of heparin . . .
Thermodynamics of Cooperative DNA Recognition at a Replication Origin and Transcription Regulatory Site (2010)

Binding cooperativity guides the formation of protein-nucleic acid complexes, in particular those that are highly regulated such as replication origins and transcription sites. Using the DNA binding domain of the origin binding and transcriptional regulator protein E2 from human papillomavirus type 16 as model, and through isothermal titration calorimetry analysis, we determined a positive, entropy-driven cooperativity upon binding of the protein to its cognate tandem double E2 site. This cooperativity is associated with a change in DNA structure, where the overall B conformation is maintained. Two homologous E2 domains, those of HPV18 and HPV11, showed that the enthalpic-entropic components of the reaction and DNA deformation can diverge. Because the DNA binding helix is almost identical in the three domains, the differences must lie dispersed throughout this unique dimeric β-barrel fold. This is in surprising agreement with previous results for this domain, which revealed a strong coupling between global dynamics and DNA recognition.
Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated (2007)

The stilbene resveratrol (RV) initiates p53-dependent apoptosis via plasma membrane integrin alphaVbeta3 in human cancer cells. A thyroid hormone (L-thyroxine, T(4)) membrane receptor also exists on alphaVbeta3. Stilbene and T(4) signals are both transduced by extracellular-regulated kinases 1 and 2 (ERK1/2); however, T(4) promotes cell proliferation in cancer cells, whereas RV is pro-apoptotic. Thyroid hormone has been shown to interfere with RV-induced apoptosis. However, the mechanisms involved are not fully understood. In this study, we examined the mechanism whereby T(4) inhibits RV-induced apoptosis in glioma cells. RV activated conventional protein kinase C and ERK1/2 and caused nuclear localization of cyclooxygenase-2 (COX-2), consequent p53 phosphorylation and apoptosis. RV-induced ERK1/2 activation is involved in not only COX-2 expression but also nuclear COX-2 accumulation. NS-398, a COX-2 inhibitor, did not affect ERK1/2 activation, but reduced the nuclear abundance of COX-2 protein and the formation of complexes of nuclear COX-2 and activated ERK1/2 that are required for p53-dependent apoptosis in RV-treated cells. T(4) inhibited RV-induced nuclear COX-2 and cytosolic pro-apoptotic protein, BcLx-s, accumulation. Furthermore, T(4) inhibited RV-induced apoptosis by interfering with the interaction of nuclear COX-2 and ERK1/2. This effect of T(4) was prevented by tetraiodothyroacetic acid (tetrac), an inhibitor of the binding of thyroid hormone to its integrin receptor. Tetrac did not, in the absence of T(4), affect induction of apoptosis by RV. Thus, the receptor sites on alphaVbeta3 for RV and thyroid hormone are discrete and activate ERK1/2-dependent downstream effects on apoptosis that are distinctive.
Multiple object recognition and scene interpretation for autonomous road vehicle guidance (2005)

The seeing car VaMoRs-P is the next step of development in computer vision for autonomous road vehicle guidance at the 'Universitat der Bundeswehr Munich' (UBM). As one of the key functions, the module 'obstacle detection and tracking (ODT)' has been developed since 1991; with several thousand kilometers of autonomous test driving a state of high reliability has been reached. For vehicles in the vehicle's own lane the well known extraction of the left and right object boundaries using fast contour analysis is performed. Additionally, a new approach for recognition of vehicles in the neighboring lanes and those approaching from the rear is being developed. The lower object boundary detection using a knowledge based edge chaining algorithm and a special edge detector is presented. VaMoRs-P is equipped with four miniature CCD-cameras with different focal lengths mounted on two platforms viewing to the front and rear of the own car. For obstacle detection a range of 6 up to 120 meters distance in the own and the neighboring left and right lane is achieved. For collision avoidance and autonomous overtaking of slower driving road users a minimum number of 4 or 5 objects must be tracked in parallel. For this task ODT comprises about 15 transputers for image processing and state estimation.
Evaluation of novel injectable hydrogels for nucleus pulposus replacement (2007)

Branched copolymers composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) are being investigated as an in situ forming replacement for the nucleus pulposus of the intervertebral disc. A family of copolymers was synthesized by varying the molecular weight of the PEG blocks and molar ratio of NIPAAm monomer units to PEG branches. Gel swelling, dissolution, and compressive mechanical properties were characterized over 90 days and stress relaxation behavior over 30 days immersion in vitro. It was found that the NIPAAm to PEG molar ratio did not affect the equilibrium swelling and compressive mechanical properties. However, gel elasticity exhibited a dependency on both the PEG block molecular weight and content. The equilibrium gel water content increased and compressive modulus decreased with increasing PEG block size. While all of the branched copolymers showed significant increases in stress relaxation time constant compared to the homopolymer (p < 0.05), the high PEG content PNIPAAm-PEG (4600 and 8000 g/mol) exhibited the maximum elasticity. Because of its high water content, requisite stiffness and high elastic response, PNIPAAm-PEG (4600 g/mol) will be further evaluated as a candidate material for nucleus pulposus replacement.
Extracellular proteolysis and cancer: meeting summary and future directions. (2003)

The contribution of extracellular proteolysis to processes of tumor invasion and metastasis has been recognized for more than 20 years. However, after millions of dollars and untold hours of investment in preclinical research and the development of broad range inhibitors of MMPs, clinical trials of late-stage tumor patients show no indication that this approach will be successful. In the basic science arena, there have been stunning advancements that illustrate novel biological activities for proteases and that suggest they are key regulators of many physiological and pathological processes. The Proteases and Cancer: Biology and Therapeutics Workshop (held in Bethesda, MD, November 20-22, 2002) was organized by the Division of Cancer Biology, National Cancer Institute (NCI) to identify research areas and directions that will accelerate understanding protease biology and enhance clinical translation. The overall consensus was that protease biology represents fertile ground for advances that will be clinically useful but perhaps not for the reasons or purpose originally thought. Protease-related technologies show particular promise for the detection, prognosis, and prevention of cancer, and for therapeutic purposes in defined situations. Promising areas for further research are identified, and specific recommendations for the development of a consortium to coordinate the efforts of the protease community are made.
Genetically determined myocarditis: clinical presentation and immunological characteristics (2008)

In myocarditis/dilated cardiomyopathy, cardiac-specific and disease-specific antibodies of IgG class are potential biomarkers for identifying 'at risk' relatives as well as those patients in whom, in the absence of active infection of the myocardium, immunosuppression, and/or immunomodulation may be beneficial. Future studies should better define the genetic basis of human autoimmune myocarditis/dilated cardiomyopathy.
Effects of Rexinoids on Glucose Transport and Insulin-mediated Signaling in Skeletal Muscles of Diabetic (db/db) Mice (2004)

Rexinoids and thiazolidinediones (TZDs) are two classes of nuclear receptor ligands that induce insulin sensitization in diabetic rodents. TZDs are peroxisome proliferator-activated receptor gamma (PPARgamma) activators, whereas rexinoids are selective ligands for the retinoid X receptors (RXRs). Activation of both the insulin receptor substrates (IRSs)/Akt and the c-Cbl-associated protein (CAP)/c-Cbl pathways are important in regulating insulin-stimulated glucose transport. We have compared the effects of a rexinoid (LG268) and a TZD (rosiglitazone) on these two signal pathways in skeletal muscle of diabetic (db/db) mice. The results we have obtained show that treatment of db/db mice with either LG268 or rosiglitazone for 2 weeks results in a significant increase in insulin-stimulated glucose transport activity in skeletal muscle. Treatment with LG268 increases insulin-stimulated IRS-1 tyrosine phosphorylation and Akt phosphorylation in skeletal muscle without affecting the activity of the CAP/c-Cbl pathway. In contrast, rosiglitazone increases the levels of CAP expression and insulin-stimulated c-Cbl phosphorylation without affecting the IRS-1/Akt pathway. The effects of LG268 on the IRS-1/Akt pathway were associated with a decrease in the level of IRS-1 Ser(307) phosphorylation. Taken together, these data suggest that rexinoids improve insulin sensitivity via changes in skeletal muscle metabolism that are distinct from those induced by TZDs. Rexinoids represent a novel class of insulin sensitizers with potential applications in the treatment of insulin resistance.
Real-time visual servoing for laparoscopic surgery. Controlling robot motion with color image segmentation (1997)

The authors propose a visual tracking method for stereo laparoscopes, which is robust, simple, and operates at a maximum rate of 17 Hz. The use of a stereo laparoscope enables the robot to track the instrument in both lateral and longitudinal motions. Due to the multiplicity of problems with shape analysis, the authors do not check for the presence of any particular shape or structure. Instead, they use color information alone for instrument segmentation. The non-uniqueness of the instrument color inspires the authors to distinguish it by use of an artificial color mark. They analyzed the color distribution of typical laparoscopic images and chose a color that did not appear to mark the instrument. With color image segmentation, the mark can be correctly located in the image and used to control the robot motion. Thus, even if only a very small part of the instrument is visible, reliable data can still be obtained for robot control. The image processing component is implemented on a commercially available image processing system MaxVideo MV200 (Datacube, Inc., Danvers, MA). The robot the authors use is the AESOP 1000 (Automated Endoscope System for Optimal Positioning) (Computer Motion, Inc., Goleta, CA).
The STING pathway and regulation of innate immune signaling in response to DNA pathogens (2010)

The innate immune system has evolved a variety of sensing mechanisms to detect and counter microbial invasion. These include the Toll-like receptor (TLR), cytoplasmic, nucleotide binding oligomerization domain (NOD)-like receptor and RIG-I-like helicase (RLH) pathways. However, how the cell detects pathogen-associated DNA to trigger host defense, including the production of interferon, remains to be fully clarified. Understanding these processes could have profound implications into how we understand and treat a variety of microbial-related disease, including viral-associated cancers, as well as autoimmune disorders. Recently, an endoplasmic reticulum-associated molecule referred to as STING (for stimulator of interferon genes) was isolated and shown to be critical for regulating the production of IFN in response to cytoplasmic DNA. Here, we review recent discoveries relating to the detection of foreign DNA, including the importance of the STING and inflammasome pathways and the triggering of innate signaling processes.
GMPLS-based hierarchical optical routing switching architecture (2001)

With the development of Generalized Multi-Protocol Label Switching (GMPLS: an optical extension to traditional Multi-Protocol Label Switching) by IETF, we envision that today's static optical networks will evolve towards dynamic optical networks with a intelligent, flexible and scalable control plane software. In this paper we firstly describes a novel IP-Centric optical network architecture called Hierarchical Optical Routing Switching Architecture (HORSA) based on GMPLS--a flexible, highly scalable IP over WDM optical network architecture for the delivery of public network IP services. Two kinds of node including Optical Core Router (OCR) and Optical Edge Router (OER) are involved in this optical network architecture. In this section we also discuss some issues such as routing, signaling and management of HORSA. Secondly, we mainly focus on the design issues of OCR and OER including multi-granularity switching fabrics, intelligent OTU, control plane software and etc. Finally, we reach conclusions that HORSA based on GMPLS is suitable for current hybrid network environment and optimistic for IP traffic transfer, it can be scaled to pure optical IP over WDM architecture based on Optical Packet Switch (OPS).
Genome-Scale Cloning and Expression of Individual Open Reading Frames Using Topoisomerase I-Mediated Ligation (1999)

The in vitro cloning of DNA molecules traditionally uses PCR amplification or site-specific restriction endonucleases to generate linear DNA inserts with defined termini and requires DNA ligase to covalently join those inserts to vectors with the corresponding ends. We have used the properties of Vaccinia DNA topoisomerase I to develop a ligase-free technology for the covalent joining of DNA fragments to suitable plasmid vectors. This system is much more efficient than cloning methods that require ligase because the rapid DNA rejoining activity of Vaccinia topoisomerase I allows ligation in only 5 min at room temperature, whereas the enzyme's high substrate specificity ensures a low rate of vector-alone transformants. We have used this topoisomerase I-mediated cloning technology to develop a process for accelerated cloning and expression of individual ORFs. Its suitability for genome-scale molecular cloning and expression is demonstrated in this report.
Stereotactic breast biopsy: a review. (2009)

In 2008, more than 40,000 women died from breast cancer in the United States. Breast cancer is a devastating public health concern that is best addressed through early detection and treatment. Once a suspicious breast finding is detected, only a biopsy can determine whether it is benign or malignant. Stereotactic breast biopsy uses mammography, ultrasound and occasionally magnetic resonance imaging to guide the placement of a biopsy needle into the breast. A computer plots the coordinates, which help guide the needle to the precise location of a mass or suspicious finding to extract a tissue sample. Stereotactic breast biopsy has its limitations, but its benefits include decreased patient pain and anxiety, quick recovery time and cost-effectiveness. Most importantly, it can prevent women with benign findings from undergoing surgical biopsy.
Plasma insulin-like growth factor binding protein-3 proteolysis is increased in primary breast cancer (2001)

Fasting blood samples were obtained before definitive surgery or biopsy in 128 patients referred to the department of surgery with suspected or manifest breast cancer. Insulin-like growth factor (IGF)-I, IGF-II and free IGF-I were measured by radioimmunoassay/immunoradiometric assay, while IGFBP-3 proteolysis was evaluated by Western immunoblot. 12 patients had ductal carcinoma in situ benign conditions, while staging revealed metastatic disease in 15 of 16 patients with invasive cancers. IGFBP-3 proteolysis above the normal range was recorded in 19 patients with invasive cancers, but in none of the patients suffering from DCIS/benign conditions. Increased IGFBP-3 proteolysis was most frequently recorded in patients harbouring large tumours and metastatic disease (Stage I: 0/19, 0%; Stage II: 3/45, 7%, Stage III: 9/37, 24%, and Stage IV: 7/15, 47%). IGFBP-3 proteolysis was significantly higher in Stage III (P =0.01) and IV (P< 0.001) patients compared to the other stage groups (P = 0.001). IGF-I and IGF-II correlated negatively to IGFBP-3 proteolysis and age. Plasma levels of IGF-I and -II were significantly lower in patients with elevated IGFBP-3 proteolysis compared to those within the normal range. Our findings reveal alterations in the IGF-system among a substantial number of patients with large primary breast cancers.
Cutting Edge: Characterization of Allorestricted and Peptide-Selective Alloreactive T Cells Using HLA-Tetramer Selection (2001)

The vast majority of alloreactive T cells recognize foreign MHC molecules in a peptide-dependent manner. A subpopulation of these peptide-dependent alloreactive T cells is peptide-specific and contains T cells that are of interest for tumor immunotherapy. Allorestricted T cells (i.e., peptide-specific and alloreactive) specific for tumor-associated Ags can be raised in vitro. However, it is technically difficult to distinguish between peptide-specific and peptide-nonspecific alloreactive T cells by functional assays in vitro. Here we show for the first time that allorestricted T cells specifically bind HLA-peptide tetrameric complexes, as nominal Ag-specific T cells would do. In consequence, fluorescent HLA-peptide tetrameric complexes can be used for sorting and cloning of allorestricted CTLs specific for a peptide of interest. We also show by the mean of HLA-peptide tetramers the existence of peptide-selective alloreactive T cells that recognize a conformation on the foreign-MHC brought about by some but not all peptides bound.