gebhart/patrepeval huggingface dataset:
Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1) (2012)

The collectins are a group of innate immune proteins structurally characterized by their content of a carbohydrate recognition domain and a collagen-like region. Collectin liver 1 (CL-L1) and collectin 11 (CL-11, alias collectin kidney 1, CL-K1) are the more recently described members of this group. Their genomic organization and protein structure reveal many similarities. However, CL-11 is a serum protein, whereas CL-L1 appears to be restricted to the cytosol of cells such as hepatocytes. Specificity analyses of the CRDs reveal some differences in their preferences for saccharides: CL-11 binds most avidly to l-fucose and d-mannose, whereas CL-L1 shows preference for d-mannose, d-fucose, N-acetylglucosamine, and surprisingly also d-galactose. CL-11 binds to various microorganisms including Escherichia coli, Candida albicans and Influenza A virus. Polymorphisms in the CL-11 gene (COLEC11) leading to deficiencies have recently been identified as causative for 3MC syndrome. The 3MC syndrome is associated with a wide spectrum of developmental features including facial dysmorphism, cognitive impairment, hearing loss and vesicorenal anomalies. Similar polymorphic associations were reported for the mannan-binding lectin-associated serine protease 3 (MASP-3), and falls into line with the observation that CL-11 is found in circulating complexes with MASP-1/3. These findings suggest dual or overlapping functions of CL-11 in innate immunity and in fetal development.
Human Induced Pluripotent Stem Cells Differentiated into Chondrogenic Lineage Via Generation of Mesenchymal Progenitor Cells (2012)

Human induced pluripotent stem cells (hiPSCs) exhibit pluripotency, proliferation capability, and gene expression similar to those of human embryonic stem cells (hESCs). hESCs readily form cartilaginous tissues in teratomas in vivo; despite extensive effort, however, to date no efficient method for inducing mature chondrocytes in vitro has been established. hiPSCs can also differentiate into cartilage in vivo by teratoma formation, but as with hESCs, no reliable system for in vitro chondrogenic differentiation of hiPSCs has yet been reported. Here, we examined the chondrogenic differentiation capability of hiPSCs using a multistep culture method consisting of embryoid body (EB) formation, cell outgrowth from EBs, monolayer culture of sprouted cells from EBs, and 3-dimensional pellet culture. In this culture process, the cell density of monolayer culture was critical for cell viability and subsequent differentiation capability. Monolayer-cultured cells exhibited fibroblast-like morphology and expressed markers for mesenchymal stem cells. After 2-3 weeks of pellet culture, cells in pellets exhibited a spherical morphology typical of chondrocytes and were surrounded by extracellular matrix that contained acidic proteoglycans. The expression of type II collagen and aggrecan in pellets progressively increased. Histological analysis revealed that over 70% of hiPSC-derived pellets successfully underwent chondrogenic differentiation. Using the same culture method, hESCs showed similar histological changes and gene expression, but differentiated slightly faster and more efficiently than hiPSCs. Our study demonstrates that hiPSCs can be efficiently differentiated into the chondrogenic lineage in vitro via generation of mesenchymal progenitor cells, using a simplified, multistep culture method.
Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance (2002)

We present the design and construction of a fiber optic probe for elastic light scattering spectroscopy in vivo with polarized excitation and polarization sensitive detection. The performance of the fiber probe is evaluated using a suspension of polystyrene spheres placed atop a diffusely scattering substrate, and it demonstrates that the size-dependent characteristics of the scatterers can be extracted in the presence of a highly diffusely scattering background using a linear combination of forward and backward Mie scattering components of the scatterers. Subsequently, Mie theory calculations are performed over a broad range of diagnostically relevant parameters of nuclei-mean diameter, size distribution, and relative refractive index-to understand how the polarized reflectance measurements with the fiber probe can be used to extract morphological information about epithelial tissue. Finally, the feasibility of in vivo measurements with the fiber optic based polarization sensitive light scattering spectroscopy is demonstrated.
Valproic Acid Attenuates Blood–Brain Barrier Disruption in a Rat Model of Transient Focal Cerebral Ischemia: The Roles of HDAC and MMP-9 Inhibition (2010)

Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is known to protect against cerebral ischemia. The effects of VPA on blood-brain barrier (BBB) disruption were investigated in rats subjected to transient middle cerebral artery occlusion (MCAO). Postischemic VPA treatment remarkably attenuated MCAO-induced BBB disruption and brain edema. Meanwhile, VPA significantly reduced MCAO-induced elevation of matrix metalloproteinase-9 (MMP-9), degradation of tight junction proteins, and nuclear translocation of nuclear factor-κB (NF-κB). Sodium butyrate, another HDAC inhibitor, mimicked these effects of VPA. Our findings suggest that BBB protection by VPA involves HDAC inhibition-mediated suppression of NF-κB activation, MMP-9 induction, and tight junction degradation.
Demand Response as a Market Resource Under the Smart Grid Paradigm (2010)

Demand response (DR), distributed generation (DG), and distributed energy storage (DES) are important ingredients of the emerging smart grid paradigm. For ease of reference we refer to these resources collectively as distributed energy resources (DER). Although much of the DER emerging under smart grid are targeted at the distribution level, DER, and more specifically DR resources, are considered important elements for reliable and economic operation of the transmission system and the wholesale markets. In fact, viewed from transmission and wholesale operations, sometimes the term ¿virtual power plant¿ is used to refer to these resources. In the context of energy and ancillary service markets facilitated by the independent system operators (ISOs)/regional transmission organizations (RTOs), the market products DER/DR can offer may include energy, ancillary services, and/or capacity, depending on the ISO/RTO market design and applicable operational standards. In this paper we first explore the main industry drivers of smart grid and the different facets of DER under the smart grid paradigm. We then concentrate on DR and summarize the existing and evolving programs at different ISOs/RTOs and the product markets they can participate in. We conclude by addressing some of the challenges and potential solutions for implementation of DR under smart grid and market paradigms.
Staphylococcus aureus Isolates Carrying Panton-Valentine Leucocidin Genes in England and Wales: Frequency, Characterization, and Association with Clinical Disease (2005)

Staphylococcus aureus isolates carrying the genes that encode for Panton-Valentine leucocidin (PVL), a highly potent toxin, have been responsible for recent outbreaks of severe invasive disease in previously healthy children and adults in the United States of America and Europe. To determine the frequency of PVL-positive isolates sent to the Staphylococcus Reference Unit (United Kingdom) for epidemiological purposes, we tested 515 isolates of S. aureus, and 8 (1.6%) were positive for the PVL locus. A further 470 isolates were selected to explore the association of PVL-positive S. aureus with clinical disease. Of these, 23 (4.9%) were PVL positive and most were associated with skin and soft tissue infections (especially abscesses). The PVL genes were also detected in isolates responsible for community-acquired pneumonia, burn infections, bacteremia, and scalded skin syndrome. Genotyping by pulsed-field gel electrophoresis and multilocus sequence typing revealed that the PVL-positive isolates were from diverse genetic backgrounds, although one prevalent clone of 12 geographically dispersed methicillin-resistant S. aureus (MRSA) isolates was identified (ST80). All 12 isolates were stapylococcal cassette chromosome mec type IVc, had an agr3 allele, and shared a common toxin gene profile (sea-see, seg-sej, eta, etb, and tst negative but etd positive). ST80 strains with similar genetic characteristics have been responsible for community-acquired infections in France and Switzerland. The remaining PVL-positive isolates were mostly methicillin-sensitive S. aureus and belonged to 12 different sequence types, including ST22 and ST30, which are closely related to the most prevalent MRSA clones in United Kingdom hospitals, EMRSA-15 and EMRSA-16, respectively.
Integrated Digital Continuous Media: A Framework Based on Mach, X11, (1990)

High-quality sound and motion video (continuous media) are potentially important elements of human/computer interfaces. Workstations will soon be available with bus-based hardware for audio/video digital conversion and video compression/decompression and will be connected by networks capable of handling continuous media traffic. This report describes an approach, called integrated digital continuous media (IDCM), to using continuous media in distributed computer systems. In the IDCM approach, continuous media data is handled like other data. It passes through system hardware (main memory, I/O bus, and CPU). User programs can input, output, process, communicate, store and retrieve continuous-media data in the same software framework (operating system, network protocols, window system) as other data types. Furthermore, such programs can run concurrently, sharing the resources of workstations, servers, and networks. IDCM has many advantages over approaches that use separate facilities for storage and communication of continuous media data. However, it raises many difficult system software design issues, ranging from real-time device scheduling to the design of user interfaces and programming toolkits. We enumerate and discuss these issues, and sketch the design of an IDCM software system that addresses many of them. Our design is based on industry-standard software components such as Mach, X11, and TCP/IP. It includes the Session Reservation Protocol (SRP) for distributed resource allocation and scheduling, and Continuous Media Extensions to X (CMEX), an extension of the X11 window system supporting IDCM.
Novel zero-voltage-transition and zero-current-transition pulse-width-modulation converters (2002)

Existing techniques for soft-switching DC-DC converters are for either zero-voltage-turn-on or zero-current-turn-off with the exception of several specialized cases. A new type of soft-switching converter is proposed which has both zero-voltage-turn-on and zero-current-turn-off functions. Its implementation requires even fewer auxiliary circuit components and almost no intentional circulating energy. An experimental converter is built to verify the concept.
cDNA clone analysis of six co-regulated mRNAs encoding skeletal muscle contractile proteins. (1982)

A cDNA cloning approach was used to investigate muscle gene regulation during differentiation of cultured embryonic quail myoblasts. A cDNA clone library of cultured myofiber poly(A)+RNA was constructed and screened by colony hybridization with cDNA probes of myoblast and myofiber RNA. Twenty-eight myofiber-specific cDNA clones were identified and, by cross-hybridization analysis, these clones were found to represent, at most, 18 different myofiber-specific RNAs. Six of these RNAs were identified by sequence analysis of the cDNA clones. These six RNAs encode the contractile proteins alpha-actin, alpha-tropomyosin, myosin heavy chain, myosin light chain 2, troponin C, and troponin I. The embryonic muscle contractile protein sequences are identical with, or closely match, those of adult skeletal muscle proteins and include both fast fiber (myosin light chain 2 and troponin I) and slow fiber (troponin C) isotypes. RNA gel transfer hybridization analysis showed that the cellular abundances of these contractile protein mRNAs increase 20- to 30-fold or more during myoblast differentiation. These findings indicate that coordinate activation of contractile protein synthesis during myogenesis is controlled by mechanisms that direct the accumulation of contractile protein mRNAs rather than their translational utilization. Furthermore, with the possible exception of myosin heavy chain, the contractile protein genes expressed by cultured embryogenic muscle encode adult muscle proteins of both basal and slow fiber types, consistent with a co-activation-selective repression model of gene regulation during fiber type differentiation in developing skeletal muscle.
PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins (2013)

A major limitation of biopharmaceutical proteins is their fast clearance from circulation via kidney filtration, which strongly hampers efficacy both in animal studies and in human therapy. We have developed conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising the small residues Pro, Ala and Ser (PAS). PAS sequences are hydrophilic, uncharged biological polymers with biophysical properties very similar to poly-ethylene glycol (PEG), whose chemical conjugation to drugs is an established method for plasma half-life extension. In contrast, PAS polypeptides offer fusion to a therapeutic protein on the genetic level, permitting Escherichia coli production of fully active proteins and obviating in vitro coupling or modification steps. Furthermore, they are biodegradable, thus avoiding organ accumulation, while showing stability in serum and lacking toxicity or immunogenicity in mice. We demonstrate that PASylation bestows typical biologics, such as interferon, growth hormone or Fab fragments, with considerably prolonged circulation and boosts bioactivity in vivo.
Cardiac Hypertrophy Induced by Mitogen-activated Protein Kinase Kinase 7, a Specific Activator for c-Jun NH2-terminal Kinase in Ventricular Muscle Cells (1998)

Activation of stress-activated protein kinases, including the p38 and the c-Jun NH2-terminal kinases (JNK), have been associated with the onset of cardiac hypertrophy and cell death in response to hemodynamic overload and ischemia/reperfusion injury. Upon infection of cultured neonatal rat cardiac myocytes with recombinant adenoviral vectors expressing a wild type and a constitutively active mutant of MKK7 (or JNKK2), JNK was specifically activated without affecting other mitogen-activated protein kinases, including extracellular signal-regulated protein kinases and p38. Specific activation of the JNK pathway in cardiac myocytes induced characteristic features of hypertrophy, including an increase in cell size, elevated expression of atrial natriuretic factor, and induction of sarcomere organization. In contrast, co-activation of both JNK (by MKK7) and p38 (by MKK3 or MKK6) in cardiomyocytes led to an induction of cytopathic responses and suppression of hypertrophic responses. These data provide the first direct evidence that activation of JNK alone is sufficient to induce characteristic features of cardiac hypertrophy, thereby supporting an active role for the JNK pathway in the development of cardiac hypertrophy. The cytopathic response, as a result of co-activation of both JNK and p38, may contribute to the loss of contractile function and viability of cardiomyocytes following hemodynamic overload and cardiac ischemia/reperfusion injury.
Endothelial Nitric Oxide Synthase in Vascular Disease (2006)

Nitric oxide (NO*) is an important protective molecule in the vasculature, and endothelial NO* synthase (eNOS) is responsible for most of the vascular NO* produced. A functional eNOS oxidizes its substrate L-arginine to L-citrulline and NO*. This normal function of eNOS requires dimerization of the enzyme, the presence of the substrate L-arginine, and the essential cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4), one of the most potent naturally occurring reducing agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen species in the vascular wall. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases represent major sources of this reactive oxygen species and have been found upregulated and activated in animal models of hypertension, diabetes, and sedentary lifestyle and in patients with cardiovascular risk factors. Superoxide (O2*-) reacts avidly with vascular NO* to form peroxynitrite (ONOO-). The cofactor BH4 is highly sensitive to oxidation by ONOO-. Diminished levels of BH4 promote O2*- production by eNOS (referred to as eNOS uncoupling). This transformation of eNOS from a protective enzyme to a contributor to oxidative stress has been observed in several in vitro models, in animal models of cardiovascular diseases, and in patients with cardiovascular risk factors. In many cases, supplementation with BH4 has been shown to correct eNOS dysfunction in animal models and patients. In addition, folic acid and infusions of vitamin C are able to restore eNOS functionality, most probably by enhancing BH4 levels as well.
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm (2010)

This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.
Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction—a pilot study (2006)

Penile erectile tissue is a highly vascularised smooth muscle which hitherto has been an unexplored target for the neuromodulatory effect of hydrogen sulphide. In this study, intracavernous injection of sodium hydrogen sulphide to primates resulted in significant increases in penile length and cavernous pressure. In another set of experiments, administration of DL-propargylglycine (inhibitor of cystathionine gamma-lyase) to rats resulted in significant reduction in cavernous nerve stimulation-evoked perfusion pressure. Our pilot experiment suggests a possible role for endogenous hydrogen sulphide in erectile physiopharmacology through facilitation of nerve-mediated penile tumescence; this is confirmed by the inhibitory effect of propargylglycine on the proerectile pathway.
Rhodium Catalyzed Chelation-Assisted C–H Bond Functionalization Reactions (2011)

Over the last several decades, researchers have achieved remarkable progress in the field of organometallic chemistry. The development of metal-catalyzed cross-coupling reactions represents a paradigm shift in chemical synthesis, and today synthetic chemists can readily access carbon-carbon and carbon-heteroatom bonds from a vast array of starting compounds. Although we cannot understate the importance of these methods, the required prefunctionalization to carry out these reactions adds cost and reduces the availability of the starting reagents. The use of C-H bond activation in lieu of prefunctionalization has presented a tantalizing alternative to classical cross-coupling reactions. Researchers have met the challenges of selectivity and reactivity associated with the development of C-H bond functionalization reactions with an explosion of creative advances in substrate and catalyst design. Literature reports on selectivity based on steric effects, acidity, and electronic and directing group effects are now numerous. Our group has developed an array of C-H bond functionalization reactions that take advantage of a chelating directing group, and this Account surveys our progress in this area. The use of chelation control in C-H bond functionalization offers several advantages with respect to substrate scope and application to total synthesis. The predictability and decreased dependence on the inherent stereoelectronics of the substrate generally result in selective and high yielding transformations with broad applicability. The nature of the chelating moiety can be chosen to serve as a functional handle in subsequent elaborations. Our work began with the use of Rh(I) catalysts in intramolecular aromatic C-H annulations, which we further developed to include enantioselective transformations. The application of this chemistry to the simple olefinic C-H bonds found in α,β-unsaturated imines allowed access to highly substituted olefins, pyridines, and piperidines. We observed complementary reactivity with Rh(III) catalysts and developed an oxidative coupling with unactivated alkenes. Further studies on the Rh(III) catalysts led us to develop methods for the coupling of C-H bonds to polarized π bonds such as those in imines and isocyanates. In several cases the methods that we have developed for chelation-controlled C-H bond functionalization have been applied to the total synthesis of complex molecules such as natural products, highlighting the utility of these methods in organic synthesis.
Transcatheter aortic valve implantation: The evolution of prostheses, delivery systems and approaches (2012)

It is two decades since the first report of transcatheter implantation of a stented aortic valve in an animal. The first implantation of a transcatheter aortic valve in a human was accomplished just one decade ago dramatically demonstrating the promise and feasibility of this new therapy. Over the past 10 years, there have been rapid developments in valves, delivery systems and technical approaches. Today, transcatheter valve implantation is a technical possibility for the great majority of patients with aortic stenosis. The next 10 years may well see this become the dominant therapy for aortic stenosis.
The complete DNA sequence and genomic organization of the avian adenovirus CELO (1996)

The complete DNA sequence of the avian adenovirus chicken embryo lethal orphan (CELO) virus (FAV-1) is reported here. The genome was found to be 43,804 bp in length, approximately 8 kb longer than those of the human subgenus C adenoviruses (Ad2 and Ad5). This length is supported by pulsed-field gel electrophoresis analysis of genomes isolated from several related FAV-1 isolates (Indiana C and OTE). The genes for major viral structural proteins (Illa, penton base, hexon, pVI, and pVIII), as well as the 52,000-molecular-weight (52K) and 100K proteins and the early-region 2 genes and IVa2, are present in the expected locations in the genome. CELO virus encodes two fiber proteins and a different set of the DNA-packaging core proteins, which may be important in condensing the longer CELO virus genome. No pV or pIX genes are present. Most surprisingly, CELO virus possesses no identifiable E1, E3, and E4 regions. There is 5 kb at the left end of the CELO virus genome and 15 kb at the right end with no homology to Ad2. The sequences are rich in open reading frames, and it is likely that these encode functions that replace the missing El, E3, and E4 functions.