gebhart/patrepeval huggingface dataset:
Intensive Care Unit Management of Patients with Severe Pulmonary Hypertension and Right Heart Failure (2011)

Despite advances in medical therapies, pulmonary arterial hypertension (PAH) continues to cause significant morbidity and mortality. Although the right ventricle (RV) can adapt to an increase in afterload, progression of the pulmonary vasculopathy that characterizes PAH causes many patients to develop progressive right ventricular failure. Furthermore, acute right ventricular decompensation may develop from disorders that lead to either an acute increase in cardiac demand, such as sepsis, or to an increase in ventricular afterload, including interruptions in medical therapy, arrhythmia, or pulmonary embolism. The poor reserve of the right ventricle, RV ischemia, and adverse right ventricular influence on left ventricular filling may lead to a global reduction in oxygen delivery and multiorgan failure. There is a paucity of data to guide clinicians caring for acute right heart failure in PAH. Treatment recommendations are frequently based on animal models of acute right heart failure or case series in humans with other causes of pulmonary hypertension. Successful treatment often requires that invasive hemodynamics be used to monitor the effect of strategies that are based primarily on biological plausibility. Herein we have developed an approach based on the current understanding of RV failure in PAH and have attempted to develop a treatment paradigm based on physiological principles and available evidence.
Control of a car with a trailer using the Driver Assistance System (2011)

Passive trailer systems provide a variety of advantages in delivery and transportation applications. The transportation capacity of the truck with multiple trailers can be increased in proportion to the number of trailers. The cost of the car with trailers is much lower than the cost of multiple cars. However, the major drawback of the trailer system is that the control problem is difficult. We concentrate on the motion control problem of "pushing" trailers because pushing is much more difficult than "pulling". In this paper, it is shown how the car with passive trailers can be easily controlled by the use of the proposed driver assist system and the motion control scheme. Since the keypad is the only additional device for the driver assist system, the proposed scheme can be implemented with the conventional trucks without many hardware modifications. The manual control strategy of pushing is established. The kinematic design of the passive trailer is adopted from the prior work (Park and Chung, 2004). The kinematic configuration design of the car with trailers is proposed for pushing control. The usefulness of the proposed scheme is experimentally verified with the small scale car with trailer system for the car parking problem. The parking control requires forward and reverse motion in narrow environment. It is shown that even beginners can easily control the pushing motion with the proposed scheme.
Defining the Intensity of Conditioning Regimens: Working Definitions (2009)

Defining conditioning regimen intensity has become a critical issue for the hemopoietic stem cell transplant (HSCT) community. In the present report we propose to define conditioning regimens in 3 categories: (1) myeloablative (MA) conditioning, (2) reduced-intensity conditioning (RIC), and (3) nonmyeloablative (NMA) conditioning. Assignment to these categories is based on the duration of cytopenia and on the requirement for stem cell (SC) support: MA regimens cause irreversible cytopenia and SC support is mandatory. NMA regimens cause minimal cytopenia, and can be given also without SC support. RIC regimens do not fit criteria for MA or NMA regimens: they cause cytopenia of variable duration, and should be given with stem cell support, although cytopenia may not be irreversible. This report also assigns commonly used regimens to one of these categories, based upon the agents, dose, or combinations. Standardized classification of conditioning regimen intensities will allow comparison across studies and interpretation of study results.
Mechanism of Rhodopsin Activation as Examined with Ring-constrained Retinal Analogs and the Crystal Structure of the Ground State Protein (2001)

The guanine nucleotide-binding protein (G-protein)-coupled receptor superfamily (GPCR) is comprised of a large group of membrane proteins involved in a wide range of physiological signaling processes. The functional switch from a quiescent to an active conformation is at the heart of GPCR action. The GPCR rhodopsin has been studied extensively because of its key role in scotopic vision. The ground state chromophore, 11-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Light induces cis-trans isomerization and rhodopsin activation. Here we show that rhodopsin regenerated with a ring-constrained 11-cis-retinal analog undergoes photoisomerization; however, it remains marginally active because isomerization occurs without the chromophore-induced conformational change of the opsin moiety. Modeling the locked chromophore analogs in the active site of rhodopsin suggests that the beta-ionone ring rotates but is largely confined within the binding site of the natural 11-cis-retinal chromophore. This constraint is a result of the geometry of the stable 11-cis-locked configuration of the chromophore analogs. These results suggest that the native chromophore cis-trans isomerization is merely a mechanism for repositioning of the beta-ionone ring which ultimately leads to helix movements and determines receptor activation.
ELAM-1 Mediates Cell Adhesion by Recognition of a Carbohydrate Ligand, Sialyl-Le x (1990)

Recruitment of neutrophils to sites of inflammation is mediated in part by endothelial leukocyte adhesion molecule-1 (ELAM-1), which is expressed on activated endothelial cells of the blood vessel walls. ELAM-1 is a member of the LEC-CAM or selectin family of adhesion molecules that contain a lectin motif thought to recognize carbohydrate ligands. In this report, cell adhesion by ELAM-1 is shown to be mediated by a carbohydrate ligand, sialyl-Lewis X (SLex; NeuAc alpha 2,3Gal beta 1,4(Fuc alpha 1,3)-GlcNAc-), a terminal structure found on cell-surface glycoprotein and glycolipid carbohydrate groups of neutrophils.
The Role of the Insulin‐like Growth Factor I Receptor in Transformation and Apoptosis (1998)

A bstract : The insulin‐like growth factor I receptor (IGF‐IR) regulates cell proliferation by at least three different mechanisms: (1) it is mitogenic; (2) it is required for the establishment and maintenance of the transformed phenotype; and (3) it protects cells from apoptosis both in vitro and in vivo .
Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. (2003)

Histone deacetylase inhibitors induce hyperacetylation of the amino-terminal lysine residues of the core nucleosomal histones, which results in chromatin remodeling and altered gene expression. Present studies demonstrate that exposure to a novel hydroxamic acid analogue histone deacetylase inhibitor, LAQ824, induced p21WAF1 and p27KIP1 and caused growth arrest and apoptosis of human breast cancer SKBR-3 and BT-474 cells that possess amplification and overexpression of Her-2/neu. Treatment with LAQ824 depleted the mRNA and protein levels of Her-2/neu-encoded Her-2, which was associated with attenuation of pAKT, c-Raf-1, and phosphorylated mitogen-activated protein kinase levels. LAQ824 also induced the acetylation of heat shock protein (hsp) 90, resulting in inhibition of its binding to ATP, which has been shown to impair the chaperone association of hsp 90 with its client proteins, Her-2, AKT, and c-Raf-1. Consistent with this, treatment with LAQ824 shifted the binding of Her-2 from hsp 90 to hsp 70, promoting proteasomal degradation of Her-2. Thus, LAQ824 depletes Her-2 through two mechanisms: attenuation of its mRNA levels and promotion of its degradation by the proteasome. Following LAQ824 treatment, the cell membrane association, autotyrosine phosphorylation, and colocalization of Her-2 with HER-3 also declined. Cotreatment with LAQ824 significantly increased trastuzumab-induced apoptosis of BT-474 and SKBR-3 cells. This was associated with greater attenuation of Her-2, c-Raf-1, and pAKT levels. LAQ824 also enhanced taxotere-induced, epothilone B-induced, and gemcitabine-induced apoptosis of BT-474 and SKBR-3 cells. These findings suggest that LAQ824 is active against human breast cancer cells and has the potential to improve the efficacy of trastuzumab, taxotere, gemcitabine, and epothilone B against breast cancer with Her-2/neuamplification.
The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins. (1994)

PKR is a serine/threonine protein kinase induced by interferon treatment and activated by double-stranded RNAs. As a result of activation, PKR becomes autophosphorylated and catalyzes phosphorylation of the alpha subunit of protein synthesis eukaryotic initiation factor 2 (eIF-2). While studying the regulation of PKR in virus-infected cells, we found that a cellular 58-kDa protein (P58) was recruited by influenza virus to downregulate PKR and thus avoid the kinase's deleterious effects on viral protein synthesis and replication. We now report on the cloning, sequencing, expression, and structural analysis of the P58 PKR inhibitor, a 504-amino-acid hydrophilic protein. P58, expressed as a histidine fusion protein in Escherichia coli, blocked both the autophosphorylation of PKR and phosphorylation of the alpha subunit of eIF-2. Western blot (immunoblot) analysis showed that P58 is present not only in bovine cells but also in human, monkey, and mouse cells, suggesting the protein is highly conserved. Computer analysis revealed that P58 contains regions of homology to the DnaJ family of proteins and a much lesser degree of similarity to the PKR natural substrate, eIF-2 alpha. Finally, P58 contains nine tandemly arranged 34-amino-acid repeats, demonstrating that the PKR inhibitor is a member of the tetratricopeptide repeat family of proteins, the only member identified thus far with a known biochemical function.
Gd(III)-Nanodiamond Conjugates for MRI Contrast Enhancement (2009)

A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized, enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles significantly reduced the T(1) of water protons with a per-Gd(III) relaxivity of 58.82 +/- 1.18 mM(-1) s(-1) at 1.5 T (60 MHz). This represents a 10-fold increase compared to the monomer Gd(III) complex (r(1) = 5.42 +/- 0.20 mM(-1) s(-1)) and is among the highest per-Gd(III) relaxivities reported.
Vaccines and their real or perceived adverse effects (1999)

Editor—In responding to Jefferson’s editorial about vaccination and its adverse effects Classen and Classen say that present immunisation schedules may exacerbate the development of type 1 diabetes and that early immunisation with a cocktail of vaccines may prevent the development of diabetes.1,2

The authors cite their unpublished reanalysis of the Finnish trial of Haemophilus influenzae type b vaccine.3 Their conclusions are at odds with the analyses and conclusions of the investigator (JT) presented at a National Institutes of Health workshop and were published recently.4 The Finnish investigators’ review of the data could not attribute the risk of type 1 diabetes in Finnish children to differences in the timing of childhood vaccination in the vaccine trial. The incidence of type 1 diabetes in Finland has risen over several decades, and the risk seems to have been almost linear since the early 1950s. Given the disparity of conclusions, it was suggested that Classen and Classen’s analysis be sent to an independent statistician. We are not aware that this has been done.

The authors quote the aim of the National Institutes of Health workshop as being “to discuss our data” when in fact the title was “an evaluation of the possible role of vaccines and infectious diseases in insulin dependent (type 1) diabetes mellitus.” Two independent reviews of available data specific to vaccines were presented by the Cochrane reviewers and the Johns Hopkins Vaccine Safety Institute; neither found an association such as that reported, and both indicated concerns about methodological issues in statistical analysis and the design and conduct of these studies. The conclusion of the workshop, presented in June 1998, was that studies in humans do not indicate an increase in type 1 diabetes attributable to any vaccine or the timing of immunisation.

Dr J B Classen has filed a European and American patent on his schedule that may have widespread implications should his views be implemented. He applies for a patent on immunisation schedules to be administered from birth, both to reduce the likelihood of type 1 diabetes developing and to protect individuals from communicable diseases.5 The safety or efficacy of one particular paediatric schedule (annex 5 of the application5) has not been shown.

The applications can be obtained for a small fee from the Search and Advisory Service, Patent Office, Cardiff Road, Newport, Gwent NP9 1RH. The full list of references for this letter is on the BMJ’s website.6 We agree that the public should be made aware of what is going on.
Knockdown of lactate dehydrogenase A suppresses tumor growth and metastasis of human hepatocellular carcinoma (2012)

In previous studies, lactate dehydrogenase A (LDHA) was identified as one of the leading genes that promote the proliferative and tumorigenic potential of malignancies. However, less definitive evidence was reported in hepatocellular carcinoma (HCC) cells. Furthermore, the role of LDHA in promoting metastasis of HCC, and its possible mechanism, is not clear. In this study, RNA interference (RNAi) mediated by lentiviral vectors (which induce strong down-regulation of gene expression) was used to analyze the role of LDHA in tumor growth and metastasis in HCC. We performed transient and stable RNAi knockdowns of LDHA in HCCLM3 cells, a line that over-expresses LDHA and has a high metastatic potential. Our studies reveal that previously unidentified effects of LHDA may mediate tumor growth and metastasic effects in HCC. First, HCC cell lines over-express LDHA. Second, LDHA inhibition results in increased apoptosis via production of reactive oxygen species in HCCLM3 cells. Thus, LDHA knockdown resulted in significant reduction in metastatic potential in a xenograft mouse model. Furthermore, we found that FAK, MMP-2, VEGF and E-cadherin proteins contribute to inhibitory effects on metastasis in HCC cells. These studies have important implications for understanding the mechanisms by which LDHA promotes tumor growth and metastasis.
Polyoxometalate Oxidation of Phenolic Lignin Models (2001)

A new environmentally friendly technology for wood pulp delignification, based on the use of polyoxometalates (POMs)and oxygen, is being developed. Polyoxometalate solutions that selectively oxidize lignin under anaerobic conditions can be reoxidized by oxygen and also catalyze the aerobic mineralization of the lignin fragments to CO2 and H2O, making possible the closed-mill manufacture of paper. Model studies on the oxidation of various lignin-like soluble compounds with POMs suggest that single-electron oxidation of phenolic substructures occurs first, followed by the hydrolysis of cationic intermediates. Detailed physico-chemical studies of the solutions of the alkali-metal salts of POMs show a correlation between the reduction potentials of POMs and the rate of oxidation of a phenolic lignin model that is ascribed to ion pairing between alkali-metal cations and POM anions.
Role of Arousals in the Pathogenesis of Obstructive Sleep Apnea (2003)

Arousal is believed to be needed for upper airway opening in obstructive hypopneas-apneas, without compelling evidence to support this notion. The association may be incidental. I studied the temporal relation between arousal and opening and impact of arousal on flow response at opening in 82 patients (apnea-hypopnea index, 46 +/- 35/hour). Obstructive apneas-hypopneas were induced by dial-down of continuous positive airway pressure. Obstructions and hypopneas occurred in 44 and 56% of dial-downs, respectively. When arousal occurred (83% of dial-downs), the temporal relation between arousal and opening was inconsistent between and within patients. Frequency of opening without or before arousal increased with milder obstructions (p < 10(-9)) and with delta power of EEG (p < 10(-6)). Time of opening was unaffected by whether arousal occurred before or after opening (18.0 +/- 9.8 vs. 18.1 +/- 10.5 seconds). Flow response was already excessive when opening occurred without or before arousal (180 +/- 148% of initial flow decline) and was considerably higher when arousal occurred (267 +/- 154%, p < 10(-10)). Flow undershoot after first ventilatory response was greater if arousal occurred (p < 0.01). It is concluded that arousals are incidental events that occur when thresholds for arousal and for arousal-independent opening are close. They are not needed to initiate opening or to obtain adequate flow and they likely increase the severity of the disorder by promoting greater ventilatory instability.
Screening for non-regulated organic compounds in municipal wastewater in Göteborg, Sweden (1996)

Organic compounds from influent and effluent wastewater were concentrated on C18 bonded phase cartridges and sequentially eluted with organic solvents of different polarity. About 80% of the toxicity (Microtox) arised from organic matter eluted with ether. Approximately 50% decrease in the overall toxicity of the influent was observed during the treatment process. More than 50 individual compounds were identified in the eluates for both influent and effluent by GC-MS and FIA-MS analysis. Perfume additives to washing powders and cleaning agents and a number of industrial volatile hydrophilic solvents were quantitatively removed by volatilization in the treatment process. Only a partial removal was observed for less volatile compounds (benzophenone, dibutyl formamide, dimethyl quinoline, benzothiazole, phosphate esters) of industrial origin. Substituted phenols, used as antioxidants in both industrial and domestic products were transformed to corresponding -ene-ones in the biological stage of the water treatment process. Polyglycols and polyglycol ether type surfactants are not removed in the activated sludge prosess, only partly transformed to highly persistant acids by oxidation of the terminal hydroxyl function. The treatability in municipal wastewater plants should be paid much more attention when introducing polar non-volatile constituents in new “environmentally friendly” water based products or processes.
Detection of Chronic Wasting Disease in the Lymph Nodes of Free-Ranging Cervids by Real-Time Quaking-Induced Conversion (2014)

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. Since the disease was first identified in northern Colorado and southern Wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two Canadian provinces and the Republic of South Korea. Identification of CWD-affected animals currently requires postmortem analysis of brain or lymphoid tissues using immunohistochemistry (IHC) or an enzyme-linked immunosorbent assay (ELISA), with no practical way to evaluate potential strain types or to investigate the epidemiology of existing or novel foci of disease. Using a standardized real-time (RT)-quaking-induced conversion (QuIC) assay, a seeded amplification assay employing recombinant prion protein as a conversion substrate and thioflavin T (ThT) as an amyloid-binding fluorophore, we analyzed, in a blinded manner, 1,243 retropharyngeal lymph node samples from white-tailed deer, mule deer, and moose, collected in the field from areas with current or historic CWD endemicity. RT-QuIC results were then compared with those obtained by conventional IHC and ELISA, and amplification metrics using ThT and thioflavin S were examined in relation to the clinical history of the sampled deer. The results indicate that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological studies in areas in which CWD is endemic or not endemic.
Reducing energy of virtual cache synonym lookup using bloom filters (2006)

Virtual caches are employed as L1 caches of both high performance and embedded processors to meet their short latency requirements. However, they also introduce the synonym problem where the same physical cache line can be present at multiple locations in the cache due to their distinct virtual addresses, leading to potential data consistency issues. To guarantee correctness, common hardware solutions either perform serial lookups for all possible synonym locations in the L1 consuming additional energy or employ a reverse map in the L2 cache that incurs a large area overhead. Such preventive mechanisms are nevertheless indispensable even though synonyms may not always be present during the execution.In this paper, we study the synonym issue using Windows applications workload and propose a technique based on Bloom filters to reduce synonym lookup energy. By tracking the address stream using Bloom filters, we can confidently exclude the addresses that were never observed to eliminate unnecessary synonym lookups, thereby saving energy in the L1 cache. Bloom filters have a very small area overhead making our implementation a feasible and attractive solution for synonym detection. Our results show that synonyms in these applications actually constitutes less than 0.1% of the total cache misses. By applying our technique, the dynamic energy consumed in L1 data cache can be reduced up to 32.5%. When taking leakage energy into account, the savings is up to 27.6%.
Antivirale Thiosemicarbazone und verwandte Verbindungen. I. Synthese und Struktur substituierter Isatinthiosemicarbazone und ‐isothiosemicarbazone (1972)

Abstract Eine Reihe substituierter Isatinthiosemicarbazone sowie am Schwefel bzw. in 1‐ und 4′‐Stellung substituierter Isatinisothiosemicarbazone wurde synthetisiert. Isatinthiosemicarbazone mit unsubstituierten NH‐Gruppen bilden zur 2‐CO‐Gruppe des Isatins in festem und gelöstem Zustand intra‐ und intermolekulare Wasserstoffbrücken aus. Die Isatinisothiosemicarbazone enthalten die Doppelbindung der Seitenkette in 2′,3′‐Position. Wasserstoffbrücken können bei diesen Verbindungen aus sterischen Gründen nur intermolekular auftreten.
Structural Organization of a Sex-comb-on-midleg/Polyhomeotic Copolymer (2005)

The polycomb group proteins are required for the stable maintenance of gene repression patterns established during development. They function as part of large multiprotein complexes created via a multitude of protein-protein interaction domains. Here we examine the interaction between the SAM domains of the polycomb group proteins polyhomeotic (Ph) and Sex-comb-on-midleg (Scm). Previously we showed that Ph-SAM polymerizes as a helical structure. We find that Scm-SAM also polymerizes, and a crystal structure reveals an architecture similar to the Ph-SAM polymer. These results suggest that Ph-SAM and Scm-SAM form a copolymer. Binding affinity measurements between Scm-SAM and Ph-SAM subunits in different orientations indicate a preference for the formation of a single junction copolymer. To provide a model of the copolymer, we determined the structure of the Ph-SAM/Scm-SAM junction. Similar binding modes are observed in both homo- and heterocomplex formation with minimal change in helix axis direction at the polymer joint. The copolymer model suggests that polymeric Scm complexes could extend beyond the local domains of polymeric Ph complexes on chromatin, possibly playing a role in long range repression.