gebhart/patrepeval huggingface dataset:
Polymeric prodrug: Synthesis, release study and antimicrobial property of poly(styrene-co-maleic anhydride)-bound acriflavine (1998)

The release behaviour of poly(methyl methacrylate-co-maleic anhydride)-bound acriflavine was compared with that of acriflavine bound to poly(styrene-co-maleic anhydride), the latter copolymer was prepared by solution polymerization and characterised. Acriflavine was covalently bound on the surface of the copolymer matrix in N,N-dimethylformamide using triethylamine as catalyst. The amount of acriflavine covalently bound to poly(styrene-co-maleic anhydride) was studied as a function of time and concentration. The in vitro drug release kinetics of acriflavine in weakly basic medium and the antimicrobial activity of the released drug were established. Das Freisetzungsverhalten von an Poly(styrol-co-maleinsäureanhydrid) gebundenem Acriflavin wurde mit dem von an Poly(methylmethacrylat-co-maleinsäureanhydrid) gebundenem Acriflavin verglichen. Polystyrol-co-maleinsäureanhydrid wurde durch Lösungspolymerisation hergestellt und charakterisiert. Das Acriflavin wurde in N,N-Dimethylformamid unter Einsatz von Triethylamin als Katalysator kovalent an das Copolymere gebunden. Die Menge des kovalent gebundenen Acriflavins wurde als Funktion der Zeit und der Konzentration bestimmt. Die in vitro gemessene Kinetik der Freisetzung von Acriflavin in schwach basischem Medium wurde untersucht und die antimikrobielle Aktivität des freigesetzten Wirkstoffs nachgewiesen.
Socially Assistive Robotics in the Treatment of Behavioural and Psychological Symptoms of Dementia (2006)

Socially assistive robotics is an emerging field of research focused on assisting people through social interaction. While much attention has been paid in the past to robots that provide assistance to people through physical contact, as well as to robots that entertain through social interaction, more recently attention has been paid on socially assistive robots that mediate communication and social exchange. In the paper the argument is developed describing an exploratory study related to the use of the seal robot Paro for the treatment of dementia. The case is illuminating since it highlights the potential of social robots in supporting non pharmacological therapeutic protocols for the dementia care
Elimination of discrete position sensor and current sensor in switched reluctance motor drives (2002)

Shaft position sensing is essential in switched reluctance motors (SRM) in order to synchronize the phase excitation pulses to the rotor position. In order to implement closed-loop torque control, current sensors are also unavoidable. These sensors can constitute a substantial portion of the total system cost and tend to reduce system reliability. A low-cost position sensing scheme using stator inductance measurement is presented. An analog electronic technique can be used to measure the inductance of a nonconducting phase by using a linear frequency-modulated (FM) converter. The output of the FM converter is decoded to get the shaft position signal. The control functions and converter switching signals are processed in a low-cost microcontroller. The discrete current sensors for closed-loop operation have been eliminated by using MOS-gated power switches with integrated current sensing capability. The combination of the above two schemes resulted in a totally sensorless SR motor drive.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Credit Derivatives Are Not “Insurance” (2009)

According to the conventional wisdom, credit derivative contracts are a form of insurance. This view is held by academics, pundits, journalists, and government officials. This essay shows why they are wrong. While there is some superficial similarity between some kinds of credit derivative contracts and insurance contracts - both involve payments by a party holding a risk to another party in return for a promise to make the first party whole under certain future conditions - providing risk-sharing does not make a contract one of insurance. All contracts involve allocating risk between parties, and the lines between insurance contracts and other contracts cannot be sensibly drawn in the abstract. Moreover, the primary reason insurance contracts are treated differently than other contracts (and 'insurance law' is a separate body of law) is not because of their nature as 'insurance' but rather because they are issued by insurance companies. We regulate insurance companies with special rules for three reasons: (1) the inverted production cycle of insurance; (2) the unique governance problems inherent in a model in which the firm's creditors are policyholders; and (3) a view that state-based consumer protection is important to ensure a functioning market. This essay shows that none of these policy justifications obtain in credit derivative markets. Finally, the essay briefly discusses how a centralized clearinghouse or exchange can help improve the credit derivatives markets, as well as potential pitfalls with this solution.
Design of Polymer-Brush-Grafted Magnetic Nanoparticles for Highly Efficient Water Remediation (2013)

Highly efficient removal of mercury(II) ions (Hg(II)) from water has been reported by employing polymer-brush-functionalized magnetic nanoparticles (MNPs). Surface-initiated conventional radical polymerization (SI-cRP) was used to grow poly(2-aminoethyl methacrylate hydrochloride) (poly-AEMA·HCl) polymer chains on magnetite nanoparticles (Fe3O4), followed by the transformation of pendant amino groups into dithiocarbamate (DTC) groups, which showed high chelating affinity toward Hg(II) ions. This polymer-brush-based DTC-functionalized MNP (MNPs-polyAEMA·DTC) platform showed the complete removal of Hg(II) from aqueous solutions. The Hg(II) ion removal capacity and efficiency of MNPs-polyAEMA·DTC were compared with its monolayer analogue, which was derived from the direct transformation of amino groups of (3-aminopropyl) triethoxysilane (APTES)-functionalized MNPs (MNPs-APTES) to DTC functional groups (MNPs-DTC). The surface chemical modifications and higher chelating functional group density, in the case of MNPs-polyAEMA·DTC, were ascertained by transmission electron microscopy (TEM), thermogravimetric analysis (TGA), physical property measurement system (PPMS), attenuated total reflectance infrared (ATR-IR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). The Hg(II) ion removal capacity and efficiency of monolayer and polymer-brush-based DTC-functionalized MNPs (MNPs-DTC and MNPs-polyAEMA·DTC, respectively) were evaluated and compared by studying the effect of various factors on the percentage removal of Hg(II) such as adsorbent amount, temperature, and contact time. Furthermore, the adsorption behavior of MNPs-DTC and MNPs-polyAEMA·DTC was analyzed by applying Langmuir and Freundlich adsorption isotherm models. In addition, the adsorption thermodynamics, as well as the adsorption kinetics, were also evaluated in detail. The higher surface functional group density of MNPs-polyAEMA·DTC led to superior remediation characteristics toward Hg(II) ions than its monolayer analogue.
Initial evaluation, diagnosis, and treatment of anorexia nervosa and bulimia nervosa. (2015)

Eating disorders are life-threatening conditions that are challenging to address; however, the primary care setting provides an important opportunity for critical medical and psychosocial intervention. The recently published Diagnostic and Statistical Manual of Mental Disorders, 5th ed., includes updated diagnostic criteria for anorexia nervosa (e.g., elimination of amenorrhea as a diagnostic criterion) and for bulimia nervosa (e.g., criterion for frequency of binge episodes decreased to an average of once per week). In addition to the role of environmental triggers and societal expectations of body size and shape, research has suggested that genes and discrete biochemical signals contribute to the development of eating disorders. Anorexia nervosa and bulimia nervosa occur most often in adolescent females and are often accompanied by depression and other comorbid psychiatric disorders. For low-weight patients with anorexia nervosa, virtually all physiologic systems are affected, ranging from hypotension and osteopenia to life-threatening arrhythmias, often requiring emergent assessment and hospitalization for metabolic stabilization. In patients with frequent purging or laxative abuse, the presence of electrolyte abnormalities requires prompt intervention. Family-based treatment is helpful for adolescents with anorexia nervosa, whereas short-term psychotherapy, such as cognitive behavior therapy, is effective for most patients with bulimia nervosa. The use of psychotropic medications is limited for anorexia nervosa, whereas treatment studies have shown a benefit of antidepressant medications for patients with bulimia nervosa. Treatment is most effective when it includes a multidisciplinary, teambased approach.
Bioluminescence of Beetle Luciferases with 6′-Amino-<scp>d</scp>-luciferin Analogues Reveals Excited Keto-oxyluciferin as the Emitter and Phenolate/Luciferin Binding Site Interactions Modulate Bioluminescence Colors (2014)

Beetle luciferases produce different bioluminescence colors from green to red using the same d-luciferin substrate. Despite many studies of the mechanisms and structural determinants of bioluminescence colors with firefly luciferases, the identity of the emitters and the specific active site interactions responsible for bioluminescence color modulation remain elusive. To address these questions, we analyzed the bioluminescence spectra with 6'-amino-D-luciferin (aminoluciferin) and its 5,5-dimethyl analogue using a set of recombinant beetle luciferases that naturally elicit different colors and different pH sensitivities (pH-sensitive, Amydetes vivianii λmax=538 nm, Macrolampis sp2 λmax=564 nm; pH-insensitive, Phrixotrix hirtus λmax=623 nm, Phrixotrix vivianii λmax=546 nm, and Pyrearinus termitilluminans λmax=534 nm), a luciferase-like enzyme (Tenebrionidae, Zophobas morio λmax=613 nm), and mutants of C311 (S314). The green-yellow-emitting luciferases display red-shifted bioluminescence spectra with aminoluciferin in relation to those with D-luciferin, whereas the red-emitting luciferases displayed blue-shifted spectra. Bioluminescence spectra with 5,5-dimethylaminoluciferin, in which enolization is blocked, were almost identical to those of aminoluciferin. Fluorescence probing using 2-(4-toluidino)naphthalene-6-sulfonate and inference with aminoluciferin confirm that the luciferin binding site of the red-shifted luciferases is more polar than in the case of the green-yellow-emitting luciferases. Altogether, the results show that the keto form of excited oxyluciferin is the emitter in beetle bioluminescence and that bioluminescence colors are essentially modulated by interactions of the 6'-hydroxy group of oxyluciferin and basic moieties under the influence of the microenvironment polarity of the active site: a strong interaction between a base moiety and oxyluciferin phenol in a hydrophobic microenvironment promotes green-yellow emission, whereas a more polar environment weakens such interaction promoting red shifts. In pH-sensitive luciferases, a pH-mediated switch from a closed hydrophobic conformation to a more open polar conformation promotes the typical red shift.
Cayman-Jamaica fiber system: the longest 2.5 Gbit/s repeaterless submarine link installed (2002)

Recent laboratory repeaterless experiments have been demonstrated at 2.5 Gbit/s over distances of up to 511 km and 529 km using advanced techniques such as forward error correction (FEC) and remotely pumped amplification. In this paper, we describe the utilization of these techniques, in the longest repeaterless 2.5 GBit/s link actually installed for commercial service. The Cayman-Jamaica fiber system is a repeaterless optical submarine cable system that has been laid between the Cayman islands and Jamaica.
Synthesis and Tribological Properties of Sulfur-Containing Methanofullerenes (2013)

Functionally substituted sulfur-containing methanofullerenes have been synthesized by cycloaddition of diazothiotates and C60 fullerene in the presence of the three-component catalyst Pd(acac)2–2PPh3–4Et3Al. The sulfur-containing fullerenes as nanomodifiers for additives (0,005wt%) improve antiwear and EP (extreme pressure) characteristics of industrial oil I-20А.
Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exon. (1988)

Homozygous inheritance of the null bellingham alpha 1-antitrypsin (alpha 1AT) gene is associated with early-onset emphysema, resulting from the lack of alpha 1AT to protect the lung from neutrophil elastase. Cloning and sequencing of the null bellingham gene demonstrated that the promoter region, coding exons, and all exon-intron junctions were normal except for a single base substitution in exon III, causing the normal lys217 (AAG) to become a stop codon (TAG). Evaluation of genomic DNA of family members by using oligonucleotides directed toward this region demonstrated that the index case had inherited this mutation in a homozygous fashion. Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of alpha 1AT deficiency has a very different genetic basis.
Molecular Therapy Targeting Sonic Hedgehog and Hepatocyte Growth Factor Signaling in a Mouse Model of Medulloblastoma (2010)

The use of genetically engineered mice has provided insights into the molecular pathogenesis of the pediatric brain tumor medulloblastoma and revealed promising therapeutic targets. Ectopic expression of Sonic hedgehog (Shh) in cerebellar neural progenitor cells induces medulloblastomas in mice, and coexpression of hepatocyte growth factor (HGF) enhances Shh-induced tumor formation. To determine whether Shh + HGF-driven medulloblastomas were responsive to Shh signaling blockade and whether treatment response could be enhanced by combination therapy targeting both HGF and Shh signaling pathways, we carried out a survival study in mice. We induced medulloblastomas by retrovirus-mediated expression of Shh and HGF, after which we treated the mice systemically with (a) HGF-neutralizing monoclonal antibody L2G7, (b) Shh signaling inhibitor cyclopamine, (c) Shh-neutralizing monoclonal antibody 5E1, (d) L2G7 + cyclopamine, or (e) L2G7 + 5E1. We report that monotherapy targeting either HGF signaling or Shh signaling prolonged survival and that anti-HGF therapy had a more durable response than Shh-targeted therapy. The effect of L2G7 + 5E1 combination therapy on cumulative survival was equivalent to that of L2G7 monotherapy and that of L2G7 + cyclopamine therapy was worse. The principal mechanism by which Shh- and HGF-targeted therapies inhibited tumor growth was a potent apoptotic death response in tumor cells, supplemented by a weaker suppressive effect on proliferation. Our observation that combination therapy either failed to improve or even reduced survival in mice bearing Shh + HGF-induced medulloblastomas compared with monotherapy underscores the importance of preclinical testing of molecular-targeted therapies in animal models of tumors in which the targeted pathways are known to be active.
Self-monitoring to improve robustness of 3D object tracking for robotics (2011)

In robotics object tracking is needed to steer towards objects, check if grasping is successful, or investigate objects more closely by poking or handling them. While many 3D object tracking approaches have been proposed in the past, real world settings pose challenges such as automatically detecting tracking failure, real-time processing, and robustness to occlusion, illumination, and view point changes. This paper presents a 3D tracking system that is capable of overcoming these difficulties using a monocular camera. We present a method of Tracking-State-Detection (TSD) that takes advantage of commercial graphics processors to map textures onto object geometry, to learn textures online, and to recover object pose in real-time. Our system is able to handle 6 DOF object motion during changing lighting conditions, partial occlusion and motion blur while maintaining an accuracy of a few millimetres. Furthermore using TSD we are able to automatically detect occlusions or whether we lost track, and can then trigger a SIFT-based recognition system that is trained during tracking to recover the pose. Evaluations are presented in relation to ground truth pose data and examples present TSD on real-world scenes presented in video sequences.
VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer (2011)

Angiogenesis inhibitors that block VEGF receptor (VEGFR) signaling slow the growth of many types of tumors, but eventually the disease progresses. Multiple strategies are being explored to improve efficacy by concurrent inhibition of other functionally relevant receptor tyrosine kinases (RTK). XL880 (foretinib, GSK1363089) and XL184 (cabozantinib) are small-molecule inhibitors that potently block multiple RTKs, including VEGFR and the receptor of hepatocyte growth factor c-Met, which can drive tumor invasion and metastasis. This study compared the cellular effects of XL880 and XL184 with those of an RTK inhibitor (XL999) that blocks VEGFR but not c-Met. Treatment of RIP-Tag2 mice with XL999 resulted in 43% reduction in vascularity of spontaneous pancreatic islet tumors over 7 days, but treatment with XL880 or XL184 eliminated approximately 80% of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal. Importantly, XL880 and XL184 also decreased invasiveness of primary tumors and reduced metastasis. Overall, these findings indicate that inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade and leads to rapid, robust, and progressive regression of tumor vasculature, increased intratumoral hypoxia and apoptosis, and reduced tumor invasiveness and metastasis.
Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy (2016)

Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO) efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.
13 eIF2α Phosphorylation in Cellular Stress Responses and Disease (2007)

Phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α) is a highly conserved regulatory event activated in response to diverse stresses (Chapter 12). It elicits translational reprogramming as its primary consequence and secondarily affects the transcriptional profile of cells (Chapter 9). Together, these two strands of the eIF2α phosphorylation-dependent integrated stress response (ISR) broadly affect gene expression, amino acid and energy metabolism, and the protein-folding environment in the cell. Rare human mutations and transgenic mice, in which components of the ISR have been severely altered, reveal the pathway’s importance to mammalian pathophysiology. Here, we review the components of the mammalian ISR and consider their function in the context of the cellular adaptation to protein mis-folding, nutrient deprivation, and other stresses. We address the potential importance of the ISR to such common human diseases as diabetes mellitus, the metabolic syndrome, osteoporosis, neurodegeneration, and demyelination. Special emphasis is placed on instances suggesting that failure of homeostasis in the ISR contributes to disease, and these are considered in the context of the hypothetical therapeutic opportunities they present. BACKGROUND Molecular and Physiological Principles That Determine the Consequences of eIF2α Phosphorylation Phosphorylation on serine 51 of its α subunit converts eIF2 from a substrate to an inhibitor of its guanine nucleotide exchange factor, eIF2B. Thus, the level of phosphorylated eIF2α regulates the rate at which eIF2 can be recycled to the GTP-bound form to join in a ternary complex with charged initiator methionyl-tRNA and promote the initiation of mRNA translation (Chapter 4).
HES1 Inhibits Cycling of Hematopoietic Progenitor Cells via DNA Binding (2006)

Notch signaling is implicated in stem cell self-renewal, differentiation, and other developmental processes, and the Drosophila hairy and enhancer of split (HES) 1 basic helix-loop-helix protein is a major downstream effector in the Notch pathway. We found that HES1 was expressed at high levels in the hematopoietic stem cell (HSC)-enriched CD34+/[CD38/Lin](- /low) subpopulation but at low levels in more mature progenitor cell populations. When CD34+ cells were cultured for 1 week, the level of HES1 remained high in the CD34+ subset that had remained quiescent during ex vivo culture but was reduced in CD34+ cells that had divided. To investigate the effects of HES1 in human and mouse hematopoietic stem-progenitor cells (HSPCs), we constructed conditional lentiviral vectors (lentivectors) to introduce transgenes encoding either wild-type HES1 or a mutant lacking the DNA-binding domain (BHES1). We found that lentivector-mediated HES1 expression in CD34+ cells inhibited cell cycling in vitro and cell expansion in vivo, associated with upregulation of the cell cycle inhibitor p21(cip1/Waf1) (p21). The HES1 DNA-binding domain was required for these actions. HES1 did not induce programmed cell death or alter differentiation in HSPCs, and while short-term repopulating activity was reduced in HES1-transduced mouse and human cells, long-term reconstituting HSC function was preserved. Our data characterize the complex, cell context-dependent actions of HES1 as a major downstream Notch signaling regulator of HSPC function.