gebhart/patrepeval huggingface dataset:
Mechanistic Studies on Hydrotropic Solubilization of Nifedipine in Nicotinamide Solution. (1998)

Nicotinamide is a hydrotropic agent that has been demonstrated to solubilize a wide variety of drugs through complexation. Past investigations on the potential interaction of nicotinamide with a solubilized drug have inadequately focused on aliphatic hydrotropes. This study examined the mechanism for the hydrotropic solubilization of nifedipine, a poorly water-soluble drug, in the aqueous solution of nicotinamide using not only nicotinamide analogues but also urea analogues as aliphatic hydrotropes. The values of stability constants, K1:2, at different temperatures in nicotinamide solution were determined by the phase solubility technique, and were utilized to estimate the thermodynamic parameters of complex formation between nifedipine and nicotinamide. The enthalpy change values suggested the participation of intermolecular forces other than hydrogen bonding in complexion. The aqueous solubility of nifedipine was measured in the presence of nicotinamide, urea and their analogues: N-methylnicotinamide, N,N-diethylnicotinamide, nipecotamide, methylurea, ethylurea and butylurea. The drug solubility increased in proportion to the amount of alkyl substituent on the amide nitrogen, and the solubilizing effect of butylurea was as high as that of nicotinamide. Furthermore, the relationship between the logarithmic drug solubilities in 1.0 M aqueous solutions of nicotinamide or urea analogues versus the logarithmic octanol-water partition coefficient values of ligands as an indication of hydrophobicity was found to be linear. The significant contributor to the hydrotropic solubilization of nifedipine with nicotinamide was therefore the ligand hydrophobicity rather than the aromaticity of the pyridine ring.
Quantum state sensitivity of an autoresonant superconducting circuit (2012)

When a frequency chirped excitation is applied to a classical high-$Q$ nonlinear oscillator, its motion becomes dynamically synchronized to the drive and large oscillation amplitude is observed, provided the drive strength exceeds the critical threshold for autoresonance. We demonstrate that when such an oscillator is strongly coupled to a quantized superconducting qubit, both the effective nonlinearity and the threshold become a nontrivial function of the qubit-oscillator detuning. Moreover, the autoresonant threshold is dependent on the quantum state of the qubit and may be used to realize a high-fidelity, latching readout whose speed is not limited by the oscillator $Q$.
Unraveling Immune Privilege (1995)

J. W. Streilein discusses the concept of immune privilege, which protects from rejection tissues grafted to certain sites in the body. The differences between immune-privileged sites and immune-privileged tissues are illustrated by two recent papers implicating the cell surface protein FasL in immune privilege in the eye ( Science , p. 1189 of this issue) and in the testis [D. Bellgrau et al ., Nature 377 , 630 (1995)].
Super crunchers: why thinking-by-numbers is the new way to be smart (2008)

The article reviews the book Super Crunchers: Why Thinking-By-Numbers Is the New Way to Be Smart, by Ian Ayers.
Design of FinFET SRAM Cells Using a Statistical Compact Model (2009)

A study of designing FinFET-based SRAM cells using a compact model is reported. Parameters for a multi-gate FET compact model, BSIM-MG are extracted from fabricated n-type and p-type SOI FinFETs. Local mismatch in gate length and fin width is calibrated to electrical measurements of 378 FinFET SRAM cells. The cell design is re-optimized through Monte Carlo statistical simulations. Variation in readability, writability and static leakage of the cell are studied.
Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Abeta stabilization. (1997)

The brains of individuals with Alzheimer's disease (AD) are characterized by extracellular deposition of beta-amyloid protein (Abeta), intracellular neurofibrillary tangles, and loss of neurons. To study molecular markers associated with dying cells in the AD brain, in situ DNA labeling techniques were used to visualize cells with DNA fragmentation. We observed that intracellular accumulation of apolipoprotein E (apoE) is correlated with the detection of intracellular Abeta-like immunoreactivity within the same cytoplasmic granules, suggesting that uptake of lipids may have stabilized the hydrophobic Abeta protein within the cell. These apoE-containing neurons also exhibit high expression of a cell surface receptor, gp330, which is known to bind apoE. Cells containing significant nuclear DNA fragmentation express the highest level of cell surface gp330. Extracellular deposition of Abeta is detected only upon neuronal cell death, initially as halos of Abeta immunoreactivity around individual dying neurons, and subsequently as Abeta plaques containing numerous neuronal cell ghosts. Based on our in situ analysis of nuclear DNA fragmentation, we conclude that neuronal cell death likely occurs before the extracellular deposition of Abeta in AD brains.
Lifetime control in silicon devices by voids induced by He ion implantation (1996)

A method to control carrier lifetime in silicon locally and efficiently is presented. Voids, formed by high dose He implants, have been characterized by transmission electron microscopy demonstrating they are well localized in depth within layers thinner than 100 nm while their lateral extent is limited only by the masking capability during He implantation. Deep level transient spectroscopy measurements, performed on diodes containing different void densities, revealed the presence of two well defined trap levels, independent of void characteristics, at Ev+0.53 for holes and Ec−0.55 for electrons. These characteristics make them ideal for lifetime control in reducing parasitic transistor gain. Gummel plots on transistors have shown that when voids are formed the gain decreases from 1 to 10−3. The other transistor characteristics are only slightly influenced by the presence of voids.
The World Health Organization Global Outbreak and Response Network – what can Europe learn from this example? (2001)

The second meeting of the Global Outbreak and Response Network (GOARN) was held on 29-30 November 2001 in Geneva, Switzerland. More than 120 attendants represented 82 institutions and governments. The network was formed in April 2000 by the Department of Communicable Disease Surveillance and Response of the World Health Organization (WHOCSR) (http://www.who.int/emc/pdfs/csr%20strategyE.pdf) and partners as an international collaboration of technical associates in the area of epidemic alert and response, including relevant public sector, intergovernmental, and non-governmental organisations, and the private sector (http://www.who.int/emc/pdfs/network.pdf).
Inner core assembly and structure of the lipooligosaccharide of Neisseria meningitidis: capacity of strain NMB to express all known immunotype epitopes (2004)

Neisseria meningitidis expresses a heterogeneous population of lipooligosaccharide (LOS) inner cores variously substituted with alpha1-3-linked glucose and O-3, O-6, and O-7 linked phosphoethanolamine (PEA), as well as glycine, attached to HepII. Combinations of these attachments to the LOS inner core represent immunodominant epitopes that are being exploited as future vaccine candidates. Historically, each LOS immunotype was structurally assessed and prescribed a certain unique inner core epitope. We report that a single isolate, strain NMB, possesses the capacity to produce all of the known neisserial LOS inner core immunotype structures. Analysis of the inner cores from parental LOS revealed the presence or absence of alpha1,3-linked glucose, O-6 and/or O-7 linked PEA, in addition to glycine attached at the 7 position of the HepII inner core. Identification and inactivation of lpt-6 in strain NMB resulted in the loss of both O-6 and O-7 linked PEA groups from the LOS inner core, suggesting that Lpt-6 of strain NMB may have bifunctional transferase activities or that the O-6 linked PEA groups once attached to the inner core undergo nonenzymatic transfer to the O-7 position of HepII. Although O-3 linked PEA was not detected in parental LOS inner cores devoid of alpha1-3-linked glucose residues, LOS glycoforms bearing O-3 PEA groups accumulated in a truncated mutant, NMBlgtK (Hep2Kdo2-lipid A). Because these structures disappeared upon inactivation of the lpt-3 locus, strain NMB expresses a functional O-3 PEA transferase. The LOS glycoforms expressed by NMBlgtK were also devoid of glycine attachments, indicating that glycine was added to the inner core after the completion of the gamma-chain by LgtK. In conclusion, strain NMB has the capability to express all known inner core structures, but in in vitro culture L2 and L4 immunotype structures are predominantly expressed.
Improve light load efficiency for synchronous rectifier buck converter (1999)

A DC/DC converter with high efficiency over very wide load range is necessary for many low voltage applications, such as battery supplied systems and microprocessor power supplies-voltage regulator module (VRM). In order to improve the efficiency of low-voltage power converters, synchronous rectifier technology is widely used. The disadvantage of this technology is low efficiency at light load. This paper proposes a new technology that can improve light load efficiency with very simple implementation. Since current sensors are not required, high density and high efficiency can be achieved that makes the whole circuit suitable for integration. In the paper, two application examples are given. Experimental results verified that this technology significantly improves synchronous rectifier buck converters light load efficiency.
Optimal Algorithm for Single-Molecule Identification with Time-Correlated Single-Photon Counting (2000)

A pattern-matching procedure for identifying single molecules according to the temporal decay characteristics of the fluorescence is presented and applied to measured single-molecule data of three different dyes. Based on the maximum likelihood principle, this procedure is the best possible identification algorithm if the fluorescence time decays of the different molecular species are exactly known. The presented algorithm is numerically simple and fast and, thus, especially suitable to possible online applications. Exact theoretical results for the misidentification errors of the algorithm are derived and compared with the errors determined from the experimental data.
JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders (2018)

JAK inhibitors have been developed following the discovery of the <i>JAK2</i>V617F in 2005 as the driver mutation of the majority of non- <i>BCR-ABL1</i> myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( <i>CALR</i> and <i>MPL</i>) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity. Thus, JAK inhibitors targeting preferentially JAK1 and JAK3 have been developed to treat inflammation, autoimmune diseases, and graft-versus-host disease. Ten years after the beginning of clinical trials, only two drugs have been approved by the US Food and Drug Administration: one JAK2/JAK1 inhibitor (ruxolitinib) in intermediate-2 and high-risk myelofibrosis and hydroxyurea-resistant or -intolerant polycythemia vera and one JAK1/JAK3 inhibitor (tofacitinib) in methotrexate-resistant rheumatoid arthritis. The non-approved compounds exhibited many off-target effects leading to neurological and gastrointestinal toxicities, as seen in clinical trials for MPNs. Ruxolitinib is a well-tolerated drug with mostly anti-inflammatory properties. Despite a weak effect on the cause of the disease itself in MPNs, it improves the clinical state of patients and increases survival in myelofibrosis. This limited effect is related to the fact that ruxolitinib, like the other type I JAK2 inhibitors, inhibits equally mutated and wild-type JAK2 (JAK2WT) and also the JAK2 oncogenic activation. Thus, other approaches need to be developed and could be based on either (1) the development of new inhibitors specifically targeting <i>JAK2</i>V617F or (2) the combination of the actual JAK2 inhibitors with other therapies, in particular with molecules targeting pathways downstream of JAK2 activation or the stability of JAK2 molecule. In contrast, the strong anti-inflammatory effects of the JAK inhibitors appear as a very promising therapeutic approach for many inflammatory and auto-immune diseases.
Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts (2003)

Recently, development of a caveolin-1-deficient (Cav-1 null) mouse model has allowed the detailed analysis of caveolin-1's function in the context of a whole animal. Interestingly, we now report that the hearts of Cav-1 null mice are markedly abnormal, despite the fact that caveolin-1 is not expressed in cardiac myocytes. However, caveolin-1 is abundantly expressed in the nonmyocytic cells of the heart, i.e., cardiac fibroblasts and endothelia. Quantitative imaging studies of Cav-1 null hearts demonstrate a significantly enlarged right ventricular cavity and a thickened left ventricular wall with decreased systolic function. Histological analysis reveals myocyte hypertrophy with interstitial/perivascular fibrosis. Because caveolin-1 is thought to act as a negative regulator of the p42/44 MAP kinase cascade, we performed Western blot analysis with phospho-specific antibodies that only recognize activated ERK1/2. As predicted, the p42/44 MAP kinase cascade is hyperactivated in Cav-1 null heart tissue (i.e., interstitial fibrotic lesions) and isolated cardiac fibroblasts. In addition, endothelial and inducible nitric oxide synthase levels are dramatically upregulated. Thus loss of caveolin-1 expression drives p42/44 MAP kinase activation and cardiac hypertrophy.
Mini-Review: Bmx Kinase Inhibitors for Cancer Therapy (2013)

Kinase inhibitors are among the fastest growing class of anti-cancer therapies. One family of kinases that has recently gained attention as a target for treating malignant disorders is the Tec kinase family. Evidence has been published that one member of this family; the Bmx kinase, may play a role in the pathogenesis of glioblastoma, prostate, breast and lung cancer. Bmx has also shown potential as an anti-vascular therapy in combination with radiation or as a sensitizer to chemotherapeutic agents. Therefore, several companies such as Pharmacyclics, Avila Therapeutics, Merck and Co., Metaproteomics, IRM, and Moerae Matrix have developed compounds or peptides that function as Bmx kinase inhibitors. These companies have subsequently been issued patents for these inhibitors. Additionally, it has been shown that current clinical stage EGFR inhibitors can irreversibly inhibit Bmx, suggesting these compounds might be rapidly moved to clinical trials for other malignancies. This review will discuss current patents issued since 2009 that contain data specifically on inhibition of the Bmx kinase, and will also discuss the scientific literature that suggests their potential application as therapeutics in the treatment of the aforementioned malignancies.
Microelectronic reliability/temperature independence (1991)

Abstract It is shown that microelectronic failures which occur within equipment operating temperature extremes are not dependent on absolute temperature! Therefore, tremendous equipment reductions can be made in size, weight and cost, and there will be an improvement in reliability by elimination of failures due to unreliable complex cooling systems.
The significance of low PU.1 expression in patients with acute promyelocytic leukemia (2012)

Our findings provide evidence that low PU.1 expression in APL patients is required for disease initiation and progression.
Zero volt switching hybrid DC circuit breakers (2002)

DC distribution networks have the advantage of easy connection of generators of different frequency, fuel cells, and storage devices like batteries and flywheels to a grid and the advantage of a lower current load of the cables. Despite these advantages, often an AC distribution network is chosen because of the lack of reliable DC switchgear. In this paper, zero current and zero volt switching hybrid DC circuit breakers are described and discussed. The construction of a 6 kA/600 V zero volt switching hybrid circuit breaker, with an opening time of 200 /spl mu/s is explained and simulation and test results of a 1 kA experiment are discussed. The concept of a zero volt switching hybrid circuit breaker is further improved by using high-density power electronic technologies.
Metastable Underwater Superhydrophobicity (2010)

Superhydrophobicity is generally considered to be a thermodynamically stable wetting state. The stability of the plastron (the thin air film separating the substrate from the water in the superhydrophobic state) was studied in underwater experiments. The plastron exhibited a rapid decay after a well defined onset time, which was found to be dependent on the immersion depth. The plastron decay is explained in terms of a model, which is based on confocal microscopy measurements. The limited underwater plastron stability explains the rarity of permanently submerged superhydrophobic surfaces in nature and limits their scope for commercial applications.
The study of phosphate transporter NAPI2B expression in different histological types of epithelial ovarian cancer. (2009)

We have shown the differential expression profile of NaPi2b phosphate transporter at protein level in various histological types of epithelial ovarian cancer. This finding might facilitate the development of more effective approaches for diagnosis and treatment of this disease.
Measurement of Local Retinal Ganglion Cell Layer Thickness in Patients With Glaucoma Using Frequency-Domain Optical Coherence Tomography (2009)

Local measures of RGC layer thickness can be obtained from fdOCT scans using a manual segmentation procedure, and these measures show qualitative agreement with visual field sensitivity.
Phase Ia and Ib studies of the novel carcinoembryonic antigen (CEA) T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab: Preliminary efficacy and safety in patients with metastatic colorectal cancer (mCRC). (2017)

3002 Background: CEA CD3 TCB (RG7802, RO6958688) is a novel T-cell bispecific antibody targeting CEA on tumor cells and CD3 on T cells. In preclinical models, CEA CD3 TCB displays potent anti-tumor activity, leads to increased intra-tumoral T cell infiltration and activation and upregulates PD-1/PD-L1. Methods: Intwo ongoing dose-escalation phase I studies, RO6958688 is given as monotherapy (S1) i.v. QW or in combination (QW) with atezolizumab 1200 mg Q3W (S2) in adult patients (pts) with advanced CEA+ solid tumors. In S1, 80 pts (mCRC: 68) were treated at dose levels from 0.05 mg to 600 mg; in S2, 38 pts (mCRC: 28) from 5 mg to 160 mg. In S1, a Bayesian logistic regression model with overdose control guided dose escalation. Data cutoff 25.01.17. Results: At doses ≥60mg (36 pts in S1; 10 in S2), CT scans revealed tumor inflammation within days of first dose, consistent with the mode of action of RO6958688. 2 (5%) pts in S1 (both microsatellite stable (MSS) and 2 (20%; 1 MSS) in S2 had a partial response (RECIST v1.1). Preliminary tumor size reduction ( &gt; -10% and &lt; -30% [stable disease]) was observed in 4 (11%) additional pts in S1 and 5 (50%) in S2. At week 4-6 FDG PET scan assessment, 10 (28%) pts with mCRC in S1 and 6 (60%) in S2 had a metabolic partial response (EORTC criteria). At all doses in S1, the most common related AEs were pyrexia (56.3%), infusion related reaction (IRR, 50%) and diarrhea (40%). The most common grade ≥ 3 (G3) related AEs were IRR (16.3%) and diarrhea (5%). 5 patients experienced DLTs: G3 dyspnea, G3 diarrhea, G3 hypoxia, G4 colitis and G5 respiratory failure (G4-5 at 600mg). DLT events were likely associated with tumor lesion inflammation. In S2, there was no evidence of new or additive toxicities, with 1 DLT at 160 mg (G3 transient increase of ALT in a patient with liver metastases). PK/PD data are reported separately. Conclusions: Evidence of antitumor activity was observed with RO6958688 monotherapy in ongoing dose escalation. Activity appeared to be enhanced with doses in combination with atezolizumab, with a manageable safety profile. Updated data will be presented. Clinical trial information: NCT02324257 and NCT02650713.
Temporal decomposition for logic optimization (2006)

Traditional approaches for sequential logic optimization include (1) explicit state-based techniques such as state minimization, (2) structural techniques such as retiming, and (3) methods that exploit sequential don't-cares derived from unreachable states. These approaches optimize a logic circuit as a single component with a single input/output behavior. In this paper we present a novel concept for sequential optimization referred to as temporal decomposition, which distinguishes the logic that initializes the circuit from the logic needed for the behavior after startup. This work was motivated by a recent observation made for bounded property verification: There is a substantial optimization potential for transition relations when the first execution steps are applied as satisfiability don't-cares. This result suggests that current designs include circuitry that is only used during the first few clock periods after reset and could be discarded or disabled after startup. In this paper we describe how temporal decomposition could be applied to treat the logic for startup separately from the remaining circuitry and discuss multiple alternatives to exploit this for an improved implementation.