gebhart/patrepeval huggingface dataset:
Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth (2013)

De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin.
Resonant infrared detector based on a piezoelectric fishnet metasurface (2015)

This paper reports on the first demonstration of a high resolution (noise equivalent power NEP of 1.9 nW/Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> at 200 Hz bandwidth) and fast (thermal time constant of 5.3 ms) infrared (IR) detector based on a nanoelectromechanical system (NEMS) resonant piezoelectric fishnet-like metasurface (PFM). For the first time, an ultrathin (650 nm) piezoelectric fishnet-like metasurface is employed to form the vibrating body of a nanomechanical resonator with a unique combination of optical, thermal and electromechanical properties. Efficient sensing and actuation (electromechanical coupling coefficient, k <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ~1.4%) of a high frequency (172 MHz) and high quality factor (Q~2254) bulk acoustic mode of vibration in the free-standing ultrathin structure is achieved thanks to the superior piezoelectric transduction properties of the proposed metasurface. Strong absorption (60%) of short wavelength infrared (SWIR) radiation in the ultra-low volume resonant device is obtained thanks to the properly engineered optical properties of the fishnet-like metasurface which provide a Fabry-Perot like resonance at ~4 μm to the structure.
The use of dexmedetomidine for refractory agitation in substance abuse patient (2010)

Psychomotor disturbance in Intensive Care Unit (ICU) continues to be a challenging issue in view of its various ranges of predisposing factors and this includes withdrawal from chronic substance abuse. A combination of opioids, benzodiazepines and antipsychotics are often used to treat such neurochemical disturbances. We report a case of 43 year-old man with 10 years history of substance abuse who presented with acute opioids intoxication. He required mechanical ventilation but exhibited significant agitation in the ICU. The conventional combination of midazolam and morphine, and later propofol infusion failed to control his agitations following admission. However, his symptoms improved and he was extubated within the first 24 hours of stay after dexmedetomidine infusion.
Multifunction biquadratic filters using current conveyors (1997)

Some novel multifunction biquadratic filters with voltage gain, each of which employs four current conveyors, two grounded capacitors, and three-five resistors, are presented. Each proposed circuit offers the following advantageous features: realization of different biquadratic filter signals from the same configuration, no requirements for component matching conditions, employment of only two grounded capacitors which are ideal for integration, orthogonal control of /spl omega//sub 0/ and Q and low sensitivities.
Alternative, Lead-free, Hybrid Organic–Inorganic Perovskites for Solar Applications: A DFT Analysis (2015)

Abstract We here theoretically investigate, by means of a density functional-based approach, the MATl0.5Bi0.5I3 (MA: CH3NH3+) perovskite, where Tl/Bi aliovalent ionic pairs replace Pb cations of the parental MAPbI3. On the basis of a pure structural and electronic analysis, considering the close similarities with the well-assessed MAPbI3 system, we predict such compounds as potential alternative materials for solar applications.
Functional single nucleotide polymorphisms of theCCL5gene and nonemphysematous phenotype in COPD patients (2008)

It was previously reported that the gain-of-function -28 guanine allele of the promoter single nucleotide polymorphism (SNP; cytosine to guanine substitution of nucleotide -28 (-28C>G)) in the CC chemokine ligand 5 gene (CCL5) was associated with susceptibility to late-onset asthma in patients who developed asthma at age > or =40 yrs. The clinical diagnosis of chronic obstructive pulmonary disease (COPD) includes emphysema and small airway disease, and upregulation of CCL5 has been described in the airways of patients with COPD. It was hypothesised that CCL5 has a genetic impact upon the variable expression of emphysema in patients with COPD. Patients with COPD were studied (n = 267). All of the patients underwent pulmonary high-resolution computed tomography (CT), and visual scoring (CT score) was performed to determine emphysema severity. Three SNPs of CCL5 were genotyped, including -403G>A, -28C>G and 375T>C. A significant difference was found in CT score according to CCL5 genotype; the -28G allele was inversely associated with CT score. When the analysis was confined to 180 patients with bronchial reversibility of <15%, even stronger evidence for this association was noted. Functional single nucleotide polymorphisms in the CC chemokine ligand 5 gene were associated with milder emphysema. Together with previous findings, the present study may identify the CC chemokine ligand 5 gene as part of a common pathway in the pathogenesis of late-onset asthma and chronic obstructive pulmonary disease with milder emphysema.
Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration (2011)

At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).
Timing-oriented routers for PCB layout design of high-performance computers (2002)

The authors present two timing-oriented routers for PCB (printed circuit board) layout designs of high-performance computers: the recursive pattern-search router and the detour-length driven line router. The recursive pattern-search router is a precise specified-length router, which does not use detour points but, instead, recursively repeats the search procedures using U-shaped and simple patterns such that the wire length is adjusted to the specified value. This router guarantees that a route can be found which satisfies the length constraint if one exists. It is also capable of pairwise routing. The detour-length-driven line router is a diagonal router based on line routing. The router finds a minimal-length route rapidly using diagonal and orthogonal directions. These routers were incorporated into a routing system for PCB layout designs of mainframe computers (e.g. M-880), and they were confirmed as practical.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Specific inhibition of formation of transcription complexes by a calicheamicin oligosaccharide: a paradigm for the development of transcriptional antagonists. (1994)

Sequence-specific DNA ligands that antagonize DNA-protein interactions represent a potentially powerful means of modulating gene expression. Calicheamicin gamma 1I, a member of the DNA-cleaving enediyne class of anticancer antibiotics, binds to specific DNA sequences through an aryltetrasaccharide domain. To take advantage of this unique sequence-specific recognition capability, the methyl glycoside of the aryltetrasaccharide of calicheamicin gamma 1I (CLM-MG) was used to investigate the ability of glycoconjugate DNA ligands to inhibit DNA-protein interactions. CLM-MG inhibits the formation of DNA-protein complexes at micromolar concentrations in a sequence-specific manner and rapidly dissociates preformed complexes. CLM-MG also inhibits transcription in vivo with similar sequence specificity. These results suggest a strategy for the development of a class of novel biological probes and therapeutic agents.
Characterisation of the catalytically active form of RecG helicase (2000)

Replication of DNA is fraught with difficulty and chromosomes contain many lesions which may block movement of the replicative machinery. However, several mechanisms to overcome such problems are beginning to emerge from studies with Escherichia coli. An important enzyme in one or more of these mechanisms is the RecG helicase, which may target stalled replication forks to generate a four-stranded (Holliday) junction, thus facilitating repair and/or bypass of the original lesion. To begin to understand how RecG might catalyse regression of fork structures, we have analysed what the catalytically active form of the enzyme may be. We have found that RecG exists as a monomer in solution as measured by gel filtration but when bound to junction DNA the enzyme forms two distinct protein-DNA complexes that contain one and two protein molecules. However, mutant inhibition studies failed to provide any evidence that RecG acts as a multimer in vitro. Additionally, there was no evidence for cooperativity in the junction DNA-stimulated hydrolysis of ATP. These data suggest that RecG functions as a monomer to unwind junction DNA, which supports an 'inchworm' rather than an 'active rolling' mechanism of DNA unwinding. The observed in vivo inhibition of wild-type RecG by mutant forms of the enzyme was attributed to occlusion of the DNA target and correlates with the very low abundance of replication forks within an E.COLI: cell, even during rapid growth.
DÉTENTE AND SOUTH ASIA (1975)

ver the years, the record of the United States in South Asia has been a mixed one at best. Our experience brought home to us the limitations on our ability, particularly regarding military assistance, to influence the actions of the major regional states, India and Pakistan. The Indo-Pakistani wars of 1965 and 1971 pushed us toward a posture of gradual disengagement.
Handwashing Compliance Depends on Professional Status (2001)

Significant opportunities exist for quality improvement, novel educational strategies, and assessment of reasons why MDs and, to a lesser extent, RNs fail to follow simple HW practices.
Enhanced Productivity of a Lutein-Enriched Novel Acidophile Microalga Grown on Urea (2010)

Coccomyxa acidophila is an extremophile eukaryotic microalga isolated from the Tinto River mining area in Huelva, Spain. Coccomyxa acidophila accumulates relevant amounts of β-carotene and lutein, well-known carotenoids with many biotechnological applications, especially in food and health-related industries. The acidic culture medium (pH < 2.5) that prevents outdoor cultivation from non-desired microorganism growth is one of the main advantages of acidophile microalgae production. Conversely, acidophile microalgae growth rates are usually very low compared to common microalgae growth rates. In this work, we show that mixotrophic cultivation on urea efficiently enhances growth and productivity of an acidophile microalga up to typical values for common microalgae, therefore approaching acidophile algal production towards suitable conditions for feasible outdoor production. Algal productivity and potential for carotenoid accumulation were analyzed as a function of the nitrogen source supplied. Several nitrogen conditions were assayed: nitrogen starvation, nitrate and/or nitrite, ammonia and urea. Among them, urea clearly led to the best cell growth (~4 × 10(8) cells/mL at the end of log phase). Ammonium led to the maximum chlorophyll and carotenoid content per volume unit (220 μg·mL(·1) and 35 μg·mL(·1), respectively). Interestingly, no significant differences in growth rates were found in cultures grown on urea as C and N source, with respect to those cultures grown on nitrate and CO(2) as nitrogen and carbon sources (control cultures). Lutein accumulated up to 3.55 mg·g(·1) in the mixotrophic cultures grown on urea. In addition, algal growth in a shaded culture revealed the first evidence for an active xanthophylls cycle operative in acidophile microalgae.
Power-Up SRAM State as an Identifying Fingerprint and Source of True Random Numbers (2008)

Intermittently powered applications create a need for low-cost security and privacy in potentially hostile environments, supported by primitives including identification and random number generation. Our measurements show that power-up of SRAM produces a physical fingerprint. We propose a system of fingerprint extraction and random numbers in SRAM (FERNS) that harvests static identity and randomness from existing volatile CMOS memory without requiring any dedicated circuitry. The identity results from manufacture-time physically random device threshold voltage mismatch, and the random numbers result from runtime physically random noise. We use experimental data from high-performance SRAM chips and the embedded SRAM of the WISP UHF RFID tag to validate the principles behind FERNS. For the SRAM chip, we demonstrate that 8-byte fingerprints can uniquely identify circuits among a population of 5,120 instances and extrapolate that 24-byte fingerprints would uniquely identify all instances ever produced. Using a smaller population, we demonstrate similar identifying ability from the embedded SRAM. In addition to identification, we show that SRAM fingerprints capture noise, enabling true random number generation. We demonstrate that a 512-byte SRAM fingerprint contains sufficient entropy to generate 128-bit true random numbers and that the generated numbers pass the NIST tests for runs, approximate entropy, and block frequency.
Sterol Intermediates from Cholesterol Biosynthetic Pathway as Liver X Receptor Ligands (2006)

The liver X receptors (LXRs) are ligand-activated transcription factors that regulate the expression of genes controlling lipid metabolism. Oxysterols bind LXRs with high affinity in vitro and are implicated as ligands for the receptor. We showed previously that accumulation of selected dietary sterols, in particular stigmasterol, is associated with activation of LXR in vivo. In the course of the defining of structural features of stigmasterol that confer LXR agonist activity, we determined that the presence of an unsaturated bond in the side chain of the sterol was necessary and sufficient for activity, with the C-24 unsaturated cholesterol precursor sterols desmosterol and zymosterol exerting the largest effects. Desmosterol failed to increase expression of the LXR target gene, ABCA1, in LXRalpha/beta-deficient mouse fibroblasts, but was fully active in cells lacking cholesterol 24-, 25-, and 27-hydroxylase; thus, the effect of desmosterol was LXR-dependent and did not require conversion to a side chain oxysterol. Desmosterol bound to purified LXRalpha and LXRbeta in vitro and supported the recruitment of steroid receptor coactivator 1. Desmosterol also inhibited processing of the sterol response element-binding protein-2 and reduced expression of hydroxymethylglutaryl-CoA reductase. These observations are consistent with specific intermediates in the cholesterol biosynthetic pathway regulating lipid homeostasis through both the LXR and sterol response element-binding protein pathways.
Supported choline hydroxide (ionic liquid) as heterogeneous catalyst for aldol condensation reactions (2004)

Choline hydroxide was used as a basic catalyst for aldol condensation reactions to produce new C-C bonds between several ketones and aldehydes. Choline supported on MgO exhibits higher TOF values than other well known basic catalysts in these reactions.
Hydrogen Production by a Hyperthermophilic Membrane-Bound Hydrogenase in Soluble Nanolipoprotein Particles (2008)

Hydrogenases constitute a promising class of enzymes for ex vivo hydrogen production. Implementation of such applications is currently hindered by oxygen sensitivity and, in the case of membrane-bound hydrogenases (MBH), poor water solubility. Nanolipoprotein particles (NLPs), formed from apolipoproteins and phospholipids, offer a novel means to incorporate MBH into in a well-defined water-soluble matrix that maintains the enzymatic activity and is amenable to incorporation into more complex architectures. We report the synthesis, hydrogen-evolving activity and physical characterization of the first MBH-NLP assembly. This may ultimately lead to the development of biomimetic hydrogen production devices.
Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats. (2001)

The biological role of the peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, has been highlighted recently. Although PPARgamma ligands have been found to inhibit mammary carcinogenesis in rodents, the effects on colon tumorigenesis are controversial. In the present study, three different experiments were conducted to investigate the modifying effects of PPARs ligands (PPARalpha and PPARgamma) on colitis and an early phase of colitis-related colon carcinogenesis in male F344 rats. In the first experiment, gastric gavage of troglitazone (PPARgamma ligand, 10 or 100 mg/kg body weight) or bezafibrate (PPARalpha ligand, 10 or 100 mg/kg body weight) inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil factor-2 content in colonic mucosa. In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. In the third experiment, dietary administration (0.01% in diet for 6 weeks) of pioglitazone (PPARgamma ligand), troglitazone, and bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both ligands significantly reduced cell proliferation activity in colonic mucosa exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands (PPARalpha and PPARgamma) can inhibit the early stages of colon tumorigenesis with or without colitis.
Effect of Phosphorylation on EGFR Dimer Stability Probed by Single-Molecule Dynamics and FRET/FLIM (2015)

Deregulation of epidermal growth factor receptor (EGFR) signaling has been correlated with the development of a variety of human carcinomas. EGF-induced receptor dimerization and consequent trans- auto-phosphorylation are among the earliest events in signal transduction. Binding of EGF is thought to induce a conformational change that consequently unfolds an ectodomain loop required for dimerization indirectly. It may also induce important allosteric changes in the cytoplasmic domain. Despite extensive knowledge on the physiological activation of EGFR, the effect of targeted therapies on receptor conformation is not known and this particular aspect of receptor function, which can potentially be influenced by drug treatment, may in part explain the heterogeneous clinical response among cancer patients. Here, we used Förster resonance energy transfer/fluorescence lifetime imaging microscopy (FRET/FLIM) combined with two-color single-molecule tracking to study the effect of ATP-competitive small molecule tyrosine kinase inhibitors (TKIs) and phosphatase-based manipulation of EGFR phosphorylation on live cells. The distribution of dimer on-times was fitted to a monoexponential to extract dimer off-rates (koff). Our data show that pretreatment with gefitinib (active conformation binder) stabilizes the EGFR ligand-bound homodimer. Overexpression of EGFR-specific DEP-1 phosphatase was also found to have a stabilizing effect on the homodimer. No significant difference in the koff of the dimer could be detected when an anti-EGFR antibody (425 Snap single-chain variable fragment) that allows for dimerization of ligand-bound receptors, but not phosphorylation, was used. These results suggest that both the conformation of the extracellular domain and phosphorylation status of the receptor are involved in modulating the stability of the dimer. The relative fractions of these two EGFR subpopulations (interacting versus free) were obtained by a fractional-intensity analysis of ensemble FRET/FLIM images. Our combined imaging approach showed that both the fraction and affinity (surrogate of conformation at a single-molecule level) increased after gefitinib pretreatment or DEP-1 phosphatase overexpression. Using an EGFR mutation (I706Q, V948R) that perturbs the ability of EGFR to dimerize intracellularly, we showed that a modest drug-induced increase in the fraction/stability of the EGFR homodimer may have a significant biological impact on the tumor cell's proliferation potential.
Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab (2013)

Obinutuzumab (GA101) is a glycoengineered type 2 CD20 antibody with enhanced CD16A-binding and natural killer-mediated cytotoxicity. CD16B is highly homologous to CD16A and a major FcγR on human polymorphonuclear neutrophils (PMNs). We show here that glycoengineered obinutuzumab or rituximab bound CD16B with approximately sevenfold higher affinity, compared with nonglycoengineered wild-type parental antibodies. Furthermore, glycoengineered obinutuzumab activated PMNs, either purified or in chronic lymphoblastic leukemia whole blood, more efficiently than wild-type rituximab. Activation resulted in a 50% increase in CD11b expression and 70% down-modulation of CD62L on neutrophils and in release of tumor necrosis factor alpha, IL-6, and IL-8. Activation was not accompanied by generation of reactive oxygen species or antibody-dependent cellular cytotoxicity activity, but led to up to 47% phagocytosis of glycoengineered anti-CD20 opsonized chronic lymphoblastic leukemia targets by purified PMNs. Significant phagocytosis was observed in whole blood, but only in the presence of glycoengineered antibodies, and was followed by up to 50% PMN death. Finally we show, using anti-CD16B and anti-CD32A Fab and F(ab')2 fragments, that both of these receptors are involved in PMN activation, phagocytosis, and cell death induced by glycoengineered antibodies. We conclude that phagocytosis by PMNs is an additional mechanism of action of obinutuzumab mediated through its higher binding affinity for CD16B.