gebhart/patrepeval huggingface dataset:
UST/DME: a clock tree router for general skew constraints (2000)

In this paper, we propose new approaches for solving the useful-skew tree (UST) routing problem [17]: Clock routing subject to general skew constraints. The clock layout synthesis engine of our UST algorithms is based on the deferred-merge embedding (DME) paradigm for zero-skew tree [5; 1] and bounded-skew tree [8; 2] routings; hence, the names UST/DME and Greedy-UST/DME for our algorithms. They simultaneously perform skew scheduling and tree routing such that each local skew range is incrementally refined to a skew value that minimizes the wirelength during the bottom-up merging phase of DME. The resulting skew schedule is not only feasible, but is also best for routing in terms of wirelength. The experimental results show very encouraging improvement over the previous BST/DME algorithm on three ISCAS89 benchmarks under general skew constraints in terms of total wirelength.
GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders. (2009)

Type 2 diabetes (T2D) and associated obesity have reached epidemic proportions, and there is an increasing need for orally effective agents that regulate glucose homeostasis with a concurrent reduction in body weight. GPR119, a class-A (rhodopsin-like) G protein-coupled receptor, expressed primarily in the human pancreas and gastrointestinal tract, has attracted considerable interest as a T2D drug target in the last three to five years. The activation of GPR119 increases the intracellular accumulation of cAMP, leading to enhanced glucose-dependent insulin secretion and increased levels of the incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic peptide). In rodent models, orally available GPR119-specific agonists have been shown to attenuate blood glucose levels with a simultaneous body weight loss. This review summarizes the research leading to the identification of GPR119 as a potential drug target for T2D and related metabolic disorders. In addition, an overview of the recent progress made in the discovery of orally active GPR119 agonists is provided.
Sustained Inhibition of Receptor Tyrosine Kinases and Macrophage Depletion by PLX3397 and Rapamycin as a Potential New Approach for the Treatment of MPNSTs (2014)

Taken together, our data strongly suggest that PLX3397 is superior to imatinib in the treatment of MPNSTs, and the combination of PLX3397 with a TORC1 inhibitor could provide a new therapeutic approach for the treatment of this disease.
Biomimetic interfacial interpenetrating polymer networks control neural stem cell behavior (2007)

Highly-regulated signals surrounding stem cells, such as growth factors at specific concentrations and matrix mechanical stiffness, have been implicated in modulating stem cell proliferation and maturation. However, tight control of proliferation and lineage commitment signals is rarely achieved during growth outside the body, since the spectrum of biochemical and mechanical signals that govern stem cell renewal and maturation are not fully understood. Therefore, stem cell control can potentially be enhanced through the development of material platforms that more precisely orchestrate signal presentation to stem cells. Using a biomimetic interfacial interpenetrating polymer network (IPN), we define a robust synthetic and highly-defined platform for the culture of adult neural stem cells. IPNs modified with two cell-binding ligands, CGGNGEPRGDTYRAY from bone sialoprotein [bsp-RGD(15)] and CSRARKQAASIKVAVSADR from laminin [lam-IKVAV(19)], were assayed for their ability to regulate self-renewal and differentiation in a dose-dependent manner. IPNs with >5.3 pmol/cm(2) bsp-RGD(15) supported both self-renewal and differentiation, whereas IPNs with lam-IKVAV(19) failed to support stem cell adhesion and did not influence differentiation. The IPN platform is highly tunable to probe stem cell signal transduction mechanisms and to control stem cell behavior in vitro.
Expression of normal and transforming H-ras genes in Escherichia coli and purification of their encoded p21 proteins. (1984)

The H-ras gene of the BALB murine sarcoma virus (BALB-MSV) was placed under the transcriptional control of the tightly regulated PL promoter of bacteriophage lambda in the expression vectors pEV-vrf-1 and pRC23. Upon derepression of the PL promoter, large amounts (10-20% of total cellular protein) of the H-ras gene product p21 are synthesized in Escherichia coli. We constructed three H-ras gene expression vectors, designated pJCL-H5, pJCL-E30, and pJCL-33. pJCL-H5 directs the synthesis of p21, a fusion protein whose four amino-terminal residues are replaced by eight amino acids coded for by plasmid sequences. The 13 5' coding nucleotides of the BALB-MSV H-ras gene missing in pJCL-H5 were regenerated in pJCL-E30 by inserting a pair of complementary synthetic oligodeoxynucleotides. As a result, pJCL-E30 encodes a p21 protein, p21T, of sequence identical to that of the transforming p21 protein of BALB-MSV. pJCL-33 is a derivative of pJCL-E30 in which the 12th codon, AAA, a lysine codon, was replaced by GGA, a glycine codon. Thus, pJCL-33 directs the synthesis of a p21 protein, p21N, whose sequence corresponds to that of a normal cellular p21 protein. We report the purification of H-ras p21 proteins to apparent homogeneity by a method involving solubilization with chaotropic agents followed by reverse-phase high-performance liquid chromatography.
Progressive activation of adult microglial cells in vitro (1996)

Bulk-isolated microglial cells from the adult rat brain grown in N2 medium supplemented with 10% fetal calf serum survived for at least 2 weeks, and their purity was > 99% at day 1 and > 93% at day 7. The phenotype of freshly plated cells was comparable to that of “resting,” ramified microglia in vivo. With time in culture and with different schedules, depending on the parameter considered, microglia acquired antigenic (e.g., positivity for vimentin, ED1, major histocompatibility complex class I antigens, leukocyte common antigen, and to a lesser extent CD4) and functional (e.g., proliferation, phagocytosis) features characteristic of “activated” microglia as described in situ. Production of nitrite and prostaglandin E2 in response to lipopolysaccharide increased greatly with time in culture. Phagocytosis was also accompanied by increased release of nitrite and prostaglandin E2, the latter being more affected than the first by the age of the cultures. The culture system described may be suitable to study the factors that can modulate “activation” of adult microglia. © 1996 Wiley-Liss, Inc.
Oral Transmucosal Fentanyl Citrate for Cancer Breakthrough Pain: A Review (2006)

Breakthrough pain in patients with cancer is a common problem with characteristics that make it difficult to treat. Oncology nurses should familiarize themselves with OTFC's unique characteristics to be able to best help patients manage their therapy.
An Anti-CD72 Immunotoxin Against Therapy-Refractory B-Lineage Acute Lymphoblastic Leukemia (1995)

CD72 is a broadly expressed B-lineage specific surface antigen. We used J3-109(anti-CD72) monoclonal antibody to examine primary neoplastic cells from patients with acute leukemia for CD72 expression. CD72 was present at high levels in 70 of 100 B-lineage acute lymphoblastic leukemias (ALL), but it was not expressed on cells from 23 T-lineage ALL patients or 9 acute myeloblastic leukemia patients. We have prepared an anti-CD72 immunotoxin by conjugating J3-109 monoclonal antibody to the ribosome-inactivating protein, PAP.J3-109-PAP effectively killed > 99.9% of clonogenic blasts from a CD72+ B-lineage ALL cell line. We used a SCID mouse model of aggressive human pre-B ALL to evaluate the in vivo anti-leukemic efficacy of the J3-109-PAP immunotoxin. An intravenous challenge with 1 x 10(6) NALM-6-UM-1(pre-B ALL) cells caused 100% of SCID mice to die of disseminated leukemia within 41 days. Importantly, a three-day treatment with non-toxic doses of J3-109-PAP significantly improved event-free survival of SCID mice. The Kaplan-Meier estimate (+/- standard error) of the probability of event-free survival at 2 months after inoculation of NALM-6-UM-1 cells was 40 +/- 16% for SCID mice treated with a total of 15 micrograms J3-109-PAP (median survival = 58 days) as compared to 0 +/- 0% for PBS treated mice (median survival = 34 days). At 6 months after the inoculation of NALM-6-UM-1 cells, 10 +/- 9% of the J3-109-PAP treated SCID mice were still alive with no evidence of leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)
A Finite Newton Method for Classi cation Problems (2001)

A fundamental classi cation problem of data mining and machine\nlearning is that of minimizing a strongly convex, piecewise quadratic\nfunction on the n-dimensional real space Rn. We show nite termination\nof a Newton method to the unique global solution starting from\nany point in Rn. If the function is well conditioned, then no stepsize\nis required from the start, and if not, an Armijo stepsize is used. In\neither case nite termination is guaranteed to the unique global minimum\nsolution.
Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes (2018)

Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day.
Push the Envelope: Design Concepts for Envelope-Tracking Power Amplifiers (2013)

As mobile communication systems evolve to handle higher data rates, their modulation schemes only become more complicated, generating signals with large bandwidth and high peak-to-average-power ratio (PAPR). To amplify such signals with high efficiency, the power amplifier (PA) should have high efficiency not only at the peak power level but also at low power, especially over the maximum power generation region. To realize these PA characteristics, the drain bias voltage of the transistor can be modulated on the basis of the input envelope power to minimize the dc supply power. Thus, the drain bias voltage should follow the envelope of the modulated signal, and this is called envelope tracking (ET). Usually, the envelope is shaped to realize the optimum performance from the ET PA. The PA is biased close to class B, and the dc current is automatically adjusted to the power level. The resulting PA has high efficiency for all power levels, comparable to the maximum efficiency of the PA at high power. In practice, the efficiency is degraded somewhat at low voltage because of the knee effect, lower transconductance, and mismatch effect for different drain bias voltages.
MicroRNA-146a regulates the maturation process and pro-inflammatory cytokine secretion by targeting CD40L in oxLDL-stimulated dendritic cells (2011)

There is increasing evidence that microRNAs (miRNAs) play important roles in cell proliferation, apoptosis and differentiation that accompany inflammatory responses. However, whether miRNAs are associated with dendritic cell (DC) immuno-inflammatory responses to oxidized low density lipoprotein (oxLDL) stimulation is yet unknown. Our study aims to explore the link of miRNA to lipid-overload and the immuno-inflammatory mechanism for atherosclerosis. Human primary monocyte-derived DCs were transfected with miR-146a mimics and inhibitor, and then stimulated by oxLDL. For the flow cytometric analysis of the DC immunophenotype, supernatants were collected to determine inflammatory chemokine markers. Our study clearly revealed that miRNA-146a regulates the maturation process and pro-inflammatory cytokine secretion in DCs by targeting CD40L in ox-LDL-stimulated DCs.
Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors (2000)

Application of fluorescence in situ hybridization (FISH) analysis has opened the way for comprehensive studies on numerical chromosome abnormalities in human sperm. During the last decade, more than five million sperm from approximately 500 normal men were analyzed by a number of laboratories from around the world by this approach. Except for chromosome 19 which has been analyzed in only one study, all other chromosomes have been examined by two or more studies with considerable differences in disomy frequency for an individual chromosome among studies. The mean disomy frequency is 0.15% for each of the autosomes and 0.26% for the sex chromosomes. Most chromosomes analyzed have an equal distribution of disomy with the exception of chromosomes 14, 21, 22 and the sex chromosomes, which display significantly higher disomy frequencies. Slight but significant increases in disomy frequency with advancing paternal age were observed for some chromosomes, in particular for the sex chromosomes. Some lifestyle factors such as smoking, alcohol drinking and caffeine consumption have been investigated and no consistent association between disomy frequency and any type of lifestyle factors has been established. The question of whether different geographic and ethnic groups of men have inherent differences in frequency of disomic sperm has been investigated by two studies with conflicting results.
Iron Metabolism Is Associated With Adipocyte Insulin Resistance and Plasma Adiponectin (2012)

The observed associations of several markers of iron metabolism with adipocyte IR and adiponectin suggest that factors related to iron and iron metabolism may contribute to adipocyte IR early in the pathogenesis of T2DM.
Biodegradable Multiblock Poly[N-(2-hydroxypropyl)methacrylamide] via Reversible Addition−Fragmentation Chain Transfer Polymerization and Click Chemistry (2011)

A new bifunctional chain transfer agent (CTA) containing alkyne end groups was designed, synthesized and used for direct synthesis of clickable telechelic polymers. Good control of reversible addition-fragmentation chain transfer (RAFT) polymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) was achieved by using the new CTA, as indicated by a linear increase of number average molecular weight (Mn) with conversion and low polydispersity (PDI) (<1.1). In particular, enzymatically degradable multiblock HPMA polymers were readily prepared by subsequent reaction with αω, -diazido oligopeptide (GFLG) sequence via Cu(I) catalyzed alkyne-azide cycloaddition. Upon exposure of high molecular weight fractions of multiblock polyHPMA to papain or cathepsin B, the polymer was degraded into segments of molecular weight and narrow polydispersity similar to those of the initial telechelic polyHPMA.
Call graph construction in object-oriented languages (1997)

Interprocedural analyses enable optimizing compilers to more precisely model the effects of non-inlined procedure calls, potentially resulting in substantial increases in application performance. Applying interprocedural analysis to programs written in object-oriented or functional languages is complicated by the difficulty of constructing an accurate program call graph. This paper presents a parameterized algorithmic framework for call graph construction in the presence of message sends and/or first class functions. We use this framework to describe and to implement a number of well-known and new algorithms. We then empirically assess these algorithms by applying them to a suite of medium-sized programs written in Cecil and Java, reporting on the relative cost of the analyses, the relative precision of the constructed call graphs, and the impact of this precision on the effectiveness of a number of interprocedural optimizations.
Noble‐Metal‐Promoted Three‐Dimensional Macroassembly of Single‐Layered Graphene Oxide (2010)

Barreling along: 3D macrostructures (cylinder; see picture) have been assembled from single-layered graphene oxide and noble-metal nanocrystals (Au, Ag, Pd, Ir, Rh, Pt, etc.). Although the density of the cylinders is very low (ca. 0.03 g cm−3), they show excellent mechanical properties and have been utilized as a fixed-bed catalyst for the Heck reaction, which proceeded with nearly 100 % selectivity and conversion. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Discovery of Topical Calcineurin Inhibitors and Pharmacological Profile of Pimecrolimus (2006)

Using a newly developed model of allergic contact dermatitis in pigs, calcineurin inhibitors of the tacrolimus and ascomycin type were shown to have a highly anti-inflammatory action after topical application. These findings provided the first pharmacological evidence of the efficacy of this novel class of topical agents in the treatment of inflammatory skin diseases, and, thus, their potential to become the first alternative to corticosteroids in more than 40 years. As a result of a large research program into ascomycins, pimecrolimus (Elidel(R), SDZ ASM 981) was selected for development due to its favorable pharmacology and safety profile, alongside tacrolimus (Protopic(R), FK 506). In vitro, pimecrolimus inhibits the transcription and release of pro-inflammatory cytokines in T cells. Similar to the corticosteroids, betamethasone-17-valerate and dexamethasone, pimecrolimus is effective at nanomolar concentrations. Targeting mainly T cells, pimecrolimus has, however, a more specific mode of action. Moreover, in contrast to corticosteroids, pimecrolimus has no effect on Langerhans' cells, the professional antigen- presenting dendritic cells of the skin that are crucial for local immunosurveillance. When applied topically, pimecrolimus exerts a high and selective anti-inflammatory activity in the skin, shows minimal percutaneous absorption, and has a low potential to affect systemic immunoreactions. Pimecrolimus cream 1% has proven to be well tolerated, safe, and highly effective in clinical studies in patients with atopic dermatitis.
Constraint Classification for Multiclass Classification and Ranking (2002)

The constraint classification framework captures many flavors of multiclass classification including winner-take-all multiclass classification, multilabel classification and ranking. We present a meta-algorithm for learning in this framework that learns via a single linear classifier in high dimension. We discuss distribution independent as well as margin-based generalization bounds and present empirical and theoretical evidence showing that constraint classification benefits over existing methods of multiclass classification. 1
ChemInform Abstract: Recent Application of Microwave Heating in Catalysis. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A Novel Approach for Amplification and Purification of Mouse Oligodendrocyte Progenitor Cells (2016)

Although transgenic and knockout mice are widely used to study the specification and differentiation of oligodendrocyte precursor cells (OPCs), mouse primary OPCs are difficult to be purified and maintained, and many in vitro studies have to resort to rat OPCs as substitutes. In this study, we reported that mouse O4 negative early-stage OPCs can be obtained by culturing cortical tissue blocks, and the simultaneous treatment of OPCs with Platelet Derived Growth Factor-AA (PDGFaa), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) is the key for the propagation of mouse OPCs in culture. EGF was found to be a potent mitogen for OPCs and cooperate with PDGFaa to extend cell division and inhibit their differentiation. EGF also collaborates with PDGFaa and bFGF to convert bipolar or tripolar OPCs to more vital fibroblast-like OPCs without compromising their oligodendrocyte differentiation potential. In addition, EGF promoted the survival and proliferation of glial progenitor cells (GPCs) derived from primary OPC cultures, and a mixture of GPCs and OPCs can be obtained and propagated in the presence of EGF, bFGF, and PDGFaa. Once EGF is withdrawn, GPC population decreased sharply and fibroblast-like OPCs changed into typical OPCs morphology, then homogeneous OPCs were obtained subsequently.
Handbook of Optical Sensing of Glucose in Biological Fluids and Tissues (2008)

Although noninvasive, continuous monitoring of glucose concentration in blood and tissues is one of the most challenging areas in medicine, a wide range of optical techniques has recently been designed to help develop robust noninvasive methods for glucose sensing. For the first time in book form, the Handbook of Optical Sensing of Glucose in Bi
Long-Term Ketamine Self-Injections in Major Depressive Disorder: Focus on Tolerance in Ketamine’s Antidepressant Response and the Development of Ketamine Addiction (2015)

Sub-anaesthetic ketamine is of special interest for depression research due to its rapid and potent but short-lived antidepressant response (after-effect). The presented case is the first one in the literature which deals in detail with the transfer from ketamine's antidepressant action to ketamine addiction. A 50-year-old anaesthetic nurse, who had never been treated with antidepressants before, started with self-injecting ketamine racemate 50 mg IM once a week to cope with her major depression. She continuously stole ketamine from hospital stocks. Due to a gradually developing tolerance to ketamine's antidepressant action, she stepwise increased dose and frequency of ketamine self-injections up to daily 2 g IM (three-fold her anaesthetic dose) over six months. This was accompanied by the development of ketamine addiction, loss of consciousness, dissociative immobility, and amnesia. Inpatient detoxification treatment was characterized by a strong craving for ketamine and, later on, by the occurrence of a severe depressive episode remitting on venlafaxine. A 14-week follow-up documented a normal condition without any ketamine sequelae, such as craving, psychosis, depression, or cognitive abnormalities. Thus, awareness of ketamine addiction potential, even in patients who received ketamine for antidepressant purposes, is important.
Monolayers of polyethilenimine on flat glass: a versatile platform for cations coordination and nanoparticles grafting in the preparation of antibacterial surfaces (2012)

A polyethylenimine (PEI) self-assembled monolayer (SAM) is prepared, capable of complexing silver and copper cations and of anchoring silver nanoparticles, exerting antibacterial activity against Escherichia coli and Staphylococcus aureus. Functionalized glassy surfaces have been fully characterized through spectroscopic techniques (UV-Vis spectroscopy, spectroscopic ellipsometry), atomic force microscopy imaging and quantitative Ag and Cu analysis (ICP optical emission spectroscopy).