gebhart/patrepeval huggingface dataset:
Observation of band bending of metal/high-k Si capacitor with high energy x-ray photoemission spectroscopy and its application to interface dipole measurement (2008)

Band bendings of Si substrates have been observed using hard x-ray photoemission spectroscopy. With a capability of collecting photoelectrons generated as deep as 40 nm, the binding energy shift in a core level caused by the potential profile at the surface of the substrate results in a spectrum broadening. The broadening is found to be significant when heavily doped substrates are used owing to its steep potential profile. The surface potential of the substrate can be obtained by deconvolution of the spectrum. This method has been applied to observe the band bending profile of metal-oxide-semiconductor capacitors with high-k gate dielectrics. By comparing the band bending profiles of heavily-doped n+- and p+-Si substrates, the interface dipoles presented at interfaces can be estimated. In the case of W gated La2O3/La-silicate capacitor, an interface dipole to shift the potential of −0.45 V has been estimated at La-silicate/Si interface, which effectively reduces the apparent work function of W. On the other hand, an interface dipole of 0.03–0.07 V has been found to exist at Hf-silicate/SiO2 interface for W gated HfO2/Hf-silicate/SiO2 capacitor.
Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all‐trans retinoic acid and arsenic trioxide (2015)

Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of complete cytogenetic response was 43% (n = 6) and the rate of complete molecular response was 21% (n = 3). Relapse was frequent with 7 of 9 responders relapsing after a median of 4·6 months (range 1·6-26·8 months). The median event-free survival (EFS) was 3·5 months [95% confidence interval (CI) 0-8·6 months] and the median overall survival (OS) was 9·5 months (95% CI 5·9-13·1 months). These results demonstrate that tamibarotene has activity in relapsed APL after treatment with ATO and ATRA and further studies using tamibarotene as initial therapy and in combination with ATO are warranted.
Inhibition of myocardial lipoprotein lipase by U‐57,908 (RHC 80267) (1992)

U-57,908 (RHC 80267) was shown to inhibit lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts; the concentrations required for inhibition to 50% of control activity were 1.1 microM and 2.5 microM for myocyte homogenates and a post-heparin medium preparation, respectively. The inhibition of LPL activity by U-57,908 was not changed when the concentration of the triolein substrate and apolipoprotein CII activator in the assay was reduced. The availability of U-57,908 as a potent and selective LPL inhibitor may provide a useful experimental approach in studies on lipoprotein metabolism.
Tunable two-dimensional femtosecond spectroscopy (2004)

We have developed a two-dimensional (2D) Fourier-transform femtosecond spectroscopy technique for the visible spectral region. Three-pulse photon echo signals are generated in a phase-matched noncollinear four-wave mixing box geometry that employs a 3-kHz repetition-rate laser system and optical parametric amplification. Nonlinear signals are fully characterized in amplitude and phase by spectral interferometry. Unlike for previous setups, we achieve long-term phase stability by employing diffractive optics and interferometric accuracy of excitation-pulse time delays by using movable glass wedges. As an example of this technique, 2D correlation and relaxation spectra at 600 nm are shown for a solution of Nile Blue dye in acetonitrile.
Inhibition by adenosine of reactive oxygen metabolite production by human polymorphonuclear leucocytes (1985)

The stimulation of reactive oxygen metabolite production from human polymorphonuclear leucocytes by chemotactic peptide (fMet-Leu-Phe) was inhibited by adenosine with a K0.5 of 0.6 microM. Dipyridamole (0.1 microM), an inhibitor of adenosine uptake, did not prevent the effect of adenosine. Non-metabolizable analogues could substitute for adenosine in the potency order N-ethoxycarboxamideadenosine greater than 2-chloroadenosine greater than adenosine greater than L-N6-(phenylisopropyl)adenosine = D-N6-(phenylisopropyl)adenosine, which is characteristic of an A2 adenosine receptor. The effects of adenosine, 2-chloroadenosine and N-ethoxycarboxamideadenosine were reversed by 8-phenyltheophylline. When endocytosis was inhibited with cytochalasin B, cells were still susceptible to adenosine receptor agonists. 2-Chloroadenosine (10 microM) reduced the activation of respiration in response to chemotactic peptide from 3.3-fold to 1.4-fold. Activation of reactive oxygen metabolite production in response to latex beads was not reversed by adenosine or its analogues. It was concluded that adenosine acts at an A2 adenosine receptor to antagonize the activation of polymorphonuclear leucocytes by those stimuli, such as chemotactic peptide, which cause an increase in the intracellular free Ca2+ concentration.
B cell-targeted therapy in diseases other than rheumatoid arthritis. (2005)

There are now numerous case reports and small series using rituximab in autoimmune diseases. While these data must be interpreted with caution, they suggest that rituximab (RTX) may be a promising addition to the therapeutic armamentarium. In patients with refractory chronic idiopathic thrombocytopenic purpura, treatment with RTX was effective in inducing complete responses in a significant proportion of patients, and these responses were usually durable. RTX has also been shown to be effective and well tolerated in children with refractory autoimmune hemolytic anemia. In patients with IgM antibody-associated polyneuropathy, RTX improved muscle strength, and repeated treatments over 2 years were well tolerated. In several case series of patients with systemic lupus erythematosus, depletion of B cells during RTX therapy was associated with improvement in global disease activity. Based on these reports, further controlled studies are warranted to optimize RTX as monotherapy and to develop combination therapies in patients with refractory autoimmune diseases.
Involvement of Hypothalamic Histamine H1 Receptor in the Regulation of Feeding Rhythm and Obesity (2004)

Histamine H(1) receptors (H(1)-Rs) are found in peripheral tissues and in regions of the hypothalamus that are concerned with regulating body composition. In the present study, we investigated the detailed mechanisms of histamine H(1)-Rs in the development of obesity. Histamine H(1)-R knockout (H1KO) mice gradually developed mature-onset obesity, which was accompanied by hyperphagia and decreased expression of uncoupling protein-1 (UCP-1) mRNA. Both younger nonobese (12-week-old) and older obese (48-week-old) H1KO mice exhibited impairment of the responsiveness to the leptin. In addition, disruption of the diurnal rhythm of feeding occurred before the onset of obesity in H1KO mice. Correction of these abnormal feeding rhythms by means of scheduled feeding caused a reduction in obesity and associated metabolic disorders in H1KO mice. Furthermore, central administration of a histamine H(1)-R agonist affected feeding behavior, body weight, and c-fos-like immunoreactivity in the hypothalamus. Taken together, these findings suggest that histamine H(1)-Rs are crucial for the regulation of feeding rhythm and in mediating the effects of leptin. Early disruption of H(1)-R-mediated functions in H1KO mice may lead to hyperphagia and decreased expression of UCP-1 mRNA, which may contribute to the development of obesity in these animals. In addition, centrally acting histamine H(1)-R may be a novel therapeutic target for the treatment of obesity and related metabolic disorders.
Current/Voltage Characteristics of Monolayers of Redox-Switchable [2]Catenanes on Gold (2000)

Redox-controllable molecular switches composed of two interlocking rings are incorporated here into Langmuir films starting from two different redox states. The morphologies of the resulting monolayers and their current–voltage characteristics are then investigated. These switches are considered to be ideal candidates for the fabrication of molecule-based electronic devices.
Purification and characterization of a thermostable carboxypeptidase from the extreme thermophilic archaebacterium Sulfolobus solfataricus (1992)

A carboxypeptidase was purified to electrophoretic homogeneity from the thermoacidophilic archaebacterium Sulfolobus solfataricus. Molecular masses assessed by SDS/PAGE and gel filtration were 42 kDa and 170 kDa, respectively, which points to a tetrameric structure for the molecule. An isoelectric point of 5.9 was also determined. The enzyme was proven to be a metalloprotease, as shown by the inhibitory effects exerted by EDTA and o-phenanthroline; furthermore, dialysis against EDTA led to a complete loss of activity, which could be restored by addition of Zn2+ in the micromolar range, and, to a lesser extent, by Co2+. The enzyme was endowed with a broad substrate specificity, as shown by its ability to release basic, acidic and aromatic amino acids from the respective benzoylglycylated and benzyloxycarbonylated amino acids. An esterase activity of the carboxypeptidase was also demonstrated on different esterified amino acids and dipeptides blocked at the N-terminus. The enzyme displayed broad pH optima ranging over 5.5-7.0, or 5.5-9.0, when using an acidic or a basic benzyloxycarbonylated amino acid, respectively. With regard to thermostability, it was proven to be completely stable on incubation for 15 min at 85 degrees C. Furthermore, thanks to its relatively low activation energy, i.e. 31.0 kJ/mol, it was still significantly active at room temperature. At 40 degrees C, the enzyme could withstand 0.1% SDS and different organic solvents: particularly ethanol up to 99%. Amino acid and N-terminal sequence analyses did not evidence any similarity to carboxypeptidases A nor thermolysin. A weak similarity was only found with bovine carboxypeptidase B.
Geometric Applications of the Split Bregman Method: Segmentation and Surface Reconstruction (2009)

Variational models for image segmentation have many applications, but can be slow to compute. Recently, globally convex segmentation models have been introduced which are very reliable, but contain TV-regularizers, making them difficult to compute. The previously introduced Split Bregman method is a technique for fast minimization of L1 regularized functionals, and has been applied to denoising and compressed sensing problems. By applying the Split Bregman concept to image segmentation problems, we build fast solvers which can out-perform more conventional schemes, such as duality based methods and graph-cuts. The convex segmentation schemes also substantially outperform conventional level set methods, such as the Chan-Vese level set-based segmentation algorithm. We also consider the related problem of surface reconstruction from unorganized data points, which is used for constructing level set representations in 3 dimensions. The primary purpose of this paper is to examine the effectiveness of “Split Bregman” techniques for solving these problems, and to compare this scheme with more conventional methods.
Metabolic engineering of the nonmevalonate isopentenyl diphosphate synthesis pathway inEscherichia coli enhances lycopene production (2001)

Isopentenyl diphosphate (IPP) is the common, five-carbon building block in the biosynthesis of all carotenoids. IPP in Escherichia coli is synthesized through the nonmevalonate pathway, which has not been completely elucidated. The first reaction of IPP biosynthesis in E. coli is the formation of 1-deoxy-D-xylulose-5-phosphate (DXP), catalyzed by DXP synthase and encoded by dxs. The second reaction in the pathway is the reduction of DXP to 2-C-methyl-D-erythritol-4-phos- phate, catalyzed by DXP reductoisomerase and encoded by dxr. To determine if one or more of the reactions in the nonmevalonate pathway controlled flux to IPP, dxs and dxr were placed on several expression vectors under the control of three different promoters and transformed into three E. coli strains (DH5alpha, XL1-Blue, and JM101) that had been engineered to produce lycopene. Lycopene production was improved significantly in strains transformed with the dxs expression vectors. When the dxs gene was expressed from the arabinose-inducible araBAD promoter (P(BAD)) on a medium-copy plasmid, lycopene production was twofold higher than when dxs was expressed from the IPTG-inducible trc and lac promoters (P(trc) and P(lac), respectively) on medium-copy and high-copy plasmids. Given the low final densities of cells expressing dxs from IPTG-inducible promoters, the low lycopene production was probably due to the metabolic burden of plasmid maintenance and an excessive drain of central metabolic intermediates. At arabinose concentrations between 0 and 1.33 mM, cells expressing both dxs and dxr from P(BAD) on a medium-copy plasmid produced 1.4-2.0 times more lycopene than cells expressing dxs only. However, at higher arabinose concentrations lycopene production in cells expressing both dxs and dxr was lower than in cells expressing dxs only. A comparison of the three E. coli strains transformed with the arabinose-inducible dxs on a medium-copy plasmid revealed that lycopene production was highest in XL1-Blue.
Comparison of codon usage measures and their applicability in prediction of microbial gene expressivity (2005)

We have established that MILC is a generally applicable measure, being resistant to changes in gene length and overall nucleotide composition, and introducing little noise into measurements. Other methods, however, may also be appropriate in certain applications. Our efforts to quantitatively predict gene expression levels in several prokaryotes and unicellular eukaryotes met with varying levels of success, depending on the experimental dataset and predictor used. Out of all methods, MELP and Rainer Merkl's GCB method had the most consistent behaviour. A 'reference set' containing known ribosomal protein genes appears to be a valid starting point for a codon usage-based expressivity prediction.
Histology and Ultrastructure of Arteries, Veins, and Peripheral Nerves During Limb Lengthening (1994)

The effects of lengthening of the metacarpal bone on peripheral nerves and blood vessels were studied in 8 calves. Specimens for light and electron microscopy were obtained from the palmar neurovascular bundle at 1 cm (8% of the initial length), 2.5 cm (20% of the initial length), and 4 cm (33% of the initial length) of metacarpal lengthening. In 2 calves, specimens were studied 2 months after the end of the lengthening procedure. At 8% of lengthening, myelinated fibers of the palmar nerve showed moderate degenerative changes in the myelin sheath. This became severe at 20% and 33% of lengthening, and affected the axoplasm as well. At 20% of lengthening, the palmar vein started to show fibrous metaplasia of the smooth muscle tissue of the tunica media. This became much thinner than normal. The palmar artery showed moderate alterations of the inner part of the tunica media and the intima. The palmar nerve and blood vessels recovered their normal structure almost completely 2 months after the end of the lengthening procedure. The morphologic alterations of peripheral nerves and vessels may constitute the pathophysiologic basis of the nervous and circulatory disturbance observed in clinical practice.
Epstein Barr virus–specific cytotoxic T lymphocytes expressing the anti-CD30ζ artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease (2007)

Adoptive transfer of Epstein Barr virus (EBV)-specific cytotoxic T-lymphocytes (EBV-CTLs) has shown that these cells persist in patients with EBV(+) Hodgkin lymphoma (HD) to produce complete tumor responses. Treatment failure, however, occurs if a subpopulation of malignant cells in the tumor lacks or loses expression of EBV antigens. We have therefore determined whether we could prepare EBV-CTLs that retained the antitumor activity conferred by their native receptor while expressing a chimeric antigen receptor (CAR) specific for CD30, a molecule highly and consistently expressed on malignant Hodgkin Reed-Sternberg cells. We made a CD30CAR and were able to express it on 26% (+/- 11%) and 22% (+/- 5%) of EBV-CTLs generated from healthy donors and HD patients, respectively. These CD30CAR(+) CTLs killed both autologous EBV(+) cells through their native receptor and EBV(-)/CD30(+) targets through their major histocompatibility complex (MHC)-unrestricted CAR. A subpopulation of activated T cells also express CD30, but the CD30CAR(+) CTLs did not impair cellular immune responses, probably because normal T cells express lower levels of the target antigen. In a xenograft model, CD30CAR(+) EBV-CTLs could be costimulated by EBV-infected cells and produce antitumor effects even against EBV(-)/CD30(+) tumors. EBV-CTLs expressing both a native and a chimeric antigen receptor may therefore have added value for treatment of HD.
Pre- and postsynthesis simulation mismatches (2002)

With the widespread adoption of top-down design methodologies using HDL and synthesis, RTL models have become the "golden" design database. However, ASIC and FPGA vendors still require a gate level netlist as the official sign-off design. Model ambiguities in RTL designs can cause differences between RTL and synthesized netlist designs. These differences in the best case cause simulation mismatches between RTL and gate designs. In the worst case, if not detected in simulation they can result in faulty hardware. This paper covers common sources of ambiguity in RTL models. Solutions are provided for avoiding these situations. Some basic simulation debug tips are provided to help identify these errors in simulation with both VHDL and Verilog. These examples are based on Synergy (Cadence's synthesis tool) but also apply to synthesis in general.
Stem Cell Factor-Displaying Simian Immunodeficiency Viral Vectors Together with a Low Conditioning Regimen Allow for Long-Term Engraftment of Gene-Marked Autologous Hematopoietic Stem Cells in Macaques (2012)

Although clinical benefits have been reported in several human hematopoietic gene therapy trials, a remaining important goal is the transition to nonmyeloablative pretransplantation conditioning to decrease toxicity. Previous attempts at reduced intensity conditioning in nonhuman primates have resulted in only temporary vector marking of autologous blood cells or their persistence at low levels, well below the thresholds for clinical efficacy. In addition, we reasoned that lentiviral vector particles displaying cytokines at their surface have the potential to preserve stem cell fitness better than current ex vivo transduction protocols, which involve exposure to cytokine overstimulation. Here we show that the classically nonmyeloablative agent fludarabine (30 mg/m(2)/day for 3 days) together with low-level total body irradiation (2 Gy) and the use of a stem cell factor-displaying simian immunodeficiency virus-based vector, resulted in sustained, single-copy vector marking of autologous blood cells in two macaques over 3 years posttransplantation at levels averaging 1% of all lineages. This percentage is within the range of anticipated efficacy levels for hemophilia and related diseases and forms a basis for further improvement.
Immunotherapy of the guinea pig line 10 hepatocarcinoma with a variety of nonviable bacteria. (1980)

A variety of heat-killed bacteria were tested for their capacity to induce regressions of established line 10 hepatocarcinomas in syngeneic guinea pigs. Multiple intralesional injections of heat-killed Escherichia coli, Streptococcus mutans, Listeria monocytogenes, and Propionibacterium acnes resulted in complete regression of the tumor in a majority of guinea pigs. Repeated injections of heat-killed Mycobacterium bovis strain Bacillus Calmette-Guérin caused no regressions. Surviving animals were immune to subsequent challenge with line 10 cells but not L2C cells, another syngeneic tumor.
Phase I/II safety and pharmacokinetic (PK) study of ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase I results of a Prostate Cancer Clinical Trials Consortium study. (2012)

43 Background: In CRPC, androgen receptor (AR) overexpression is associated with resistance to first-generation anti-androgen therapy such as bicalutamide. ARN-509 is a novel small molecule AR antagonist that impairs AR nuclear translocation and binding to DNA, inhibiting tumor growth and promoting apoptosis, with no partial agonist activity. Preclinical data shows that ARN-509 binds AR with 5-fold greater affinity than bicalutamide, and induces tumor regression in hormone-sensitive and CRPC xenograft models. Methods: In this open-label, Phase 1/2 study, mCRPC patients received ARN-509 orally on a continuous daily dosing schedule. In Phase 1 , 7 doses (30, 60, 90, 120, 180, 240, 300 mg) were tested using standard 3x3 dose escalation criteria to assess safety, PK, and determine the recommended Phase 2 dose (RP2D). Preliminary anti-tumor activity was assessed by PSA kinetics, radiographic responses, circulating tumor cells (CTCs), and FDHT-PET imaging. Results: Twenty-four patients (median age 68 yrs, Gleason Score 8; prior docetaxel 13%) were enrolled. The most common Grade 1-2 treatment-related adverse events were fatigue (38%), nausea (29%), and pain (24%). There was only 1 treatment-related Grade 3 adverse event (abdominal pain) at 300 mg, possibly related to a higher pill burden, which led to an additional 3 patients being enrolled at the highest dose with no further dose limiting toxicities. PK was shown to be linear and dose-dependent. Twelve patients (55%) had ≥ 50% PSA declines. To date, 7 patients have discontinued the study due to progression, with the longest patient still on study for more than 1 year. FDHT-PET imaging demonstrated AR blockade at 4 weeks across multiple dose levels. Based on preclinical assessment of maximum efficacious dose, PK, and promising activity across all doses, 240 mg was selected as the RP2D. Conclusions: In this Phase 1 study, ARN-509 was shown to be safe and well tolerated, with promising preliminary activity based on PSA and pharmacodynamic evidence of AR antagonism. The Phase 2 portion of the study will enroll up to 90 patients with treatment-naïve non-metastatic and mCRPC.