gebhart/patrepeval huggingface dataset:
Instance Normalization: The Missing Ingredient for Fast Stylization (2016)

It this paper we revisit the fast stylization method introduced in Ulyanov et. al. (2016). We show how a small change in the stylization architecture results in a significant qualitative improvement in the generated images. The change is limited to swapping batch normalization with instance normalization, and to apply the latter both at training and testing times. The resulting method can be used to train high-performance architectures for real-time image generation. The code will is made available on github at https://github.com/DmitryUlyanov/texture_nets. Full paper can be found at arXiv:1701.02096.
Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC. (2014)

8021^ Background: Lung cancer is the leading cause of cancer death in both men and women. PD-L1 is upregulated in NSCLC and may be associated with a poor prognosis. MEDI4736 is a human IgG1 antibody which binds specifically to PD-L1 preventing binding to PD-1 and CD80. Methods: An ongoing phase 1, multicenter, open-label study (NCT01693562) is evaluating the safety and efficacy of MEDI4736 administered IV every 2 wks (q2w) or every 3 wks (q3w) using a 3+3 dose escalation followed by expansion cohorts. NSCLC pts were assigned to expansion cohorts by histology and line of therapy (including treatment- naïve pts). Retreatment was permitted for progression after 12 mos of therapy. Response is assessed by immune-related response criteria (irRC) in escalation and RECIST v1.1 in expansion. Results: As of Jan 17, 2014, 13 NSCLC pts in dose escalation (median age 65 yrs; 40-76), all PS 0-1, with a median of 4 prior treatments, received a median of 7 doses (1-25) of MEDI4736 across 6 cohorts (0.1 – 10 mg/kg q2w; 15 mg/kg q3w). Treatment-related AEs occurred in 43% of pts, all of which were Grade 1-2; none led to discontinuation of study drug. No pneumonitis or colitis was reported in dose escalation. Of 13 pts, 3 PRs were observed, with 2 additional pts achieving tumor shrinkage not meeting PR per irRC (46% and 48% decreases). Tumor shrinkage was reported as early as first assessment (6 wks) and benefit was durable; 4/13 pts remain on study (10+, 10+, 11.1+, 14.9+ mos) as of the data cutoff. Expansion cohorts opened Sep 2013; 43 pts (including treatment-naïve pts) have been dosed, with the opportunity to enroll > 300 NSCLC pts in total. Preliminary clinical activity has been observed with acceptable safety, no ≥ grade 3 pneumonitis, and no apparent differences in toxicity between treatment-naïve vs pretreated pts. Assessment of clinical activity by PD-L1 expression, underlying mutation, smoking history, and line of therapy patient-reported outcomes is ongoing. Conclusions: The preliminary safety and durable clinical efficacy profile of MEDI4736 in NSCLC supports continued clinical development; AEs are manageable, even in highly pretreated pts. Recruitment continues and development of MEDI4736 in NSCLC as monotherapy and in combination is ongoing. Clinical trial information: NCT01693562.
Quantifying Temporal Glucose Variability in Diabetes via Continuous Glucose Monitoring: Mathematical Methods and Clinical Application (2005)

Advanced analysis and visualization of CGM data allow for evaluation of dynamical characteristics of diabetes and reveal clinical information that is inaccessible via standard statistics, which do not take into account the temporal structure of the data. The use of such methods improves the assessment of patients' glycemic control.
Greater selective uptake by Hep G2 cells of high-density lipoprotein cholesteryl ester hydroperoxides than of unoxidized cholesteryl esters (1993)

We have observed recently that high-density lipoproteins (HDL) are the predominant carriers of cholesteryl ester hydroperoxides (CEOOH), the major class of lipid hydroperoxides detectable at nanomolar concentrations in the plasma of healthy fasting humans. The present study investigates the effect of such very low levels of CEOOH in apolipoprotein E-free HDL3 on lipoprotein particle metabolism and 'selective uptake' of its CE by human Hep G2 cells. Minimal oxidation with aqueous peroxyl radicals had a negligible effect on the binding, internalization and degradation of 125I-labelled HDL3. In contrast, with an increasing degree of radical-mediated oxidation of labelled HDL3, [3H]cholesteryl linoleate ([3H]Ch18:2) was taken up at an increasingly greater rate than were 125I-apoproteins. When [3H]cholesteryl linoleate hydroperoxide ([3H]Ch18:2-OOH was incorporated into unoxidized HDL3 by exchange from donor liposomes, it was taken up at a more than 8-fold higher rate than was incorporated [3H]Ch18:2. The same degree of preferential uptake of oxidized CE was observed when HDL3 was used that was doubly labelled with [3H]Ch18:2-OOH and cholesteryl [14C]oleate ([14C]Ch18:1). In both situations, uptake of [3H]Ch18:2-OOH exceeded that of 125I-apolipoprotein A-I some 40-fold. This increased selective uptake of [3H]Ch18:2-OOH from very mildly oxidized HDL3 was accompanied by a parallel increase in the intracellular levels of labelled free cholesterol. In contrast, lipid hydroperoxides were not detectable within Hep G2 cells, suggesting efficient detoxification of CEOOH by these cells. Neither the increased selective uptake of Ch18:2-OOHs nor the levels of intracellular free cholesterol were influenced by the presence of 50 microM chloroquine, suggesting extralysosomal hydrolysis of oxidized CEs. These results show that the selective uptake of HDL CEOOH by Hep G2 cells is more efficient than that of unoxidized CE, and support a protective role for rapid selective uptake in the removal of circulating HDL CEOOH.
MS/MS with High Detection Efficiency and Mass Resolving Power for Product Ions in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (1994)

We present a new FT-ICR method for MS/MS of trapped ions. Parent ions isolated in the source trap of a dual-trap FT-ICR/MS instrument are subjected to off-resonance dipolar excitation to promote collision-induced dissociation (CID), while product ions are simultaneously axialized by broad-band azimuthal quadrupolar excitation in the presence of argon collision gas. In this way, radial diffusional loss of product ions is greatly reduced; moreover, the axialized product ions may then be efficiently transferred to the analyzer trap for high-resolution detection. Significant improvements in FT-ICR detection efficiency, mass resolving power (m/delta m > or = 20,000 at m/z < or = 1000), and mass accuracy (< or = 50 ppm for peptide fragments of m/z < or = 1000) are demonstrated for CID product ions of the cyclic peptide, gramicidin S.
The Dorsal Root Ganglia in Adrenomyeloneuropathy: Neuronal Atrophy and Abnormal Mitochondria (2001)

Adrenomyeloneuropathy (AMN), a disease of spinal cord, brain, adrenal, and testis, mostly affects men with spastic paraparesis or ataxia beginning in their second or third decade. The spinal cord displays bilateral, usually symmetrical, long tract degeneration particularly of the gracile tract in a "dying-back" pattern. The available data strongly indicate that the fundamental lesion in AMN is an axonopathy or neuronopathy. We compared lumbar dorsal root ganglia (DRG) from 3 AMN patients to 6 age-matched controls histologically, morphometrically, immunohistochemically, and ultrastructurally. There was no apparent neuronal loss, necrosis or apoptosis, nor obvious atrophy; nodules of Nageotte were sparse in both groups. The morphometric studies, however, did reveal neuronal atrophy with a decrease in the number of large neurons and a corresponding increase in neurons less than 2,000 microm2, especially in the 1,500-1,999 microm2 range. No consistent immunohistochemical differences were observed, and no specific cell type appeared to be lost. Many mitochondria in the AMN neurons demonstrated lipidic inclusions; this raises the possibility that, in addition to the well-known peroxisomal defect, impaired mitochondrial function may lead to a failure of ATP-dependent axoplasmic transport in AMN spinal tracts with consequent "dying-back" axonal degeneration. The observation that the DRG parent neurons of the degenerate gracile tracts in AMN undergo atrophy and do not display appreciable evidence of cell death, even at autopsy, provides a wide window of opportunity for the development of therapeutic strategies to combat or prevent this myeloneuropathy.
Protein binding alters the activity of suramin, carboxyamidotriazole, and UCN-01 in an ex vivo rat aortic ring angiogenesis assay. (2001)

Angiogenesis inhibitors are currently in clinical development for cancer. These agents pose unique developmental challenges: (a) determining maximum biological doses versus maximum tolerated doses; (b) defining response criteria other than objective tumor responses; and (c) defining safe regimens for prolonged, chronic administration. The current in vitro angiogenesis assays used in the screening and preclinical development of antiangiogenic agents each have their own advantages and disadvantages, yet all seem to underestimate the importance and impact of in vivo protein-drug interactions. We have developed a human serum rat aortic ring angiogenesis bioassay that highlights protein binding concerns using three anticancer agents that have documented antiangiogenic activity: suramin, carboxyamidotriazole, and 7-hydroxystaurosporine. We have determined that the bioassay concentrations of suramin (100 microg/ml) and 7-hydroxystaurosporine (> 1 microg/ml), but not carboxyamidotriazole (> or = 60 microg/ml), that inhibit microvessel formation are consistent with target plasma levels achievable in the clinic. We conclude that assays such as the human serum rat aortic ring bioassay may prove useful in predicting the concentrations of protein-bound antiangiogenic agents required for free fraction biological activity.
Application of Bacterial Foraging Optimization PID Control in VAV System (2013)

Considering the control characteristics of the variable air volume air-conditioning system, this paper presents the optimized PID control strategy based on bacterial foraging optimization, and applies it to the optimal adjustment of PID parameters of VAV air conditioning control system. Compared with the traditional PID control, the new PID control strategy improves the performance of the system by digital simulation in the circumstances of MATLAB/Simulink.
The human 26S proteasome is a target of antiretroviral agents (2002)

The human 26S proteasome is a target of antiretroviral agents. This suggests that the antiviral action and some clinical and immunological benefits of combined antiretroviral therapy rely not only on its known effects on viral enzymes, but also on host cell components.
Detection of single-base mutations by reaction of DNA heteroduplexes with a water-soluble carbodiimide followed by primer extension: application to products from the polymerase chain reaction (1990)

A new method was developed for the detection of single-base mutations in DNA. The polymerase chain reaction was used to prepare DNA fragments of up to 1 kb. Fragments that differed by a single-base were combined, denatured and renatured to generate heteroduplexes. The heteroduplexes were reacted with a water-soluble carbodiimide under conditions in which the carbodiimide modified Gs and Ts that were not base paired. The DNA was then used as a template for primer extension with Taq DNA polymerase under conditions in which extension terminated at the site of the carbodiimide-modified base and generated a 32P-labeled fragment that was identified by polyacrylamide gel electrophoresis as a fragment smaller than the full length product. The procedure detected all four general classes of single-base mutations in several different sequence contexts. The site of the mutation was located to within about 15 bp. Extension with both a 5'- and a 3'-primer made it possible to confirm the site of the mutation in most DNA samples or detect a mutation in heteroduplexes even if a G or T in one strand was unreactive because of its sequence context. The procedure appears to have several advantages over previously published techniques.
One-Pot Synthesis of Spirocyclic or Fused Pyrazoles from Cyclic Ketones: Calcium Carbide as the Carbon Source in Ring Expansion (2017)

N-Tosylhydrazones generated in situ from cyclic ketones smoothly underwent a [3 + 2] cycloaddition to afford saturated spirocyclic pyrazoles and further transformed to the fused analogues via a ring expansion in certain cases. An inexpensive and renewable resource, calcium carbide, was utilized as the carbon source in the ring expansion. The salient features of this reaction include widely available starting materials, convenient one-pot/two-step procedure, great efficiency, and high regioselectivity. Remarkably, this reaction underwent a [1,5]-sigmatropic rearrangement process, which was supported by deuterium-labeling experiments.
IL-1 Receptor Accessory Protein Is an Essential Component of the IL-1 Receptor (1998)

The recently described IL-1R accessory protein (IL-1R AcP) interacts with IL-1beta and the IL-1 type-IR (IL-1RI), but an essential requirement for IL-1R AcP in IL-1 signaling in vitro has not been established and its role in vivo has not been examined. In this study, IL-1R AcP-deficient mice and fibroblasts were produced and characterized. All IL-1 agonists bound to IL-1R AcP-deficient cells through the type I IL-1R, but failed to activate gene expression through either the nuclear factor-kappaB or AP-1-dependent signaling pathways. Absence of IL-1R AcP differentially affected the affinity for IL-1 ligands. IL-1R AcP-deficient fibroblasts bound murine IL-1alpha and human IL-1R antagonist protein (IL-1Ra) with only moderately reduced affinity when compared with wild-type cells, whereas murine IL-1beta affinity was reduced by 70-fold. IL-1 also failed to produce a biologic response in vivo in IL-1R AcP-deficient mice. These data demonstrate that a type I IL-1R/IL-1R AcP complex is required for signaling by all IL-1 agonists and for high affinity binding by IL-1beta. Finally, IL-1R AcP is an essential signal transducing component of the functional IL-1R and should represent a novel target for blocking IL-1 function in human disease.
Photoprotection: update in UV-filter molecules, the "new wave" of sunscreens. (2010)

In this review, we provide a wide, non-comprehensive overview of the latest trends in protection against the deleterious effects of the sun. The review is divided into physical blockade of UV photons, UV photon absorption and/or reflection provided by topical sunscreens and topical antioxidant compounds. The last section is devoted to the newest generation of dietary photoprotective compounds. Possible mechanisms, particularly antioxidant, are discussed.
ChemInform Abstract: ENANTIOMERIC FORMS OF 9‐(5,6‐DIDEOXY‐α‐D‐ARABINO‐HEX‐5‐ENOFURANOSYL)ADENINE AND PREPARATION OF 9‐(6‐DEOXY‐β‐D‐GALACTOFURANOSYL)ADENINE. FURTHER RESULTS WITH THE ACETOLYSIS OF HEXOFURANOSIDES (1978)

Abstract Durch Acetolyse des β‐D‐Ribofuranosids (I) und Kondensation.
β-Endorphin and Adrenocorticotropin in Extrapituitary Sites: Gastrointestinal Tract (1980)

Beta-Endorphin and ACTH immunoassays were employed to examine the concentrations, distributions, and character of those peptides in rat gastrointestinal tissues. Sections of the gastrointestinal tract were obtained from fasted and fed animals and were extracted in 5 N acetic acid containing proteolytic enzyme inhibitors. Aliquots immunoassayed for beta-enddorphin and ACTH revealed highest concentrations to be present in the small bowel, with stomach and colon containing little immunoreactivity. Tissues from fasted animals contained more immunoreactivity than did those from fed animals. Gel chromatography showed the presence of large molecular weight forms of beta-endorphin and ACTH in gut extracts. Concanavalin A affinity chromatography revealed that approximately 5% of gut immunoreactivity contained carbohydrate. Therefore, beta-enddorphin and ACTH immunoreactivities are present im the gut. The demonstration of large molecular weight and glycosylated forms of immunoreactivity suggests the presence of biosynthetic precursors of beta-endorphin and ACTH. The increase in immunoreactivity in response to fasting suggests that these peptides play a role in gut physiology.
Increasing immunogenicity of antigens fused to Ig-binding proteins by cell surface targeting. (1998)

Fusion of antigenic proteins to Ig-binding proteins such as protein A from Staphylococcus aureus and its derived ZZ fragment is known to increase immunogenicity of the fused Ag in vivo. To shed light on the origin of this effect, we used snake toxins as Ags and observed that 1) fusion of toxins to ZZ enhanced their presentation to a toxin-specific T cell hybridoma (T1B2), using A20 B lymphoma cells, splenocytes, or peritoneal exudate cells as APCs; 2) this enhancement further increased when the number of fused Ig-binding domains varied from two with ZZ to five with protein A; and 3) the phenomenon vanished when the fusion protein was preincubated with an excess of free ZZ or when P388D1 monocytes cells were used as APCs. Therefore, ZZ-fused toxins are likely to be targeted to surface Igs of APCs by their ZZ moiety. Furthermore, ZZ-alpha and toxin alpha stimulated similar profiles of toxin-specific T cells in BALB/c mice, suggesting a comparable processing and presentation in vivo for both toxin forms. To improve the targeting efficiency, ZZ-alpha was noncovalently complexed to various Igs directed to different cell surface components of APCs. The resulting complexes were up to 10(3)-fold more potent than the free toxin at stimulating T1B2. Also, they elicited both a T cell and an Ab response in BALB/c mice, without the need of any adjuvant. This simple approach may find practical applications by increasing the immunogenicity of recombinant proteins without the use of adjuvant.
Generating efficient virtual worlds for visualization using partial evaluation and dynamic compilation (1997)

We argue that runtime program transformation, partial evaluation, and dynamic compilation are essential tools for automated generation of flexible, highly interactive graphical interfaces. In particular, these techniques help bridge the gap between a high-level, functional description and an efficient implementation. To support our claim, we describe our application of these techniques to a functional implementation of n-Vision, a real-time visualization system that represents multivariate relations as nested 3D interactors, and to Auto Visual, a rule-based system that designs n-Vision visualizations from high-level task specifications. n-Vision visualizations are specified using a simple functional language. These programs are transformed into a cached dataflow graph. A partial evaluator is used on particular computation-intensive function applications, and the results are compiled to native code. The functional representation simplifies generation of correct code, and the program transformations ensure good performance. We demonstrate why these transformations improve performance and why they cannot be done at compile time.
Attenuation of seismic waves in methane gas hydrate-bearing sand (2005)

Compressional wave (P wave) and shear wave (S wave) velocities (Vp and Vs, respectively) from remote seismic methods have been used to infer the distribution and volume of gas hydrate within marine sediments. Recent advances in seismic methods now allow compressional and shear wave attenuations (Q−1p and Q−1s, respectively) to be measured. However, the interpretation of these data is problematic due to our limited understanding of the effects of gas hydrate on physical properties. Therefore, a laboratory gas hydrate resonant column was developed to simulate pressure and temperature conditions suitable for methane gas hydrate formation in sand specimens and the subsequent measurement of both Q−1p and Q−1s at frequencies and strains relevant to marine seismic surveys. 13 dry (gas saturated) sand specimens were investigated with different amounts of methane gas hydrate evenly dispersed throughout each specimen. The results show that for these dry specimens both Q−1p and Q−1s are highly sensitive to hydrate saturation with unexpected peaks observed between 3 and 5 per cent hydrate saturation. It is thought that viscous squirt flow of absorbed water or free gas within the pore space is enhanced by hydrate cement at grain contacts and by the nanoporosity of the hydrate itself. These results show for the first time the dramatic effect methane gas hydrate can have on seismic wave attenuation in sand, and provide insight into wave propagation mechanisms. These results will aid the interpretation of elastic wave attenuation data obtained using marine seismic prospecting methods.
Measurement of Molecular Interactions in Living Cells by Fluorescence Resonance Energy Transfer Between Variants of the Green Fluorescent Protein (2000)

Many signal transduction pathways operate through oligomerization of proteins into multi-subunit complexes. Although biochemical assays can identify potential protein-protein interactions, studying these interactions in living cells is more challenging. Fluorescence resonance energy transfer (FRET) has been used as a "spectroscopic ruler" to measure molecular proximity, but these methods have been limited by the need for chemical labeling of target proteins or labeled antibodies. We present methods for examining interactions between target proteins molecularly fused to cyan and yellow variants of the green fluorescent protein (GFP) by FRET in living cells. Flow cytometric and microscope-based methods are described that have been applied to a variety of interacting proteins.
Inactivation and removal of Zika virus during manufacture of plasma‐derived medicinal products (2016)

Pasteurization and S/D treatment very rapidly inactivated ZIKV and filters with a pore size of not more than 40 nm removed all infectious ZIKV, demonstrating the effectiveness of these virus reduction strategies used during the manufacture of plasma-derived medicinal products.
Single-molecule high-resolution imaging with photobleaching (2004)

Conventional light microscopy is limited in its resolving power by the Rayleigh limit to length scales on the order of 200 nm. On the other hand, spectroscopic techniques such as fluorescence resonance energy transfer cannot be used to measure distances >10 nm, leaving a "gap" in the ability of optical techniques to measure distances on the 10- to 100-nm scale. We have previously demonstrated the ability to localize single dye molecules to a precision of 1.5 nm with subsecond time resolution. Here we locate the position of two dyes and determine their separation with 5-nm precision, using the quantal photobleaching behavior of single fluorescent dye molecules. By fitting images both before and after photobleaching of one of the dyes, we may localize both dyes simultaneously and compute their separation. Hence, we have circumvented the Rayleigh limit and achieved nanometer-scale resolution. Specifically, we demonstrate the technique by measuring the distance between single fluorophores separated by 10-20 nm via attachment to the ends of double-stranded DNA molecules immobilized on a surface. In addition to bridging the gap in optical resolution, this technique may be useful for biophysical or genomic applications, including the generation of super-high-density maps of single-nucleotide polymorphisms.