gebhart/patrepeval huggingface dataset:
Glide:  A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening (2004)

Glide's ability to identify active compounds in a database screen is characterized by applying Glide to a diverse set of nine protein receptors. In many cases, two, or even three, protein sites are employed to probe the sensitivity of the results to the site geometry. To make the database screens as realistic as possible, the screens use sets of "druglike" decoy ligands that have been selected to be representative of what we believe is likely to be found in the compound collection of a pharmaceutical or biotechnology company. Results are presented for releases 1.8, 2.0, and 2.5 of Glide. The comparisons show that average measures for both "early" and "global" enrichment for Glide 2.5 are 3 times higher than for Glide 1.8 and more than 2 times higher than for Glide 2.0 because of better results for the least well-handled screens. This improvement in enrichment stems largely from the better balance of the more widely parametrized GlideScore 2.5 function and the inclusion of terms that penalize ligand-protein interactions that violate established principles of physical chemistry, particularly as it concerns the exposure to solvent of charged protein and ligand groups. Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and co-workers (J. Med. Chem. 2000, 43, 4759-4767) show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01.
Zebrafish orthologs of human muscular dystrophy genes (2007)

This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome. Coupled with the ability to conduct genetic screens and small molecule screens, zebrafish are thus an attractive model organism for isolating new dystrophy-causing genes/pathways and for use in high-throughput therapeutic discovery.
Through-the-lens camera control (1992)

article Free Access Share on Through-the-lens camera control Authors: Michael Gleicher School of Computer Science, Carnegie Mellon University, Pittsburgh, PA School of Computer Science, Carnegie Mellon University, Pittsburgh, PAView Profile , Andrew Witkin School of Computer Science, Carnegie Mellon University, Pittsburgh, PA School of Computer Science, Carnegie Mellon University, Pittsburgh, PAView Profile Authors Info & Claims ACM SIGGRAPH Computer GraphicsVolume 26Issue 2July 1992 pp 331–340https://doi.org/10.1145/142920.134088Online:01 July 1992Publication History 173citation1,425DownloadsMetricsTotal Citations173Total Downloads1,425Last 12 Months73Last 6 weeks20 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Oxygenated fluorocarbon perfusion as treatment of acute spinal cord compression injury in dogs (1981)

Experiments were conducted to determine the therapeutic value of subarachnoid perfusion of the traumatized dog spinal cord with the fluorocarbon, Fluosol-DA (20%). Control dogs without lesions, but which had durotomy, subarachnoid catheter placement, and saline irrigation for 4 hours, did not have any residual neurological deficit. A series of 41 dogs underwent an acute spinal cord compression using an epidural balloon inflated to a pressure of 160 mm Hg and maintained for 1 hour. Treatment included durotomy only (11 dogs), durotomy with saline perfusion at room temperature (15 dogs), and durotomy with oxygenated Fluosol-DA perfusion at room temperature (15 dogs). The dogs underwent daily grading of neurological status for a 60-day period. Dogs undergoing perfusion of the spinal cord with either saline or oxygenated Fluosol-DA had significantly improved motor recovery (p less than 0.004) compared with dogs undergoing durotomy only. Perfusion with oxygenated Fluosol-DA resulted in significantly better motor recovery (p less than 0.05) than did perfusion with normal saline. Microscopic examination of the traumatized spinal cords failed to reveal a substantial difference between the three groups. However, dogs with better functional results tended to have less destruction of the white matter. Hemorrhagic necrosis of the central gray matter was consistently observed in all traumatized spinal cords.
Evaluation of tumour-infiltrating CD4+CD25+FOXP3+ regulatory T cells in human cutaneous benign and atypical naevi, melanomas and melanoma metastases (2007)

The strong prevalence of CD25+FOXP3+ Tregs both in junctional and compound atypical naevi and radial growth phase melanomas, suggests that they induce immunotolerance early during melanoma genesis, favouring melanoma growth. Their evaluation within a tumour site could be useful for prognostic and therapeutic purposes.
Comparison of culture and PCR for detection of Bordetella pertussis and Bordetella parapertussis under routine laboratory conditions (2004)

A PCR assay for the detection of Bordetella pertussis and Bordetella parapertussis was compared with the conventional culture method under routine laboratory conditions. Detection of B. pertussis was based on the amplification of a section of the IS481 insertion sequence and confirmation of positive results was based on a sequence of the pertussis toxin promoter region. Detection of B. parapertussis was based on the amplification of a section of the IS1001 insertion sequence. An internal control was included. Data were available for the period 28 November 2000 to 9 July 2003. In this period, 3096 patients were examined for infection with B. pertussis and B. parapertussis by culture and PCR on the same day. B. pertussis was found in 496 (16 %) patients; 208 (42 %) were diagnosed by PCR alone whereas 17 (3 %) were diagnosed by culture alone. B. parapertussis was found in 64 (2 %) patients. The sensitivity of the PCR was 97 % and of culture 58 %. The specificity of PCR was 93 % when regarding culture as 100 % sensitive. There was a significant relationship between laboratory method and age, as the superiority of PCR was most marked in the age group 0.5-3 years. The PCR assay proved highly sensitive for the diagnosis of pertussis. The specificity estimate of the PCR assay suffers from the influence of a gold-standard method with a low sensitivity. The PCR assay is considered highly specific due to the amplification of two different sequences in two separate assays.
Silicon transfer layer for multilayer resist systems (1981)

Thin film silicon is found to be a desirable interlayer material for e-beam lithography with multilayer resist systems. It is easily etched in CF4 plasma (Si/PMMA: 30/1) yet resists O2 reactive ion etch (Si/HPR: 1/300). It is sufficiently conductive to avoid charging effects, both during lithography and SEM inspection. High optical contrast aids in inspection. Monte Carlo calculations show that a 2.5 μm bottom layer of polymer can substantially alleviate the proximity effect, even with an 80 nm Si interlayer. Pattern transfer with less than 100 nm linewidth loss is demonstrated. Lines as narrow as 200 nm in 2 μm of Hunt positive resist were holographically produced.
Stem‐Cell Nanoengineering (2015)

With increasing understanding of stem-cell biology, the use of stem cells in clinical treatment has become more of a reality for a variety of incurable diseases. To achieve the clinical use of stem cells, however, their biological and physiological complexity must be understood in detail. Current conventional techniques used can only reveal some basic aspects of stem cells and not their complex biology. With the advent of micro- and nanoengineering tools it has become possible to develop highly precise and standardized protocols to study stem-cell biology in detail and with high throughput and consistency. This chapter describes the different aspects of the need for nanoengineering tools in studying stem-cell biology and some of the developments of nanoengineering tools in this direction, as well as the potential challenges in this field.
Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system. (2002)

This preliminary study shows that the association of NTX further amplifies the lymphocytosis obtained by IL-2 plus MLT. Since the lymphocytosis represents the most important favourable prognostic variable predicting the anticancer efficacy of IL-2 immunotherapy, it is probable that a cancer neuroimmunotherapy with IL-2 plus both MLT and NTX to activate TH1 and suppress TH2 cells respectively, may deserve more promising results in the treatment of human neoplasms according to the psychoneuroimnunological knowledge.
Identification of a sequence within the C-terminal 26 amino acids of cholesteryl ester transfer protein responsible for binding a neutralizing monoclonal antibody and necessary for neutral lipid transfer activity. (1992)

The cholesteryl ester transfer protein (CETP; 476 amino acids) mediates the transfer of neutral lipids and phospholipids between plasma lipoproteins. Previous studies showed that the epitope of a neutralizing monoclonal antibody (TP2) was located within the C-terminal 26 amino acids (aa) of CETP. To determine possible involvement of this region in lipid transfer activities, we generated six deletion mutants between Arg-451 and Leu-475 by in vitro mutagenesis and expressed mutant proteins in mammalian cells. Only deletion mutants between aa Phe-463 and Leu-475 failed to bind TP2; these mutant proteins were well secreted by cells but showed markedly reduced cholesteryl ester transfer activity. One of the deletion mutants (delta 470-475) showed similar reductions in cholesteryl ester and triglyceride transfer activities but normal or increased phospholipid transfer activity. Limited proteolysis of this mutant protein indicated a similar overall folding pattern to the wild-type protein. Thus, aa between Phe-463 and Leu-475 are necessary for binding TP2. Deletions within this sequence selectively impair neutral lipid transfer activity, suggesting a direct involvement in neutral lipid transfer.
Growth and Metabolic Responses in Low-Birth-Weight Infants Fed Human Milk Fortified with Human Milk Protein or with a Bovine Milk Protein Preparation (1991)

Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.
Cellular Localization and Function of the Antiviral Protein, Ovine Mx1 (oMx1): I. Ovine Mx1 Is Secreted By Endometrial Epithelial Cells Via an ‘Unconventional’ Secretory Pathway (2006)

This is the first report that the antiviral protein, oMx1, is secreted and provides evidence that secretion occurs via unconventional secretory pathway(s).
Analysis of Seizure EEG in Kindled Epileptic Rats (2007)

Using wavelet analysis we have detected the presence of chirps in seizure EEG signals recorded from kindled epileptic rats. Seizures were induced by electrical stimulation of the amygdala and the EEG signals recorded from the amygdala were analyzed using a continuous wavelet transform. A time–frequency representation of the wavelet power spectrum revealed that during seizure the EEG signal is characterized by a chirp‐like waveform whose frequency changes with time from the onset of seizure to its completion. Similar chirp‐like time–frequency profiles have been observed in newborn and adult patients undergoing epileptic seizures. The global wavelet spectrum depicting the variation of power with frequency showed two dominant frequencies with the largest amounts of power during seizure. Our results indicate that a kindling paradigm in rats can be used as an animal model of human temporal lobe epilepsy to detect seizures by identifying chirp‐like time–frequency variations in the EEG signal.
Differential Mass Spectrometry Profiles of Tau Protein in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease, Progressive Supranuclear Palsy, and Dementia with Lewy Bodies (2016)

Microtubule-associated Tau proteins are major actors in neurological disorders, the so-called tauopathies. In some of them, and specifically in Alzheimer's disease (AD), hyperphosphorylated forms of Tau aggregate into neurofibrillary tangles. Following and understanding the complexity of Tau's molecular profile with its multiple isoforms and post-translational modifications represent an important issue, and a major analytical challenge. Immunodetection methods are, in fact, limited by the number, specificity, sensitivity, and capturing property of the available antibodies. Mass spectrometry (MS) has recently allowed protein quantification in complex biological fluids using isotope-labeled recombinant standard for absolute quantification (PSAQ). To study Tau proteins, which are found at very low concentrations within the cerebrospinal fluid (CSF), we relied on an innovative two-step pre-fractionation strategy, which was not dependent on immuno-enrichment. We then developed a sensitive multiplex peptide detection capability using targeted high-resolution MS to quantify Tau-specific peptides covering its entire sequence. This approach was used on a clinical cohort of patients with AD, progressive supranuclear palsy (PSP), and dementia with Lewy body (DLB) and with control non-neurodegenerative disorders. We uncovered a common CSF Tau molecular profile characterized by a predominance of central core expression and 1N/3R isoform detection. While PSP and DLB tau profiles showed minimal changes, AD was characterized by a unique pattern with specific modifications of peptide distribution. Taken together these results provide important information on Tau biology for future therapeutic interventions, and improved molecular diagnosis of tauopathies.
Three-Dimensional Structure of Aleutian Mink Disease Parvovirus: Implications for Disease Pathogenicity (1999)

The three-dimensional structure of expressed VP2 capsids of Aleutian mink disease parvovirus strain G (ADVG-VP2) has been determined to 22 A resolution by cryo-electron microscopy and image reconstruction techniques. A structure-based sequence alignment of the VP2 capsid protein of canine parvovirus (CPV) provided a means to construct an atomic model of the ADVG-VP2 capsid. The ADVG-VP2 reconstruction reveals a capsid structure with a mean external radius of 128 A and several surface features similar to those found in human parvovirus B19 (B19), CPV, feline panleukopenia virus (FPV), and minute virus of mice (MVM). Dimple-like depressions occur at the icosahedral twofold axes, canyon-like regions encircle the fivefold axes, and spike-like protrusions decorate the threefold axes. These spikes are not present in B19, and they are more prominent in ADV compared to the other parvoviruses owing to the presence of loop insertions which create mounds near the threefold axes. Cylindrical channels along the fivefold axes of CPV, FPV, and MVM, which are surrounded by five symmetry-related beta-ribbons, are closed in ADVG-VP2 and B19. Immunoreactive peptides made from segments of the ADVG-VP2 capsid protein map to residues in the mound structures. In vitro tissue tropism and in vivo pathogenic properties of ADV map to residues at the threefold axes and to the wall of the dimples.
Effects of Photoperiod During the Dry Period on Prolactin, Prolactin Receptor, and Milk Production of Dairy Cows (2005)

Cows exposed to short day photoperiod during the dry period produce significantly more milk in their subsequent lactation than cows exposed to long days. The mechanism(s) underlying this effect are unknown. Because concentrations of prolactin (PRL) in circulation are consistently affected by changes in photoperiod, we hypothesized that alterations in the prolactin axis and sensitivity of the mammary gland to prolactin signaling may mediate photoperiodic effects in dry cows. The objective of this study was to determine the effects of exposure to different lengths of daylight during the dry period on circulating PRL and PRL receptor (PRL-R) mRNA expression in lymphocytes and mammary tissue during the transition to lactation. Multiparous Holstein cows were dried off 62 d before calving and assigned to long day (16 h light: 8 h dark) or short day photoperiod (8 h light: 16 h dark). During the dry period, PRL and PRL-R mRNA were analyzed biweekly in plasma and lymphocytes, respectively. Expression of PRL-R mRNA was assessed in mammary biopsies during the dry and periparturient periods. Dry matter intake (DMI) was recorded through 21 d of lactation, and milk yield was recorded until 120 d in milk. Short day photoperiod was associated with reduced PRL, whereas milk yield and expression of PRL-R mRNA in lymphocytes and mammary tissue were increased. Cows on short days had higher DMI during the dry period but did not differ in DMI after parturition. These data support the concept that greater responsiveness and sensitivity to PRL during transition to lactation may be associated with an increase in subsequent milk yield.
l-Arginine Deprivation Regulates Cyclin D3 mRNA Stability in Human T Cells by Controlling HuR Expression (2010)

Myeloid-derived suppressor cells are a major mechanism of tumor-induced immune suppression in cancer. Arginase I-producing myeloid-derived suppressor cells deplete l-arginine (L-Arg) from the microenvironment, which arrests T cells in the G(0)-G(1) phase of the cell cycle. This cell cycle arrest correlated with an inability to increase cyclin D3 expression resulting from a decreased mRNA stability and an impaired translation. We sought to determine the mechanisms leading to a decreased cyclin D3 mRNA stability in activated T cells cultured in medium deprived of L-Arg. Results show that cyclin D3 mRNA instability induced by L-Arg deprivation is dependent on response elements found in its 3'-untranslated region (UTR). RNA-binding protein HuR was found to be increased in T cells cultured in medium with L-Arg and bound to the 3'-untranslated region of cyclin D3 mRNA in vitro and endogenously in activated T cells. Silencing of HuR expression significantly impaired cyclin D3 mRNA stability. L-Arg deprivation inhibited the expression of HuR through a global arrest in de novo protein synthesis, but it did not affect its mRNA expression. This alteration is dependent on the expression of the amino acid starvation sensor general control nonderepressible 2 kinase. These data contribute to an understanding of a central mechanism by which diseases characterized by increased arginase I production may cause T cell dysfunction.
Comparison of Amperometric and Coulometric Electrchemical Detectors for HPLC Through a Figure of Merit (1983)

Abstract Performance characteristics of electrochemical detectors for high performance liquid chromatooraphy are difficult to predict from presently avaliable information relating response to design parameters. A fiqure of merit is proposed which allows an operational comparison to be made, based upon specific response, noise and band spread. On this basis, it is shown that a meaningful comparison of an amperometric design with a coulometric design can be obtained and that, contrary to previous predictions, this coulometric type is generally superior.
Suppression of IL-12 Transcription in Macrophages Following Fcγ Receptor Ligation (2001)

Ligating Fc gamma R on macrophages results in suppression of IL-12 production. We show that Fc gamma R ligation selectively down-regulates IL-12 p40 and p35 gene expression at the level of transcription. The region responsive to this inhibition maps to the Ets site of the p40 promoter. PU.1, IFN consensus sequence binding protein, and c-REL: form a complex on this element upon macrophage activation. Receptor ligation abolishes the binding of this PU.1-containing activation complex, and abrogates p40 transcription. A dominant-negative construct of PU.1 diminishes IL-12 p40 promoter activity and endogenous IL-12 p40 protein secretion. Thus, the specificity of IL-12 down-regulation following receptor ligation lies in the inhibition of binding of a PU.1-containing complex to the Ets site of the IL-12 promoter. These findings provide evidence demonstrating for the first time the importance of PU.1 in the transcriptional regulation of IL-12 gene expression.
Scaffold-Hopping Approach To Discover Potent, Selective, and Efficacious Inhibitors of NF-κB Inducing Kinase (2018)

NF-κB-inducing kinase (NIK) is a protein kinase central to the noncanonical NF-κB pathway downstream from multiple TNF receptor family members, including BAFF, which has been associated with B cell survival and maturation, dendritic cell activation, secondary lymphoid organ development, and bone metabolism. We report herein the discovery of lead chemical series of NIK inhibitors that were identified through a scaffold-hopping strategy using structure-based design. Electronic and steric properties of lead compounds were modified to address glutathione conjugation and amide hydrolysis. These highly potent compounds exhibited selective inhibition of LTβR-dependent p52 translocation and transcription of NF-κB2 related genes. Compound 4f is shown to have a favorable pharmacokinetic profile across species and to inhibit BAFF-induced B cell survival in vitro and reduce splenic marginal zone B cells in vivo.