gebhart/patrepeval huggingface dataset:
Thalidomide and immunomodulatory drugs as cancer therapy (2002)

The demonstration of increased angiogenesis in cancer pathogenesis prompted the use of thalidomide in both solid tumors and hematologic malignancies. Its broad spectrum of actions besides its antiangiogenic potential, specifically, its immunomodulatory properties, antiinflammatory actions, and direct effect on tumor cells and their microenvironment, provides an alternative strategy in the armamentarium against cancer. Thalidomide is being evaluated for treatment of hematologic cancers like multiple myeloma and myelodysplasia, and solid tumors like lung, breast, renal, and colon cancer. Thalidomide analogues, the immunomodulatory drugs have increased potency and have demonstrated efficacy and reduced toxicity in phase I and II clinical studies. This article reviews both laboratory-based and clinical studies with thalidomide and the immunomodulatory drugs and their application in different cancers.
Scalable planning for distributed stream processing systems (2006)

Recently the problem of automatic composition of workflows has been receiving increasing interest. Initial investigation has shown that designing a practical and scalable composi-tion algorithm for this problem is hard. A very general com-putational model of a workflow (e.g., BPEL) can be Turing-complete, which precludes fully automatic analysis of com-positions. However, in many applications, workflow model can be simplified. We consider a model known as the Stream Processing Planning Language (SPPL), applicable in stream processing and other related domains. SPPL replaces the no-tion of concurrency by timeless functional computation. In addition, SPPL defines workflow metrics of resource con-sumption and quality of service. Experiments have shown earlier that even a naı̈ve SPPL planning algorithm signifi-cantly outperforms existing metric PDDL planners on stream processing workflow composition problems. In this paper we describe an efficient and scalable algorithm for finding high-quality approximate solutions for large instances of SPPL problems. We demonstrate the scalability of the algorithm on synthetic benchmarks that are derived from practical prob-lems. We also give an example of SPPL model for practical problems.
Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. (1998)

Loss of chromosome 10q is a frequently observed genetic defect in prostate cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identified and mapped to chromosome 10q23.3. We studied PTEN structure and expression in 4 in vitro cell lines and 11 in vivo xenografts derived from six primary and nine metastatic human prostate cancers. DNA samples were allelotyped for eight polymorphic markers within and surrounding the PTEN gene. Additionally, the nine PTEN exons were tested for deletions. In five samples (PC3, PC133, PCEW, PC295, and PC324), homozygous deletions of the PTEN gene or parts of the gene were detected. PC295 contained a small homozygous deletion encompassing PTEN exon 5. In two DNAs (PC82 and PC346), nonsense mutations were found, and in two (LNCaP and PC374), frame-shift mutations were found. Missense mutations were not detected. PTEN mRNA expression was clearly observed in all cell lines and xenografts without large homozygous deletions, showing that PTEN down-regulation is not an important mechanism of PTEN inactivation. The high frequency (60%) of PTEN mutations and deletions indicates a significant role of this tumor suppressor gene in the pathogenesis of prostate cancer.
Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic (2014)

This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop.
High frequency ofOTOFmutations in Chinese infants with congenital auditory neuropathy spectrum disorder (2016)

Auditory neuropathy spectrum disorder (ANSD) is one of the most common diseases leading to hearing and speech communication barriers in infants and young children. The OTOF gene is the first gene identified for autosomal recessive non-syndromic ANSD, and patients with OTOF mutations have shown marked improvement of auditory functions from the cochlear implantation, but the true involvement of OTOF mutations in Chinese ANSD patients is still unknown which precludes the effective management of this disease. Here, we investigated the contribution of OTOF mutations to congenital ANSD patients in China. In all, 37 infants and young Children with ANSD were screened for all the exons of OTOF gene, of them 34 patients had no neonatal risk factors who were considered as congenital ANSD. The clinical manifestation and audiometric features were also investigated and compared in patients with and without OTOF mutations. In all, 14 of these subjects were shown to carry two or three mutant alleles of OTOF with the high frequency of 41.2% in congenital ANSD patients. In total, 15 novel pathogenic mutations and 10 reported mutations were identified. Our results confirmed that mutations in OTOF gene were a major cause of congenital ANSD in China. Identification of OTOF mutations can facilitate diagnosis, clinical intervention and counseling for congenital ANSD.
High Proteolytic Resistance of Spider-Derived Inhibitor Cystine Knots (2015)

Proteolytic stability in gastrointestinal tract and blood plasma is the major obstacle for oral peptide drug development. Inhibitor cystine knots (ICKs) are linear cystine knot peptides which have multifunctional properties and could become promising drug scaffolds. ProTx-I, ProTx-II, GTx1-15, and GsMTx-4 were spider-derived ICKs and incubated with pepsin, trypsin, chymotrypsin, and elastase in physiological conditions to find that all tested peptides were resistant to pepsin, and ProTx-II, GsMTx-4, and GTx1-15 showed resistance to all tested proteases. Also, no ProTx-II degradation was observed in rat blood plasma for 24 hours in vitro and ProTx-II concentration in circulation decreased to half in 40 min, indicating absolute stability in plasma and fast clearance from the system. So far, linear peptides are generally thought to be unsuitable in vivo, but all tested ICKs were not degraded by pepsin and stomach could be selected for the alternative site of drug absorption for fast onset of the drug action. Since spider ICKs are selective inhibitors of various ion channels which are related to the pathology of many diseases, engineered ICKs will make a novel class of peptide medicines which can treat variety of bothering symptoms.
Engineering a Synthetic Ligand for Tumor Necrosis Factor–Alpha (2011)

One approach to prepare protein binding ligands is to join two low-affinity ligands that bind different sites on the target protein to create a high-affinity bivalent ligand. This typically requires some knowledge of the ligand binding site and requires exquisite orientation of the ligands in order to achieve maximum binding affinity. Here, we explored the limit of affinity improvement possible with no a priori knowledge of peptide binding site and with minimal effort spent in linking the lead peptides. We compared the affinity enhancement from linking two peptides with low affinity for tumor necrosis factor-α (TNFA) to the affinity enhancement from linking affinity improved versions of these peptides using several different scaffolds. We found that we achieved the highest affinity gain not by the precise positioning of the peptides, but rather by using affinity improved versions of the lead peptides to produce synbodies with apparent K(D)'s of 9 to 48 nM. Kinetic analysis showed that the binding kinetics of the synbody are strongly influenced by the kinetics of the starting peptide. This suggests that careful selection of peptides based on their kinetic profile prior to linking will influence the kinetics of the final binding agent.
Some remarks upon the relationship between the concept of happiness and morality. (1970)

This thesis represents an attempt to dissolve the problem of the relationship between happiness and morality. Morality is often seen as a barrier to the achievement of happiness, and many theories have been created to show that this is not so. Unfortunately most of these theories assume that man acts only in his own interest and therefore attempt to treat morality as a means to happiness. This is held to be a misunderstanding of the nature of morality. The concept of self-interest is examined briefly here and found not to be so self-explanatory as is sometimes thought. For this and other reasons, these theories are rejected. An attempt is then made to generate a different way of viewing human action. To this end, the nature of emotional behaviour is discussed at length, both because it is related to the concept of happiness and because its investigation permits the generation of a methodologically useful concept - the concept of 'importance'. This concept is explained only by a description of its behaviour, for it is to some extent an artificial one, generated to serve a function, although it is held that it is implicit in ordinary language. The concept is used as a bridge between morality and happiness, both of which are discussed in terms of it. It is argued that reasons for human action do not often spring from internal 'forces' or 'states', but from a man's appreciation of what matters in the world. The conclusion of the thesis is difficult to summarise, but depends upon the fact that what matters, may often be what matters morally. Thus, it is held that, for the good man, happiness is inseparable from right action, and that when morality is seen as a barrier to happiness, it is possible that it is either being mis- understood or that the particular form of it is fossilised.
Up-regulation of vascular endothelial growth factor in breast cancer cells by the heregulin-beta1-activated p38 signaling pathway enhances endothelial cell migration. (2001)

Heregulin (HRG) belongs to a family of polypeptide growth factors that bind to receptor tyrosine kinases ErbB3 and ErbB4. HRG binding induces ErbB3 and ErbB4 heterodimerization with ErbB2, activating downstream signal transduction. Vascular endothelial growth factor (VEGF) is a primary regulator of physiological angiogenesis and is a major mediator of pathological angiogenesis, such as tumor-associated neovascularization. In this study, we demonstrate that HRG-beta1 increased secretion of VEGF from breast cancer cells in a time- and dosage-dependent manner and that this increase resulted from up-regulation of VEGF mRNA expression via transcriptional activation of the VEGF promoter. Deletion and mutational analysis revealed that a CA-rich upstream HRG response element located between nucleotide-2249 and -2242 in the VEGF promoter mediated HRG-induced transcriptional up-regulation of VEGF. While investigating the downstream signaling pathways involved in HRG-mediated up-regulation of VEGF, we found that HRG activated extracellular signal-regulated protein kinases, Akt kinase, and p38 mitogen-activated protein kinase (MAPK). However, only the specific inhibitor of p38 MAPK (SB203580), not extracellular signal-regulated kinase inhibitor PD98059 nor the inhibitor of phosphatidylinositol 3-kinase-Akt pathway (Wortmannin), blocked the up-regulation of VEGF by HRG. The HRG-stimulated secretion of VEGF from breast cancer cells resulted in increased migration of murine lung endothelial cells, an activity that was inhibited by either VEGF-neutralizing antibody or SB203580. These results show that HRG can activate p38 MAPK to enhance VEGF transcription via an upstream HRG response element, leading to increased VEGF secretion and angiogenic response in breast cancer cells.
Adhesive studies of synthetic polypeptides: A model for marine adhesive proteins (1987)

Abstract As a basic approach to clarify the adhesive power of marine proteins, the bonding strength (tensile and compressive shear) of a variety of synthetic polypeptides including polydecapeptide dissolved in water or organic solvents on metals (Fe and Al2O3) and rubber (Buna) has been investigated. High-molecular-weight poly(Lys) HBr was found to have the highest tensile strength of 123 kg/cm2 on Fe, whereas gelatin showed the highest compressive shear strength of 21 kg/cm2 on Al2O3 and 20 kg/cm2 on Buna. Water-soluble polypeptides containing lysyl residues were effective adhesives on metals. For polypeptides dissolved in organic solvents, poly(DLMet) in dicholoromethane showed the maximum adhesive strength on metals. Synthetic poly(Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Dopa-Lys 2HBr)n (n=10), which is a sequence of the adhesive proteins from marine mussels, exhibited a tensile strength of 28 kg/cm2 on Fe and a compressive shear strength of 3 kg/ cm2 on Al2O3 and 2 kg/cm2 on Buna. The bonding strength is compared with those of natural marine adhesive proteins. Keywords: Marine adhesive proteinssynthetic polypeptidespoly(Lys)polydecapeptidebonding strengthmetalsrubber Buna
High room temperature peak-to-valleycurrent ratio in Sibased Esaki diodes (1999)

Room temperature (RT) I–V characteristics of epitaxially grown Si/SiGe/Si p+/i/n+ Esaki diodes are presented. The incorporation of Ge within the intrinsic (i) zone gives rise to an increased peak current density (jP = 3 kA/cm2) and peak-to-valley current ratio (PVCR) compared to pure Si structures (jP = 80 A/cm2). A detailed investigation and optimisation of post-growth annealing has demonstrated a record PVCR of 4.2 for Si based Esaki diodes.
Majority Voting: Material Classification by Tactile Sensing Using Surface Texture (2011)

In this paper, we present an application of machine learning to distinguish between different materials based on their surface texture. Such a system can be used for the estimation of surface friction during manipulation tasks; quality assurance in the textile, cosmetics, and harvesting industries; and other applications requiring tactile sensing. Several machine learning algorithms, such as naive Bayes, decision trees, and naive Bayes trees, have been trained to distinguish textures sensed by a biologically inspired artificial finger. The finger has randomly distributed strain gauges and polyvinylidene fluoride (PVDF) films embedded in silicone. Different textures induce different intensities of vibrations in the silicone. Consequently, textures can be distinguished by the presence of different frequencies in the signal. The data from the finger are preprocessed, and the Fourier coefficients of the sensor outputs are used to train classifiers. We show that the classifiers generalize well for unseen datasets with performance exceeding previously reported algorithms. Our classifiers can distinguish between different materials, such as carpet, flooring vinyls, tiles, sponge, wood, and polyvinyl-chloride (PVC) woven mesh with an accuracy of on unseen test data.
Reaction channels for the catalytic oxidation of CO on Pt(111) (1999)

The catalytic oxidation of CO on O-precovered Pt(111) surfaces has been modeled via ab initio local-density-functional calculations. It is shown that at coverages of ${\ensuremath{\Theta}}_{\mathrm{O}}\ensuremath{\sim}0.5$ the coadsorption of CO stabilizes the chemisorbed molecular precursor of ${\mathrm{O}}_{2}$ over the dissociated atomic oxygen. The barrier for the reaction between the coadsorbed molecules is lowest if first the molecular ${\mathrm{O}}_{2}$ bond is broken. However, at this high coverage the barrier for the ${\mathrm{O}}_{2}+\mathrm{CO}$ reaction is higher than for ${\mathrm{O}}_{2}$ desorption. Therefore oxidation will be preceded by a partial desorption of ${\mathrm{O}}_{2}.$ At reduced coverage, the barrier for the oxidation reaction is strongly reduced. At the transition state the nascent O atoms are only bridge or top bonded and therefore quite reactive. After desorption of ${\mathrm{CO}}_{2},$ the adsorbed atomic O can react with a second CO molecule via a transition state similar to that for the molecular reaction.
Erythropoietin resistance: the role of inflammation and pro‐inflammatory cytokines (2002)

Up to 10% of patients with renal disease receiving recombinant human erythropoietin (rHuEPO) therapy show poor responsiveness to the drug. Even in patients who do respond to rHuEPO, there is a marked variability in drug sensitivity. Several factors have been recognized as causing resistance to rHuEPO, notably iron deficiency, infection/inflammation, and under dialysis. However, when these factors are excluded, the wide variation in responsiveness to rHuEPO persists. The mechanism of this effect needs to be fully elucidated. One hypothesis is that patients with uraemia showing resistance to rHuEPO may have enhanced levels of immune activation, causing increased release of pro-inflammatory cytokines in the bone marrow. Uraemia is known to be a chronic inflammatory state, with some patients showing considerably increased laboratory markers of inflammation and immune activation. Chronic inflammation can modify the process of erythropoiesis, probably mediated via pro-inflammatory cytokines such as interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The concept that rHuEPO resistance is due to enhanced levels of immune activity has been investigated by studying T-cell phenotypes using flow cytometry, as well as cytokine release from T cells and monocytes in 'good' and 'poor' responders to rHuEPO. Poor responders had significantly reduced CD28 expression on both CD4+ and CD8+ cells, enhanced IL-10 generation from peripheral blood mononuclear cells (PBMCs), higher plasma IL-12 levels, and increased TNF-alpha and IFN-gamma release from PBMCs. Anti-cytokine antibodies may be useful for studying inflammatory cytokine secretion from T cells in patients with renal failure. Strategies utilizing anti-cytokine therapy may prove to be a useful adjuvant in optimizing the response to rHuEPO therapy.
Effects of Surface Oxidation of AlGaN on DC Characteristics of AlGaN/GaN High-Electron-Mobility Transistors (2009)

We have investigated the effects of thin native oxide layers on the AlGaN surface on the DC characteristics of AlGaN/GaN high electron mobility transistors (HEMTs). After HEMT fabrication, the AlGaN surface between the electrodes was intentionally oxidized using either O2 or N2O plasma. X-ray photoelectron spectroscopy (XPS) analysis showed that both methods produced a native oxide of AlGaN with a thickness of about 1 nm and that an N–O chemical bond was present in the N2O plasma oxide. We observed pronounced degradation in the DC characteristics and current collapse in the HEMT with O2 plasma oxidation. In contrast, the formation of native oxide by the N2O plasma had no effect on the DC characteristics or current stability of the AlGaN/GaN HEMT. Possible mechanisms for device degradation were discussed in terms of stress and deep levels in the AlGaN layer induced by oxide formation or oxygen incorporation.
Topography of Ligand-induced Binding Sites, Including a Novel Cation-sensitive Epitope (AP5) at the Amino Terminus, of the Human Integrin β3 Subunit (1995)

Changes in ligand binding ability of the integrin alpha IIb beta 3 can be monitored by the concomitant expression of ligand-inducible binding sites (LIBS). A new LIBS, the hexapeptide sequence GPNICT (residues 1-6) at the amino terminus of beta 3 recognized by the murine monoclonal antibody (mAb) AP5, is sensitive both to the binding of ligand and to micromolar differences in divalent cation levels. Calcium or magnesium can completely inhibit the binding of AP5 to alpha IIb beta 3 on platelets, with ID50 values of 80 and 1500 microM, respectively. The inhibitory effect of calcium plus magnesium is cumulative. In the presence of 1 mM calcium plus 1 mM magnesium, the peptide RGDW overcomes this inhibition and induces maximal binding of AP5. Maximal AP5 binding is also induced by a molar excess of EDTA. The unique location of the AP5 LIBS was determined by comparing the binding of LIBS-specific mAb to recombinant human-Xenopus beta 3 chimeras produced in a baculovirus expression system. AP5 defines one region at the amino terminus beta 3 1-6. A second region, defined by mAb D3GP3, is probably located within beta 3 422-490, confirming the finding of Kouns et al. (Kouns, W. C., Newman, P.J., Puckett, K. J., Miller, A. A., Wall, C. D., Fox, C. F., Seyer, J. M., and Jennings, L. K. (1991) Blood 78, 3215-3223). The third region, encompassing at most residues 490-690, and perhaps more precisely located within 602-690 (Du X., Gu, M., Weise, J. W., Nagaswami, C., Bennett, J. S., Bowditch, R., and Ginsberg, M. H. (1993) J. Biol. Chem. 268, 23087-23092), is recognized by the four mAb, anti-LIBS2, anti-LIBS3, anti-LIBS6, and P41. Since its exposure is uniquely regulated by both divalent cations and ligand, the amino terminus of beta 3 may be involved in control of ligand binding by divalent cation mobilization.
Immunopathological mechanisms in dengue and dengue hemorrhagic fever (2006)

The immune mechanisms that lead to dengue hemorrhagic fever are complex and need to be elucidated further for the development of therapeutics as well as safe and efficacious dengue vaccines.
Protein turnover in the whole animal. (1980)

Methods of measuring whole body protein turnover (WBPT) are discussed briefly. In a range of species from mouse to cow WBPT in the adult bears a fairly constant relationship to metabolic mass and to basal oxygen consumption. In young animals WBPT per unit metabolic mass is higher than in adults. During growth there appears to be an increase in the rate of protein breakdown as well as of synthesis. Of all tissues which have been studied, muscle shows the greatest developmental changes in the rate of protein synthesis. In the absence of food, for example during the night, the rate of protein turnover falls. Studies on the effects of different levels of protein and energy supply have not so far given a constant picture. Very few measurements of WBPT in disease states have been made. Preliminary results suggest that the loss of nitrogen after injury may be due to a block in synthesis rather than to an increase in body protein breakdown.
Plant‐adapted green fluorescent protein is a versatile vital reporter for gene expression, protein localization and mitosis in the filamentous fungus, Aspergillus nidulans (1998)

Green fluorescent protein (GFP) is a useful reporter to follow the in vivo behaviour of proteins, but the wild-type gfp gene does not function in many organisms, including many plants and filamentous fungi. We show that codon-modified forms of gfp, produced for use in plants, function effectively in Aspergillus nidulans both as gene expression reporters and as vital reporters for protein location. To demonstrate the use of these modified gfps as reporter genes we have used fluorescence to follow ethanol-induced GFP expression from the alcA promoter. Translational fusions with the modified gfp were used to follow protein location in living cells; plant ER-retention signals targeted GFP to the endoplasmic reticulum, whereas fusion to the GAL4 DNA-binding domain targeted it to the nucleus. Nuclear-targeted GFP allowed real-time observation of nuclear movement and division. These modified gfp genes should provide useful markers to follow gene expression, organelle behaviour and protein trafficking in real time.