gebhart/patrepeval huggingface dataset:
Receptor-ligand interaction: a new method for determining binding parameters without a priori assumptions on non-specific binding (1989)

Analysis of receptor-ligand binding characteristics can be greatly hampered by the presence of non-specific binding, defined as low-affinity binding to non-receptor domains which is not saturable within the range of ligand concentrations used. Conventional binding analyses, e.g. according to the methods described by Scatchard or Klotz, relate the amount of specific receptor-ligand binding to the concentration of free ligand, and therefore require assumptions on the amount of non-specific binding. In this paper a method is described for determining the parameters of specific receptor-ligand interaction which does not require any assumption or separate determination of the amount of non-specific binding. If the concentration of labelled free ligand is constant, a plot of Fu/(B0*-B*) versus Fu yields a linear relationship, in the case of a single receptor class, in which Fu is the concentration of unlabelled free ligand, B0* is the total amount of labelled bound ligand in the absence of unlabelled ligand and B* is the total amount of labelled bound ligand in the presence of an unlabelled ligand concentration Fu; all of these data are readily obtained from binding studies. This linear relationship holds irrespective of the amount of non-specific binding, and the values for receptor density, ligand dissociation constant and a constant for non-specific binding can be readily obtained from it. If the concentration of labelled free ligand is not a constant for all data points, data are first converted according to a straightforward normalization procedure to permit the use of this relationship. The presence of multiple receptor classes with dissociation constants in the range of the ligand concentrations used results in a negative deviation from this linearity, and therefore the presence of multiple receptor classes can be discriminated unequivocally from non-specific binding. Both theoretical and practical advantages of the present method are described. The method, which will be referred to as the linear subtraction method, is illustrated using the binding of tumour promoters and polypeptide growth factors to their specific cellular receptors.
Engineering of Bacterial Methyl Ketone Synthesis for Biofuels (2011)

We have engineered Escherichia coli to overproduce saturated and monounsaturated aliphatic methyl ketones in the C₁₁ to C₁₅ (diesel) range; this group of methyl ketones includes 2-undecanone and 2-tridecanone, which are of importance to the flavor and fragrance industry and also have favorable cetane numbers (as we report here). We describe specific improvements that resulted in a 700-fold enhancement in methyl ketone titer relative to that of a fatty acid-overproducing E. coli strain, including the following: (i) overproduction of β-ketoacyl coenzyme A (CoA) thioesters achieved by modification of the β-oxidation pathway (specifically, overexpression of a heterologous acyl-CoA oxidase and native FadB and chromosomal deletion of fadA) and (ii) overexpression of a native thioesterase (FadM). FadM was previously associated with oleic acid degradation, not methyl ketone synthesis, but outperformed a recently identified methyl ketone synthase (Solanum habrochaites MKS2 [ShMKS2], a thioesterase from wild tomato) in β-ketoacyl-CoA-overproducing strains tested. Whole-genome transcriptional (microarray) studies led to the discovery that FadM is a valuable catalyst for enhancing methyl ketone production. The use of a two-phase system with decane enhanced methyl ketone production by 4- to 7-fold in addition to increases from genetic modifications.
Human and Murine Immune Responses to a NovelLeishmania majorRecombinant Protein Encoded by Members of a Multicopy Gene Family (1998)

Vaccination of BALB/c mice with Leishmania major promastigote culture filtrate proteins plus Corynebacterium parvum confers resistance to infection with L. major. To define immunogenic components of this protein mixture, we used sera from vaccinated mice to screen an L. major amastigote cDNA expression library. One of the immunoreactive clones thus obtained encoded a novel protein of L. major with a molecular mass of 22.1 kDa. The predicted amino acid sequence of this clone exhibited significant homology to eukaryotic thiol-specific-antioxidant (TSA) proteins. Therefore, we have designated this protein L. major TSA protein. Southern blot hybridization analyses indicate that there are multiple copies of the TSA gene in all species of Leishmania analyzed. Northern blot analyses demonstrated that the TSA gene is constitutively expressed in L. major promastigotes and amastigotes. Recombinant TSA protein containing an amino-terminal six-histidine tag was expressed in Escherichia coli with the pET17b system and was purified to homogeneity by affinity chromatography. Immunization of BALB/c mice with recombinant TSA protein resulted in the development of strong cellular immune responses and conferred protective immune responses against infection with L. major when the protein was combined with interleukin 12. In addition, recombinant TSA protein elicited in vitro proliferative responses from peripheral blood mononuclear cells of human leishmaniasis patients and significant TSA protein-specific antibody titers were detected in sera of both cutaneous-leishmaniasis and visceral-leishmaniasis patients. Together, these data suggest that the TSA protein may be useful as a component of a subunit vaccine against leishmaniasis.
Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate (1993)

The syntheses and cytotoxic activities of substituted N-phenylacetamido derivatives of doxorubicin and melphalan are described. The derivatives were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates. N-(Phenylacetamido)doxorubicin (2) and N-(phenylacetyl)melphalan (6) were found to be 10- and 20-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin and melphalan, respectively. When incubated with PGA, the cytotoxicity of 2 and 6 increased and became equivalent to that of the corresponding drugs from which they were made. The poor solubility characteristics of 2 in aqueous solutions provided the basis for the development of the more soluble doxorubicin derivatives, N-(4-aminophenylacetyl)doxorubicin (3) and N-(4-phosphonooxy)phenylacetyl)-doxorubicin (4). In vitro cytotoxicity assays indicated that 3 and 4 were at least 1000-fold less toxic than doxorubicin against H2981 cells. PGA and the mAb conjugate L6-PGA were able to effect the activation of 3 and 6 on H2981 cells (L6-antigen positive). Hydrolysis of the phosphate group of 4 was required prior to activation with PGA or L6-PGA. This was achieved using alkaline phosphatase, or by exposing 4 to phosphatases present in cell culture medium. The activation of 3, 4, and 6 on H2981 cells by L6-PGA occurred in an immunologically specific manner, since activation could be blocked by saturating cell surface antigens with L6 prior to treatment with L6-PGA. These results demonstrate that 3, 4, and 6 are prodrugs that can be specifically activated to release clinically approved anticancer agents by a mAb-PGA conjugate.
A Unix network protocol security study (1992)

article A Unix network protocol security study: network information service Share on Authors: David K. Hess View Profile , David R. Safford View Profile , Udo W. Pooch View Profile Authors Info & Claims ACM SIGCOMM Computer Communication ReviewVolume 22Issue 5Oct. 1992 pp 24–28https://doi.org/10.1145/141809.141811Online:02 October 1992Publication History 6citation427DownloadsMetricsTotal Citations6Total Downloads427Last 12 Months7Last 6 weeks0 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 SiteGet Access
Red Blood Cell Storage Lesion (2009)

The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC) transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L), lysophosphatidylcholine (lyso-PC), and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.
Formation and Rheology of Viscoelastic “Double Networks” in Wormlike Micelle−Nanoparticle Mixtures (2010)

We present a systematic study of thermodynamics, structure, and rheology of mixtures of cationic wormlike micelles and like-charged nanoparticles. Structural and thermodynamic measurements in dilute surfactant-nanoparticle mixtures show the formation of micelle-nanoparticle junctions that act as physical cross-links between micelles. The presence of these junctions is shown to build significant viscosity and viscoelasticity in dilute and semidilute WLMs, even in cases where the fluid is Newtonian in the absence of nanoparticles. Increases in viscosity, shear modulus, and relaxation time, as well as decreases in entanglement concentration, are observed with increasing particle concentration. As such, nanoparticle addition gives rise to a so-called "double network" comprised of micellar entanglements and particle junctions. A simple model for such networks is proposed, where the elasticity can be tuned through two energetic scales, the micellar end-cap energy and micelle-nanoparticle adsorption energy. As a practical application, the results demonstrate that nanoparticle addition provides formulators a unique method to tailor surfactant solution rheology over a wide range of conditions.
Sensitive in situ hybridization with catalyzed reporter deposition, streptavidin-Nanogold, and silver acetate autometallography: detection of single-copy human papillomavirus. (1997)

The usefulness of standard in situ hybridization for viral nucleic acid detection is occasionally limited by its sensitivity limit of 10 to 50 copies per cell. A modified version of the recently described signal amplification method, catalyzed reporter deposition (CARD), and its application to formalin-fixed cells and tissue sections is presented. Deposition of the reporter is facilitated by using horseradish peroxidase catalyzing the deposition of biotinylated tyramide on the location of the probe target. The biotin accumulation created is usually detected with streptavidin-labeled enzymes or fluorochromes. In the present investigation, this step was replaced by streptavidin-Nanogold and combined with silver acetate autometallography. This resulted in deep-black precipitation at positive in situ hybridized reaction sites. The sensitivity of this new approach was tested with a biotinylated, genomic probe specific for human papillomavirus (HPV)-16/18. SiHa cells, a cervical carcinoma-derived cell line with one to two HPV16 copies per cell, and 10 histologically confirmed cervical carcinomas were used for the study. All samples were previously HPV16 positive with solution polymerase chain reaction, but only two of the cervical carcinomas were positive with standard in situ hybridization with barely visible signals. When employing CARD-Nanogold, SiHa cells and 9 of 10 biopsies proved positive with marked signals. It is concluded that this nonisotopic method can detect single viral copies in situ in routinely fixed material and may have the potential to replace in situ polymerase chain reaction in many applications.
Synthesis of 2'-C-Methylcytidine and 2'-C-Methyluridine Derivatives Modified in the 3'-Position as Potential Antiviral Agents (2006)

As part of our anti-hepatitis C program, we recently discovered 2'- C -methylcytidine ( 1 ) and 2'- C -methyluridine ( 2 ), which are potent inhibitors in cell culture of several viruses (bovine viral diarrhea virus (BVDV), yellow fever virus (YFV)) closely related to HCV. In order to characterize structure-activity relationships, we introduced some structural and functional modifications into the 3'-position of 2'- C -methylcytidine and 2'- C -methyluridine. All these hitherto unknown compounds thus synthesized were tested for the activity against a wide range of viruses and found to be inactive.
Use of superpages and subblocking in the address translation hierarchy (1995)

Most computers that support virtual memory translate virtual addresses to physical addresses using a translation lookaside buffer (TLB) and a page table. Time spent in TLB miss handling--number of TLB misses times average TLB miss penalty--is increasing due to workload, architectural, and technological trends. This thesis studies TLB architectures that reduce the number of TLB misses by increasing TLB reach--the maximum address space mapped by a TLB--and page table designs that decrease TLB miss penalty or support new TLB architectures without increasing TLB miss penalty.
First, this thesis evaluates two TLB architectures in commercial use--superpages and complete subblocking. This thesis studies the benefits of superpages and the issues involved in modifying operating systems and page tables to support superpages. Complete subblocking allows processor designers to use larger chip areas to build large TLBs within cycle time constraints. Simulation results show that for comparable chip area, complete-subblock TLBs have faster access times and incur fewer TLB misses than single-page-size TLBs without requiring operating system changes.
Second, this thesis proposes a new TLB architecture, partial subblocking, that combines the best features of complete subblocking and superpages. Simulation results show that superpage and subblock TLBs, for comparable chip area, incur fewer TLB misses than single-page-size TLBs. Further, partial-subblock TLBs require simpler operating systems and incur fewer misses than superpage TLBs.
Third, superpage and partial-subblock TLBs are ineffective without operating system support. This thesis identifies the policies and mechanisms required to support these TLBs. In particular, this thesis proposes a physical memory allocation algorithm, page reservation, that makes partial-subblock TLBs effective or eliminates page copying in superpage creation.
Fourth, this thesis suggests modifications to conventional page tables to support superpage and subblock TLBs and proposes a new page table structure, clustered page table, that augments hashed page tables with subblocking. Simulation results show that clustered page tables are smaller and have a faster access time than conventional page tables when using single-page-size TLBs. A clustered page table improves on these advantages when storing superpage and subblock PTEs.
Optical Interconnects For High Speed Computing (1986)

We compare optical interconnect techniques with conventional electrical interconnects as applied to high speed electronic computing systems. Theoretical and semiempirical data are used to identify the advantages of optical interconnects at various levels. Besides the inherent advantages of optics such as reduced electromagnetic and radio frequency interference and crosstalk, optical interconnects are capable of providing larger fanouts at higher bandwidths, with possibly lower system power and complexity. In addition, optics has an advantage over conventional interconnects via the density potential of free-space interconnects. We also present issues related to the implementation of optical interconnects within conventional hardware configurations and describe a packaging technique to overcome several of these issues.
The differentiation primary response gene MyD118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21WAF1/CIP1. (1996)

Towards dissecting the regulation of terminal differentiation, including growth arrest and apoptosis, myeloid differentiation primary response (MyD) genes, induced in the absence of de novo protein synthesis following induction of M1 myeloblastic leukemia cells for terminal differentiation have been isolated. MyD118 was one of the novel MyD genes cloned, subsequently observed also to be a primary response gene to TGF-beta, which induces M1 cells for growth arrest and apoptosis uncoupled from differentiation. The MyD118 encoded protein was observed to be remarkably similar to the protein encoded by Gadd45, a growth arrest and DNA damage induced gene, regulated in part by the tumor suppressor p53. Though evidence has accumulated that MyD118 functions as an important modulator of negative growth control both in hematopoietic and non-hematopoietic cells, its mechanism of action is unknown. To better understand the role(s) of MyD118 in negative growth control, we have analysed the expression and biological characteristics of the MyD118 protein, compared to the Gadd45 protein, in distinct pathways of growth arrest and apoptosis, including p53 dependent and independent pathways either coupled or uncoupled from differentiation. It is shown that MyD118 and Gadd45 differentially accumulated upon induction of distinct pathways of growth arrest and apoptosis; notably, MyD118, but not Gadd45, was induced by TGF-beta, whereas Gadd45, but not MyD118, was induced by activating wild type (wt) p53 function. It is also shown that MyD118 is a nuclear protein, which regardless of the pathway induced, predominantly localized within the cell nucleus, and interacted with the DNA replication and repair protein PCNA and the cyclin dependent kinase inhibitor P21WAF1/CIP1. MyD118 also modestly stimulated DNA repair in vitro. All of these characteristics were shared with Gadd45. Finally, it is demonstrated that MyD118, Gadd45 and p21 synergized in the suppression of colony formation by NIH3T3 cells. Taken together, these findings demonstrate that MyD118 and Gadd45 are representative of a new protein family that share remarkable functional similarities in the control of distinct pathways of negative growth, including the suppression of cellular growth and programmed cell death.
Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression (2007)

Markers within GRIK2 and GRIA3 were associated with treatment-emergent suicidal ideation during citalopram therapy. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk.
Light dosimetry for photodynamic therapy in the esophagus (1997)

The proposed approach allows for improved safety and efficacy of PDT in the esophagus, particularly in the clinical tests of new photosensitizers.
Structural Characterization of a Partly Folded Apomyoglobin Intermediate (1990)

To understand why proteins adopt particular three-dimensional structures, it is important to elucidate the hierarchy of interactions that stabilize the native state. Proteins in partly folded states can be used to dissect protein organizational hierarchies. A partly folded apomyoglobin intermediate has now been characterized structurally by trapping slowly exchanging peptide NH protons and analyzing them by two-dimensional 1H-NMR (nuclear magnetic resonance). Protons in the A, G, and H helix regions are protected from exchange, while protons in the B and E helix regions exchange freely. On the basis of these results and the three-dimensional structure of native myoglobin, a structural model is presented for the partly folded intermediate in which a compact subdomain retains structure while the remainder of the protein is essentially unfolded.
CFTR with a partially deleted R domain corrects the cystic fibrosis chloride transport defect in human airway epithelia in vitro and in mouse nasal mucosa in vivo (2002)

In developing gene therapy for cystic fibrosis (CF) airways disease, a transgene encoding a partially deleted CF transmembrane conductance regulator (CFTR) Cl- channel could be of value for vectors such as adeno-associated virus that have a limited packaging capacity. Earlier studies in heterologous cells indicated that the CFTR R (regulatory) domain is predominantly random coil and that parts of the R domain can be deleted without abolishing channel function. Therefore, we designed a series of CFTR variants with shortened R domains (between residues 708 and 835) and expressed them in well-differentiated cultures of CF airway epithelia. All of the variants showed normal targeting to the apical membrane, and for the constructs we tested, biosynthesis was like wild type. Moreover, all constructs generated transepithelial Cl- current in CF epithelia. Comparison of the Cl- transport suggested that the length of the R domain, the presence of phosphorylation sites, and other factors contribute to channel activity. A variant deleting residues 708-759 complemented CF airway epithelia to the same extent as wild-type CFTR and showed no current in the absence of cAMP stimulation. In addition, expression in nasal mucosa of CF mice corrected the Cl- transport defect. These data provide insight into the structure and function of the R domain and identify regions that can be deleted with retention of function. Thus they suggest a strategy for shortening the transgene used in CF gene therapy.
Bezafibrate for X-Linked Adrenoleukodystrophy (2012)

ClinicalTrials.gov NCT01165060.
Iris recognition: an emerging biometric technology (1997)

This paper examines automated iris recognition as a biometrically based technology for personal identification and verification. The motivation for this endeavor stems from the observation that the human iris provides a particularly interesting structure on which to base a technology for noninvasive biometric assessment. In particular the biomedical literature suggests that irises are as distinct as fingerprints or patterns of retinal blood vessels. Further, since the iris is an overt body, its appearance is amenable to remote examination with the aid of a machine vision system. The body of this paper details issues in the design and operation of such systems. For the sake of illustration, extant systems are described in some amount of detail.
Performance analysis of experimentally viable photonic crystal enhanced thermophotovoltaic systems (2013)

One of the keys towards high efficiency thermophotovoltaic (TPV) energy conversion systems lies in spectral control. Here, we present detailed performance predictions of realistic TPV systems incorporating experimentally demonstrated advanced spectral control components. Compared to the blackbody emitter, the optimized two-dimensional (2D) tantalum (Ta) photonic crystal (PhC) selective emitter enables up to 100% improvement in system efficiency. When combined with the well characterized cold side tandem filter and the latest InGaAs TPV cells, a TPV energy conversion system with radiant heat-to-electricity efficiency of 25% and power density of 0.68 W cm(-2) is achievable today even at a relatively low temperature of 1320 K. The efficiency could be increased to ∼ 40% (the theoretical 0.62 eV single bandgap TPV thermodynamic limit at 1320 K is 55%) as future implementation of more optimized TPV cells approach their theoretical thermodynamic limit.