gebhart/patrepeval huggingface dataset:
Limiting the Persistence of a Chromosome Break Diminishes Its Mutagenic Potential (2009)

To characterize the repair pathways of chromosome double-strand breaks (DSBs), one approach involves monitoring the repair of site-specific DSBs generated by rare-cutting endonucleases, such as I-SceI. Using this method, we first describe the roles of Ercc1, Msh2, Nbs1, Xrcc4, and Brca1 in a set of distinct repair events. Subsequently, we considered that the outcome of such assays could be influenced by the persistent nature of I-SceI-induced DSBs, in that end-joining (EJ) products that restore the I-SceI site are prone to repeated cutting. To address this aspect of repair, we modified I-SceI-induced DSBs by co-expressing I-SceI with a non-processive 3' exonuclease, Trex2, which we predicted would cause partial degradation of I-SceI 3' overhangs. We find that Trex2 expression facilitates the formation of I-SceI-resistant EJ products, which reduces the potential for repeated cutting by I-SceI and, hence, limits the persistence of I-SceI-induced DSBs. Using this approach, we find that Trex2 expression causes a significant reduction in the frequency of repair pathways that result in substantial deletion mutations: EJ between distal ends of two tandem DSBs, single-strand annealing, and alternative-NHEJ. In contrast, Trex2 expression does not inhibit homology-directed repair. These results indicate that limiting the persistence of a DSB causes a reduction in the frequency of repair pathways that lead to significant genetic loss. Furthermore, we find that individual genetic factors play distinct roles during repair of non-cohesive DSB ends that are generated via co-expression of I-SceI with Trex2.
Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells (1996)

For some time it has been thought that antigenic challenge in neonatal life is a tolerogenic rather than immunogenic event. Reexamination of the classic neonatal tolerance experiments of Billingham, Brent, and Medawar showed that tolerance is not an intrinsic property of the newborn immune system, but that the nature of the antigen-presenting cell determines whether the outcome is neonatal tolerance or immunization.
A cone-beam reconstruction algorithm for circle-plus-arc data-acquisition geometry (1999)

In cone-beam computerized tomography (CT), projections acquired with the focal spot constrained on a planar orbit cannot provide a complete set of data to reconstruct the object function exactly. There are severe distortions in the reconstructed noncentral transverse planes when the cone angle is large. In this work, a new method is proposed which can obtain a complete set of data by acquiring cone-beam projections along a circle-plus-arc orbit. A reconstruction algorithm using this circle-plus-arc orbit is developed, based on the Radon transform and Grangeat's formula. This algorithm first transforms the cone-beam projection data of an object to the first derivative of the three-dimensional (3-D) Radon transform, using Grangeat's formula, and then reconstructs the object using the inverse Radon transform. In order to reduce interpolation errors, new rebinning equations have been derived accurately, which allows one-dimensional (1-D) interpolation to be used in the rebinning process instead of 3-D interpolation. A noise-free Defrise phantom and a Poisson noise-added Shepp-Logan phantom were simulated and reconstructed for algorithm validation. The results from the computer simulation indicate that the new cone-beam data-acquisition scheme can provide a complete set of projection data and the image reconstruction algorithm can achieve exact reconstruction. Potentially, the algorithm can be applied in practice for both a standard CT gantry-based volume tomographic imaging system and a C-arm-based cone-beam tomographic imaging system, with little mechanical modification required.
Prevention of Domain Swapping Inhibits Dimerization and Amyloid Fibril Formation of Cystatin C (2004)

Amyloidogenic proteins like cystatin C and prion proteins have been shown to form dimers by exchange of subdomains of the monomeric proteins. This process, called "three-dimensional domain swapping," has also been suggested to play a part in the generation of amyloid fibrils. One variant of cystatin C, L68Q cystatin C, is highly amyloidogenic, and persons carrying the corresponding gene suffer from massive cerebral amyloidosis leading to brain hemorrhage and death in early adult life. The present work describes the production of two variants of wild type and L68Q cystatin C with disulfide bridges at positions selected to inhibit domain swapping without affecting the biological function of the four cystatin C variants as cysteine protease inhibitors. The capacity of the four variant proteins to form dimers was tested and compared with that of wild type and L68Q cystatin C. In contrast to the latter two proteins, all four protein variants stabilized by disulfide bridges were resistant toward the formation of dimers. The capacity of the two stabilized variants of wild type cystatin C to form amyloid fibrils was investigated and found to be reduced by 80% compared with that of wild type cystatin C. In an effort to investigate whether exogenous agents could also suppress the formation of dimers of wild type and L68Q cystatin C, a monoclonal antibody or carboxymethylpapain, an inactivated form of a cysteine protease, was added to systems inducing dimerization of wild type and L68Q cystatin C. It was observed that catalytic amounts of both the monoclonal antibody and carboxymethylpapain could suppress dimerization.
Biochemical and physiological function of stearoyl-CoA desaturase (2008)

A key and highly regulated enzyme that is required for the biosynthesis of monounsaturated fatty acids is stearoyl-CoA desaturase (SCD), which catalyzes the D(9)-cis desaturation of a range of fatty acyl-CoA substrates. The preferred substrates are palmitoyl- and stearoyl-CoA, which are converted into palmitoleoyl- and oleoyl-CoA respectively. Oleate is the most abundant monounsaturated fatty acid in dietary fat and is therefore readily available. Studies of mice that have a naturally occurring mutation in the SCD-1 gene isoform as well as a mouse model with a targeted disruption of the SCD gene (SCD-1(-/-)) have revealed the role of de novo synthesized oleate and thus the physiological importance of SCD-1 expression. SCD-1 deficiency results in reduced body adiposity, increased insulin sensitivity, and resistance to diet-induced obesity. The expression of several genes of lipid oxidation are upregulated, whereas lipid synthesis genes are downregulated. SCD-1 was also found to be a component of the novel metabolic response to the hormone leptin. Therefore, SCD-1 appears to be an important metabolic control point, and inhibition of its expression could be of benefit for the treatment of obesity, diabetes, and other metabolic diseases. In this article, we summarize the recent and timely advances concerning the important role of SCD in the biochemistry and physiology of lipid metabolism.
Analysis of the solubility behaviour of irradiated polyethylene and other polymers (1959)

Abstract The equation for the sol fraction (s) of a cross-linked polymer network becomes readily tractable when applied to special cases of the generalized distribution function n(u) = C(u/u1)λ-1 exp ( — λu/u1). For values of λ = ∞, 1 and 0 respectively, this function yields the uniform distribution, the exponential distribution and a hypothetical pseudo-random distribution. Assuming that cross-linking and fracture occur at random and in proportion to the radiation dose, simple expressions are derived relating sol fraction to radiation dose (r) for each of the three distributions. The most useful of these is the relation involving the fracture density per unit dose (p0) and the density of cross-linked units per unit dose (q0). s+√s = p0/q0 + 1/q0u1r. This holds strictly for exponential distributions, whether or not main-chain fracture occurs simultaneously with cross-linking, and also holds at high doses for the other distributions considered, providing that cross-linking is accompanied by fracture. This treatment is applied to experimental results on low-density and high-density polyethylenes, polyvinyl acetates, polyvinyl chloride, polypropylene and polyalkyl acrylates. The relevant radiation parameters p0, q0 and the corresponding G values are deduced. It is found, in the case of polyethylene, that q0 is, within experimental error independent of the molecular weight, degree of branching or crystallinity, but is affected by the presence of air. Similar values of q0 are also observed for polyvinyl acetate and polyvinyl chloride.
Preliminary Evaluation of the Use of Mussel Adhesive Protein in Experimental Epikeratoplasty (1988)

We have used a preliminary formulation of a bioadhesive in an experimental model of epikeratoplasty in rabbits. The adhesive, termed mussel adhesive protein (MAP), is a repeating decapeptide polymer that is the natural adhesive substance produced by the common blue mussel (Mytilus edulis) and is used here in conjunction with an enzymatic cross-linking agent. This study marked the first in vivo use of this material in adhering ophthalmic tissue planes. We used a simplified epikeratoplasty technique highlighted by freehand dissection of donor lenticules and host keratotomies. Approximately 10 microL of a combination of MAP and the cross-linking agent was applied directly to the host cornea and the donor lenticules were secured into the keratotomies using eight interrupted 10-0 nylon sutures. All of the sutures were removed 72 hours postoperatively. Eleven of the 15 animals retained their epikeratoplasty lenticules throughout the entire postoperative period. Four animals had initially intact lenticules that sloughed within the first postoperative week; this sloughing, we believe, was attributable to difficulties in tucking irregularly thickened lenticule edges into the keratotomy. In control animals that had lenticules secured with sutures alone, suture removal at 72 hours consistently produced immediate lenticule sloughing. Clinical examinations and histopathologic studies disclosed no untoward effects of the adhesive on the donor or host corneal tissue. We believe that this preliminary study indicates a potential adjunctive role for MAP in epikeratoplasty.
Kalman filtering for real-time orientation tracking of handheld microsurgical instrument (2005)

This paper presents the theory and modeling of a quaternion-based augmented state Kalman filter for real-time orientation tracking of a handheld microsurgical instrument equipped with a magnetometer-aided all-accelerometer inertial measurement unit (IMU). The onboard sensing system provides two complementary sources of orientation information. The all-accelerometer IMU provides a high resolution but drifting angular velocity estimate, while the magnetic north vector is combined with the estimated gravity vector to yield a non-drifting but noisy orientation estimate. Analysis of the dominant stochastic noise components of the sensors and derivation of the noise covariance are presented. The proposed Kalman filter obtains a non-drifting orientation estimate with improved resolution by incorporating the motion dynamics of the instrument during microsurgery and models the angular velocity drift explicitly as extra dynamic states.
Characterization of Cre–loxP interaction in the major groove: Hint for structural distortion of mutant Cre and possible strategy for HIV‐1 therapy (2001)

Although the crystal structure of Cre recombinase complexed with DNA, named loxA, was elucidated a couple of years ago, it has not yet been determined which amino acids of the protein are involved in the specific Cre–loxP interaction. Arg259 and Gln90 interact with DNA substrate in the major groove from which the specificity of protein–DNA interaction comes. In this study, we substituted these residues for other amino acids. Also, two mutated DNA substrates were constructed. In each mutant, one of the bases that interact with Arg259 or Gln90 was changed into another base. In vitro binding assays and recombination assays of variant lox sites with wild-type and mutant-type Cre revealed that Arg259 plays a key role in Cre–loxP binding but Gln90 does not. However, the recombination activity still remained intact, although the binding between Cre and DNA substrate was not ensured. J. Cell. Biochem. 80:321–327, 2001. © 2001 Wiley-Liss, Inc.
Structural and Functional Modeling of Human Lysozyme Reveals a Unique Nonapeptide, HL9, with Anti-HIV Activity (2005)

We previously reported that lysozyme accounts for anti-HIV activity associated with the beta-core fraction of human chorionic gonadotropin [Lee-Huang, S., Huang, P. L., Sun, Y., Kung, H. F., Blithe, D. L. & Chen, H. C. (1999) Proc Natl Acad Sci U S A 96, 2678-81]. To define the structural and sequence requirements for anti-HIV activity, we carried out peptide fragmentation and activity mapping of human lysozyme. We identified two peptides that consist of 18 and 9 amino acids of human lysozyme (HL18 and HL9), corresponding to residues 98-115 and 107-115. HL18 and HL9 are potent inhibitors of HIV-1 infection and replication with EC(50)s of 50 to 55 nM, comparable to intact lysozyme. Scrambling the sequence or substitution of key arginine or tryptophan residues results in loss of antiviral activity. HL9, with the sequence RAWVAWRNR, is the smallest peptide we identified with full anti-HIV activity. It forms a pocket with its basic residues on the surface of the molecule. HL9 exists as an alpha-helix in native human lysozyme, in a region of the protein distinct from the muramidase catalytic site. Monte Carlo peptide folding energy minimizing simulation modeling and CD studies indicate that helical propensity does not correlate with antiviral activity. HL9 blocks HIV-1 viral entrance and replication, and modulates gene expression of HIV-infected cells, affecting pathways involved in survival, stress, TGFbeta, p53, NFkappaB, protein kinase C and hedgehog signaling.
TWO-DIMENSIONAL ELECTRONS IN FIELD EFFECT TRANSISTORS (1998)

In deep submicron silicon MOSFETs, GaAs-based HEMTs, and in new emerging heterostructure systems, such as AlGaN/GaN, electrons forming a two-dimensional (2D) conducting channel exhibit new interesting effects that might find important device applications. Some of these effects are related to the space dependence of the electron mass. Other effects are linked to a large sheet electron concentration, when electrons behave not as a 2D gas but rather as a 2D electron electron fluid. We consider plasma effects in this fluid and discuss plasma wave electronic devices that rely on these effects. We also discuss the properties of 2D electrons in silicon devices, where plasma effects might also play an important role in deep submicron MOSFETs.
A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae (1999)

Vaccinia virus (VV) proteins that interfere with the host response to infection are of interest because they provide insight into virus-host relationships and may affect the safety and immunogenicity of recombinant VV (rVV) vaccines. Such vaccines need assessment in animal models and with this aim a model of VV infection based on intradermal injection of BALB/c ear pinnae was developed and characterized. In this model, the outcome of infection is affected by the dose of virus inoculated but virus spread is minimal and the mice suffer no signs of systemic illness. Cellular and humoral immune responses to these infections were measured readily and were independent of virus dose over a 100-fold range. Thus the model seems suitable for the analysis of the safety and immunogenicity of VV mutants lacking specific immunomodulatory proteins or bearing foreign antigens.
A double blind comparison of the effects of fluoxetine and amitriptyline on cognitive function in elderly depressed patients (1993)

Abstract Sixty‐six elderly depressed patients received fluoxetine 20 mg (FLU) or amitriptyline 75 mg (AMI) for 42 days in a double blind parallel group study. Each week, subjects completed a test battery which is sensitive to the residual effects of psychoactive drugs. The results show that FLU and AMI were equally effective in relieving depression. However, the psychometric test battery showed that, compared to FLU, AMI, as expected, produced impairments in cognitive function and psychomotor performance. The relative impairment of cognitive and psychomotor skills following the tricyclic AMI and the lack of such activity after administration of the selective serotonin reuptake inhibition, FLU are important considerations when prescribing antidepressants, especially when the safety and well being of ambulant patients is essential.
Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study (2001)

The frequency of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CdAD) was prospectively determined in a population of 2462 patients recruited from five Swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. AAD developed in 4.9% of the treated patients. Faecal samples were obtained from 69% of patients with AAD and 55.4% were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9% at the participating centres (P < 0.001). The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units (6.7 and 7.1%, respectively). There was no difference in frequency of AAD when analysed with respect to gender or age. Medical interventions (laxative treatment, endoscopy and abdominal surgery) or presence of one concomitant disease (diabetes, malignancy, chronic renal disease and inflammatory bowel disease) did not significantly affect the frequency of AAD, whereas patients suffering from two or more of these illnesses had significantly (P = 0.001) higher frequencies of AAD. Patients treated with antibiotics for 3 days had a significantly (P = 0.009) lower frequency of AAD than those treated for longer periods. Treatment with cephalosporins, clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD. With specimens from one centre, 62.5% of tested patients with AAD and 33.8% of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool samples was significantly associated with AAD (P = 0.003), the causal relationship with diarrhoea is not always evident.
Heparin, Its Fractions, Fragments and Derivatives Some Newer Perspectives (1985)

A brief attempt has been made to provide an overview of the field of heparinology. As stated, in coming years one should witness significant developments in this area. It is, however, important to caution that the newer products derived from heparin may not behave like heparin, and one must consider their individual molecular and biochemical interactions. The available limited data on heparin may or may not be applicable to the newer heparin fractions or derivatives. Independent preclinical and clinical trials are needed to investigate the pharmacology and therapeutic actions of newer heparin derivatives.
Two Multiplex Assays That Simultaneously Identify 22 Possible Mutation Sites in the KRAS, BRAF, NRAS and PIK3CA Genes (2010)

Recently a number of randomized trials have shown that patients with advanced colorectal cancer do not benefit from therapies targeting the epidermal growth factor receptor when their tumors harbor mutations in the KRAS, BRAF and PIK3CA genes. We developed two multiplex assays that simultaneously screen 22 nucleotides in the KRAS, NRAS, BRAF and PIK3CA genes for mutations. The assays were validated on 294 tumor DNA samples from patients with advanced colorectal cancer. In these samples 119 KRAS codon 12 and 13 mutations had been identified by sequence analysis, 126 tumors were wild-type for KRAS and the analysis failed in 49 of the 294 samples due to poor DNA quality. The two mutation assays detected 130 KRAS mutations, among which were 3 codon 61 mutations, and in addition 32 PIK3CA, 13 BRAF and 6 NRAS mutations. In 19 tumors a KRAS mutation was found together with a mutation in the PIK3CA gene. One tumor was mutant for both PIK3CA and BRAF. In summary, the mutations assays identified 161 tumors with a mutation, 120 were wild-type and the analysis failed in 13. The material cost of the 2 mutation assays was calculated to be 8-fold lower than the cost of sequencing required to obtain the same data. In addition, the mutation assays are less labor intensive. We conclude that the performance of the two multiplex mutation assays was superior to direct sequencing. In addition, these assays are cheaper and easier to interpret. The assays may also be of use for selection of patients with other tumor types.
Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development (2003)

Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to direct either T helper cell (Th) type 1 or Th2 development, although more recently different pathogen products or stimuli have been shown to render these DCs more flexible. It is still unclear how distinct mouse DC subsets cultured from bone marrow precursors, blood, or their lymphoid tissue counterparts direct Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can induce the development of both Th1 and Th2 effector cells depending on the dose of antigen. In general, high antigen doses induced Th1 cell development whereas low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic plasmacytoid-derived DCs enhanced CD4(+) T cell proliferation and induced strong Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage colony-stimulating factor enhanced Th1 cell development when stimulated with LPS as a result of their high level of TLR4 expression. Polarized Th1 responses resulting from high antigen dose were not additionally enhanced by stimulation of DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops.
Deep Representation Learning for Human Motion Prediction and Classification (2017)

Generative models of 3D human motion are often restricted to a small number of activities and can therefore not generalize well to novel movements or applications. In this work we propose a deep learning framework for human motion capture data that learns a generic representation from a large corpus of motion capture data and generalizes well to new, unseen, motions. Using an encoding-decoding network that learns to predict future 3D poses from the most recent past, we extract a feature representation of human motion. Most work on deep learning for sequence prediction focuses on video and speech. Since skeletal data has a different structure, we present and evaluate different network architectures that make different assumptions about time dependencies and limb correlations. To quantify the learned features, we use the output of different layers for action classification and visualize the receptive fields of the network units. Our method outperforms the recent state of the art in skeletal motion prediction even though these use action specific training data. Our results show that deep feedforward networks, trained from a generic mocap database, can successfully be used for feature extraction from human motion data and that this representation can be used as a foundation for classification and prediction.