gebhart/patrepeval huggingface dataset:
Somatic hypermutation of an artificial test substrate within an Ig kappa transgene. (1998)

We have characterized a novel substrate for somatic hypermutation, confirming that non-Ig sequences can be targeted for mutation and demonstrating that this substrate allows for the rapid assay for mutations. An artificial sequence containing alternating EcoRV and PvuII sites (EPS) was inserted into the Vkappa167 transgene, which is known to be a target for mutation. To assay for somatic hypermutation, the EPS is amplified using flanking transgene primers, and the PCR product is subsequently digested with either EcoRV or PvuII. A mutation is seen as the appearance of a larger fragment, indicating a base change in a restriction enzyme site. The original transgene, Vkappa167/EPS, showed evidence of a low level of mutation in both splenic hybridomas and Peyer's patch-derived or immunized splenic B220+ cells with high peanut agglutinin levels. Two derivative lines of Vkappa167/EPS were made, Vkappa167/POX and Vkappa167/PEPS. While none of the Vkappa167/POX transgenic lines demonstrated mutation, the Vkappa167/PEPS transgene was highly mutated in B220+ splenic B cells with high peanut agglutinin levels at a frequency similar to that of endogenous Ig genes. An analysis of splenic RNA from the unimmunized transgenic mice indicated that the levels of stable message in splenic B cells could not be correlated with the mutation seen in GC B cells. The mutable Vkappa167/PEPS transgenic line is a unique tool to study somatic hypermutation in vivo.
A pilot study of PLX3397, a selective colony-stimulating factor 1 receptor (CSF1R) kinase inhibitor, in pigmented villonodular synovitis (PVNS). (2014)

10503^ Background: PLX3397 is a novel, oral small molecule that potently and selectively inhibits CSF1R, Kit, and Flt3 kinases. CSF1R and Kit regulate key components of both the tumor and its microenvironment (macrophages, osteoclasts, mast cells). PVNS is a rare proliferative neoplasm involving the synovium of joints or tendon sheaths. Tumors contain CSF1R-bearing macrophages recruited by local overexpression of CSF-1 due to a gene translocation. Methods: Patients (pts) with advanced PVNS were enrolled onto an expansion cohort of an ongoing single-arm, multicenter, clinical study. PLX3397 was given orally, 1000 mg daily (600 mg AM, 400 mg PM – 28 day cycles). MRI assessment by a central musculoskeletal radiologist blinded to chronology was performed every 2 cycles using a novel Tumor Volume Score (TVS) developed specifically for PVNS. Partial response (PR) was defined as ≥50% decrease in TVS compared to screening and progressive disease was ≥30% increase relative to lowest score. Patients remained on treatment until disease progression or intolerability. Results: 17 PVNS pts have been enrolled to date. Median exposure 166 days (range 23- 264). 59% pts were women; median age 46 yrs (range 22-80). Tumor locations: knees (12), ankles (2), feet (2), elbow (1). Of the 11 pts with evaluable MRI scans at this interim analysis, 7 pts (64%) achieved a PR and 4 pts (36%) had stable disease (SD). Mean tumor size reduction was 51% (range: -10% to -88%). Clinical improvements were seen in pain, stiffness, and overall function. Common AEs (>10%): fatigue, nausea, hair color changes, and diarrhea. Treatment-related AEs ≥Grade 3: anemia (1), hyponatremia (2), elevated ALT and AST (1), fatigue (1) and diarrhea (1). Conclusions: PLX3397 was well tolerated and demonstrated profound activity as measured by a novel response criterion in pts with advanced PVNS. PLX3397 warrants further study in a larger clinical trial. Clinical trial information: NCT01004861.Percent change in TVS compared to screening. Patient Cycle Best response 3 5 7 9 1 -64% -40% -68% -64% PR 2 -85% -85% -87% -88% PR 3 -50% -50% -50% -58% PR 4 -60% -75% - -83% PR 5 -13% -13% -13% - SD 6 -42% -50% -58% - PR 7 -5% -10% - - SD 8 -40% - - - SD 9 -43% -57% - - PR 10 -50% - - - PR 11 -39% - - - SD
CP-690550, a Janus Kinase Inhibitor, Suppresses CD4+ T-Cell–Mediated Acute Graft-Versus-Host Disease by Inhibiting the Interferon-γ Pathway (2010)

The targeting of Janus kinase with a sensitive and specific inhibitor, CP-690550, conferred effective protection from acute GVHD induced by a semiallogeneic major histocompatibility complex class II-disparate combination. Protection from acute GVHD was largely mediated by the inhibition of IFN-γ production.
Absence of T Cells Confers Increased Pulmonary Arterial Hypertension and Vascular Remodeling (2007)

These studies demonstrate the importance of a complete, intact immune system in protecting against pulmonary angioproliferation in this new model of SPH as well as the importance of intact VEGF receptor signaling for lung endothelial cell homeostasis.
Ustekinumab Induction and Maintenance Therapy in Refractory Crohn's Disease (2012)

Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.).
Free radical catalysed additions to the double bond of diketene: a synthesis of novel oxetan-2-ones (1986)

Free radical-catalysed additions to the exocyclic double bond of diketene are described. Thiols give unstable 4-thiomethyloxetan-2-one adducts which could be oxidised to their more stable sulphoxides or sulphones. Addition of a range of P–H compounds led, with a few exceptions, to stable phosphorus-substituted 4-methyloxetan-2-ones. The radical-catalysed chlorination of diketene by sulphuryl chloride has been shown to give 4-chloro-4-chloromethyloxetan-2-one. Further 4-halogeno-oxetan-2-ones were prepared by addition of halocarbons such as carbon tetrachloride, bromotrichloromethane, and carbon tetrabromide and of trichloromethanesulphenyl chloride to diketene.
Hematopoietic Stem Cell Quiescence Maintained by p21 cip1/waf1 (2000)

Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G1 checkpoint regulator, cyclin-dependent kinase inhibitor, p21cip1/waf1 (p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle-specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21-/- mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death.
Multiple indications for anti-inflammatory apolipoprotein mimetic peptides. (2008)

Apolipoprotein mimetic peptides dramatically reduce atherosclerosis in animal models, and may be an excellent mode of therapy to treat a variety of vascular inflammatory conditions, including atherosclerosis. Studies of apolipoprotein mimetic peptides in models of inflammatory disorders other than atherosclerosis, including viral influenza, asthma, chronic rejection after heart transplantation, sickle cell disease, scleroderma, diabetes, cognitive dysfunction and renal inflammation, suggest that apolipoprotein mimetic peptides may have efficacy in a wide range of inflammatory conditions.
Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer (2000)

p53 tumour suppressor gene alterations are one of the most frequent genetic events in lung cancer. A subset of patients with p53 mutation and cancer exhibited circulating serum anti-p53 self-antibodies (p53-Ab). The prevalence of these antibodies in lung cancer is currently being analysed in a multicentric study. In a group of homogeneous SCLC patients, p53-Ab were detected in 20/97 (20.6%) individuals. In this group of patients, Cox's multivariate analysis identified disease extent (p = 0.022), WHO initial performance status greater than 0 (p = 0.005), and the absence of a complete response after 6 months of treatment (p < 0.0001) as independent prognostic variables, with p53-Ab being of borderline significance (p = 0.051). In the subset of limited-stage SCLC patients, Cox's multivariate analysis found p53-Ab (p = 0.033), WHO initial performance status greater than 0 (p = 0.028), and absence of a complete response (p < 0.001) to be independent prognostic variables. Thus, actuarial analysis showed that patients with limited-stage SCLC and p53-Ab had a median survival time of 10 months, whereas limited-stage SCLC patients without p53-Ab had a 17-month median survival time (p = 0.014).Therefore, serum assay of p53-Ab could help to identify a population of SCLC patients with an especially poor prognosis. This population could represent patients with tumours harboring aggressive p53 mutations.
Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis (2004)

Natural killer (NK) cells constitute the first line of host defense against invading pathogens. They usually become activated in an early phase of a viral infection. Liver is particularly enriched in NK cells, which are activated by hepatotropic viruses such as hepatitis C virus (HCV). The activated NK cells play an essential role in recruiting virus-specific T cells and in inducing antiviral immunity in liver. They also eliminate virus-infected hepatocytes directly by cytolytic mechanisms and indirectly by secreting cytokines, which induce an antiviral state in host cells. Therefore, optimally activated NK cells are important in limiting viral replication in this organ. This notion is supported by the observations that interferon treatment is effective in HCV-infected persons in whom it increases NK cell activity. Not surprisingly, HCV has evolved multiple strategies to counter host's NK cell response. Compromised NK cell functions have been reported in chronic HCV-infected individuals. It is ironic that activated NK cells may also contribute toward liver injury. Further studies are needed to understand the role of these cells in host defense and in liver pathology in HCV infections. Recent advances in understanding NK cell biology have opened new avenues for boosting innate and adaptive antiviral immune responses in HCV-infected individuals.
Enhanced repair of extensive articular defects by insulin‐like growth factor‐I‐laden fibrin composites (1999)

Stem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repair. Insulin-like growth factor-I facilitates chondrogenesis of bone marrow-derived stem cells in long-term culture and may enhance chondrogenesis in healing cartilage lesions in vivo. This study examined the impact of insulin-like growth factor-I, gradually released from fibrin clots polymerized in situ, on the recruitable stem-cell pool in a full-thickness critical cartilage defect model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by an injection of autogenous fibrin containing 25 microg of human recombinant insulin-like growth factor-I or, in control joints, fibrin without the growth factor. All horses were killed at 6 months, and cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, types I and II collagen immunohistochemistry, types I and II collagen in situ hybridization, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor-treated defects being more completely filled and securely attached to the subchondral bone. A moderately improved chondrocyte population, more columnar cellular organization, and better attachment to the underlying bone were evident on histological evaluation of growth factor-treated defects. Type-II procollagen mRNA was abundantly present in the deeper half of the treated sections compared with moderate message expression in control tissues. Immunolocalization of type-II collagen showed a preponderance of the collagen in growth factor-treated lesions, confirming translation of type-II message to protein. Composite histologic healing scores for treated defects were significantly improved over those for control defects. DNA content in the cartilage defects was similar in treated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surrounding and remote cartilage of the treated and control joints. The proportion of type-II collagen significantly increased in growth factor-treated tissues. Fibrin polymers laden with insulin-like growth factor-I improved the histologic appearance and the proportion of type-II collagen in healing, full-thickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.
Microorganisms: Extremely Thermophilic (2009)

Abstract Extremely thermophilic microorganisms ( T opt ≥ 70°C) are found in geographically diverse marine and terrestrial environments and represent a wide range of growth physiologies. Extreme thermophiles thrive at high temperatures and, as such, different approaches must be taken to cultivate them in laboratory settings. Genome sequences of many extreme thermophiles have been completed and offer a glimpse into the basis for their high temperature life styles. A number of biotechnological applications have been envisioned that take strategic advantage of their thermophilicity, including the production of biohydrogen and recovery of base and precious metals from ores. As genetic systems are developed and implemented for extreme thermophiles, metabolic engineering approaches will be possible to tune the unique characteristics of these microorganisms for bioprocessing uses.
A novel digital tomosynthesis (DTS) reconstruction method using a deformation field map (2008)

We developed a novel digital tomosynthesis (DTS) reconstruction method using a deformation field map to optimally estimate volumetric information in DTS images. The deformation field map is solved by using prior information, a deformation model, and new projection data. Patients' previous cone-beam CT (CBCT) or planning CT data are used as the prior information, and the new patient volume to be reconstructed is considered as a deformation of the prior patient volume. The deformation field is solved by minimizing bending energy and maintaining new projection data fidelity using a nonlinear conjugate gradient method. The new patient DTS volume is then obtained by deforming the prior patient CBCT or CT volume according to the solution to the deformation field. This method is novel because it is the first method to combine deformable registration with limited angle image reconstruction. The method was tested in 2D cases using simulated projections of a Shepp-Logan phantom, liver, and head-and-neck patient data. The accuracy of the reconstruction was evaluated by comparing both organ volume and pixel value differences between DTS and CBCT images. In the Shepp-Logan phantom study, the reconstructed pixel signal-to-noise ratio (PSNR) for the 60 degrees DTS image reached 34.3 dB. In the liver patient study, the relative error of the liver volume reconstructed using 60 degrees projections was 3.4%. The reconstructed PSNR for the 60 degrees DTS image reached 23.5 dB. In the head-and-neck patient study, the new method using 60 degrees projections was able to reconstruct the 8.1 degrees rotation of the bony structure with 0.0 degrees error. The reconstructed PSNR for the 60 degrees DTS image reached 24.2 dB. In summary, the new reconstruction method can optimally estimate the volumetric information in DTS images using 60 degrees projections. Preliminary validation of the algorithm showed that it is both technically and clinically feasible for image guidance in radiation therapy.
Inhibitory Effects of Specific Apolipoprotein C-III Isoforms on the Binding of Triglyceride-rich Lipoproteins to the Lipolysis-stimulated Receptor (1997)

ApoC-III overexpression in mice results in severe hypertriglyceridemia due primarily to a delay in the clearance of triglyceride-rich lipoproteins. We have, in primary cultures of rat hepatocytes, characterized a lipolysis-stimulated receptor (LSR). The apparent number of LSR that are available on rat liver plasma membranes is negatively correlated with plasma triglyceride concentrations measured in the fed state. We therefore proposed that the primary physiological role of the LSR is to contribute to the cellular uptake of triglyceride-rich lipoproteins. We have now tested the effect of apoC-III on the binding of triglyceride-rich lipoproteins to LSR. Supplementation of 125I-very low density lipoprotein (VLDL) with apoC-III inhibited the LSR-mediated binding, internalization, and degradation of 125I-VLDL in primary cultures of rat hepatocytes. Studies using isolated rat liver plasma membranes showed that enrichment of human VLDL and chylomicrons with synthetic or purified human apoC-III decreased their binding to the LSR by about 40%. Supplementation of triglyceride-rich lipoproteins under the same conditions with human apoC-II had no such inhibitory effect, despite the fact that this apoprotein bound as efficiently as apoC-III to these particles. Preincubation of LDL with apoC-III did not modify its binding to LSR. Partitioning studies using 125I-apoC-III showed that this lack of effect was due to apoC-III's inability to efficiently associate with LDL. Purified human apoC-III1 was as efficient as the synthetic nonsialylated form of apoC-III in inhibiting binding of VLDL to LSR. However, despite a 2-fold greater binding of apoC-III2 to VLDL, this isoform was a less efficient inhibitor of the binding of VLDL to LSR than apoC-III1 or nonsialylated apoC-III. Desialylation of apoC-III2 by treatment with neuraminidase increased the inhibition of VLDL binding to LSR to a level similar to that observed with apoC-III1 and nonsialylated apoC-III. We propose that apoC-III regulates in part the rate of removal of triglyceride-rich particles by inhibiting their binding to the LSR, and that the level of inhibition is determined by the degree of apoC-III sialylation.
A Short Note about Kinetics-600 (2018)

We describe an extension of the DeepMind Kinetics human action dataset from 400 classes, each with at least 400 video clips, to 600 classes, each with at least 600 video clips. In order to scale up the dataset we changed the data collection process so it uses multiple queries per class, with some of them in a language other than english -- portuguese. This paper details the changes between the two versions of the dataset and includes a comprehensive set of statistics of the new version as well as baseline results using the I3D neural network architecture. The paper is a companion to the release of the ground truth labels for the public test set.
A general approach to the reconstruction of x‐ray helical computed tomography (1996)

Helical Computed Tomography (HCT) has become the method of choice for many routine clinical studies. The advantages of HCT include the capability of scanning a complete anatomical volume in a single breath hold, the capability of generating images at any desired location, and the improved patient throughput. However, these advantages come at the expense of some image quality compromises. This is mainly caused by the fact that the projection set is inherently incomplete and inconsistent, due to the constant patient translation during the data acquisition process. In this paper, we will briefly review the research work performed in this area and present a more general approach to the problem. We give two specific examples of the general approach and compare the performance of one of the examples with one of the best methods available today.
Striving for Simplicity: The All Convolutional Net (2014)

Most modern convolutional neural networks (CNNs) used for object recognition are built using the same principles: Alternating convolution and max-pooling layers followed by a small number of fully connected layers. We re-evaluate the state of the art for object recognition from small images with convolutional networks, questioning the necessity of different components in the pipeline. We find that max-pooling can simply be replaced by a convolutional layer with increased stride without loss in accuracy on several image recognition benchmarks. Following this finding -- and building on other recent work for finding simple network structures -- we propose a new architecture that consists solely of convolutional layers and yields competitive or state of the art performance on several object recognition datasets (CIFAR-10, CIFAR-100, ImageNet). To analyze the network we introduce a new variant of the "deconvolution approach" for visualizing features learned by CNNs, which can be applied to a broader range of network structures than existing approaches.
In Vivo Incorporation of Unnatural Amino Acids into Proteins (2000)

Abstract : A method for the site-specific incorporation of unnatural amino acids into proteins in vivo would significantly facilitate studies of the cellular function of proteins, as well as make possible the biosynthesis of unnatural polymers and proteins with novel structures and activities. Our approach consists of the generation of amber suppressor tRNA/aminoacyl-tRNA synthetase pair that are not catalytically competent with all the endogenous Escherichia coli tRNAs an aminoacyl-tRNA synthetases, followed by directed evolution of such orthogonal aminoacyl-tRNA synthetases to alter their amino acid specificities. A new orthogonal suppressor tRNA/aminoacyl-tRNA synthetase pair in E. coli has been derived from the Saccharomyces cerevisiae tRNA (sub Asp) and aspartyl-tRNA syathetase, and the in vitro and in vivo characteristics of this pair were determined. In order to achieve a high specificity for the amino acid, a direct selection for site-specific incorporation of unnatural amino acids into a reporter epitope displayed on the surface of M13 phage has been developed and characterized. Under simulated selection conditions, phage particles displaying aspartate were enriched over 300-fold from a pool of phage displaying asparagine using monoclonal antibodies raised against the aspartate-containing epitope. The direct phage selection offers very high specificity for the amino acid of interest, Which cannot be achieved by conventional methods.
Membrane damage: common mechanisms of induction and prevention (1992)

Common features in the induction of pores by various agents are as follows: induction is stochastic and progressive; damage by different agents is often synergistic and limited. The prevention of membrane damage is affected by trivalent and divalent cations, by low pH, by low ionic strength and by high osmotic pressure. The inhibitory role of protons and divalent cations is considered in greater detail: pore-forming agents can be classified into two groups: channels across planar lipid bilayers induced by the first group display voltage-sensitive, reversible inhibition by divalent cations; channels of the second group show voltage-insensitive, irreversible inhibition by divalent cations. A search for the ligands to which divalent cations and protons bind has proved elusive. Comparison with the phenomenon of 'surface conductance' through narrow apertures, that is manifest in the absence of any pore-forming agent, may prove fruitful.