gebhart/patrepeval huggingface dataset:
Protein splicing in trans by purified N- and C-terminal fragments of the Mycobacterium tuberculosis RecA intein (1998)

Protein splicing involves the self-catalyzed excision of protein splicing elements, or inteins, from flanking polypeptide sequences, or exteins, leading to the formation of new proteins in which the exteins are linked directly by a peptide bond. To study the enzymology of this interesting process we have expressed and purified N- and C-terminal segments of the Mycobacterium tuberculosis RecA intein, each approximately 100 amino acids long, fused to appropriate exteins. These fragments were reconstituted into a functional protein splicing element by renaturation from 6 M urea. When renaturation was carried out in the absence of thiols, the reconstituted splicing element accumulated as an inactive disulfide-linked complex of the two intein fragments, which could be induced to undergo protein splicing by reduction of the disulfide bond. This provided a useful tool for separately investigating the requirements for the reconstitution of the intein fragments to yield a functional protein splicing element and for the protein splicing process per se. For example, the pH dependence of these processes was quite different, with reconstitution being most efficient at pH 8.5 and splicing most rapid at pH 7.0. The availability of such an in vitro protein splicing system opens the way for the exploration of intein structure and the unusual enzymology of protein splicing. In addition, this trans-splicing system is a potential protein ligase that can link any two polypeptides fused to the N- and C-terminal intein segments.
Integrality and separability of input devices (1994)

Current input device taxonomies and other frameworks typically emphasize the mechanical structure of input devices. We suggest that selecting an appropriate input device for an interactive task requires looking beyond the physical structure of devices to the deeper perceptual structure of the task, the device, and the interrelationship between the perceptual structure of the task and the control properties of the device. We affirm that perception is key to understanding performance of multidimensional input devices on multidimensional tasks. We have therefore extended the theory of processing of percetual structure to graphical interactive tasks and to the control structure of input devices. This allows us to predict task and device combinations that lead to better performance and hypothesize that performance is improved when the perceptual structure of the task matches the control structure of the device. We conducted an experiment in which subjects performed two tasks with different perceptual structures, using two input devices with correspondingly different control structures, a three-dimensional tracker and a mouse. We analyzed both speed and accuracy, as well as the trajectories generated by subjects as they used the unconstrained three-dimensional tracker to perform each task. The result support our hypothesis and confirm the importance of matching the perceptual structure of the task and the control structure of the input device.
Cloned Antigens and Antiidiotypes (1995)

Both monoclonal and polyclonal antiidiotypic antibodies mimicking the human colorectal carcinoma (CRC) associated antigen CO17-1A/GA733 have induced antigen-specific humoral and cellular immunity in CRC patients. The immune responses may underlie the clinical responses observed in some of the treated patients. Recently, the CO17-1A/GA733 antigen has been molecularly cloned and expressed in baculo-, adeno-, and vaccinia viruses. In preclinical studies, these recombinant antigen preparations elicited specific humoral immunity (cytotoxic antibodies) and cellular immunity (DTH-reactive and proliferative T cells). Antibody titers elicited in animals by recombinant antigen were significantly higher than those elicited by antiidiotypes. The recombinant antigen has a potential as a vaccine for CRC patients.
Epitomic location recognition (2008)

This paper presents a novel method for location recognition, which exploits an epitomic representation to achieve both high efficiency and good generalization. A generative model based on epitomic image analysis captures the appearance and geometric structure of an environment while allowing for variations due to motion, occlusions and non-Lambertian effects. The ability to model translation and scale invariance together with the fusion of diverse visual features yield enhanced generalization with economical training. Experiments on both existing and new labelled image databases result in recognition accuracy superior to state of the art with real-time computational performance.
Conditionally Stabilized dCas9 Activator for Controlling Gene Expression in Human Cell Reprogramming and Differentiation (2015)

CRISPR/Cas9 protein fused to transactivation domains can be used to control gene expression in human cells. In this study, we demonstrate that a dCas9 fusion with repeats of VP16 activator domains can efficiently activate human genes involved in pluripotency in various cell types. This activator in combination with guide RNAs targeted to the OCT4 promoter can be used to completely replace transgenic OCT4 in human cell reprogramming. Furthermore, we generated a chemically controllable dCas9 activator version by fusion with the dihydrofolate reductase (DHFR) destabilization domain. Finally, we show that the destabilized dCas9 activator can be used to control human pluripotent stem cell differentiation into endodermal lineages.
The Effects of Different Electrical Stimulation Protocols on Nerve Regeneration Through Silicone Conduits (2004)

Stimulation protocols had significant influences on the benefit of electrical stimulation in nerve regeneration.
Wnt Proteins Prevent Apoptosis of Both Uncommitted Osteoblast Progenitors and Differentiated Osteoblasts by β-Catenin-dependent and -independent Signaling Cascades Involving Src/ERK and Phosphatidylinositol 3-Kinase/AKT (2005)

Genetic studies in humans and mice have revealed an important role of the Wnt signaling pathway in the regulation of bone mass, resulting from potent effects on the control of osteoblast progenitor proliferation, commitment, differentiation, and perhaps osteoblast apoptosis. To establish the linkage between Wnts and osteoblast survival and to elucidate the molecular pathways that link the two, we have utilized three cell models: the uncommitted bipotential C2C12 cells, the pre-osteoblastic cell line MC3T3-E1, and bone marrow-derived OB-6 osteoblasts. Serum withdrawal-induced apoptosis was prevented by the canonical Wnts (Wnt3a and Wnt1) and the noncanonical Wnt5a in all cell types. Wnt3a induced LRP5-independent transient phosphorylation and nuclear accumulation of ERKs and phosphorylation of Src and Akt. The anti-apoptotic effect of Wnt3a was abrogated by inhibitors of canonical Wnt signaling, as well as by inhibitors of MEK, Src, phosphatidylinositol 3-kinase (PI3K), or Akt kinases, or by the addition of cycloheximide to the culture medium. Wnt3a-induced phosphorylation of GSK-3beta and downstream activation of beta-catenin-mediated transcription required ERK, PI3K, and Akt signaling. Wnt3a increased the expression of the anti-apoptotic protein Bcl-2 in an ERK-dependent manner. Beta-catenin-mediated transcription was permissive for the anti-apoptotic actions of Wnt1 and Wnt3a but was dispensable for the anti-apoptotic action of Wnt5a. However, Src, ERKs, PI3K, and Akt kinases were required for the anti-apoptotic effects of Wnt5a. These results demonstrate for the first time that Wnt proteins, irrespective of their ability to stimulate canonical Wnt signaling, prolong the survival of osteoblasts and uncommitted osteoblast progenitors via activation of the Src/ERK and PI3K/Akt signaling cascades.
cDNA Cloning of a Novel, Developmentally Regulated Immediate Early Gene Activated by Fibroblast Growth Factor and Encoding a Nuclear Protein (1997)

We have utilized the polymerase chain reaction (PCR)-based differential display methodology (Liang, P., and Pardee, A. B. (1992) Science 257, 967-969) to identify a novel transcript whose expression levels increased in Xenopus embryo explants during mesoderm induction by fibroblast growth factor. The PCR product was used to clone a 2.3-kilobase pair cDNA representing this transcript, which we have named er1 (early response 1). The er1 cDNA contained a single open reading frame predicted to encode a protein of 493 amino acid residues. A data base homology search revealed that the predicted ER1 amino acid sequence contains three regions of similarity to the rat and human proteins encoded by the metastasis-associated gene, mta1, and two regions of similarity to the Caenorhabditis elegans sequence that is similar to mta1. The fibroblast growth factor-induced increase in er1 steady-state levels was not dependent on de novo protein synthesis, demonstrating that er1 is an immediate-early gene. Northern blot analysis revealed a single 2.8-kilobase pair mRNA that was observed predominantly during the initial cleavage and blastula stages of Xenopus development, with little or no detectable mRNA during subsequent development. Quantitative PCR analysis of early developmental stages showed that er1 peaked during late blastula. Computer-assisted analysis of the predicted ER1 amino acid sequence revealed two putative nuclear localization signals, four highly acidic regions clustered at the N terminus and a proline-rich region located near the C terminus. Subcellular localization by immunocytochemistry revealed that the ER1 protein was targeted exclusively to the nucleus. Transactivation assays using various regions of ER1 fused to the DNA binding domain of GAL4 demonstrated that the N-terminal acidic region is a potent transactivator. These data suggest that ER1 may function as a transcription factor.
Broadband Analytical Solution to the Scattering of Plane SV Waves by Circular Cylindrical Canyons (2011)

基于波浪函数的 Fourier-Bessel 系列扩大，与可变 depth-to-width 比率由圆形的圆柱的峡谷事件飞机 SV 波浪散布的 2-D 的一个分析答案在这份报纸被推出。不同于另外的分析答案，这份报纸使用圆柱的功能的 asymptotic 行为这样，直接定义散布波浪的未经决定的系数避免在高周波的事件波浪下面解决线性方程系统和相关数字计算问题，从而拓宽分析答案的适用的频率范围。通过有存在分析答案的比较，这个答案的正确性被表明。最后，在更宽的频率乐队在圆形的圆柱的峡谷下面散布效果的事件飞机 SV 波浪被探索。
Truncated Horizon Policy Search: Combining Reinforcement Learning & Imitation Learning (2018)

In this paper, we propose to combine imitation and reinforcement learning via the idea of reward shaping using an oracle. We study the effectiveness of the near-optimal cost-to-go oracle on the planning horizon and demonstrate that the cost-to-go oracle shortens the learner's planning horizon as function of its accuracy: a globally optimal oracle can shorten the planning horizon to one, leading to a one-step greedy Markov Decision Process which is much easier to optimize, while an oracle that is far away from the optimality requires planning over a longer horizon to achieve near-optimal performance. Hence our new insight bridges the gap and interpolates between imitation learning and reinforcement learning. Motivated by the above mentioned insights, we propose Truncated HORizon Policy Search (THOR), a method that focuses on searching for policies that maximize the total reshaped reward over a finite planning horizon when the oracle is sub-optimal. We experimentally demonstrate that a gradient-based implementation of THOR can achieve superior performance compared to RL baselines and IL baselines even when the oracle is sub-optimal.
A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity (2005)

A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up.
Kinetic analysis of lamB mutants suggests the signal sequence plays multiple roles in protein export. (1986)

We have developed a quantitative assay to measure the rate of processing of precursor LamB into mature protein and have used this assay to characterize 10 previously isolated and 3 new lamB signal sequence mutants. The data suggest that the LamB signal sequence serves a complex function. Our assay has revealed five types of signal sequence defect: 1) a strong kinetic defect resulting from alteration of the secondary structure in the putative alpha-helical region in the hydrophobic core, 2) a strong, or 3) a weak kinetic defect due to placement of a charged residue in the hydrophobic core, 4) decreased synthesis of LamB, and 5) both a decrease in synthesis and a strong kinetic defect. The effect of an extragenic suppressor, prlA4 on the rate of processing pLamB containing signal sequence mutations was also examined and compared to the rates in wild-type strains. It was found that prlA4 increases the rate of processing in some, but not all, mutants having a kinetic defect while having no effect on the decreased synthesis seen in mutants of types 4 and 5.
Binding of cationic dyes to DNA: distinguishing intercalation and groove binding mechanisms using simple experimental and numerical models (2010)

Simple methods for predicting intercalation or groove binding of dyes and analogous compounds with double stranded DNA are described. The methods are based on a quantitative assessment of the aspect (width to length) ratio of the dyes. The procedures were validated using a set of 38 cationic dyes of varied chemical structures binding to well oriented DNA fibers and assessing binding orientation by linear dichroism and polarized fluorescence. We demonstrated that low aspect ratio dyes bound by intercalation, whereas more rod-like dyes were groove binders. Some problems that result and possible applications are discussed briefly.
Iron metabolism: current facts and future decisions (2012)

Iron metabolism has been intensively examined over the last decade and there are many new players in this field which are worth to be introduced. Since its discovery many studies confirmed role of liver hormone hepcidin as key regulator of iron metabolism and pointed out liver as the central organ of system iron homeostasis. Liver cells receive multiple signals related to iron balance and respond by transcriptional regulation of hepcidin expression. This liver hormone is negative regulator of iron metabolism that represses iron efflux from macrophages, hepatocytes and enterocytes by its binding to iron export protein ferroportin. Ferroportin degradation leads to cellular iron retention and decreased iron availability. At level of a cell IRE/IRP (iron responsive elements/iron responsive proteins) system allows tight regulation of iron assimilation that prevents an excess of free intracellular iron which could lead to oxidative stress and damage of DNA, proteins and lipid membranes by ROS (reactive oxygen species). At the same time IRE/IRP system provides sufficient iron in order to meet the metabolic needs. Recently a significant progress in understanding of iron metabolism has been made and new molecular participants have been characterized. Article gives an overview of the current understanding of iron metabolism: absorption, distribution, cellular uptake, release, and storage. We also discuss mechanisms underlying systemic and cellular iron regulation with emphasis on central regulatory hormone hepcidin.
Calcium dependence of membrane sealing at the cut end of the cockroach giant axon (1985)

Following transection of a nerve fiber, the ruptured membrane must be resealed before regeneration from the proximal cut end. However, it is not certain how fast the cut end is resealed or how it is resealed. We have examined the membrane sealing process following transection of the cockroach giant axon, using recovery of decreased membrane potential and input resistance as criteria. The cable analysis and the injury current profile measured under voltage clamp suggested that the injured site is resealed by a structure with high electrical resistances 5 to 30 min after the transection. This recovery of membrane properties roughly coincided in time with the appearance of a partition-like structure formed near the cut end. The membrane resealing process was highly dependent upon temperature and extracellular Ca2+. Substitution of Ca2+ by equimolar Mg2+, Mn2+, or Sr2+ failed to induce the membrane sealing following transection. However, even in a Ca2+-free solution, the membrane resealing occurred if Ca2+ was injected into the axoplasm near the cut end. Thus, the membrane resealing appears to require Ca2+ entry into the axoplasm. The resealing process was not affected by colchicine or cytochalasin. However, the resealing was prevented by the application of phospholipase A2 inhibitors. These results suggest that the membrane resealing is triggered by phospholipase A2, which is activated by excess Ca2+ entering the axoplasm at the injured site.
Epidermal growth factor stimulates fluid phase endocytosis in human fibroblasts through a signal generated at the cell surface (1982)

We have investigated the stimulation of fluid phase endocytosis by epidermal growth factor (EGF) in normal human fibroblasts using 125I-labeled polyvinylpyrrolidone (125I-PVP) as a fluid phase marker. We found that EGF initially induced a threefold increase in the rate of 125I-PVP uptake. This initial burst of fluid uptake terminated within 10 min. Thereafter, the rate of fluid uptake in EGF-treated cells was approximately 40% higher than in control cells. To identify the cellular site of EGF action in stimulating fluid phase endocytosis, we examined the kinetics of the induction of this response as well as the kinetics of cell surface binding and internalization of 125I-EGF. Although there was no detectable lag between binding of EGF to the cell surface and its internalization, the kinetics of the two processes were quite different. Significantly, the kinetics of induction of 125I-PVP uptake matched the kinetics of binding of 125I-EGF to its cell surface receptors, indicating that the signal for the increase in fluid phase endocytosis is generated at the cell surface. To determine if EGF-stimulated fluid phase endocytosis was related to EGF-stimulated endocytosis of its own receptor, we compared the EGF dose dependency and time course of the two processes. Although the stimulated endocytosis of the EGF receptor was not saturable with respect to the concentration of EGF used, the stimulation of fluid phase endocytosis was half maximal at an EGF concentration of 1 ng/ml and saturated at a concentration of 5 ng/ml. Also, the stimulation of fluid phase endocytosis was sevenfold greater initially after adding EGF than after a 30-min continuous incubation with the hormone, whereas the enhanced clearance of the EGF receptor did not change during this time period. We conclude that the EGF-stimulated increase in fluid phase endocytosis is not directly coupled to EGF-stimulated endocytosis of its own receptor but instead to a separate signal generated at the cell surface.
d-Amino Acids in Sequences of Secreted Peptides of Multicellular Organisms (1998)

Characterization and analysis of d-amino acids.- Characterization and analysis of d-amino acids.- Occurence and function of d-amino acids-containing peptides and proteins.- Occurrence and function of d-amino acids-containing peptides and proteins: Antimicrobial peptides.- Molluscan neuropeptides.- Opioid peptides from frog skin.- d-Amino acids in crustacean hyperglycemic neurohormones.- Biosynthesis: A new family of isomerases.- Biosynthesis of d-amino acid-containing peptides: Exploring the role of peptide isomerases.- Appearance of d-amino acids during aging.- Appearance of d-amino acids during aging: d-Amino acids in tumor proteins.- d-Amino acids in aging erythrocytes.- d-Amino acid hydrolysing enzymes.- d-Amino acid hydrolyzing enzymes.- Homochirality and life.- Homochirality and life.
Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity (2014)

Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19(+) MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA(-) cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR(+)CD45RA(-) cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR(+) cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA(-) cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA(+) cells, CD45RA(-) cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR(+)CD45RA(-) cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells.
FGFR-4, a new member of the fibroblast growth factor receptor family, expressed in the definitive endoderm and skeletal muscle lineages of the mouse (1991)

We have used the polymerase chain reaction to clone from fetal cerebellar RNA a novel member of the fibroblast growth factor receptor family, FGFR-4. cDNAs encoding a full-length receptor were isolated and RNA expression examined in adult and fetal tissues by RNA blot analysis. Transcripts were detected in adult lung, liver and kidney and in fetal RNAs from 11.5 to 16.5 days post coitum (p.c.). In situ hybridization was performed to examine developmental expression. FGFR-4 RNA was expressed in definitive endoderm of the developing gut and extraembryonic endoderm of the yolk-sac from 8.5 to 14.5 days p.c. At early somite stages, FGFR-4 was also expressed in the myotomal component of the somite, and by 14.5 days p.c. in the myotomally derived skeletal muscle. No expression was seen at any stage in cardiac muscle. Several endodermal derivatives, the liver, lung and pancreas, expressed FGFR-4 at 14.5 days p.c. In addition, FGFR-4 RNA was detected in the adrenal cortex, collecting tubules of the kidney and condensing cartilage at this time. These results suggest that FGFR-4 is likely to have diverse roles in development, which may include regulation of definitive endoderm and skeletal muscle lineages.