gebhart/patrepeval huggingface dataset:
A Principled Design for an Integrated Computational Environment (1985)

This paper aims at the principled design of a computational environment; it aims at being as explicit as possible about the space of possibilities and about the assumptions made in choosing from among them in the design process. The point is to develop a more systematic, if not yet scientific, basis for the design of complex but understandable artifacts. The particular object of design here is a simple but multifunctional system for naive and inexperienced users. We begin theoretically by elaborating the notion of understandability, the key characteristic for which we must design. We present various models people can make of computational systems, each with its own learning curve, advantages, and disadvantages. Then we propose a pragmatic framework for a particular system. The framework includes the principle of naive realism: that users should be able to pretend that they see the system itself in the display. It also includes the pervasive use of a spatial metaphor whereby users' commonsense spatial knowledge is used to make the system easy to understand. The theoretical and pragmatic levels are linked, in that a number of important decisions about issues (such as reference, scoping and the meaning of evaluation) are based on the theoretical modeling considerations.
Flesh and Machines: How Robots Will Change Us (2002)

From the Publisher:
Flesh and Machines explores the startlingly reciprocal connection between humans and their technological brethren, and explains how this relationship is being redefined as humans develop increasingly complex machines. The impetus to build machines that exhibit lifelike behaviors stretches back centuries, but for the last fifteen years much of this work has been done in Rodney Brooks’s laboratory at MIT. His goal is not simply to build machines that are like humans but to alter our perception of the potential capabilities of robots. Our current attitude toward intelligent robots, he asserts, is simply a reflection of our own view of ourselves. 

In Flesh and Machines, Brooks challenges that view by suggesting that human nature can be seen to possess the essential characteristics of a machine. Our instinctive rejection of that idea, he believes, is itself a conditioned response: we have programmed ourselves to believe in our “tribal specialness” as proof of our uniqueness. 

Provocative, persuasive, compelling, and unprecedented, Flesh and Machines presents a vision of our future and our future selves.
The binding site for [3H]glibenclamide in the rat cerebral cortex does not recognize K‐channel agonists or antagonists other than sulphonylureas (1991)

The binding of the potent oral antidiabetic sulphonylurea [3H]glibenclamide was studied in rat cerebral cortex membranes. A single population of high affinity and saturable binding sites with equilibrium constants, Kd = 0.2 +/- 0.06 nM and Bmax = 58.6 +/- 6.2 fmol/mg protein was found. Specific [3H]glibenclamide binding to rat cerebral cortex membranes was inhibited by glibenclamide and other sulphonylureas, glibenclamide being the most potent drug and the sulphonylurea of the second generation chlorpropamide the least potent. This observation suggests that this site may be related to the hypoglycaemic properties of sulphonylureas and possibly to their interaction with ATP-sensitive K(+)-channel. Nevertheless, other non-selective K(+)-channel antagonists such as TEA, 4-aminopyridine, quinine, quinidine or apamin failed to interact with this site (IC50 greater than 100 microM). Similarly, both non-selective K(+)-channel agonists such as cromakalim, pinacidil or minoxidil as well as the pancreatic ATP-sensitive K(+)-channel agonist diazoxide failed to interact with this site. It may thus be concluded that this site, under the present experimental conditions, represents a drug specific recognition site which may be coupled to the hypoglycaemic activity of sulphonylureas, possibly on a particulate ATP-dependent K(+)-channel.
"Calciosome," a cytoplasmic organelle: the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells? (1988)

Calsequestrin (CS) is the protein responsible for the high-capacity, moderate affinity binding of Ca2+ within the terminal cisternae of the sarcoplasmic reticulum, believed up to now to be specific for striated muscle. The cells of two nonmuscle lines (HL-60 and PC12) and of two rat tissues (liver and pancreas) are shown here to express a protein that resembles CS in many respects (apparent mass and pH-dependent migration in NaDodSO4/PAGE; blue staining with StainsAll dye; Ca2+ binding ability) and is specifically recognized by affinity-purified antibodies against skeletal muscle CS. In these cells, the CS-like protein is shown by immunofluorescence and immunogold procedures to be localized within peculiar, heretofore unrecognized structures distributed throughout the cytoplasm. These structures appear to be discrete organelles, which we propose to be named "calciosomes." By cell fractionation (Percoll gradient and free-flow electrophoresis), the CS-like protein of HL-60 cells is shown to copurify with the markers of the inositol 1,4,5-trisphosphate (Ins-P3)-sensitive Ca2+ store, whereas the markers of other organelles (endoplasmic reticulum, Golgi complex, mitochondria, endosomes) and of the plasma membrane do not. Calciosome might thus be the intracellular target of Ins-P3--i.e., the source of the Ca2+ redistributed to the cytosol following receptor-triggered generation of the messenger.
Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line (1993)

PC cell line is a highly tumorigenic insulin-independent variant from the teratoma-derived adipogenic cell line 1246. Culture medium of PC cells contains a growth promoting activity for 3T3 cells and producer cells. PC cell-derived growth factor (PCDGF) was purified to homogeneity from PC cell-conditioned medium as an apparent 88-kDa protein by chromatography on heparin-Sepharose, Sephacryl S-200, and phenyl-Sepharose. Digestion with peptide-N-glycosidase F yielded an apparent 68-kDa protein component indicating that PCDGF is a glycoprotein containing about 20 kDa of carbohydrate. Partial sequence from Edman degradation of peptide fragments obtained by digestion of PCDGF with cyanogen bromide and trypsin demonstrates that PCDGF contains regions of sequence identity to that deduced from the granulin or epithelin precursor cDNAs. Granulins are small polypeptides purified from granulocyte extracts with no apparent biological functions. Epithelins are cell growth modulators purified as small molecular mass 6-kDa polypeptides from kidney extracts. The existence of a large molecular mass precursor for granulin or epithelin has been predicted based upon recently cloned cDNAs encoding these biomolecules within a 63.5-kDa protein with putative glycosylation sites. No biological activity has previously been attributed to the precursor. The present results indicate that PCDGF is a potential precursor for epithelin and/or granulin, that this 88-kDa protein is secreted and glycosylated, and that it can function as a mitogen for 3T3 cells as well as an autocrine growth factor for PC cells.
Radiation-Induced Genomic Instability: Delayed Mutagenic and Cytogenetic Effects of X Rays and Alpha Particles (1997)

The frequency of mutations at the Hprt locus was measured in clonal populations of Chinese hamster ovary cells derived from single cells surviving exposure to 0-12 Gy of X rays or 2 Gy of alpha particles. Approximately 8-9% of 446 clonal populations examined 23 population doublings after irradiation showed high frequencies of late-arising mutations as indicated by mutant fractions 10(2)-10(4)-fold above background. The frequency with which such clones occurred was similar for alpha-particle irradiation and X irradiation, with no apparent dose dependence for X irradiation over the range of 4-12 Gy. The molecular structure of Hprt mutations was determined by analysis by multiplex polymerase chain reaction of all nine exons. Of mutations induced directly after exposure to X rays, 75% involved partial or total gene deletions. Only 19-23% of late-arising (delayed) mutations were associated with deletions, the preponderance of these being partial deletions involving one or two exons. This spectrum was very similar to that for spontaneously arising mutations. To determine whether delayed mutations were non-clonal, the spectrum of exons deleted was examined among 29 mutants with partial deletions derived from a single clonal population. The results indicated that at least 15 of these mutants arose independently. To examine the relationship between the occurrence of delayed mutations and chromosomal instability, 60 Hprt mutant subclones isolated from a clonal population showing a high frequency of delayed mutations were serially cultivated in vitro. Of these, 14 showed a slow-growth phenotype with a high frequency of polyploid cells (10-38%) and a markedly enhanced frequency of non-clonal chromosomal rearrangements including both chromosome-type and chromatid-type aberrations. These clones also showed a 3- to 30-fold increase in the frequency of ouabain-resistant mutations; no ouabain-resistant mutants were induced directly by X irradiation. These results suggest that among clones showing a high frequency of delayed mutations there may be a subpopulation of cells that are particularly unstable; selection for the slow-growth phenotype has the effect of selecting for this chromosomally unstable subpopulation.
Exploring Architectures, Data and Units For Streaming End-to-End Speech Recognition with RNN-Transducer (2018)

We investigate training end-to-end speech recognition models with the recurrent neural network transducer (RNN-T): a streaming, all-neural, sequence-to-sequence architecture which jointly learns acoustic and language model components from transcribed acoustic data. We explore various model architectures and demonstrate how the model can be improved further if additional text or pronunciation data are available. The model consists of an `encoder', which is initialized from a connectionist temporal classification-based (CTC) acoustic model, and a `decoder' which is partially initialized from a recurrent neural network language model trained on text data alone. The entire neural network is trained with the RNN-T loss and directly outputs the recognized transcript as a sequence of graphemes, thus performing end-to-end speech recognition. We find that performance can be improved further through the use of sub-word units (`wordpieces') which capture longer context and significantly reduce substitution errors. The best RNN-T system, a twelve-layer LSTM encoder with a two-layer LSTM decoder trained with 30,000 wordpieces as output targets achieves a word error rate of 8.5\% on voice-search and 5.2\% on voice-dictation tasks and is comparable to a state-of-the-art baseline at 8.3\% on voice-search and 5.4\% voice-dictation.
Efficacy of the Branched-Chain Amino Acids in the Treatment of Tardive Dyskinesia in Men (2003)

Branched-chain amino acids constitute a novel, safe treatment for tardive dyskinesia, with a strong potential for providing significant improvement in the diseased physiognomy of the afflicted person.
Optical volume and mass measurements show that mammalian cells swell during mitosis (2015)

The extent, mechanism, and function of cell volume changes during specific cellular events, such as cell migration and cell division, have been poorly studied, mostly because of a lack of adequate techniques. Here we unambiguously report that a large range of mammalian cell types display a significant increase in volume during mitosis (up to 30%). We further show that this increase in volume is tightly linked to the mitotic state of the cell and not to its spread or rounded shape and is independent of the presence of an intact actomyosin cortex. Importantly, this volume increase is not accompanied by an increase in dry mass and thus corresponds to a decrease in cell density. This mitotic swelling might have important consequences for mitotic progression: it might contribute to produce strong pushing forces, allowing mitotic cells to round up; it might also, by lowering cytoplasmic density, contribute to the large change of physicochemical properties observed in mitotic cells.
Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy (1999)

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19–29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 ± 1.2 and 5.3 ± 1.2 mmol/kg wet wt (mean ± SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed. Magn Reson Med 41:657–663, 1999. © 1999 Wiley-Liss, Inc.
Molecular Characterization of a Novel Short-chain Dehydrogenase/Reductase That Reduces All-trans-retinal (1998)

The reduction of all-trans-retinal in photoreceptor outer segments is the first step in the regeneration of bleached visual pigments. We report here the cloning of a dehydrogenase, retSDR1, that belongs to the short-chain dehydrogenase/reductase superfamily and localizes predominantly in cone photoreceptors. retSDR1 expressed in insect cells displayed substrate specificities of the photoreceptor all-trans-retinol dehydrogenase. Homology modeling of retSDR1 using the carbonyl reductase structure as a scaffold predicted a classical Rossmann fold for the nucleotide binding, and an N-terminal extension that could facilitate binding of the enzyme to the cell membranes. The presence of retSDR1 in a subset of inner retinal neurons and in other tissues suggests that the enzyme may also be involved in retinol metabolism outside of photoreceptors.
Recovery of Cytopathogenic Agent from Chimpanzees with Goryza (1956)

SummaryA virus was recovered from throat materials of a chimpanzee with coryza during an epizootic of respiratory disease in a colony of these animals. The new agent produced degenerative changes in tissue culture, but was not pathogenic for common laboratory animals. The donor chimpanzee as well as other chimpanzees involved in the epizootic developed specific antibodies against the coryza agent during the months following the outbreak. Susceptible chimpanzees following intranasal instillation of tissue culture materials infected with the coryza agent developed clinical coryza and subsequently made specific antibody. A presumptive etiologic association was established between the new agent and respiratory illness in a laboratory worker, but has not been implicated in the illnesses of small groups of patients with several common types of respiratory disease. However, a number of human beings, particularly adolescents and young adults, have antibodies in their sera directed against the coryza agent suggest...
Structure-Based Approaches to Improve Selectivity:  CDK2−GSK3β Binding Site Analysis (2005)

An evaluation and comparison of two different approaches, GRID/CPCA and GRIND/CPCA (CPCA = consensus principal component analysis; GRIND = GRid-INdependent Descriptors), suitable for visualizing the structural differences between related proteins is presented. Ten crystal structures of CDK2/cyclin A and GSK3beta solved in-house with different inhibitors were compared with the aim of highlighting regions that could be potential sites for gaining selectivity for CDK2 versus GSK3beta. The analyses pointed out remarkable differences in the backs of the CDK2-GSK3beta ATP binding pockets that guided the optimization toward a selective benzodipyrazole CDK2 inhibitor. The gain in selectivity can be associated with the two main differences in the ATP pocket between the enzymes. Phe80 of CDK2, the so-called gatekeeper residue often exploited for the design of kinase selective ligands, is replaced by a leucine in GSK3beta, and Ala144 is replaced by a cysteine. As a consequence of these mutations, CDK2 has a less elongated and less flat buried region at the back of the ATP pocket.
Development and Evaluation of anompAQuantitative Real-Time PCR Assay forChlamydia trachomatisSerovar Determination (2010)

Knowledge of circulating Chlamydia trachomatis serovars can be beneficial for sexual network surveillance, monitoring treatment success, and associating specific clinical manifestations. Typically, C. trachomatis serovars are predicted by nucleotide sequencing of four variable domains within the ompA gene. However, sequencing procedures can be labor-intensive, are not readily available, and can lack the capacity to identify multiple serovars. This study describes the development and evaluation of a quantitative real-time PCR (qPCR) test algorithm for the rapid prediction of C. trachomatis serovars, including ocular (A to C) and anogenital (D to L3) strains. This test comprises a primary qPCR to confirm C. trachomatis positivity and the phylogenetic group(s) present and a secondary set of qPCRs to determine specific serovars. Cell culture isolates from 15 prototypic C. trachomatis serovars were correctly identified using this assay, with no cross-reactivity observed among serovars or with other common pathogenic microorganisms. Five hundred clinical specimens (previously diagnosed as being C. trachomatis positive) were evaluated by qPCR, with their results compared to results obtained by conventional sequencing. The qPCR identified 88.9% (423/476) complete matches (95% confidence interval [CI], 86 to 92%) of serovars compared to the results obtained using the sequence-based approach. Among the anogenital specimens, 2.4% (12/494) (95% CI, 1.3 to 4.2%) contained multiple serovars, categorized as single-serovar infections by conventional sequencing. Overall, this test exhibited high discriminatory success for predicting C. trachomatis serovars, particularly among anogenital infections. This is the first report of a qPCR typing assay offering differentiation of C. trachomatis serovars associated with both anogenital and ocular diseases.
The Platelet-Activating Factor Receptor Antagonist WEB 2170 Prevents Neonatal Necrotizing Enterocolitis in Rats (1997)

The data support the role of PAF in the final common pathway of neonatal NEC.
Biological Activities of Anti-IgE Antibodies (1993)

Naturally occurring anti-IgE autoantibodies represent a heterogeneous mixture of antibodies with diverse specificities and biological functions. By using murine monoclonal anti-IgE autoantibodies directed against different epitopes on the IgE molecule as a model for autoantibodies, we could show that only a minority of antibodies combine all beneficial biological activities, such as the activity of inhibiting in vitro IgE synthesis, removing IgE from the surface of CD23+ cells and not being anaphylactogenic. While it is difficult to isolate and measure anti-IgE antibodies in human serum, it is now possible to generate such human anti-IgE antibodies by the method of repertoire cloning. Thus, human recombinant antibodies against IgE may become available for the treatment of atopic disease.
Challenges and opportunities of allogeneic donor-derived CAR T cells (2015)

In the allogeneic environment, the potential effects of TCR signaling on the efficacy of CAR could affect the clinical responses with the use of donor-derived CAR T cells. Better understanding of the functionality of donor-derived T cells for therapy is essential for the development of universal effector cells for CAR therapy.
Higher-Order Concurrent Programs with Finite Communication Topology (1994)

Concurrent ML (CML) is an extension of the functional language Standard ML (SML) with primitives for the dynamic creation of processes and channels and for the communication of values over channels. Because of the powerful abstraction mechanisms the communication topology of a given program may be very complex and therefore an efficient implementation maybe facilitated by knowledge of the topology. This paper presents an analysis for determining when a bounded number of processes and channels will be generated. The analysis proceeds in two stages. First we extend a polymorphic type system for SML to deduce not only the type of CML programs but also their communication behaviour expressed as terms in a new process algebra. Next we develop an analysis that given the communication behaviour predicts the number of processes and channels required during the execution of the CML program. The correctness of the analysis is proved using a subject reduction property for the type system. Permission to copy without fee all or part of this material is granted provided that the copies are not mada or distributed for direct commercial advantaga, tha ACM copyright notica and tha titla of tha publication and its data appear, and notica ia givan that copying is by permission of the Association for Computing Machinery. To copy otherwise, or to republish, requires a foe ar-dor spacific permission. POPL 941K14, Portland Oregon, USA @ 1994 ACM 0-89791436-0/94/001 ..$3.50
Nucleolin mediates nucleosome disruption critical for DNA double-strand break repair (2013)

Recruitment of DNA repair factors and modulation of chromatin structure at sites of DNA double-strand breaks (DSBs) is a complex and highly orchestrated process. We developed a system that can induce DSBs rapidly at defined endogenous sites in mammalian genomes and enables direct assessment of repair and monitoring of protein recruitment, egress, and modification at DSBs. The tight regulation of the system also permits assessments of relative kinetics and dependencies of events associated with cellular responses to DNA breakage. Distinct advantages of this system over focus formation/disappearance assays for assessing DSB repair are demonstrated. Using ChIP, we found that nucleosomes are partially disassembled around DSBs during nonhomologous end-joining repair in G1-arrested mammalian cells, characterized by a transient loss of the H2A/H2B histone dimer. Nucleolin, a protein with histone chaperone activity, interacts with RAD50 via its arginine-glycine rich domain and is recruited to DSBs rapidly in an MRE11-NBS1-RAD50 complex-dependent manner. Down-regulation of nucleolin abrogates the nucleosome disruption, the recruitment of repair factors, and the repair of the DSB, demonstrating the functional importance of nucleosome disruption in DSB repair and identifying a chromatin-remodeling protein required for the process. Interestingly, the nucleosome disruption that occurs during DSB repair in cycling cells differs in that both H2A/H2B and H3/H4 histone dimers are removed. This complete nucleosome disruption is also dependent on nucleolin and is required for recruitment of replication protein A to DSBs, a marker of DSB processing that is a requisite for homologous recombination repair.