gebhart/patrepeval huggingface dataset:
Genetic analysis of interferon and other mammalian signaling pathways. (2000)

Systematic forward genetics, so powerful for analyzing pathways in haploid organisms, has contributed much less to our understanding of diploid mammalian cells. With Ian Kerr, we have used regulated expression of selectable markers in heavily mutagenized cells to isolate mutant mammalian cell lines defective in eight different proteins required for interferon signaling. These cells have been valuable in studying the roles of the deleted Janus Kinase (JAK), signal transducer and activator of transcription (STAT), and receptor proteins in interferon and other signaling pathways. Mutant cells defective in the induction of class II major histocompatibility complex (MHC) antigens by interferon-gamma or in repressing interferon-regulated genes have also been obtained. More recently, mutant cells unresponsive to double-stranded RNA, tumor necrosis factor alpha (TNF-alpha), or interleukin-1 (IL-1) have been isolated and characterized and a mutant line defective in expressing the tumor suppressor protein p53 has also been obtained. Systematic forward genetics can now be applied more easily to mammalian cells, to help elucidate signaling pathways.
Evidence for Prion-Like Mechanisms in Several Neurodegenerative Diseases: Potential Implications for Immunotherapy (2013)

Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases. While the impact of TSEs on human health is relatively minor, these diseases are having a major influence on how we view, and potentially treat, other more common neurodegenerative disorders. Until recently, TSEs encapsulated a distinct category of neurodegenerative disorder, exclusive in their defining characteristic of infectivity. It now appears that similar mechanisms of self-propagation may underlie other proteinopathies such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. This link is of scientific interest and potential therapeutic importance as this route of self-propagation offers conceptual support and guidance for vaccine development efforts. Specifically, the existence of a pathological, self-promoting isoform offers a rational vaccine target. Here, we review the evidence of prion-like mechanisms within a number of common neurodegenerative disorders and speculate on potential implications and opportunities for vaccine development.
Implementing Execution Controls in Unix (1993)

Current implementations of UNIX offer security features in the form of discretionary access controls (DACs). DACs are implemented with file access permissions and access control lists (ACLs). Unfortunately, neither of these facilities provide for access control to active processes. In order to provide many users access to a process (and its associated data) the current practice at our site is to establish a group account, where members on a project team share the login and password for an application. This practice is both insecure, and a violation of our site's security policies.

This paper describes the implementation of a new tool, medex , which eliminates the need for group login accounts. Medex mediates the access of users to privileged accounts and executables. The history behind our use of group accoutns and a complete methodology for UNIX application management are presented. Details of the implementation of medex , including its interaction with the existing security features of UNIX, are given. The tool utilizes execution control lists (ECLs) as a means to allow controlled execution of programs under accounts other than the current login. Medex also re-authenticates the user's password upon each instatiation and maintains an audit trial via log files or the use of the UNIX syslog facility. A complete project management example utilizing medex is given along with a comparison to related tools.
Aberrant Expression of Human Achaete-Scute Homologue Gene 1 in the Gastrointestinal Neuroendocrine Carcinomas (2005)

These findings revealed that hASH1 is distinctly up-regulated in gastrointestinal NECs. hASH1 may be used as a more sensitive and specific marker than conventional pan-endocrine markers for clinical diagnosis of gastrointestinal NECs.
Chemiluminescent reporter gene assays: sensitive detection of the GUS and SEAP gene products. (1994)

Chemiluminescent assays are described for the secreted alkaline phosphatase (SEAP) and beta-glucuronidase (GUS) reporter gene products. These assays provide simple, sensitive, non-isotopic alternatives to existing detection methods and are performed in microplate or tube luminometers or in a scintillation counter. The SEAP reporter gene product is secreted from mammalian cells and is thus easily detected in a sample of culture medium. Sensitive detection of secreted placental alkaline phosphatase is performed with CSPD chemiluminescent alkaline phosphatase substrate, and approximately 3 fg of enzyme can be detected. GUS has become the major reporter gene used for the analysis of plant gene expression. Sensitive chemiluminescent detection of GUS activity can be performed with an assay system we have developed using Glucuron, a beta-glucuronidase substrate. This chemiluminescent assay detects 60 fg of GUS and is linear over six orders of magnitude of enzyme concentration. CSPD and Glucuron substrates have been incorporated into two new chemiluminescent reporter gene assay kits for SEAP and GUS.
Hardware-assisted data compression for energy minimization in systems with embedded processors (2003)

In this paper, we suggest hardware-assisted data compression as a tool for reducing energy consumption of core-based embedded systems. We propose a novel and efficient architecture for on-the-fly data compression and decompression whose field of operation is the cache-to-memory path. Uncompressed cache lines are compressed before they are written back to main memory, and decompressed when cache refills take place. We explore two classes of compression methods, profile-driven and differential, since they are characterized by compact HW implementations, and we compare their performance to those provided by some state-of-the-art compression methods (e.g., we have considered a few variants of the Lempel-Ziv encoder). We present experimental results about memory traffic and energy consumption in the cache-to-memory path of a core-based system running standard benchmark programs. The achieved average energy savings range from 4.2% to 35.2%, depending on the selected compression algorithm.
Increase in Incidence of Insulin-Dependent Diabetes Mellitus among Children in Finland (1995)

The incidence of IDDM in Finnish children seems to increase further. During the last decades the increase in incidence has been almost linear with occasional peaks. The age-at-diagnosis of IDDM has been moving towards the younger ages, and differences in incidence between age groups have now almost disappeared among Finnish children aged 1-14 years.
Practical Black-Box Attacks against Machine Learning (2017)

Machine learning (ML) models, e.g., deep neural networks (DNNs), are vulnerable to adversarial examples: malicious inputs modified to yield erroneous model outputs, while appearing unmodified to human observers. Potential attacks include having malicious content like malware identified as legitimate or controlling vehicle behavior. Yet, all existing adversarial example attacks require knowledge of either the model internals or its training data. We introduce the first practical demonstration of an attacker controlling a remotely hosted DNN with no such knowledge. Indeed, the only capability of our black-box adversary is to observe labels given by the DNN to chosen inputs. Our attack strategy consists in training a local model to substitute for the target DNN, using inputs synthetically generated by an adversary and labeled by the target DNN. We use the local substitute to craft adversarial examples, and find that they are misclassified by the targeted DNN. To perform a real-world and properly-blinded evaluation, we attack a DNN hosted by MetaMind, an online deep learning API. We find that their DNN misclassifies 84.24% of the adversarial examples crafted with our substitute. We demonstrate the general applicability of our strategy to many ML techniques by conducting the same attack against models hosted by Amazon and Google, using logistic regression substitutes. They yield adversarial examples misclassified by Amazon and Google at rates of 96.19% and 88.94%. We also find that this black-box attack strategy is capable of evading defense strategies previously found to make adversarial example crafting harder.
An Efficient Method for the Assessment of DNA Quality of Archival Microdissected Specimens (2002)

There will be an increasing need of methods for assessing the suitability of specimens for genetic-based assays as DNA markers become an integral part of molecular diagnosis. The targeting of specimens for specific analyses will require the ability to rapidly screen for DNA quality. Conventional methods such as Southern analysis and gene specific-polymerase chain reaction (PCR) often require quantities of material that represent a significant portion of the specimen, especially in microdissected samples. Here we describe a novel application of a commonly used PCR-based DNA-fingerprinting technology that requires minimal quantities of DNA to simultaneously assess multiple regions throughout the genome for DNA quality. Randomly amplified polymorphic DNA (RAPD) PCR generates DNA fragments of a broad size range with the product size reflecting the degree of sample fragmentation. Fourteen DNA samples extracted from cells microdissected from seven formalin-fixed, paraffin-embedded oral cancer biopsies were assessed for DNA quality using gene-specific PCR and RAPD-PCR. Although the more conventional assay required 2-ng DNA (or 300-cell equivalents) to examine DNA quality at a single locus, RAPD-PCR provided a more informative profile of DNA quality from the same microdissected archival specimens.
Proactive server roaming for mitigating denial-of-service attacks (2003)

We propose a framework based on proactive server roaming to mitigate the effects of denial-of-service (DoS) attacks. The active server proactively changes its location within a pool of servers to defend against unpredictable and undetectable attacks. Only legitimate clients can follow the active server as it roams. We present algorithms that are secure, distributed, randomized, and adaptive for triggering the roaming and determining the next server to roam to. We propose some modifications to the state recovery process of existing TCP connection-migration schemes to suit roaming. Preliminary experiments in a FreeBSD network show that the overhead of server roaming is small, in terms of response time, in the absence of attacks. Further, during an attack, roaming significantly improves the response time.
Refolding and Reconstitution of Functionally Active Complexes of Human Leukocyte Antigen DR2 and Myelin Basic Protein Peptide from Recombinant α and β Polypeptide Chains (1995)

Major histocompatibility complex (MHC) class II molecules are cell surface heterodimeric glycoproteins consisting of one alpha and one beta polypeptide chain of similar size. These molecules play a critical role in immune recognition by displaying processed antigens to CD4-positive T helper cells. Several attempts to express the MHC class II molecules by recombinant methods in various systems resulted in either failure or poor recovery of the intact heterodimer. The present study describes our successful effort to refold and reconstitute HLA DR2 heterodimer from individually expressed alpha and beta polypeptide chains lacking the transmembrane hydrophobic regions in Escherichia coli, in the presence of an immunodominant epitope analog from human myelin basic protein (b-MBP(83-102)Y83). The reconstituted DR2 heterodimer complex was selectively purified from unfolded alpha and beta chains using heterodimer-specific monoclonal antibody (L243) coupled to a solid support. The detection of two polypeptide chains in the purified refolded DR2-peptide complex preparations was accomplished by Western blot analysis and enzyme-linked immunosorbent assay using heterodimer- and chain-specific polyclonal antibodies, and the presence of equimolar amounts of both alpha chain and beta chain in the reconstituted complex preparation was confirmed by a double label experiment. The quantitation of the bound peptide in complex preparation was measured by incubating two chains in the presence of 125I-labeled peptide. An increase in the yield of refolded and reconstituted DR2-peptide complexes was observed with increasing peptide concentration in the reaction mixture. Finally, the functional activity of the reconstituted DR2 complexes was measured by their ability to stimulate gamma-interferon production by SS8T cloned T cells in an antigen-specific and dose-dependent manner. These results demonstrate that biologically active complexes of human DR2.b-MBP (83-102)Y83 can be prepared by proper folding of human leukocyte antigen DR2 alpha and beta chains in the presence of antigenic peptide. The yield of such DR2 heterodimers with bound peptide is several thousand-fold higher over native DR2 purified from transformed B cells. Since purified MHC class II-peptide complexes have been shown to prevent autoimmune diseases in various animal models, reconstituted heterodimer complexes may have significant clinical relevance in antigen-specific treatment of various autoimmune diseases. In addition, such complexes with increased yield will provide better understanding of the trimolecular interactions between MHC-peptide and T cell receptor.
Conjugative Pili of IncP Plasmids, and the Ti Plasmid T Pilus Are Composed of Cyclic Subunits (1999)

TrbC propilin is the precursor of the pilin subunit TrbC of IncP conjugative pili in Escherichia coli. Likewise, its homologue, VirB2 propilin, is processed into T pilin of the Ti plasmid T pilus in Agrobacterium tumefaciens. TrbC and VirB2 propilin are truncated post-translationally at the N terminus by the removal of a 36/47-residue leader peptide, respectively. TrbC propilin undergoes a second processing step by the removal of 27 residues at the C terminus by host-encoded functions followed by the excision of four additional C-terminal residues by a plasmid-borne serine protease. The final product TrbC of 78 residues is cyclized via an intramolecular covalent head-to-tail peptide bond. The T pilin does not undergo additional truncation but is likewise cyclized. The circular structures of these pilins, as verified by mass spectrometry, represent novel primary configurations that conform and assemble into the conjugative apparatus.
Trafficking of Mammalian Chemosensory Receptors by Receptor‐transporting Proteins (2009)

Although mammalian odorant receptors (ORs) were identified more than 15 years ago, we still do not understand how odorant molecules interact with ORs at a molecular level. Previous studies of mammalian ORs have tested few ORs against many odorants. Some fundamental properties of the olfactory system, however, require investigation of a wide panel of diverse ORs with many chemically diverse odorants. Previously, we identified OR accessory proteins, receptor-transporting protein (RTP) 1 and RTP2. They are expressed specifically in olfactory neurons, are associated with OR proteins, and facilitate the OR trafficking to the plasma membrane when coexpressed in mammalian cell lines. With this approach, high-throughput screening using a large repertoire of mammalian ORs is now possible. The activation profiles can be used to develop a predictive model relating physicochemical odorant properties, receptor sequences, and their interactions, enabling us to predict a tested receptor's response to a novel odorant and a novel receptor's response to a tested odorant. Doing so will provide a basis for understanding how structurally diverse odorant molecules activate the mammalian OR repertoire. Similarly, two families of vomeronasal receptors, V1Rs and V2Rs, are also notoriously difficult to functionally express in heterologous cells. However, coexpression of the RTP family members with V1Rs or V2Rs does not seem to facilitate trafficking of the receptor proteins. This finding suggests that the vomeronasal organ has a unique biosynthetic pathway for membrane proteins.
The Making of Taiwan Policy in Mainland China: Structure and Process (1997)

This article examines the structure and process of Beijing’s Taiwan policymaking. Although policymaking structure and process do not equal decisionmaking itself; they can still reveal some important information about the latter. 
Beijing’s Taiwan policymaking is not completely institutionalized; it has flexibly made use of both institutional and noninstitutional mechanisms. Within the established system, Taiwan affairs offices, and military, security, and foreign policy units may transmit their opinions to higher-level units through official administrative channels. Outside the established system, relevant organizations and persons may pass their opinions directly to the central decisionmaking body, either in the form of important or special reports or opinion exchanges. 
The author’s study indicates that the Chinese Communist Party (CCP), military, and security organizations handling Taiwan affairs and research organizations carrying on specialized studies about Taiwan enjoy comparatively greater influence in the shaping of Beijing’s Taiwan policy.
Metadata support for safe component upgrades (2003)

Component platforms play a major role in current distributed information systems. As these systems evolve, components need to be upgraded without breaking the consistency of component interconnections. In this paper we present a method for the support of automated safe upgrades of black-box components. It relates component versioning with indication of changes between revisions of the same component and uses pre-computed information stored in component meta-data. We show how this information is derived from component specifications and used to speed up pre-upgrade checks.
Functional Mechanisms Underlying Tachycardia-Induced Sustained Atrial Fibrillation in a Chronic Dog Model (1997)

Rapid atrial activation causes time-dependent decreases in ERP, conduction velocity, and wavelength, which, along with increased regional heterogeneity, provide a substrate for AF. The conduction abnormalities and increased regional heterogeneity previously noted in patients with AF may be a consequence, as well as a cause, of the tachyarrhythmia.
Prognostic role of urokinase-type plasminogen activator in human gliomas. (1995)

Urokinase-type plasminogen activator (u-PA) is a 54-kd enzyme shown to participate in tissue degradation under certain normal and pathological conditions, including cancer invasion and metastasis. Increased u-PA expression has been found in cancers of the breast, lung, colon, and prostate, and correlated with worse outcome in patients with lung and breast cancer. We examined the correlation between u-PA expression in gliomas and patient survival. Seventy-seven gliomas from 41 men and 36 women (ages 2 to 73) were immunostained for u-PA using monoclonal antibody 394 directed against human urokinase. The tumors included 32 grade 4, 16 grade 3, and 20 grade 2 astrocytomas (Daumas-Duport scale), and 9 pilocytic astrocytomas. Strong cytoplasmic staining was found in tumor cells of all grade 4, most of the grade 3, and a few of the lower grade tumors. Adjacent normal brain tissue showed faint staining associated with subpial cell processes and white matter fibers. The fiber staining was stronger in brain tissue infiltrated by tumor cells. Cytoplasmic u-PA staining in tumor cells was scored from 0 (no staining) to 6 (strong and widespread staining). The mean u-PA scores were 5.08 +/- 0.19 (mean +/- SEM) for grade 4, 3.97 +/- 0.46 for grade 3, 1.65 +/- 0.39 for grade 2, and 1.22 +/- 0.60 for pilocytic astrocytomas. The statistical analysis was based on cytoplasmic staining only. Analysis of variance revealed significant differences between the mean u-PA scores of different grades (P < 0.02 between grades 4 and 3, and P = 0.0001 between grades 4 or 3 and 2, and between grades 4 or 3 and pilocytic), except between grade 2 and pilocytic astrocytomas. Univariate analysis indicated that u-PA score > or = 4 (P = 0.0001), tumor grade 4 (P = 0.01), and age > 50 (P < 0.001) were all significant predictors for shorter disease survival. A three-way interaction model by multivariate analysis indicated that u-PA score > or = 4, tumor grade 4, and age > 50, taken together, were significant factors for shorter patient survival (P < 0.02). We conclude that u-PA may be used as a prognostic tool in conjunction with tumor grade and patients' age in predicting survival for patients with gliomas.
Characterization and Sequence Analysis of the Human Ornithine Decarboxylase Gene (1989)

This report describes the characterization and complete sequence of the human ornithine decarboxylase (ODC) gene. Genomic Southern blot analysis shows only a single gene hybridizing at high stringency, in contrast to the murine multigene family. A Pst I restriction fragment length polymorphism was identified and an allele of the human ODC gene containing the polymorphic Pst I site was cloned and sequenced. The ODC gene is divided into 12 exons and spans 8 kb. Comparison of the human, rat, and mouse ODC genes shows striking conservation of genomic organization, as well as 82% identity in the first 148 bp of the 5'-flanking region. This region contains a TATA box, cAMP-responsive element, CCAAT box, and AP-2 binding site and is consistent with induction of ODC gene expression by both the cAMP and protein kinase C-mediated signaling pathways. The first intron of the human gene is 2,849 bp in length, and contains two putative Sp1 binding sites, as well as an Ap1 binding site, suggesting a role for the first intron in transcriptional regulation. The 5' noncoding region of the predicted mRNA contains regions of virtual identity with that of mouse and rat ODC mRNA, suggesting sequences involved in translational regulation. In addition, it was found that the exon segments corresponding to the amino and carboxyl termini of Saccharomyces cerevisiae and Trypanosoma b. brucei are unrelated to their mammalian counterparts, whereas the middle segments of the protein are conserved. These differences may influence the difference in protein half-life seen between T. b. brucei and mammalian ODC.
An anti-ferroelectric gated Landau transistor to achieve sub-60 mV/dec switching at low voltage and high speed (2015)

Landau field effect transistors promise to lower the power-dissipation of integrated circuits (ICs) by reducing the subthreshold swing (S) below the Boltzmann limit of 60 mV/dec. The key idea is to replace the classical gate insulator with dielectrics that exhibit negative capacitance (NC) associated with double-well energy landscape, for example, ferroelectrics (FE), air-gap capacitors, or a combination thereof. Indeed, S is dramatically reduced, constrained only by the limits of hysteresis-free operation. Unfortunately, the following limitations apply (i) the need for capacitance matching constrains steep S only to the small subthreshold region for FE based negative capacitance field effect transistor (NCFET) and requires an insulator too thick for sub-20 nm scaling; (ii) the kinetics of mechanical switching for airgap based NCFET obviate high-speed operation; and (iii) the lattice mismatch between the substrate and the dielectric makes defect-free integration difficult. In this article, we demonstrate that a FET integrated with 10 nm HfO2-based anti-ferroelectric and FE hetero stack would achieve ultralow S with ON-current (Ion) at par with classical transistors at significantly lower voltage and would simplify integration. Our results address the well-known challenges/criticisms of classical Landau transistors, thereby, making them technology relevant for modern ICs.