gebhart/patrepeval huggingface dataset:
Consensus Design of Repeat Proteins (2004)

Consensus design is a valuable protein-engineering method that is based on statistical information derived from sequence alignments of homologous proteins. Recently, consensus design was adapted to repeat proteins. We discuss the potential of this novel repeat-based approach for the design of consensus repeat proteins and repeat protein libraries and summarize recent results from such experiments.
Monolithic 3D Integrated Circuits (2007)

3D IC's promise to solve the 2D communication bottleneck, and enable the integration of heterogeneous materials, devices and systems. There are at least three approaches to realize 3D IC's : chip stacking, wafer stacking and full monolithic integration. Each approach is at a different level of maturity and offers various degree of improvement. This paper will focus on the monolithic 3D approach, which offers a high density of device-dimension vertical interconnects and thereby facilitates the optimal assembly of transistors and interconnects in a 3D volume. The performance advantages of such a technology are demonstrated with a 3D-FPGA. Technology challenges of monolithic approach are discussed.
Computational Biology and Bioinformatics (2023)

<i> Computational Biology and Bioinformatics (CBB) </i> aims to publish high quality, original research articles, expository tutorial papers and review papers as well as short, critical comments on technical issues associated with the analysis of computational biology and bioinformatics. The research papers will be technical presentations of new assertions, discoveries and tools, intended for a narrower specialist community. The tutorials, reviews and critical commentary will be targeted at a broader readership of biologists who are interested in using computers but are not knowledgeable about scientific computing, and equally, computer scientists who have an interest in biology but are not familiar with current thrusts nor the language of biology.
Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. (1995)

A mutation within the obese gene was recently identified as the genetic basis for obesity in the ob/ob mouse. The obese gene product, leptin, is a 16-kDa protein expressed predominantly in adipose tissue. Consistent with leptin's postulated role as an extracellular signaling protein, human embryonic kidney 293 cells transfected with the obese gene secreted leptin with minimal intracellular accumulation. Upon differentiation of 3T3-L1 preadipocytes into adipocytes, the leptin mRNA was expressed concomitant with mRNAs encoding adipocyte marker proteins. A factor(s) present in calf serum markedly activated expression of leptin by fully differentiated 3T3-L1 adipocytes. A 16-hr fast decreased (by approximately 85%) the leptin mRNA level of adipose tissue of lean (ob/+ or +/+) mice but had no effect on the approximately 4-fold higher level in obese (ob/ob) littermates. Since the mutation at the ob locus fails to produce the functional protein, yet its cognate mRNA is overproduced, it appears that leptin is necessary for its own downregulation. Leptin mRNA was also suppressed in adipose tissue of rats during a 16-hr fast and was rapidly induced during a 4-hr refeeding period. Insulin deficiency provoked by streptozotocin also markedly down-regulated leptin mRNA and this suppression was rapidly reversed by insulin. These results suggest that insulin may regulate the expression of leptin.
Facilitation of β Selection and Modification of Positive Selection in the Thymus of Pd-1–Deficient Mice (2000)

PD-1 is an immunoglobulin superfamily member bearing an immunoreceptor tyrosine-based inhibitory motif, and disruption of the PD-1 gene results in the development of lupus-like autoimmune diseases. In this study, we examined effects of the PD-1 deficiency on the thymocyte differentiation at the clonal level using T cell receptor (TCR)-beta (Vbeta8) and TCR-alpha/beta (H-Y and 2C) transgenic mice. In these TCR transgenic lines, PD-1 expression in the thymus was variably augmented, but as in the normal mice, confined largely to the CD4(-)CD8(-) thymocytes. The transgenic mice crossed with PD-1(-/)- mice in the neutral genetic backgrounds exhibited selective increase in the CD4(+)CD8(+) (DP) population with little effect on other thymocytes subsets. Similarly, the absence of PD-1 facilitated expansion of DP thymocytes in recombination activating gene (RAG)-2(-/)- mice by anti-CD3epsilon antibody injection. On the other hand, H-Y or 2C transgenic PD-1(-/)- mice with the positively selecting background showed significantly reduced efficiency for the generation of CD8(+) single positive cells bearing the transgenic TCR-alpha/beta in spite of the increased DP population. These results collectively indicate that PD-1 negatively regulates the beta selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire.
Voice recognition (1997)

From the Publisher:
Here's a scientific look at computer-generated speech verification and identification  its underlying technology, practical applications, and future direction. This book provides you with a solid background in voice recognition technology and helps you make informed decisions on which voice recognition-based software to use in your company or organization. It is unique in its clear explanations of mathematical concepts, as well as its full-chapter presentation of the successful new Multi-Granular Segregating System for accurate, context-free speech identification.

Page after page of actual case studies and experimental results supported by clear, easy-to-follow charts and graphs help...

 Speech scientists get up to speed in voice recognition technology and conduct future research

 Security specialists and managers choose the speech identification-based security system best suited for their needs

 Law enforcement and justice officials better understand the benefits and limitations of forensic voice recognition technology
Responsiveness to Cetuximab without Mutations inEGFR (2005)

T790M mutation was shown to confer resistance to gefitinib after it was introduced into the sequence of the wild-type EGFR and L858R mutant EGFR in vitro. 2,3 The T790M mutation results in steric hindrance of binding of gefitinib to the ATPkinase-binding pocket.The T790M mutation may cause acquired resistance to gefitinib. 2,3Our patient had concomitant T790M and L858R EGFR mutations in the original lung-biopsy specimen and showed primary resistance to gefitinib -a finding implying that a mutation in the T790M kinase domain can occur during the natural evolution of lung cancer.T790M mutant gefitinibresistant clones may preexist at levels below the threshold of detection 5 in some patients with lung cancer at presentation and then may expand selectively under gefitinib treatment, leading to the failure of gefitinib therapy.
Design and Performance Evaluation of a Proxy-based Java Rewriting Security System (2006)

Binary rewriting techniques have been developed to allow users to enforce security policies directly on mobile code. However, the performance overheads incurred for improved security, particularly in large organizations with many end-hosts, accentuate the inherent challenges of code rewriting and limit the rate of improvement in these systems. We integrate a binary code rewriter with a web caching proxy and build the security system called PBJARS, a Proxy-based JAva Rewriting System. PBJARS compliments existing JVM security mechanisms by placing another line of security defense in the code path code associated with code downloads. It gives system administrators centralized security control at the level of administrative domains at proxy servers. We evaluated PB-JARS using real Java binary traffic models derived from analyzing real web trace records. Our experimental results show that the overhead added by binary rewriting can be significantly amortized by web caching and PB-JARS adds negligible performance impact on proxy servers.
The κB DNA Sequence from the HIV Long Terminal Repeat Functions as an Allosteric Regulator of HIV Transcription (2002)

NF-kappaB is an inducible transcription factor involved in the immune response, inflammation, and viral transcription. To address how the two NF-kappaB and three Sp1 binding sites of the human immunodeficiency virus (HIV) long terminal repeat (LTR) control multiple activator assembly and transcription, we first observed and compared unique conformations between the crystallographic structure of the NF-kappaB p50.p65 heterodimer bound to the uPA-kappaB target site to that of the p50.p65.HIV-kappaB complex. Next, cooperativity between two NF-kappaB molecules bound to tandem HIV-kappaB sequences was measured as well as that of NF-kappaB and transcription factor Sp1 when bound to adjacent sites. The cooperativity of hybrid HIV-LTR enhancers was measured with the 3' kappaB site converted to uPA-kappaB or to interferon beta gene enhancer kappaB. The hybrids were defective in transcriptional activator assembly and less active transcriptionally. These functional differences correlate with observed conformational differences and demonstrate that distinct kappaB DNA sequences function as allosteric regulators in a gene-specific manner.
Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. (1991)

The finding of capillary-obstructing polymorphonuclear leukocytes in the microvascular bed following middle cerebral artery reperfusion in focal ischemia in this model satisfies an essential requirement for postulating their role in early microvascular injury and the "no-reflow" phenomenon.
Cell cycle control in breast cancer cells (2005)

In breast cancer, cyclins D1 and E and the cyclin-dependent kinase inhibitors p21 (Waf1/Cip1)and p27 (Kip1) are important in cell-cycle control and as potential oncogenes or tumor suppressor genes. They are regulated in breast cancer cells following mitogenic stimuli including activation of receptor tyrosine kinases and steroid hormone receptors, and their deregulation frequently impacts on breast cancer outcome, including response to therapy. The cyclin-dependent kinase inhibitor p16 (INK4A) also has a critical role in transformation of mammary epithelial cells. In addition to their roles in cell cycle control, some of these molecules, particularly cyclin D1, have actions that are not mediated through regulation of cyclin-dependent kinase activity but may be important for loss of proliferative control during mammary oncogenesis.
The future of Englishes (1999)

Does an increasing awareness of the sheer international variety in the English language complex necessitate a new pedagogy for a new century?
Towards multifocal ultrasonic neural stimulation: pattern generation algorithms (2010)

Focused ultrasound (FUS) waves directed onto neural structures have been shown to dynamically modulate neural activity and excitability, opening up a range of possible systems and applications where the non-invasiveness, safety, mm-range resolution and other characteristics of FUS are advantageous. As in other neuro-stimulation and modulation modalities, the highly distributed and parallel nature of neural systems and neural information processing call for the development of appropriately patterned stimulation strategies which could simultaneously address multiple sites in flexible patterns. Here, we study the generation of sparse multi-focal ultrasonic distributions using phase-only modulation in ultrasonic phased arrays. We analyse the relative performance of an existing algorithm for generating multifocal ultrasonic distributions and new algorithms that we adapt from the field of optical digital holography, and find that generally the weighted Gerchberg-Saxton algorithm leads to overall superior efficiency and uniformity in the focal spots, without significantly increasing the computational burden. By combining phased-array FUS and magnetic-resonance thermometry we experimentally demonstrate the simultaneous generation of tightly focused multifocal distributions in a tissue phantom, a first step towards patterned FUS neuro-modulation systems and devices.
Holistic Scene Understanding for 3D Object Detection with RGBD Cameras (2013)

In this paper, we tackle the problem of indoor scene understanding using RGBD data. Towards this goal, we propose a holistic approach that exploits 2D segmentation, 3D geometry, as well as contextual relations between scenes and objects. Specifically, we extend the CPMC [3] framework to 3D in order to generate candidate cuboids, and develop a conditional random field to integrate information from different sources to classify the cuboids. With this formulation, scene classification and 3D object recognition are coupled and can be jointly solved through probabilistic inference. We test the effectiveness of our approach on the challenging NYU v2 dataset. The experimental results demonstrate that through effective evidence integration and holistic reasoning, our approach achieves substantial improvement over the state-of-the-art.
Density fluctuation measurements in ATF using correlation reflectometry (1992)

A two-frequency correlation reflectometer has been operated on the Advanced Toroidal Facility (ATF) to measure plasma electron density fluctuations. This reflectometer uses quadrature phase detection to permit true phase measurement of the reflected microwave signal (probing beam). By measuring the phase fluctuations in the reflected probing beam, the amplitude of the density fluctuations can be estimated. Simultaneous two-frequency operation makes it possible to measure the coherence between fluctuations at two radially separated cut-off layers, from which the radial correlation lengths and wavenumbers can be estimated. This reflectometer has been used to study the density fluctuations in the edge gradient region of low density ATF plasmas produced by electron cyclotron heating. These studies have revealed globally coherent turbulence with a radial correlation length of up to approximately 5 cm, a radial wavenumber kr ≈ 0 cm-1 and a poloidal wavenumber kθ ≈ 1 cm-1. The rms amplitude of the fluctuations reaches a maximum of ≈ 5% at the plasma edge (ρ = 1, where ρ is the flux surface normalized radius) and decreases with decreasing radius to a level of ≲1%. Simultaneous measurements of the fluctuations with the reflectometer, the heavy ion beam probe and the fast reciprocating Langmuir probe provide consistent results. A comparison of the measurements with simplistic mixing length estimates, ne/ne = 1/kθLn or ne/ne = 1/krLn, shows that these estimates are too high by factors of two to more than 100, while a comparison with a more detailed estimate for the pressure gradient driven resistive interchange turbulence yields reasonable agreement with the experimentally measured fluctuation characteristics
Rapid Construction in Yeast of Complex Targeting Vectors for Gene Manipulation in the Mouse (1996)

Targeting vectors for embryonic stem (ES) cells typically contain a mouse gene segment of >7 kb with the neo gene inserted for positive selection of the targeting event. More complex targeting vectors carry additional genetic elements (e.g. lacZ, loxP, point mutations). Here we use homologous recombination in yeast to construct targeting vectors for the incorporation of genetic elements (GEs) into mouse genes. The precise insertion of GEs into any position of a mouse gene segment cloned in an Escherichia coli/yeast shuttle vector is directed by short recombinogenic arms (RAs) flanking the GEs. In this way, complex targeting vectors can be engineered with considerable ease and speed, obviating extensive gene mapping in search for suitable restriction sites.
In vitro selection with artificial expanded genetic information systems (2013)

Artificially expanded genetic information systems (AEGISs) are unnatural forms of DNA that increase the number of independently replicating nucleotide building blocks. To do this, AEGIS pairs are joined by different arrangements of hydrogen bond donor and acceptor groups, all while retaining their Watson-Crick geometries. We report here a unique case where AEGIS DNA has been used to execute a systematic evolution of ligands by exponential enrichment (SELEX) experiment. This AEGIS-SELEX was designed to create AEGIS oligonucleotides that bind to a line of breast cancer cells. AEGIS-SELEX delivered an AEGIS aptamer (ZAP-2012) built from six different kinds of nucleotides (the standard G, A, C, and T, and the AEGIS nonstandard P and Z nucleotides, the last having a nitro functionality not found in standard DNA). ZAP-2012 has a dissociation constant of 30 nM against these cells. The affinity is diminished or lost when Z or P (or both) is replaced by standard nucleotides and compares well with affinities of standard GACT aptamers selected against cell lines using standard SELEX. The success of AEGIS-SELEX relies on various innovations, including (i) the ability to synthesize GACTZP libraries, (ii) polymerases that PCR amplify GACTZP DNA with little loss of the AEGIS nonstandard nucleotides, and (iii) technologies to deep sequence GACTZP DNA survivors. These results take the next step toward expanding the power and utility of SELEX and offer an AEGIS-SELEX that could possibly generate receptors, ligands, and catalysts having sequence diversities nearer to that displayed by proteins.
Correlation-based branch prediction (2003)

To enhance the accuracy of branch prediction, a correlation-based branch prediction scheme which takes into consideration the information provided by the outcomes of other branches as well is proposed. The scheme is examined using traces collected from running the SPEC benchmark suite on an IBM RISC System/6000 workstation. The results show that up to an addition of 11% prediction accuracy is achievable by the new scheme. For a branch target buffer, further reduction in branch delay is attained when it is used in conjunction with the new scheme.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cellular Delivery In Vivo of siRNA-Based Therapeutics (2008)

RNAi interference (RNAi) is an almost standard method for the knockdown of any target gene of interest in vitro, exploring a naturally occurring catalytic mechanism. Beyond functional analyses, the downregulation of pathologically relevant genes which are aberrantly expressed in a given disease will offer novel therapeutic approaches, also with regard to otherwise 'undruggable' genes. RNAi is mediated by small interfering RNAs (siRNA), and thus siRNA delivery in vivo is of critical importance for its implementation. Due to the instability and physicochemical properties of siRNAs, the development of strategies and formulations for siRNA protection, cellular uptake, correct intracellular localization and endosomal release, in combination with favourable pharmacokinetic properties, preferential delivery to the target organ, high biocompatibility and absence of unwanted side effects is crucial for the success of RNAi-based therapeutics. Approaches include the encapsulation in lipids, the complex formation with a variety of liposomes or cationic polymers, the chemical conjugation of siRNAs for example to peptides, aptamers or antibodies as well as other formulations. This review discusses non-viral strategies, based on different siRNA formulations and various modes of administration, for the delivery of therapeutic siRNAs to induce RNAi in vivo. It gives a comprehensive overview including a detailed listing of in vivo studies which have successfully employed various strategies for analytical or therapeutic siRNA-mediated gene targeting in different animal models, and presents a more in-depth description of some promising approaches with a special emphasis on polymers.
Lipoprotein-Associated and Secreted Phospholipases A 2 in Cardiovascular Disease (2010)

International audience
Genetic content and evolution of adenoviruses (2003)

This review provides an update of the genetic content, phylogeny and evolution of the family Adenoviridae. An appraisal of the condition of adenovirus genomics highlights the need to ensure that public sequence information is interpreted accurately. To this end, all complete genome sequences available have been reannotated. Adenoviruses fall into four recognized genera, plus possibly a fifth, which have apparently evolved with their vertebrate hosts, but have also engaged in a number of interspecies transmission events. Genes inherited by all modern adenoviruses from their common ancestor are located centrally in the genome and are involved in replication and packaging of viral DNA and formation and structure of the virion. Additional niche-specific genes have accumulated in each lineage, mostly near the genome termini. Capture and duplication of genes in the setting of a 'leader-exon structure', which results from widespread use of splicing, appear to have been central to adenovirus evolution. The antiquity of the pre-vertebrate lineages that ultimately gave rise to the Adenoviridae is illustrated by morphological similarities between adenoviruses and bacteriophages, and by use of a protein-primed DNA replication strategy by adenoviruses, certain bacteria and bacteriophages, and linear plasmids of fungi and plants.
Measurement of Orientation in Polypropylene Film (1960)

An average fiber axis orientation in polypropylene film was measured quantitatively from x-ray diffraction determination of orientation of two planes containing this axis. This orientation was expressed as the average square cosine of the angle between the fiber axis and a chosen reference direction in the sample. It was necessary to use an indirect method since there are no crystal planes perpendicular to the fiber axis. The nature of the fiber axis orientation thus determined was found to be consistent with birefringence measurements and qualitative deductions from pole figures. Films produced by flat die extrusion showed a double orientation in which the fiber axis is preferentially oriented in the extrusion direction, and the (010) crystal face is parallel to the film surface. Both components of the orientation tended to be of the same magnitude.
Isoprenoids: Remarkable diversity of form and function (2004)

The isoprenoid biosynthetic pathway is the source of a wide array of products. The pathway has been highly conserved throughout evolution, and isoprenoids are some of the most ancient biomolecules ever identified, playing key roles in many life forms. In this review we focus on C-10 mono-, C-15 sesqui-, and C-20 diterpenes. Evidence for interconversion between the pathway intermediates farnesyl pyrophosphate and geranylgeranyl pyrophosphate and their respective metabolites is examined. The diverse functions of these molecules are discussed in detail, including their ability to regulate expression of the beta-HMG-CoA reductase and Ras-related proteins. Additional topics include the mechanisms underlying the apoptotic effects of select isoprenoids, antiulcer activities, and the disposition and degradation of isoprenoids in the environment. Finally, the significance of pharmacological manipulation of the isoprenoid pathway and clinical correlations are discussed.