gebhart/patrepeval huggingface dataset:
Antisense Oligonucleotide Drug Design (2004)

Maneuvering single gene expression is not only an optimal way to study gene function but also an ambitious goal, which will lead to the treatment of a variety of human diseases whose main pathogenetic event is a genetic alteration. The recent efforts focusing on the genome project have led to array based, high throughput, gene expression analysis techniques that allow the study of complex molecular networks. Combining these powerful new technologies with modulation of gene expressions is making it possible to unravel complex molecular networks or, vice versa, to find new gene products responsible for pathological conditions on which exogenous modulation can be productive. Efficient and specific modulation of gene expression can be obtained either by producing transgenic or gene knockout organisms or cells (gene targeting), or by treating organisms or cells with short synthetic nucleic acid segments in antisense orientation with respect to the targeted mRNAs (mRNA targeting by antisense strategy). While genome manipulation is a time consuming and expensive approach, requiring invasive intervention, the "antisense strategy" is characterized by high flexibility resulting from safeness, specificity, reversibility, modulability, and low cost. The rationale of the antisense strategy is that, once one gene sequence is known, its expression can be silenced by application of synthetic single-strand nucleic acid segments (oligonucleotides) whose sequence is in antisense orientation compared to the targeted mRNA. Recently, this "informational" strategy has been boosted by the discovery of the RNA interference: a natural mechanism by which cells are thought to fight detrimental exogenous viruses and endogenous transposons. Despite promising futures, antisense-based therapeutics are far from being an established reality. This review analyses the recent improvements in antisense-based gene expression modulation, focuses on the treatment of diseases in the light of the past, and provides our personal findings on this topic.
No efficacious treatment for age-related macular degeneration. (2000)

There is a need for more efforts to find ways that influence the survival of the complex photoreceptor--retinal pigment epithelium--Bruch's membrane in the aging population.
The laboratory diagnosis of severe acute respiratory syndrome: emerging laboratory tests for an emerging pathogen. (2004)

The 2003 pandemic of Severe Acute Respiratory Syndrome (SARS) profiled the ability of modern diagnostic microbiology and molecular biology to identify, isolate and characterize, within weeks, a previously unknown viral infectious pathogen. The culprit, SARS coronavirus (SARS-CoV), was detected in patient specimens by traditional cell culture using an unusual cell line for respiratory viruses, Vero E6, and by reverse transcriptase polymerase chain reaction (RT-PCR) targeting the polymerase 1 B region of the genome. In addition, serologic assays were rapidly developed, and the genome of this large virus was sequenced within one month of its spread to North America. At the present time, diagnostics have progressed to the point that RT-PCR has a sensitivity approaching 80% within the first few days of onset of illness, while serology has a sensitivity close to 100% on convalescent sera taken >21 days after illness onset. Viral culture remains a method confined to biosafety level III laboratories. The specificity of RT-PCR and serology remains to be conclusively defined, but in most studies to date seems to be >90%. Serologic cross-reactivity with human coronaviruses causing the common cold may be a problem with some serologic assays. The early development of SARS-CoV diagnostics is now being replaced by refinement and optimization of these assays. Although at the present time we do not have a test that will definitively rule in or rule out SARS at the time of initial presentation of a patient with a respiratory infection, modifications of existing assays will hopefully result in our ability to make this diagnosis with a high degree of accuracy in the future.
Encrypted optical memory system using three-dimensional keys in the Fresnel domain (1999)

An encrypted optical memory system using double random phase codes in the Fresnel domain is proposed. In this system, two random phase codes and their positions form three-dimensional keys for encryption of images and are used as keys to recover the original data. The third dimension is the positions of the codes, which can have as many as three degrees of freedom. Original images encrypted by use of the two phase codes located in the Fresnel domain are stored holographically in a photorefractive material. We demonstrate in preliminary experiments encryption and decryption of optical memory in a LiNbO(3) :Fe photorefractive crystal by use of angular multiplexing.
2‘-C-Branched Ribonucleosides:  Synthesis of the Phosphoramidite Derivatives of 2‘-C-β-Methylcytidine and Their Incorporation into Oligonucleotides (1999)

We describe a strategy for the incorporation of a 2'-C-branched ribonucleoside, 2'-C-beta-methylcytidine, into oligonucleotides via solid-phase synthesis using phosphoramidite derivatives. 4-N-Benzoyl-2'-C-beta-methylcytidine (2b) was synthesized by coupling persilylated 4-N-benzoylcytosine with 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-alpha-(and beta)-D-ribofuranose (1) in the presence of SnCl(4) in acetonitrile, followed by selective deprotection with NaOH in pyridine/methanol. The 3'- and 5'-hydroxyl groups were blocked as a cyclic di-tert-butylsilanediyl ether 3 by treatment with di-tert-butyldichlorosilane/AgNO(3) in DMF. The 2'-hydroxyl group was then protected as a tert-butyldimethylsilyl ether 4a by treatment with tert-butylmagnesium chloride followed by addition of tert-butyldimethylsilyl trifluoromethanesulfonate in THF. As an alternative to 2'-silyl protection, the corresponding 2'-O-tetrahydropyranyl ether 4b was prepared by treatment of 3 with 4,5-dihydro-2H-pyran in the presence of a catalytic amount of 10-camphorsulfonic acid in methylene chloride. The di-tert-butylsilanediyl groups of 4a and 4b were removed by treatment with pyridinium poly(hydrogen fluoride) to afford 5a and 5b, respectively. Protection of the 5'-hydroxyl group as a dimethoxytrityl ether and phosphitylation of the 3'-hydroxyl group by the standard procedure gave the phosphoramidite derivatives 7a and 7b. Both 7a and 7b could be used to incorporate 2'-C-beta-methylcytidine into oligonucleotides efficiently via standard solid-phase synthesis, but the tetrahydropyranyl group of 7b was more readily removed from oligonucleotides than the tert-butyldimethylsilyl group of 7a. Oligonucleotides containing 2'-C-beta-methylcytidine undergo base-catalyzed degradation analogous to natural RNA.
Mitochondria, the killer organelles and their weapons (2002)

Apoptosis is a cell-autonomous mode of death that is activated to eradicate superfluous, damaged, mutated, or aged cells. In addition to their role as the cell's powerhouse, mitochondria play a central role in the control of apoptosis. Thus, numerous pro-apoptotic molecules act on mitochondria and provoke the permeabilization of mitochondrial membranes. Soluble proteins contained in the mitochondrial intermembrane space are released through the outer membrane and participate in the organized destruction of the cell. Several among these lethal proteins can activate caspases, a class of cysteine proteases specifically activated in apoptosis, whereas others act in a caspase-independent fashion, by acting as nucleases (e.g., endonuclease G), nuclease activators (e.g., apoptosis-inducing factor), or serine proteases (e.g., Omi/HtrA2). In addition, mitochondria can generate reactive oxygen species, following uncoupling and/or inhibition of the respiratory chain. The diversity of mitochondrial factors participating in apoptosis emphasizes the central role of these organelles in apoptosis control and unravels novel mechanisms of cell death execution.
Enteric Campylobacter: Purging Its Secrets? (2003)

Campylobacterial infections are the most common cause of bacterial enterocolitis in humans. Among children, especially in developing countries, Campylobacter infections can cause severe life-threatening diarrheal disease. Although usually associated with a benign outcome in the developed world, the burden of illness posed by Campylobacter infections is enormous, and serious neurologic sequelae also can occur. For a variety of reasons our understanding of the molecular and cellular pathogenesis of Campylobacter infection has lagged far behind that of other enteric pathogens. However, recent completion of the genome sequence of Campylobacter jejuni promises to open up the Campylobacter research field with the prospect of developing novel therapeutic and preventive strategies.
The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide‐binding sites (1994)

From an analysis of current data on 16 protein structures with defined nucleotide-binding sites consensus motifs were determined for the peptide segments that form such nucleotide-binding sites. This was done by using the actual residues shown to contact ligands in the different protein structures, plus an additional 50 sequences for various kinases. Three peptide segments are commonly required to form the binding site for ATP or GTP. Binding motif Kinase-1a is found in almost all sequences examined, and functions in binding the phosphates of the ligand. Variant versions, comparable to Kinase-1a, are found in a subset of proteins and appear to be related to unique functions of those enzymes. Motif Kinase-2 contains the conserved aspartate that coordinates the metal ion on Mg-ATP. Motif Kinase-3 occurs in at least four versions, and functions in binding the purine base or the pentose. Two protein structures show ATP-binding at a separate regulatory site, formed by the motifs Regulatory-1 and Regulatory-2. Structures for adenylate kinase and guanylate kinase show three different sequence motifs that form the binding site for a nucleoside monophosphate (NMP). NMP-1 and NMP-2 bind to the pentose and phosphate of the bound ligand. NMP-1 is found in almost all the kinases that phosphorylate AMP, CMP, GMP, dTMP, or UMP. NMP-3a is found in kinases for AMP, GMP, and UMP, while NMP-3b binds only GMP. For the binding of NTPs, three distinct types of nucleotide-binding fold structures have been described. Each structure is associated with a particular function (e.g. transfer of the gamma-phosphate, or of the adenylate to an acceptor) and also with a particular spatial arrangement of the three Kinase segments evident in the linear sequence for the protein.
High Performance, Variable-Length Instruction Encodings (2002)

Minimizing program code size reduces power consumption and space, which is especially important in embedded systems. Existing variable-length instruction formats provide higher code densities than fixed-length formats, but are ill-suited to pipelined or parallel instruction fetch and decode. This thesis presents a new variable-length instruction format that supports parallel fetch and decode of multiple instructions per cycle, allowing both high code density and rapid execution for high-performance processors. The new headsand -tails (HAT) format splits each instruction into a fixed-length head and a variable-length tail, and packs heads and tails in separate sections within a larger fixed-length instruction bundle. The heads can be easily fetched and decoded in parallel as they are a fixed distance apart in the instruction stream, while the variable-length tails provide improved code density. Compared to earlier schemes that expand compressed formats on cache refills, the new format is suitable for direct execution from the instruction cache, thereby increasing effective cache capacity and reducing cache power. Various implementations of the HAT format have been evaluated on re-encoded RISC and VLIW instruction sets, yielding compression ratios between 60% and 75% using only simple statistical compression techniques.
A selective-repeat-ARQ protocol for parallel channels and its resequencing analysis (1992)

A communications system in which multiple parallel channels are available to carry traffic from a transmitter to a receiver is considered, and an extension of the selective-repeat automatic repeat request (SR-ARQ) protocol that dynamically assigns packets to channels for each (re)transmission is presented. Because of selective retransmission, packets arrive at the receiver out of order and must be stored in a resequencing buffer. A queuing model for the resequencing buffer is constructed. The generating function of the buffer occupancy and the packet-delay distribution are derived, and procedures for simplifying the computation are presented. The dynamic assignment scheme is compared with, and shown to have performance superior to, a static assignment scheme.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Macrocyclic Chelator with Unprecedented Th4+ Affinity (2014)

A novel macrocyclic octadentate ligand incorporating terephthalamide binding units has been synthesized and evaluated for the chelation of Th(4+). The thorium complex was structurally characterized by X-ray diffraction and in solution with kinetic studies and spectrophotometric titrations. Dye displacement kinetic studies show that the ligand is a much more rapid chelator of Th(4+) than prevailing ligands (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and diethylenetriaminepentaacetic acid). Furthermore, the resulting complex was found to have a remarkably high thermodynamic stability, with a formation constant of 10(54). These data support potential radiotherapeutic applications.
Heat shock proteins in immune responses. (1993)

The assembly of functional MHC-I and MHC-II complexes is rapid, specific, and efficient. Recent advances in the area of antigen processing and presentation suggest that members of the heat shock protein (hsp) family facilitate the molecular events in the assembly process. Furthermore, hsps themselves have been shown to be the dominant antigens of a variety of pathogens as well as serving as targets of the immune system in healthy individuals. Hsps may play a fundamental role in immune responses, serving as an early warning to the host's immune system during the onset of infection.
The impact of attenuated phase shift mask topography on hyper-NA lithography (2005)

Thin mask approximations and Kirchhoff boundary conditions for imaging calculations are justified when patterns on masks are large compared to the imaging wavelength and the thickness of absorber films were relatively small compared with the wavelength. For the future technology nodes, these assumptions will not be sufficiently accurate for simulation of attenuated phase shift masks. At very high numerical apertures and extreme off-axis illumination angles, changes in the optical path length and shadowing by the mask topography can lead to phase and amplitude deviations between the thin mask approximation and the more rigorous, full Maxwell equations approach. We have found a systematic, non-constant transmission and phase variation through pitch for low k1 imaging that is not found with the thin-mask approach. In this paper, the major impacts of attenuated phase shift mask topography in the presence of extreme off-axis illumination with numerical apertures greater than one is investigated and the contribution of mask topography to CD errors on the wafer is explored. Consideration of this new mask component to CD error budgets is needed when debating the advantages and disadvantages in a reticle magnification change.
Copper-Catalyzed Diastereoselective Arylation of Tryptophan Derivatives: Total Synthesis of (+)-Naseseazines A and B (2013)

A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials. The utility of this transformation is highlighted in the five-step syntheses of the natural products (+)-naseseazine A and B.
OFDM-based cognitive radio for DSA networks (2007)

Dissertation (Ph.D.)--University of Kansas, Electrical Engineering & Computer Science, 2007.
The implementation of digital echo cancellation in codecs (1990)

The architecture of a codec in which the echo cancellation is done in two stages, an analog hybrid to reduce the echo level at the input of the A/D converter and a programmable digital balance filter, is presented. The design problems connected with this architecture, such as the signal-to-noise performance of the A/D converter and the limiting effects of the variation of the analog components on the echo cancellation performance of the device and on the structure of the digital balance filters, are discussed. These results were used in the design of a single-power-supply CMOS device implemented in 1.5- mu m technology using Sigma Delta modulation techniques for A/D and D/A conversion. Its echo cancellation performance is sufficiently high that only one set of coefficients per national standard is necessary.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Optimization of microencapsulation parameters: Semipermeable microcapsules as a bioartificial pancreas (1985)

An improved membrane has been developed for the microencapsulation of islets of Langerhans which protects these cells from the immune system. These requirements were accomplished through the optimization of important microencapsulation parameters and through the improved biocompatibility of a new alginate-poly-l-lysine (PLL)-alginate capsule membrane. Spherical and smooth microcapsules could be formed by utilizing a purer sodium alginate and by keeping the viscosity of the sodium alginate solution above 30 cps. The strength of the capsule membrane was enhanced by increasing the alginate-PLL reaction time as well as the PLL concentration. The permeability of the membrane [4 mum thick, 93% (w/w) water] was a function of the viscosity average molecular weight (Mv) of the PLL (Mv = 4000-4 x 10(5)) used in the encapsulation procedure. Microcapsules prepared with PLL with Mv = 1.7 x 10(4) were the least permeable, being impermeable to normal serum immunoglobulin, albumin, and haemoglobin. The microencapsulation procedure, by protecting transplanted tissue from the components of the immune system, has great clinical potential as a new form of treatment for diseases such as diabetes and liver disease.
Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. (2002)

Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins that are being developed for the targeted therapy of cancer. RFB4 (Fv)-Pseudomonas exotoxin 38 (PE38) is an immunotoxin that targets CD22 expressed on B cells and B-cell malignancies. A disulfide-stabilized form of RFB4 (Fv)-PE38 is being evaluated in a Phase I clinical trial. The aim of the present study was to improve the activity of RFB4 (Fv)-PE38 to more effectively treat patients with leukemias and lymphomas. To increase the affinity of RFB4 (Fv), we used the techniques of phage display and hot spot mutagenesis. We identified mutational hot spot sequences in heavy chain complementary determining region 3 (V(H) CDR3) and randomized these in a phage display library. Mutant phages were panned on CD22-positive Daudi cells. A variety of mutant Fvs were obtained, and the corresponding immunotoxins were prepared. Several mutant immunotoxins with increased binding affinity and cytotoxic activity were obtained. The most active immunotoxin contained amino acid residues Thr-His-Trp (THW) in place of Ser-Ser-Tyr (SSY) at positions 100, 100A, and 100B of the Fv and had an affinity improved from 85 nM to 6 nM. The THW mutant had a 5- to 10-fold increase in activity on various CD22-positive cell lines and was up to 50 times more cytotoxic to cells from patients with chronic lymphocytic leukemia and hairy-cell leukemia.
Selection of Active ScFv to G-Protein-Coupled Receptor CCR5 Using Surface Antigen-Mimicking Peptides (2004)

This study describes the use of cyclic peptides for use in the selection of single-chain (ScFv) antibodies specific for the HIV-1 coreceptor CCR5, a representative G-protein-coupled receptor (GPCR). A tandem ligation strategy was developed for preparing biotinylated cyclic peptides, first through an orthogonal end-to-end ligation and then a chemoselective ligation with functionalized biotin. Cyclic peptides mimicking the extracellular loops of CCR5 and their unconstrained counterparts were then used for solution-phase selection of ScFv antibodies from a phage display antibody library. Antibodies reactive with CCR5 on cells were detected using a homogeneous high throughput assay. Of 19 isolated ScFv antibodies that bound to CCR5+ cells, three inhibited CCR5-mediated but not CXCR4-mediated HIV infection. Only ScFvs selected by binding to cyclic constrained peptides exhibited inhibitory activity. Our results demonstrate that surface-antigen mimetics of a GPCR are effective tools for selecting active, site-specific ScFv antibodies that hold promise as immunological reagents and therapeutics.
Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective (2013)

We present a comprehensive overview of the hierarchical network of intracellular processes revolving around central nitrogen metabolism in Escherichia coli. The hierarchy intertwines transport, metabolism, signaling leading to posttranslational modification, and transcription. The protein components of the network include an ammonium transporter (AmtB), a glutamine transporter (GlnHPQ), two ammonium assimilation pathways (glutamine synthetase [GS]-glutamate synthase [glutamine 2-oxoglutarate amidotransferase {GOGAT}] and glutamate dehydrogenase [GDH]), the two bifunctional enzymes adenylyl transferase/adenylyl-removing enzyme (ATase) and uridylyl transferase/uridylyl-removing enzyme (UTase), the two trimeric signal transduction proteins (GlnB and GlnK), the two-component regulatory system composed of the histidine protein kinase nitrogen regulator II (NRII) and the response nitrogen regulator I (NRI), three global transcriptional regulators called nitrogen assimilation control (Nac) protein, leucine-responsive regulatory protein (Lrp), and cyclic AMP (cAMP) receptor protein (Crp), the glutaminases, and the nitrogen-phosphotransferase system. First, the structural and molecular knowledge on these proteins is reviewed. Thereafter, the activities of the components as they engage together in transport, metabolism, signal transduction, and transcription and their regulation are discussed. Next, old and new molecular data and physiological data are put into a common perspective on integral cellular functioning, especially with the aim of resolving counterintuitive or paradoxical processes featured in nitrogen assimilation. Finally, we articulate what still remains to be discovered and what general lessons can be learned from the vast amounts of data that are available now.