gebhart/patrepeval huggingface dataset:
Development of a novel biocompatible polymer system for extended drug release in a next‐generation drug‐eluting stent (2007)

Drug-eluting stents have proven superior to bare metal stents with lower restenosis rates. Local delivery of drugs from these stents is achieved in most cases with the help of biostable polymer coatings. However, since the polymer coating remains in the body well after all the drug is released, patients can potentially develop hypersensitivity to these polymers--leading to complications such as late-stent thrombosis. It is therefore important that the polymers are designed to be biocompatible and well tolerated by the body. The polymer coatings are also expected to be robust and provide good control over elution of the desired drug. This paper describes the development of a unique, proprietary polymer blend system, specially designed to meet these requirements. Mutually compatible, free-radical-initiated elastomeric polymers were designed to provide a robust coating and offer a steady, sustained release of the highly hydrophobic drug zotarolimus over an extended period. The polymer blend system is also well tolerated by the hydrophilic environment in vivo, as demonstrated through porcine studies.
The p97 Inhibitor CB-5083 Is a Unique Disrupter of Protein Homeostasis in Models of Multiple Myeloma (2017)

Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system, and CB-5083, a first-in-class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematologic and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma cell lines and a number of <i>in vivo</i> multiple myeloma models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response, and apoptosis. CB-5083 decreases viability in multiple myeloma cell lines and patient-derived multiple myeloma cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs, which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. <i>In vivo</i> studies using clinically relevant multiple myeloma models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with multiple myeloma standard-of-care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several multiple myeloma disease models and provide the rationale for clinical evaluation as monotherapy and in combination in multiple myeloma. <i>Mol Cancer Ther; 16(11); 2375-86. ©2017 AACR</i>.
Principles of Digital Transmission: With Wireless Applications (1999)

From the Publisher:
Principles of Digital Transmission is designed for advanced undergraduate and graduate level students and professions in telecommunications. Teachers and learners can mix and match chapters to create four distinct courses: (1) a one-term basic course in digital communications; (2) a one-term course in advanced digital communications; (3) a one-term course in information theory and coding; (4) a two-term course sequence in digital communications and coding. 

The book provides rigorous mathematical tools for the analysis and design of digital transmission systems. The authors emphasize methodology in their aim to teach the reader how to do it rather than how it is done. They apply the fundamental tools of the discipline onto a number of systems, such as wireless data transmission systems.
Purification and Partial Characterization of Immobilization Antigens from Ichthyophthirius multifiliis (1992)

Ichthyophthirius multifiliis, a parasitic ciliate of freshwater fishes, was found to have surface antigens (Ag) which elicited immobilizing antibodies (Ab) when injected into rabbits. An effort was made to purify and characterize these Ag (referred to as immobilization Ag) because of their potential role in protective immunity in fishes. Mice immunized with theront cilia were used for production of immobilizing monoclonal antibodies (MAb). Hybridomas were screened by indirect immunofluorescent light microscopy and immobilization of live parasites. Six hybridomas producing immobilizing MAb were cloned. Immobilizing MAb were used to affinity purify Ag solubilized with Triton X-114 and Na deoxycholate. Two membrane protein Ag of approximately 48 and 60 kDa were identified. Immobilizing MAb failed to react with these Ag on Western blots and, conversely, MAb that reacted with the Ag on Western blots did not immobilize live organisms. These results suggest that immobilization required native conformational epitopes which were altered by Western blotting procedures. Individual MAb reactive on Western blots recognized both the 48- and 60-kDa proteins indicating the presence of common epitopes. Affinity purified Ag elicited immobilizing antisera when injected into rabbits, mice, and channel catfish.
Cytotoxicity of two proteins isolated from Bacillus thuringiensis var. israelensis crystals to insect and mammalian cell lines (1985)

Two toxic proteins (proteins A and B) were isolated from Bacillus thuringiensis var. israelensis crystals using ion-exchange chromatography. A cell cytotoxicity assay based on the uptake of [3H]uridine by tissue culture cells following exposure to the toxic proteins, was used to measure the viability of the cells. Proteins A and B were cytotoxic to Aedes aegypti and MA104 cells. Protein B was also cytotoxic to Spodoptera frugiperda cells.
On the Reaction of Tryptophan Derivatives with N-Phenylselenyl Phthalimide:  The Nature of the Kinetic and Thermodynamic Hexahydropyrrolo[2,3-b]indole Products. Alkylation of Tryptophan with Inversion of Configuration (1999)

The cyclization of a range of tryptophan derivatives with N-phenylselenyl phthalimide leading to 3a-phenylselenyl-1,2,3,3a,8,8a-hexahydro[2,3-b]pyrroloindoles has been studied. It is established that in each case the kinetic diastereomer has the C-2 substituent on the exo face of the diazabicyclo[3.3.0]octane skeleton, whereas the thermodynamic isomers have the C-2 substituent endo. A simple protocol for the alkylation of tryptophan, leading to α-substituted tryptophans with clean inversion of configuration, is presented.
Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases (2009)

Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjögren's syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions--a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.
311C90: Increasing the options for therapy with effective acute antimigraine 5HT 1B/1D receptor agonists (1997)

The novel antimigraine drug 311C90 (Zomig; zolmitriptan) has a high selectivity for serotonin (5HT)1 receptors, mainly 5HT1B and 5HT1D subtypes, and in preclinical studies it has been shown to act on four different sites within the trigemino-vascular system (blockade of neurogenic inflammation by inhibition of peptide release, vasoconstriction, inhibition of neuronal depolarization at peripheral sites, and effects at central sites). Oral 311C90 has a favorable pharmacokinetic profile. It is rapidly absorbed, with 75% of maximal plasma concentration (Cmax) attained within 1 hour and good absolute oral bioavailability (approximately 40%). Clinical studies have shown 311C90 to be rapidly and consistently effective in relieving migraine headache, with initial doses of between 2.5 and 5 mg providing an optimal balance between efficacy and safety considerations. Moreover, the good tolerability of 311C90 is supported by clinical data showing that doses up to 10-fold the therapeutic dose (2.5 mg) did not raise any serious safety concerns, highlighting the favorable safety profile of this drug.
Effects on Faecal Microbiota of Dietary and Acidic Oligosaccharides in Children During Partial Formula Feeding (2008)

Infant formulae appear to be clinically safe and effective on infant microbiota. They minimize the alteration of faecal microbiota after cessation of breast-feeding and promote bifidobacteria proportions, with a stronger effect when acidic oligosaccharides are present.
Insertional Inactivation of Methylmalonyl Coenzyme A (CoA) Mutase and Isobutyryl-CoA Mutase Genes in Streptomyces cinnamonensis : Influence on Polyketide Antibiotic Biosynthesis (1999)

The coenzyme B(12)-dependent isobutyryl coenzyme A (CoA) mutase (ICM) and methylmalonyl-CoA mutase (MCM) catalyze the isomerization of n-butyryl-CoA to isobutyryl-CoA and of methylmalonyl-CoA to succinyl-CoA, respectively. The influence that both mutases have on the conversion of n- and isobutyryl-CoA to methylmalonyl-CoA and the use of the latter in polyketide biosynthesis have been investigated with the polyether antibiotic (monensin) producer Streptomyces cinnamonensis. Mutants prepared by inserting a hygromycin resistance gene (hygB) into either icmA or mutB, encoding the large subunits of ICM and MCM, respectively, have been characterized. The icmA::hygB mutant was unable to grow on valine or isobutyrate as the sole carbon source but grew normally on butyrate, indicating a key role for ICM in valine and isobutyrate metabolism in minimal medium. The mutB::hygB mutant was unable to grow on propionate and grew only weakly on butyrate and isobutyrate as sole carbon sources. (13)C-labeling experiments show that in both mutants butyrate and acetoacetate may be incorporated into the propionate units in monensin A without cleavage to acetate units. Hence, n-butyryl-CoA may be converted into methylmalonyl-CoA through a carbon skeleton rearrangement for which neither ICM nor MCM alone is essential.
Expression of Genes Encoding Multi-Transmembrane Proteins in Specific Primate Taste Cell Populations (2009)

Identification of genes encoding multi-transmembrane domain proteins expressed in primate taste buds provides new insights into the processes of taste cell development, signal transduction, and information coding. Discrete taste cell populations exhibit highly specific gene expression patterns, supporting a model whereby each mature taste receptor cell is responsible for sensing, transmitting, and coding a specific taste quality.
Effect of Preexisting Immunity to Adenovirus Human Serotype 5 Antigens on the Immune Responses of Nonhuman Primates to Vaccine Regimens Based on Human- or Chimpanzee-Derived Adenovirus Vectors (2007)

In this study we compared a prime-boost regimen with two serologically distinct replication-defective adenovirus (Ad) vectors derived from chimpanzee serotypes C68 and C1 expressing Gag, Pol, gp140, and Nef of human immunodeficiency virus type 1 with a regimen in which replication-defective Ad vectors of the human serotype 5 (AdHu5) were given twice. Experiments were conducted in rhesus macaques that had or had not been preexposed to antigens of AdHu5. There was no significant difference in T-cell responses tested from peripheral blood of the different groups, although responses were overall highest in nonpreexposed animals immunized with the chimpanzee Ad vectors. Preexisting immunity to AdHu5 completely inhibited induction of transgene product-specific antibodies by the AdHu5 vectors without affecting antibody responses to the chimpanzee vectors. Upon euthanasia, T-cell responses were tested from a number of tissues. Preexisting immunity to AdHu5, commonly found in humans, changed the homing pattern of vaccine-induced T cells. In AdHu5-preexposed animals vaccinated with the chimpanzee Ad vectors, frequencies of transgene-specific T cells were higher in spleens than in blood, and in most preexposed animals vaccinated either with AdHu5 vectors or chimpanzee adenovirus vectors, frequencies of such T cells were exceptionally high in livers. The latter results indicate that analysis of T-cell responses solely from blood mononuclear cells of vaccine recipients may not suffice to compare the potencies of different vaccine regimens.
RNA Polymerase II cluster dynamics predict mRNA output in living cells (2016)

Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output.
Multispeaker speech activity detection for the ICSI meeting recorder (2005)

As part of a project into speech recognition in meeting environments, we have collected a corpus of multichannel meeting recordings. We expected the identification of speaker activity to be straightforward given that the participants had individual microphones, but simple approaches yielded unacceptably erroneous labelings, mainly due to crosstalk between nearby speakers and wide variations in channel characteristics. Therefore, we have developed a more sophisticated approach for multichannel speech activity detection using a simple hidden Markov model (HMM). A baseline HMM speech activity detector has been extended to use mixtures of Gaussians to achieve robustness for different speakers under different conditions. Feature normalization and crosscorrelation processing are used to increase the channel independence and to detect crosstalk. The use of both energy normalization and crosscorrelation based postprocessing results in a 35% relative reduction of the frame error rate. Speech recognition experiments show that it is beneficial in this multispeaker setting to use the output of the speech activity detector for presegmenting the recognizer input, achieving word error rates within 10% of those achieved with manual turn labeling.
10.1016/j.ohc.2006.05.009 (2000)

Ranibizumab therapy is the first treatment for neovascular AMD to improve vision for most patients. The benefits apply to all angiographic subtypes of neovascular AMD and across all lesion sizes. Although the pivotal phase III trials (MARINA and ANCHOR) used monthly injections of ranibizumab for 2 years, the ongoing PIER, PrONTO, and SAILOR trials are investigating less frequent dosing regimens, and preliminary results from the PrONTO study suggest that fewer injections will most likely result in visual acuity improvements similar to the results from the phase III trials. When comparing the ANCHOR results with the FOCUS results, it also becomes apparent that the combination of ranibizumab with PDT does not necessarily result in better visual acuity outcomes, and the use of PDT may even reduce the visual acuity benefits achieved with ranibizumab alone (see Figs. 1-3). It seems unlikely that combination therapy provides any significant advantage over ranibizumab alone unless the combination of PDT and ranibizumab can decrease the need for frequent retreatment. The results from the PrONTO Study already suggest that less frequent treatment with ranibizumab is possible by using a variable dosing regimen with OCT. Ranibizumab also seems to be safe, with the 2-year MARINA data showing no increase in the incidence of systemic adverse events that could be associated with anti-VEGF therapy, such as myocardial infarction and stroke. There was a hint of a safety concern, however, in the pooled 1-year safety results from the MARINA and ANCHOR trials. Although the combined rate of myocardial infarction and stroke during the first year of the ANCHOR and MARINA trials was similar in the control and the 0.3-mg ranibizumab arms (1.3% and 1.6% respectively), these adverse events were slightly higher in the 0.5-mg ranibizumab arm (2.9%). These differences are not statistically significant, however, and probably do not represent a dose-dependent increase in risk because the 2-year results from the MARINA trial with the same monthly injection regimen showed no increased risk of thromboembolic events. In December 2005, Genentech submitted a Biologics License Application to the FDA for the use of ranibizumab in the treatment of neovascular wet AMD based on 1-year clinical efficacy and safety data from the two pivotal phase III trials, ANCHOR and MARINA, and the phase I-II FOCUS trial. Genentech has been granted a 6-month Priority Review from the FDA with a decision anticipated 6 months from the December submission date or by the end of June 2006 [29]. By the summer of 2006, this revolutionary therapy should be available for the treatment of neovascular AMD. At that time, the major dilemma facing most retina specialists will be whether to use intravitreal ranibizumab or intravitreal bevacizumab, the low cost alternative, for the treatment of neovascular AMD.
Antigen-presenting Capacity of Epidermal Cells Infected with Vaccinia Virus Recombinants Containing the Herpes Simplex Virus Glycoprotein D, and Protective Immunity (1989)

We studied the association of herpes simplex type 1 (HSV-1) glycoprotein D (gD-1) expression in epidermal cells (EC) with virus-specific immunity and protection of mice from fatal HSV-2 challenge. Vaccinia virus recombinants containing gD-1 under the control of an early (VP176) or late (VP254) vaccinia virus promoter were used. Mature gD-1 protein was expressed in VP176-infected EC and they had accessory cell function for HSV-2-induced T cell proliferation of immune lymph node cells (LNC). It was not expressed in VP254-infected EC and they did not act as accessory cells. LNC from VP176- but not VP254-immunized mice proliferated in response to HSV antigen and only VP176-immunized mice had complete long-term protection from HSV-2 challenge.
Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease (2016)

Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.
Cleavage of p75 Neurotrophin Receptor by α-Secretase and γ-Secretase Requires Specific Receptor Domains (2005)

The p75 neurotrophin receptor (p75(NTR)), a member of the tumor necrosis factor superfamily of receptors, undergoes multiple proteolytic cleavage events. These events are initiated by an alpha-secretase-mediated release of the extracellular domain followed by a gamma-secretase-mediated intramembrane cleavage. However, the specific determinants of p75(NTR) cleavage events are unknown. Many other substrates of gamma-secretase cleavage have been identified, including Notch, amyloid precursor protein, and ErbB4, indicating there is broad substrate recognition by gamma-secretase. Using a series of deletion mutations and chimeric receptors of p75(NTR) and the related Fas receptor, we have identified domains that are essential for p75(NTR) proteolysis. The initial alpha-secretase cleavage was extracellular to the transmembrane domain. Unfortunately, deletion mutants were not capable of defining the requirements of ectodomain shedding. Although this cleavage is promiscuous with respect to amino acid sequence, its position with respect to the transmembrane domain is invariant. The generation of chimeric receptors exchanging different domains of noncleavable Fas receptor with p75(NTR), however, revealed that a discrete domain above the membrane is sufficient for efficient cleavage of p75(NTR). Mass spectrometric analysis confirmed the cleavage can occur with a truncated p75(NTR) displaying only 15 extracellular amino acids in the stalk region.
Architecture and technology considerations for multimedia broadband communications (2003)

The author highlights some of the rules and design tradeoffs which have to be considered in the evolution to an asynchronous transfer mode (ATM) based transport network. The first rules addressed refer to the connection control partitioning between out-of-band and in-band signalling for the design of generic ATM transport and recommend that the split should consider differentiation between connection-specific and generic control functions. The second set of rules refers to ATM system design for performance and efficiency and indicates the critical service parameters responsible for optimum system operation. The third set of rules refers to services integration under performance constraints for different traffic volumes and recommends transport separation of certain performance-sensitive applications in the early network-evolution phases.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Q-Switching In Fibre Lasers (1990)

The performance and charactersics of various Q-switched fibre lasers are examined. All results presented are for laser diode pumped systems, emphasizing the practicality of the Q-switched fibre laser. Operation at 0.94, 1.06, 1.09 and 1.57Am wavelengths are covered. The results presented show that Q-switching is currently limited by the performance of the modulator. Theoretical modelling of the process allows us to determine the required properties for a modulator and in addition to predict the expected performance of Q-switched fibre lasers under different conditions.
Yb and Yb-K fulleride formation, bonding, and electrical character (1992)

Yb mixing with ${\mathrm{C}}_{60}$ produces a phase with approximately two Yb atoms per fullerene but showed no indication of ${\mathrm{Yb}}_{\mathit{x}}$${\mathrm{C}}_{60}$ phases with x=3, 4, and 6. Thin-film resistivity measurements indicate that this Yb fulleride is a semiconductor with a resistivity of 100 m\ensuremath{\Omega} cm at 300 K and 38 m\ensuremath{\Omega} cm at 400 K. Yb condensation onto metallic ${\mathrm{K}}_{3}$${\mathrm{C}}_{60}$ produces a ternary compound.
Ligand-Gated Split-Kinases (2014)

The activity of protein kinases are naturally gated by a variety of physiochemical inputs, such as phosphorylation, metal ions, and small molecules. In order to design protein kinases that can be gated by user-defined inputs, we describe a sequence dissimilarity based approach for identifying sites in protein kinases that accommodate 25-residue loop insertion while retaining catalytic activity. We further demonstrate that the successful loop insertion mutants provide guidance for the dissection of protein kinases into two fragments that cannot spontaneously assemble and are thus inactive but can be converted into ligand-gated catalytically active split-protein kinases. We successfully demonstrate the feasibility of this approach with Lyn, Fak, Src, and PKA, which suggests potential generality.