gebhart/patrepeval huggingface dataset:
Potent Induction of Tumor Immunity by Combining Tumor Cryoablation with Anti–CTLA-4 Therapy (2011)

Thermal ablation to destroy tumor tissue may help activate tumor-specific T cells by elevating the presentation of tumor antigens to the immune system. However, the antitumor activity of these T cells may be restrained by their expression of the inhibitory T-cell coreceptor CTLA-4, the target of the recently U.S. Food and Drug Administration-approved antibody drug ipilumimab. By relieving this restraint, CTLA-4-blocking antibodies such as ipilumimab can promote tumor rejection, but the full scope of their most suitable applications has yet to be fully determined. In this study, we offer a preclinical proof-of-concept in the TRAMP C2 mouse model of prostate cancer that CTLA-4 blockade cooperates with cryoablation of a primary tumor to prevent the outgrowth of secondary tumors seeded by challenge at a distant site. Although growth of secondary tumors was unaffected by cryoablation alone, the combination treatment was sufficient to slow growth or trigger rejection. In addition, secondary tumors were highly infiltrated by CD4(+) T cells and CD8(+) T cells, and there was a significant increase in the ratio of intratumoral T effector cells to CD4(+)FoxP3(+) T regulatory cells, compared with monotherapy. These findings documented for the first time an effect of this immunotherapeutic intervention on the intratumoral accumulation and systemic expansion of CD8(+) T cells specific for the TRAMP C2-specific antigen SPAS-1. Although cryoablation is currently used to treat a targeted tumor nodule, our results suggest that combination therapy with CTLA-4 blockade will augment antitumor immunity and rejection of tumor metastases in this setting.
RNAi as a gene therapy approach (2003)

RNA duplexes of 21 - 23 nucleotides (nts), with approximately 2 nt 3' overhangs (called small interfering RNAs or siRNAs), have recently been shown to mediate sequence-specific inhibition of gene expression in mammalian cells via a post-transcriptional gene silencing (PTGS) mechanism termed RNA interference (RNAi). RNAi has been rapidly adopted as a functional genomics tool in a wide range of species, has been adapted to allow for the transient or stable knockdown of gene expression generation in cell lines and animals, and has been developed for high-throughput analysis of gene function in Caenorhabditis elegans. With an increasing list of genes successfully knocked-down by RNAi in mammalian cells and improvements in the delivery of siRNAs to cells, including in vivo delivery to mice, attention is now turning to assessing the potential RNAi has as a gene therapy approach. RNAi is likely to have the greatest impact as a therapeutic tool in two key clinical areas, cancer and infectious disease, but it also has the potential as a therapy for other disorders including some dominant genetic diseases. This review will describe the status of the science behind this novel mechanism and will illustrate the therapeutic potential of RNAi-based technologies, using examples from these critical clinical research areas.
Minimum-energy broadcast in all-wireless networks (2002)

In all-wireless networks a crucial problem is to minimize energy consumption, as in most cases the nodes are battery-operated. We focus on the problem of power-optimal broadcast, for which it is well known that the broadcast nature of the radio transmission can be exploited to optimize energy consumption. Several authors have conjectured that the problem of power-optimal broadcast is NP-complete. We provide here a formal proof, both for the general case and for the geometric one; in the former case, the network topology is represented by a generic graph with arbitrary weights, whereas in the latter a Euclidean distance is considered. We then describe a new heuristic, Embedded Wireless Multicast Advantage. We show that it compares well with other proposals and we explain how it can be distributed.
Single-Molecule Detection of DNA Separations in Microfabricated Capillary Electrophoresis Chips Employing Focused Molecular Streams (1999)

DNA separations have been performed using microfabricated capillary electrophoresis chips and detected using a single-molecule fluorescence burst counting technique. We enhanced the percentage of electromigrating DNA molecules that were detected by focusing the sample through the 1-microm-diameter focused laser beam. The sample was focused by introducing a taper in the separation channel and by a sheath flow delivered from cross channels. The sample stream width, single-molecule velocities, and single-molecule count rates varied linearly with the current density ratio as expected. The optimal laser power for each focusing condition was investigated using dilute solutions of pBluescript DNA. Although fluorescence burst heights and background varied with laser power, the signal-to-noise ratio was only weakly dependent on this parameter using our single-molecule counting technique. Focused single-molecule counting was used to detect separations of a 100-1000-bp DNA sizing ladder. The increase in molecular detection efficiency was quantified by applying a focusing current midway through the ladder separation and comparing observed count rates to the known molecular concentration in the bands. The molecular detection efficiency varied linearly with the applied current density ratio, and greater than 3-fold enhancements in detection efficiency were achieved.
Effectiveness of erythrosine-mediated photodynamic antimicrobial chemotherapy on dental plaque aerobic microorganisms: A randomized controlled trial (2017)

Erythrosine-mediated PACT reduces the extent of dental plaque microbial count and has a potential preventive and therapeutic use in day-to-day life and dental clinics.
Receptor-mediated Gene Transfer to Airway Epithelial Cells in Primary Culture (1993)

A variety of methods have been utilized for gene transfer to the cells of the airway epithelium. These have included DNA-mediated mechanisms of gene transfer as well as recombinant viral vectors. Despite the availability of these methods, limitations in their utility warrant the development of alternate systems. As an alternative, receptor-mediated endocytosis using transferrin-polylysine conjugates has been shown to transduce immortalized airway epithelial cells efficiently via a physiologic pathway. When transferrin-polylysine conjugates were used to transduce airway epithelial cells grown in primary culture, however, gene transfer occurred inefficiently. Investigation into this relative inefficiency centered on endosomal entrapment of the conjugate-DNA complex. Pretreatment of the cells with chloroquine, which causes vacuolization and disruption of the endosome, or co-delivery of adenoviral particles, which serves to lyse the endosomal membrane, were both associated with greatly improved gene transfer efficiency. These studies established that the relative refractory state of the airway epithelial cells in primary culture was secondary to the retention of the internalized material within the endosome. We thus explored the efficiency of conjugates that possessed a mechanism to escape this endosomal entrapment; adenovirus-polylysine conjugates and transferrin-polylysine/adenovirus-polylysine conjugates were thus employed. Gene transfer efficiency improved significantly with the adenovirus-containing conjugates. These data support the concept that conjugates can be synthesized that mediate highly efficient gene transfer to airway epithelial cells in primary culture via the receptor-mediated endocytosis pathway.
Paired-end sequencing of Fosmid libraries by Illumina (2012)

Eliminating the bacterial cloning step has been a major factor in the vastly improved efficiency of massively parallel sequencing approaches. However, this also has made it a technical challenge to produce the modern equivalent of the Fosmid- or BAC-end sequences that were crucial for assembling and analyzing complex genomes during the Sanger-based sequencing era. To close this technology gap, we developed Fosill, a method for converting Fosmids to Illumina-compatible jumping libraries. We constructed Fosmid libraries in vectors with Illumina primer sequences and specific nicking sites flanking the cloning site. Our family of pFosill vectors allows multiplex Fosmid cloning of end-tagged genomic fragments without physical size selection and is compatible with standard and multiplex paired-end Illumina sequencing. To excise the bulk of each cloned insert, we introduced two nicks in the vector, translated them into the inserts, and cleaved them. Recircularization of the vector via coligation of insert termini followed by inverse PCR generates a jumping library for paired-end sequencing with 101-base reads. The yield of unique Fosmid-sized jumps is sufficiently high, and the background of short, incorrectly spaced and chimeric artifacts sufficiently low, to enable applications such as mapping of structural variation and scaffolding of de novo assemblies. We demonstrate the power of Fosill to map genome rearrangements in a cancer cell line and identified three fusion genes that were corroborated by RNA-seq data. Our Fosill-powered assembly of the mouse genome has an N50 scaffold length of 17.0 Mb, rivaling the connectivity (16.9 Mb) of the Sanger-sequencing based draft assembly.
A taxonomy of sequential pattern mining algorithms (2010)

Owing to important applications such as mining web page traversal sequences, many algorithms have been introduced in the area of sequential pattern mining over the last decade, most of which have also been modified to support concise representations like closed, maximal, incremental or hierarchical sequences. This article presents a taxonomy of sequential pattern-mining techniques in the literature with web usage mining as an application. This article investigates these algorithms by introducing a taxonomy for classifying sequential pattern-mining algorithms based on important key features supported by the techniques. This classification aims at enhancing understanding of sequential pattern-mining problems, current status of provided solutions, and direction of research in this area. This article also attempts to provide a comparative performance analysis of many of the key techniques and discusses theoretical aspects of the categories in the taxonomy.
P2–402: Double–blind, placebo–controlled study of three different dosages of cerebrolysin in patients with mild to moderate Alzheimer's disease (2006)

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease (AD) in previous trials. In this study we investigated the efficacy and safety of three dosages of Cere in mild to moderate AD patients included in a randomized, double–blind, placebo–controlled trial. AD patients (intent–to–treat (ITT) dataset: 251 cases; 73 male/178 female; age: 50–90 years) received iv infusions of Cere (10, 30 or 60 ml) or placebo (0.9% saline, 100 ml) 5 days/week for four weeks (20 infusions) and thereafter two times per week for 8 weeks (16 infusions). The patients were then without treatment for another 12 weeks until the end of the study (week 24). The effects of Cere on cognition and clinical global impression were evaluated by using the modified AD Assessment Scale (ADAS–cog) and the CIBIC+ (Clinical Interview–based Impression of Change). Primary efficacy parameters were CIBIC+ score and change from baseline in the ADAS–cog+ at week 24. Secondary efficacy (activities of daily living and neuropsychiatric symptoms) and safety parameters were also evaluated. Significant improvements of cognitive performance on the ADAS–cog (−4.1; p=0.038) and global function (CIBIC+; p<0.001) were observed at week 24 for the 10 ml dose. Doses of 30 and 60 ml showed significant improvement of the global outcome but failed to show significant improvement of cognition (30 ml: −3.62, p=0.069; 60 ml: −2.33, p=0.330). Neuropsychiatric symptoms were also improved significantly (p<0.05) by the 60 ml dose. The percentage of patients reporting adverse events was similar across all study groups. According to these results demonstrating that the neurotrophic compound Cere is well tolerated and improves cognition and global clinical functioning in a reversed U–shaped dose–dependent manner, it is concluded that Cere is safe and effective for the treatment of patients with mild to moderate AD. Since the effects of Cere on efficacy parameters were similar at the end of the active treatment and three months later (week 24), it is suggested that Cere might slow the progression of AD.
Fabrication and Electrical Characterization of 3D Vertical Interconnects (2006)

3D die-stacking (Tanida et al, 2003; Hara et al, 2005) and wafer-stacking (Morrow et al, 2004) integration have recently been demonstrated using copper (Cu) interconnections and through silicon via technology. In 3D die-stacking approach, the Cu vertical interconnections are fabricated on the front-side of the silicon wafer along with the active circuitry followed by wafer thinning and die-stacking. The limitation of this approach is the impact to active circuitry from vertical interconnects processing. With the 3D wafer stacking approach, the wafers are bonded with the prefabricated active circuitry face-to-face prior to wafer thinning and Cu interconnects fabrication and inherently limit stack die configuration to matched die sizes. This approach has inherent benefits and limitations depend to a large extent on the targeted applications. In this paper, we present an alternate 3D die-stacking approach which involves wafer thinning prior to Cu interconnect fabrication in a silicon wafer consisting of pre-fabricated active circuitry. This approach allows for mixed die size and technology node integration in multi-chip packages while maximizing known good die yields. In this approach the electrical connection to the active circuitry is made through the Cu plated through-silicon via to large arrays of tungsten (W) contacts at the bulk silicon interface. The challenges in through-silicon via processing using this 3D die-stacking approach will be discussed. Backside processing impact to pre-fabricated transistors and fundamental RC performance of the through silicon via landing on contact will be presented
Hydrogen-Induced Crack Growth Rate in Steel Plates Exposed to Sour Environments (1997)

A mathematical model was proposed for determining the crack growth rate of hydrogen-induced cracking (HIC) in steel plates exposed to a sour gas. The model assumes that the extension of an embedded circular crack results from accumulation of internal hydrogen pressure that produces a rise of the stress intensity factor in excess of the plane strain fracture toughness of the steel with dissolved hydrogen. Upon crack extension, the volume of the crack cavity increases, and the pressure drops, causing the crack to arrest. As the cavity is filled again with hydrogen, the process is repeated. HIC experiments were conducted on API 5L-X52 steel plates, using ultrasonic inspection to measure crack sizes. Data from inspected sour gas pipelines were gathered and compared to the predicted crack growth rates. The model showed reasonable agreement with experimental results, which corresponded to the first stages of HIC growth. It failed to approximate values for large crack lengths found in pipelines after long exposure to sour gas. This suggested either that there were important crack delay processes or that the cracking criterion changed as the crack grew. These delay processes were related to the effect of metallurgical variables.
Secure spread spectrum watermarking for images, audio and video (2002)

We describe a digital watermarking method for use in audio, image, video and multimedia data. We argue that a watermark must be placed in perceptually significant components of a signal if it is to be robust to common signal distortions and malicious attack. However, it is well known that modification of these components can lead to perceptual degradation of the signal. To avoid this, we propose to insert a watermark into the spectral components of the data using techniques analogous to spread spectrum communications, hiding a narrow band signal in a wideband channel that is the data. The watermark is difficult for an attacker to remove, even when several individuals conspire together with independently watermarked copies of the data. It is also robust to common signal and geometric distortions such as digital-to-analog and analog-to-digital conversion, resampling, quantization, dithering, compression, rotation, translation, cropping and scaling. The same digital watermarking algorithm can be applied to all three media under consideration with only minor modifications, making it especially appropriate for multimedia products. Retrieval of the watermark unambiguously identifies the owner, and the watermark can be constructed to make counterfeiting almost impossible. We present experimental results to support these claims.
Binding of phosphorylated peptides and inhibition of their interaction with disease‐relevant human proteins by synthetic metal‐chelate receptors (2009)

The modulation of biological signal transduction pathways by masking phosphorylated amino acid residues represents a viable route toward pharmacologic protein regulation. Binding of phosphorylated amino acid residues has been achieved with synthetic metal-chelate receptors. The affinity and selectivity of such receptors can be enhanced if combined with a second binding site. We demonstrate this principle with a series of synthetic ditopic metal-chelate receptors, which were synthesized and investigated for their binding affinity to phosphorylated short peptides under conditions of physiological pH. The compounds showing highest affinity were subsequently used to inhibit the interaction of the human STAT1 protein to a peptide derived from the interferon-gamma receptor, and between the checkpoint kinase Chk2 and its preferred binding motif. Two of the investigated ditopic synthetic receptors show a significant increase in inhibition activity. The results show that regulation of protein function by binding to phosphorylated amino acids is possible. The introduction of additional binding sites into the synthetic receptors increases their affinity, but the flexibility of the structures investigated so far prohibited stringent amino acid sequence selectivity in peptide binding.
Deeply-Etched Optical MEMS Tunable Filter for Swept Laser Source Applications (2013)

In this letter, we report a wide tuning range MEMS-based swept laser source using deep reactive ion etching on an SoI substrate. A MEMS Fabry-Pérot filter with a free-spectral range and a tuning range wider than 94 nm is presented. The measured transmission loss of the filter is between -10.2 and -13.6 dB. This filter is used to construct a swept laser source with 85 nm tuning range. These results represent the widest tuning range reported in literature for an in-plane SoI-MEMS based swept laser source using deeply-etched free-standing distributed-Bragg-reflection mirrors. The recorded tuning range enables the use of the in-plane MEMS filter in optical coherence tomography applications.
The Machado–Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability (2010)

Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner. The interaction between ataxin-3 and parkin is direct, involves multiple domains and is greatly enhanced by parkin self-ubiquitination. Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells. Compared with wild-type ataxin-3, MJD-linked polyQ-expanded mutant ataxin-3 is more active, possibly owing to its greater efficiency at DUB K27- and K29-linked Ub conjugates on parkin. Remarkably, mutant but not wild-type ataxin-3 promotes the clearance of parkin via the autophagy pathway. The finding is consistent with the reduction in parkin levels observed in the brains of transgenic mice over-expressing polyQ-expanded but not wild-type ataxin-3, raising the intriguing possibility that increased turnover of parkin may contribute to the pathogenesis of MJD and help explain some of its parkinsonian features.
“Switchable Water”: Aqueous Solutions of Switchable Ionic Strength (2010)

"Salting out" is a standard method for separating water-soluble organic compounds from water. In this method, adding a large amount of salt to the aqueous solution forces the organic compound out of the aqueous phase. However, the method can not be considered sustainable because it creates highly salty water. A greener alternative would be a method that allows reversible salting out. Herein, we describe aqueous solutions of switchable ionic strength. Aqueous solutions of a diamine in water have essentially zero ionic strength but are converted by CO(2) into solutions of high ionic strength. The change is reversible. Application to the reversible salting out of THF from water is described.
Binding of Discoidin Domain Receptor 2 to Collagen I:  An Atomic Force Microscopy Investigation (2002)

Collagens have recently been identified as ligands for discoidin domain receptors (DDR1 and DDR2), generating an interest in studying the properties of binding of DDR to its ligand. We are interested in the interaction of DDR2 with collagen I because of its potential role in liver fibrosis. Our in vitro binding assay utilizes DDR2-Fc fusion proteins, which can be clustered (multimerized) by use of antibodies to form DDR2 complexes. Binding of DDR2 complexes to collagen I coated on plastic plates was established by a microplate-based assay using Eu(3+)-labeled proteins and time-resolved fluorometry. Clustering of the DDR2-Fc with antibody was found to be requisite for binding to collagen in vitro. Using atomic force microscopy (AFM) in an aqueous environment, we characterized the surface topographies of DDR2 complexes and collagen I, and investigated binding of this receptor-ligand pair. We were able to image and identify binding of DDR2 complexes onto individual molecules of triple-helical collagen and provide insight into the number and locations of binding sites on collagen I. In most cases, a single receptor complex bound to a single collagen molecule and there were preferred DDR2 binding sites on the collagen I triple helix. These data were validated by rotary-replication transmission electron microscopy (TEM) of glycerol-sprayed samples.
Diffie-Hellman key distribution extended to group communication (1996)

Ever since a-party Diffie-Hellman key exchange was first proposed in 1976, there have been efforts to extend its simplicity and elegance to a group setting. Notable solutions have been proposed by Ingemarsson et al. (in 1982) and Burmester/Desmedt (in 1994). In this paper, we consider a class of protocols that we call natural extensions of DiffieHellman to the n-party case. After demonstrating the security of the entire class based on the intractability of the Diffie-Hellman problem we introduce two novel and practical protocols and compare them to the previous results. We argue that our protocols are optimal with respect to certain aspects of protocol complexity.