gebhart/patrepeval huggingface dataset:
The Dream of the Automated Highway (2007)

Transportation planners have long dreamed of an automated highway in which an automatic, intelligent guidance system would allow cars to travel quickly in a tight formation, improving highway safety and reducing traffic congestion. This article discusses some of the progress that has been made to making the automated highway a reality, as well as some of the challenges to such a project. Although proponents of the automated highway envision that the concept could solve transportation problems within a 2030 to 2060 timeframe, others believe that the technical and institutional challenges make it unlikely that an automated system would be viable even in the distant future. A look at how technology may realistically improve transportation by the year 2050 is provided.
Do security toolbars actually prevent phishing attacks? (2006)

Security toolbars in a web browser show security-related information about a website to help users detect phishing attacks. Because the toolbars are designed for humans to use, they should be evaluated for usability -- that is, whether these toolbars really prevent users from being tricked into providing personal information. We conducted two user studies of three security toolbars and other browser security indicators and found them all ineffective at preventing phishing attacks. Even though subjects were asked to pay attention to the toolbar, many failed to look at it; others disregarded or explained away the toolbars' warnings if the content of web pages looked legitimate. We found that many subjects do not understand phishing attacks or realize how sophisticated such attacks can be.
In vivo site-directed mutagenesis of Neurospora crassa beta-tubulin gene by spheroplasts transformation with oligonucleotides (1996)

The use of Polymerase Chain Reaction (PCR) to incorporate mutated oligonucleotides into newly synthesized segments of DNA and the subsequent introduction of this DNA into competent cells is one of the most widely used methods of site-directed mutagenesis (Zoller et al.1984 DNA 3:479-488; Dalbodie-McFarland et al. 1982 Proc. Natl. Acad. Sci. USA 79:6409-6413). Several variations of this technique exist, but all require several and some time-consuming steps. Here we report the results of a rapid method of in vivo site-directed mutagenesis involving the direct transformation of Neurospora crassa spheroplasts with mutated oligonucleotides.
Feasibility and Safety of Vagal Stimulation In Monkey Model (1990)

The feasibility, safety, and preliminary effects of chronic vagal stimulation were studied in an aluminagel monkey model. Pilot studies to perfect the equipment, determine stimulation thresholds, and insure the comfort and safety of the animals preceded this study. Four monkeys were equipped with an indwelling, 2-electrode cuff (titanium bands spaced 7 mm apart; silicone encased; 1.5 cm total length) in contact around the right vagus nerve; avoidance of the cardiac branch was confirmed by electrocardiograms. After postsurgical recovery, the intact and awake animals received constant-current stimulation (5 mA; 83 Hz, 143 Hz, or 50-250 Hz randomly; 0.5-ms pulse width) at the onset of every spontaneous seizure for the duration of the seizure or every 3 h for 40 s if stimulation had not occurred in the preceding hour. Stimulation periods of 2-6 weeks, with differing levels of stimulation, were preceded and followed by at least a 2-week baseline period of no stimulation. During the stimulation periods, the seizure rate decreased to zero in two monkeys and the interseizure intervals became invariable in the remaining two monkeys. These effects carried over temporarily into the poststimulation baseline periods. Vagal stimulation had no consistent effects on seizure severity or EEG interictal spikes. Histological studies of six vagus nerves were unable to separate electrode cuff damage from any direct effects stimulation may have had on the nerves. Although it appears that chronic vagal stimulation is feasible and that epileptogenic processes are influenced, the safety and efficacy of the procedure are still in question.
17 beta-estradiol acts directly on the clonal osteoblastic cell line UMR106. (1987)

We studied the effect of 17 beta-estradiol (E) on the proliferation and alkaline phosphatase activity of cultured UMR106 cells, a clonal osteoblastic cell line. Growth rates were reduced and alkaline phosphatase activity was increased in cells incubated for 2 days in medium containing E (10(-8) M). In contrast, E had no effect on the growth rates or alkaline phosphatase of a human fibroblastic cell line, S90E. The effect of E was not observed with low cell density or at confluence. 1,25-Dihydroxyvitamin D3 antagonized the response to E. Preincubation of the cells with dexamethasone, a potent inducer of differentiation, reversed the effect of E or 1,25-dihydroxyvitamin D3. These results indicate that cellular and/or extracellular factors such as cell density, the phase of the cell cycle, the state of differentiation, and the presence or absence of other steroids influenced the response of UMR106 cells to E. Serum was removed from the culture medium to minimize the effect of the steroids, growth factors, and nutrients present in serum. A striking stimulation of alkaline phosphatase by E occurred with serum-free conditions. This stimulation was biphasic over an E concentration from 10(-12) to 10(-8) M, with the peak response at 10(-10) M. The action of E on UMR106 cells was metabolite-specific, since the isomer 17 alpha-estradiol produced no effect on proliferation rates or alkaline phosphatase activity. The cyclic AMP response to parathyroid hormone (residues 1-34) was not altered by E treatment of these cells. In contrast, dexamethasone exposure did increase the cyclic AMP response to parathyroid hormone. These results demonstrate a direct effect of E on an osteoblastic cell line. They also raise the possibility that similar or identical actions of E occur in cultured normal osteoblasts.
A Novel Small-Molecule Compound Targeting CCR5 and CXCR3 Prevents Acute and Chronic Allograft Rejection (2005)

Antagonism of CCR5 and CXCR3 has a substantial therapeutic effect on inhibiting both acute and chronic allograft rejection. CCR5 and CXCR3 are functional in the process of allograft rejection and may be potential targets in clinical transplantation in the future.
High-resolution visualization by field emission scanning electron microscopy of Enterococcus faecalis surface proteins encoded by the pheromone-inducible conjugative plasmid pCF10 (1993)

Enterococcus faecalis can acquire antibiotic resistance and virulence genes by transfer of pheromone-inducible conjugative plasmids such as pCF10, which encodes tetracycline resistance. Two pCF10-encoded cell surface proteins, Sec10 and Asc10, have been previously shown to play an important role in the transfer of this plasmid. We used high-resolution, field emission scanning electron microscopy to visualize these proteins on the surfaces of a series of isogenic strains of E. faecalis. Immunogold labeling, using both 6- and 12-nm colloidal gold, unambiguously demonstrated the expression and distribution of Sec10 and Asc10 on the surface of the E. faecalis cells. On unlabeled E. faecalis cells which expressed either Sec10 or Asc10, the former appeared to be more readily detected. Immunogold labeling of E. faecalis cells expressing both Asc10 and Sec10 clearly demonstrated the abundance and intermixing of both proteins on the cell surface except at septal regions. Sec10 was observed to be distributed over the cell surface. At regions of cell-cell contact, fine strands representing Asc10 were observed directly attaching adjacent cells to one another.
Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer (2012)

Abstract Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na<sub>2</sub>B<sub>12</sub>H<sub>11</sub>SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.
The gapped duplex DNA approach to oligonucleotide-directed mutation construction (1984)

A simple and efficient method is described to introduce structurally pre-determined mutations into recombinant genomes of filamentous phage M13. The method rests on gapped duplex DNA (gdDNA) molecules of the phage M13 genome as the key intermediate. In this gdDNA, the (+) and the (shorter) (-) strand carry different genetic markers in such a way, that a rigorous selection can be applied for phage carrying the markers of the (-) strand. For introduction of the mutation, a synthetic oligonucleotide with partial homology to a target site within the single stranded DNA region is annealed to the gdDNA. The oligonucleotide subsequently becomes part of the (-) strand by enzymatic DNA gap filling and sealing. This physical linkage is preserved at the genetic level after transfection of a recipient E.coli strain deficient in DNA mismatch correction, so that the synthetic marker can be selected from the phage progeny independent from its potential phenotype. It is demonstrated that by this method mutants can be constructed with marker yields in excess of 70%.
Estrogen induction of alcohol dehydrogenase in the uropygial gland of mallard ducks (1992)

Treatment of mallard ducks with estradiol, or a combination of estradiol and thyroxine, has been shown to result in the proliferation of peroxisomes and production of diesters of 3-hydroxy fatty acids, the female pheromones, in the uropygial gland of male and female mallard ducks. Such a treatment results in the induction of a unique set of proteins. A cDNA library enriched in hormone-induced transcripts was subjected to differential screening. The nucleotide sequence of one of the two unique cDNA clones, DGH1, had high similarity to the Human class I alcohol dehydrogenase (ADH) gamma subunit and represented the carboxy-terminus of the protein from amino acid 190-374. SDS/PAGE and Western blot analysis of the proteins indicated that the level of a 38-kDa protein that cross-reacted with antibodies prepared against the chicken ADH was increased 5-7-fold by hormone treatment. Assays for ADH activity in the uropygial gland extracts of male mallards showed a 5-7-fold induction of the enzyme by hormone treatment. The 1.9-kb ADH mRNA levels were increased 12-14-fold under these conditions. Of all the tissues tested, the uropygial gland had the highest levels of ADH mRNA. Induction of ADH by estradiol treatment occurred only in this tissue. Elevated levels of ADH were also observed in the glands of male mallards in eclipse, the post-nuptial condition when the hormonal balance is shifted to higher estrogen levels, suggesting that this enzyme is regulated by estrogens in this period. Estradiol treatment caused an 80% decrease in the NAD+/NADH ratio in the uropygial gland and a twofold increase in the fatty alcohol oxidation rate catalyzed by the gland extract. These observations could help explain how increased levels of ADH could contribute to the production of the diesters.
Real-world one-year overall survival among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan in the NAPOLI-1 based regimen. (2021)

392 Background: Pancreatic cancer remains one of the most lethal cancers in the United States (US) with a 5-year relative survival of 9%. Among patients who received liposomal irinotecan + 5-fluorouracil (5-FU) and leucovorin in the NAPOLI-1 study, a randomized phase 3 study in patients with mPDAC previously treated with gemcitabine-based therapy, 25% (n = 29) were alive at ≥ 1 year. This study examines the real world one-year survival of patients with mPDAC treated with liposomal irinotecan as a doublet with 5-FU in the NAPOLI-1 based regimen. Methods: This retrospective observational study utilized the Flatiron Health EHR database from over 280 cancer clinics in the US. Data were analyzed for adult patients with mPDAC treated with liposomal irinotecan-based regimens between November 2015 and July 2020. Patient characteristics and one-year overall survival (OS) based on Kaplan-Meier estimates were assessed. Cycles were defined as unique days with an administration of liposomal irinotecan. Results: There were 669 patients (median age: 69y, IQR: 62-75) included in the study. ECOG performance status (PS) of 0-1 and 2+ were reported for 78.3% (n = 396) and 21.7% (n = 110) of patients, respectively. ECOG PS was not captured for 24.4% (n = 163) of patients. 16.3% (n = 109) of patients initiated liposomal irinotecan-based in the first line (1L) metastatic setting, 47.5% (n = 318) in second line (2L), and 36.2% (n = 242) in the third line or later (3L+). The median number of cycles received was 4 (IQR: 2 – 8). Among all patients, one-year OS was 17.2% (95% CI: 14.3% - 20.7%). One-year OS was 31.5% (22.1% – 41.3%) for patients treated in 1L, 16.4% (12.2% - 21.1%) for patients treated in 2L, and 12.2% (7.5% - 18.0%) for patients treated in 3L. The median number of cycles for 1L, 2L, and 3L were 5, 4, and 3, respectively. One-year OS increased as patients were able to receive more cycles of liposomal irinotecan. Patients who received at least 2 cycles of liposomal irinotecan (n = 551) had a one-year OS of 20.4% (16.8% - 24.2%). Among patients who received at least 4 cycles (n = 359) and at least 8 cycles (n = 170), the one-year OS estimates were 29.1% (24.0% - 34.3%) and 47.9% (39.7% - 55.7%), respectively. Conclusions: In this real-world cohort of patients with mPDAC treated with liposomal irinotecan, as expected, one-year OS increased as patients remained on therapy. Patients in this cohort were older, had more prior lines of therapy, worse ECOG PS, and similar exposure to treatment compared with patients in the registrational phase 3 NAPOLI-1 study. Among patients who received at least 4 cycles of liposomal irinotecan, one-year OS (29%) was similar to both the intent-to-treat (25%) and per protocol treated patient populations in the NAPOLI-1 trial (34%). Further studies are needed to understand the predictors of long-term survival among patients with mPDAC.
Panning for gold: genome-wide scanning for linkage in type 1 diabetes (1996)

Genome-wide scans for linkage of chromosome regions to type 1 diabetes in affected sib pair families have revealed that the major susceptibility locus resides within the major histocompatibility complex (MHC) on chromosome 6p21 (lambda S = 2.4). It is recognized that the MHC contains multiple susceptibility loci (referred to collectively as IDDM1), including the class II antigen receptor genes, which control the major pathological feature of the disease: T-lymphocyte-mediated autoimmune destruction of the insulin-producing pancreatic beta cells. However, the MHC genes, and a second locus, the insulin gene minisatellite on chromosome 11p15 (IDDM2; lambda S = 1.25), cannot account for all of the observed clustering of disease in families (lambda S = 15), and the scans suggested the presence of other susceptibility loci scattered throughout the genome. There are four additional loci for which there is currently sufficient evidence from linkage and association studies to justify fine mapping experiments: IDDM4 (FGF3/11q13), IDDM5 (ESR/6q22), IDDM8 (D6S281/6q27) and IDDM12 (CTLA-4/2q33). IDDM4, 5 and 8 were detected by genome scanning, and IDDM12 by a candidate gene strategy. Seven other named loci are not discounted but remain to be replicated widely. Multiple susceptibility loci were expected as genome-wide scans of the mouse model of type 1 diabetes had shown that although the MHC is the major mouse locus, at least 13 genes unlinked to the MHC are involved in the development of disease. Genome-wide scans using 1000 affected sibpair families will be required to be confident that all genes with effects on familial clustering equivalent to the insulin gene locus (lambda S = 1.25) have been detected. The identification of aetiological determinants requires exclusion of hitchhiking polymorphisms in regions of linkage disequilibrium, as demonstrated for the MHC and the insulin gene loci, and functional studies implicating the disease-associated variant in pathogenesis. Ultimately, targeting of specific candidate mutations in mice by homologous recombination and replacement will be necessary to prove the primary role of any candidate mutation.
Up‐regulation of a Chondroitin Sulphate Epitope during Regeneration of Mouse Sciatic Nerve: Evidence that the Immunoreactive Molecules are Related to the Chondroitin Sulphate Proteoglycans Decorin and Versican (1995)

After transection of adult mouse sciatic nerve, the expression of a chondroitin sulphate epitope recognized by the monoclonal antibody 473-HD (mAb 473-HD) was found to be up-regulated. The epitope was localized immunocytochemically mainly in Schwann cell basal laminae and, more weakly, also in the endoneurium. In cultures of mouse dorsal root ganglion cells, Schwann cells expressed high levels but fibroblasts only low levels of the epitope. To identify the molecule(s) carrying this chondroitin sulphate epitope, human sciatic nerves were extracted with phosphate-buffered saline and shown to contain two chondroitin sulphate proteoglycans of apparent molecular weights of 130 and 900 kDa. The 900 kDa and, more weakly, the 130 kDa proteoglycan were reactive with mAb 473-HD, which was found to recognize chondroitin-6-sulphate as epitope. Following chondroitinase ABC treatment of the 130 kDa proteoglycan, a core protein of approximately 45 kDa was seen and shown to react with polyclonal antibodies against the chondroitin-dermatan sulphate proteoglycan decorin from human fibroblasts. Chondroitinase ABC treatment of the 900 kDa proteoglycan yielded a core protein with a molecular weight of approximately 400 kDa that was recognized by polyclonal antibodies against recombinantly expressed fusion proteins from human versican. After transection of adult mouse sciatic nerves, the distal nerve stumps showed up-regulation of the chondroitin-6-sulphate epitope of the 900 kDa proteoglycan, whereas the core protein of this proteoglycan did not show any detectable change in the level of expression. In contrast, the core protein of the 130 kDa proteoglycan was up-regulated in expression. These observations suggest that versican- and decorin-like molecules may contribute to successful regeneration in the peripheral nervous system of mammals.
Azim: direction based service using azimuth based position estimation (2004)

Here, we propose a system named Azim that provides service based on both location and direction, which uses position estimation method based on azimuth data. In this system, a user's position is estimated by having the user point to and measure azimuths of several markers or objects whose positions are already known. Because the measurements are naturally associated with some degree of error, the user's position is calculated as a probability distribution. Since both the user's position and azimuth data are obtained in this method, both sources of data are used to realize more advanced services such as identifying the object pointed to by a user. The proposed system utilizes a wireless LAN for supporting these advanced services. Finally, a prototype system was implemented using a direction sensor that combines a magnetic compass and accelerometer, and we exemplify the usefulness of our approach through an experiment.
Impaired interferon signaling is a common immune defect in human cancer (2009)

Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the functional responses to IFN in peripheral blood lymphocytes from patients with 3 major cancers: breast cancer, melanoma, and gastrointestinal cancer. Type-I IFN (IFN-alpha)-induced signaling was reduced in T cells and B cells from all 3 cancer-patient groups compared to healthy controls. Type-II IFN (IFN-gamma)-induced signaling was reduced in B cells from all 3 cancer patient groups, but not in T cells or natural killer cells. Impaired-IFN signaling was equally evident in stage II, III, and IV breast cancer patients, and downstream functional defects in T cell activation were identified. Taken together, these findings indicate that defects in lymphocyte IFN signaling arise in patients with breast cancer, melanoma, and gastrointestinal cancer, and these defects may represent a common cancer-associated mechanism of immune dysfunction.
Somatic mutation and gain of copy number of PIK3CA in human breast cancer (2005)

Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.
Number theory (1989)

Number theory, an abstract branch of mathematics that deals with relationships between whole numbers, has provided highly useful answers to numerous real-world problems. The author briefly reviews earlier uses of number theory and then examines recent applications to music, cryptography, and error-correction codes. >
Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women (2009)

Our data suggest a significant role of ADIPOQ variants at positions +45 and +276 in the development of IR in healthy Greek women possibly through an interaction with BF.