gebhart/patrepeval huggingface dataset:
Cholesteryl Ester Transfer Protein Inhibition for Preventing Cardiovascular Events (2019)

Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100-containing lipoproteins. Evidence from genetic studies that variants in the CETP gene were associated with higher blood HDL cholesterol, lower low-density lipoprotein cholesterol, and lower risk of coronary heart disease suggested that pharmacological inhibition of CETP may be beneficial. To date, 4 CETP inhibitors have entered phase 3 cardiovascular outcome trials. Torcetrapib was withdrawn due to unanticipated off-target effects that increased risk of death, and major trials of dalcetrapib and evacetrapib were terminated early for futility. In the 30,000-patient REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, anacetrapib doubled HDL cholesterol, reduced non-HDL cholesterol by 17 mg/dl (0.44 mmol/l), and reduced major vascular events by 9% over 4 years, but anaceptrapib was found to accumulate in adipose tissue, and regulatory approval is not being sought. Therefore, despite considerable initial promise, CETP inhibition provides insufficient cardiovascular benefit for routine use.
NRG1 is required for glucose repression of the SUC2 and GAL genes of Saccharomyces cerevisiae (2001)

The analysis of nrg1Delta demonstrates that Nrg1 plays a role in glucose repression of the SUC2 and GAL genes of S. cerevisiae. Thus, three repressors, Nrg1, Mig1, and Mig2, are involved as the downstream targets of the glucose signaling in S. cerevisiae.
Mammalian Wax Biosynthesis (2004)

The conversion of fatty acids to fatty alcohols is required for the synthesis of wax monoesters and ether lipids. The mammalian enzymes that synthesize fatty alcohols have not been identified. Here, an in silico approach was used to discern two putative reductase enzymes designated FAR1 and FAR2. Expression studies in intact cells showed that FAR1 and FAR2 cDNAs encoded isozymes that reduced fatty acids to fatty alcohols. Fatty acyl-CoA esters were the substrate of FAR1, and the enzyme required NADPH as a cofactor. FAR1 preferred saturated and unsaturated fatty acids of 16 or 18 carbons as substrates, whereas FAR2 preferred saturated fatty acids of 16 or 18 carbons. Confocal light microscopy indicated that FAR1 and FAR2 were localized in the peroxisome. The FAR1 mRNA was detected in many mouse tissues with the highest level found in the preputial gland, a modified sebaceous gland. The FAR2 mRNA was more restricted in distribution and most abundant in the eyelid, which contains wax-laden meibomian glands. Both FAR mRNAs were present in the brain, a tissue rich in ether lipids. The data suggest that fatty alcohol synthesis in mammals is accomplished by two fatty acyl-CoA reductase isozymes that are expressed at high levels in tissues known to synthesize wax monoesters and ether lipids.
A Prospective European Organization for Research and Treatment of Cancer Genitourinary Group Randomized Trial Comparing Transurethral Resection Followed by a Single Intravesical Instillation of Epirubicin or Water in Single Stage Ta, T1 Papillary Carcinoma of the Bladder (1993)

A total of 431 eligible patients with solitary, primary or recurrent stages Ta and T1 transitional cell carcinoma of the bladder was included in a randomized multicenter trial to compare a single intravesical instillation of 80 mg. epirubicin with water given immediately after resection, with respect to the disease-free interval and recurrence rate. The interval to initial recurrence was significantly better in favor of the epirubicin group. After a mean followup of 2 years it became evident that the recurrence rate after a single epirubicin instillation was decreased by nearly half with the same trend being found in all subgroups examined. Toxicity was mainly restricted to bladder irritation in plus or minus 10% of the cases. Pathology review brought considerable changes in T category from stages T1 to Ta (53%). Changes in grade were less pronounced but nevertheless important.
Corporate Strategy in Crisis Management: Johnson & Johnson and Tylenol (1990)

This paper focuses on the Tylenol poisonings and the actions J & J employed to recover from this existence-threatening situation. The paper reviews the 1982 case in which Johnson & Johnson literally rewrote the book on crisis management in handling unexpected, catastrophic consumer issues. It demonstrated a high degree of integrity and moral responsibility in its handling of the poisonings. CEO Burke demonstrated decisive leadership at a time when the company needed it the most.
Search strategies in multimodal image retrieval (2008)

This paper reports on a study on search strategies in multimodal image retrieval. We analyzed the queries and search tactics employed by image journalism professionals and non-professionals in a user test. Transaction log data show that searchers are able to combine up to four query modes into a query. Most queries combined at least two of the modes (text, color, sketch, quality, and category). Task type was shown to affect the choice of which modes to employ. Known item and data search tasks led to queries combining text, color and category modes. Visually cued tasks resulted in searches combining several content-based and textual modes. Conceptual tasks led to a large number of queries by text and category only. User background also significantly affected the types of queries constructed. Professionals used the color mode more whereas non-professionals drew more sketches. Non-professionals were more likely to switch query modes whereas professionals edited the content of their queries. We described the search processes with Markov models and maximal repeating patterns. Common patterns and probable transitions dealt with querying, inspecting result images and saving them into the workspace or iterating queries of the same type. The results indicate a need to support multimodal image query formulation.
Epidemiological study on porcine circovirus type 2 (PCV2) infection in the European wild boar (Sus scrofa) (2004)

Porcine circovirus type 2 (PCV2) is considered as the causative agent of postweaning multisystemic wasting syndrome (PMWS) in domestic pigs, where the virus is ubiquitous as evidenced by serological surveys. We present the results of the first nationwide sero-survey on the presence of PCV2 antibodies in European wild boars, and report the first PMWS case in a wild boar from Spain. Sera from 656 hunter harvested wild boars from 45 different geographical sites and 22 additional imported animals were analysed by means of an immunoperoxidase monolayer assay (IPMA). We also examined the tissues from 55 healthy and one diseased wild boars for the presence of PCV2 nucleic acid and PMWS lesions by in situ hybridisation and histopathology, respectively. Additionally, abundance estimates of wild boars and field interviews were carried out on 30 sampling sites. The prevalence of medium to high PCV2 serological titres among the examined wild boars was 47.89 1.9%. Seropositive wild boars appeared in all but one of the geographical regions analysed. Seroprevalence and titre of PCV2 antibodies were closely related to the management of the wild boar populations. Wild boars from intensively managed, farm-like populations had higher prevalence than wild boars living in more natural situations. The effect of wild boar abundance and management on PCV2 antibody prevalence was further evidenced by the high correlation existing between the relative abundance estimates of animals and the percentage of wild boars with medium to high levels of PCV2 antibodies. PCV2 nucleic acid was detected in the tissues of three wild boars. One of these was diagnosed as PMWS. The results, in addition to information on piglet mortalities, suggest a potential role of PMWS in piglet mortality in intensively managed wild boar populations.
Cloning and sequencing of the adenylate kinase gene (adk) ofEscherichia coli (1985)

Adenylate kinase, the product of the adk locus in Escherichia coli K12, catalyzes the conversion of AMP and ATP to two molecules of ADP. The gene has been cloned by complementation of an adk temperature sensitive mutation. The DNA sequence of the complete coding region and of 5′- and 3′- untranslated regions were determined. The resulting protein sequence was found to contain several regions of high homology with cytosolic adenylate kinase of pig muscle (AK1), whose three-dimensional structure has been determined. The most significant of the amino acid exchanges is the replacement of histidine 36 with glutamine. This residue is believed to play a role in catalysis through metal ion binding. The codon usage pattern and the determination of adenylate kinase molecules per cell shows that the enzyme is one of the more abundant soluble proteins of the bacterial cells.
Novel cationic lipids for gene delivery and gene therapy (1998)

The ability to produce and express foreign genes in humans might cure or even prevent many important human diseases that are either treated poorly or are untreatable by present therapies. However, insufficient transgene expression in vivo has so far impaired the development of effective gene therapy. Thus, it is of interest to develop compositions and delivery methods for gene therapy that lead to high level transgene expression in a variety of cell and tissue types. Synthetic DNA delivery agents are of crucial interest for gene therapy as an alternative to viral vectors, since they potentially display fewer risks in terms of immunogenicity and propagation and are easier to produce under GMP conditions. In the last decade, a significant number of industrial and academic groups have emerged with a number of important patents claiming a variety of synthetic DNA delivery agents. Some of these agents were launched into clinical trials at very early stages of development leading to rather modest results. The lack of physicochemical characterisation of the self-assembling complexes in those early clinical trials prevented interpretation, correlation and comparison of transgene expression and biodistribution with the supramolecular state of these self-assemblies. On the other hand, in the last two years, a significant body of information has emerged from academic and academic-industrial groups regarding the exhaustive physicochemical characterisation of some complexes and the impact of these characteristics on transgene biodistribution and expression both in vitro and in vivo. Additionally, the intracellular fate of different self-assemblies has been studied by different groups. Together, these studies provide a rational basis for designing novel DNA delivery agents. Synthetic agents for gene delivery are classified into different chemical families. In this manuscript, we have focused on the cationic lipids family. We choose to show the approaches that introduce original elements into the backbone of the synthetic delivery agent. Data on the physicochemical characterisation of different synthetic agents for gene delivery are given when available. Clinical data (reported in other reviews) are beyond the scope of this article. Finally, a discussion on how to improve the results obtained so far in order to advance towards new human trials is presented.
Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy (2017)

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain.
Impact of Curing Protocol on Conversion and Shrinkage Stress (2005)

Since considerable shrinkage stress develops during the curing of dental composites, various soft-start photocuring protocols, aiming to lower stress but not compromise conversion, have been proposed. We hypothesized that utilizing soft-start photocuring will result in not only reduced stress, but also decreased conversion. We evaluated the impact of 3 protocols (soft-start, pulse, and standard) on the stress development and polymerization extent of an experimental composite. A novel set-up capable of simultaneous shrinkage stress, conversion, and temperature measurements on the same specimen was utilized. Analysis of the data shows that stress rises dramatically as a function of conversion in the vitrified state, and the utilization of soft-start or pulse curing results in specimens with reduced final conversion and shrinkage stress, compared with specimens cured according to the standard full-intensity protocol. Finally, this study demonstrates that the predominant reason for the reduced shrinkage stress attained with soft-start or pulse curing is a modest decrease in final conversion.
A fluorescently labeled intestinal fatty acid binding protein. Interactions with fatty acids and its use in monitoring free fatty acids. (1992)

The fatty acid-binding protein from rat intestine (I-FABP) has been covalently modified with the fluorescent compound Acrylodan. Acrylodan was found to label Lys27, one of the few amino acid residues found by x-ray diffraction studies to change orientation upon fatty acid (FA) binding to I-FABP. Binding of FA to this Acrylodan-modified I-FABP (ADIFAB) induces a large shift in fluorescence emission wavelength from 432 to 505 nm. As a consequence, the ratio of emission intensities provides a direct measure of the concentration of FA bound to the protein. Binding of FA is well described by single site equilibrium for FA concentrations below the critical micelle concentration. ADIFAB dissociation constants (Kd) determined at 37 degrees C and at concentrations below the critical micelle concentration for oleate, palmitate, linoleate, arachidonate, and linolenate were, respectively, 0.28, 0.33, 0.97, 1.6, and 2.5 microM. The variation of these Kd values with FA molecular species is highly correlated with the solubility of the FA in water, suggesting that all these FA bind with a similar conformation in the I-FABP binding site. The ADIFAB response together with the measured equilibrium constants allows a direct determination of the concentration of long chain free fatty acid (FFA) in the concentration range, depending upon the FA molecular species, between 1 nM and > 20 microM. As an example of its use as a probe to measure FFA levels, ADIFAB is used here to monitor the time course for FFA release from IgE receptor- and ionomycin-activated rat basophilic leukemia (RBL) cells.
Hematopoiesis (2012)

Enormous numbers of adult blood cells are constantly regenerated throughout life from hematopoietic stem cells through a series of progenitor stages. Accessibility, robust functional assays, well-established prospective isolation, and successful clinical application made hematopoiesis the classical mammalian stem cell system. Most of the basic concepts of stem cell biology have been defined in this system. At the same time, many long-standing disputes in hematopoiesis research illustrate our still limited understanding. Here we discuss the embryonic development and lifelong maintenance of the hematopoietic system, its cellular components, and some of the hypotheses about the molecular mechanisms involved in controlling hematopoietic cell fates.
Electro‐mediated gene transfer and expression are controlled by the life‐time of DNA/membrane complex formation (2009)

The life-time of DNA/membrane complex formation is of the order of 1 s and has to be taken into account to improve protocols of electro-mediated gene delivery.
Design of a wearable wide-angle projection color display (2002)

In this paper, we investigate the design and fabrication of ultra-light weight projection lenses for color wearable displays. Driven by field of view requirements from 40 degree to 90 degrees, we employed the combination of plastic, glass, and diffractive optics to yield <10g optics per eye. The approach centers on the use of projection optics instead of eyepiece optics to yield most compact and high image quality designs. The implementation of the fabricated 52 degrees lens in a teleportal head-mounted display and remote collaborative environment is demonstrated. We also present the design results for a 70 degrees design.
IEEE 802.11 downlink traffic shaping scheme for multi-user service enhancement (2004)

In IEEE 802.11 wireless LAN (WLAN), due to the combination of a first-in-first-out (FIFO) transmission queue and the retransmission policy in the serving access point (AP), a single station that is moving away from the AP, e.g., thus handing off to a neighbouring AP, can have a significant negative impact on the services other users receive in the same basic service set (BSS). In this paper, we present a traffic shaping algorithm to control this undesirable effect. Experimental results show that our algorithm manages to maintain stable throughput levels in networking applications that otherwise would have experienced high throughput degradation. This algorithm constitutes an innovative implementation of a traffic shaper that can be easily adopted by the current state-of-the-art IEEE 802.11 AP products to enhance the performance of WLANs, since the algorithm can be implemented in the device driver and no specific modification of hardware is needed.
Mucins bearing the cancer-associated sialosyl-Tn antigen mediate inhibition of natural killer cell cytotoxicity. (1992)

The sialosyl-Tn (STn) antigen is a mucin-associated carbohydrate antigen expressed by a variety of adenocarcinomas. In the colon, expression of this antigen has been associated with a poor prognosis, independent of tumor stage or histology. The present study was performed to determine whether this adverse clinical outcome might be due to an interaction between STn-positive mucin and natural killer (NK) cell cytotoxicity. Ovine submaxillary mucin (OSM), a mucin highly rich in STn antigen, partially inhibited NK cell cytotoxicity against K562 target cells, but only at high concentrations. Low concentrations of OSM were not inhibitory but became markedly inhibitory in the presence of ammonium ions. Two other STn-positive submaxillary mucins also markedly inhibited NK cytotoxicity when combined with ammonium ions. Removal of sialic acid from OSM reversed the OSM/ammonium-mediated inhibition of NK cell activity. Unlike the submaxillary mucins, two mucins derived from human breast and lung cancer cells which lack the STn antigen, did not inhibit NK cell activity in this system. Likewise, four other non-mucin glycoproteins which lack STn expression did not inhibit NK cells despite having levels of sialic acid that were, in some cases, comparable to submaxillary mucin. These results indicate that mucins bearing the cancer-associated STn antigen can effectively inhibit NK cell cytotoxicity in the presence of ammonium ions. While this NK cell inhibition is likely to be caused by ammonium, mucin markedly enhances this effect, thereby implicating a novel immunomodulatory property of mucin.
An Advanced VHF/UHF Short Range, Groundwave Propagation Model for Paths With Near-Earth Antennas (2006)

Short range VHF and UHF paths between devices with antennas very close to, or on the earth such as: Unattended Ground Sensors (UGS) and Intelligent Munitions Systems (IMS), are attenuated above free space values by the lossy earth itself and any obstructions between a transmitter and receiver pair. Due to a paucity of measured data and propagation methods for the cases of military interest, an innovative propagation model is described that combines the seminal work of Franceschetti et al and Norton.
Long regions of homologous DNA are incorporated into the tobacco plastid genome by transformation. (1992)

We investigated the size of flanking DNA incorporated into the tobacco plastid genome alongside a selectable antibiotic resistance mutation. The results showed that integration of a long uninterrupted region of homologous DNA, rather than of small fragments as previously thought, is the more likely event in plastid transformation of land plants. Transforming plasmid pJS75 contains a 6.2-kb DNA fragment from the inverted repeat region of the tobacco plastid genome. A spectinomycin resistance mutation is encoded in the gene of the 16S rRNA and, 3.2 kb away, a streptomycin resistance mutation is encoded in exon II of the ribosomal protein gene rps12. Transplastomic lines were obtained after introduction of pJS75 DNA into leaf cells by the biolistic process and selection for the spectinomycin resistance marker. Homologous replacement of resident wild-type sequences resulted in integration of all, or almost all, of the 6.2-kb plastid DNA sequence from pJS75. Plasmid pJS75, which contains engineered cloning sites between two selectable markers, can be used as a plastid insertion vector.
PROSTATE-SPECIFIC ANTIGEN VELOCITY AND REPEATED MEASURES OF PROSTATE-SPECIFIC ANTIGEN (1997)

Numerous studies evaluating different populations have shown similar findings with respect to repeated PSA measurements and PSAV. First, there is substantial within-individual variability between repeated PSA measures. Second, this variability between PSA measurements precludes the use of a simple change in PSA as a marker for prostate cancer. Third, when one adjusts the changes that occur in PSA over an elapsed time of 1.5 to 2 years (PSAV), less than 5% of men without prostate cancer will have a PSAV of 0.75 ng/mL/ y or greater, and approximately 70% of men with prostate cancer will have a PSAV of 0.75 ng/mL/ y or greater. These data strongly suggest that PSAV is a specific marker for the presence of prostate cancer.
Estimation of allele frequencies with data on sibships (2001)

Allele frequencies are generally estimated with data on a set of unrelated individuals. In genetic studies of late-onset diseases, the founding individuals in pedigrees are often not available, and so one is confronted with the problem of estimating allele frequencies with data on related individuals. We focus on sibpairs and sibships, and compare the efficiency of four methods for estimating allele frequencies in this situation: (1) use the data for one individual from each sibship; (2) use the data for all individuals, ignoring their relationships; (3) use the data for all individuals, taking proper account of their relationships, considering a single marker at a time; and (4) use the data for all individuals, taking proper account of their relationships, considering a set of linked markers simultaneously. We derived the variance of estimator 2, and showed that the estimator is unbiased and provides substantial improvement over method 1. We used computer simulation to study the performance of methods 3 and 4, and showed that method 3 provides some improvement over method 2, while method 4 improves little on method 3.