gebhart/patrepeval huggingface dataset:
Europart. European Research Programme for Partitioning of Minor Actinides Within High Active Wastes Issuing from the Reprocessing of Spent Nuclear Fuels (2006)

The radiotoxicity of the vitrified nuclear wastes issuing from the reprocessing of nuclear spent fuels is mainly due to the presence of minor actinides (MAs = Np, Am and Cm) in these wastes. To simplify the definition of a deep underground repository, the elimination of MAs from the wastes followed by their destruction by transmutation is a positive strategy (PandT strategy). The Integrated Project (IP) EUROPART concerns the definition of partitioning methods for the elimination of MAs from the wastes. Two chemical domains were selected for the research: i) hydrometallurgy, ii) pyrometallurgy. The research work is organised into 9 Work Packages (WP): 5 for hydrometallurgy and 4 for pyrometallurgy. The partnership involved in the research comprises 23 partners from 10 European countries, 1 the EC-JRC-ITU, 1 from Japan (JAERI) and near 1 partner from Australia (ANSTO). This paper will present: i) the WPs, ii) some recent results related to the WPs and iii) the partnership and the organisation of the Integrated Project.
Correction for Dietrich et al., Differential Influence of Nutrient-Starved Mycobacterium tuberculosis on Adaptive Immunity Results in Progressive Tuberculosis Disease and Pathology (2016)

Volume 83, no. 12, p. [4731–4739][1], 2015. Page 4732, column 1: Lines 12 and 13 should read as follows. “…For Coxiella burnetii, Leishmania, Legionella pneumophila, and Chlamydia trachomatis,…”

Page 4734: Figure 3 should appear as shown below.

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An integrable 60-Hz notch filter (1999)

Previous configurations of continuous-time 60-Hz notch filters were difficult to integrate on a silicon chip because of the large component values required. A new method based on first-order all-pass networks has been introduced that lends itself more to integration. These networks use time constant multiplication circuitry to achieve large time constants using resistors and capacitors that can be integrated. With this new configuration, a 60-Hz notch filter with notch attenuation exceeding -60 dB can be implemented on a silicon chip.
Visualizing Chemistry (2002)

Chemistry is a challenging field to master. Models, particularly visual models, can help us understand the underlying concepts. With the rapid advances occurring in computer graphics, scientists have powerful tools to elucidate challenging chemical concepts. It is our obligation as scientists and teachers to learn to use these tools to better communicate what chemistry is all about.
Risk Factors for Early Reconstruction Failure of Multilevel Cervical Corpectomy With Dynamic Plate Fixation (2010)

Postoperative cervical hyperlordosis may adversely affect graft stability in the early postoperative period of the surgery of corpectomy and reconstruction with dynamic plate fixation.
Who Pays for Water Security? (2005)

I’ve been attending quite a few meetings and workshops on water system security lately and one of the issues that comes up is how to pay the extra costs associated with providing security for water supply systems. Some say that the federal government should pay the bill, but I’m not sure if the individuals who propose this understand where the federal government gets its money. The costs are not trivial and include vulnerability assessments, emergency management planning, physical security measures, security personnel, monitoring and surveillance, and redundant facilities. While most utilities have always had some of these measures in place, the needs and costs have significantly increased in recent years because of the increased concern over potential terrorism directed at water supplies. Basically, the issue boils down to one of whether we should pay for water system security with rate water bill money or tax money. There are good arguments on both sides.
Cardiopulmonary Bypass-Associated Acute Kidney Injury: A Pigment Nephropathy? (2007)

Acute kidney injury (AKI) is a common and serious postoperative complication following exposure to cardiopulmonary bypass (CPB). Several mechanisms have been proposed by which the kidney can be damaged and interventional studies addressing known targets of renal injury have been undertaken in an attempt to prevent or attenuate CPB-associated AKI. However, no definitive strategy appears to protect a broad heterogeneous population of cardiac surgery patients from CPB-associated AKI. Although the association between hemoglobinuria and the development of AKI was recognized many years ago, this idea has not been sufficiently acknowledged in past and current clinical research in the context of cardiac surgery-related AKI. Hemoglobin-induced renal injury may be a major contributor to CPB-associated AKI. Accordingly, we now describe in detail the mechanisms by which hemoglobinuria may induce renal injury and raise the question as to whether CPB-associated AKI may actually be, in a significant part, a form of pigment nephropathy where hemoglobin is the pigment responsible for renal injury. If CPB-associated AKI is a pigment nephropathy, alkalinization of urine with sodium bicarbonate might protect from: (1) tubular cast formation from met-hemoglobin; (2) proximal tubular cell necrosis by reduced endocytotic hemoglobin uptake, and (3) free iron-mediated radical oxygen species production and related injury. Sodium bicarbonate is safe, simple to administer and inexpensive. If part of AKI after CPB is truly secondary to hemoglobin-induced pigment nephropathy, prophylactic sodium bicarbonate infusion might help attenuate it. A trial of such treatment might be a reasonable future investigation in higher risk patients receiving CPB.
Recurrence of an early postzygotic rescue of an inherited unbalanced translocation resulting in mosaic segmental uniparental isodisomy of chromosome 11q in siblings (2021)

Balanced translocations are associated with a risk of transmission of unbalanced chromosomal rearrangements in the offspring. Such inherited chromosomal abnormalities are typically non-mosaic as they are present in the germline. We report the recurrence in two siblings of a mosaicism for a chromosomal rearrangement inherited from their asymptomatic father who carried a balanced t(2;11)(q35;q25) translocation. Both siblings exhibited a similar phenotype including intellectual disability, dysmorphic features, kyphoscoliosis, and cervical spinal stenosis. Karyotyping, fluorescence in situ hybridization and SNP array analysis of blood lymphocytes of both siblings identified two cell lines: one carrying a 2q35q37.3 duplication and a 11q25qter deletion (~90% cells), and one carrying an 11q uniparental isodisomy of maternal origin (~10% cells). We hypothesize that these mosaics were related to a postzygotic rescue mechanism which unexpectedly recurred in both siblings.
Alterations of the Tumor Suppressor Gene ARLTS1 in Ovarian Cancer (2006)

ARLTS1 is a tumor suppressor gene initially described as a low-penetrance cancer gene: a truncated Trp149Stop (MUT) polymorphism is associated with general familial cancer aggregation and, particularly, high-risk familial breast cancer. DNA hypermethylation has been identified as a mechanism of ARLTS1 expression down-regulation in lung carcinomas and B-cell chronic lymphocytic leukemia. We found that, in the majority of ovarian carcinomas (61.5%) and in a significant proportion of ovarian and breast cancer cell lines (45%), ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After ARLTS1 restoration by adenoviral transduction, only the negative TOV-112 and the homozygously mutated (MUT) MCF7 cells, but not the OV-90 cells expressing a normal ARLTS1 product, underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the tumorigenic potential of TOV-112 in nude mice. On the contrary, the ARLTS1-MUT induced significantly lower levels of apoptosis in infected cells and reduced in vivo tumorigenesis only partially, supporting the hypothesis that Trp149Stop polymorphism is retained in the general population and predisposes to cancer because of a reduction, but not full loss, of normal ARLTS1 function.
Reversed Phase High Performance Liquid Chromatography Using Carboxylic Acids in the Mobile Phase (1981)

Abstract This report describes the use of different carboxylic acids as mobile phase modifiers. The effect on retention of acid chain length, pH, and eluent composition for a series of phenylalkanols, phenol, and the amines aniline, N-methylaniline, and benzylamine is discussed. The retention of both neutral and positively charged compounds is influenced by the dissociation equilibrium of the carboxylic acid in the mobile phase. By using l-pentanol to coat excess exposed silanol groups on the reversed phase column used, the inflection in the retention of both neutral and charged solutes as pH is changed occurs at the pKa of the acid in the mobile phase. In addition, by using an acid and amine with the same or similar pKa values, selective ion-pairing of this pair over others with dissimilar pKa values can be promoted. Application of this technique to the selective retention of amino acids and peptides was unsuccessful.
Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial (2021)

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.
Critical Technologies For Electronic Still Imaging Systems (1989)

Electronic still camera systems are now in the consumer market place. The hard copy image quality of these systems is poor in comparison with the ever improving photographic film systems. However, the rate at which solid state image sensor technology, signal processing technology, mass storage technology, and non-photographic hard copy technology are advancing indicates that these electronic still camera imaging systems will someday find a place alongside traditional photographic systems. The current and future status of these critical technologies is the subject of this paper.
Discovery of Novel Conotoxin Candidates Using Machine Learning (2018)

Cone snails (genus Conus) are venomous marine snails that inject prey with a lethal cocktail of conotoxins, small, secreted, cysteine-rich peptides. Given the diversity and often high affinity for their molecular targets, consisting of ion channels, receptors or transporters, many conotoxins have become invaluable pharmacological probes, drug leads and therapeutics. Transcriptome sequencing of Conus venom glands followed by de novo assembly and homology-based toxin identification and annotation is currently the state-of-the-art for discovery of new conotoxins. However, homology-based search techniques, by definition, can only detect novel toxins that are homologous to previously reported conotoxins. To overcome these obstacles for discovery we have created ConusPipe, a machine learning tool that utilizes prominent chemical characters of conotoxins to predict whether a certain transcript in a Conus transcriptome, which has no otherwise detectable homologs in current reference databases, is a putative conotoxin. By using ConusPipe on RNASeq data of 10 species, we report 5,230 new putative conotoxin transcripts that have no homologues in current reference databases. 893 of these were identified by at least 3 out of 4 models used. These data significantly expand current publicly available conotoxin datasets and our approach provides a new computational avenue for the discovery of novel toxin families.
Biotransformation of Sildenafil in the Male Rat: Evaluation of Drug Interactions with Testosterone and Carbamazepine (2008)

The biotransformation of sildenafil to its major circulating metabolite, UK-103,320, was studied in male rat liver microsomes. The conversion of sildenafil to UK-103,320 by rat microsomes followed Michaelis-Menten kinetics, for which the parameters were V(max) = 1.96 microM/minand K(m) = 27.31 microM. Using substrates of CYP3A4 of testosterone and carbamazepine, the active sites on CYP3A4 responsible for metabolizing sildenafil were also evaluated. Sildenafil biotransformation was inhibited in the individual presence of testosterone and carbamazepine. The results showed drug interaction was observed in the sildenafil-testosterone and sildenafil-carbamazepine. Although testosterone and carbamazepine can inhibit sildenafil demethylation in concentration- and incubation time-dependent manners, sildenafil did not inhibit testosterone hydroxylation or carbamazepine epoxidation. These results may be explained by a model in which multiple substrates or ligands can concurrently bind to the active site of a single CYP3A4 molecule. However, the contribution of separate allosteric sites and conformational heterogeneity to the atypical kinetics of CYP3A4 cannot be ruled out in this study.
Saragossasäure A/Squalestatin S1: synthetische und retrosynthetische Untersuchungen (1994)

Schritt um Schritt zur ersten Totalsynthese: Saragossasäuren/Squalestatine können möglicherweise als Therapeutica für die Senkung des Serum‐Cholesterinspiegels eingesetzt werden. Die wichtigste Verbindung dieser neuartigen Naturstoffklasse, der wirkungsvolle Squalensynthase‐ Inhibitor Saragossasäure A/Squalestatin S1 1 , wurde nun über die Schlüsselzwischenstufen 2 und 3 synthetisiert. Zunächst wurden dazu die Schlußsequenz ( 2 → 1 ) erarbeitet und die Seitenketten an C1 und C6 in effizienten asymmetrischen Synthesen hergestellt. Die erste Synthese des hochoxygenierten Gerüstes der Saragossasäuren/Squalestatine gelang ausgehend von einem einfachen prochiralen Dien über die Zwischenstufe 3. Darauf aufbauend wurde ein Syntheseweg 3 → 2 entwickelt, so daß die Totalsynthese erfolgreich abgeschlossen werden konnte. Bb = Benzyl, PMB = para ‐Methoxybenzyl, TMS = Trimethylsilyl. magnified image
A genetic basis for the variation in the vulnerability of cancer to DNA damage (2016)

Radiotherapy is not currently informed by the genetic composition of an individual patient's tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumour cell lines. We show that sensitivity to radiation is characterized by significant variation across and within lineages. We combine results from our platform with genomic features to identify parameters that predict radiation sensitivity. We identify somatic copy number alterations, gene mutations and the basal expression of individual genes and gene sets that correlate with the radiation survival, revealing new insights into the genetic basis of tumour cellular response to DNA damage. These results demonstrate the diversity of tumour cellular response to ionizing radiation and establish multiple lines of evidence that new genetic features regulating cellular response after DNA damage can be identified.
Epidemiology of Diabetes (1998)

Diabetes mellitus now occurs in at least 100 million people worldwide, and it is estimated that by 2010 this will have more than doubled to 230 million. The impact of this increase will be far reaching through the micro- and macrovascular complications of diabetes, which lead to blindness, amputation, renal failure, and cardiovascular disease Epidemiology is but one branch of medical science involved in the study of diabetes and is directed mainly at understanding the changing disease distribution, the causes and risk factors of diabetes, and the likely effect of interventions to prevent diabetes or its complications. Classification and diagnostic criteria for diabetes are integral to diabetes epidemiology because changes in these can dramatically alter prevalence estimates; at the same time, however, epidemiology can inform the debate on revised classification systems for diabetes This review examines some of the key issues in diabetes epidemiology today: the National Diabetes Data Group and World Health Organization revised diabetes classifications based on etiology, the anticipated epidemic of diabetes, and factors contributing to increases in both Type 1 and Type 2 diabetes, complications of diabetes, and issues involved with diabetes screening In the absence of effective interventions for both Type 1 diabetes and Type 2 diabetes, the disease appears set to escalate world-wide with the main impact being seen in developing nations. Thus, finding ways to prevent or delay the onset of diabetes and finding effective treatment to prevent its microvascular and macrovascular complications are essential components of future public health strategies for all nations
HJV gene mutations in European patients with juvenile hemochromatosis (2005)

A large variety of mutations within the genes encoding hepcidin (HAMP) and hemojuvelin (HJV) have been identified in patients with the severe iron overload disorder juvenile hemochromatosis (JH). The aim of the present study was to evaluate the molecular background of JH in patients from central parts of Europe. Sequence analyses of HAMP and HJV were performed in seven JH patients from six families from Germany, Slovakia, and Croatia. For detection of the G320V mutation in HJV, a rapid polymerase chain reaction-based assay was developed. No mutations were found within the HAMP gene. Six of seven (86%) JH patients carried at least one copy of the G320V mutation within the HJV gene. Four of these patients were homozygous for the G320V mutation. In addition, two novel HJV mutations were identified (C119F and S328fsX337). Taken together, the present study demonstrates that molecular analysis of the HJV gene is a powerful tool for an early and reliable diagnosis of JH. As in affected patients from Greece, the G320V mutation seems to be widely distributed among JH patients from central parts of Europe. Therefore, detection of the G320V mutation could identify the majority of JH cases from these regions non-invasively.
Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome (2008)

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by many features, including obesity and cardiovascular disease. We previously developed knockout mouse models of 3 BBS genes: BBS2, BBS4, and BBS6. To dissect the mechanisms involved in the metabolic disorders associated with BBS, we assessed the development of obesity in these mouse models and found that BBS-null mice were hyperphagic, had low locomotor activity, and had elevated circulating levels of the hormone leptin. The effect of exogenous leptin on body weight and food intake was attenuated in BBS mice, which suggests that leptin resistance may contribute to hyperleptinemia. In other mouse models of obesity, leptin resistance may be selective rather than systemic; although mice became resistant to leptin's anorectic effects, the ability to increase renal sympathetic nerve activity (SNA) was preserved. Although all 3 of the BBS mouse models were similarly resistant to leptin, the sensitivity of renal SNA to leptin was maintained in Bbs4 -/- and Bbs6 -/- mice, but not in Bbs2 -/- mice. Consequently, Bbs4 -/- and Bbs6 -/- mice had higher baseline renal SNA and arterial pressure and a greater reduction in arterial pressure in response to ganglionic blockade. Furthermore, we found that BBS mice had a decreased hypothalamic expression of proopiomelanocortin, which suggests that BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons.
The Identification of Particles in a Polymer Film Using Nano-Thermal Analysis (2006)

Abstract Nano-TA is a local thermal analysis technique that combines the high spatial resolution imaging capabilities of atomic force microscopy (AFM) with the ability to obtain understanding of the thermal behaviour of materials with a spatial resolution of sub-100nm. This breakthrough in spatial resolution of thermal analysis, which is ~50× better than previously reported, has profound implications for the fields of polymers and pharmaceuticals where local thermal understanding is key. The conventional AFM tip is replaced by a special nano-TA probe that has an embedded miniature heater and is controlled by the specially designed nano-TA hardware and software. The nano-TA probe enables a surface to be visualised at nanoscale resolution using the routine imaging modes of AFM. The user is able to select the spatial locations for the investigation of the thermal properties of the surface. Heat is supplied locally via the probe tip and the thermomechanical response is measured.
353 Artificial immune modulation adoptive cell therapies for virally driven malignancies (2022)

<h3>Background</h3> NexImmune is developing novel, antigen-specific immunotherapies to meet serious unmet clinical needs. Here we report on the development of adoptive cell therapies (ACT) for virally driven malignancies. The proprietary Artificial Immune Modulation (AIM™) platform mimics natural T cell biology to target, activate and expand antigen-specific CD8<sup>+</sup> T cells. EBV, HPV, and HTLV are estimated to contribute to 6-7% of global cancer cases. The targeted antigens are implicated in multiple malignancies including B cell lymphomas (EBV), adult T cell leukemia/lymphoma (HLTV1) as well as multiple HPV related malignancies such as oropharyngeal, cervical, and anal cancers. <h3>Methods</h3> Using the paramagnetic AIM nanoparticle as an artificial antigen presenting cell (aAPC), in two-weeks T cells were enriched and expanded from HLA-A*02:01 donor apheresis material against immunodominant antigens of EBV, HTLV, and HPV. The memory phenotype of these cells was determined by CD45RA, CD62L, and CD95 expression. Antigen specific killing was observed on HLA-A2+ cell lines and polyfunctional activity characterized by an intracellular cytokine staining assay. <h3>Results</h3> Greater than 90% of the total resulting CD8<sup>+</sup> T cells display a phenotype of effector, central, or long-lived stem-like memory. From 8 independent healthy donor clinical scale manufacturing runs of NEXI-003, a pentavalent specific AIM ACT against the E6 and E7 antigens of both HPV-16 and HPV-18, as well as the tumor-associated antigen Survivin, 0.28E9 to 3.79E9 cells were generated. These cells showed dual HPV-16<sup>+</sup> and HPV-18<sup>+</sup> cancer antigen specificity and cytotoxic activity against HLA-A2<sup>+</sup> cell lines, without significant cytotoxic activity against autologous PBMCs. With respect to EBV, using HLA-A2<sup>+</sup> cell lines we further show antigen specific killing directed at LMP2, BRLF1, BMLF1, EBNA3, and LMP1 from a single healthy donor AIM ACT selected on 6 EBV antigens. In addition, these expanded memory T cells demonstrate a high degree of polyfunctional activity upon stimulation. <h3>Conclusions</h3> NEXI-003 is an immunotherapy for HPV cancers in HLA*A02:01 patients that recently received IND clearance and it is anticipated to begin clinical trials in 2022. In addition to B cell lymphomas, B cells that are present in the plaques of multiple sclerosis patients have been found to express EBV antigens. Therefore, by directing a multivalent EBV T cell response there is the potential to treat other EBV-associated diseases using one AIM ACT product. Results reported here, will support the expansion of the AIM platform modalities for use in the treatment of virally driven malignancies, as well as potential virally associated autoimmune and infection diseases.