gebhart/patrepeval huggingface dataset:
CRISPR-Cas Controls Cryptic Prophages (2022)

The bacterial archetypal adaptive immune system, CRISPR-Cas, is thought to be repressed in the best-studied bacterium, <i>Escherichia coli</i> K-12. We show here that the <i>E. coli</i> CRISPR-Cas system is active and serves to inhibit its nine defective (i.e., cryptic) prophages. Specifically, compared to the wild-type strain, reducing the amounts of specific interfering RNAs (crRNA) decreases growth by 40%, increases cell death by 700%, and prevents persister cell resuscitation. Similar results were obtained by inactivating CRISPR-Cas by deleting the entire 13 spacer region (CRISPR array); hence, CRISPR-Cas serves to inhibit the remaining deleterious effects of these cryptic prophages, most likely through CRISPR array-derived crRNA binding to cryptic prophage mRNA rather than through cleavage of cryptic prophage DNA, i.e., self-targeting. Consistently, four of the 13 <i>E. coli</i> spacers contain complementary regions to the mRNA sequences of seven cryptic prophages, and inactivation of CRISPR-Cas increases the level of mRNA for lysis protein YdfD of cryptic prophage Qin and lysis protein RzoD of cryptic prophage DLP-12. In addition, lysis is clearly seen via transmission electron microscopy when the whole CRISPR-Cas array is deleted, and eliminating spacer #12, which encodes crRNA with complementary regions for DLP-12 (including <i>rzoD</i>), Rac, Qin (including <i>ydfD</i>), and CP4-57 cryptic prophages, also results in growth inhibition and cell lysis. Therefore, we report the novel results that (i) CRISPR-Cas is active in <i>E. coli</i> and (ii) CRISPR-Cas is used to tame cryptic prophages, likely through RNAi, i.e., unlike with active lysogens, active CRISPR-Cas and cryptic prophages may stably co-exist.
The mortality risk of overhydration in haemodialysis patients (2009)

The results of our study indicate that the hydration state is an important and independent predictor of mortality in chronic HD patients secondary only to the presence of diabetes. We believe that it is essential to measure the hydration status objectively and quantitatively in order to obtain a more clearly defined assessment of the prognosis of haemodialysis patients.
Green server design: beyond operational energy to sustainability (2010)

“Green ” server and datacenter design requires a focus on environmental sustainability. Prior studies have focused on operational energy consumption as a proxy for sustainability, but this metric only captures part of the environmental impact. In this paper, we argue that to understand the total impact, we need to examine the entire lifecycle of the system, beyond operational energy to also include material use and manufacturing. We make two main contributions. We present a methodology that allows such a lifecycle analysis, specifically providing attribution of sustainability bottlenecks to individual system architecture components. Using this methodology, we compare the sustainability tradeoffs between popular energy-efficiency optimizations and discuss sustainability bottlenecks and optimizations for future system designs. 1.
Integrin αVβ3 restrains fibrosis and elevated interstitial fluid pressure in syngeneic mouse carcinoma : Integrin β3-ablation affects tumor microenvironment (2010)

In addition to malignant cells, solid tumors comprise supporting stromal tissue that consists of extra cellular matrix (ECM), connective tissue cells, inflammatory cells and blood vessels. The stromal compartment and the malignant cells together shape the tumor microenvironment that in turn determines tumor progression and efficacy of anti-tumor treatments. In this thesis, studies that investigate the roles of different kinds of interactions between tumor cells and stromal cells were undertaken. Further, growth factors that have important roles in interactions between tumor cells and stromal cells were investigated in a non-tumor environment. Tumor cells were found to modulate the response to the platelet derived growth factor (PDGF) by microvascular pericytes, a cell type found in the vasculature of solid tumors. The importance of this growth factor in biology of tumors has earlier been shown, but here it was shown that PDGF also modulate the ECM phenotype of solid tumors. The ECM of tumors treated with an inhibitor of PDGF receptor (PDGFR) signaling induced a less fibrotic collagen scaffold, which could explain how PDGFR inhibition in earlier reports lowered tumor interstitial fluid pressure (IFP). Lowering the normally high IFP in tumors increases efficacy of chemotherapy. The integrin αVβ3 is activated downstream of PDGF-B in acute inflammations, and this integrin is important for raising IFP in loose connective tissue in such conditions. However, in tumors we found that lack of the β3 subunit lead to an increased IFP, which were attributed to a more fibrotic ECM phenotype. In addition to PDGF-B, transforming growth factor β (TGFβ) is an important growth factor in the biology of tumors. These two growth factors were separately overexpressed in mouse skin and they both induced an inflammatory response. Expressed in a tumor free context, they evoked a response that was in many ways reminiscent of what can be observed in the tumor microenvironment. This thesis contributes further understanding of how the complex tumor microenvironment affects the phenotype of solid tumors.
Study of the flow induced by a sliding discharge (2009)

In this work, we report on electrical and fluid-dynamics studies concerning the flow induced by a sliding discharge (SD). This kind of discharge was created with a three electrode system configuration: one excited with AC and the others with a DC negative voltage. The SD was activated on a quiescent fluid at atmospheric pressure. The flow field induced by the SD was analysed by measurements undertaken with Pitot probes and Schlieren Image Velocimetry. Under the conditions of our experiments two "jet flows", that blown towards the interelectrode space, were induced from the air exposed electrodes. As a consequence of the mutual interaction of these two flows and of the magnitude of each flow, a resulting plume like planar jet of adjustable direction (0-180deg) could be formed. A robust control of the axis direction of the plume could be achieved by modifying the AC voltage value.
Achromatization of solar concentrator using diffractive optics (2009)

Photovoltaic energy suffers from payback time. High solar concentration (above 500 suns) is a very interesting way to reduce production cost. The use of lenses allows more flexibility to make light flux more uniform. In addition lenses are less prone to errors of manufacture and can be easily duplicated. Unfortunately, optical materials are very dependent on the wavelength which causes important chromatic aberrations. One can think about achromatic doublets but doublets are thick, heavy and require exotic glasses which make them expensive. During the conference, I would like to present an innovative way to achromatize solar concentrators using hybrid (refractive/diffractive) lenses. Indeed, an hybrid lens is as thin as a Fresnel lens and is made in only one glass. But diffractive lenses suffer from limited broadband diffraction efficiency due to spurious orders. To overcome the lake of efficiency we are investigating the use of multi-layer diffractive optical element. This technique allows to achieve an efficiency greater than 97% over the full visible spectrum using only three components (e.g. two optical elements + air).
SYST-14 CLINICAL EFFICACY OF ONC201 IN RECURRENT H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA (DMG) PATIENTS (2022)

Abstract BACKGROUND H3 K27M-mutant DMG predominantly affects children and young adults; no effective therapy is known. ONC201 is a first-in-class, anti-cancer DRD2 antagonist and ClpP agonist. METHODS Fifty pediatric and adult patients with recurrent H3 K27M DMG who received oral ONC201 monotherapy in clinical trials and expanded access were selected for a planned efficacy analysis. Eligibility criteria included measurable contrast-enhancing disease by RANO-HGG criteria (excluding pontine and spinal cord tumors), KPS/LPS≥60, ≥90 days from prior radiation, and adequate washout from prior anti-cancer therapy. The primary endpoint was overall response rate (ORR) by RANO-HGG criteria. Secondary endpoints included duration of response, time to response, progression-free survival (PFS), overall survival (OS), corticosteroid response rate, performance status response rate, and ORR by RANO-LGG criteria. Radiographic endpoints were assessed by dual-reader blinded independent central review. Data cutoff was May 31, 2021. RESULTS ORR was 20.0% (95%CI, 10.0–33.7) by RANO-HGG criteria. Median duration of response was 11.2 months (95%CI, 3.8–not reached) and median time to response was 8.3 months (range, 1.9–15.9). PFS at 6 months was 35.1% (95%CI, 21.2–49.3). The ORR was 26.0% (95%CI, 14.6–40.3) by RANO-LGG criteria. Fifteen patients (30.0%; 95%CI, 17.9–44.6) achieved an objective response by RANO-HGG and/or RANO-LGG criteria. Of 15 patients receiving ≥4 mg daily dexamethasone at baseline, 7 (46.7%; 95%CI, 21.3–73.4) achieved ≥50% confirmed reduction in dose. Of 34 patients with baseline KPS/LPS &amp;lt;80, 7 (20.6%; 95%CI, 8.7–37.9) achieved a confirmed performance status improvement. With a median follow-up of 18.8 months, median OS was 13.7 months (95%CI, 8.0–20.3) and OS at 24 months was 34.7% (95%CI, 20.7–49.2). Twenty-five patients had serious adverse events with one possibly related to ONC201 by investigator assessment. CONCLUSIONS ONC201 monotherapy exhibits durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.
Survival in a bad neighborhood: pancreatic islets in cystic fibrosis (2019)

In cystic fibrosis (CF), ductal plugging and acinar loss result in rapid decline of exocrine pancreatic function. This destructive process results in remodeled islets, with only a modest reduction in insulin-producing β cells. However, β-cell function is profoundly impaired, with decreased insulin release and abnormal glucose tolerance being present even in infants with CF. Ultimately, roughly half the CF subjects develop diabetes (termed CF-related diabetes (CFRD)). Importantly, CFRD increases CF morbidity and mortality via worsening catabolism and pulmonary disease. Current accepted treatment options for CFRD are aimed at insulin replacement, thereby improving glycemia as well as preventing nutritional losses and lung decline. CFRD is a unique form of diabetes with a distinct pathophysiology that is as yet incompletely understood. Recent studies highlight emerging areas of interest. First, islet inflammation and lymphocyte infiltration are common even in young children with CF and may contribute to β-cell failure. Second, controversy exists in the literature regarding the presence/importance of β-cell intrinsic functions of CFTR and its direct role in modulating insulin release. Third, loss of the CF transmembrane conductance regulator (CFTR) from pancreatic ductal epithelium, the predominant site of its synthesis, results in paracrine effects that impair insulin release. Finally, the degree of β-cell loss in CFRD does not appear sufficient to explain the deficit in insulin release. Thus, it may be possible to enhance the function of the remaining β-cells using strategies such as targeting islet inflammation or ductal CFTR deficiency to effectively treat or even prevent CFRD.
ChemInform Abstract: POTENTIAL ANTITUMOR AGENTS. 30. MUTAGENIC ACTIVITY OF SOME 9‐ANILINOACRIDINES: RELATIONSHIPS BETWEEN STRUCTURE, MUTAGENIC POTENTIAL, AND ANTILEUKEMIC ACTIVITY (1979)

Abstract Untersucht werden die mutagene Wirkung und Toxizität der Anilinoderivate (II) bei verschiedenen Salmonella typhimurium‐Stämmen, wobei die Antibiotica Adriamycin (Ia) und Daunomycin (Ib) als Standard dienen.
Abstract A045: Inhibition of tumor growth by combination of metronomic chemotherapy and checkpoint inhibitor with a cancer vaccine (2016)

Abstract The efficacy of cancer immunotherapies can be significantly limited by the immune suppressive soluble factors and cell types characterizing the tumor microenvironment. Strategies combining anti-immune suppressive therapies and cancer vaccines need to be evaluated. In the present study, a novel combinatorial strategy was assessed in a mouse model using an aggressive therapeutic setting based on sub-cutaneous ectopic implantation of B16 melanoma cells. The anti-immune suppressive therapy included a novel mix of chemotherapy agents, administered in a metronomic fashion (MCT), and an anti-PD-1 checkpoint inhibitor (CI). The vaccine (VAC) was a multi-peptide cocktail, including melanoma-specific tumor-associated antigens. The newly designed strategy was shown to be safe, well tolerated and highly effective. Animals treated with MCT or CI showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such effect was significantly enhanced by the combination with the multi-peptide vaccine. In particular, the multi-pronged MCT+CI+VAC combination resulted in a remarkable inhibition of tumor growth in 5/6 animals. The anti-tumor effect was associated with a strong T cell immune response to vaccine peptides as well as significant intra-tumor T cell infiltration associated with reduction in Tregs. Overall, the results showed that the combination of anti-immune suppressive therapy and vaccine was able to strongly potentiate the anti-tumor effects. The described approach is highly promising to significantly enhance the anti-tumor effects induced by a therapeutic cancer vaccine. Citation Format: Maria Tagliamonte, Annacarmen Petrizzo, Angela Mauriello, Antonio Luciano, Domenica Rea, Antonio Barbieri, Claudio Arra, Piera Maiolino, Maria Lina Tornesello, Gennaro Ciliberto, Franco M. Buonaguro, Luigi Buonaguro. Inhibition of tumor growth by combination of metronomic chemotherapy and checkpoint inhibitor with a cancer vaccine [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A045.
A Remarkable Ligand Orientational Effect in Osmium‐Atom‐Induced Blue Phosphorescence (2004)

A new series of Os(II)-based carbonyl complexes cis(CO),trans(Npy,Npy),cis(Ntz,Ntz)-[Os(CO)2(bptz)2] (1), cis(CO),cis(Npy,Npy),trans(Ntz,Ntz)-[Os(bptz)2(CO)2] (2), and cis(CO),trans(Npy,Npy),cis(Ntz,Ntz)-[Os(CO)2(fptz)2] (3), where bptz and fptz denote 3-tert-butyl-5-(2-pyridyl)- and 3-trifluoromethyl-5-(2-pyridyl)-1,2,4-triazolate, respectively, have been designed and synthesized in an effort to achieve high efficiency, room-temperature blue phosphorescence. Although 1 and 2 are geometric isomers, remarkably different excited-state relaxation pathways were observed. Complex 1 exhibits strong phosphorescence in CH3CN (Phi(p) approximately 0.47) and as a single crystal at room temperature, whereas complex 2 is nearly nonemissive under similar conditions. The associated relaxation dynamics have been comprehensively investigated by spectroscopic and relaxation dynamics as well as by theoretical approaches. Our results lead us to the conclusion that for complex 2, the "loose bolt" effect of metal-ligand bonding interactions plays a crucial role in the fast radiationless deactivation of this type of geometrical isomer. Fine adjustment can also be achieved by functionalizing the ligands so that the electron-withdrawing nature of the CF3 group in 3 stabilizes the HOMO of the triazolate moiety, thus moving the emission further into the pure "blue" region; this results in highly efficient phosphorescence and renders 3 particularly attractive for application in blue OLED devices.
The EMSLAB Electromagnetic Sounding Experiment (1988)

EMSLAB (Electromagnetic Sounding of the Lithosphere and Beyond)—Juan de Fuca is the largest electromagnetic (EM) induction experiment ever carried out. The two general objectives are to investigate the electrical structure of the lithosphere and asthenosphere beneath a complete oceanic plate and the adjacent continent under which it is subducted and to study tidal, mesoscale eddy, and other large‐scale oceanic motions by measuring the electric currents induced in seawater as it moves in the geomagnetic field. More than 40 scientists, from 18 university and government institutions in the United States, Canada, Japan, Mexico, and Australia, are taking part.
Kinetics and Mechanism of Turanite Reduction by Hydrogen (2020)

Turanite, Cu&lt;sub&gt;5&lt;/sub&gt;(VO&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;(OH)&lt;sub&gt;4&lt;/sub&gt;, is a naturally occurring mineral whose physical and chemical properties are of interest for magnetic data storage, battery applications, and catalysis. In this study, the reduction of nanostructured Cu&lt;sub&gt;5&lt;/sub&gt;(VO&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;(OH)&lt;sub&gt;4&lt;/sub&gt; by H&lt;sub&gt;2&lt;/sub&gt; is investigated using a combination of scanning transmission electron microscopy–electron energy-loss spectroscopy, X-ray photoelectron spectroscopy, &lt;i&gt;in situ&lt;/i&gt; diffuse reflectance infrared Fourier transform spectroscopy, &lt;i&gt;in situ&lt;/i&gt; X-ray absorption spectroscopy, first-principles calculations, and kinetic analysis based on thermogravimetry. A two-step mechanism is proposed, in which Cu&lt;sub&gt;5&lt;/sub&gt;(VO&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;(OH)&lt;sub&gt;4&lt;/sub&gt; is first reduced, following exponential growth kinetics, to form a stable intermediate consisting of a mix of Cu&lt;sub&gt;3&lt;/sub&gt;VO&lt;sub&gt;4&lt;/sub&gt;, Cu&lt;sub&gt;2&lt;/sub&gt;O, and CuV&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;5&lt;/sub&gt;. The intermediate phase is then subsequently reduced in a 3-D diffusion-limited process to form two segregated phases consisting of Cu metal and V&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; particles. The apparent energy barriers for these two steps, obtained from the kinetic analysis, were found to be 52.5 and 71.2 kJ mol&lt;sup&gt;–1&lt;/sup&gt; for Stages 1 and 2 of the reduction, respectively. These results highlight the importance of developing a rigorous understanding of the reduction processes involved in metal oxide catalyst preparation.
Challenge of developing new tuberculosis vaccines to generate life-long protective immunity (2009)

A major hurdle in the eradication of important human pathogens is the development of vaccines to combat the three big killers: HIV, tuberculosis (TB) and malaria. While several factors could be att...
Using wearable technology to detect prescription opioid self-administration (2021)

Appropriate monitoring of opioid use in patients with pain conditions is paramount, yet it remains a very challenging task. The current work examined the use of a wearable sensor to detect self-administration of opioids after dental surgery using machine learning. Participants were recruited from an oral and maxillofacial surgery clinic. Participants were 46 adult patients (26 female) receiving opioids after dental surgery. Participants wore Empatica E4 sensors during the period they self-administered opioids. The E4 collected physiological parameters including accelerometer x-, y-, and z-axes, heart rate, and electrodermal activity. Four machine learning models provided validation accuracies greater than 80%, but the bagged-tree model provided the highest combination of validation accuracy (83.7%) and area under the receiver operating characteristic curve (0.92). The trained model had a validation sensitivity of 82%, a specificity of 85%, a positive predictive value of 85%, and a negative predictive value of 83%. A subsequent test of the trained model on withheld data had a sensitivity of 81%, a specificity of 88%, a positive predictive value of 87%, and a negative predictive value of 82%. Results from training and testing model of machine learning indicated that opioid self-administration could be identified with reasonable accuracy, leading to considerable possibilities of the use of wearable technology to advance prevention and treatment.
Improved deep brain assessments resulted in reduced cortical FDG uptake after normalization with a new semiconductor PET (2010)

468 Objectives Newly developed semiconductor PET has superior spatial resolution yielding images relatively independent from the partial volume effect. The purpose of this study was to investigate the effects of thalamic vs. global normalizations to the statistical analyses for brain FDG-PET images. Methods Sixteen volunteers underwent brain FDG-PET using the following scanners; 1) Siemens HR+ , 10 minutes acquisition in 3D yielding 256 x 256 matrix with FWHM of 6.4 mm after fourier rebinning reconstruction, and 2) Hitachi semiconductor PET, 12 minutes acquisition in 3D yielding 256 x 256 matrix with FWHM of 2.5 mm. The new PET uses a the median root prior reconstruction integrated with a resolution recovery in the maximum a posteriori iterative process. Images were spatially normalized to a standard brain atlas, and compared with an available normal database using 3D-SSP to evaluate regional variations in a form of z-scores in 16 cortical regions. Comparison was made after global and thalamic normalization. Results The new semiconductor system showed 22% higher z-score values (lower relative uptake) in the cortical regions with thalamic (1.29 ± 0.62) than with global normalization (1.13 ± 0.55), indicating an effect of better spatial resolution resulting in a lower cortical uptake relative to the thalamus compared to the normal database. Conventional system showed relatively constant z-scores with thalamic (0.93±0.41) or global normalization (0.85 ± 0.39), indicating constant effects of differences from the normal database. Conclusions The new system demonstrated a different pattern of FDG distribution in healthy volunteers. Superior spatial resolution permits better delineation of deep brain function resulting in a lower relative cortical uptake after normalization, thus requiring a dedicated normal database for statistical analyses
ChemInform Abstract: Pyrido(3,4‐e)‐1,2,4‐triazines and Related Heterocycles as Potential Antifungal Agents. (1990)

Abstract 4‐Hydroxypyridine (I) is nitrated to give 4‐hydroxy‐3‐nitropyridine (III) which is chlorinated, forming the 4‐chloro derivative (IV).