gebhart/patrepeval huggingface dataset:
Compassionate Use of Bacteriophages for Failed Persistent Infections During the First 5 Years of the Israeli Phage Therapy Center (2023)

The use of bacteriophages (phages) is reemerging as a potential treatment option for antibiotic-resistant or nonresolving bacterial infections. Phages are bacteria-specific viruses that may serve as a personalized therapeutic option with minimal collateral damage to the patient or the microbiome. In 2018 we established the Israeli Phage Therapy Center (IPTC) as a shared initiative of the Hadassah Medical Center and the Hebrew University of Jerusalem, aiming to conduct all of the steps required for phage-based solutions, from phage isolation and characterization to treatments, for nonresolving bacterial infections. So far, a total of 159 requests for phage therapy arrived to the IPTC; 145 of them were from Israel and the rest from other countries. This number of registered requests is growing annually. Multidrug-resistant bacteria accounted for 38% of all phage requests. Respiratory and bone infections were the most prevalent among clinical indications and accounted for 51% of the requests. To date, 20 phage therapy courses were given to 18 patients by the IPTC. In 77.7% (n = 14) of the cases, a favorable clinical outcome of infection remission or recovery was seen. Clearly, establishing an Israeli phage center has led to an increased demand for compassionate use of phages with favorable outcomes for many previously failed infections. As clinical trials are still lacking, publishing patient data from cohort studies is pertinent to establish clinical indications, protocols, and success and failure rates. Last, workflow processes and bottlenecks should be shared to enable faster availability and authorization of phages for clinical use.
DIPG-11. ACTIVATION OF RAS SIGNALING AND DISTINCT MITOGEN-ACTIVATED PROTEIN KINASES (MAPKs) PROVIDES UNIQUE THERAPEUTIC VULNERABILITIES IN MUTANT HISTONE DIPG (2019)

Diffuse intrinsic pontine gliomas (DIPGs) are incurable pediatric brain tumors with an aggressive onset. Apart from irradiation, there are currently no effective therapies available for DIPG patients, who have a median survival time of less than one year. DIPG cells possess a mutation in histone H3 (H3K27M) that results in a reduction of H3K27 trimethylation and activation of oncogenic signaling pathways. We show that the H3K27M mutation induces RAS pathway signaling which is augmented by additional RAS activators including PDGFRA. We observed that the H3K27M mutation leads to silencing of GTPase-activating proteins, namely RASAL1, which when ectopically expressed, reduced proliferation and RAS activation. An siRNA screen of RAS pathway effectors identified ERK5, but not ERK1/2, as important for DIPG growth. Suppression of ERK5, which is highly expressed in DIPG, decreased DIPG cell proliferation and induced apoptosis both in vitro and in vivo. Mechanistically, we show that ERK5 directly activates and stabilizes the proto-oncogene MYC. ERK5 overexpression fully rescued ERK5-depleted cells and partial rescue was achieved by expression of ERK5 mutants lacking kinase activity or the transactivation domain (ΔTAD). However, no rescue was achieved with kinase-dead, ΔTAD double mutants. Additionally, ERK5 knockdown or treatment with ERK5 inhibitors significantly increased survival of mice intracranially engrafted with DIPG cells. TG02, a pan-CDK and ERK5 inhibitor currently in phase II trials for various cancers, was the most effective treatment, extending median survival time nearly two-fold. Collectively, our data demonstrate DIPG reliance on RAS and MYC activities, and in so doing reveal novel therapeutic targets for treating these tumors.
Abstract 3341: Synthetic lethality by targeting ribonucleotide reductase in PP2A deficient uterine serous carcinoma (2022)

Abstract Uterine serous carcinoma (USC) is a highly aggressive endometrial cancer subtype with limited therapeutic options and a lack of targeted therapies. While mutations to PPP2R1A, encoding the predominant protein phosphatase 2A (PP2A) scaffolding protein Aα, occur in 30-40% of cases, the clinical actionability of these mutations has not been studied. Here, we show that mutation to Aα results in synthetic lethality to treatment with inhibitors of ribonucleotide reductase (RNR), and multiple models of Aα mutant uterine serous tumors were sensitive to Clofarabine, an RNR inhibitor in vivo. Aα mutant cells displayed impaired checkpoint signaling upon RNRi treatment, and subsequently accumulated more DNA damage than wild type cells. This was PP2A dependent as complete inhibition of PP2A activity using LB-100, a catalytic site inhibitor, sensitized wild type USC cells to RNRi. Analysis of TCGA data indicated that inactivation of PP2A, through loss of PP2A subunit expression, was prevalent in USC, with 88% of USC patients harboring loss of at least one PP2A gene. In contrast, loss of PP2A subunit expression was rare in uterine endometrioid carcinomas. While RNR inhibitors are not routinely used for uterine cancers, we identified a cohort of patients with recurrent disease treated with gemcitabine at MSKCC as a second or later line therapy. In a retrospective analysis of this cohort there was a trend for improved outcomes in USC patients treated with RNRi gemcitabine compared to patients with endometrioid histology. Overall, our data provide experimental evidence to support the use of ribonucleotide reductase inhibitors for the treatment of USC. Citation Format: Caitlin M. O'Connor, Sarah E. Taylor, Kathryn M. Miller, Lauren Hurst, Terrance J. Haanen, Tahra K. Suhan, Kaitlin P. Zawacki, Fallon K. Noto, Jonida Trako, Arathi Mohan, Jaya Sangodkar, Dmitriy Zamarin, Analisa DiFeo, Goutham Narla. Synthetic lethality by targeting ribonucleotide reductase in PP2A deficient uterine serous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3341.
Securing Wireless Data Networks against Eavesdropping using Smart Antennas (2008)

In this paper, we focus on securing communication over wireless data networks from malicious eavesdroppers, using smart antennas. While conventional cryptography based approaches focus on hiding the meaning of the information being communicated from the eavesdropper, we consider a complimentary class of strategies that limit knowledge of the existence of the information from the eavesdropper. We profile the performance achievable using simple beamforming strategies using a newly defined metric called exposure region. We then present three strategies within the context of an approach called virtual arrays of physical arrays to significantly improve the exposure region performance of a wireless LAN environment. Using simulations and analysis, we validate and evaluate the proposed strategies.
Supplemental Table 1 from RB Loss Promotes Prostate Cancer Metastasis (2023)

&lt;p&gt;nucleotide sequence&lt;/p&gt;
Intraoperative 68Ga-PSMA Cerenkov Luminescence Imaging for Surgical Margins in Radical Prostatectomy: A Feasibility Study (2020)

Our objective was to assess the feasibility and accuracy of Cerenkov luminescence imaging (CLI) for assessment of surgical margins intraoperatively during radical prostatectomy. <b>Methods:</b> A single-center feasibility study included 10 patients with high-risk primary prostate cancer (PC). <sup>68</sup>Ga-prostate-specific membrane antigen (PSMA) PET/CT scans were performed followed by radical prostatectomy and intraoperative CLI of the excised prostate. In addition to imaging the intact prostate, in the first 2 patients the prostate gland was incised and imaged with CLI to visualize the primary tumor. We compared the tumor margin status on CLI to postoperative histopathology. Measured CLI intensities were determined as tumor-to-background ratio. <b>Results:</b> Tumor cells were successfully detected on the incised prostate CLI images as confirmed by histopathology. Three of 10 men had histopathologically positive surgical margins (PSMs), and 2 of 3 PSMs were accurately detected on CLI. Overall, 25 (72%) of 35 regions of interest proved to visualize a tumor signal according to standard histopathology. The median tumor radiance in these areas was 11,301 photons/s/cm<sup>2</sup>/sr (range, 3,328-25,428 photons/s/cm<sup>2</sup>/sr), and median tumor-to-background ratio was 4.2 (range, 2.1-11.6). False-positive signals were seen mainly at the prostate base, with PC cells overlaid by benign tissue. PSMA immunohistochemistry revealed strong PSMA staining of benign gland tissue, which impacts measured activities. <b>Conclusion:</b> This feasibility showed that <sup>68</sup>Ga-PSMA CLI is a new intraoperative imaging technique capable of imaging the entire specimen's surface to detect PC tissue at the resection margin. Further optimization of the CLI protocol, or the use of lower-energy imaging tracers such as <sup>18</sup>F-PSMA, is required to reduce false-positives. A larger study will be performed to assess diagnostic performance.
PdII‐ and PtII‐Mediated Polycyclization Reactions of 1,5‐ and 1,6‐Dienes: Evidence in Support of Carbocation Intermediates (2004)

Die relative Konfiguration von Verbindung 11 wurde in der Zuschrift falsch wiedergegeben. Die richtige Struktur ist das Epimer bezüglich des Carbinol-Kohlenstoffatoms (hier abgebildet); diese Zuordnung wird durch ein NOE-Kreuzsignal für das Carbinol-Wasserstoffatom und die angulare Methylgruppe im NOESY-Spektrum gestützt. Die Autoren bitten, dieses Versehen zu entschuldigen.1
Editorial (2012)

Welcome to this issue of Learning and Teaching: The International Journal of Higher Education in the Social Sciences. Our thanks go to the authors of articles, the essay and the reviews, the anonymous referees who read the articles and the essay, the publishers who provided review copies of the books, our own publisher Berghahn and the Editorial Board.
Drug compatibility with the sponge phases formed in monoolein, water, and propylene glycol or poly(ethylene glycol) (1998)

The liquid sponge phase, a bicontinuous lipid-water system, formed in solvent-monoolein-water systems was investigated with respect to drug compatibility. The solvents propylene glycol and poly(ethylene glycol) swell the bicontinuous cubic phase of the monoolein-water system and form the sponge phase at constant water contents, 40 and 30% w/w, respectively. Amphiphilic drugs such as lidocaine participate in the bilayer and act on the interfacial curvature according to the amphiphilic packing concept. The interfacial curvatures increase/decrease depending on the salt/base forms of the molecules. The quantity of lidocaine that can be incorporated into the sponge phase depends not only on the form of lidocaine but also on the lipid content and the solvent used in the sponge phase. Addition of the water-insoluble gramicidin S to the sponge phase resulted in a stiff isotropic phase, possibly a cubic phase, indicating interaction of gramicidin S with the lipid bilayer. The in vitro release of lidocaine was significantly faster from the sponge phase in the propylene glycol system than from the corresponding cubic phase without solvent.
P06.07 * GRADE 2 MENINGIOMA AND RADIOSURGERY (2014)

BACKGROUND: Grade 2 meningiomas are aggressive tumors associated a high recurrence rate, leading to repeated surgical procedures, which can seriously worsen the patients' neurological status. Although, radiosurgery is an increasingly popular technique, its role in the management of grade 2 meningiomas has yet to be precised. OBJECTIVE: Our study aims to evaluate radiosurgery in achieving tumor control of proven tumor progression occurring after the surgical resection of grade 2 meningioma. METHODS: This retrospective study included 27 consecutive patients who underwent radiosurgery for the treatment of a proven radiological progression of a previously surgically treated grade 2 meningioma between 2000 and 2012. The mean radiation dose was 15.2 grays (range 12 to 21) and the mean target volume was 5.4 cm3 (range 0.194 to 14.2). There were 9 men and 18 women with a mean age of 59 years. Thirty-four radiosurgical procedures were performed in 27 patients. RESULTS: The mean progression-free survival after radiosurgery was 32.4 months concerning the target irradiated volume and 26.4 months regarding all intracranial meninges. With a mean follow-up time of 56.4 months (range 12 to 120), the 12-, 24-, and 36-month actuarial local and regional control rates for all patients were 75%, 52%, 40%, and 75%, 48%, 33%, respectively. We reported a single case of transient hemiparesis that completely resolved without sequelae. CONCLUSION: Radiosurgery appears to be a safe and effective treatment for local control of delayed progression after surgical resection of a grade 2 meningioma. Higher doses, similar to those applied for malignant tumors should be recommended when possible.
Succinic Acid Production from Jerusalem Artichoke Tubers (2013)

In this work, A. succinogenes 130Z was used to produce succinic acid from Jerusalem artichoke tuber hydrolysate. Results showed that both fructose and glucose in the tuber hydrolysate were utilized for succinic acid production. The sugar utilization was found to be dependent on process control, hence, when pH was fixed at 6.8 the sugar utilization of fructose was increased from 68.6% to 96.5% and the succinic acid production was also increased by 26.4% to yield 26.8 g/L succinic acid. In this study a one­step pretreatment/hydrolysis method was used where no enzymes were used. Our work suggests that Jerusalem artichoke tubers could be utilized for production of bio­succinic acid.
ChemInform Abstract: REACTION OF CARBOHYDRATE HALIDES WITH MAGNESIUM. NOVEL CARBON‐CARBON COUPLING OF SUGAR DERIVATIVES VIA ORGANOMETALLIC INTERMEDIATES (1982)

Abstract Die aus dem D‐Allofuranose‐Derivat (Ia) zugänglichen Halogenzucker (Ib) und (Ic) ergeben bei der Behandlung mit Magnesium nur geringe Mengen eines Reduktionsproduktes (Id) neben dem Dimeren (II); (Ib) wird unter Zusatz katalytischer Mengen Iodid umgesetzt.
Morphology Change of Artificial Crystal Originated Particles, and the Effect on Gate Oxide Integrity (2000)

The surface morphology and gate oxide integrity was examined on wafers containing Artificial Crystal Originated Particles. The wafers were subjected to heat treatments, epitaxial silicon deposition and polishing. All treatments except polishing result in a significant defect smoothening, or even in complete defect annihilation. On these wafers, the defects no longer degrade the gate oxide integrity. Polishing only smoothes convex defect edges, leading to a reduction of the leakage current with positive gate bias. The breakdown voltage remains nearly unaltered, implying that it is determined by the concave tip of the defect.
Preganglionic Stimulation Increases Calcium Uptake by Sympathetic Ganglia (1971)

Isolated superior cervical ganglia of rats accumulate more calcium during preganglionic stimulation than do unstimulated controls; uptake of calcium-45 is approximately doubled by stimulation of 12 impulses per second. The extra uptake is markedly reduced by a high concentration of magnesium, but not by mecamylamine hydrochloride or tetraethylammonium chloride, although all three agents eliminate the postsynaptic action potential. Uptake of calcium-45 is also greatly increased by a high external concentration of potassium.
Floating Hamster Ball: A Locomotion Method for Free Flight in Virtual Environments (2018)

3D navigation is an important task in many virtual reality applications. Several virtual reality locomotion techniques were introduced in the literature trying to obtain a navigation with high quality and comfort, avoiding cybersickness. In this work, we propose a hands-free locomotion technique which uses intuitive mechanics with a considerable level of accuracy. Our method is inspired in a hamster ball, where the user has to roll a sphere from its interior in order to move in a 3d space. We evaluate three variants of our method in order to obtain a desired configuration. Objective and subjective measurements were applied to compare efficiency, user experience and cybersickness.
Seed Germination of Fraser Fir: Timing of Irradiation and Involvement of Phytochrome (1990)

Two experiments investigated the relationship of light and temperature in seed germination of Fraser fir [Abies fraseri (Pursh) Poir.]. Irradiation during the warm portion of 9/15 hr thermoperiod of 20/10C and 30/20C increased germination percentages after 42 days, and the degree of stimulation depended on the timing of the light exposures. A 1-hr exposure was most effective during the latter part of the warm portion of the thermoperiods, and varying the time of irradiation had the greatest effect at 20/10C. The involvement of phytochrome in this photomorphogenic response was ascertained by demonstration of red/far-red reversibility.
Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck (2016)

Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure of the F-BAR protein Nervous Wreck (Nwk) in both soluble and membrane-bound states. On membrane binding, Nwk SH3 domains do not completely dissociate from the F-BAR dimer, but instead shift from its concave surface to positions on either side of the dimer. Unexpectedly, along with controlling membrane binding, these autoregulatory interactions inhibit the ability of Nwk-SH3a to activate Wiskott-Aldrich syndrome protein (WASp)/actin related protein (Arp) 2/3-dependent actin filament assembly. In Drosophila neurons, Nwk autoregulation restricts SH3a domain-dependent synaptopod formation, synaptic growth, and actin organization. Our results define structural rearrangements in Nwk that control F-BAR-membrane interactions as well as SH3 domain activities, and suggest that these two functions are tightly coordinated in vitro and in vivo.
Regulation of the Transfected Human Glycoprotein Hormone α-Subunit Gene by Dexamethasone and Thyroid Hormone (1989)

A chimeric plasmid, (-1,500)h alpha CAT, containing approximately 1,500 bp of 5'-flanking DNA of the human glycoprotein hormone alpha-subunit gene directing the expression of the bacterial chloramphenicol acetyl transferase (CAT) gene, was transfected transiently into rat pituitary-derived GH3 cells. (-1,500)h alpha CAT expression was stimulated 5- to 20-fold by dexamethasone and 3- to 5-fold by 8-bromo-cAMP (8-Br-cAMP), and was inhibited by 50% by L-triiodothyronine (T3). Thus, suppression by T3 in this system was similar to that seen in pituitary thyrotropes. Induction of (-1,500)h alpha CAT expression by dexamethasone was antagonized by T3 but was unaffected by 8-Br-cAMP. However, T3 augmented the stimulation of (-1,500)h alpha CAT activity by 8-Br-cAMP. Deletants containing less than 346 bp of 5'-flanking alpha DNA showed a stepwise decrease in induction by dexamethasone, suggesting that multiple sequence elements located in this region are required for full induction of h alpha CAT activity. Deletion analysis also indicated that a thyroid hormone response element is located between 207 and 172 bp of the alpha gene transcriptional start site. Our finding of induction of alpha expression by dexamethasone in pituitary cells contrasts with the inhibition of alpha gene activity by glucocorticoids which has previously been shown in placental cells. Therefore, these data indicate that cell-type-specific factors play an important role in the modulation of alpha gene transcription.
THE PERCEPTION OF FAMILY HISTORY RISK AND ITS ESTIMATE ROLE OF HAVING PROSTATE CANCER IN THE CONTEMPORARY ERA (2009)

You have accessJournal of Urology1 Apr 2009THE PERCEPTION OF FAMILY HISTORY RISK AND ITS ESTIMATE ROLE OF HAVING PROSTATE CANCER IN THE CONTEMPORARY ERA Ayman S Moussa, Shah Gaurang, Susan Luay, Changhong Yu, Michael W Kattan, and J Stephen Jones Ayman S MoussaAyman S Moussa More articles by this author , Shah GaurangShah Gaurang More articles by this author , Susan LuaySusan Luay More articles by this author , Changhong YuChanghong Yu More articles by this author , Michael W KattanMichael W Kattan More articles by this author , and J Stephen JonesJ Stephen Jones More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(09)62086-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "THE PERCEPTION OF FAMILY HISTORY RISK AND ITS ESTIMATE ROLE OF HAVING PROSTATE CANCER IN THE CONTEMPORARY ERA." The Journal of Urology, 181(4S), pp. 747–748 © 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 181 Issue 4S April 2009 Page: 747-748 Advertisement Copyright & Permissions© 2009 by American Urological AssociationMetrics Author Information Ayman S Moussa More articles by this author Shah Gaurang More articles by this author Susan Luay More articles by this author Changhong Yu More articles by this author Michael W Kattan More articles by this author J Stephen Jones More articles by this author Expand All Advertisement PDF downloadLoading ...
Relative uptake of the αvβ3 radiopharmaceutical Tc-99m maraciclatide and Tc-99m sestamibi in the breast tissue of patients with suspected breast cancer (2014)

1547 Objectives Tc-99m maraciclatide (Tc-Mara) is a radiolabeled ligand with a high affinity for the integrin αvβ3 which is upregulated during angiogenesis and tumor growth. The purpose of this study was to compare the relative uptake of Tc-99m sestamibi (Tc-Sest) and Tc-Mara in breast lesions. Methods 21 patients with BI-RADS 4/5 lesions or biopsy-proven cancer underwent consecutive molecular breast imaging (MBI) studies with Tc-Mara and Tc-Sest, with Results 19 patients completed both MBI studies. 10 had invasive breast cancer and 9 had benign lesions. Concordant findings were observed in all malignant and benign lesions with Tc-Sest and Tc-Mara. Lesion to background radio (L/B) of breast cancers was 2.76+0.68 (mean+std dev)for Tc-Mara and 2.46+0.30 for Tc-Sest (p=0.216). L/B of benign lesions 2.57+0.82 for Tc-Mara and 2.94+0.84 for Tc-Sest. Overall count density in the breast (in cts/mCi/pixel) was significantly greater with Tc-Mara (6.3+3.3) than with Tc-Sest (3.7+1.9), (p = 0.004). Conclusions Tc-Mara demonstrated higher absolute L/B in breast tumors than Tc-Sest and lower absolute L/B than Tc-Sest in benign lesions (p = N.S.). Tc-Mara appears to demonstrate more distinct patterns of background uptake than Tc-Sest. Overall uptake of Tc-Mara is 1.7 times that of Tc-Sest, allowing for a reduction in radiation dose by a comparable factor while maintaining the same image quality. Research Support GE Healthcare
Effect of Silicon, Titanium, and Zirconium Ion Implantation on NiTi Biocompatibility (2012)

The objective of the work was to study the effect of high-dose ion implantation (HDII) of NiTi surface layers with Si Ti, or Zr, on the NiTi biocompatibility. The biocompatibility was judged from the intensity and peculiarities of proliferation of mesenchymal stem cells (MSCs) on the NiTi specimen surfaces treated by special mechanical, electrochemical, and HDII methods and differing in chemical composition, morphology, and roughness. It is shown that the ion-implanted NiTi specimens are nontoxic to rat MSCs. When cultivated with the test materials or on their surfaces, the MSCs retain the viability, adhesion, morphology, and capability for proliferation in vitro , as evidenced by cell counting in a Goryaev chamber, MTT test, flow cytometry, and light and fluorescence microscopy. The unimplanted NiTi specimens fail to stimulate MSC proliferation, and this allows the assumption of bioinertness of their surface layers. Conversely, the ion-implanted NiTi specimens reveal properties favorable for MSC proliferation on their surface.