gebhart/patrepeval huggingface dataset:
The N azarov Cyclization (1994)

Abstract The Nazarov cyclization is named after the eminent Russian chemist I. N. Nazarov (1900–1957). In the course of an extensive study on the formation of allyl vinyl ketones by the mercuric ion and acid‐catalyzed hydration of dienynes, Nazarov and his co‐workers discovered a secondary reaction to form 2‐cyclopentenones. Nazarov initially formulated a direct acid‐catalyzed closure of the allyl vinyl ketones and demonstrated the preparation of 2‐cyclopentenones from these precursors in dozens of cases. However in 1952, Braude and Coles suggested the intermediacy of carbocations and demonstrated that the formation of 2‐cyclopentenones actually proceeds via the α,α′‐divinyl ketones. This fact, together with further mechanistic clarification, has led to the current formulation of the Nazarov cyclization as the acid‐catalyzed closure of divinyl ketones to 2‐cyclopentenones. This process was already documented in 1903. Treatment of dibenzylideneacetone with concentrated sulfuric acid and acetic anhydride followed by mild alkaline hydrolysis afforded a ketol, the correct structure of which was finally proposed in 1955. Other examples of acid‐catalyzed cyclizations of divinyl ketones exist in the early literature, as do reactions which must have proceeded via divinyl ketones. A broader definition of the Nazarov cyclization includes a wide variety of precursors that under specific reaction conditions also produce 2‐cyclopentenones via divinyl ketones or their functional equivalents. A case in point is the formation of a cyclopentenone by treatment of either divinyl ketone or tetrahydropyrone with ethanolic hydrochloric acid. It is the structural variety of precursors that lends versatility to the Nazarov cyclization and which also serves as the organizational framework for this chapter. To facilitate presentation, the reaction is divided into six categories defined by the structure of the precursor: (1) cyclization of divinyl and allyl vinyl ketones, (2) cyclization of silylated (stannylated) divinyl ketones, (3) in situ generation/cyclization of divinyl ketones or equivalents, (4) generation/cyclization of divinyl ketone equivalents by solvolysis, (5) alkyne‐based precursors of divinyl ketones, and (6) coupling reactions to form and cyclize divinyl ketones. The logic of this sequence follows from the order of decreasing structural similarity of the precursors to divinyl ketones. This is intended to be comprehensive in the coverage of cyclizations which produce 2‐cyclopentenones. The related electrocyclic closure of less oxidized pentadienylic cations is not covered. The reaction was most recently reviewed in 1991. Prior to that, the Nazarov cyclization had been reviewed in 1983 and also in the context of pentannulation.
Is there a benefit for administration of antivenom following local and mild systemic reactions toDaboia (Vipera) Palaestinaesnake bites? (2018)

Background: Daboia (Vipera) palaestinae envenomation (DPE) is the most common snake-bite in Israel. Current practice has supported antivenom treatment, including those with local or systemic manifestations.Objective: To evaluate a conservative approach vs. fixed dose D. palaestinae antivenom for patients with advance local (AL)/mild systemic (MS) manifestations.Methods: Retrospective analysis of 41 patients bitten by D. palaestinae who were treated with expectant management or administration of a fixed-dose of 50 mL antivenom.Results: Antivenom was withheld in 16/21 patients (76%) with AL or MS reaction. After expectant management, no adverse events were recorded.Conclusion: We found that a selective approach towards antivenom administration yields similar clinical outcomes in patients following DPE.
Submicron mapping of silicon-on-insulator strain distributions induced by stressed liner structures (2008)

Strain distributions within a silicon-on-insulator (SOI) layer induced by overlying compressively stressed Si3N4 features were measured using x-ray microbeam diffraction. A comparison of analytical and numerical mechanical models of the depth-averaged strain distributions to the measured strain profiles in the SOI layer indicated a blanket film stress of −2.5 GPa in the Si3N4 features. A two-dimensional boundary element model, implemented to analyze thin film/substrate systems, reproduced the observed strain distributions better than an edge-force formulation due to the incorporation of loading along the Si3N4/Si interface.
Host-Specific NS5 Ubiquitination Determines Yellow Fever Virus Tropism (2019)

The recent yellow fever virus (YFV) epidemic in Brazil in 2017 and Zika virus (ZIKV) epidemic in 2015 serve to remind us of the importance of flaviviruses as emerging human pathogens. With the current global flavivirus threat, there is an urgent need for antivirals and vaccines to curb the spread of these viruses. However, the lack of suitable animal models limits the research questions that can be answered. A common trait of all flaviviruses studied thus far is their ability to antagonize interferon (IFN) signaling so as to enhance viral replication and dissemination. Previously, we reported that YFV NS5 requires the presence of type I IFN (IFN-α/β) for its engagement with human signal transducer and activator of transcription 2 (hSTAT2). In this manuscript, we report that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hSTAT2 but not murine STAT2 (mSTAT2). Contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, replacing mSTAT2 with hSTAT2 cannot rescue the YFV NS5-STAT2 interaction, as YFV NS5 is also unable to interact with hSTAT2 in murine cells. We show that the IFN-α/β-dependent ubiquitination of YFV NS5 that is required for STAT2 binding in human cells is absent in murine cells. In addition, we demonstrate that mSTAT2 restricts YFV replication <i>in vivo</i> These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.<b>IMPORTANCE</b> Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens. A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-α/β) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-α/β-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.
Intravascular Ultrasound: Potential Tool to Assess Coronary Anastomosis Quality (2003)

Coronary angiography and Doppler flow measurements are most commonly used to assess the patency of anastomoses in the operating theater. Intravascular ultrasound might be another means of monitoring the surgical procedure during coronary artery bypass. Five sheep underwent off-pump bypass of the left anterior descending coronary artery using the left internal mammary artery. The running suture was evaluated by intraoperative fluoroscopy and a coronary intravascular ultrasound probe inserted into the target artery proximal to the anastomosis. Macroscopic examination of the anastomosis was performed to validate the angiographic and intravascular ultrasound images. The diameter, cross-sectional area, and compliance of each anastomosis were calculated in systole and diastole. All anastomoses were patent without signs of stenosis. In one case, intravascular ultrasound showed an intimal flap, which was confirmed by macroscopic examination. The mean major anastomotic diameter was 4.5 +/- 0.5 mm on angiography and 4.0 +/- 0.5 mm on intravascular ultrasound. From the ultrasound data, the mean cross-sectional anastomotic area was calculated as 6.21 +/- 0.1 mm(2) in systole and 5.49 +/- 0.1 mm(2) in diastole, and these data were used to calculate the cross-sectional anastomosis compliance. Coronary intravascular ultrasound can visualize intima-to-intima apposition and provide reliable calculations of anastomosis compliance.
Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia (2013)

P. falciparum GLURP-R0 and MSP3 separately as well as in a fused form in GMZ2 are readily recognized by the sera of the study populations. The significantly higher antibody prevalence and level detected against GMZ2 compared to either of its subunits separately, in naturally exposed populations, suggests the synergistic effect of GLURP-R0 and MSP3 and that GMZ2 could be a more relevant blood-stage malaria vaccine candidate than the individual components. Detection of high-level antibody responses in non-febrile, smear-negative individuals may possibly be an indication of a low-grade, asymptomatic sub-microscopic infection in the induction and maintenance of high-level malaria immunity.
Lactoferrin Sequestration and Its Contribution to Iron Deficiency Anemia in Helicobacter pylori Infected Gastric Mucosa (2002)

Purpose: It is known that lactoferrin serves as a source of iron for H. pylori in gastric mucosa.This study was undertaken to investigate the relationship between lactoferrin and H. pylori infection coexistent with iron-deficiency anemia by determining the lactoferrin levels in gastric biopsy specimens, and by locating the major sites of lactoferrin expression, according to the presence or absence of iron-deficiency anemia.Methods: Fifty-five adolescents that underwent gastroduodenoscopy were divided into three groups: NL (n=19) for normal controls, HP (n=15) for patients with H. pylori, and IDA (n=21) for patients with H. pylori gastritis and coexisting iron-deficiency anemia.Histopathologic features were graded from null to marked on the basis of the Updated Sydney System.The gastric mucosal levels of lactoferrin were measured by immunoassay.Immunohistochemical technique was used to allow identification of the location and quantification of the lactoferrin expression.Results: Lactoferrin levels in the antrum increased significantly, in proportion to, H. pylori density, polymorphonuclear cell infiltration, and chronic inflammation in the histologic specimens.Patients in the HP and IDA groups showed significantly increased mucosal levels of lactoferrin compared with that observed in the normal group (p=0.0001).The lactoferrin level in IDA group tended to be higher than that in the HP group (p=0.2614).The major sites of lactoferrin expression by immunohistochemistry were in glands and neutrophils within epithelium.Lactoferrin was stained
Innovative Geotextiles for Reinforcement of Roadside Ditch (2016)

Geotextiles consisting of meandrically arranged coarse ropes were produced. For the production of the ropes Kemafi l technology was applied and the wastes of various nonwovens were used. The geotextiles were used for the protection of the roadside ditch in a clay ground. After instalation of the geotextiles ensured immediate and eff ective protection of the ditch. During heavy rains the meandrically arranged geotextiles formed a system of cascades which slowed down the stream of water fl owing in the ditch. Additionally, the retention of water between the meanders of geotextiles and water absorption inside the ropes was observed. The materials used for the production of geotextiles had suffi cient resistance to biodegradation and ensured the protection of the ditch at least for one growing season.
Comparative Studies on the Phase Stability, Electronic Structure, and Topology of the Charge Density in the Li3XO4 (X = P, As, V) Lithium Orthosalt Polymorphs (2009)

Density functional theory (DFT) calculations within the generalized gradient approximation (GGA) were performed to study phase transitions in lithium orthosalts Li3XO4 (X = P, As, V). The equilibrium crystal structure parameters and the total energies of the Li3XO4 polymorphs were calculated for the β- and γ-phases. The relative lattice stabilities of the two polymorphs were examined in the light of various peculiarities at atomic scale. The β-polymorph was systematically found to be the most stable one, agreeing well with experimental results. Using an all electron full potential method, we have investigated densities of states and the topology of charge density through the Bader’s quantum theory of “atoms in molecules” (AIM) along with electrostatic energy density maps in order to evaluate factors governing the stability of each polymorph. Higher stability of the β-polymorph or differences in energy between β- and γ-phases according to the nature of X along with the experimental temperatures of phase transitions can be connected to several microscopic features, including differences in constraint within XO4 tetrahedron or chemical bonding characteristics. This new approach can be applied to other phase stability studies, including the family of Li2MSiO4, which is of great interest for cathode materials in lithium batteries.
Tumor-specific recognition of human myeloma cells by idiotype-induced CD8+ T cells (2000)

Immunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein–specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper 1–type cytokines in response to stimulation with myeloma cells from their recipients. The T-cell–mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether Id-specific CD8+ T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer–sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I–restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response.
High-Fidelity Ion State Detection Using Trap-Integrated Avalanche Photodiodes (2022)

Integrated technologies greatly enhance the prospects for practical quantum information processing and sensing devices based on trapped ions. High-speed and high-fidelity ion state readout is critical for any such application. Integrated detectors offer significant advantages for system portability and can also greatly facilitate parallel operations if a separate detector can be incorporated at each ion-trapping location. Here we demonstrate ion quantum state detection at room temperature utilizing single-photon avalanche diodes (SPADs) integrated directly into the substrate of silicon ion trapping chips. We detect the state of a trapped $^{88}\text{Sr}^{+}$ ion via fluorescence collection with the SPAD, achieving $99.92(1)\%$ average fidelity in 450 $μ$s, opening the door to the application of integrated state detection to quantum computing and sensing utilizing arrays of trapped ions.
Early human embryo metabolism (1993)

Non-invasive microanalytical methods have been devised to study the energy metabolism of single human preimplantation embryos. Pyruvate, which is added routinely to all media used to culture human embryos, is consumed throughout the preimplantation period, with glucose assuming an increasing role at embryo compaction and blastocyst formation. All of the glucose consumed may be accounted for by the appearance of lactate in the incubation medium. The enzyme hexokinase may be involved in regulating this aerobic glycolysis. There is considerable indirect evidence for the utilisation of endogenous as opposed to exogenous energy substrates, the most likely candidate being protein. Information on early human embryo metabolism is likely to find application in a number of areas: these include the improvement of techniques for assisted human conception, notably in the selection of embryos for transfer following In Vitro Fertilisation; the diagnosis of genetic defects at the preimplantation stage; increased understanding of the causes of implantation failure and miscarriage, and the development of novel post-coital contraceptives.
On Learning the $c\mu$ Rule in Single and Parallel Server Networks (2018)

We consider learning-based variants of the $c \\mu$ rule for scheduling in\nsingle and parallel server settings of multi-class queueing systems.\n In the single server setting, the $c \\mu$ rule is known to minimize the\nexpected holding-cost (weighted queue-lengths summed over classes and a fixed\ntime horizon). We focus on the problem where the service rates $\\mu$ are\nunknown with the holding-cost regret (regret against the $c \\mu$ rule with\nknown $\\mu$) as our objective. We show that the greedy algorithm that uses\nempirically learned service rates results in a constant holding-cost regret\n(the regret is independent of the time horizon). This free exploration can be\nexplained in the single server setting by the fact that any work-conserving\npolicy obtains the same number of samples in a busy cycle.\n In the parallel server setting, we show that the $c \\mu$ rule may result in\nunstable queues, even for arrival rates within the capacity region. We then\npresent sufficient conditions for geometric ergodicity under the $c \\mu$ rule.\nUsing these results, we propose an almost greedy algorithm that explores only\nwhen the number of samples falls below a threshold. We show that this algorithm\ndelivers constant holding-cost regret because a free exploration condition is\neventually satisfied.\n
Effect of liposome-treated red blood cells in an anemic rat model (2016)

Liposome treatment improved in vitro quality of stored rat RBCs. However, the changes observed in vitro were not sufficient to improve the in vivo outcomes of myocardial I/R in anemic rats transfused with liposome-treated RBCs.
Abstract LB-132: MOSPD2: A novel target for Bi-specific Ab mediated killing of tumor cells (2018)

Abstract Introduction: We have previously described motile sperm domain-containing protein 2 (MOSPD2) as essential for breast cancer metastasis in vitro and in vivo. In this study, we detected high expression of MOSPD2 in different organ tumors and cancer cells, and subsequently developed CD3xMOSPD2 BiTE, a firstly generated bi-specific antibody that directs killing of MOSPD2 expressing cancer cells. Experimental procedure: The prevalence of MOSPD2 was evaluated by IHC in tissue microarrays layered with cores, representing multiple organ tumors and normal tissue. MOSPD2 abundance was scored according to the staining intensity on a scale from 0 to 3. Human monoclonal antibody against the extracellular region of human MOSPD2 was generated. To determine the presence of cell surface MOSPD2 expression, FACS analysis was performed on cell lines derived from different tumor origins. BiTE was generated to comprise the scFv region of anti-human CD3 and the scFv region of a human anti-human MOSPD2. Cancer cell lines were co-cultured with freshly isolated T-cells or effector CD8 T-cells in the presence of CD3xMOSPD2 or a control BiTE. Cancer cell survival rate and T cell activation was determined after 2-3 days by FACS. Results: MOSPD2 expression was evident in the majority of organ tumors, with high prevalence in tumors such as colon, liver and breast. Normal tissue was either devoid of MOSPD2, or had low expression relative to its parallel tumor tissue. Within normal or normal adjacent tissue (NAT), staining could be detected primarily in lymphoid tissues where myeloid cells abundantly reside. FACS staining using a human anti-MOSPD2 mAb demonstrated that MOSPD2 is expressed on the surface of different cancer cell lines. Employing CD3xMOSPD2 BiTE on myeloid or solid tumor-derived cell lines induced T-cell activation and yielded profound killing of cancer cells. Conclusions: IHC staining demonstrates MOSPD2 expression profile supportive of targeting cancer cells. CD3xMOSPD2 BiTE directs T-cells to MOSPD2 expressing cancer cells and induces their destruction in-vitro. Therefore, we propose CD3xMOSPD2 bi-specific antibodies as a potential therapy for the treatment of cancer via a unique target, directed for the destruction of hematological cancers and solid tumors expressing MOSPD2. Citation Format: Itzhak Mendel, Yaniv Salem, Niva Yacov, Osharat Prhopheta-Meiran, Pinhas Kafri, Eyal Breitbart. MOSPD2: A novel target for Bi-specific Ab mediated killing of tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-132.
Snail knockdown reverses stemness and inhibits tumour growth in ovarian cancer (2018)

To develop effective therapies for advanced high grade serous ovarian cancer (HGSOC), understanding mechanisms of recurrence and metastasis is necessary. In this study, we define the epithelial/mesenchymal status of cell lines that accurately model HGSOC, and evaluate the therapeutic potential of targeting Snai1 (Snail), a master regulator of the epithelial/mesenchymal transition (EMT) in vitro and in vivo. The ratio of Snail to E-cadherin (S/E index) at RNA and protein levels was correlated with mesenchymal morphology in four cell lines. The cell lines with high S/E index (OVCAR8 and COV318) showed more CSC-like, motile, and chemoresistant phenotypes than those with low S/E index (OVSAHO and Kuramochi). We tested the role of Snail in regulation of malignant phenotypes including stemness, cell motility, and chemotherapy resistance: shRNA-mediated knockdown of Snail reversed these malignant phenotypes. Interestingly, the expression of let-7 tumour suppressor miRNA was upregulated in Snail knockdown cells. Furthermore, knockdown of Snail decreased tumour burden in an orthotopic xenograft mouse model. We conclude that Snail is important in controlling HGSOC malignant phenotypes and suggest that the Snail/Let-7 axis may be an attractive target for HGSOC treatment.
NY-ESO-1 DNA Vaccine Induces T-Cell Responses That Are Suppressed by Regulatory T Cells (2009)

Regulatory T cells play a role in diminishing vaccine-induced antigen-specific effector T-cell responses in cancer patients. The NY-ESO-1 DNA vaccine represents a feasible immunotherapeutic strategy to induce antigen-specific T-cell responses. Counteracting regulatory T-cell activity before vaccination may lead to prolonged effector T-cell responses and possibly antitumor responses in cancer patients.