Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the t(t)over-barb(b)over-bar production cross section in the all-jet final state in pp collisions at root s=13 TeV

A measurement of the production cross section of top quark pairs in association with two b jets (t (t) over barb (b) over bar) is presented using data collected in proton-proton collisions at root s=13 TeV by the CMS detector at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The cross section is measured in the all-jet decay channel of the top quark pair by selecting events containing at least eight jets, of which at least two are identified as originating from the hadronization of b quarks. A combination of multivariate analysis techniques is used to reduce the large background from multijet events not containing a top quark pair, and to help discriminate between jets originating from top quark decays and other additional jets. The cross section is determined for the total phase space to be 5.5 +/- 0.3 (stat)(-1.3)(+)(1.6) (syst)pb and also measured for two fiducial t (t) over barb (b) over bar, definitions. The measured cross sections are found to be larger than theoretical predictions by a factor of 1.5-2.4, corresponding to 1-2 standard deviations. (C) 2020 The Author. Published by Elsevier B.V.Peer reviewe

Modulation of the Cytotoxic Properties of Pd(II) Complexes Based on Functionalized Carboxamides Featuring Labile Phosphoryl Coordination Sites

Platinum-based drugs are commonly recognized as a keystone in modern cancer chemotherapy. However, intrinsic and acquired resistance as well as serious side effects often caused by the traditional Pt(II) anticancer agents prompt a continuous search for more selective and efficient alternatives. Today, significant attention is paid to the compounds of other transition metals, in particular those of palladium. Recently, our research group has suggested functionalized carboxamides as a useful platform for the creation of cytotoxic Pd(II) pincer complexes. In this work, a robust picolinyl- or quinoline-carboxamide core was combined with a phosphoryl ancillary donor group to achieve hemilabile coordination capable of providing the required level of thermodynamic stability and kinetic lability of the ensuing Pd(II) complexes. Several cyclopalladated derivatives featuring either a bi- or tridentate pincer-type coordination mode of the deprotonated phosphoryl-functionalized amides were selectively synthesized and fully characterized using IR and NMR spectroscopy as well as X-ray crystallography. The preliminary evaluation of the anticancer potential of the resulting palladocycles revealed a strong dependence of their cytotoxic properties on the binding mode of the deprotonated amide ligands and demonstrated certain advantages of the pincer-type ligation

Редкий случай синдрома Моркио (мукополисахаридоз IVА типа): трудности диагностического поиска и лечения

Background. This clinical case is of practical interest due to the lack of epidemiological and clinical data in Russian Federation and worldwide, difficulties in diagnosis at the disease onset, as well as little experience in enzyme replacement therapy for mucopolysaccharidosis type IVA (MPS IVA).Clinical case description. MPS IV (Morquio syndrome) diagnosis at the age of 11 was based on typical progressive external signs such as thoracolumbar scoliosis, coxarthrosis with restriction of both active and passive movements. Enzymodiagnostics in dried blood spots has shown dramatic decrease of N-acetylgalactosamine-6-sulfatase activity — 0.01 μM/l/h specific to MPS IVA. Direct automatic sequencing of the GALNS gene has revealed pathogenic nucleotide variants in the compound heterozygous state: c.143T>G; p(Val48Gly) and c.697G>A; p.(Asp233Asn). That allowed us to establish MPS IVA diagnosis. Enzyme replacement therapy with elosulfase alpha was started according to the protocol. According to significant changes in the musculoskeletal system, the expected therapeutic effect (stabilization and no disease progression) can be achieved not earlier than after 8–12 months.Conclusion. Timely MPS diagnosis allows us to implement enzyme replacement therapy at the earliest possible time and thereby to avoid non-reversible complications of the disease itself.Обоснование. Настоящий клинический случай представляет практический интерес ввиду недостаточности эпидемио логических и клинических данных в России и мире, трудностей диагностики на начальном этапе болезни, а также малого опыта ферментозаместительной терапии мукополисахаридоза IVА типа (МПС IVА).Описание клинического случая. Диагностика МПС IV (синдром Моркио) в возрасте 11 лет основывалась на характерных внешних проявлениях прогрессирующего характера, таких как грудопоясничный кифосколиоз, коксартроз с ограничением как активных, так и пассивных движений. При проведении энзимодиагностики в высушенных пятнах крови выявлено резкое снижение активности N-ацетилгалактозамин-6-сульфатазы — 0,01 мкМ/л/ч, что характерно для МПС IVA. При проведении прямого автоматического секвенирования в гене GALNS были выявлены патогенные нуклеотидные варианты в компаунд-гетерозиготном состоянии: c.143T>G; p.(Val48Gly) и c.697G>A; p.(Asp233Asn), что позволило установить диагноз МПС IVА. Начата ферментозаместительная терапия элосульфазой альфа согласно протоколу. Учитывая значительные изменения в опорно-двигательном аппарате, ожидаемый терапевтический эффект — стабилизация и отсутствие прогрессирования болезни — может быть достоверно зафиксирован не ранее чем через 8–12 мес.Заключение. Своевременная диагностика МПС позволяет использовать ферментозаместительную терапию в возможно более ранние сроки и тем самым избежать необратимых осложнений заболевания

Highly Cytotoxic Palladium(II) Pincer Complexes Based on Picolinylamides Functionalized with Amino Acids Bearing Ancillary <i>S</i>‑Donor Groups

The reactions of picolinyl and 4-chloropicolinyl chlorides with methyl esters of <i>S</i>-methyl-l-cysteine, l- and d-methionine, and l-histidine afforded a series of functionalized carboxamides, which readily formed pincer-type complexes upon interaction with PdCl₂(NCPh)₂ in solution under mild conditions. The direct cyclopalladation of the ligands derived was also accomplished in the solid phase, in particular, mechanochemically, although it was complicated by the partial deactivation of the starting amides. The resulting complexes with 5,5- and 5,6-membered fused metallocycles were fully characterized by IR and NMR spectroscopy, including variable-temperature and 2D-NMR studies. In the case of some cysteine- and methionine-based derivatives, the realization of κ³-<i>N,N,S-</i>coordination was supported by X-ray diffraction. The cytotoxic effects of these complexes were examined on HCT116, MCF7, and PC3 human cancer cell lines as well as HEK293 as a representative of normal cells. The comparative studies allowed us to determine that the presence of the sulfide ancillary donor group is crucial for cytotoxic activity of this type of Pd­(II) complexes. The main structure–activity relationships and the most promising palladocycles were outlined. The additional studies by gel electrophoresis revealed that 4-chloropicolinyl derivatives, despite the nature of an amino acid, can bind with DNA and inhibit topoisomerase I activity

Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 &mu;g/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking

The 6^{6}H states studied in the d(8He,α)d(^8\text{He},\alpha) reaction and evidence of extremely correlated character of the 5^{5}H ground state

The extremely neutron-rich system $^{6}$H was studied in the direct $^2\text{H}(^8\text{He},{^4\text{He}})^{6}$H transfer reaction with a 26 $A$MeV secondary $^{8}$He beam. The measured missing mass spectrum shows a resonant state in $^{6}$H at $6.8(3)$ MeV relative to the $^3$H+$3n$ threshold. There is also some evidence of a resonant state at $4.5(3)$ MeV which is a realistic candidate for the $^{6}$H ground state (g.s.). The population cross section of the presumably $p$-wave states in the energy range from 4 to 8 MeV is $d\sigma/d\Omega_{\text{c.m.}} \sim 190$$\mu$b/sr in the angular range $5^{\circ}<\theta_{\text{c.m.}}<16^{\circ}$. The obtained missing mass spectrum is free of the $^{6}$H events below 3.5 MeV ($d\sigma/d\Omega_{\text{c.m.}} \lesssim 3$$\mu$b/sr in the angular range $5^{\circ}<\theta_{\text{c.m.}}<20^{\circ}$), which indicates that the value of 4.5 MeV is the lower limit of the possible $^{6}$H g.s. location. The obtained results confirm that the decay mechanism of the $^{7}$H g.s. (located at 2.2 MeV above the $^{3}$H+$4n$ threshold) is the ``true'' (or simultaneous) $4n$ emission. The resonance energy profiles and the momentum distributions of the sequential $^{6}$H \,\rightarrow \, ^5H(g.s.)+n\, \rightarrow \, ^3H+$3n$ decay fragments were analyzed by the theoretically-updated direct four-body-decay and sequential-emission mechanisms. The measured momentum distributions of the $^{3}$H fragments in the $^{6}$H rest frame indicate a very strong ``dineutron-type'' correlations in the $^{5}$H ground state decay