Measurement of the Analyzing Power in p⃗d→(pp)n\vec{p}d \to (pp)n \\with a Fast Forward 1S0^1S_0--Diproton

A measurement of the analyzing power $A_y$ of the $\vec{p}d \to (pp) + n$ reaction was carried out at beam energies of 0.5 and 0.8 GeV by detection of a fast forward proton pair of small excitation energy $E_{pp} < 3$ MeV. The kinematically complete experiment made use of the ANKE spectrometer at the internal beam of COSY and a deuterium cluster--jet target. For the first time the $S$--wave dominance in the fast diproton is experimentally demonstrated in this reaction. While at $T_p=0.8$ GeV the measured analyzing power $A_y$ vanishes, it reaches almost unity at $T_p=0.5$ GeV for neutrons scattered at $\theta_n^{c.m.}=167^\circ$. The results are compared with a model taking into account one--nucleon exchange, single scattering and $\Delta$ (1232) excitation in the intermediate state. The model describes fairly well the unpolarized cross section obtained earlier by us and the analyzing power at 0.8 GeV, it fails to reproduce the angular dependence of $A_y$ at 0.5 GeV.Comment: 4 pages, 4 figures, 1 tabl

RNA-Seq gene expression profiling of HepG2 cells: The influence of experimental factors and comparison with liver tissue

© Tyakht et al.; licensee BioMed Central. Background: Human hepatoma HepG2 cells are used as an in vitro model of the human liver. High-throughput transcriptomic sequencing is an advanced approach for assessing the functional state of a tissue or cell type. However, the influence of experimental factors, such as the sample preparation method and inter-laboratory variation, on the transcriptomic profile has not been evaluated. Results: The whole-transcriptome sequencing of HepG2 cells was performed using the SOLiD platform and validated using droplet digital PCR. The gene expression profile was compared to the results obtained with the same sequencing method in another laboratory and using another sample preparation method. We also compared the transcriptomic profile HepG2 cells with that of liver tissue. Comparison of the gene expression profiles between the HepG2 cell line and liver tissue revealed the highest variation, followed by HepG2 cells submitted to two different sample preparation protocols. The lowest variation was observed between HepG2 cells prepared by two different laboratories using the same protocol. The enrichment analysis of the genes that were differentially expressed between HepG2 cells and liver tissue mainly revealed the cancer-associated gene signature of HepG2 cells and the activation of the response to chemical stimuli in the liver tissue. The HepG2 transcriptome obtained with the SOLiD platform was highly correlated with the published transcriptome obtained with the Illumina and Helicos platforms, with moderate correspondence to microarrays. Conclusions: In the present study, we assessed the influence of experimental factors on the HepG2 transcriptome and identified differences in gene expression between the HepG2 cell line and liver cells. These findings will facilitate robust experimental design in the fields of pharmacology and toxicology. Our results were supported by a comparative analysis with previous HepG2 gene expression studies

Clinical and genetic characteristics of Charcot–Marie–Tooth disease type 4D (type Lom) in Russia

Introduction. Charcot–Marie–Tooth disease type 4D is a hereditary demyelinating neuropathy, that occurs with the high frequency in patients of Roma origin. It is characterized by early onset at the age of 2–10 years and hearing impairment, manifested by the 3rd decade of life.Aim of the study. To describe the clinical and genetic characteristics of Charcot–Marie–Tooth disease type 4D in Russian patients of Roma origin.Materials and methods. For 14 probands from unrelated families of Roma origin with a clinical diagnosis of Charcot–Marie–Tooth disease, genetic tests for the pathogenic variants c. 442C&gt;T in the NDRG1 gene and c. 3325C&gt;T in the SH3TC2 gene was carried out. For 8 patients with Charcot–Marie–Tooth disease type 4D, detailed clinical and electrophysiological examination was performed.Results. In 11 families of Roma origin, the c. 442C&gt;T pathogenic variant in the NDRG1 gene in a homozygous state was detected, which accounted for 79 % all observed Roma patients with Charcot–Marie–Tooth disease. There are 12 of the 14 tested families live in the European part of Russia, 7 of them are from nearby regions. The average age of onset was 3.3 years. The first symptom in 7 of 8 patients was gait disturbances. At the time of examination (age range 6–19 years), all patients showed marked hypotrophy and weakness of the feet, lower leg, hands muscles, feet deformities, reduction or loss of tendon reflexes.Discussion. Due to the detection of only one pathogenic variant in most Russian patients of Roma origin with Charcot–Marie–Tooth disease, the knowledge of the ethnicity of a proband with early myelinopathy can significantly simplify the confirmation of the diagnosis on the molecular level

Measurement of the Spin-Dependence of the pbar-p Interaction at the AD-Ring

We propose to use an internal polarized hydrogen storage cell gas target in the AD ring to determine for the first time the two total spin-dependent pbar-p cross sections sigma_1 and sigma_2 at antiproton beam energies in the range from 50 to 450 MeV. The data obtained are of interest by themselves for the general theory of pbar-p interactions since they will provide a first experimental constraint of the spin-spin dependence of the nucleon-antinucleon potential in the energy range of interest. In addition, measurements of the polarization buildup of stored antiprotons are required to define the optimum parameters of a future, dedicated Antiproton Polarizer Ring (APR), intended to feed a double-polarized asymmetric pbar-p collider with polarized antiprotons. Such a machine has recently been proposed by the PAX collaboration for the new Facility for Antiproton and Ion Research (FAIR) at GSI in Darmstadt, Germany. The availability of an intense stored beam of polarized antiprotons will provide access to a wealth of single- and double-spin observables, thereby opening a new window on QCD spin physics.Comment: 51 pages, 23 figures, proposal submitted to the SPS committee of CER

Случай наследственной моторной сенсорной нейропатии IVА типа с необычной родословной

Background. Hereditary motor and sensory neuropathies (HMSN) are a genetically diverse group of disorders of the peripheral nerves characterized by gradual development of weakness, muscular hypo-/atrophy, sensory disturbances in distal areas of the extremities. Currently among the recessive forms, the most prevalent HMSN is associated with the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene (GDAP1-HMSN).The objective is to present an observation of a family case of HMSN type IVA with unusual genealogy.Materials and methods. Clinical, electrophysiological, and genetic characteristics of a Russian family with GDAP1-HMSN were examined.Results. We describe a family with autosomal recessive HMSN and unusual genealogy due to homozygous and compound heterozygous mutations of GDAP1.Conclusion. The particularity of the described family case is the unusual genealogy with the patients in two non-consecutive generations. This type of inheritance is caused by presence of mutations in compound heterozygous state in the proband's grandson which was confirmed by genetic analysis. The presented case demonstrates the importance and necessity of full analysis of the GDAP1 gene or identification of 2 mutations in trans-position in the proband and subsequent assessment of possible risks for future generations. Multiple stroke-like episodes in the 2 affected members of the family are described that have not been previously reported for GDAP1-HMSN. Stroke has been presented in HMSN associated with mitofusin-2 gene which also as GDAP1, affects mitochondrial function in the neurons.Введение. Наследственные моторные сенсорные нейропатии (НМСН) – генетически гетерогенная группа заболеваний периферических нервов, характеризующихся постепенным развитием слабости, гипо-/атрофии мышц, чувствительных нарушений в дистальных отделах конечностей. Среди рецессивных форм в настоящее время наиболее распространенной является НМСН, ассоциированная с изменениями в гене GDAP1 (GDAP1-НМСН).Цель исследования – представить наблюдение семейного случая аксональной GDAP1-НМСН с необычной родословной. Материалы и методы. Проведены клинические, электрофизиологические и молекулярно-генетические исследования больных GDAP1-НМСН и здоровых членов семьи.Результаты. Представлено описание семьи с аутосомно-рецессивной GDAP1-НМСН с больными в двух не следующих друг за другом поколениях, мутациями как в гомозиготном, так и в компаунд-гетерозиготном состоянии.Заключение. Особенностью случая является обнаружение больных не только в одном поколении, что характерно для рецессивных форм, а в двух не следующих друг за другом поколениях. Такой тип наследования обусловлен наличием у внука пробанда мутаций в компаунд-гетерозиготном состоянии, что подтверждено молекулярно-генетическим анализом. Описанное наблюдение показывает необходимость проведения полного анализа гена GDAP1 или выявления 2 мутаций в транс-положении независимо от предполагаемого типа наследования для корректного медико-генетического консультирования и профилактики повторных случаев заболевания в отягощенных семьях. Интересно отметить многократно возникавшие инсультопоподобные эпизоды у 2 больных членов семьи, что при GDAP1-НМСН ранее не было описано. Известны случаи нарушения мозгового кровообращения при изменениях в гене MFN2, ответственном за развитие НМСН и так же, как и GDAP1, влияющем на функцию митохондрий в нервных клетках

Клинико-генетические характеристики аутосомно-рецессивной аксональной нейропатии с нейромиотонией у больных из России

Introduction. Hereditary motor and sensory neuropathies are genetically heterogeneous group of disorders characterized by a progressive muscle weakness, atrophy of hand and leg muscles often associated with deformations, and mild to moderate sensory loss. Axonal neuropathy with neuromyotonia (AR-ANM) is one of the rarest autosomal recessive hereditary neuropathies. Materials and methods. Six (6) patients (4 men, 2 women) aged 14–40 years from unrelated families with suspicion of HMSN were examined clinically, neurophysiologically and using DNA analysis. Results. Neurophysiological examination revealed motor and sensory neuropathy with neuromyotonia signs in all patients. In all cases homozygous variant of recessive mutations с.110G/C (р.Arg37Pro) in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) has been revealed. Conclusion. There is the first description of the clinical and neurophysiological features of six patients with AR-ANM in Russia. Введение. Наследственные моторно-сенсорные нейропатии (НМСН) – группа генетически гетерогенных болезней, характеризующихся прогрессирующей дистальной слабостью, гипо-/атрофией мышц стоп, кистей с последующей их деформацией, расстройствами чувствительности. Аксональная нейропатия в сочетании с нейромиотонией (АР-АНМ) считается одним из редких аутосомно-рецессивных вариантов НМСН. Материалы и методы. Клинически, нейрофизиологически и посредством ДНК-анализа обследованы 6 больных (4 мужчины, 2 женщины) в возрасте 14–40 лет из неродственных семей с предположительным диагнозом НМСН. Результаты. Нейрофизиологическое исследование у пациентов выявило моторную и сенсорную нейропатию в сочетании с нейромиотонией при исследовании мышц игольчатыми электродами. Молекулярно-генетическое исследование у всех пациентов обнаружило мутацию с.110G&gt;C (р.Arg37Pro) в гомозиготном состоянии в гене HINT1. Заключение. Представлено первое в России описание клинических, нейрофизиологических и генетических особенностей 6 больных АР-АНМ.

Младенческая и детская форма митохондриальной миопатии с мутациями в гене ТК2 с фенотипом спинальной мышечной атрофии 5q: первые случаи в России

Introduction. Mitochondrial myopathy with thymidine kinase 2 deficiency and spinal muscular atrophy 5q (SMA-5q) are two potentially curable hereditary diseases with different levels of damage to the neuromuscular system and etiology. Early childhood forms have a similar phenotype and are difficult for differential diagnosis.The aim of the study — the description of the clinical and paraclinical characteristics of the mitochondrial myopathy with TK2 deficiency and informing health care specialists about the possibility of optimizing differential diagnosis.Materials and methods. This study involved patients with a previously excluded by molecular genetic method a spinal muscular atrophy 5q diagnosis. Clinical and paraclinical descriptions are presented for 5 patients from 3 families. In addition, 96 patient samples were obtained from the archive of the Research Center for Medical Genetics. The diagnosis based on the clinical and paraclinical features of the disease and the detection of mutations in TK2 gene by sequencing of the NGS panel or TK2 gene directly.Results. Eight patients with mitochondrial myopathy with TK2 from 5 unrelated families have been diagnosed. Three of them have been found retrospectively by analyze of 96 spinal muscular atrophy 5q negative samples.Conclusions. Clinical and molecular genetic characteristics of mitochondrial myopathy with TK2 are presented. The feasibility of differential diagnosis of this rare myopathy with other neuromuscular diseases, including such frequent as spinal muscular atrophy 5q, is shown. The study revealed four previously undescribed mutations in the TK2 gene (c.169G&gt;A (p.Gly57Ser), c.310C&gt;T (p.Arg104Cys), c.338T&gt;A (p.Val113Glu), c.655T&gt;C(p.Trp219Arg)).Введение. Митохондриальная миопатия с недостаточностью тимидинкиназы 2 (ТК2) и спинальная мышечная атрофия 5q — два потенциально курабельных наследственных заболевания с различным уровнем поражения нервно-мышечной системы и этиологией. Ранние детские формы имеют схожий фенотип, сложный для дифференциальной диагностики.Цель исследования — описание клинико-параклинических характеристик митохондриальной миопатии с недостаточностью ТК2, информирование специалистов о возможности оптимизации дифференциальной диагностики.Материалы и методы. Всем больным, включенным в обследование, предварительно по результатам молекулярных исследований был исключен диагноз «спинальная мышечная атрофия 5q». Клинико-параклинические описания представлены по 5 пациентам из 3 семей. От 96 пациентов представлен только биоматериал. Диагноз устанавливался на основании клинико-параклинических особенностей проявления заболевания и выявлением мутаций методами прямого секвенирования гена TK2 или с применением таргетных NGS-панелей.Результаты. Диагностировано 8 больных c митохондриальной миопатией с недостаточностью ТК2 из 5неродственных семей, из них 3 больных — ретроспективно при скрининге 96 биообразцов.Выводы. Приведена клиническая и молекулярно-генетическая характеристика митохондриальной миопатии с недостаточностью ТК2. Показана необходимость дифференциальной диагностики этой редкой патологии с другими нервно-мышечными заболеваниями, в том числе таким частым, как спинальная мышечная атрофия 5q. В результате исследования выявлены 4ранее не описанные мутации в гене TK2 (c.169G&gt;A (p.Gly57Ser), c.310C&gt;T(p.Arg104Cys), c.338T&gt;A (p.Val113Glu), c.655T&gt;C (p.Trp219Arg))

Клинико-генетические характеристики болезни Шарко–Мари–Тута типа 4D (типа Lom) в России

Introduction. Charcot–Marie–Tooth disease type 4D is a hereditary demyelinating neuropathy, that occurs with the high frequency in patients of Roma origin. It is characterized by early onset at the age of 2–10 years and hearing impairment, manifested by the 3rd decade of life.Aim of the study. To describe the clinical and genetic characteristics of Charcot–Marie–Tooth disease type 4D in Russian patients of Roma origin.Materials and methods. For 14 probands from unrelated families of Roma origin with a clinical diagnosis of Charcot–Marie–Tooth disease, genetic tests for the pathogenic variants c. 442C&gt;T in the NDRG1 gene and c. 3325C&gt;T in the SH3TC2 gene was carried out. For 8 patients with Charcot–Marie–Tooth disease type 4D, detailed clinical and electrophysiological examination was performed.Results. In 11 families of Roma origin, the c. 442C&gt;T pathogenic variant in the NDRG1 gene in a homozygous state was detected, which accounted for 79 % all observed Roma patients with Charcot–Marie–Tooth disease. There are 12 of the 14 tested families live in the European part of Russia, 7 of them are from nearby regions. The average age of onset was 3.3 years. The first symptom in 7 of 8 patients was gait disturbances. At the time of examination (age range 6–19 years), all patients showed marked hypotrophy and weakness of the feet, lower leg, hands muscles, feet deformities, reduction or loss of tendon reflexes.Discussion. Due to the detection of only one pathogenic variant in most Russian patients of Roma origin with Charcot–Marie–Tooth disease, the knowledge of the ethnicity of a proband with early myelinopathy can significantly simplify the confirmation of the diagnosis on the molecular level.Введение. Болезнь Шарко–Мари–Тута типа 4D – наследственная демиелинизирующая нейропатия, встречающаяся с наибольшей частотой у пациентов цыганского происхождения и характеризующаяся ранним дебютом в возрасте 2–10 лет и нарушением слуха, проявляющимся к 3-й декаде жизни.Цель исследования – описать клинико-генетические характеристики болезни Шарко–Мари–Тута типа 4D у российских пациентов цыганского происхождения.Материалы и методы. Пробандам из 14 неродственных семей цыганского происхождения с клиническим диагнозом «наследственная моторно-сенсорная нейропатия» проведен поиск патогенных вариантов c. 442C&gt;T в гене NDRG1 и с. 3325C&gt;T в гене SH3TC2. У 8 пациентов с болезнью Шарко–Мари–Тута типа 4D проведена оценка клинического статуса, у 3 пациентов – анализ электронейромиографических данных.Результаты. В 11 семьях цыганского происхождения обнаружен патогенный вариант c. 442C&gt;T в гене NDRG1 в гомозиготном состоянии, что составило 79 % всех обследованных цыган с наследственной моторно-сенсорной нейропатией. Из 14 обследованных семей 12 проживают в европейской части России, 7 из них – в близкорасположенных субъектах Российской Федерации. Возраст дебюта болезни составил в среднем 3,3 года. У 7 из 8 пациентов 1-м симптомом было нарушение походки. На момент осмотра (возраст пациентов от 6 до 19 лет) у всех пациентов выявлены выраженная гипотрофия и слабость мышц стоп, голеней, кистей, деформация стоп, снижение или отсутствие сухожильных рефлексов с ног.Обсуждение. Учитывая выявление одного и того же патогенного варианта у большинства пациентов цыганского происхождения с наследственной моторной сенсорной нейропатией, знание этнической принадлежности пробанда с ранней миелинопатией значительно упрощает поиск молекулярно-генетической причины болезни

The SHiP experiment at the proposed CERN SPS Beam Dump Facility

The Search for Hidden Particles (SHiP) Collaboration has proposed a general-purpose experimental facility operating in beam-dump mode at the CERN SPS accelerator to search for light, feebly interacting particles. In the baseline configuration, the SHiP experiment incorporates two complementary detectors. The upstream detector is designed for recoil signatures of light dark matter (LDM) scattering and for neutrino physics, in particular with tau neutrinos. It consists of a spectrometer magnet housing a layered detector system with high-density LDM/neutrino target plates, emulsion-film technology and electronic high-precision tracking. The total detector target mass amounts to about eight tonnes. The downstream detector system aims at measuring visible decays of feebly interacting particles to both fully reconstructed final states and to partially reconstructed final states with neutrinos, in a nearly background-free environment. The detector consists of a 50 m long decay volume under vacuum followed by a spectrometer and particle identification system with a rectangular acceptance of 5 m in width and 10 m in height. Using the high-intensity beam of 400 GeV protons, the experiment aims at profiting from the 4 x 10(19) protons per year that are currently unexploited at the SPS, over a period of 5-10 years. This allows probing dark photons, dark scalars and pseudo-scalars, and heavy neutral leptons with GeV-scale masses in the direct searches at sensitivities that largely exceed those of existing and projected experiments. The sensitivity to light dark matter through scattering reaches well below the dark matter relic density limits in the range from a few MeV/c(2) up to 100 MeV-scale masses, and it will be possible to study tau neutrino interactions with unprecedented statistics. This paper describes the SHiP experiment baseline setup and the detector systems, together with performance results from prototypes in test beams, as it was prepared for the 2020 Update of the European Strategy for Particle Physics. The expected detector performance from simulation is summarised at the end