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Christine Battersby describes the aesthetic category of the sublime as "overwhelming [...] terrifying; unrepresentable; revolutionary [while] also slippery, denoting a concept [...] subject to metamorphosis and flux," and resulting in the experience of "surrender or displacement of the ego." A similar definition may be claimed for the notion of queer, a subversive "category in flux" devoted to troubling both subjects and objects by submitting them to the lenses of strangeness and difference, ultimately destabilising regimes of cis-hetero-normativity. How and where do the categories of sublime and queer intersect? What type of cinematic aesthetics stems from their encounter, and what are its resulting social and political implications? This essay attempts to answer such questions through the close textual analysis of two West German productions - Werner Schroeter's Der Rosenkönig (1986) and Ulrike Ottinger's Johanna d'Arc of Mongolia (1989) - and the ways in which both films seek to introduce new canons of visual pleasure by employing highly stylized aesthetic elements symptomatic of a larger, political category of queer sublimity that is found to revolve around the eroticization of boundaries between Self and Other. Keywords: Ulrike Ottinger; Werner Schroeter; German cinema; queer sublime; queer theory

Molecular hybrids obtained by connecting two or more bioactive molecules through a metabolizable linker are used as multi-target drugs for the therapy of multifactorial diseases. Ascorbic acid, as well as the ketone bodies acetoacetate and (R)-3-hydroxybutyrate, are bioactive molecules that have common fields of application in the treatment and prevention of neurodegenerative diseases and cardiac injuries as well. In spite of this, the preparation of ascorbic acid ketone body hybrids is uncovered by the literature. Herein, we report the lipase-catalyzed condensation of methyl acetoacetate with ascorbic acid, which affords the 6-O-acetoacetyl ascorbic acid in quantitative yield. The same approach, employing the methyl (R)-3-hydroxybutyrate in place of the methyl acetoacetate, allows the preparation of the 6-O-(R)-3-hydroxybutyryl ascorbic acid in 57% yield. A better result (90% overall yield) is achieved through the lipase-catalyzed coupling of ascorbic acid with methyl (R)-3-O-methoxymethyl-3-hydroxybutyrate followed by the cleavage of the MOM protecting group. The two novel products are fully characterized and additional information on the antioxidant activity of the new products is also given.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

A new beam dump has been designed, built, installed and operated to withstand the future proton beam extracted from the proton synchrotron booster (PSB) in the framework of the LHC Injector Upgrade (LIU) Project at CERN. The future proton beam consists of up to 1×1014 protons per pulse at 2 GeV and is foreseen after the machine upgrades planned for CERN’s Long Shutdown 2 (2019-2020). In order to be able to efficiently dissipate the heat deposited by the primary beam, the new dump was designed as a cylindrical block assembly, made out of a copper alloy and cooled by forced airflow. In order to determine the energy density distribution deposited by the beam in the dump, Monte Carlo simulations were performed using the fluka code, and thermomechanical analyses were carried out by importing the energy density into ANSYS®. In addition, computational fluid dynamics (CFD) simulations of the airflow were performed in order to accurately estimate the heat transfer convection coefficient on the surface of the dump. This paper describes the design process, highlights the constraints and challenges of integrating a new dump for increased beam power into the existing facility and provides data on the operation of the dump. A new beam dump has been designed, built, installed and operated to withstand the future proton beam extracted from the Proton Synchrotron Booster (PSB) in the framework of the LHC Injector Upgrade (LIU) Project at CERN, consisting of up to 1E14 protons per pulse at 2 GeV, foreseen after the machine upgrades planned for CERN's Long Shutdown 2 (2019-2020). In order to be able to efficiently dissipate the heat deposited by the primary beam, the new dump was designed as a cylindrical block assembly, made out of a copper alloy and cooled by forced airflow. In order to determine the energy density distribution deposited by the beam in the dump, Monte Carlo simulations were performed using the FLUKA code, and thermo-mechanical analyses were carried out by importing the energy density into ANSYS. In addition, Computational Fluid Dynamics (CFD) simulations of the airflow were performed in order to accurately estimate the heat transfer convection coefficient on the surface of the dump. This paper describes the design process, highlights the constraints and challenges of integrating a new dump for increased beam power into the existing facility and provides data on the operation of the dump.

A customised multi-task equipment, combining supercritical carbon dioxide (sc-CO2) and pressurized liquid extraction (PLE) with ethanol, was developed to selectively recover antioxidant compounds from cocoa bean hulls, praising this agro-industrial by-product. Total phenolic content of the extracts was determined by Folin-Ciocalteu method, while the in vitro antioxidant activity was obtained by DPPH and by β-carotene bleaching methods, whereas the chemical profile of selected extracts was carried out by gas-chromatography-mass spectrometry (GC–MS) analysis. PLE extracts from sc-CO2 residue showed higher total phenol content and antioxidant performance, compared to extracts from separated methods, providing TPC values from 35 to 51 mg GAE g−1 and EC50 values from 115 to 177 μg mL−1, respectively. The combined application of sc-CO2 and PLE to selectively recover bioactive extracts from cocoa bean hulls, representing green methods, is a promising alternative to provide supplies for cosmetic and food industries, performed at a costumised low cost multi-task unit.

In the frame of the FCC study we are designing a 27 TeV hadron collider in the LHC tunnel, called the High Energy LHC (HE-LHC). The HE-LHC can be realized by replacing the LHC’s 8.33 T niobium-titanium dipole magnets with 16 T niobium-tin magnets developed for FCC-hh. A high-quality beam available from the upgraded LHC injector complex and significant radiation damping allow achieving the challenging target values for both peak and integrated luminosity required by particle physics. Tunnel integration determines the maximum outer size of the magnet cryAPCostat. The HE-LHC arc optics maximizes the dipole filling factor and optimizes the dynamic aperture, while limiting the field strengths of quadrupoles and sextupoles. The low-beta optics for the experimental insertions features a shielded quadrupole triplet even longer than the HL-LHC’s, which can support an interaction-point beta function of 25 cm, and survive an integrated luminosity above 10/ab. Other challenges include collimation and extraction. The choice of injection energy and injector is another important element, and so are various collective effects. We here report the HE-LHC design status. In the frame of the FCC study we are designing a 27 TeV hadron collider in the LHC tunnel, called the High Energy LHC (HE-LHC).

The homocoupling reaction of α-diketones, e.g. (I), is smoothly mediated by thiazolium salt HETP or, more conveniently, by catalytic amounts of commercially available thiazolium salt HEBT.

By mimicking the peculiar behavior of thiamine diphosphate-dependent acetylacetoin synthase, it has been demonstrated that thiamine hydrochloride 2a and its simple analogue thiazolium salt 2b are able to activate α-diketones as acyl anion equivalents in nucleophilic acylations, such as the homo-coupling of α-diketones and the hitherto unreported cross-coupling between α-diketones and α-ketoesters. These carboligation reactions were optimized under stoichiometric (2a) and catalytic conditions (2b) by using eco-friendly PEG400 as the reaction medium, thus allowing both solvent and thiazolium salt recycling.

The synthesis of α-hydroxy-1,3-diketones 2 and 3 from the corresponding 1,2-diketones with Bacillus stearothermophilus ATCC2027 acetylacetoin synthase (AAS) was described. The enzyme catalyzed the condensation of the dialkyl- or alkyl-aryl-1,2-diketones 1 with the elimination of a carboxylic acid moiety. The reactions were carried out using either one diketone both acting as donor and acceptor (homo-coupling) or with two different reacting species (cross-coupling). The homo-coupling reactions of the asymmetric dialkyl-1,2-diketones 1c–d afforded a mixture of the regioisomers 2 (30–42%, ee 67–70%) and 3 (19–25%), while only the 1,3-diketones 2a (57%), 2b (60%), and 2e (45%, ee 76%) were obtained using 2,3-butanedione 1a, 3,4-hexanedione 1b, and 1-phenyl-1,2-propanedione 1e, respectively. The cross-coupling reactions of the diketones 1a and 1b, and 1b and 1e were carried out using various ratios of the donor and the acceptor. In both cases the only cross-coupling product was 3-ethyl-3-hydroxy-2,4-hexanedione 4 (62%, ee 91%).

OBJECTIVE: To report the accuracy of ultrasound scanning (US) in predicting neurodevelopmental and sensorineural outcome in patients with congenital cytomegalovirus (CMV) infection. STUDY DESIGN: Fifty-seven neonates with congenital CMV infection underwent brain US and were observed prospectively for motor skills, developmental quotient, and hearing function. RESULTS: Abnormal results on US were found in 12 of 57 neonates. US lesions were more frequent in newborns with clinical and laboratory signs of congenital CMV infection at birth (10/18) than in newborns who had no symptoms at birth (2/39; P < .001). At least 1 sequela developed in all neonates with symptoms who had abnormal US results, whereas none of the neonates with symptoms who had normal US results had long-term sequelae (P < .001). In the population without symptoms, sensorineural hearing loss developed in 3 of 37 (8.1%) neonates with normal US results, whereas severe sequelae developed in 1 of 2 neonates with abnormal US results. CONCLUSIONS: A good correlation was found between cerebral US abnormalities and the prediction of outcome in newborns who were congenitally infected with CMV and had symptoms at birth. US could be performed as the first neuroimaging study in these newborns. Data are insufficient to permit any suggestions for the population without symptoms.

OBJECTIVE. Human cytomegalovirus (CMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection in developed countries leading to psychomotor impairment and deafness. Diagnostic techniques for CMV detection have greatly improved during recent years with the advent of sophisticated serological and virological methods. The aim of the present study was to assess the diagnostic and prognostic value of detection and quantification of virus in neonatal blood samples of symptomatic and asymptomatic newborns with CMV congenital infection.METHODS. Between January 1997 and December 2003, we studied 99 newborns who were born to women with primary, recurrent, and undefined CMV infection during pregnancy. CMV congenital infection was identified by isolation of the virus in urine within the second week of life. Fifty-eight of 99 infants were infected and were assessed clinically for disease in the newborn period and classified as having symptomatic or asymptomatic infection on the basis of physical, instrumental, and laboratory findings. The infants were followed up from birth according to a protocol of the tertiary NICU at the University of Bologna in a prospective study of long-term sequelae of congenital infection. Forty-seven blood samples were obtained from 47 infants in the neonatal period: 34 were examined for pp65 antigenemia test and 44 for qualitative and quantitative polymerase chain reaction (PCR and qPCR). Sequelae at 12 months were evaluated in a group of 50 infants.RESULTS. Antigenemia was positive in only 10 of 34 samples of infected newborns (29.4% sensitivity). PCR was performed in 44 samples of infected newborns and was positive in all (100% sensitivity). qPCR showed a finding of ≥100 copies per 105 of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 105 PMNLs was 10000 copies did develop sequelae.CONCLUSIONS. Different viremia value ranges are correlated to a different risk of sequelae: ∼70% sequelae were found in newborns with a qPCR higher than 10000 copies per 105 PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia

BACKGROUND: Risk factors for mother-to-child transmission of hepatitis C virus (HCV) are poorly quantified. METHODS: We conducted a European multicenter prospective study of HCV-infected pregnant women and their infants. Children with > or =2 positive HCV RNA polymerase chain reaction test results and/or anti-HCV antibodies after 18 months of age were considered to be infected. RESULTS: The overall HCV vertical transmission rate was 6.2% (95% confidence interval [CI], 5.0%-7.5%; 91/1479). Girls were twice as likely to be infected as boys (adjusted odds ratio [OR], 2.07 [95% CI, 1.23-3.48]; P=.006). There was no protective effect of elective cesarean section (CS) delivery on HCV vertical transmission (adjusted OR, 1.46 [95% CI, 0.86-2.48]; P=.16). HCV/human immunodeficiency virus-coinfected women more frequently transmitted HCV than did women with HCV infection only, although the difference was not statistically significant (adjusted OR, 1.82 [95% CI, 0.94-3.52]; P=.08). Maternal history of injection drug use, prematurity, and breast-feeding were not significantly associated with transmission. Transmission occurred more frequently from viremic women, but it also occurred from a few nonviremic women. CONCLUSIONS: Our results strongly suggest that women should neither be offered an elective CS nor be discouraged from breast-feeding on the basis of HCV infection alone. The sex association is an intriguing finding that probably reflects biological differences in susceptibility or response to infection.

Human herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The virus has been found in the cerebrospinal fluid of many children with aseptic meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA detection in cord blood specimens of apparently healthy newborns and in fetuses following spontaneous abortions. A patient is described with early neonatal afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed by repeated detection of viral genome by polymerase chain reaction (PCR) in cerebrospinal fluid in the first days of life. At follow-up, magnetic resonance imaging (MRI) studies disclosed hyperintensities in the periventricular white matter and basal ganglia, associated with cerebral atrophy. Further follow-up at 18 months revealed poor neurological outcome with mild neurodevelopmental retardation, strabismus and hypertonia of legs. This report provides evidence of neurological involvement after HHV 6 vertical transmission, and the association with neurological sequelae.

Risk factors affecting vertical hepatitis C virus (HCV) transmission are not completely known, if we exclude maternal HIV coinfection. We hypothesized that immunogenetic factors related to maternal or neonatal HLA profiles may affect HCV vertical transmission. HLA typing (microcytotoxicity assay on blood samples) was performed in 18 infants affected by vertically transmitted HCV infection and in 17 serum-reverted infants. (Serum-reversion is defined as antibody negative by 1 year of age and persistently HCV-RNA negative.) Moreover, HLA typing was performed in 20 mothers. Logistic regression analysis showed a significant negative association between children's HLA-DR13 antigens and risk of HCV vertical transmission (p < 0.01). This association persisted in a model including the maternal HIV status: HLA DR13 and maternal HIV coinfection showed a separate, opposite effect on vertical HCV infection (p < 0.01 and p < 0.001, respectively). The relative risk estimate for the ratio of not-infected to infected children in the presence of DR13 was 8.4 (95% confidence bounds, 1.1-60.8). Breast-feeding did not affect the risk of vertical HCV transmission. Maternal HLA profile did not relate to vertical infection. The present study reveals a significant association between HLA-DR13 and the likelihood of seroreversion in infants born to HCV-infected mothers. The findings of the present study could help in better understanding the pathogenesis of vertical HCV infection and in better identifying the cases at higher risk, which would be useful for the development of prevention strategies. It is possible that DR13 modulates the immune response to viruses, enhancing their clearance and, thus, in the case of HCV, exerting a protective role against the development of vertical infection.

An enzymatic strategy for the preparation of optically pure α-alkyl-α,β-dihydroxyketones is reported. Homo- and cross-coupling reactions of α-diketones catalyzed by acetylacetoin synthase (AAS) produce a set of α-alkyl-α-hydroxy-β-diketones (30–60%, ee 67–90%), which in turn are reduced regio-, diastereo-, and enantioselectively to the corresponding chiral α-alkyl-α,β-dihydroxyketones (60–70%, ee >95%) using acetylacetoin reductase (AAR) as catalyst. Both enzymes are obtained from Bacillus licheniformis and used in a crude form. The relative syn stereochemistry of the enantiopure α,β-dihydroxy products is assigned by NOE experiments, whereas their absolute configuration is determined by conversion of the selected 3,4-dihydroxy-3-methyl-pentan-2-one to the natural product (+)-citreodiol.

Thrombotic disease is rare in neonates. The main risk factors at this age are perinatal asphyxia, maternal diabetes, sepsis, polycythemia, dehydration, a low cardiac output, and in primis the catheterization of central lines. Another important risk factor is inherited thrombophilia. Arterial thrombosis is even more rare than venous thrombosis and less related to most of the risk factors listed above; it occurs more frequently in the iliac, femoral, and cerebral arteries but very rarely in the aorta. Most of the described cases of aortic thrombosis are associated with the catheterization of an umbilical artery and involve the descending tract and the renal arteries; very few relate to the ascending tract and the aortic arch. The possible role of virus-induced primary vascular endothelium damage in the etiopathogenesis of neonatal arterial thrombosis has been previously hypothesized. Herpesviruses, particularly human cytomegalovirus (HCMV), can infect endothelial cells and directly damage intact vascular endothelium, altering its thromboresistant surface as a result of procoagulant activity mediated by specific viral surface phospholipids, necessary for the coagulation enzyme complex assembly that leads to thrombin generation. We describe a case of congenital aortic arch thrombosis. The clinical, laboratory, and virologic pictures; the anatomopathologic findings (fully compatible with viral infection); the detection of HCMV in various tissues (including the aorta); and the absence of other causes of aortic thrombosis make it possible to attribute the case to a severe congenital HCMV infection with multiple organ involvement, after the primary infection of the mother. The hemostatic system disorders and hemodynamic disturbances related to viral cardiac damage explain the clinical features of the case and indicate that congenital HCMV infection should be included among the causes of neonatal aortic thrombosis.

HLA-DR13 Is Preferentially Associated with a Diminution in Maternally Transmitted Hepatitis C Virus Infection