Relaxation dynamics in excited helium nanodroplets probed with high resolution, time-resolved photoelectron spectroscopy.

Superfluid helium nanodroplets are often considered as transparent and chemically inert nanometer-sized cryo-matrices for high-resolution or time-resolved spectroscopy of embedded molecules and clusters. On the other hand, when the helium nanodroplets are resonantly excited with XUV radiation, a multitude of ultrafast processes are initiated, such as relaxation into metastable states, formation of nanoscopic bubbles or excimers, and autoionization channels generating low-energy free electrons. Here, we discuss the full spectrum of ultrafast relaxation processes observed when helium nanodroplets are electronically excited. In particular, we perform an in-depth study of the relaxation dynamics occurring in the lowest 1s2s and 1s2p droplet bands using high resolution, time-resolved photoelectron spectroscopy. The simplified excitation scheme and improved resolution allow us to identify the relaxation into metastable triplet and excimer states even when exciting below the droplets' autoionization threshold, unobserved in previous studies.

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.

Single-ion dosemeter based on floating gate memories.

Floating Gate (FG) nonvolatile memories are based on a tiny polysilicon layer (the FG) which can be permanently charged with electrons or holes, thus changing the threshold voltage of a MOSFET. Every time a FG is hit by a high energy ion, it experiences a charge loss, depending on the ion linear energy transfer (LET) and on the transistor geometrical and electrical characteristics. This paper discusses the opportunities to use this devices as single an ion dosemeter with sub-micrometer spatial resolution and capable of distinguish the impinging ion LET.

Sensitivity and dynamic range of FGMOS dosemeters.

UVPROM memory devices employing FGMOS transistors as memory cells make excellent dosemeters for applications involving ionising radiation. With proper preparation and programming, these devices can be used in remote-sensing applications in high-radiation environments with no power required during exposure.

Male fertility: core chemical structure in pharmacological research.

Research in male fertility is of interest in connection with both contraception and treatment of sterility. Several compounds have been shown to inhibit fertility by various mechanisms. The most significant of them are reviewed, including some recently described indazole carboxylic acids. Concerning sterility treatment, no effective treatment is so far available, with the exception of hormonal dysfunctions. The hypothesized role of an excess of free radicals in male sterility suggests a potential therapeutic value of free radicals scavengers. In this connection, indazole derivatives appear of special interest, as some of them display an anti-denaturant activity resulting in a peculiar scavenger-like activity. Some synthetic approaches are proposed, leading to new compounds of potential interest either as male contraceptives or in the treatment of male sterility.

Callosal transfer in different subtypes of developmental dyslexia.

Sixteen controls (age 6-13) and 20 native Italian children with developmental dyslexia (age 7-15) received a test of callosal transfer of tactile information. Among the dyslexic children, 7 had a diagnosis of L-type, 7 of P-type and 6 of M-type dyslexia according to Bakker's classification. Both control children and children with dyslexia made a significantly larger number of errors in the crossed localization condition (implying callosal transfer of tactile information) vs. the uncrossed condition. In the same condition, children with dyslexia made a significantly larger number of errors than controls. In the crossed localization condition L-types and M-types made a significantly larger number of errors than P-types and controls, while there was no significant difference in performance between P-types and controls. These findings are discussed in terms of defective callosal transfer or deficient somatosensory representation in children with L- and M-dyslexia.

Idiopathic juxtafoveolar retinal telangiectasis: clinical pattern in 19 cases.

BACKGROUND: Idiopathic juxtafoveolar telangiectasis (IJT) is a rare retinal vasculopathy of adulthood that may cause central loss of visual acuity. The purpose of this paper is to evaluate the type and distribution of fundus changes in patients with this disorder. METHODS: Medical records of 19 patients with IJT using the Gass & Blodi classification were studied. Eight patients in group 1A (42%) and 11 in group 2A (58%) were analyzed. By projecting color photographs we divided the macula into four quadrants and studied the fundus changes in each one. RESULTS: All patients in group 1A presented unilateral disease with easily seen telangiectasis, lipid deposits and cystic macular edema. The mean age of this group was 55.8 years. Five (63%) patients were male and 3 (37%) were female. All patients in group 2A, 2 males (18%) and 9 females (82%), had bilateral disease evidenced by fluorescein angiography. The mean age of this group was 54.5 years. Fundoscopic findings included: intraretinal pigment plaques, grayish coloring of the macular retina, superficial crystalline deposits, right-angle venules, subretinal and intraretinal neovascularization. CONCLUSIONS: All patients in this survey were adults. In group 1A, men were affected 2 times more often than women, and the main affected macular quadrant was the inferior temporal, followed by the inferior nasal. In group 2A, women were affected 4 times more often than men and all eyes had inferior and superior temporal macular quadrant involvement.

A comparative study of behavioural and autonomic effects of atropine and Atropa belladonna.

Atropa belladonna L. (Solanaceae) tincture was compared with atropine for its anticholinergic activity, both in vivo and in vitro. In all tests, the biological activity of A. belladonna resulted greater than that suggested by its alkaloid content. The results suggest the presence in A. belladonna leaves of unknown compounds with a significant biological activity.

Funduscopic alterations in SS and SC hemoglobinopathies. Study of a Brazilian population.

Fundus changes in sickle cell disease are well studied and documented according to their clinical and angiographic aspects. Sickle cell retinopathy was studied in a Brazilian population of 63 patients (41 with SS hemoglobinopathy, and 22 with SC hemoglobinopathy). All ophthalmoscopic changes observed in our patients were more frequent in the SC group with the exception of atrophic retinal tears, found only in the SS group. Proliferative retinopathy including its complications was seen in 54.54% of the eyes of the SC group, and in only 14.64% of the eyes of the SS group. Decreased vision is consequently greater in the SC group. Despite the great frequency of funduscopic changes in both groups, only 1 patient suffered irreversible visual loss due to retinal detachment operated on without success.

Fate of different kinds of liposomes containing dexamethasone palmitate after intra-articular injection into rabbit joints.

The fate of oligolamellar and multilamellar vesicles containing dexamethasone palmitate after intra-articular injection into healthy rabbit joints was investigated to improve the liposome formulation in respect to better bioavailability of the effective substance within the arthritic joint. The defined negatively charged oligolamellar vesicles (dexamethasone) palmitate, egg phosphatidylcholine, phosphatidic acid, molar ratio 0.24:10.1) of a mean diameter of 0.75 micron gave better results than multilamellar vesicles (dexamethasone palmitate, dipalmitoylphosphatidylcholine, phosphatidic acid, molar ratio 0.24:10:1) used for the same purpose by several other authors. The positive charge carrier stearylamine does not induce any improvement.

Studies of pharmacokinetics and therapeutic effects of glucocorticoids entrapped in liposomes after intraarticular application in healthy rabbits and in rabbits with antigen-induced arthritis.

Dexamethasone palmitate (DMP) entrapped in liposomes of defined sizes was administered intraarticularly in healthy rabbits and in rabbits with antigen-induced arthritis. The pharmacokinetics and therapeutic effect of liposomal DMP were measured and compared with corresponding experiments using microcrystalline triamcinolone acetonide (TAC). The small DMP liposomes (diameter 160 nm) showed a greater decrease in joint circumference than the 3-times-higher dose of microcrystalline TAC. Moreover, about 98% of administered TAC had already disappeared from the joint 6 h after injection, whereas about 36% of liposomal DMP was still measured in synovial fluid and synovium at the same time. Increasing the vesicle diameter from 160 to 750 nm (large liposomes) improved the retention of DMP by a factor of 2.6 within 48 h after injection in healthy rabbits. In addition, none of the liposomal glucocorticoid preparations ever suppressed the endogenous plasma cortisol level, which is in contrast to the suppression measured after administration of the microcrystalline preparation.

Ferimentos perfurantes do globo ocular por acidentes automobilisticos. / Perforating eyeball wounds caused by automobile accidents

Apresenta-se um estudo de 50 pacientes com ferimentos oculares durante 29 meses e da proporcao de tais ferimentos no total de cirurgias

Ferimento perfurante de globo ocular na infancia. / Perforating eyeball injury in children

Foram estudados 364 casos de ferimentos perfurantes de globo ocular em criancas de ate 15 anos de idade, admitidos no Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, no periodo de 1970 a 1977. Estes casos representaram 47,3% do total de ferimentos perfurantes atendidos durante este periodo, encontrando-se uma incidencia de 74,7% do sexo masculino, com uma relacao de 2/1 no grupo de 0 a 6 anos de idade, 3/1 no grupo de 7 a 11 anos e de 5/1 no grupo de 12 a 15 anos de idade. As causas mais comuns de ferimentos perfurantes oculares foram: objetos pontiagudos (31,6%), contusao (30,7%) e objetos volantes (20,0%).Ressalta-se a correlacao entre a gravidade do ferimento e o prognostico visual, mostrandose que 80% dos pacientes com catarata traumatica (FPO de grau II), tiveram acuidade visual final menor ou igual a 20/400. Excisao imediata do globo ocular foi realizada em apenas 1,3% dos FPOs e sempre ditada pela impossibilidade de reconstituicao cirurgica.Nao foi constatado nenhum caso de oftalmia simpatica nos casos estudados

Cirurgia filtrante no glaucoma agudo primario. Resultados cirurgicos. / Filtering surgery in acute primary glaucoma. Surgical results

Estudaram-se 50 olhos com crise de glaucoma agudo primario. A pressao intra-ocular foi controlada no periodo pre-operatorio, em 50% dos olhos, e este controle demonstrou-se correlacionado com a ausencia de glaukomflecken.Destes olhos, 25 foram submetidos a cirurgia filtrante: 12 a cirurgia de Sheile e 13 a trabeculectomia. Houve sucesso cirurgico em todos os pacientes, nao sendo necessaria a reoperacao em nenhum olho. Em um periodo de seguimento de 21 + ou - 3 meses, a cirurgia de Sheile, mostrou-se superior, quanto ao controle de pressao intra-ocular, nao havendo necessidade do uso de medicacao pos-operatoria em nenhum olho, ao passo que no grupo trabeculectomizado, houve esta necessidade em 42,85% dos olhos, seguidos pelo mesmo intervalo de tempo. Em um periodo de seguimento de 3 anos, todos os pacientes submetidos a cirurgia de Sheile, desenvolveram catarata, enquanto que nenhum dos trabeculectomizados apresentou esta complicacao, no mesmo intervalo de tempo

Avaliacao da pressao intra-ocular no pos-operatorio do glaucoma agudo primario na ausencia de medicacao antihipertensiva. / Evaluation of intraocular pressure in the postoperative period of acute primary glaucoma without antihypertensive medication

Foram estudados 31 pacientes (42 olhos) iridectomizados por terem apresentado crise de glaucoma agudo primario. Tais pacientes foram acompanhados por um periodo de tempo de 2 a 48 meses. 45,2% dos olhos apresentarm PIO entre 20 - 50 mmHg nos dois primeiros meses de pos-operatorio. 5 dos 19 olhos (26,3%) tiveram suas pressoes intraoculares normalizadas com a simples suspensao do uso de esteroides e midriaticos topicos. 3 olhos que durante 17 meses apresentaram suas pressoes normalizadas apos a cirurgia, desenvolveram PIO de 26 a 30 mmHg apos este periodo. A importancia clinica destes achados e discutida

Alteracoes isquemicas e necroticas no glaucoma agudo primario. / Ischemic and necrotic changes in acute primary glaucoma

47 pacientes num total de 58 olhos, que apresentaram crise de glaucoma agudo foram estudados. Analisou-se a frequencia quanto ao sexo, raca e idade dos pacientes e a bilateralidade do comprometimento ocular. A frequencia no sexo feminino foi de 85,1%, sendo que somente 4,2% eram da raca negra. Nao foi possivel correlacionar-se a presenca de atrofia setorial da iris e glaukomflecken com a duracao ou valor da pressao intra ocular no momento da crise. A possibilidade de que a atrofia de iris precede o aparecimento de glaukomflecken na maioria dos pacientes e discutida

[Products of a reaction between 1H-indazol-3-ol and ethyl chloroacetate]. / Prodotti di una reazione tra 1H-indazol-3-olo e cloroacetato di etile.

Ethyl esters of [(1-carbethoxymethyl-1H-indazol-3-yl)oxy]-acetic acid; (2-carbethoxy-3,4-dihydro-4-oxo-3-quinazolinacetic acid; [(1H-indazol-3-yl)oxy] acetic acid; o.aminoippuric acid; (2-carbethoxy-4-oxo-1,2,3,4--tetrahydro)-3-quinazolin acetic acid; (3-hydroxy-1H-indazol-1-yl)acetic acid; (1H-indazol-3-on-2-yl)acetic acid have been isolated and identified from a reaction between equivalent quantities of 1H-indazol-3-ol and ethyl chloroacetate in ethanol. The mechanism of their formation and, particularly, the ring enlargement of indazole to tetrahydroquinazoline is discussed. I.R. and N.M.R. spectra of these esters and of the acids obtained from them by alkaline hydrolysis are also described.