Evolutionary Effects of Irradiation in Cataclysmic Variables

The orbital evolution of cataclysmic variables in which the companion is illuminated by a fraction of the accretion luminosity consists of irradiation-driven limit cycles on thermal timescales, superimposed on a secular evolution toward shorter periods due to systemic angular momentum losses. We show that positive orbital period derivatives during bright phases are a natural consequence of the expansion of the companion during high mass transfer phases in the limit cycle. The irradiation instability may be enhanced by consequential angular momentum losses, CAML, accompanying the limit cycle. We investigate the secular evolution of cataclysmic binaries under the combined effects of irradiation and CAML and show that faster than secular transfer fluctuations that occur during these cycles can account for the observed dispersion in disk luminosities or estimated accretion rates at a given orbital period. If indeed irradiation-driven and CAML--assisted mass transfer fluctuations on timescales faster than secular occur, as discussed in this paper, then we may be able to predict the relative abundances of the different types of cataclysmic variable at a given orbital period. For example this mechanism may explain the relative paucity of dwarf novae with respect to nova-like variables between 3 and 4 hours.Comment: 35 pages, AAS LATEX macros v4.0, 16 postscript figures, Accepted for publication in the Astrophysical Journal; [email protected], [email protected]

K-Ras protein as a drug target

K-Ras proteins are major drivers of human cancers, playing a direct causal role in about one million cancer cases/year. In cancers driven by mutant K-Ras, the protein is locked in the active, GTP-bound state constitutively, through a defect in the off-switch mechanism. As such, the mutant protein resembles the normal K-Ras protein from a structural perspective, making therapeutic attack extremely challenging. K-Ras is a member of a large family of related proteins, which share very similar GDP/GTP-binding domains, making specific therapies more difficult. Furthermore, Ras proteins lack pockets to which small molecules can bind with high affinity, with a few interesting exceptions. However, new insights into the structure and function of K-Ras proteins reveal opportunities for intervention that were not appreciated many years ago, when efforts were launched to develop K-Ras therapies. Furthermore, K-Ras undergoes post-translational modification and interactions with cellular signaling proteins that present additional therapeutic opportunities, such as specific binding to calmodulin and regulation of non-canonical Wnt signaling

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Cilj istraživanja: Cilj je ovog istraživanja odrediti epidemiološke, demografske i kliničke karakteristike u djece operirane zbog varikocele laparoskopskim pristupom koristeći polimerski klip, analizirati ishode liječenja, stopu komplikacija i spermiogram u odnosu na stadij varikocele nakon operacije. Ispitanici i metode: U studiju je uključeno 120 pacijenata koji su operirani laparoskopskim pristupom zbog varikocele u razdoblju od travnja 2012. do svibnja 2017. godine u Zavodu za dječju kirurgiju Kliničkog Bolničkog Centra Split. Svakom ispitaniku analizirani su sljedeći parametri: dob, lateralizacija i stupanj varikocele, promjer vena, indikacije za operacijski zahvat, duljina trajanja operacijskog zahvata, ishod liječenja, komplikacije i stopa recidiva. Analiza sjemena učinjena je šest mjeseci i godinu dana nakon operacije u pacijenata starijih od 16 godina, te su rezultati uspoređivani u odnosu na klinički stadij varikocele. Rezultati: Srednja dob u vrijeme operacijskog zahvata iznosila je 15 godina. Od ukupnog broja pacijenata, lijevostrana varikocela pronađena je u 119 (99%), a bilateralna u jednog (1%) pacijenta. Od 120 varikocela, 8 (7%) ih je bilo klasificirano u stadij I, 58 (48%) u stadij II i 54 (45%) u stadij III. Medijan promjera vena varikocela stadija I, II i III iznosio je 2.95 mm, 3.20 mm i 4.0 mm. Indikacije za operaciju su bile: abnormalan nalaz spermiograma u 37 (26%) pacijenata, smanjen volumen testisa >20% u 62 (43%) pacijenta, bol, odnosno nelagoda u skrotumu u 36 (25%) pacijenata te povišene razine serumskog LH/FSH u 9 (6%) pacijenata. Medijan duljine boravka u bolnici iznosio je 1 dan. Medijan operacijskog vremena iznosio je 12 min (raspon 10 - 35 min). Nisu zabilježene ozbiljne intraoperacijske komplikacije. Do formiranja konsekutivne hidrocele došlo je u 2 (1.6%) pacijenta. Nije zabilježen slučaj recidiva. Koncentracija spermija (p<0.01), morfologija (p<0.01) i motilitet (p<0.01; p=0.02) poboljšali su se šest mjeseci nakon operacije u pacijenata s varikocelom stadija I i II. U stadiju III varicocele zabilježeno je poboljšanje u koncentraciji spermija (p<0.01) i morfologiji (p=0.03), dok se motilitet spermija (p=0.150) nije značajno oporavio. Do značajnog poboljšanja u volumenu testisa došlo je u 81% pacijenata. U 92% pacijenata koji su operirani zbog subjektvnih tegoba one su se povukle u periodu od godine dana nakon operacijskog zahvata. Zaključci: Laparoskopska varikocelektomija pri kojoj se koriste polimerski klipovi je sigurna, jednostavna i isplativa metoda, s niskom stopom poslijeoperacijskih komplikacija i recidiva te dovodi do značajnog poboljšanja kvalitete sjemena u adolescenata.Objectives: The aim of this study was to evaluate demographic and clinical characteristics of the children undergoing laparoscopic varicocelectomy using polymeric ligating clips and to evaluate postoperative outcomes and analyze semen according to the grade of varicocele after surgery. Patients and methods: The case records of 120 pediatric patients who underwent laparoscopic varicocelectomy with polymer ligating clips between May, 2012 and May, 2017 at University Hospital of Split in Croatia were retrospectively reviewed. The following parameters were examined: age, grade of varicocele, lateralization, diameter of spermatic veins, indications for surgery, duration and outcomes of surgery, complications and recurrence rate. For patients older than 16-years of age semen analyses were obtained before and after the surgery and were compared according to the clinical grade of varicocele. Results: The median age of the patients was 15 years. Of the total number of patients, left-sided varicocele was found in 119 (99%) and bilateral in one patient (1%). Of 120 varicoceles, 8 (7%) were grade I, 58 (48%) grade II and 54 (45%) were grade III. Median diameters of veins in varicocele grades I, II and III was 2.95 mm, 3.20 mm and 4.0 mm, respectively. The indications for surgery were: abnormal spermiogram in 37 patients (26%), significant decrease in testicular volume in 62 patients (43%), scrotal pain/discomfort in 36 (25%) and elevated levels of serum LH/FSH in 9 patients (6%). Hospital stay was 1 day for all of the patients. The median of operation duration was 12 min. There were no major intraoperative complications. Hydrocele was found in 2 (1.6%) patients. There were no cases of recurrence recorded. Sperm concentration (p<0.01), morphology (p<0.01) and motility (p<0.01; p=0.02) improved six months after surgery in patients with varicocele grades of I and II, respectively. In grade III varicocele only sperm concentration (p<0.01) and morphology (p=0.03) improved while motility (p=0.150) did not change significantly. Significant improvement of difference in testicular volume was found in 80% of the patients, and 92% of the patients who reported pain or discomfort prior to the surgery were pain free at on year follow up. Conclusion: Laparoscopic varicocelectomy using polymeric ligating clips is a safe, feasible and cost effective technique, with a low rate of postoperative complications and recurrence and it significantly improves sperm parameters in adolescents