Scaling and Formulary cross sections for ion-atom impact ionization

The values of ion-atom ionization cross sections are frequently needed for many applications that utilize the propagation of fast ions through matter. When experimental data and theoretical calculations are not available, approximate formulas are frequently used. This paper briefly summarizes the most important theoretical results and approaches to cross section calculations in order to place the discussion in historical perspective and offer a concise introduction to the topic. Based on experimental data and theoretical predictions, a new fit for ionization cross sections is proposed. The range of validity and accuracy of several frequently used approximations (classical trajectory, the Born approximation, and so forth) are discussed using, as examples, the ionization cross sections of hydrogen and helium atoms by various fully stripped ions.Comment: 46 pages, 8 figure

An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool. © 2013 Sejdić et al

Not the number but the location of lymph nodes matters for recurrence rate and disease-free survival in patients with differentiated thyroid cancer

BACKGROUND: Several Japanese studies have focused on identifying prognostic factors in patients with positive lymph nodes to predict recurrence rate and disease-free survival (DFS). However, different treatment protocol is followed in Japan compared with the European and American approach. This study was designed to investigate whether the number and/or location of lymph nodes predicts prognosis in patients with DTC treated with total thyroidectomy, lymph node dissection, and postoperative radioactive iodine ablation. METHODS: All 402 patients who were treated at the Department of Nuclear Medicine between 1998 and 2010 for DTC were reviewed. Patients were treated with (near) total thyroidectomy, lymph node dissection on indication, and postoperative I-131 ablation. Median follow-up was 49 (range, 10-240) months. Outcome measures were recurrence rate, disease-free survival, and mean time to recurrence. RESULTS: Ninety-seven patients had proven lymph node metastases. Recurrence rate was significantly higher in patients with positive lymph nodes in the lateral compartment vs. patients with lymph node metastasis in the central compartment (60 vs. 30%, p = 0.007). Disease-free survival and mean time to recurrence also were significantly shorter (30 vs. 52 months, p = 0.035 and 7 vs. 44 months, p = 0.004, respectively). The number of lymph nodes and extranodal growth were not significantly associated with the outcome measures used. CONCLUSIONS: The location of positive lymph nodes was significantly correlated with the risk of recurrence and a shorter DFS. Hence, the TNM criteria are useful in subdividing patients based on risk of recurrence and DFS

MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients

Contains fulltext : 170909.pdf (publisher's version ) (Open Access)BACKGROUND: Multiple Endocrine Neoplasia type 1 (MEN1) is diagnosed when two out of the three primary MEN1-associated endocrine tumors occur in a patient. Up to 10-30 % of those patients have no mutation in the MEN1 gene. It is unclear if the phenotype and course of the disease of mutation-negative patients is comparable with mutation-positive patients and if these patients have true MEN1. The present study aims to describe and compare the clinical course of MEN1 mutation-negative patients with two out of the three main MEN1 manifestations and mutation-positive patients during long-term follow-up. METHODS: This is a cohort study performed using the Dutch MEN1 database, including > 90 % of the Dutch MEN1 population. RESULTS: A total of 293 (90.7 %) mutation-positive and 30 (9.3 %) mutation-negative MEN1 patients were included. Median age of developing the first main MEN1 manifestation was higher in mutation-negative patients (46 vs. 33 years) (P = 0.007). Mutation-negative patients did not develop a third main MEN1 manifestation in the course of follow-up compared to 48.3 % of mutation-positive patients (P < 0.001). Median survival in mutation-positive patients was estimated at 73.0 years (95 % CI, 69.5-76.5) compared to 87.0 years (95 % CI not available) in mutation-negative patients (P = 0.001). CONCLUSIONS: Mutation-positive and mutation-negative MEN1 patients have a different phenotype and clinical course. Mutation-negative patients develop MEN1 manifestations at higher age and have a life expectancy comparable with the general population. The apparent differences in clinical course suggest that MEN1 mutation-negative patients do not have true MEN1, but another MEN1-like syndrome or sporadic co-incidence of two neuro-endocrine tumors

Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25 mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months' streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the molecular and functional expression of TRPV4 channels in retinal microvascular endothelial cells. These changes may contribute to diabetes induced endothelial dysfunction and retinopathy

Interdomain Interactions Control Ca2+-Dependent Potentiation in the Cation Channel TRPV4

Several Ca2+-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca2+-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca2+-dependent facilitation of TRPV4. In the resting state, an intracellular domain from the channel N terminus forms an autoinhibitory complex with a C-terminal domain that includes a high-affinity CaM binding site. CaM binding, secondary to rises in intracellular Ca2+, displaces the N-terminal domain which may then form a homologous interaction with an identical domain from a second subunit. This represents a novel potentiation mechanism that may also be relevant in other Ca2+-permeable channels