Miracle-dz/UniFAR-FTUs huggingface dataset:
A Rational Approach to Radiological Screening in Von Hippel-Lindau Disease

Objectives— To optimise radiological screening in von Hippel-Lindau disease (VHL) while minimising cost and morbidity. Methods— A model of VHL was based on retrospective studies, and Bayes's theorem used to calculate the probability of the gene's presence and the likelihood of further lesions in affected families. A six year follow up was conducted to test the validity of the model. Results— Follow up confirmed the accuracy and validity of the model. Posterior fossa haemangioblastomas occur in 79·2% of VHL cases, supratentorial, retinal and spinal haemangioblastomas in 6·9%, 42·8%, and 22·0%, phaeochromocytomas in 5·2%, and renal carcinomas in 14·5%. Population incidences are 1:15 700 live births (posterior fossa), 1:780 000 (supratentorial), and 1:116 000 (spinal). The birth rate of subjects with VHL is 1:43 000; new mutations occur in 1:178 000 live births. Penetrance is 90%; 40% present with multiple lesions and 6·4% die within two years after diagnosis. Conclusions— For most patients presenting with a VHL-type lesion, with sufficient clinical and pedigree data, the presence or absence of the VHL gene, and the probability of further lesions occurring, can be assessed with a high degree of accuracy using the method described in this paper. Those cases in the non-VHL group do not require long term radiological follow up, nor do their relatives require radiological screening. Subjects in the VHL group should be screened for renal carcinoma indefinitely from the age of 20 years, and all clinically unaffected relatives should be screened genetically for the VHL gene. (Those found negative for the gene do not require further screening, but those found positive should be screened.)
Land Suitability Modeling Using a Geographic Socio-Environmental Niche-Based Approach: A Case Study from Northeastern Thailand

Understanding the pattern–process relations of land use and land cover change is an important area of research that provides key insights into human–environment interactions. The suitability or likelihood of occurrence of land use such as agricultural crop types across a human-managed landscape is a central consideration. Recent advances in niche-based geographic species distribution models (SDMs) offer a novel approach to understanding land suitability and land use decisions. SDMs link species presence and location data with geospatial information and use machine learning algorithms to develop nonlinear and discontinuous species–environment relationships. Here, we apply the maximum entropy (MaxEnt) model for land suitability modeling by adapting niche theory to a human-managed landscape. In this article, we use data from an agricultural district in northeastern Thailand as a case study for examining the relationships among the natural, built, and social environments and the likelihood of crop choice for the commonly grown crops that occur in the Nang Rong District—cassava, heavy rice, and jasmine rice, as well as an emerging crop, fruit trees. Our results indicate that although the natural environment (e.g., elevation and soils) is often the dominant factor in crop likelihood, the likelihood is also influenced by household characteristics, such as household assets and conditions of the neighborhood or built environment. Furthermore, the shape of the land use–environment curves illustrates the noncontinuous and nonlinear nature of these relationships. This approach demonstrates a novel method of understanding nonlinear relationships between land and people. The article concludes with a proposed method for integrating the niche-based rules of land use allocation into a dynamic land use model that can address both allocation and quantity of agricultural crops.
Preventative Effects of Ginkgo biloba Extract (EGb761) on High Glucose‐Cultured Opacity of Rat Lens

Diabetic cataract is one of the earliest secondary complications of diabetes, and it is characterized by opacification of the eye lens. In this study, we examined the protective effects of Ginkgo biloba extract (EGb761) on rat lenses cultured in high‐glucose conditions. The cultured rat lenses were divided into six groups: normal group, high‐glucose group, high glucose plus low, medium, and high concentrations of EGb761 groups, and a high glucose plus bendazac lysine group. The activities of antioxidases, aldose reductase, advanced glycosylation end products, transforming growth factor‐β2, Smad2/3, E‐cadherin, and α‐smooth muscle actin were assessed by different methods. Compared with the levels in the high glucose group, EGb761 decreased the intensity of oxidative stress, decreased aldose reductase activation and the level of advanced glycosylation end products, and suppress the transforming growth factor‐β2 or Smad pathway activation, further increase the expression of E‐cadherin and decrease α‐smooth muscle actin, and therefore, prevents the pathological changes of high glucose‐induced lens epithelial cells and ameliorated lens opacity. These results suggest that EGb761 has protective effects on several pharmacological targets in the progress of diabetic cataract and is a potential drug for the prevention of diabetic cataract. Copyright © 2013 John Wiley & Sons, Ltd.
Does stretching induce lasting increases in joint ROM? A systematic review.

BACKGROUND AND PURPOSE Stretching (that is, interventions that apply tension to soft tissues) induces increases in the extensibility of soft tissues, and is therefore widely administered to increase joint mobility and reverse contractures. However, it is not clear whether the effects of stretching are lasting. A systematic review was conducted to determine if stretching (either self-administered, administered manually by therapists or by some external device such as a splint) produces lasting increases in the mobility of joints not directly affected by surgery, trauma or disease processes. METHOD In order to determine the lasting effects of stretching, only studies that measured joint range of motion (ROM) at least one day after the cessation of stretching were included. MEDLINE (from 1966 to June 2000), EMBASE (from 1988 to June 2000), the Cochrane Controlled Trials Register and PEDro databases were searched, and citation tracking was used to identify randomized studies that met the inclusion criteria. Each study was rated by two independent assessors on the PEDro scale, which rated trials according to criteria such as concealed allocation, blinding and intention-to-treat analysis. RESULTS Thirteen studies satisfied the inclusion criteria. All examined the effect of stretching (median number of stretch sessions = eight) on joint ROM in healthy subjects without functionally significant contractures. Four studies were of 'moderate' quality and the remaining nine were of 'poor' quality. The 'moderate' quality studies suggest that regular stretching increases joint ROM (mean increase in ROM = 8 degrees; 95% CI 6 degrees to 9 degrees) for more than one day after cessation of stretching and possibly that the effects of stretching are greater in muscle groups with limited extensibility. CONCLUSIONS The results of four 'moderate' quality studies show a convincing effect of stretching in people without functionally significant contracture. These findings require verification with high-quality studies. Lasting effects of intensive stretching programmes (for example, stretching applied for more than six weeks or for more than 20 minutes a day) or of stretching on people with functionally significant contracture have not yet been investigated with randomized studies.
Ovarian follicular dominance in cattle: relationship between prolonged growth of the ovulatory follicle and endocrine parameters.

In cattle, the development of ovarian follicles 5 mm or larger occurs in either two or three consecutive follicular waves per estrous cycle. When the luteal phase is artificially lengthened with an intravaginal progesterone-releasing device (CIDR) that maintains subluteal levels (i.e. levels of progesterone that are below normal luteal levels, but higher than basal follicular phase levels), prolonged development of the ovulatory follicle is observed. To study the endocrinological correlates of prolonged follicular dominance and to test the hypothesis that it is mediated by effects of plasma progesterone on LH pulse frequency, heifers (n = 6/group) were treated with blank CIDRs (no progesterone, control group), with one CIDR for 14 days from day 14 of the cycle (1 CIDR group), or with one CIDR for 14 days from day 14 plus a second CIDR during days 24-28 (2 CIDR group). Cycle length was significantly longer in the 1 and 2 CIDR groups than in the controls (30.2 +/- 0.2 and 31.8 +/- 0.5 vs. 21.6 +/- 0.4 days, respectively; P < 0.0001). Follicular dynamics were normal in the control heifers. In the 1 CIDR group, the ovulatory follicle grew larger than in control or 2 CIDR animals, was maintained as the largest follicle on the ovaries for a much longer time, and ovulated after CIDR removal. In the 2 CIDR group, a similar growth pattern was observed until day 24; after insertion of a second CIDR, however, prolonged dominance was reversed, a new wave was recruited, and the dominant follicle of this wave ovulated after CIDR removal. The size of the ovulatory follicle and the length of the dominance phase in the 2 CIDR group were similar to those in control animals. Reversal of prolonged dominance in the 2 CIDR group was associated with changes in progesterone. Progesterone remained at subluteal levels (1.5-2.3 ng/ml) in both CIDR groups until day 24, when insertion of the second CIDR in the 2 CIDR group restored progesterone concentrations to normal luteal levels (3.5-6 ng/ml). Pulsatile LH secretion was assessed by frequent blood sampling every 12 min for 6 h (0800-1400 h) on selected days of the treatment cycle. LH pulse frequency was not different among groups before treatment started (days 12 and 13). However, LH pulse frequency was significantly higher in the 1 CIDR than in the 2 CIDR group on both day 26 (P < 0.03) and day 28 (P < 0.05), i.e. during the reversal of prolonged dominance in the 2 CIDR group. (ABSTRACT TRUNCATED AT 400 WORDS)
Large serine recombinase domain structure and attachment site binding

Abstract Large serine recombinases (LSRs) catalyze the movement of DNA elements into and out of bacterial chromosomes using site-specific recombination between short DNA “attachment sites”. The LSRs that function as bacteriophage integrases carry out integration between attachment sites in the phage (attP) and in the host (attB). This process is highly directional; the reverse excision reaction between the product attL and attR sites does not occur in the absence of a phage-encoded recombination directionality factor, nor does recombination typically occur between other pairings of attachment sites. Although the mechanics of strand exchange are reasonably well understood through studies of the closely related resolvase and invertase serine recombinases, many of the fundamental aspects of the LSR reactions have until recently remained poorly understood on a structural level. In this review, we discuss the results of several years worth of biochemical and molecular genetic studies of LSRs in light of recently described structural models of LSR–DNA complexes. The focus is understanding LSR domain structure, how LSRs bind to the attP and attB attachment sites, and the differences between attP-binding and attB-binding modes. The simplicity, site-selectivity and strong directionality of the LSRs has led to their use as important tools in a number of genetic engineering applications in a wide variety of organisms. Given the important potential role of LSR enzymes in genetic engineering and gene therapy, understanding the structure and DNA-binding properties of LSRs is of fundamental importance for those seeking to enhance or alter specificity and functionality in these systems.
Consequences of anthelmintic resistance on liveweight gain of lambs on commercial sheep farms

Abstract AIM: To assess the consequences of anthelmintic resistance on commercial sheep farms on liveweight (LW) gains and susceptibility to diarrhoea of growing lambs. METHODS: Five farms with a history of resistance to benzimidazole drenches were selected. On each farm, 150 ewe lambs were randomly allocated to 1 of 3 treatment groups (n=50). Group 1 was treated 5 times at 28-day intervals with oxfendazole (to which nematode resistance had been demonstrated); Group 2 was treated 5 times at 28-day intervals with levamisole or levamisole + oxfendazole (to which nematode resistance had not been demonstrated) and; Group 3 was treated with a combination of slow-release albendazole capsules and oral moxidectin (intended to totally suppress nematode infection). Differentiated faecal egg counts (FECs), FEC reduction tests (FECRT), LW gain and degree of faecal soiling around the breech (dag scores) were determined and compared between groups. RESULTS: Pre-treatment FECs in Group 1 were similar to or slightly lower than those of Group 2. Efficacy of oxfendazole in Group 1 varied between farms and over time within farms, the reduction in FECs after treatment varying from 0 % to >95 %. The genera identified as resistant on each farm also varied over time. Lambs from Group 3 had lower FECs, lower dag scores and higher growth rates than lambs from Group 2, which in turn had higher LW gains than lambs from Group 1. The overall LW gains during the 5 months of the study were 7.03 ±0.27 kg for Group 1,8.33 ±0.27 kg for Group 2, and 9.91 ±0.31 kg for Group 3 (mean ±SEM; means differed significantly from each other, p<0.01). CONCLUSIONS: The decrease in growth rates associated with the continued use of an incompletely effective anthelmintic were surprisingly small in situations where all lambs grazed together.
Cloning of a Third Mammalian Na+-Ca2+ Exchanger, NCX3*

NCX3 is the third isoform of a mammalian Na+-Ca2+ exchanger to be cloned. NCX3 was identified from rat brain cDNA by polymerase chain reaction (PCR) using degenerate primers derived from the sequences of two conserved regions of NCX1 and NCX2. The NCX3 PCR product was used to isolate two overlapping clones totalling 4.8 kilobases (kb) from a rat brain cDNA library. The overlapping clones were sequenced and joined at a unique Bsp106I restriction enzyme site to form a full-length cDNA clone. The NCX3 cDNA clone has an open reading frame of 2.8 kb encoding a protein of 927 amino acids. At the amino acid level, NCX3 shares 73% identity with NCX1 and 75% identity with NCX2 and is predicted to share the same membrane topology as NCX1 and NCX2. Following addition of a poly(A)+ tail to the NCX3 clone, exchanger activity could be expressed in Xenopus oocytes. NCX3 was also expressed in the mammalian BHK cell line. NCX3 transcripts are 6 kb in size and are highly restricted to brain and skeletal muscle. Linkage analysis in the mouse indicated that the NCX family of genes is dispersed, since the NCX1, NCX2, and NCX3 genes mapped to mouse chromosomes 17, 7, and 12, respectively.
Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates.

OBJECTIVE The purpose of this study was to examine the relationship between behavior and serotonin in nonhuman primates. METHOD During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Blood samples (N = 23) and CSF samples (N = 22) were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. RESULTS CSF 5-hydroxyindoleacetic acid (5-HIAA) concentration was positively correlated with three measures of sociality: 1) total time spent grooming others, 2) total time spent in close proximity to other group members, and 3) mean number of neighbors within a 5-m radius. In addition, CSF 5-HIAA concentration was positively correlated with age at emigration from the natal group (in months). CONCLUSIONS In adolescent male rhesus macaques living in naturalistic settings, CSF 5-HIAA concentration is positively correlated with affiliative sociality. Rhesus males with low CSF 5-HIAA concentrations exhibit less social competence and emigrate from their social groups at a younger age than do males with higher concentrations of CSF 5-HIAA.
Reconstitution of abscisic acid activation of SLAC1 anion channel by CPK6 and OST1 kinases and branched ABI1 PP2C phosphatase action

The plant hormone abscisic acid (ABA) is produced in response to abiotic stresses and mediates stomatal closure in response to drought via recently identified ABA receptors (pyrabactin resistance/regulatory component of ABA receptor; PYR/RCAR). SLAC1 encodes a central guard cell S-type anion channel that mediates ABA-induced stomatal closure. Coexpression of the calcium-dependent protein kinase 21 (CPK21), CPK23, or the Open Stomata 1 kinase (OST1) activates SLAC1 anion currents. However, reconstitution of ABA activation of any plant ion channel has not yet been attained. Whether the known core ABA signaling components are sufficient for ABA activation of SLAC1 anion channels or whether additional components are required remains unknown. The Ca2+-dependent protein kinase CPK6 is known to function in vivo in ABA-induced stomatal closure. Here we show that CPK6 robustly activates SLAC1-mediated currents and phosphorylates the SLAC1 N terminus. A phosphorylation site (S59) in SLAC1, crucial for CPK6 activation, was identified. The group A PP2Cs ABI1, ABI2, and PP2CA down-regulated CPK6-mediated SLAC1 activity in oocytes. Unexpectedly, ABI1 directly dephosphorylated the N terminus of SLAC1, indicating an alternate branched early ABA signaling core in which ABI1 targets SLAC1 directly (down-regulation). Furthermore, here we have successfully reconstituted ABA-induced activation of SLAC1 channels in oocytes using the ABA receptor pyrabactin resistant 1 (PYR1) and PP2C phosphatases with two alternate signaling cores including either CPK6 or OST1. Point mutations in ABI1 disrupting PYR1–ABI1 interaction abolished ABA signal transduction. Moreover, by addition of CPK6, a functional ABA signal transduction core from ABA receptors to ion channel activation was reconstituted without a SnRK2 kinase.
Realizability for constructive theory of functions and classes and its application to program synthesis

This paper gives a q-realizability interpretation for Feferman's constructive theory T/sub 0/ of functions and classes by using a set completion program without doubling variables, and proves its soundness. This result solves an open problem proposed by Feferman in 1979. Moreover by using this interpretation we can prove a program extraction theorem for T/sub 0/, which enables us to use constructive sets of T/sub 0/ for program synthesis.
Paroxysmal inhibitory potentials mediated by GABAB receptors in partially disinhibited rat hippocampal slice cultures.

1. Intracellular recording techniques were used to study synaptic potentials in CA3 pyramidal cells elicited with mossy fibre stimulation in partially disinhibited hippocampal slice cultures. Two experimental protocols were used: (1) high concentrations (20‐40 microM) of the A‐type gamma‐aminobutyric acid (GABAA) receptor antagonist bicuculline plus low concentrations (2‐4 microM) of the glutamate receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), or (2) low concentrations (1‐2.5 microM) of bicuculline alone. 2. Under the first condition, stimulation of mossy fibre afferents evoked epileptic bursts alternating with a response consisting of an excitatory postsynaptic potential (EPSP) followed by an unusually large and long‐lasting hyperpolarizing potential with a maximal amplitude in the range of ‐30 mV from the resting membrane potential. 3. This paroxysmal inhibitory potential (PIP) had a reversal potential near that of potassium. The amplitude of the PIP was not dependent on action potentials superimposed on the preceding EPSP, and was present in cells recorded with microelectrodes containing the Ca2+ chelator EGTA. These data suggest that the PIP is not a Ca(2+)‐activated K+ potential. 4. The PIP was prolonged by the GABA‐uptake blocker nipecotic acid, was reduced by hyperpolarizing interneurons with the opioid agonist FK 33‐824, and was abolished by the GABAB‐receptor antagonist CGP 35 348. These data indicate that the PIP is mediated by the activation of GABAB receptors following GABA release from interneurons. 5. The NMDA‐receptor antagonist D‐2‐amino‐5‐phosphonovalerate (D‐APV) strongly reduced the amplitude of the PIP, but had no effect on the GABAB receptor‐mediated inhibitory postsynaptic potential (IPSP) under control conditions. 6. Under the first condition, regular stimulation elicited a cyclical pattern of evoked responses. There was either an alternation between an epileptic burst and a PIP or, at shorter interstimulus intervals, a sequence of gradually increasing PIPs followed by an epileptic burst, which then reset the cycle. 7. Under the second condition, in low concentrations of bicuculline alone, the early GABAA‐mediated IPSP was little affected, but the late GABAB‐mediated IPSP was greatly enhanced. These enhanced late IPSPs were comparable in amplitude and duration to the PIPs seen under the first conditions, could exhibit cyclical behaviour, and were reduced by D‐APV. 8. Application of CGP 35 348 abolished the late IPSP under control conditions, but had no effect on hippocampal excitability. In contrast, CGP 35 348 blocked the PIP elicited in low bicuculline, and consequently led to intense epileptic discharge. (ABSTRACT TRUNCATED AT 400 WORDS)
Psychiatric comorbidity following traumatic brain injury

Primary objective: Survivors of traumatic brain injury (TBI) are at increased risk for development of severe, long-term psychiatric disorders. However, the aetiology of these disorders remains unclear. This article systematically reviews the most current prevalence rates and evidence for causality, in terms of established criteria. Main outcome and results: Psychiatric syndromes are consistently present at an elevated rate following TBI. Survivors of TBI are particularly susceptible to major depression, generalized anxiety disorder and post-traumatic stress disorder. Evidence for a biological gradient is generally lacking, although this criterion may not be appropriate in the case of TBI. The temporal pattern of onset is variable and reliable critical periods for the post-injury development of a psychiatric disorder remain to be identified; however, individuals appear to remain at risk for years following injury. Conclusions: Non-organic factors, including pre-morbid personality traits and post-injury psychological reactions to disability and trauma, are implicated in the generation and maintenance of post-TBI psychiatric disorder. There remains insufficient evidence to conclude what role the neuropathological consequences of TBI play in the development of post-TBI psychiatric disorder.