Miracle-dz/UniFAR-FTUs huggingface dataset:
Unusual temperature dependence in the cis/trans-oxetane formation discloses competitive syn versus anti attack for the Paternò-Büchi reaction of triplet-excited ketones with cis- and trans-cylooctenes. Conformational control of diastereoselectivity in the cyclization and cleavage of preoxetane dirad

Toluene-d(8) solutions of cis- and trans-cyclooctene (cis- and trans-1a) as well as (Z)- and (E)-1-methylcyclooctene (cis- and trans-1b) have been irradiated at temperatures between -95 and +110 degrees C in the presence of benzophenone (BP) to afford mixtures of the cis- and trans-configured oxetanes 2a,b and the regioisomeric 2b'. Correspondingly, benzoquinone (BQ) gave with cis- and trans-1a the cycloadducts cis- and trans-3a. The cis/trans diastereomeric ratios of the [2 + 2]-cycloadducts 2 and 3 display a strong temperature dependence; with cis- and trans-1a or cis-1b as starting materials, the diastereoselectivity of the oxetane formation is high at low temperature, under preservation of the initial cyclooctene configuration. With increasing temperature, the cis diastereoselectivity decreases continuously for the cis-cyclooctenes; in the case of the cis-1a, the diastereoselectivity is even switched to trans (cis/trans ca. 20:80) at very high temperatures. For the strained trans-1a, the trans-oxetanes are strongly preferred over the entire temperature range, with only minor leakage (up to 10%) to the cis-oxetanes at very high temperatures. Oxetane formation is accompanied by nonthermal trans-to-cis isomerization of the cyclooctene. The methyl-substituted trans-1b constitutes an exceptional substrate; it displays cis diastereoselectivity in the [2 + 2] photocycloaddition at low temperatures for both regioisomers 2b and 2b', and the trans selectivity increases at moderate temperature (cis/trans = 4:96), to decrease again at high temperature, especially for the minor regioisomer 2b'. This complex temperature behavior of the cis/trans diastereoselectivity may be rationalized in terms of the triplet-diradical mechanism of the Paternò-Büchi reaction. We propose that the cyclooctene may be competitively attacked by the triplet-excited ketone from the higher (syn) or the less (anti) substituted side; such syn and anti trajectories have hitherto not been considered. To account for the unusual temperature behavior in the diastereoselectivity of the present [2 + 2] photocycloaddition, we suggest that temperature-dependent conformational changes of the resulting triplet preoxetane diradicals compete with their cyclization to the cis/trans-oxetane diastereomers and retro cleavage to the cis-cyclooctene.
α‐Adrenoceptor Influence on Plasma Levels of Neuropeptide Y‐Like Immunoreactivity and Catecholamines During Rest and Sympathoadrenal Activation in Humans

Antecubital venous plasma neuropeptide Y-like immunoreactivity (NPY-LI) and catecholamines were analyzed in six healthy, volunteers performing a graded bicycle exercise without medication and after acute administration of clonidine, phentolamine, and nifedipine. During the control exercise, plasma noradrenaline (NA), adrenaline (A), and NPY-LI increased to 17-, 7-, and 3-fold the resting values, respectively, at a maximal workload. Clonidine (300 μg p.o.) reduced resting and exercising heart rate (HR) and systolic blood pressure (SBP). Plasma NA at rest decreased and NA, A, and NPY-LI were 40–60% lower during the exercise after clonidine compared to the control. Phentolamine (0.07 mg × kg−1 every 10 min i.v.) and nifedipine (20 mg p.o.) increased HR and reduced SBP during the exercise. Plasma NA at rest was elevated threefold and the exercise-induced increases in NA and A were also enhanced after phentolamine. Plasma NPY-LI at rest was unchanged by phentolamine, while it was increased fivefold, as compared to the control, at the highest workload. Nifedipine slightly enhanced plasma NA and NPY-LI but not A during exercise. It is suggested that NPY is released mainly at high levels of sympathetic activity and that blood-pressure-lowering drugs acting on α adrenoceptors acutely influence the release of both NA and NPY-LI from sympathetic nerves in humans.
Small intestinal bacterial overgrowth in patients with irritable bowel syndrome

Background: Small intestinal bacterial overgrowth (SIBO) has been proposed to be common in irritable bowel syndrome (IBS), with altered small-bowel motility as a possible predisposing factor. Aim: To assess the prevalence of SIBO, by culture of small-bowel aspirate, and its correlation to symptoms and motility in IBS. Methods: 162 patients with IBS who underwent small-bowel manometry and culture of jejunal aspirate were included. Cultures from 26 healthy subjects served as controls. Two definitions of altered flora were used: the standard definition of SIBO (⩾105 colonic bacteria/ml), and mildly increased counts of small-bowel bacteria (⩾95th centile in controls). Results: SIBO (as per standard definition) was found in 4% of both patients and controls. Signs of enteric dysmotility were seen in 86% of patients with SIBO and in 39% of patients without SIBO (p = 0.02). Patients with SIBO had fewer phase III activities (activity fronts) than patients without SIBO (p = 0.08), but otherwise no differences in motility parameters were seen. Mildly increased bacterial counts (⩾5×103/ml) were more common in patients with IBS than in controls (43% vs 12%; p = 0.002), but this was unrelated to small intestinal motility. No correlation between bacterial alterations and symptom pattern was observed. Conclusions: The data do not support an important role for SIBO according to commonly used clinical definitions, in IBS. However, mildly increased counts of small-bowel bacteria seem to be more common in IBS, and needs further investigation. Motility alterations could not reliably predict altered small-bowel bacterial flora.
Multifocal motor neuropathy improved by IVIg

Objective: To determine the effect of IV immunoglobulin (IVIg) on neurologic function and electrophysiologic studies in multifocal motor neuropathy with conduction block (MMN). Background: MMN is characterized by progressive, asymmetric, lower motor neuron weakness and is probably immune-mediated. IVIg treatment has been shown to have beneficial effects in several open-label studies and in one small controlled trial. However, larger randomized controlled studies are lacking. Methods: The authors recruited 16 patients with MMN. All subjects were given each of two treatments (IVIg [0.4 g/kg/d for 5 consecutive days] or placebo [dextrose or saline]) that were assigned according to a randomized, crossover design under double-blind conditions. Patients were evaluated before and about 28 days after trial treatment for subjective functional improvement, neurologic disability score, grip strength, distal and proximal compound muscle action potential amplitude, and conduction block. Results: Subjective functional improvement with IVIg treatment was rated as dramatic or very good in nine patients, moderate in one, mild in one, and absent in five patients. This improvement was absent after placebo. The neurologic disability score improved by 6.7 ± 3.3 points with IVIg treatment, whereas it decreased by 2.1 ± 3.0 with placebo (p = 0.038). Grip strength on the weaker side was increased by 6.4 ±1.9 kg with IVIg treatment; it decreased by 1.0 ± 0.8 kg with placebo (p = 0.0021). Conduction block worsened by 12.98 ± 6.52 % with placebo, but improved by 12.68 ± 5.62 % with IVIg treatment (p = 0.037). Conduction block was reversed in five patients with IVIg but not placebo. Conclusion: IVIg improved conduction block as well as subjective and objective clinical measures of function in patients with MMN.
Overcoming body obstruction for robust data communication in wireless body sensor networks by placing relay nodes

The primary requirement for a wireless body sensor networks (WBSN) is to collect data with a high sampling rate from on-body wireless sensors, and yet transmit the data with very low power radio. The problem is that the body can easily obstruct the transmission of low-power radio signals, thereby significantly reducing the success rate of data communication from the sensor nodes to the sinks. In this paper, we propose a novel relay node placement scheme for preserving network connectivity, and therefore enhance the success rate of data communication. We empirically evaluate our approach using a wearable sensor platform to show the improvements in packet success rates. Our experiments show that in most cases the average improvement can reach 34.74 %.
The deformation time series prediction based on wavelet and neural network

In the paper, the research present situation and development in the wavelet neural network model and a novel learning algorithm for wavelet neural network based on extended Kalman filter are discussed. Based on combining the exceptional property of localization of the wavelet transform and characteristics of self-learning of neural networks, the non-line time series model and network architecture model which combines affine transform with revolving transform is discussed. A novel learning algorithm for wavelet neural network based on extended Kalman filter is proposed to predict the deformation of structure. In comparison with the WNN algorithm, the EKF learning algorithm has improved convergence and can provide much more accuracy learning results.
Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer

Background: Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors involved in genetic control of many cellular processes. PPAR and PPAR have been implicated in colonic malignancy. Here we provide three lines of evidence suggesting an inhibitory role for PPAR in colorectal cancer development. Methods: Levels of PPAR mRNA and protein in human colorectal cancers were compared with matched non-malignant mucosa using RNAse protection and western blotting. APCMin/+ mice were randomised to receive the PPAR activator methylclofenapate 25 mg/kg or vehicle for up to 16 weeks, and small and large intestinal polyps were quantified by image analysis. The effect of methylclofenapate on serum stimulated mitogenesis (thymidine incorporation), linear cell growth, and annexin V and propidium iodide staining were assessed in human colonic epithelial cells. Results: PPAR (mRNA and protein) expression levels were significantly depressed in colorectal cancer compared with matched non-malignant tissue. Methylclofenapate reduced polyp area in the small intestine from 18.7 mm2 (median (interquartile range 11.1, 26.8)) to 9.90 (4.88, 13.21) mm2 (p=0.003) and in the colon from 9.15 (6.31, 10.5) mm2 to 3.71 (2.71, 5.99) mm2 (p=0.009). Methylclofenapate significantly reduced thymidine incorporation and linear cell growth with no effect on annexin V or propidium iodide staining. Conclusions: PPAR may inhibit colorectal tumour progression, possibly via inhibition of proliferation, and may be an important therapeutic target.
Oligodeoxynucleotide Studies in Primates: Antisense and Immune Stimulatory Indications

Antisense oligodeoxynucleotide compounds (AS ODN) are being developed as therapeutics for various disease indications. Their safety and pharmacokinetics are most commonly evaluated in rodents and nonhuman primates. Traditional AS ODN are short, single strands of DNA, and they target specific mRNA sequences. Plasma clearance of AS ODN is rapid, broad tissue distribution occurs, and elimination is by nuclease metabolism. Structural modifications to AS ODN have been made to enhance their efficacy and improve their safety. A number of class effects are observed with AS ODN that are unrelated to the specific targeted mRNA sequence. Acute effects include activation of the alternative complement pathway and inhibition of the intrinsic coagulation pathway. In monkeys, rodents, and dogs given repeated doses of AS ODN, accumulation of AS ODN and/or metabolites occurs in the form of basophilic granules in various tissues, including the kidney, lymph nodes and liver. A new potential therapeutic application of ODN is that of immune stimulation. Immunostimulatory ODN (IS ODN) are being investigated for use in treating cancer, infectious disease, and allergy. For the development of both AS and IS ODN, primates will continue to be important for safety assessment.
Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity Published, JLR Papers in Press, June 1, 2004. DOI 10.1194/jlr.M300522-JLR200

The roles of polymorphisms of the sitosterolemia genes ABCG5 and ABCG8 in the regulation of cholesterol metabolism and insulin sensitivity were studied in mildly hypercholesterolemic noncoronary subjects (n = 263, 144 men and 119 women) divided into tertiles by baseline serum cholestanol-to-cholesterol ratio (≤118.3 and ≥147.7 102 × mmol/mol cholesterol), a surrogate marker of cholesterol absorption efficiency. The lowest cholestanol tertile was associated with high body mass index (BMI), plasma glucose, serum insulin and triglycerides, and cholesterol synthesis markers (cholestenol, desmosterol, lathosterol) and low HDL cholesterol and cholesterol absorption markers (campesterol, sitosterol) (P <0.01 for all). The 19H allele of the ABCG8 gene accumulated in the lowest cholestanol tertile (P < 0.001) and was associated with low total and LDL cholesterol and absorption markers and with high synthesis markers (P < 0.05 for all). The 604E allele of the ABCG5 gene in men was associated with high BMI, plasma insulin, low serum sitosterol, and high serum cholestenol levels (P < 0.05 for all). In a subgroup of 71 men, the 604E allele was associated with insulin resistance measured with the hyperinsulinemic euglycemic clamp. In conclusion, low cholesterol absorption efficiency was associated with characteristics of the metabolic syndrome. Low serum cholesterol and cholesterol absorption were linked to the D19H polymorphism of the ABCG8 gene, and characteristics of the insulin resistance syndrome in men were linked with the Q604E polymorphism of the ABCG5 gene.
An Efficient Decomposition Method for the Integrated Dispatch of Generation and Load

In response to the computational challenges produced by the integrated dispatch of generation and load (IDGL), this paper proposes a novel and efficient decomposition method. The IDGL is formulated using the mixed-integer quadratic constrained programming (MIQCP) method. To efficiently solve this complex optimization problem, the nodal equivalent load shifting bidding curve (NELSBC) is proposed to represent the aggregated response characteristics of customers at a node. The IDGL is subsequently decomposed into a two-level optimization problem. At the upper level, grid operators optimize load shifting schedules based on the NELSBC of each node. Transmission losses are explicitly incorporated into the model to coordinate them with generating costs and load shifting costs. At the bottom level, customer load adjustments are optimized at individual nodes given the nodal load shifting requirement imposed by the grid operators. The key advantage of the proposed method is that the load shifting among different nodes can be coordinated via NELSBCs without iterations. The proposed decomposition method significantly improves the efficiency of the IDGL. Parallel computing techniques are utilized to accelerate the computations. Using numerical studies of IEEE 30-bus, 118-bus, and practically sized 300-bus systems, this study demonstrates that accurate and efficient IDGL scheduling results, which consider the nonlinear impact of transmission losses, can be achieved.
Detecting hybridization in African schistosome species: does egg morphology complement molecular species identification?

SUMMARY Hybrid parasites may have an increased transmission potential and higher virulence compared to their parental species. Consequently, hybrid detection is critical for disease control. Previous crossing experiments showed that hybrid schistosome eggs have distinct morphotypes. We therefore compared the performance of egg morphology with molecular markers with regard to detecting hybridization in schistosomes. We studied the morphology of 303 terminal-spined eggs, originating from 19 individuals inhabiting a hybrid zone with natural crosses between the human parasite Schistosoma haematobium and the livestock parasite Schistosoma bovis in Senegal. The egg sizes showed a high variability and ranged between 92·4 and 176·4 µm in length and between 35·7 and 93·0 µm in width. No distinct morphotypes were found and all eggs resembled, to varying extent, the typical S. haematobium egg type. However, molecular analyses on the same eggs clearly showed the presence of two distinct partial mitochondrial cox1 profiles, namely S. bovis and S. haematobium, and only a single nuclear ITS rDNA profile (S. haematobium). Therefore, in these particular crosses, egg morphology appears not a good indicator of hybrid ancestry. We conclude by discussing strengths and limitations of molecular methods to detect hybrids in the context of high-throughput screening of field samples.
Diagnosis of Diabetes Mellitus and Pre-Diabetes with Fasting Plasma Glucose, Oral Glucose Tolerance Test and A1c Level: A1c Based Screening May Be A Better Diagnostic Tool For Diabetes Mellitus

OBJECTIVE: The International Diabetes Federation estimates that 285 million people around the world have diabetes. The American Diabetes Association (ADA) has proposed hemoglobin A1C 6.5% (HbA1c) for the diagnosis of diabetes, and 5.7-6.4% as a risk factor for progression to diabetes. This new criterions accuracy is controversial and has not yet been adopted internationally. We aimed to clarify the power of A1C in diagnosis of diabetes and pre-diabetes.
Combined treatment with Ad-hTRAIL and DTIC or SAHA is associated with increased mitochondrial-mediated apoptosis in human melanoma cell lines.

BACKGROUND Currently, dacarbazine (DTIC) is the only approved systemic treatment for metastatic malignant melanoma. However, the modest treatment effect encourages studies on novel therapeutic molecules, delivery systems and combination therapies. Full-length TRAIL, delivered from an adenoviral vector (Ad-hTRAIL), was studied in combination with DTIC or the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in human melanoma cell lines. METHODS The cytotoxic potential of the combination treatments was assessed by cell viability measurements and CalcuSyn analysis. Involvement of apoptosis was analyzed by TUNEL staining, mitochondrial membrane potential measurements, and activation and expression levels of caspases and other mediators of apoptosis. RESULTS Ad-hTRAIL in combination with DTIC or SAHA resulted in additive or synergistic growth inhibition compared to each treatment used as single agent. Both combinations augmented apoptosis, which was mediated through the death receptor (DR) pathway by enhanced activation of caspase-8, and through increased loss of mitochondrial integrity. Provoked cleavage of Bid, which bridges the extrinsic and intrinsic apoptosis pathways, and downregulation of the anti-apoptotic mediators Bcl-X(L), Mcl-1 and XIAP (but not Bcl-2) were critical contributing factors. Increased levels of DR4 and DR5 were not a common underlying mechanism as DTIC did not affect the levels of either of the receptors. However, SAHA-induced expression of DR4 may have reduced the TRAIL resistance in the SKMEL-28 cell line. CONCLUSION Administration of Ad-hTRAIL in combination with DTIC or SAHA enhances apoptosis in human melanoma cell lines, and suggests that the therapeutic potential of such treatment strategies should be further evaluated for possible clinical use.
Partial Shading Analysis of Multistring PV Arrays and Derivation of Simplified MPP Expressions

In this paper, the electrical response of a partially shaded photovoltaic (PV) array, comprising several strings connected in parallel, is investigated. The PV array is simulated by employing an enhanced version of the widely used single-diode model, reformulated in an explicit manner employing the Lambert W function. The multiple maximum power points (MPPs) that appear on the P-V characteristic of the array in partial shading conditions are analyzed, in terms of their number and properties. Simplified empirical expressions are then derived to calculate the voltage, current, and power for each local MPP, at any irradiance level and temperature, using only datasheet information, in a most simple and straightforward manner, without resorting to detailed modeling and simulations. The derived formulae are validated using both simulation and experimental results.
Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome.

The impact of weight reduction on metabolic, endocrine, and anthropometric variables was studied in 13 obese, insulin-resistant women with the polycystic ovary syndrome (PCOS). Insulin sensitivity (euglycemic insulin clamp), insulin secretion and glucose tolerance (iv glucose tolerance test), basal sex steroid hormones, gonadotropins and free fatty acids (FFA), skin folds and waist hip ratio (WHR) were evaluated before (PCO-BD) and after (PCO-AD) diet-induced weight reduction to a weight stable level [mean (SD) diet duration 14.9 (6.2) months]. Mean weight loss was 12.4 kg (4.7; P < 0.0001), equalling a reduction from a body mass index (BMI) of 32.2 (3.7) kg/m2 to 27.6 (3.7; P < 0.0001) kg/m2. The results were compared with those of two groups of weight stable (no diet) women, 21 with PCOS (PCO-ND) and 23 normal control subjects (C), who were matched to the BMI the diet group reached after weight loss. Insulin sensitivity index (M/I) improved on average 132% (P < 0.001) and plasma FFA by 32% (P < 0.01), serum sex hormone binding globulin levels increased by 35% (P < 0.01), and the sum of truncal-abdominal skin-folds (subscapular, umbilical, and suprailiacal) were reduced by 28% (P < 0.0001), whereas the early insulin response to iv glucose, the levels of gonadotropins and androstenedione, and the femoral sc fat did not change significantly with weight loss. M/I, levels of SHBG and FFA and truncal-abdominal fat reached levels similar to the controls, whereas PCO-ND had lower M/I (P < 0.01) and SHBG levels (P < 0.0001), greater concentrations of FFA (P < 0.01) and truncal-abdominal fat (P < 0.05) than C. Among women with normal glucose tolerance, the insulin increment was higher in both PCO-AD (P < 0.05) and PCO-ND (P < 0.01) than in C. There was a strong correlation between M/I and sum of truncal-abdominal skinfolds in all groups (PCO-BD: r = 0.82; P < 0.001, PCO-AD: r = 0.68; P < 0.05, PCO-ND: r = 0.81; P < 0.0001, C: r = 0.44; P < 0.05). The variation in M/I in PCO-AD and PCO-ND (pooled) was best explained by FFA and truncal-adbominal fat (model R2 = 0.67). In conclusion, insulin resistance in obese women with PCOS was reduced by weight loss to similar levels as BMI-matched control subjects, suggesting that insulin resistance in PCOS is not a feature of PCOS per se. (ABSTRACT TRUNCATED AT 400 WORDS)
The Impact of Geography Boundary-Spanning Search on Product Innovation

Geography boundary-spanning search is the focus of current research. Researchers have a debate on the relationship between geography boundary-spanning search and product innovation. To address this controversy, this paper suggests that the relationship between the geography boundary-spanning search and product innovation is not linear, but follows a u-shaped pattern. Meanwhile this relationship is moderated by external market environment.Using an original data set of 270 manufacturing firms in China, we find that:(1) The relationship between geography boundary-spanning search and innovation follows a u-shaped pattern;(2) Industry growth negatively moderates this relationship, whereas the moderating role of industry competition intensity is not significant.