Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Influence of episodic wind events on thermal stratification and bottom water hypoxia in a Great Lakes estuary

Hypoxia formation and breakdown were tracked during 2015 in Muskegon Lake estuary at multiple locations, and five years (2011–2015) of time-series buoy observatory data were evaluated for the effect of episodic wind-events on lake mixing. Bi-weekly water temperature and dissolved oxygen (DO) profiles at four locations revealed that hypoxia occurred at all sites and persisted for 2–3 months during summer 2015. On one date in late-summer, up to 24% of the lake’s volume was estimated to be mildly hypoxic (DO < 4 mg L^?1) as defined by lake sturgeon requirements. Patterns of wind speed and water column stability in late spring indicated that high winds and low stability delayed the onset of hypoxia while in late summer low winds and high stability delayed degradation of hypoxia. Wind speeds appear to play a great role in the interannual variability of stratification and subsequent hypoxia. Water temperature and DO profiles taken before and after one mid-summer mixing event (wind speed >7.7 m s^?1 for 10 h), indicated that while the wind was unable to completely mix the entire water column, it deepened the epilimnion by ～1.5 m and sheared a thin layer from the upper hypolimnion. By entraining internally loaded nutrients, such episodic wind-events may initiate and sustain algal blooms in nutrient limited surface waters. Quantifying the variable role of wind and mixing events will be key to integrating limnological processes into climate models of the future.     

Research on the overall architecture of Internet of Things middleware for intelligent industrial parks

With the continuous development of the Internet of Things technology and the proposal of “Made in China 2025”, the construction of IoT applicat     

不断增强RF功率测量

精确的RF功率管理是现代无线发射器的热点话题，从基站的功率放大器保护到移动应用中的延长电池使用时间，它都有很多的优点。RF功率监测器，比如对数放大器，允许RF功率测量系统在一个较宽的范围监控和动态调整发射功率。尽管近几年来功率监测的精度已经有了很大改进，但是对于像那些需要高功率发射的应用甚至受到0dB功率监测误差微小变化引起的显著影响。因此这也促使检测器性能不断提高。     

Patient characteristics, MRI examination, and dopaminergic drug response in clinical possible Parkinson''s disease

As hypersensitivity to natural rubber latex (NRL) has become an increasingly recognized problem in children, identification of all groups at risk seems important. In this study hypersensitivity to NRL was evaluated in 337 children with potential risk factors. We identified by questionnaire children's underlying diseases, history of surgical procedures, evidence of atopy and patient's history of NRL-specific reactions. Hypersensitivity to NRL and other allergens relevant in the Düsseldorf area was evaluated by skin prick test and specific IgE. In 9.2% of all children hypersensitivity to NRL was observed. Significant risk factors for hypersensitivity to NRL were, among the underlying diseases, spina bifida (odds ratio 29.2), hydrocephalus internus (10.1), gastrointestinal malformation (5.2) and atopy (2.2). Surgical procedures with significant risk were the implantation of a ventriculo-peritoneal shunt (15.7) and surgery of the gastrointestinal tract (3.1). Frequency of surgical procedures correlated (p < 0.001) with risk of hypersensitivity. Frequent surgery and atopy were found to have an additional effect on the risk of hypersensitivity. Information about previous NRL-specific reactions obtained by questionnaire was of little predictive value when performing multivariate analysis. For children at high risk for hypersensitivity to NRL preoperative evaluation and, in case of hypersensitivity, preventive measures seem to be advised.     

Synthesis of Hexp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O) (CH2)7 CH3 probes for exploration of the substrate specificity of glycosyltransferases: Part II, Hex = 3-O-methyl-beta-D-Gal, 3-deoxy-beta-D-Gal, 3-deoxy-3-fluoro-beta-D-Gal, 3-amino-3-deoxy-beta-D-Gal, beta-D-Gul, alpha-L-Alt, or beta-L-Gal

Seven analogues of the trisaccharide beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH 2)7CH3 have been synthesized as potential substrates for glycosyltransferases involved in the chain-termination of N-acetyllactosamine-type N-glycans. These compounds include: 3-O-methyl-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp -(1-->O) (CH2)7CH3, 3-deoxy-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1 -->O) (CH2)7CH3, 3-deoxy-3-fluoro-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-M anp- (1-->O)(CH2)7Ch3, 3-amino-3-deoxy-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Ma np- (1-->O)(CH2)7CH3, beta-D-Gulp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-- >O)(CH2)7CH3, beta-L-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH 2)7CH3, and alpha-L-Altp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1- ->O) (CH2)7CH3. All trisaccharides were obtained by condensation of suitably modified glycosyl donors based on imidates or thioglycosides with the same disaccharide acceptor, octyl 3,4,6-tri-O-benzyl-2-O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D- glucopyranosyl)-alpha-D-mannopyranoside, followed by deprotection.     

Cerebrovascular effects of analgosedation

The in vitro drug sensitivity of three dihydrofolate reductase inhibitors (pyrimethamine, cycloguanil, trimethoprim) was determined against 29 strains and isolates of Plasmodium falciparum by an isotopic semi-microtest. Trimethoprim is less active than pyrimethamine or cycloguanil and its activity is correlated with that of two other inhibitors, suggesting cross-resistance in vitro among the dihydrofolate reductase inhibitors.     

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.