Wernicke’s aphasia reflects a combination of acoustic-phonological and semantic control deficits: A case-series comparison of Wernicke’s aphasia, semantic dementia and semantic aphasia

Wernicke’s aphasia (WA) is the classical neurological model of comprehension impairment and, as a result, the posterior temporal lobe is assumed to be critical to semantic cognition. This conclusion is potentially confused by (a) the existence of patient groups with semantic impairment following damage to other brain regions (semantic dementia and semantic aphasia) and (b) an ongoing debate about the underlying causes of comprehension impairment in WA. By directly comparing these three patient groups for the first time, we demonstrate that the comprehension impairment in Wernicke’s aphasia is best accounted for by dual deficits in acoustic-phonological analysis (associated with pSTG) and semantic cognition (associated with pMTG and angular gyrus). The WA group were impaired on both nonverbal and verbal comprehension assessments consistent with a generalised semantic impairment. This semantic deficit was most similar in nature to that of the semantic aphasia group suggestive of a disruption to semantic control processes. In addition, only the WA group showed a strong effect of input modality on comprehension, with accuracy decreasing considerably as acoustic-phonological requirements increased. These results deviate from traditional accounts which emphasise a single impairment and, instead, implicate two deficits underlying the comprehension disorder in WA.

Isolation from a sheep of an attaching and effacing Escherichia coli O115:H- with a novel combination of virulence factors

Attaching and effacing (AE) lesions were observed in the caecum, proximal colon and rectum of one of four lambs experimentally inoculated at 6 weeks. of age with Escherichia coli O157:H7. However, the attached bacteria did not immunostain with O157-specific antiserum. Subsequent bacteriological analysis of samples from this animal yielded two E. coli O115:H- strains, one from the colon (CO) and one from the rectum (RC), and those bacteria forming the AE lesions were shown to be of the O115 serogroup by immunostaining. The O115:H(-)isolates formed microcolonies and attaching and effacing lesions, as demonstrated by the fluorescence actin staining test, on HEp-2 tissue culture cells. Both isolates were confirmed by PCR to encode the epsilon (epsilon) subtype of intimin. Supernates of both O115:H- isolates induced cytopathic effects on Vero cell monolayers, and PCR analysis verified that both isolates encoded EAST1, CNF1 and CNF2 toxins but not Shiga-like toxins. Both isolates harboured similar sized plasmids but-PCR analysis indicated that only one of the O115:H- isolates (CO) possessed the plasmid-associated virulence determinants ehxA and etpD. Neither strain possessed the espP, katP or bfpA plasmid-associated virulence determinants. These E. coli O115:H- strains exhibited a novel combination of virulence determinants and are the first isolates found to possess both CNF1 and CNF2.

Local orientational disorder in peptide fibrils probed by a combination of residue-specific 13C-18O labelling, polarised infrared spectroscopy and molecular combing

A novel combination of site-specific isotope labelling, polarised infrared spectroscopy and molecular combing reveal local orientational ordering in the fibril-forming peptide YTIAALLSPYSGGRADS. Use of 13C-18O labelled alanine residues demonstrates that the Nterminal end of the peptide is incorporated into the cross-beta structure, while the C-terminal end shows orientational disorder

An unusual axial–axial combination of alternating cyclic rings in the chair conformations of hexameric water and chlorine-water clusters

An alternating hexameric water (H2O)(6) cluster and a chlorine-water cluster [Cl-2(H2O)(4)](2-) in the chair forms combine axially to each other to form a 1D chain [{Cl-2(H2O)(6)}(2-)](n) in complex [FeL2]Cl center dot(H2O)(3) (L=2-[(2-methylaminoethylimino)-methyl]-phenol)]. The water molecules display extensive H-bonding interactions with monomeric iron-organic units to form a hydrogen-bonded 2D supramolecular assembly.

Janus PEG-based dendrimers for use in combination therapy: controlled multi-drug loading and sequential release

The increasing use of drug combinations to treat disease states, such as cancer, calls for improved delivery systems that are able to deliver multiple agents. Herein, we report a series of novel Janus dendrimers with potential for use in combination therapy. Different generations (first and second) of PEG-based dendrons containing two different “model drugs”, benzyl alcohol (BA) and 3-phenylpropionic acid (PPA), were synthesized. BA and PPA were attached via two different linkers (carbonate and ester, respectively) to promote differential drug release. The four dendrons were coupled together via (3 + 2) cycloaddition chemistries to afford four Janus dendrimers, which contained varying amounts and different ratios of BA and PPA, namely, (BA)2-G1-G1-(PPA)2, (BA)4-G2-G1-(PPA)2, (BA)2-G1-G2-(PPA)4, and (BA)4-G2-G2-(PPA)4. Release studies in plasma showed that the dendrimers provided sequential release of the two model drugs, with BA being released faster than PPA from all of the dendrons. The different dendrimers allowed delivery of increasing amounts (0.15–0.30 mM) and in exact molecular ratios (1:2; 2:1; 1:2; 2:2) of the two model drug compounds. The dendrimers were noncytotoxic (100% viability at 1 mg/mL) toward human umbilical vein endothelial cells (HUVEC) and nontoxic toward red blood cells, as confirmed by hemolysis studies. These studies demonstrate that these Janus PEG-based dendrimers offer great potential for the delivery of drugs via combination therapy.

Polymer therapeutics designed for a combination therapy of hormone-dependent cancer

Designer drug: A polymer therapeutic was designed for a combination therapy of breast cancer. N-(2-Hydroxypropyl)methacrylamide was used as the model polymer platform to prepare a unimolecular polymer conjugate (see picture, radius of gyration: 12.8 nm) that combines an endocrine (the aromatase inhibitor aminoglutethimide, blue) and a chemotherapeutic agent (the anthraxcycline antibiotic doxorubicin, red).

Fusion of infrared polarization and intensity images using support value transform and fuzzy combination rules

Infrared polarization and intensity imagery provide complementary and discriminative information in image understanding and interpretation. In this paper, a novel fusion method is proposed by effectively merging the information with various combination rules. It makes use of both low-frequency and highfrequency images components from support value transform (SVT), and applies fuzzy logic in the combination process. Images (both infrared polarization and intensity images) to be fused are firstly decomposed into low-frequency component images and support value image sequences by the SVT. Then the low-frequency component images are combined using a fuzzy combination rule blending three sub-combination methods of (1) region feature maximum, (2) region feature weighting average, and (3) pixel value maximum; and the support value image sequences are merged using a fuzzy combination rule fusing two sub-combination methods of (1) pixel energy maximum and (2) region feature weighting. With the variables of two newly defined features, i.e. the low-frequency difference feature for low-frequency component images and the support-value difference feature for support value image sequences, trapezoidal membership functions are proposed and developed in tuning the fuzzy fusion process. Finally the fused image is obtained by inverse SVT operations. Experimental results of visual inspection and quantitative evaluation both indicate the superiority of the proposed method to its counterparts in image fusion of infrared polarization and intensity images.

A new understanding of El Niño's impact over East Asia: dominance of the ENSO combination mode

Previous studies have shown that the Indo-Pacific atmospheric response to ENSO comprises two dominant modes of variability: a meridionally quasi-symmetric response (independent from the annual cycle) and an anti-symmetric response (arising from the nonlinear atmospheric interaction between ENSO variability and the annual cycle), referred to as the combination mode (C-Mode). This study demonstrates that the direct El Niño signal over the tropics is confined to the equatorial region and has no significant impact on the atmospheric response over East Asia. The El Niño-associated equatorial anomalies can be expanded towards off-equatorial regions by the C-Mode through ENSO’s interaction with the annual cycle. The C-Mode is the prime driver for the development of an anomalous low-level anticyclone over the western North Pacific (WNP) during the El Niño decay phase, which usually transports more moisture to East Asia and thereby causes more precipitation over southern China. We use an Atmospheric General Circulation Model that well reproduces the WNP anticyclonic anomalies when both El Niño sea surface temperature (SST) anomalies as well as the SST annual cycle are prescribed as boundary conditions. However, no significant WNP anticyclonic circulation anomaly appears during the El Niño decay phase when excluding the SST annual cycle. Our analyses of observational data and model experiments suggest that the annual cycle plays a key role in the East Asian climate anomalies associated with El Niño through their nonlinear atmospheric interaction. Hence, a realistic simulation of the annual cycle is crucial in order to correctly capture the ENSO-associated climate anomalies over East Asia.

Rainfall estimation by rain gauge-radar combination: a concurrent multiplicative-additive approach

A procedure (concurrent multiplicative-additive objective analysis scheme [CMA-OAS]) is proposed for operational rainfall estimation using rain gauges and radar data. On the basis of a concurrent multiplicative-additive (CMA) decomposition of the spatially nonuniform radar bias, within-storm variability of rainfall and fractional coverage of rainfall are taken into account. Thus both spatially nonuniform radar bias, given that rainfall is detected, and bias in radar detection of rainfall are handled. The interpolation procedure of CMA-OAS is built on Barnes' objective analysis scheme (OAS), whose purpose is to estimate a filtered spatial field of the variable of interest through a successive correction of residuals resulting from a Gaussian kernel smoother applied on spatial samples. The CMA-OAS, first, poses an optimization problem at each gauge-radar support point to obtain both a local multiplicative-additive radar bias decomposition and a regionalization parameter. Second, local biases and regionalization parameters are integrated into an OAS to estimate the multisensor rainfall at the ground level. The procedure is suited to relatively sparse rain gauge networks. To show the procedure, six storms are analyzed at hourly steps over 10,663 km2. Results generally indicated an improved quality with respect to other methods evaluated: a standard mean-field bias adjustment, a spatially variable adjustment with multiplicative factors, and ordinary cokriging.

Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study.

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25–65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.

Klebsiella pneumoniae subsp. pneumoniae–bacteriophage combination from the caecal effluent of a healthy woman

A sample of caecal effluent was obtained from a female patient who had undergone a routine colonoscopic examination. Bacteria were isolated anaerobically from the sample, and screened against the remaining filtered caecal effluent in an attempt to isolate bacteriophages (phages). A lytic phage, named KLPN1, was isolated on a strain identified as Klebsiella pneumoniae subsp. pneumoniae (capsular type K2, rmpA+). This Siphoviridae phage presents a rosette-like tail tip and exhibits depolymerase activity, as demonstrated by the formation of plaque-surrounding haloes that increased in size over the course of incubation. When screened against a panel of clinical isolates of K. pneumoniae subsp. pneumoniae, phage KLPN1 was shown to infect and lyse capsular type K2 strains, though it did not exhibit depolymerase activity on such hosts. The genome of KLPN1 was determined to be 49,037 bp (50.53 %GC) in length, encompassing 73 predicted ORFs, of which 23 represented genes associated with structure, host recognition, packaging, DNA replication and cell lysis. On the basis of sequence analyses, phages KLPN1 (GenBank: KR262148) and 1513 (a member of the family Siphoviridae, GenBank: KP658157) were found to be two new members of the genus “Kp36likevirus”.

A constrained recursive least squares algorithm for adaptive combination of multiple models

In this paper, we develop a novel constrained recursive least squares algorithm for adaptively combining a set of given multiple models. With data available in an online fashion, the linear combination coefficients of submodels are adapted via the proposed algorithm.We propose to minimize the mean square error with a forgetting factor, and apply the sum to one constraint to the combination parameters. Moreover an l1-norm constraint to the combination parameters is also applied with the aim to achieve sparsity of multiple models so that only a subset of models may be selected into the final model. Then a weighted l2-norm is applied as an approximation to the l1-norm term. As such at each time step, a closed solution of the model combination parameters is available. The contribution of this paper is to derive the proposed constrained recursive least squares algorithm that is computational efficient by exploiting matrix theory. The effectiveness of the approach has been demonstrated using both simulated and real time series examples.

Combination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease in Immunodeficient Mice Caused by Fluconazole-resistant Cryptococcus neoformans

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 x 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.

A review on the combination of binary classifiers in multiclass problems

Several real problems involve the classification of data into categories or classes. Given a data set containing data whose classes are known, Machine Learning algorithms can be employed for the induction of a classifier able to predict the class of new data from the same domain, performing the desired discrimination. Some learning techniques are originally conceived for the solution of problems with only two classes, also named binary classification problems. However, many problems require the discrimination of examples into more than two categories or classes. This paper presents a survey on the main strategies for the generalization of binary classifiers to problems with more than two classes, known as multiclass classification problems. The focus is on strategies that decompose the original multiclass problem into multiple binary subtasks, whose outputs are combined to obtain the final prediction.