Phylogenomic analyses based on the plastid genome and concatenated nrDNA sequence data reveal cytonuclear discordance in genus Atractylodes (Asteraceae: Carduoideae).
Atractylodes species are widely distributed across East Asia and are cultivated as medicinal herbs in China, Japan, and Korea. Their unclear morphological characteristics and low levels of genetic divergence obscure the taxonomic relationships among these species. In this study, 24 plant samples were collected representing five species of Atractylodes located in China; of these, 23 belonged to members of the A. lancea complex. High-throughput sequencing was used to obtain the concatenated nrDNA sequences (18S-ITS1-5.8S-ITS2-28S) and plastid genomes. The concatenated nrDNA sequence lengths for all the Atractylodes species were 5,849 bp, and the GC content was 55%. The lengths of the whole plastid genome sequences ranged from 152,138 bp (A. chinensis) to 153,268 bp (A. lancea), while their insertion/deletion sites were mainly distributed in the intergenic regions. Furthermore, 33, 34, 36, 31, and 32 tandem repeat sequences, as well as 30, 30, 29, 30, and 30 SSR loci, were detected in A. chinensis, A. koreana, A. lancea, A. japonica, and A. macrocephala, respectively. In addition to these findings, a considerable number of heteroplasmic variations were detected in the plastid genomes, implying a complicated phylogenetic history for Atractylodes. The results of the phylogenetic analysis involving concatenated nrDNA sequences showed that A. lancea and A. japonica formed two separate clades, with A. chinensis and A. koreana constituting their sister clade, while A. lancea, A. koreana, A. chinensis, and A. japonica were found based on plastid datasets to represent a mixed clade on the phylogenetic tree. Phylogenetic network analysis suggested that A. lancea may have hybridized with the common ancestor of A. chinensis and A. japonica, while ABBA-BABA tests of SNPs in the plastid genomes showed that A. chinensis was more closely related to A. japonica than to A. lancea. This study reveals the extensive discordance and complexity of the relationships across the members of the A. lancea complex (A. lancea, A. chinensis, A. koreana, and A. japonica) according to cytonuclear genomic data; this may be caused by interspecific hybridization or gene introgression.


High-affinity adaptors for switchable recognition of histidine-tagged proteins.
We aspired to create chemical recognition units, which bind oligohistidine tags with high affinity and stability, as tools for selectively attaching spectroscopic probes and other functional elements to recombinant proteins. Several supramolecular entities containing 2-4 nitrilotriacetic acid (NTA) moieties were synthesized, which additionally contained an amino group, to which fluorescein was coupled as a sensitive reporter probe. These multivalent chelator heads (MCH) (termed bis-, tris-, and tetrakis-NTA) were characterized with respect to their interaction with hexahistidine (H6)- and decahistidine (H10)-tagged targets. Substantially increased binding stability with increasing number of NTA moieties was observed by analytical size exclusion chromatography. The binding enthalpies as determined by isothermal titration calorimetry increased nearly additively with the number of possible coordinative bonds between chelator heads and tags. Yet, a substantial excess of histidines in the oligohistidine tag was required for obtaining fully additive binding enthalpies. Dissociation kinetics of MCH/oligohistidine complexes measured by fluorescence dequenching showed an increase in stability by 4 orders of magnitude compared to that of mono-NTA, and subnanomolar affinity was reached for tris-NTA. The gain in free energy with increasing multivalency was accompanied by an increasing loss of entropy, which was ascribed to the high flexibility of the binding partners. Numerous applications of these MCHs for noncovalent, high affinity, yet reversible tethering of spectroscopic probes and other functional elements to the recombinant proteins can be envisioned.


Prevalence of selected pathogens in western pond turtles and sympatric introduced red-eared sliders in California, USA.
Pathogen introduction by invasive species has been speculated to be a cause of declining western pond turtle Emys marmorata populations in California, USA. This study determined the prevalence of Ranavirus spp., Herpesvirus spp., Mycoplasma spp. (via polymerase chain reaction of blood and nasal flush contents), and Salmonella spp. infection (via fecal culture) in native E. marmorata and invasive red-eared sliders Trachemys scripta elegans and compared infection prevalence in E. marmorata populations sympatric with T. scripta elegans to E. marmorata populations that were not sympatric by sampling 145 E. marmorata and 33 T. scripta elegans at 10 study sites throughout California. Mycoplasma spp. were detected in both species: prevalence in E. marmorata was 7.8% in the northern, 9.8% in the central, and 23.3% in the southern California regions. In T. scripta elegans, Mycoplasma spp. were not detected in the northern California region but were detected at 4.5 and 14.3% in the central and southern regions, respectively. All turtles tested negative for Herpesvirus spp. and Ranavirus spp. Enteric bacteria but not Salmonella spp. were isolated from feces. E. marmorata populations that were sympatric with T. scripta elegans did not have increased risk of Mycoplasma spp. infection. For E. marmorata, there was a significant association between Mycoplasma spp. infection and lower body weight and being located in the southern California region. This study is the first of its kind to document pathogen prevalence in native E. marmorata habitats and those sympatric with T. scripta elegans in California.


Emerging Nondopaminergic Medications for Parkinson's Disease: Focusing on A2A Receptor Antagonists and GLP1 Receptor Agonists.
Parkinson's disease (PD) is a severe neurodegenerative disease characterized by classic motor features associated with the loss of dopaminergic neurons and appearance of Lewy bodies in the substantia nigra. Due to the complexity of PD, a definitive diagnosis in the early stages and effective management of symptoms in later stages are difficult to achieve in clinical practice. Previous research has shown that colocalization of A2A receptors (A2AR) and dopamine D2 receptors (D2R) may induce an antagonistic interaction between adenosine and dopamine. Clinical trials have found that the A2AR antagonist istradefylline decreases dyskinesia in PD and could be used as an adjuvant to levodopa treatment. Meanwhile, the incretin hormone glucagon-like peptide 1 (GLP1) mainly facilitates glucose homeostasis and insulin signaling. Preclinical experiments and clinical trials of GLP1 receptor (GLP1R) agonists show that they may be effective in alleviating neuroinflammation and sustaining cellular functions in the central nervous system of patients with PD. In this review, we summarize up-to-date findings on the usefulness of A2AR antagonists and GLP1R agonists in PD management. We explain the molecular mechanisms of these medications and their interactions with other neurotransmitter receptors. Furthermore, we discuss the efficacy and limitations of A2AR antagonists and GLP1R agonists in clinical practice.


Risk of locoregional recurrence in patients with false-negative frozen section or close margins of retroareolar specimen in nipple-sparing mastectomy.
Our purpose was to evaluate the locoregional recurrence (LRR) of patients with false-negative, frozen-section or close margins of retroareolar specimen in nipple-sparing mastectomy (NSM) procedure. From 2002-2008, we recruited patients who had atypia or presence of cancer cells in definitive histology of retroareolar tissue despite of absence of tumor cell in intraoperative retroareolar frozen section. We also included the close margin cases defined as the presence of tumor cells at the first frozen section, but after deeper core out of retroareolar tissue were revealed free of malignancy. The incidence of LRR and NAC recurrence were reported, and the factors associated were analyzed. Of 948 NSM procedures, there were 88 false-negative, frozen-sections and 10 close margin cases. The 5-year cumulative incidence of LRR and NAC recurrence was 11.2 % (10/98 patients) and 2.4 % (2/98 patients), respectively. Analyzing the definitive results of retroareolar tissue, the 5-year cumulative incidence of LRR was 42.9 % (n = 4) for atypia, 10 % (n = 2) for lobular carcinoma in situ (LCIS), 10 % (n = 1) for close margins, 8.7 % (n = 3) for ductal carcinoma in situ (DCIS), and 0 % for invasive carcinoma. In situ carcinoma as a primary tumor was a significant predictor of NAC recurrence (P < 0.01). Despite a high reliability of frozen section, there is still a minority of false-negative results. Nevertheless, the LRR is considerably low. This fact suggests the possibility of preservation of the NAC after discussion with the patient.


A Systematic Review of Donor Serum Sodium Level and Its Impact on Transplant Recipients.
An important aspect of donor management is the optimization of serum sodium levels. To perform a systematic review to determine the effects of donor sodium levels on heart, lung, kidney, and pancreas graft function, recipient mortality, and to identify the optimal donor serum sodium target. We searched MEDLINE, Cochrane, Guideline databases, and trial registries from 1946 to May 2019 for studies investigating the effects of donor serum sodium levels on transplant outcomes in all non-hepatic organs. A two-step independent review process was used to identify relevant articles based on inclusion/exclusion criteria. We describe the results narratively, assess the risk of bias, and apply GRADE methodology to evaluate the certainty in the evidence. We included 18 cohort studies in our final analysis (n=28,007). 3 of 4 studies demonstrated an association between donor serum sodium and successful organ transplantation. 5 studies reported no association with graft function, while 6 studies did. 5 studies reported on recipient survival, 3 of which suggested donor sodium is unlikely to be associated with recipient survival. The included studies had serious risk of bias, and the certainty in evidence was deemed to be very low. In low risk of bias studies, donor sodium dysregulation is unlikely to affect kidney graft function or mortality of heart and kidney recipients, but the certainty in the evidence is very low due to inconsistency and imprecision. Further research is required to refine the serum sodium target range, quantify the dose-response curve, and identify organs most vulnerable to sodium dysregulation.


Role of alpha2-adrenergic receptors and cyclic adenosine monophosphate-dependent protein kinase in the regulation of norepinephrine release in the central nervous system of spontaneously hypertensive rats.
There has been much evidence showing that the central sympathetic nervous system may be involved in the control of blood pressure. In the present study, we investigated the role of the presynaptic alpha2-adrenergic receptors and the cyclic adenosine monophosphate-dependent protein kinase (protein kinase A) in the regulation of norepinephrine release in the central nervous system in hypertension. The alpha2-adrenergic receptor agonists UK 14, 304 and clonidine inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner in the medulla oblongata of Sprague-Dawley rats. Pretreatment of pertussis toxin (a potent inhibitor of the Gi-protein) attenuated the suppression of NE release by UK 14, 304. The protein kinase A inhibitor H-8 also reduced the stimulation-evoked [3H]norepinephrine release in rat medulla oblongata. In spontaneously hypertensive rats, the inhibitory effect of UK 14, 304 on the stimulation-evoked norepinephrine release was significantly less than in age-matched normotensive Wistar-Kyoto rats. By contrast, the protein kinase A inhibitor H-8 reduced the stimulation-evoked norepinephrine release to a greater extent in hypertension than in normotensive controls. The results of the present study showed that the alteration in the presynaptic alpha2-receptor-protein kinase A system might actively participate in the regulation of norepinephrine release in the central nervous system in hypertension.


Care of the pediatric foot in myelodysplasia.
Foot deformity is present in almost all patients paralyzed by myelomeningocele. This article outlines the pertinent pathoanatomy resulting in differing foot deformities and their effects on normal gait. Treatment of these deformities is discussed, and the most common deformities present for the different levels of paralysis are outlined. Emphasis is placed on surgical and orthotic treatments, which result in functional improvements for the pediatric patient with spina bifida.


Synthesis, characterization, and antitumor evaluation of the albumin-SN38 conjugate.
7-Ethyl-10-hydroxycamptothecin (SN38), the active metabolite of irinotecan, exerts a 100-fold to 1000-fold higher effect than irinotecan itself against several tumor cell lines. However, the water insolubility of SN38 has prevented its direct use as an antitumor drug in the clinic. To improve the water solubility and antitumor efficacy, SN38 was covalently attached to the only free sulfhydryl at cysteine-34 on the BSA site specifically through a thiol-binding linker to form a prodrug BSA-SN38 conjugate (BSA : SN38=1 : 1). The water solubility of this conjugate was similar to albumin using the current method. Also, SN38 loading in this conjugate became controllable. Size-exclusion chromatography purification and UV characterization of the SDS-PAGE electrophoresis product were carried out. Then, an MTT assay was carried out to test the antitumor effect of this conjugate on five colon cancer cell lines in vitro. The 72 h IC50 values of the BSA-SN38 conjugate ranged from 1.5 to 6.1 μmol/l. A colorectal peritoneal carcinomatosis model in mice was established to determine the intraperitoneal chemotherapy effect of the BSA-SN38 conjugate. The BSA-SN38 conjugate at an SN38 equivalent dose of 10 mg/kg/day was administrated every 4 days. Eighteen days after manipulation, the mice were euthanized and the tumors in the abdominal cavity were collected and weighed. Tumors in the BSA-SN38 conjugate treatment group (m=0.21 ± 0.15 g) were found to be significantly (P=5) lighter than those in the NS control group (m=4.74±0.73 g). The results indicated that this water-soluble BSA-SN38 conjugate exerted a strong antitumor effect on colorectal carcinoma.


miR-142-3p Reduces the Size, Migration, and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-Related Pathways That Regulate Cytoskeletal Function.
Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis, an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates Rho-associated protein kinase 2 (ROCK2), cofilin 2 (CFL2), Ras-related C3 botulinum toxin substrate 1 (RAC1), neural Wiskott-Aldrich syndrome protein (WASL), and integrin α-V (ITGAV). qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters, and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.


When sex meets syntactic gender on a neural basis during pronoun processing.
We used event-related functional magnetic resonance imaging (erfMRI) to investigate the neural basis of biological and syntactic gender integration during pronoun processing in German sentences about persons or things. German allows for separating both processes experimentally. Overall, syntactic processing activated areas adjacent to Broca's area (BA 44), whereas processing of the biological sex, in addition, involved the supramarginal gyrus (BA 39). A previously reported event-related potential study using identical material suggests that syntactic and semantic information is integrated 400-700 ms after target onset, visible in both cases as a P600 but with different effect sizes. The fMRI and ERP results illuminate that pronoun processing involves a highly dynamic spatiotemporal integration of syntactic and biological information depending on the type of the antecedent and whether or not a violation is involved. The results are discussed in the context of cognitive models of pronoun processing.


A ToxIN homolog from Salmonella enterica serotype Enteritidis impairs bacteriophage infection.
To determine if the bacteriophage abortive infection system ToxIN is present in foodborne Salmonella and if it protects against infection by bacteriophages specific to enteric bacteria. A set of foodborne Salmonella enteritidis isolates from a 2010 eggshell outbreak was identified via BLASTN (basic local alignment search tool nucleotide) queries as harboring a close homolog of ToxIN, carried on a plasmid with putative mobilization proteins. This homolog was cloned into a plasmid vector and transformed into the laboratory strain Salmonella typhimurium LT2 and tested against a set of Salmonella-specific phages (FelixO1, S16, Sp6, LPST153, and P22 HT105/1 int-201). ToxIN reduced infection by FelixO1, S16, and LPST153 by ∼1-4 log PFU ml-1 while reducing the plaque size of Sp6. When present in LT2 and Escherichia coli MG1655, ToxIN conferred cross-genus protection against phage isolates, which infect both bacteria. Finally, the putative ToxIN plasmid was found in whole-genome sequence contigs of several Salmonella serovars, pathogenic E. coli, and other pathogenic enterobacteria. Salmonella and E. coli can resist infection by several phages via ToxIN under laboratory conditions; ToxIN is present in foodborne pathogens including Salmonella and Shiga-toxigenic E. coli.


Measuring kinaesthetic sensitivity in typically developing children.
This study presents a method to quantify a child's sensitivity to passive limb motion, which is an important aspect of kinaesthesia not easily examined clinically. Psychophysical detection thresholds to passive forearm motion were determined in a group of 20 typically developing pre-adolescent children (mean age 12y 6mo, SD 10mo, range 11-13y) and a group of 10 healthy adults (mean age 29y 10mo, SD 10y 7mo, range 18-50y). A newly designed passive motion apparatus was used to measure the time to detection of forearm motion and the errors in determining movement direction. Results showed that limb motion sensitivity became increasingly variable below 0.3 degrees /s in children and adults. In comparison with adults, movement detection times in the pediatric group were increased by between 4% and 108% for the range of tested velocities (0.075-1.35 degrees /s). At 0.075 degrees /s, 5% of the children, but 50% of the adults, made no directional error, indicating that motion perception became unreliable at such low velocity in both groups. The findings demonstrate that sensitivity to passive forearm motion in children should be tested at a range between 0.075 and 0.3 degrees /s. They further suggest that passive motion sensitivity may not be fully developed in pre-adolescent children.


A rapid method for the isolation of ribonuclease from yeast (Saccharomyces carlsbergensis).
A ribonuclease (RNAase; EC 220.127.116.11) from brewer's yeast was purified 90-fold. Crude RNAase was initially separated from other proteins by precipitation at pH 4.0 after incubation of the mechanically disrupted yeast cells at pH 6.0 and 52 degrees C for 30 min. The RNAase was purified from the supernatant by ultrafiltration with a PM-30 membrane and adsorption chromatography on hydroxyapatite. RNAase preparation was free of phosphatase, deoxyribonuclease and phosphodiesterase activities. It showed maximum activity at pH 6.0 and a temperature optimum of 52 degrees C with yeast RNA as substrate. This RNAase hydrolysed yeast RNA to nucleoside 3'-phosphates and showed no evidence of base specificity.


Kinesin- and myosin-driven steps of vesicle recruitment for Ca2+-regulated exocytosis.
Kinesin and myosin have been proposed to transport intracellular organelles and vesicles to the cell periphery in several cell systems. However, there has been little direct observation of the role of these motor proteins in the delivery of vesicles during regulated exocytosis in intact cells. Using a confocal microscope, we triggered local bursts of Ca2+-regulated exocytosis by wounding the cell membrane and visualized the resulting individual exocytotic events in real time. Different temporal phases of the exocytosis burst were distinguished by their sensitivities to reagents targeting different motor proteins. The function blocking antikinesin antibody SUK4 as well as the stalk-tail fragment of kinesin heavy chain specifically inhibited a slow phase, while butanedione monoxime, a myosin ATPase inhibitor, inhibited both the slow and fast phases. The blockage of Ca2+/calmodulin-dependent protein kinase II with autoinhibitory peptide also inhibited the slow and fast phases, consistent with disruption of a myosin-actin- dependent step of vesicle recruitment. Membrane resealing after wounding was also inhibited by these reagents. Our direct observations provide evidence that in intact living cells, kinesin and myosin motors may mediate two sequential transport steps that recruit vesicles to the release sites of Ca2+-regulated exocytosis, although the identity of the responsible myosin isoform is not yet known. They also indicate the existence of three semistable vesicular pools along this regulated membrane trafficking pathway. In addition, our results provide in vivo evidence for the cargo-binding function of the kinesin heavy chain tail domain.


Cerebellar long-term potentiation: cellular mechanisms and role in learning.
Activity-dependent long-term plasticity of synaptic transmission, such as in long-term potentiation (LTP) and long-term depression (LTD), provides a cellular correlate of experience-driven learning. While at excitatory synapses in the hippocampus and neocortex LTP is seen as the primary learning mechanism, it has been widely assumed that cerebellar motor learning is mediated by LTD at parallel fiber (PF)-Purkinje cell synapses instead. However, recent work on mouse mutants with deficits in AMPA receptor internalization has demonstrated that motor learning can occur in the absence of LTD, suggesting that LTD is not essential. Another recent study has shifted attention toward LTP at PF synapses, showing that blockade of LTP severely affects motor learning. Here, we review the cellular and molecular events that are involved in LTP induction and discuss whether LTP might indeed play a more significant role in cerebellar learning than previously anticipated.


Influenza A Virus Uses PSMA2 for Downregulation of the NRF2-Mediated Oxidative Stress Response.
Influenza A virus (IAV), an obligatory intracellular parasite, uses host cellular molecules to complete its replication cycle and suppress immune responses. Proteasome subunit alpha type 2 (PSMA2) is a cellular protein highly expressed in IAV-infected human lung epithelial A549 cells. PSMA2 is part of the 20S proteasome complex that degrades or recycles defective proteins and involves proteolytic modification of many cellular regulatory proteins. However, the role of PSMA2 in IAV replication is not well understood. In this study, PSMA2 knockdown (KD) in A549 cells caused a significant reduction in extracellular progeny IAV, but intracellular viral protein translation and viral RNA transcription were not affected. This indicates that PSMA2 is a critical host factor for IAV maturation. To better understand the interplay between PSMA2 KD and IAV infection at the proteomic level, we used the SomaScan 1.3K version, which measures 1,307 proteins to analyze alterations induced by these treatments. We found seven cellular signaling pathways, including phospholipase C signaling, Pak signaling, and nuclear factor erythroid 2p45-related factor 2 (NRF2)-mediated oxidative stress response signaling, that were inhibited by IAV infection but significantly activated by PSMA2 KD. Further analysis of NRF2-mediated oxidative stress response signaling indicated IAV inhibits accumulation of reactive oxygen species (ROS), but ROS levels significantly increased during IAV infection in PSMA2 KD cells. However, IAV infection caused significantly higher NFR2 nuclear translocation that was inhibited in PSMA2 KD cells. This indicates that PSMA2 is required for NRF2-mediated ROS neutralization and that IAV uses PSMA2 to escape viral clearance via the NRF2-mediated cellular oxidative response. IMPORTANCE Influenza A virus (IAV) remains one of the most significant infectious agents, responsible for 3 million to 5 million illnesses each year and more than 50 million deaths during the 20th century. The cellular processes that promote and inhibit IAV infection and pathogenesis remain only partially understood. PSMA2 is a critical component of the 20S proteasome and ubiquitin-proteasome system, which is important in the replication of numerous viruses. This study examined host protein responses to IAV infection alone, PSMA2 knockdown alone, and IAV infection in the presence of PSMA2 knockdown and determined that interfering with PSMA2 function affected IAV maturation. These results help us better understand the importance of PSMA2 in IAV replication and may pave the way for designing additional IAV antivirals targeting PSMA2 or the host proteasome for the treatment of seasonal flu.


Mode of action of lipid II-targeting lantibiotics.
The antimicrobial action of bacteriocins from Gram-positive bacteria is based on interaction with the cytoplasmic membrane of sensitive bacteria. Models based on studies with artificial membrane systems propose that nisin forms wedge-like poration complexes in the membrane by electrostatic interaction between the positively charged C terminus of the peptide and anionic membrane phospholipids. Nisin can also permeabilise membranes via a targeted mechanism by using lipid II, the bactoprenol-bound precursor of the bacterial cell wall, as a docking molecule. Another consequence of binding with lipid II is the inhibition of peptidoglycan biosynthesis. Mersacidine and actagardine also form a complex with lipid II, but binding only blocks the incorporation of lipid II into peptidoglycan, resulting in slow cell lysis rather than pore formation. Both peptides share a conserved sequence motif with plantaricin C and pediocin PD-1, which is most probably involved in the binding of these bacteriocins to lipid II. Although pediocin PD-1 and plantaricin C may inhibit peptidoglycan biosynthesis, pore formation is rather due to electrostatic interaction between the positively charged unbridged N-terminus and anionic phospholipids in the cytoplasmic membrane of sensitive cells. In the light of increased antibiotic resistance, this review focuses on the mode of action of lantibiotics that involve lipid II, possible candidates for the development of new-generation novel antibiotic drugs.


Spontaneous bimanual independence during parallel tapping and sawing.
The performance of complex polyrhythms-rhythms where the left and right hand move at different rates-is usually the province of highly trained individuals. However, studies in which hand movement is guided haptically show that even novices can perform polyrhythms with no or only brief training. In this study, we investigated whether novices are able to tap with one hand by matching different rates of a metronome while sawing with the other hand. This experiment was based on the assumption that saw movement is controlled consistently at a predictable rate without the need for paying primary attention to it. It would follow that consciously matching different stipulated metronome rates with the other hand would result in the spontaneous performance of polyrhythms. Six experimental conditions were randomised: single handed tapping and sawing as well as four bimanual conditions with expected ratios of 1:1 (performed with and without matching a metronome) as well as 3:4 and 4:3 (performed matching a metronome). Results showed that participants executed the saw movement at a consistent cycle duration of 0.44 [0.20] s to 0.51 [0.19] s across single and bimanual conditions, with no significant effect of the condition on the cycle duration (p = 0.315). Similarly, free tapping was executed at a cycle duration of 0.48 [0.22] s. In the bimanual conditions, we found that for a ratio of 4:3 (4 taps against 3 sawing cycles per measure), the observed and predicted ratio of 0.75 were not significantly different (p = 0.369), supporting our hypothesis of the spontaneous adoption of polyrhythms. However, for a ratio of 3:4 (3 taps against 4 sawing cycles per measure), the observed and predicted ratio differed (p = 0.016), with a trend towards synchronisation. Our findings show that bimanual independence when performing complex polyrhythms can in principle be achieved if the movement of one hand can be performed without paying much-if any-attention to it. In this paradigm, small rhythmic arm movements are possibly driven by an intrinsic timing which leads to spontaneous convergence on a cycle duration of around 0.5 s, while the movement of the other hand can be controlled consciously to occur at desired rates.


Mood disorders and non-celiac gluten sensitivity.
The association between gluten related disorders and psychiatric diseases has been firmly demonstrated. Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients responsive to gluten-free diet after ruling out celiac disease and wheat allergy. The pathogenesis of neuro-psychiatric disorders in NCGS is unclear. An association between gluten and schizophrenia was described for the first time in 1950 by Bender et al. In the 1950's, Dicke noted that gluten-free diet improved mood in celiac patients. In 1970, Goldberg et al., in a study of 80 celiac patients, found that 34% of them showed minor affective disorders. Bipolar disorder patients show an increase of blood anti gliadin deamidated antibodies (IgG). The effect of diet and nutrition on autistic spectrum disorders has been investigated in the last two decades, particularly focusing on the symptoms of hyperactivity and attention. Toxoplasma gondii and other neurotropic pathogens as Influenzavirus and Coronavirus may be associated with mood disorders, probably secondary to an increased intestinal permeability. Abnormalities of host-microbiota interactions or of gut-microbiota composition have been associated with central nervous system disorders, such as autism, anxiety, depression and the integrity of intestinal microbiota may be considered a potential therapeutic goal to treat these conditions.


Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy.
Adjuvant therapy for breast cancer with tamoxifen is suggested to be of benefit to both women with negative and women with positive axillary nodes, and treatment lasting several years is currently being investigated. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible mechanisms of this effect, we evaluated changes in antithrombin III levels, fibrinogen levels, and platelet counts in 140 postmenopausal women with surgically resected breast cancer who were disease free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. Antithrombin III levels, elevated at baseline evaluation, decreased in tamoxifen-treated subjects at 6 months, but no subject exhibited a drop to clinically significant levels. Fibrinogen levels decreased 15% (0.4 g/L) in tamoxifen-treated subjects at 6 months. Platelet counts decreased 7% to 9% from baseline to evaluations at 3, 6, 12, 18, and 24 months in tamoxifen-treated subjects. While these changes do not explain the possible small thrombophlebitis-promoting effect of tamoxifen, the decrease in fibrinogen levels might be expected to be associated with a decreased risk of arterial thrombosis.


A cell wall-associated polysaccharide is required for bacteriophage adsorption to the Streptococcus thermophilus cell surface.
Streptococcus thermophilus strain ST64987 was exposed to a member of a recently discovered group of S. thermophilus phages (the 987 phage group), generating phage-insensitive mutants, which were then characterized phenotypically and genomically. Decreased phage adsorption was observed in selected bacteriophage-insensitive mutants, and was partnered with a sedimenting phenotype and increased cell chain length or aggregation. Whole genome sequencing of several bacteriophage-insensitive mutants identified mutations located in a gene cluster presumed to be responsible for cell wall polysaccharide production in this strain. Analysis of cell surface-associated glycans by methylation and NMR spectroscopy revealed a complex branched rhamno-polysaccharide in both ST64987 and phage-insensitive mutant BIM3. In addition, a second cell wall-associated polysaccharide of ST64987, composed of hexasaccharide branched repeating units containing galactose and glucose, was absent in the cell wall of mutant BIM3. Genetic complementation of three phage-resistant mutants was shown to restore the carbohydrate and phage resistance profiles of the wild-type strain, establishing the role of this gene cluster in cell wall polysaccharide production and phage adsorption and, thus, infection.


Tissue scaffolds for skin wound healing and dermal reconstruction.
One of the major applications of tissue-engineered skin substitutes for wound healing is to promote the healing of cutaneous wounds. In this respect, many important clinical milestones have been reached in the past decades. However, currently available skin substitutes for wound healing often suffer from a range of problems including wound contraction, scar formation, and poor integration with host tissue. Engineering skin substitutes by tissue engineering approach has relied upon the creation of three-dimensional scaffolds as extracellular matrix (ECM) analog to guide cell adhesion, growth, and differentiation to form skin-functional and structural tissue. The three-dimensional scaffolds can not only cover wound and give a physical barrier against external infection as wound dressing, but also can provide support both for dermal fibroblasts and the overlying keratinocytes for skin tissue engineering. A successful tissue scaffold should exhibit appropriate physical and mechanical characteristics and provide an appropriate surface chemistry and nano and microstructures to facilitate cellular attachment, proliferation, and differentiation. A variety of scaffolds have been fabricated based on materials ranging from naturally occurring ones to those manufactured synthetically. This review discusses a variety of commercial or laboratory-engineered skin substitutes for wound healing. Central to the discussion are the scaffolds/materials, fabrication techniques, and their characteristics associated with wound healing. One specifically highlighted emerging fabrication technique is electrospinning that allows the design and fabrication of biomimetic scaffolds that offer tremendous potential applications in wound healing of skin.


The Performance of Patient-reported Outcome Measures as Diagnostic Tools for Eustachian Tube Dysfunction.
To develop and validate a novel patient-reported outcome measure (PROM) to distinguish patulous from obstructive Eustachian Tube Dysfunction (ETD). To determine accuracy of PROMs and ET function tests as diagnostic tools for ETD. 1) PROM development and validation. 2) Test case-control diagnostic accuracy study. Cambridge ETD Assessment (CETDA) and ETDQ-7 PROMs, sonotubometry and tubomanometry ET function tests. Tertiary referral center. Cases with patulous (n = 7) or obstructive (n = 60) ETD, controls with either no ear symptoms (n = 33), or symptoms arising from hearing loss or Menière's disease (n = 24). PROMs were assessed in terms of internal consistency, ceiling and floor effects, test-retest reliability and content, structural and criterion validity. PROMs and function test sensitivity and specificity was determined as diagnostic tests for ETD. The 10-item CETDA was developed. CETDA validity and performance were good, though five items suffered floor effects. There was no difference in scores for either PROM in the patulous ETD, obstructive ETD, and symptomatic control groups. Both PROMS had excellent diagnostic accuracy using only healthy controls as comparator for ETD, but specificity was very poor when controls with other otological disorders were included. Both objective tests had sensitivity and specificity of 63% and 79% for obstructive ETD. The CETDA and ETDQ-7 are not disease-specific and cannot distinguish obstructive from patulous ETD subtypes. A relatively weak correlation between sonotubometry and tubomanometry results, PROM scores, and the clinical diagnosis suggests that a varied core set of outcome measures is required to monitor response to treatments for ETD.


Investigation into the vibrational yield of OH products in the OH+H+H channel arising from the dissociative recombination of H(3)O(+).
The vibrational population of the hydroxyl radical, OH, formed in the OH+H+H channel arising from the dissociative recombination of the hydronium ion, H(3)O(+), has been investigated at the storage ring CRYRING using a position-sensitive imaging detector. Analysis shows that the OH fragments are predominantly produced in the v=0 and v=1 states with almost equal probabilities. This observation is in disagreement with earlier FALP experiments, which reported OH(v=0) as the dominant product. Possible explanations for this difference are discussed.


Lack of relationship of calcium and vitamin D intake to bone mineral density in premenopausal women with inflammatory bowel disease.
Low bone mineral density has been widely reported in patients with inflammatory bowel disease (IBD). The exact etiology of this condition is not completely understood but is suggested to be multifactorial, possibly including low calcium and vitamin D intake. The objective of this study was to assess calcium and vitamin D intake and its relationship to bone mineral density (BMD) in premenopausal women with IBD. A total of 70 premenopausal women with IBD (mean age 33.3 yr, range 18-44 yr) drawn from the population-based University of Manitoba IBD Research Registry participated in the study. Calcium and vitamin D intake was determined using a semiquantitative food frequency questionnaire and compared to the Dietary Reference Intake values for adequacy. BMD of total body, lumbar spine, femoral neck, and hip was measured using dual-energy x-ray absorptiometry. Of the 70 subjects, 66 successfully completed the study. Inadequate calcium intake (<1000 mg/day) was found in 69.7% of the subjects. This low intake group had a mean calcium intake of 508 mg/day. Inadequate vitamin D intake (<200 IU/day) was found in 53% of the subjects with a mean vitamin D intake of 76 IU/day in this group. Calcium and vitamin D intake correlated with each other with R2=0.57, p<0.00001. Daily calcium intake was not significantly different for subjects with T scores greater than -1 (901 mg) and for subjects with T scores less than -1 (875 mg, p=0.44). Daily vitamin D intake was not significantly different for subjects with T scores greater than -1 (297 IU) compared with subjects with T scores less than -1 was (267 IU, p=0.33). Comparing subjects with T scores greater than -1 to those with T score less than -1, there was no difference in the percentage of subjects ingesting >1 g/day calcium (14/43 vs 8/23, p=0.86) or in those with vitamin D intake >200 IU/day (21/43 vs 9/23, p=0.45). The results show that, on average, premenopausal women with IBD have less than the recommended intake for calcium and vitamin D. However, this does not seem to influence BMD. Calcium and vitamin D intake is not a predictor of bone status in premenopausal women with IBD.


Eliminating friction with friction: 2D Janssen effect in a friction-driven system.
The Janssen effect is a unique property of confined granular materials experiencing gravitational compaction in which the pressure at the bottom saturates with an increasing filling height due to frictional interactions with side walls. In this Letter, we replace gravitational compaction with frictional compaction. We study friction-compacted 2D granular materials confined within fixed boundaries on a horizontal conveyor belt. We find that even with high-friction side walls the Janssen effect completely vanishes. Our results demonstrate that gravity-compacted granular systems are inherently different from friction-compacted systems in at least one important way: vibrations induced by sliding friction with the driving surface relax away tangential forces on the walls. Remarkably, we find that the Janssen effect can be recovered by replacing the straight side walls with a sawtooth pattern. The mechanical force introduced by varying the sawtooth angle θ can be viewed as equivalent to a tunable friction force. By construction, this mechanical friction force cannot be relaxed away by vibrations in the system.


Systematic errors for a Mueller matrix dual rotating compensator ellipsometer.
The characterization of anisotropic materials and complex systems by ellipsometry has pushed the design of instruments to require the measurement of the full reflection Mueller matrix of the sample with a great precision. Therefore Mueller matrix ellipsometers have emerged over the past twenty years. The values of some coefficients of the matrix can be very small and errors due to noise or systematic errors can induce distored analysis. We present a detailed characterization of the systematic errors for a Mueller Matrix Ellipsometer in the dual-rotating compensator configuration. Starting from a general formalism, we derive explicit first-order expressions for the errors on all the coefficients of the Mueller matrix of the sample. The errors caused by inaccuracy of the azimuthal arrangement of the optical components and residual ellipticity introduced by imperfect optical elements are shown. A new method based on a four-zone averaging measurement is proposed to vanish the systematic errors.


Lysine Methyltransferase NSD1 and Cancers: Any Role in Melanoma?
Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or promoter functions according to the tissue context and we discuss the role of NSD1 in melanoma. Finally, we examine the ongoing efforts to target NSD1 signaling in cancers.


Climate change and waterborne and vector-borne disease.
This paper considers the potential impact on human health from waterborne and vector-borne infections. It concentrates on the impact of two possible changes to climate; increased frequency of heavy rainfall events, with associated flooding and increased temperature. Flooding is associated with increased risk of infection in developing nations but not in the West unless water sources are compromised. There have been numerous reported of outbreaks that followed flooding that led to contamination of underground sources of drinking water. Heavy rainfall also leads to deterioration in the quality of surface waters that could adversely affect the health of those engaged in recreational water contact. It is also concluded that there may be an increase in the number of cyanobacterial blooms because of a combination of increased nutrient concentrations and water temperature. It is considered unlikely that climate change will lead to an increase in disease linked to mains drinking water, although private supplies would be at risk from increased heavy rainfall events. Although increased temperature could lead to climatic conditions favourable to increases in certain vector-borne diseases such as malaria, the infrastructure in the UK would prevent the indigenous spread of malaria.


Development of therapies for autoimmune disease at Stanford: a tale of multiple shots and one goal.
The title of this contribution on Immunology at Stanford is purposely ambiguous. One goal is the development of safe and effective therapy for autoimmune diseases. Another definition of goal is to score, and this would ultimately mean the development of an approved drug. Indeed, the efforts in my four decades at Stanford, have included the discovery and subsequent development of a monoclonal antibody to block homing to the inflamed brain, leading to natalizumab, an approved therapeutic for two autoimmune diseases: relapsing-remitting MS and for inflammatory bowel disease. Multiple attempts to develop new therapies for autoimmune disease are described here: The trimolecular complex and the immune synapse serve as one major set of targets, with attempts to inhibit particular major histocompatibility molecules, the variable regions of the T cell receptor, and CD4. Other approaches focusing on antigen-specific tolerance include ongoing attempts with tolerizing DNA vaccines in type 1 diabetes. Finally, the repurposing of popular drugs approved for other indications, including statins and inhibitors of angiotensin converting enzyme is under development and showing promise in the clinic, particularly for secondary progressive multiple sclerosis. The milieu within Stanford Immunology has helped to nurture these efforts to translate discoveries in immunology and to take them from bench to bedside.


Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells.
Cell migration and wound contraction requires assembly of actin into a functional myosin motor unit capable of generating force. However, cell migration also involves formation of actin-containing membrane ruffles. Evidence is provided that actin-myosin assembly and membrane ruffling are regulated by distinct signaling pathways in the migratory cell. Interaction of cells with extracellular matrix proteins or cytokines promote cell migration through activation of the MAP kinases ERK1 and ERK2 as well as the molecular coupling of the adaptor proteins p130CAS and c-CrkII. ERK signaling is independent of CAS/Crk coupling and regulates myosin light chain phosphorylation leading to actin-myosin assembly during cell migration and cell-mediated contraction of a collagen matrix. In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180. Thus, during cell migration ERK and CAS/Crk coupling operate as components of distinct signaling pathways that control actin assembly into myosin motors and membrane ruffles, respectively.


Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort.
To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. The median OS was 71.4 months (interquartile range: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89-0.98); 0.94 (0.89-0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09-0.53); 0.30 (0.12-0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01-1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08-6.57)] and adventitial involvement [2.54 (1.36-4.72)] also influenced OS, while involved margins [3.12 (1.24-7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44-0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57-0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.


Animal models for bipolar disorder: from bedside to the cage.
Bipolar disorder is characterized by recurrent manic and depressive episodes. Patients suffering from this disorder experience dramatic mood swings with a wide variety of typical behavioral facets, affecting overall activity, energy, sexual behavior, sense of self, self-esteem, circadian rhythm, cognition, and increased risk for suicide. Effective treatment options are limited and diagnosis can be complicated. To overcome these obstacles, a better understanding of the neurobiology underlying bipolar disorder is needed. Animal models can be useful tools in understanding brain mechanisms associated with certain behavior. The following review discusses several pathological aspects of humans suffering from bipolar disorder and compares these findings with insights obtained from several animal models mimicking diverse facets of its symptomatology. Various sections of the review concentrate on specific topics that are relevant in human patients, namely circadian rhythms, neurotransmitters, focusing on the dopaminergic system, stressful environment, and the immune system. We then explain how these areas have been manipulated to create animal models for the disorder. Even though several approaches have been conducted, there is still a lack of adequate animal models for bipolar disorder. Specifically, most animal models mimic only mania or depression and only a few include the cyclical nature of the human condition. Future studies could therefore focus on modeling both episodes in the same animal model to also have the possibility to investigate the switch from mania-like behavior to depressive-like behavior and vice versa. The use of viral tools and a focus on circadian rhythms and the immune system might make the creation of such animal models possible.


Synteny conservation between two distantly-related Rosaceae genomes: Prunus (the stone fruits) and Fragaria (the strawberry).
The Rosaceae encompass a large number of economically-important diploid and polyploid fruit and ornamental species in many different genera. The basic chromosome numbers of these genera are x = 7, 8 and 9 and all have compact and relatively similar genome sizes. Comparative mapping between distantly-related genera has been performed to a limited extent in the Rosaceae including a comparison between Malus (subfamily Maloideae) and Prunus (subfamily Prunoideae); however no data has been published to date comparing Malus or Prunus to a member of the subfamily Rosoideae. In this paper we compare the genome of Fragaria, a member of the Rosoideae, to Prunus, a member of the Prunoideae. The diploid genomes of Prunus (2n = 2x = 16) and Fragaria (2n = 2x = 14) were compared through the mapping of 71 anchor markers - 40 restriction fragment length polymorphisms (RFLPs), 29 indels or single nucleotide polymorphisms (SNPs) derived from expressed sequence tags (ESTs) and two simple-sequence repeats (SSRs) - on the reference maps of both genera. These markers provided good coverage of the Prunus (78%) and Fragaria (78%) genomes, with maximum gaps and average densities of 22 cM and 7.3 cM/marker in Prunus and 32 cM and 8.0 cM/marker in Fragaria. Our results indicate a clear pattern of synteny, with most markers of each chromosome of one of these species mapping to one or two chromosomes of the other. A large number of rearrangements (36), most of which produced by inversions (27) and the rest (9) by translocations or fission/fusion events could also be inferred. We have provided the first framework for the comparison of the position of genes or DNA sequences of these two economically valuable and yet distantly-related genera of the Rosaceae.


The effects of graduated driver licensing on teenage body weight.
The graduated driver licensing (GDL) program requires teenage drivers to pass through an intermediate stage, which contains specific driving restrictions such as a night curfew or a limit on the number of teen passengers to be carried, before earning full driving privileges. Using individual data from the 1999 to 2017 biennial Youth Risk Behavior Surveillance System (YRBS) combined with state-level GDL policy variations, we estimate the effects of GDL on teenage body weight in the United States. We find that the presence of GDL raises adolescents' body mass index Z-score and their likelihood of being overweight or obese. Among the restrictions imposed, a night curfew implemented together with a passenger restriction makes the most significant impact. These estimated effects are concentrated among states with more restrictive GDL policies. We also find that the presence of GDL reduces adolescent physical activity and heavy smoking, while increasing their time spent watching TV and milk intake, perhaps contributing to youth weight gain. An event study analysis reveals that the effects of GDL on adolescent weight increase may be transitory.


A TinyOS-enabled MICA2-based wireless neural interface.
Existing approaches used to develop compact low-power multichannel wireless neural recording systems range from creating custom-integrated circuits to assembling commercial-off-the-shelf (COTS) PC-based components. Custom-integrated-circuit designs yield extremely compact and low-power devices at the expense of high development and upgrade costs and turn-around times, while assembling COTS-PC-technology yields high performance at the expense of large system size and increased power consumption. To achieve a balance between implementing an ultra-compact custom-fabricated neural transceiver and assembling COTS-PC-technology, an overlay of a neural interface upon the TinyOS-based MICA2 platform is described. The system amplifies, digitally encodes, and transmits neural signals real-time at a rate of 9.6 kbps, while consuming less than 66 mW of power. The neural signals are received and forwarded to a client PC over a serial connection. This data rate can be divided for recording on up to 6 channels, with a resolution of 8 bits/sample. This work demonstrates the strengths and limitations of the TinyOS-based sensor technology as a foundation for chronic remote biological monitoring applications and, thus, provides an opportunity to create a system that can leverage from the frequent networking and communications advancements being made by the global TinyOS-development community.


Mycorrhizal Switching and the Role of Fungal Abundance in Seed Germination in a Fully Mycoheterotrophic Orchid, Gastrodia confusoides.
Mycorrhizal associations are essential for orchid germination and seedling establishment, and thus may constrain the distribution and abundance of orchids under natural conditions. Previous studies have shown that germination and seedling establishment in several orchids often decline with increasing distance from adult plants, resulting in non-random spatial patterns of seedling establishment. In contrast, individuals of the fully mycoheterotrophic orchid Gastrodia confusoides often tend to have random aboveground spatial patterns of distribution within bamboo forests. Since G. confusoides is parasitic on litter-decaying fungi, its random spatial patterns of distribution may be due to highly scattered patterns of litter-decaying fungi within bamboo forests. To test this hypothesis, we first identified the main mycorrhizal fungi associating with developing seeds and adult plants at a bamboo forest site in Taiwan using Miseq high-throughput DNA sequencing. Next, we combined seed germination experiments with quantitative PCR (qPCR) analyses to investigate to what extent the abundance of mycorrhizal fungi affected spatial patterns of seed germination. Our results show that seed germination and subsequent growth to an adult stage in G. confusoides required a distinct switch in mycorrhizal partners, in which protocorms associated with a single Mycena OTU, while adults mainly associated with an OTU from the genus Gymnopus. A strong, positive relationship was observed between germination and Mycena abundance in the litter, but not between germination and Gymnopus abundance. Fungal abundance was not significantly related to the distance from the adult plants, and consequently germination was also not significantly related to the distance from adult plants. Our results provide the first evidence that the abundance of litter-decaying fungi varies randomly within the bamboo forest and independently from G. confusoides adults.


Fluorination of graphene enhances friction due to increased corrugation.
The addition of a single sheet of carbon atoms in the form of graphene can drastically alter friction between a nanoscale probe tip and a surface. Here, for the first time we show that friction can be altered over a wide range by fluorination. Specifically, the friction force between silicon atomic force microscopy tips and monolayer fluorinated graphene can range from 5-9 times higher than for graphene. While consistent with previous reports, the combined interpretation from our experiments and molecular dynamics simulations allows us to propose a novel mechanism: that the dramatic friction enhancement results from increased corrugation of the interfacial potential due to the strong local charge concentrated at fluorine sites, consistent with the Prandtl-Tomlinson model. The monotonic increase of friction with fluorination in experiments also demonstrates that friction force measurements provide a sensitive local probe of the degree of fluorination. Additionally, we found a transition from ordered to disordered atomic stick-slip upon fluorination, suggesting that fluorination proceeds in a spatially random manner.


AMPA-induced dark cell degeneration of cerebellar Purkinje neurons involves activation of caspases and apparent mitochondrial dysfunction.
Cerebellar Purkinje neurons (PNs) are selectively vulnerable to AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepriopionic acid)-induced delayed neurotoxicity known as dark cell degeneration (DCD) that is expressed as cytoplasmic and nuclear condensation, neuron shrinkage, and failure of physiology. The present study was initiated to determine whether AMPA-receptor-induced DCD in PNs is associated with Bax translocation to the mitochondria, cytochrome C release from the mitochondria, changes in mitochondrial potential, and activation of representative initiator and executor caspases that include caspase-9, caspase-3, and caspase-7. AMPA consistently and rapidly hyperpolarized mitochondria as reflected by an increase in MitoTracker Red CMS Ros fluorescence. Increases in Bax immunoreactivity were quantitatively and temporally variable and Bax failed to localize to mitochondria. Additionally, we observed a marked increase in immunoreactivity of cytochrome C although its release from mitochondria was not apparent. Mitochondrial membrane hyperpolarization and increases in cytochrome C immunoreactivity preceded caspase activation. Immunohistochemical analyses revealed the active form of caspases-3 and -9 were markedly and significantly increased in PNs following 30 microM AMPA, and caspase-9 activation preceded caspase-3. Increases in active caspase-7 immunoreactivity were less frequently encountered in PNs. Thus DCD shares some characteristics of apoptotic programmed cell death, but lacks typical mitochondrial pathophysiology associated with classic apoptosis. These findings suggest that AMPA-induced DCD is a form of active PCD that lies on a spectrum between classical apoptosis and passive necrosis.


Agitation in the older adult with traumatic brain injury.
Improvements in medical care and health have resulted in an increase in life expectancy and with it a steady increase in the number of older adults, which has resulted in an increasing number of brain-injured older adults. There is limited information available however, which specifically defines the incidence, management and outcome of behavioral sequelae, specifically agitation, in the older adult with TBI. The vast majority of the available literature addressing interventions in the agitated older adult, focuses on the individual with a psychiatric or dementing process who is a resident of a long-term care facility. Agitated behavior in the older adult with acute brain injury differs from this patient population and therefore management must also differ. Management includes behavioral strategies, environmental modifications, structured therapy sessions, appropriate medical management and neuropharmacologic interventions. There are no controlled studies which utilize standardized measures and examine the efficacy of these behavioral, environmental, therapeutical and pharmacological interventions for agitation in the older adult following TBI. In general, considerable care must be taken when using medications in the older adult. Alterations in absorption, pharmacokinetics, liver and renal metabolism, receptor sensitivity, side-effect tolerance, and compliance must all be considered. This article aims to present available information and provide a practical and clinically effective guide for the management of agitation in the older adult with brain injury.


Renal senescence in 2008: progress and challenges.
Kidneys are significantly affected by profound anatomic and functional changes with senescence. These changes lead to decline in glomerular filtration rate, decreased urinary concentrating and diluting ability, diminished urinary acidification, and impaired potassium clearance, to list a few. Such changes make the elderly prone to drug toxicity and serious fluid and electrolyte imbalance. While the entire mystery of aging is far from being clear, the role of oxidative stress, telomere length, Klotho gene expression, and the renin angiotensin system seem to be the key mechanisms involved in aging. Aging, being a complex process, involves an array of intertwined molecular pathways. Simultaneous study of multiple molecular pathways in parallel could provide invaluable information in understanding the clinical course of kidney aging and elucidating mechanisms that play key roles in the aging process. A better understanding of these mechanisms may help to preserve renal function, improve morbidity and mortality, and hopefully reduce healthcare costs for the aging population.


[Safety of Non-anesthesiologist Administration of Propofol for Gastrointestinal Endoscopy].
Propofol (2,6-diisopropylphenol) is a hypnotic drug with a very rapid onset and offset of action. It has increasingly been used in gastrointestinal endoscopy. Administration of propofol by nurses or endoscopists is commonly referred to as non-anesthesiologist-administered propofol (NAAP). There have been a lot of studies on the safety of NAAP compared with those by anesthesiologists. Safety results of those studies are summarized in this review.


Methodology to estimate particulate matter emissions from certified commercial aircraft engines.
Today, about one-fourth of U.S. commercial service airports, including 41 of the busiest 50, are either in nonattainment or maintenance areas per the National Ambient Air Quality Standards. U.S. aviation activity is forecasted to triple by 2025, while at the same time, the U.S. Environmental Protection Agency (EPA) is evaluating stricter particulate matter (PM) standards on the basis of documented human health and welfare impacts. Stricter federal standards are expected to impede capacity and limit aviation growth if regulatory mandated emission reductions occur as for other non-aviation sources (i.e., automobiles, power plants, etc.). In addition, strong interest exists as to the role aviation emissions play in air quality and climate change issues. These reasons underpin the need to quantify and understand PM emissions from certified commercial aircraft engines, which has led to the need for a methodology to predict these emissions. Standardized sampling techniques to measure volatile and nonvolatile PM emissions from aircraft engines do not exist. As such, a first-order approximation (FOA) was derived to fill this need based on available information. FOA1.0 only allowed prediction of nonvolatile PM. FOA2.0 was a change to include volatile PM emissions on the basis of the ratio of nonvolatile to volatile emissions. Recent collaborative efforts by industry (manufacturers and airlines), research establishments, and regulators have begun to provide further insight into the estimation of the PM emissions. The resultant PM measurement datasets are being analyzed to refine sampling techniques and progress towards standardized PM measurements. These preliminary measurement datasets also support the continued refinement of the FOA methodology. FOA3.0 disaggregated the prediction techniques to allow for independent prediction of nonvolatile and volatile emissions on a more theoretical basis. The Committee for Aviation Environmental Protection of the International Civil Aviation Organization endorsed the use of FOA3.0 in February 2007. Further commitment was made to improve the FOA as new data become available, until such time the methodology is rendered obsolete by a fully validated database of PM emission indices for today's certified commercial fleet. This paper discusses related assumptions and derived equations for the FOA3.0 methodology used worldwide to estimate PM emissions from certified commercial aircraft engines within the vicinity of airports.


Treatment of allergic bronchopulmonary aspergillosis: from evidence to practice.
Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder caused by dysregulated immune responses against Aspergillus fumigatus. The disorder usually complicates the course of patients with asthma and cystic fibrosis. Patients with ABPA most often present with asthma that is poorly controlled despite inhaled corticosteroids and long-acting β2 agonists. The treatment of ABPA is complicated due to the occurrence of recurrent exacerbations and spontaneous remissions. The drugs used for treating ABPA include systemic glucocorticoids, antifungal agents and biologics, each with its own benefits and drawbacks. In this review, we illustrate the treatment pathway for ABPA in different situations, using a case-based approach. In each case, we present the options for treatment based on the available evidence from recent clinical trials.


Culture age of Tulasnella affects symbiotic germination of the critically endangered Wyong sun orchid Thelymitra adorata (Orchidaceae).
Orchids (Orchidaceae) are dependent on mycorrhizal fungi for germination and to a varying extent as adult plants. We isolated fungi from wild plants of the critically endangered terrestrial orchid Thelymitra adorata and identified them using a multi-region barcoding approach as two undescribed Tulasnella species, one in each of phylogenetic group II and III (OTU1) of the Tulasnellaceae. Using symbiotic propagation methods, we investigated the role of Tulasnella identity (species and isolate) and age post isolation, on the fungus's ability and efficacy in germinating T. adorata. The group II isolate did not support germination. Seed germination experiments were conducted using either (i) three different isolates of OTU1, (ii) 4- and 12-week-old fungal cultures (post isolation) of a single isolate of OTU1, and (iii) T. subasymmetrica which is widespread and known to associate with other species of Thelymitra. Culture age and fungal species significantly (P < 0.05) affected the time to germination and percentage of seed germination, with greater and faster germination with 4-week-old cultures. Tulasnella subasymmetrica was able to germinate T. adorata to leaf stage, although at slightly lower germination percentages than OTU1. The ability of T. adorata to germinate with T. subasymmetrica may allow for translocation sites to be considered outside of its native range. Our findings on the age of Tulasnella culture affecting germination may have applications for improving the symbiotic germination success of other orchids. Furthermore, storage of Tulasnella may need to take account of the culture age post-isolation, with storage at - 80 °C as soon as possible recommended, post isolation.


Educational needs of families caring for Chinese patients with schizophrenia.
Schizophrenia is a disruptive and distressing illness for patients and family members who care for them. As in Western countries more than 20% of people with schizophrenia in Hong Kong are discharged to their homes, but their families are unprepared to care for them. Studies of caregivers' opinions about the information required to supervise patients are limited, particularly for the purposes of optimizing family-centred care. The aim of this study was to identify the educational needs of Chinese families caring for a relative with schizophrenia. A cross-sectional survey was conducted in Hong Kong with a random sample of 204 family members caring for a relative with schizophrenia. A Chinese version of the Modified Educational Needs Questionnaire, validated in a previous study, was used to identify educational needs that family caregivers considered important in caring for mentally ill relatives. Educational needs perceived as important by caregivers included gaining information about early warning signs of illness and relapse, effects of medication and ways of coping with patients' bizarre and assaulting behaviour. Gender, education level and closeness of the relationship with the patient correlated positively and significantly with need importance. Conversely, the relationship between duration of caring for patient and need importance correlated significantly but negatively, indicating the adverse effect of enduring mental illness on family caregivers' interest in mental health education. This study emphasizes the importance of assessing specific family needs in caring for a relative with mental illness. It also raises concern about the negative effects of the length of time of caring for such patients and the role of socio-economic factors on the perceived educational needs of these families.


Clarifications on breakpoints in HSAX and BTAX by comparative mapping of F9, HPRT, and XIST in cattle.
The coagulation factor IX gene (F9), the hypoxanthine phosphoribosyl transferase 1 gene (HPRT1), and the X-inactive specific transcript gene (XIST) were physically assigned in cattle to analyze chromosomal breakpoints on BTAX recently identified by radiation hybrid (RH) mapping experiments. Whereas the FISH assignment of XIST indicates a similar location on the q-arm of the human and cattle X chromosomes, the locus of HPRT1 supported the assumption of a chromosome rearrangement between the distal half of the q-arm of HSAX and the p-arm of BTAX identified by RH mapping. F9 previously located on the q-arm of BTAX was assigned to the p-arm of BTAX using RH mapping and FISH. The suggested new position of F9 close to HPRT1 supports the homology between HSAXq and BTAXp. The F9 locus corresponds with the gene order found in the homologous human chromosome segment. XIST was assigned on BTAXq23, HPRT1 and F9 were mapped to BTAXp22, and the verification of the location of F9 in a 5000 rad cattle-hamster whole genome radiation hybrid panel linked the gene to markers URB10 and HPRT1.


Effect of egg size and strain and age of hens on the solids content of chicken eggs.
A study was conducted to determine the effect of egg size and the age and strain of hens on the content of egg solids. Eggs were obtained from commercial farms from four strains of hens with similar age groups and received diets formulated to contain the same dietary energy and protein levels across the strains within a farm. Eggs were collected on 2 different d when the flocks reached the average ages of 28, 55, 75, and 97 wk. The eggs collected form each farm were pooled and sorted by size. Each individual egg was used as a replicate for yolk:white ratio; however, five yolks, five whites, and five whole eggs from each strain at each age period were pooled, homogenized, and then used as a replicate to determine the solids contents of yolk, white, and whole eggs. The yolk:white ratio of eggs from 28-wk-old hens was the lowest, that from 55- and 78-wk-old hens was the highest, and that from 97-wk-old hens was intermediate; however, the solids content (percentage) of whole eggs increased with the age of the hens. The solids content of egg white was highest in eggs from 28-wk-old hens. The white solids content of extra large eggs was greater than that of medium eggs, and yolk solids increased with egg size; however, the solids of whole egg were not affected by egg size. The strain of hens had a significant effect on the solids of whole egg, white, and yolk; however, the strain effect on yolk:white ratio was not significant. The results showed that young (28-wk-old) and old birds (97-wk-old) produced eggs with low solids content and intermediate aged hens (55- to 78-wk-old) produced eggs with high solids content. Therefore, it may be more beneficial for egg producers and processors to use young (28-wk-old) and old birds (97-wk-old) for table egg production and birds of intermediate age (55- to 78-wk-old) for liquid egg production.


Higher order vortex gyrotropic modes in circular ferromagnetic nanodots.
Magnetic vortex that consists of an in-plane curling magnetization configuration and a needle-like core region with out-of-plane magnetization is known to be the ground state of geometrically confined submicron soft magnetic elements. Here magnetodynamics of relatively thick (50-100 nm) circular Ni80Fe20 dots were probed by broadband ferromagnetic resonance in the absence of external magnetic field. Spin excitation modes related to the thickness dependent vortex core gyrotropic dynamics were detected experimentally in the gigahertz frequency range. Both analytical theory and micromagnetic simulations revealed that these exchange dominated modes are flexure oscillations of the vortex core string with n = 0,1,2 nodes along the dot thickness. The intensity of the mode with n = 1 depends significantly on both dot thickness and diameter and in some cases is higher than the one of the uniform mode with n = 0. This opens promising perspectives in the area of spin transfer torque oscillators.


Community beliefs about intentional injury and responsibility for prevention.
Community beliefs related to intentional injury inflicted by others were examined in a population-based telephone survey (n = 1032) in Queensland, Australia. Young adults 18 to 24 years old were nominated as the most likely to be intentionally injured. It was found that 89.1% of respondents nominating this group believed that the injury incidents occur in alcohol environments. Though respondents from this age group also identified 18- to 24-year-olds as most likely to be intentionally injured, this was at a significantly lower level when compared with parents or 25- to 64-year-olds respondents. Responsibility for preventing injuries was placed on proprietors of licensed premises, schools, and parents/family of the victim for alcohol, school, and home environments, respectively. Beliefs were aligned with prevalence data on intentional injury, demonstrating a high level of awareness in the community about likely victims and situations where intentional injuries occur. Interventions could target families of young adults to capitalize on high levels of awareness about young adult vulnerability.


Can non-lytic CD8+ T cells drive HIV-1 escape?
The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control.


Survey of Premium Versus Large Manufactured Cigars Use in U.S. Consumers.
An Internet questionnaire was used to determine smoking behavior, purchasing behavior, and risk perceptions among exclusive or nearly exclusive current users of either large manufactured (LMC) or premium cigars (PC). Respondents (n = 250) were recruited from a nationally representative market research panel. An a priori designation of PC users was adapted from criteria in published literature and the recent National Academy of Science report. Examination of responses revealed a (n = 19) disagreement between cigar users' self-classifications and the a priori classification. After eliminating ineligible respondents 188 participants were classified as PC (n = 92; 55 male) or LMC (n = 96; 49 male) users. There were no significant differences in age or gender between groups. Respondents were all over 21 years old. The largest age groups were 30-39 years and 60-69 years. PC users were significantly more likely to have higher annual incomes and to buy cigars online or through tobacco specialty shops, whereas LMC users purchased from convenience stores. Most participants had used other combustible tobacco products (88%) but few had used ENDS (24%) or oral tobacco (7.5%). There was no significant difference in the frequency of smoke inhalation or perceptions of risk for health. There was marked uncertainty in self-characterization of cigar type; our sample had higher female representation than expected (n = 84, 45%), and inhalation was frequently endorsed in both groups (52%, overall). The results support the need for standardized classifications and suggest current trends may indicate shifts in gender and use behavior but provide no evidence supporting less restrictive regulation of PC. An Internet questionnaire was used to determine smoking behavior, purchasing behavior, and risk perceptions among current users of LMC or PC. There was uncertainty about cigar classification even in this sample of regular users. Our results demonstrated more than expected inhalation of cigar smoke, considerable use by females, and under appreciation of health risks. No results supported less restrictive regulations for premium cigars.


Effect of antalarmin, a novel corticotropin-releasing hormone antagonist, on the dynamic function of the preterm ovine fetal hypothalamo-pituitary-adrenal axis.
This study describes the effect of antalarmin on basal and stimulated activity of the hypothalamo-pituitary-adrenal (HPA) axis function in the late gestation ovine fetus. Fetuses received antalarmin (15 mg/h i.v.) or vehicle (cremophor El 50% in ethanol) from day 130 gestational age. Antalarmin infusion did not significantly affect immunoreactive corticotropin (ir-ACTH) concentrations, although there was a tendency for ir-ACTH to be lower and cortisol concentrations were lower in the antalarmin-treated fetuses (p < 0.01). The ir-ACTH response to corticotropin-releasing hormone (CRH) challenge was attenuated (p < 0.05) in the antalarmin-treated fetuses, but neither antalarmin- nor vehicle-treated fetuses had significant cortisol responses to CRH. The ir-ACTH response to hypoxia was diminished (p < 0.05) in the antalarmin-treated fetuses while the cortisol responses of antalarmin- and vehicle-treated fetuses were indistinguishable. Deconvolution analysis revealed no effect of antalarmin treatment on ir-ACTH secretory dynamics. In contrast, antalarmin decreased (p < 0.05) basal, mean and integrated cortisol. The plasma cortisol responses of antalarmin- and vehicle-treated fetuses to exogenous ACTH(1-24) were indistinguishable. These data indicate that, while antalarmin inhibits CRH- and stress-induced ir-ACTH secretion, basal ir-ACTH secretion may be less affected by antalarmin treatment. Paradoxically, cortisol secretion is impaired by antalarmin infusion, although adrenal responsiveness to ACTH is not impaired. These results confirm a role for CRH in stress-induced ACTH secretion in the ovine fetus, though its role in the regulation of basal ACTH and cortisol secretion is unclear.


Influence of plasma osmolality on baroreflex control of sympathetic activity.
The purpose of this study was to determine if plasma osmolality alters baroreflex control of sympathetic activity when controlling for a change in intravascular volume; we hypothesized that baroreflex control of sympathetic activity would be greater during a hyperosmotic stimulus compared with an isoosmotic stimulus when intravascular volume expansion was matched. Seven healthy subjects (25 +/- 2 yr) completed two intravenous infusions: a hypertonic saline infusion (HSI; 3% NaCl) and, on a separate occasion, an isotonic saline infusion (ISO; 0.9% NaCl), both at a rate of 0.15 ml x kg(-1) x min(-1). To isolate the effect of osmolality, comparisons between HSI and ISO conditions were retrospectively matched based on hematocrit; therefore, baroreflex control of sympathetic outflow was determined at 20 min of a HSI and 40 min of an ISO. Muscle sympathetic outflow (MSNA) was directly measured using the technique of peroneal microneurography; osmolality and blood pressure (Finometer) were assessed. The baroreflex control of sympathetic outflow was estimated by calculating the slope of the relationship between MSNA and diastolic blood pressure during controlled breathing. Plasma osmolality was greater during the HSI compared with the ISO (HSI: 292 +/- 0.9 mosmol/kg and ISO: 289 +/- 0.8 mosmol/kg, P < 0.05). Hematocrits were matched (HSI: 39.1 +/- 1% and ISO: 39.1 +/- 1%, P > 0.40); thus, we were successful in isolating osmolality. The baroreflex control of sympathetic outflow was greater during the HSI compared with the ISO (HSI: -8.3 +/- 1.2 arbitrary units x beat(-1) x mmHg(-1) vs. ISO: -4.0 +/- 0.8 arbitrary units x beat(-1) x mmHg(-1), P = 0.01). In conclusion, when controlling for intravascular volume, increased plasma osmolality enhances baroreflex control of sympathetic activity in humans.


Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study.
The aim of this study was to investigate the long-term efficacy and safety of paresthesia-free high-frequency spinal cord stimulation (HF10 SCS) for the treatment of chronic, intractable pain of the low back and legs. Prospective, multicenter, observational study. Patients with significant chronic low back pain underwent implantation of a spinal cord stimulator capable of HF10 SCS. Patients' pain ratings, disability, sleep disturbances, opioid use, satisfaction, and adverse events were assessed for 24 months. After a trial period, 88% (72 of 82) of patients reported a significant improvement in pain scores and underwent the permanent implantation of the system. Ninety percent (65 of 72) of patients attended a 24-month follow-up visit. Mean back pain was reduced from 8.4 ± 0.1 at baseline to 3.3 ± 0.3 at 24 months (P < 0.001), and mean leg pain from 5.4 ± 0.4 to 2.3 ± 0.3 (P < 0.001). Concomitantly to the pain relief, there were significant decreases in opioid use, Oswestry Disability Index score, and sleep disturbances. Patients' satisfaction and recommendation ratings were high. Adverse Events were similar in type and frequency to those observed with traditional SCS systems. In patients with chronic low back pain, HF10 SCS resulted in clinically significant and sustained back and leg pain relief, functional and sleep improvements, opioid use reduction, and high patient satisfaction. These results support the long-term safety and sustained efficacy of HF10 SCS.


Effects of Design Variants in Lower-Limb Prostheses on Gait Synergy.
A lower-limb prosthesis is the mechanical device with which an amputee's residual limb interacts with the walking surface. The pressure and shear forces that affect the residuum due to prosthesis use are the sources of pain, residual-limb skin problems and gait deviations. Direct approaches to reducing these problems include improving fit, alignment technique and socket design as well as increasing cushioning with socket liners. A summary of typical malalignments and their consequences is presented. The malalignments are considered sources of excessive moments applied to the residuum, which simplifies the analysis of a patient's gait. A better design of prosthetic joints could improve prosthetic gait. This article addresses the key mechanical parameter of prosthetic joints, namely the dependence "moment of resistance/angle of deflection." A mathematical model has been developed that links stresses on the residuum in transtibial amputees with the moment of resistance in the prosthetic ankle at the critical gait phases. Analysis of the model yields a substantial decrease in stresses on the residuum during the most demanding, load-bearing phase of stance if the moment of resistance in the ankle is similar to that seen in the biological ankle joint. Gait study shows use of the experimental rolling-joint prosthetic foot more closely simulates normal gait synergy than the SACH foot.


The Sociology of Discrimination: Racial Discrimination in Employment, Housing, Credit, and Consumer Markets.
Persistent racial inequality in employment, housing, and a wide range of other social domains has renewed interest in the possible role of discrimination. And yet, unlike in the pre-civil rights era, when racial prejudice and discrimination were overt and widespread, today discrimination is less readily identifiable, posing problems for social scientific conceptualization and measurement. This article reviews the relevant literature on discrimination, with an emphasis on racial discrimination in employment, housing, credit markets, and consumer interactions. We begin by defining discrimination and discussing relevant methods of measurement. We then provide an overview of major findings from studies of discrimination in each of the four domains; and, finally, we turn to a discussion of the individual, organizational, and structural mechanisms that may underlie contemporary forms of discrimination. This discussion seeks to orient readers to some of the key debates in the study of discrimination and to provide a roadmap for those interested in building upon this long and important line of research.


False recollection induced by photographs: a comparison of older and younger adults.
Looking at photographs constitutes an important everyday memory activity for older adults. The authors found that reviewing photographs of events seen earlier in a videotape increases the likelihood that both older and younger adults remember specific details from the reviewed event (W. Koutstaal, D. L. Schacter, M. K. Johnson, K. E. Angell, & M. S. Gross, 1977). In the present study, the authors report 2 experiments demonstrating that photo review can also produce false recollection in elderly adults: After reviewing photos of events that had not been shown earlier in a videotape, older but not younger adults were later more likely to "remember" that those events had been shown in the videotape. False recollection induced by photo review appears to reflect an age-related deficit in source-monitoring abilities.


Fat distribution in women with HIV infection.
Both peripheral fat loss and central fat gain have been reported in women with HIV infection. We determined the fat changes that are specific to HIV infection in women. HIV-infected and control women from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) were compared. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of fat change and clinical examination. Whole-body magnetic resonance imaging measured regional adipose tissue volumes. The relationship among different adipose tissue depots was assessed. Factors associated with individual depots were analyzed using multivariate linear regression. HIV-infected women reported more fat loss than controls in all peripheral and most central depots. Peripheral lipoatrophy was more frequent in HIV-infected women than controls (28% vs. 4%, P < 0.001), whereas central lipohypertrophy was similar (62% vs. 63%). Among HIV-infected women, those with central lipohypertrophy were less likely to have peripheral lipoatrophy (odds ratio, 0.39; 95% confidence interval, 0.20 to 0.75, P = 0.006) than those without central lipohypertrophy. On magnetic resonance imaging, HIV-infected women with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-infected women without peripheral lipoatrophy. Compared with controls, HIV-infected women had less SAT in the legs, regardless of the presence or absence of lipoatrophy. However, those without lipoatrophy had more VAT and upper trunk SAT than controls. Use of the antiretroviral drug stavudine was associated with less leg SAT but was not associated with VAT. The use of highly active antiretroviral therapy, however, was associated with more VAT. Peripheral lipoatrophy occurs commonly in HIV-infected women but is not associated with reciprocally increased VAT or trunk fat.


Formulation development and evaluation of innovative two-polymer (SR-2P) bioadhesive vaginal gel.
The main objective of this investigation was to study the feasibility of developing a vaginal bioadhesive microbicide using a SRI's proprietary two-polymer gel platform (SR-2P). Several formulations were prepared with different combinations of temperature-sensitive polymer (Pluronic® F-127) and mucoadhesive polymer (Noveon® AA-1), producing gels of different characteristics. Prototype polymeric gels were evaluated for pH, osmolality, buffering capacity, and viscosity under simulated vaginal semen dilutions, and bioadhesivity using ex vivo mini pig vaginal tissues and texture analyzer. The pH of the polymeric gel formulations ranged from 5.1 to 6.4; the osmolality varied from 13 to 173 mOsm. Absolute viscosity ranged from 513 to 3,780 cPs, and was significantly reduced (1.5- to 3-fold) upon incubation with simulated vaginal and semen fluid mixture. Among the tested gels (indicated in the middle row as a molar ratio of a mixture of Noveon vs. Pluronic), only SR-2P retained gel structure upon dilution with simulated fluids and mild simulated coital stress. The pH of the SR-2P gel was maintained at about 4.6 in simulated vaginal fluid and also showed high peak force of adhesion in mini pig vaginal tissue. Furthermore, SR-2P gel caused no or only minimal irritation in a mouse vaginal irritation model. The results of this preliminary study demonstrated the potential application of SR-2P gel as a vaginal microbicide vehicle for delivery of anti-HIV agents.


Immunophenotypic and diagnostic characterization of angioimmunoblastic T-cell lymphoma by advanced flow cytometric technology.
Angioimmunoblastic T-cell lymphoma (AITL) often shows systemic symptoms related to immune dysregulation and cytokine production. Biopsy usually harbors few malignant cells in an abundant reactive background, which can be diagnostically challenging in cases with small biopsies. This study was performed to assess the value of flow cytometry (FC) and to determine the immunophenotypic alterations in 155 samples from 38 patients with AITL. FC detected an aberrant T-cell population in 97 of 155 samples that represented 0.5-90% of lymphocytes. Blood was involved in 11 of 16 patients. The most frequent immunophenotypic aberrancies included loss of CD3; altered T-cell receptor expression and aberrant CD10 expression. Altered CD3 expression was more frequently seen in peripheral blood (PB) and bone marrow (BM), whereas aberrant CD10 expression was more common in lymph node (LN). AITL cells often exhibit abnormal CD4+ immunophenotype with diminished or absent CD3 and variable CD10 expression. Multiparameter FC is an effective tool for supporting the diagnosis of AITL in any fluid and various tissue specimens types.


Experimental and numerical investigations on the use of polymer Hopkinson pressure bars.
Split Hopkinson pressure bar (SHPB) testing has traditionally been carried out using metal bars. For testing low stiffness materials such as rubbers or low strength materials such as low density cellular solids considered primarily herein, there are many advantages to replacing the metal bars with polymer bars. An investigation of a number of aspects associated with the accuracy of SHPB testing of these materials is reported. Test data are used to provide qualitative comparisons of accuracy using different bar materials and wave-separation techniques. Sample results from SHPB tests are provided for balsa, Rohacell foam and hydroxyl-terminated polybutadiene. The techniques used are verified by finite-element (FE) analysis. Experimentally, the material properties of the bars are determined from impact tests in the form of a complex elastic modulus without curve fitting to a rheological model. For the simulations, a rheological model is used to define the bar properties by curve fitting to the experimentally derived properties. Wave propagation in a polymer bar owing to axial impact of a steel bearing ball is simulated. The results indicate that the strain histories can be used to determine accurately the viscoelastic properties of polymer bars. An FE model of the full viscoelastic SHPB set-up is then used to simulate tests on hyperelastic materials.


Defluorinative Alkylboration of Alkenes Enabled by Dual Photoredox and Copper Catalysis.
A regioselectivity-reversed three-component defluorinative alkylboration of alkenes with trifluoromethyls and bis(pinacolato)diboron via dual photoredox/copper catalysis is reported. The mild conditions are compatible with a wide array of nonactivated trifluoromethyl aromatics bearing electron-donating or -neutral substituents, trifluoroacetamides, and various nonactivated terminal and internal alkenes, enabling straightforward access to synthetically valuable γ-gem-difluoroalkyl boronates with high efficiency. Furthermore, this protocol is applicable to alkene-tethered trifluoromethyl aromatics to furnish gem-difluoromethylene-containing cyclic compounds. Synthetic applications and preliminary mechanistic studies are also presented.


Sadism linked to loneliness: psychodynamic dimensions of the sadistic serial killer Jeffrey Dahmer.
In this article the psychodynamic link between loneliness and sadism is examined on basis of a case report of the sadistic and cannibalistic serial killer Jeffery Dahmer. Envy, shame/rage mechanism, a disturbed oral-sadistic development, castration fear and severe feelings of inferiority, the conviction of being unlovable and unacceptable, need to diminish tension, powerful and sadistic fantasies as a consequence of inadequate and frustrated parenting, and reality distortion appear to be involved in sadistic etiology.