High-speed combustion diagnostics in a rapid compression machine by broadband supercontinuum absorption spectroscopy.
The first results under fired internal combustion engine conditions based on a supercontinuum absorption spectrometer are presented and discussed. Temperature, pressure, and water mole fraction are inferred simultaneously from broadband H2O absorbance spectra ranging from 1340 nm to 1440 nm. The auto-ignition combustion process is monitored for two premixed n-heptane/air mixtures with 10 kHz in a rapid compression machine. Pressure and temperature levels during combustion exceed 65 bar and 1900 K, respectively. To allow for combustion measurements, the robustness of the spectrometer against beam steering has been improved compared to its previous version. Additionally, the detectable wavelength range has been extended further into the infrared region to allow for the acquisition of distinct high-temperature water transitions located in the P-branch above 1410 nm. Based on a theoretical study, line-of-sight (LOS) effects introduced by temperature stratification on the broadband fitting algorithm in the complete range from 1340 nm to 1440 nm are discussed. In this context, the recorded spectra during combustion were evaluated only within a narrower spectral region exhibiting almost no interference from low-temperature molecules (here, P-branch from 1410 nm to 1440 nm). It is shown that this strategy mitigates almost all of the LOS effects introduced by cold molecules and the evaluation of the spectrum in the entirely recorded wavelength range at engine combustion conditions.


p15PAF binding to PCNA modulates the DNA sliding surface.
p15PAF is an oncogenic intrinsically disordered protein that regulates DNA replication and lesion bypass by interacting with the human sliding clamp PCNA. In the absence of DNA, p15PAF traverses the PCNA ring via an extended PIP-box that contacts the sliding surface. Here, we probed the atomic-scale structure of p15PAF-PCNA-DNA ternary complexes. Crystallography and MD simulations show that, when p15PAF occupies two subunits of the PCNA homotrimer, DNA within the ring channel binds the unoccupied subunit. The structure of PCNA-bound p15PAF in the absence and presence of DNA is invariant, and solution NMR confirms that DNA does not displace p15PAF from the ring wall. Thus, p15PAF reduces the available sliding surfaces of PCNA, and may function as a belt that fastens the DNA to the clamp during synthesis by the replicative polymerase (pol δ). This constraint, however, may need to be released for efficient DNA lesion bypass by the translesion synthesis polymerase (pol η). Accordingly, our biochemical data show that p15PAF impairs primer synthesis by pol η-PCNA holoenzyme against both damaged and normal DNA templates. In light of our findings, we discuss the possible mechanistic roles of p15PAF in DNA replication and suppression of DNA lesion bypass.


Trends in Risks for Second Primary Cancers Associated With Index Human Papillomavirus-Associated Cancers.
In the last 4 decades, survival among patients with human papillomavirus (HPV)-associated cancers has improved, while the incidence of these cancers has increased among younger cohorts. Among survivors of HPV-associated cancers, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancers (HPV-SPCs). To investigate the risk of HPV-SPCs among survivors of HPV-associated index cancers and to test the hypothesis that the HPV-SPC risk among these persons has increased over the last 4 decades. A retrospective cohort study of 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HPV-associated (cervical, vaginal, vulvar, oropharyngeal, anal, and penile) cancers diagnosed from January 1, 1973, through December 31, 2014. The dates of analysis were July 1, 2017, to January 31, 2018. The HPV-SPC risk was quantified by calculating standard incidence ratios (SIRs) and excess absolute risks (EARs) per 10 000 person-years at risk (PYR). The HPV-SPC risk by time was estimated using Poisson regression. From 113 272 (73 085 female and 40 187 male) survivors of HPV-associated cancers, 1397 women and 1098 men developed HPV-SPCs. The SIRs for HPV-SPCs were 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men. The EARs were 18.2 per 10 000 PYR for women and 53.5 per 10 000 PYR for men. Among both women and men, those who had index oropharyngeal cancers had the highest HPV-SPC risk (SIR, 19.8 [95% CI, 18.4-21.4] and EAR, 80.6 per 10 000 PYR among women; SIR, 18.0 [95% CI, 16.9-19.1] and EAR, 61.5 per 10 000 PYR among men). Women who had index cervical cancers and men who had index anal cancers had the lowest HPV-SPC risk (SIR, 2.4 [95% CI, 2.2-2.7] and EAR, 4.5 per 10 000 PYR among women; SIR, 6.5 [95% CI, 4.7-8.8] and EAR, 18.5 per 10 000 PYR among men). Both women and men who had index HPV-associated cancers of any kind had a significantly higher risk of oropharyngeal HPV-SPCs. Over the last 4 decades, the risk of developing most types of HPV-SPCs after index cervical, vaginal, and vulvar cancers increased. According to this study, the HPV-SPC risk among survivors of HPV-associated cancers is significant, implying that persistent HPV infection at multiple sites may be associated with HPV-SPCs. These findings have the potential to inform surveillance recommendations for survivors of HPV-associated cancers.


Opposing auxiliary conformations produce the same torquoselectivity in an oxazolidinone-directed Nazarov cyclization.
Most applications of chiral oxazolidinone auxiliaries in asymmetric synthesis operate through a common set of stereocontrol principles. That is, the oxazolidinone is made to adopt a specific, coplanar conformation with respect to the prochiral substrate, and reaction occurs preferentially at whichever stereoheterotopic face is not blocked by the substituents on the oxazolidinone. In contrast to these principles, we report here the discovery of an alternative mechanism of oxazolidinone-based stereocontrol that does not require coplanarity and is driven instead by allylic strain. This pathway has been uncovered through computational studies of an asymmetric Nazarov cyclization. Chiral oxazolidinone auxiliaries provide essentially complete control over the torquoselectivity of ring closure and the regioselectivity of subsequent deprotonation. Density functional theory calculations (M06-2X//B3LYP) reveal that in the transition state of 4π electrocyclic ring closure, the oxazolidinone ring and the cyclizing pentadienyl cation are distorted from coplanarity in a manner that gives two transition state conformations of similar energy. These two conformers are distinguished by a 180° flip in the auxiliary orientation such that in one conformer the oxazolidinone carbonyl is oriented toward the OH of the pentadienyl cation (syn-conformer) and in the other it is oriented away from this OH (anti-conformer). Surprisingly, both conformations induce the same sense of torquoselectivity, with a 3-5 kcal/mol preference for the C5-β epimer of the ring-closed cation. In both conformations, the conrotatory mode that leads to the C5-α epimer is disfavored due to higher levels of allylic strain between the oxazolidinone substituent and adjacent groups on the pentadienyl cation (R(4) and OH). The excellent torquoselectivities obtained in the oxazolidinone-directed Nazarov cyclization suggest that the allylic strain-driven stereoinduction pathway represents a viable alternative mechanism of stereocontrol for reactions of sterically congested substrates that lie outside of the traditional coplanar (N-acyloxazolidinone) paradigm.


Emotions and neurones.
It was shown previously (Simonov, 1964), that emotion is a function of need and that it estimates the probability (possibility) of its satisfaction. Changes in command neuronal activity of alimentary and defensive behaviour in response to food, showed to a hungry or replete Helix lucorum L., suggest a complex internal organization of the reaction to the external stimulus. Two types of neurones were revealed in the self-stimulation zones the rat hypothalamus, one of them being connected with motivational mechanism, the other with reinforcement. Thus, relative independence of motivations and emotions is also manifested at the neuronal level.


Purposes and duties in scientific modelling.
More people than ever are paying attention to philosophical questions about epidemiological models, including their susceptibility to the influence of social and ethical values, sufficiency to inform policy decisions under certain conditions, and even their fundamental nature. One important question pertains to the purposes of epidemiological models, for example, are COVID-19 models for 'prediction' or 'projection'? Are they adequate for making causal inferences? Is one of their goals, or virtues, to change individual responses to the pandemic? In this essay, we offer our perspective on these questions and place them in the context of other recent philosophical arguments about epidemiological models. We argue that clarifying the intended purpose of a model, and assessing its adequacy for that purpose, are moral-epistemic duties, responsibilities which pertain to knowledge but have moral significance nonetheless. This moral significance, we argue, stems from the inherent value-ladenness of models, along with the potential for models to be used in political decision making in ways that conflict with liberal values and which could lead to downstream harms. Increasing conversation about the moral significance of modelling, we argue, could help us to resist further eroding our standards of democratic scrutiny in the COVID-19 era.


Geo-spatial reporting for monitoring of household immunization coverage through mobile phones: Findings from a feasibility study.
The addition of Global Positioning System (GPS) to a mobile phone makes it a very powerful tool for surveillance and monitoring coverage of health programs. This technology enables transfer of data directly into computer applications and cross-references to Geographic Information Systems (GIS) maps, which enhances assessment of coverage and trends. Utilization of these systems in low and middle income countries is currently limited, particularly for immunization coverage assessments and polio vaccination campaigns. We piloted the use of this system and discussed its potential to improve the efficiency of field-based health providers and health managers for monitoring of the immunization program. Using "30×7" WHO sampling technique, a survey of children less than five years of age was conducted in random clusters of Karachi, Pakistan in three high risk towns where a polio case was detected in 2011. Center point of the cluster was calculated by the application on the mobile. Data and location coordinates were collected through a mobile phone. This data was linked with an automated mHealth based monitoring system for monitoring of Supplementary Immunization Activities (SIAs) in Karachi. After each SIA, a visual report was generated according to the coordinates collected from the survey. A total of 3535 participants consented to answer to a baseline survey. We found that the mobile phones incorporated with GIS maps can improve efficiency of health providers through real-time reporting and replacing paper based questionnaire for collection of data at household level. Visual maps generated from the data and geospatial analysis can also give a better assessment of the immunization coverage and polio vaccination campaigns. The study supports a model system in resource constrained settings that allows routine capture of individual level data through GPS enabled mobile phone providing actionable information and geospatial maps to local public health managers, policy makers and study staff monitoring immunization coverage.


Ultra-trace element analysis of human follicular fluid by ICP-MS/MS: pre-analytical challenges, contamination control, and matrix effects.
Follicular fluid (FF), which is the fluid that envelops the developing oocyte (egg cell) in the ovary, can be analyzed to assess trace element content as well as to determine potential exposure to toxic elements in women seeking in vitro fertilization (IVF) treatment. Such measurements may be useful in establishing associations with potential adverse effects on oocyte viability and subsequent pregnancy outcomes. The principal goal of this study was to leverage the next generation of inorganic mass spectrometry based on ICP-MS/MS to address the numerous analytical challenges of (ultra-)trace element analysis of human FF specimens. Ultra-trace element measurements are defined by the Clinical Laboratory Standards Institute as fluid concentrations below 10 μg L-1 or tissue mass fractions below 1 μg g-1. Stringent pre-analytical procedures were developed to minimize exogenous contamination during FF specimen collection and storage in a prospective study of 56 women seeking IVF treatment. ICP-MS/MS instrumental parameters were carefully optimized, and the method validated for 11 biologically important elements that included 4 at trace levels (Cu, Se, Sr, and Zn) and 7 at ultra-trace levels (As, Cd, Co, Mo, Mn, Hg, and Pb). Method limits of detection (LODs) for ultra-trace elements varied from 5.6 ng L-1 for Cd to 0.11 μg L-1 for Mo. A total of 197 human FF specimens were analyzed using the proposed ICP-MS/MS method with 84% of specimens detectable for Pb and 100% detectable for Co, Cu, Mn, Mo, Sr, and Zn. The method based on ICP-MS/MS was compared to a previous method developed for FF using SF-ICP-MS.


Defining life: synthesis and conclusions.
The first part of the paper offers philosophical landmarks on the general issue of defining life. Section 1 defends that the recognition of "life" has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. Section 2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. Section 3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about "life". The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (Section 4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. Section 5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers to two conditions: individual self-maintenance and the open-ended evolution of a collection of similar entities. The other category refuse to include reproduction and evolution, and take a sort of psychic view of the living. Section 6 examines the relationship between the question of the definition of life and that of the origins of life. There is a close parallel between the general conceptions of the origins of life and the definitions of life.


A Future for Simulation in Acute Neurology.
Acute neurologic (and potentially disability prone) conditions are rarely taught and, if so, at the bedside and usually after the fact. Simulation training offers a realistic environment to teach rapid-fire decision making, how to take charge, and how best to approach a deteriorating, acutely ill neurologic patient.Simulating acute neurology is a newly emerging educational program. Proven principles of simulation, which may include teaching technical skills, can be applied to acute neurology (and neurointensive care). Communication skills pertaining to catastrophic neurologic injury with all its ethical ramifications can be taught and practiced. There is a growing need for well-designed, tested teaching scenarios and a need to validate this approach. This review provides an overview of the potential opportunities available in medical institutions with a simulation center.


Modeling the Relationships Between Historical Redlining, Urban Heat, and Heat-Related Emergency Department Visits: An Examination of 11 Texas Cities.
Place-based structural inequalities can have critical implications for the health of vulnerable populations. Historical urban policies, such as redlining, have contributed to current inequalities in exposure to intra-urban heat. However, it is unknown whether these spatial inequalities are associated with disparities in heat-related health outcomes. The aim of this study is to determine the relationships between historical redlining, intra-urban heat conditions, and heat-related emergency department visits using data from eleven Texas cities. At the zip code level, the proportion of historical redlining was determined, and heat exposure was measured using daytime and nighttime land surface temperature (LST). Heat-related inpatient and outpatient rates were calculated based on emergency department visit data that included ten categories of heat-related diseases between 2016 and 2019. Regression or spatial error/lag models revealed significant associations between higher proportions of redlined areas in the neighborhood and higher LST (Coef. = 0.0122, 95% CI = 0.0039 - 0.0205). After adjusting for indicators of social vulnerability, neighborhoods with higher proportions of redlining showed significantly elevated heat-related outpatient visit rate (Coef. = 0.0036, 95% CI = 0.0007-0.0066) and inpatient admission rate (Coef. = 0.0018, 95% CI = 0.0001-0.0035). These results highlight the role of historical discriminatory policies on the disparities of heat-related illness and suggest a need for equity-based urban heat planning and management strategies.


One21: A Novel, Customizable Injection Protocol for Treatment of the Forehead with IncobotulinumtoxinA.
It is well known that incobotulinumtoxinA (INCO) is an effective approved treatment for dynamic wrinkles of the upper face caused by the action of mimetic muscles over time. In doing so, it is important to maintain a balance between muscle groups and a natural facial appearance. Patients differ enormously in their facial anatomy regarding structure and function, both within and between genders, ethnicities, and age. Therefore, treating all patients with the same injection pattern and the same doses can result in undesired outcomes. There is a need for a tailored approach to achieve optimal results, as well as to increase patient satisfaction. With this in mind, the novel one21 injection technique which allows for individualized treatment has been developed for the treatment of horizontal forehead lines using INCO, resulting in a positive impact on eyebrow position and shape. This technique is the next step in a customized approach, giving natural-looking results and high patient satisfaction.


Nucleus accumbens dopamine increases sexual motivation in sexually satiated male rats.
The influence of the main dopaminergic brain regions controlling copulation, the medial preoptic area (mPOA) and the nucleus accumbens (NAcc), on male rat sexual behavior expression has not been fully established. This work analyzes the sexual effects of dopamine (DA) receptor activation in the mPOA or the NAcc of sexually active male rats, with an intact (sexually experienced) or a reduced (sexually exhausted) sexual motivation. The non-specific DA receptor agonist apomorphine and the D2-like receptor agonist quinpirole were infused into the mPOA or the NAcc of sexually experienced or sexually exhausted male rats and their sexual behavior recorded. DA receptor activation neither in the mPOA nor in the NAcc modified the copulatory behavior of sexually experienced male rats. DA receptor stimulation in the NAcc, but not in the mPOA, reversed the characteristic sexual inhibition of sexually satiated rats, and D2-like receptors were found to participate in this effect. The optimal sexual performance of sexually experienced male rats cannot be further improved by DA receptor activation at either brain region. In sexually satiated rats, which are sexually inhibited and have a diminished sexual motivation, NAcc DA receptor stimulation appears to play a key role in their capacity to respond to a motivational significant stimulus, the receptive female, with the participation of D2-like receptors. Activation of DA receptors with the same drug, at the same dose and in the same brain region, produces different effects on copulatory behavior that depend on the animal's sexual motivational state.


Isolation and genome sequence annotation of SallyK, a newly discovered cluster EG bacteriophage infecting Microbacterium.
Discovered from soil in a flower planter in Pocatello, Idaho and using Microbacterium foliorum, SallyK is a lytic bacteriophage with a siphovirus morphology. It has a 62,883 bp-long genome with 103 putative genes. Based on gene content similarity to actinobacteriophages, SallyK is assigned to cluster EG.


Minimally invasive surgical aortic valve replacement versus transfemoral transcatheter aortic valve implantation in low-risk octogenarians : Observational, retrospective and single-center study.
The aim of this study was to compare short-term and mid-term outcomes in low-risk octogenarian population treated with transfemoral transcatheter aortic valve implantation (tf-TAVI) or minimally invasive aortic valve replacement (mini-AVR) for severe aortic stenosis. In this single-center, retrospective cohort study we gathered data on low-risk (Society of Thoracic Surgeons [STS] score < 4%) octogenarians before and after tf-TAVI and mini-AVR performed between January 2013 and May 2019; follow-up was completed in May 2022. Short-term outcomes were hospital length of stay, in-hospital all-cause mortality and other major postoperative outcomes. Mid-term clinical outcomes were 1‑year and 3‑year all-cause mortality. Propensity score-based matching was performed. In total 106 patients were matched, resulting in 53 pairs. In-hospital complications were similar between the matched groups of patients with the exception of mild and moderate paravalvular leak (mini-AVR vs. tf-TAVI: mild PVL: 3.8% vs. 45.3%, p < 0.001; moderate PVL: 0% vs. 3.8%, p = 0.4952) and of postprocedural acute kidney injury that was more frequent in mini-AVR group (mini-AVR vs. tf-TAVI: 22.6% vs. 5.7%; p = 0.023). Hospital length of stay (p = 0.239) and in-hospital mortality (p = 0.495) did not differ between groups. The 1-year and 3‑year all-cause mortality Kaplan-Meier estimates were similar between mini-AVR and tf-TAVI. In the present study on low-risk octogenarians, transfemoral TAVI and minimally invasive AVR showed comparable short-term and mid-term results. Both procedures are deemed safe and effective. Larger RCTs will be required to determine which low-risk patients will benefit most from TAVI.


Reduced frequency of lateral root branching improves N capture from low-N soils in maize.
Suboptimal nitrogen (N) availability is a primary constraint for crop production in developing countries, while in developed countries, intensive N fertilization is a primary economic, energy, and environmental cost for crop production. We tested the hypothesis that under low-N conditions, maize (Zea mays) lines with few but long (FL) lateral roots would have greater axial root elongation, deeper rooting, and greater N acquisition than lines with many but short (MS) lateral roots. Maize recombinant inbred lines contrasting in lateral root number and length were grown with adequate and suboptimal N in greenhouse mesocosms and in the field in the USA and South Africa (SA). In low-N mesocosms, the FL phenotype had substantially reduced root respiration and greater rooting depth than the MS phenotype. In low-N fields in the USA and SA, the FL phenotype had greater rooting depth, shoot N content, leaf photosynthesis, and shoot biomass than the MS phenotype. The FL phenotype yielded 31.5% more than the MS phenotype under low N in the USA. Our results are consistent with the hypothesis that sparse but long lateral roots improve N capture from low-N soils. These results with maize probably pertain to other species. The FL lateral root phenotype merits consideration as a selection target for greater crop N efficiency.


Complexity in treatment of syntactic deficits.
This article addresses complexity in the context of treatment for sentence structural impairments in agrammatic aphasia, with emphasis on noncanonical sentences involving linguistic movement and their related counterparts. Extensions of the complexity effect to recovery of canonical sentences also are discussed, stressing the linguistic properties of verbs as well as grammatical morphology in building complexity hierarchies. A number of variables to consider in developing complexity hierarchies in the syntactic domain are addressed, and a series of studies using single-subject controlled experimental analysis are discussed. Findings across studies show that training complex sentences results in improvement of simpler structures when, and only when, the underlying linguistic properties are shared by both. The opposite approach, training simple structures first and building to more complex ones, does not provide the full benefit of treatment, in that little or no generalization occurs across structures. Using complex language material as a starting point for treatment of sentence structural deficits in aphasia results in cascading generalization to simpler, linguistically related material and expands spontaneous language production in many language-disordered adults with aphasia. Clinicians are, therefore, urged to adopt this approach in clinical practice, even though it is counterintuitive and departs significantly from conventional treatment methods.


Laparoscopic Nissen fundoplication after failed EsophyX fundoplication.
Reflux control may be ineffective in a substantial number of patients after endoluminal EsophyX fundoplication for gastro-oesophageal reflux disease. Subsequent laparoscopic Nissen fundoplication (LNF) might be required to relieve symptoms. The aim of this study was to evaluate the outcome of LNF after previous EsophyX fundoplication. EsophyX failure was defined as recurrence or persistence of typical symptoms, with or without anatomical failure of the wrap or persisting pathological oesophageal acid exposure. Consecutive patients who underwent LNF after failed EsophyX fundoplication were identified. Symptomatic outcome was obtained by standardized questionnaire, and objective outcome by endoscopy, oesophageal manometry and pH monitoring. Eleven patients were included. During LNF, intraoperative gastric perforation occurred in two patients and one developed a subphrenic abscess after operation. Daily heartburn was present in one patient after LNF and three had troublesome daily dysphagia. General quality of life after LNF was not significantly better than that before EsophyX fundoplication. Oesophageal acid exposure was normalized in all patients after surgery. Oesophagitis was absent after LNF in all except one patient who had persisting grade A oesophagitis. Symptomatic and objective reflux control are satisfactory after LNF for a failed EsophyX procedure. Previous EsophyX fundoplication, however, is associated with a risk of gastric injury during LNF and a relatively high rate of postfundoplication dysphagia.


Bro1 is an endosome-associated protein that functions in the MVB pathway in Saccharomyces cerevisiae.
Multivesicular bodies are late endosomal compartments containing lumenal vesicles that are formed by inward budding of the limiting endosomal membrane. In the yeast Saccharomyces cerevisiae, integral membrane proteins are sorted into the lumenal vesicles of multivesicular bodies, and this process requires the class E subset of VPS genes. We show that one of the class E VPS genes, BRO1/VPS31, encodes a cytoplasmic protein that associates with endosomal compartments. The dissociation of Bro1 from endosomes requires another class E Vps protein, Vps4, which is an ATPase that also regulates the endosomal dissociation of ESCRT-III, a complex of four class E Vps proteins (Vps2, Vps20, Vps24 and Snf7/Vps32) that oligomerize at the endosomal membrane. We also show that the endosomal association of Bro1 is specifically dependent on one of the ESCRT-III components, Snf7. Our data suggest that the function of Bro1 in the MVB pathway takes place on endosomal membranes and occurs in concert with or downstream of the function of the ESCRT-III complex.


[Distal biceps tendon tear. A case report].
Distal tears of the biceps tendon are rare lesions and account for 3-5% of all biceps lesions. Surgical treatment produces better outcomes than conservative treatment from the perspective of forearm flexion and supination. Different implants and approaches are currently available to improve the course of patients and reduce the postoperative complications. The case of a patient who underwent surgical treatment with anatomical reattachment with anchors is presented herein as well as his two-year follow-up. This is considered as an excellent outcome given that the patient remained asymptomatic and returned to his previous athletic activity without complications.


[Neuromediator systems in the brain of rats in alcohol abstinence syndrome].
The content of key neuromediators in the brain cortex, brain stem, and thalamus was studied in rats under conditions of alcohol abstinence syndrome. At the peak of the abstinence syndrome manifestation (one day), these parts of the brain were characterized by an increase in the level of dopamine, which was normalized by the end of a one-week period of abstinence. On the third day of abstinence, there was a decrease in the content of noradrenaline in the brain stem on the background of normalization of the neurotransmission processes in the brain cortex and thalamus. Upon a one-week abstinence, the content of noradrenaline in the brain stem and cortex changed in the opposite directions.


Mitogen-activated protein kinase activity drives cell trajectories in colorectal cancer.
In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional states of colorectal cancer cells and signals controlling their development by performing single-cell transcriptome analysis of tumors and matched non-cancerous tissues of twelve colorectal cancer patients. We defined patient-overarching colorectal cancer cell clusters characterized by differential activities of oncogenic signaling pathways such as mitogen-activated protein kinase and oncogenic traits such as replication stress. RNA metabolic labeling and assessment of RNA velocity in patient-derived organoids revealed developmental trajectories of colorectal cancer cells organized along a mitogen-activated protein kinase activity gradient. This was in contrast to normal colon organoid cells developing along graded Wnt activity. Experimental targeting of EGFR-BRAF-MEK in cancer organoids affected signaling and gene expression contingent on predictive KRAS/BRAF mutations and induced cell plasticity overriding default developmental trajectories. Our results highlight directional cancer cell development as a driver of non-genetic cancer cell heterogeneity and re-routing of trajectories as a response to targeted therapy.


Increased friction coefficient and superficial zone protein expression in patients with advanced osteoarthritis.
To quantify the concentration of superficial zone protein (SZP) in the articular cartilage and synovial fluid of patients with advanced osteoarthritis (OA) and to further correlate the SZP content with the friction coefficient, OA severity, and levels of proinflammatory cytokines. Samples of articular cartilage and synovial fluid were obtained from patients undergoing elective total knee replacement surgery. Additional normal samples were obtained from donated body program and tissue bank sources. Regional SZP expression in cartilage obtained from the femoral condyles was quantified by enzyme-linked immunosorbent assay (ELISA) and visualized by immunohistochemistry. Friction coefficient measurements of cartilage plugs slid in the boundary lubrication system were obtained. OA severity was graded using histochemical analyses. The concentrations of SZP and proinflammatory cytokines in synovial fluid were determined by ELISA. A pattern of SZP localization in knee cartilage was identified, with load-bearing regions exhibiting high SZP expression. SZP expression patterns were correlated with friction coefficient and OA severity; however, SZP expression was observed in all samples at the articular surface, regardless of OA severity. SZP expression and aspirate volume of synovial fluid were higher in OA patients than in normal controls. Expression of cytokines was elevated in the synovial fluid of some patients. Our findings indicate a mechanochemical coupling in which physical forces regulate OA severity and joint lubrication. The findings of this study also suggest that SZP may be ineffective in reducing joint friction in the boundary lubrication mode at an advanced stage of OA, where other mechanisms may dominate the observed tribological behavior.


Age modifies the effect of body size on fecundity in Culex quinquefasciatus Say (Diptera: Culicidae).
Fecundity of mosquitoes can vary with many factors and can have a strong effect on population growth. This study reports the effects of body size, blood meal size, and age on the reproductive output of nulliparous Culex quinquefasciatus, a vector of arboviruses and other pathogens. Mated adult female mosquitoes from a colony were reared under standard conditions and fed on chickens at different ages post-eclosion. Blood meal size and wing length were recorded, as well as the number of eggs in the first-cycle egg raft. Each of these factors had a significant influence on fecundity considered in a simple regression context. Multiple regression analysis revealed a significant interaction effect between age and body size on fecundity. Up to 13 days of age, fecundity was positively correlated with body size, but in mosquitoes older than 13 days, this relationship was not significantly different from zero. These results are discussed in terms of the known physiology of this and other species.


Morphology-dependent light trapping in thin-film organic solar cells.
The active layer materials used in organic photovoltaic (OPV) cells often self-assemble into highly ordered morphologies, resulting in significant optical anisotropies. However, the impact of these anisotropies on light trapping in nanophotonic OPV architectures has not been considered. In this paper, we show that optical anisotropies in a canonical OPV material, P3HT, strongly affect absorption enhancements in ultra-thin textured OPV cells. In particular we show that plasmonic and gap-mode solar cell architectures redistribute electromagnetic energy into the out-of-plane field component, independent of the active layer orientation. Using analytical and numerical calculations, we demonstrate how the absorption in these solar cell designs can be significantly increased by reorienting polymer domains such that strongly absorbing axes align with the direction of maximum field enhancement.


Blood metabolomics and impacted cellular mechanisms during transition into lactation in dairy cows that develop metritis.
The objective of this study was to identify metabolites associated with metritis and use them for identification of cellular mechanisms affected during transition into lactation. Holstein cows (n = 104) had blood collected in the prepartum period (d -14 ± 6 relative to calving), at calving (d 0), and at the day of metritis diagnosis (d 7 ± 2 after calving). Cows with reddish or brownish, watery, and fetid discharge were diagnosed with metritis (n = 52). Cows with metritis were paired with herdmates without metritis (n = 52) based on days in milk. The metabolome of plasma samples was evaluated using untargeted gas chromatography time-of-flight mass spectrometry. Univariate analyses included t-tests and fold change analyses. Metabolites with false discovery rate adjusted P ≤ 0.10 on t-tests were used for partial least squares discriminant analysis coupled with permutational analysis using 2,000 permutations. Metabolites with false discovery rate adjusted P ≤ 0.10 on t-tests were also used for enriched pathway analyses and identification of cellular processes. Cows that developed metritis had affected cellular processes associated with lower amino acid metabolism in the prepartum period, greater lipolysis, cell death, and oxidative stress at calving and at metritis diagnosis, and greater leukocyte activation at calving, but lower immune cell activation at metritis diagnosis. In summary, cows that developed metritis had plasma metabolomic changes associated with greater lipolysis, oxidative stress, and a dysregulated immune response which may predispose cows to metritis development.


Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program.
The epigenome changes that underlie cellular differentiation in developing organisms are poorly understood. To gain insights into how pancreatic beta-cells are programmed, we profiled key histone methylations and transcripts in embryonic stem cells, multipotent progenitors of the nascent embryonic pancreas, purified beta-cells, and 10 differentiated tissues. We report that despite their endodermal origin, beta-cells show a transcriptional and active chromatin signature that is most similar to ectoderm-derived neural tissues. In contrast, the beta-cell signature of trimethylated H3K27, a mark of Polycomb-mediated repression, clusters with pancreatic progenitors, acinar cells and liver, consistent with the epigenetic transmission of this mark from endoderm progenitors to their differentiated cellular progeny. We also identified two H3K27 methylation events that arise in the beta-cell lineage after the pancreatic progenitor stage. One is a wave of cell-selective de novo H3K27 trimethylation in non-CpG island genes. Another is the loss of bivalent and H3K27me3-repressed chromatin in a core program of neural developmental regulators that enables a convergence of the gene activity state of beta-cells with that of neural cells. These findings reveal a dynamic regulation of Polycomb repression programs that shape the identity of differentiated beta-cells.


Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells.
The next steps of deep space exploration are manned missions to Moon and Mars. For safe space missions for crew members, it is important to understand the impact of space flight on the immune system. We studied the effects of 21 days dry immersion (DI) exposure on the transcriptomes of T cells isolated from blood samples of eight healthy volunteers. Samples were collected 7 days before DI, at day 7, 14, and 21 during DI, and 7 days after DI. RNA sequencing of CD3+ T cells revealed transcriptional alterations across all time points, with most changes occurring 14 days after DI exposure. At day 21, T cells showed evidence of adaptation with a transcriptional profile resembling that of 7 days before DI. At 7 days after DI, T cells again changed their transcriptional profile. These data suggest that T cells adapt by rewiring their transcriptomes in response to simulated weightlessness and that remodeling cues persist when reexposed to normal gravity.


Kinetic analysis of 125I-iodorotenone as a deposited myocardial flow tracer: comparison with 99mTc-sestamibi.
The goal of this investigation was to assess the accuracy of 7'-Z-[125I]iodorotenone (125I-iodorotenone) as a new deposited myocardial flow tracer and compare the results with those for 99mTc-sestamibi. The kinetics of these two flow tracers were evaluated in 25 isolated, erythrocyte- and albumin-perfused rabbit hearts over a flow range relevant to patients. The two flow tracers and a vascular reference tracer (131I-albumin) were introduced simultaneously as a compact bolus through a port just above the aortic cannula in the absence of tracer recirculation. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves using the multiple-indicator dilution technique and spectral analysis. The extraction of 125I-iodorotenone was much higher than the extraction of 99mTc-sestamibi (0.84 +/- 0.05 vs. 0.48 +/- 0.10, respectively, P < 0.001). 125I-iodorotenone extraction was also less affected by flow than was 99mTc-sestamibi (P < 0.001). Net retention of 125I-iodorotenone was significantly greater than 99mTc-sestamibi net retention at 1 min (0.77 +/- 0.08 vs. 0.41 +/- 0.11, respectively, P < 0.001) and 26 min (0.46 +/- 0.13 vs. 0.27 +/- 0.11, respectively, P < 0.001) after tracer injection. Flow had less effect on 125I-iodorotenone net retention than on 99mTc-sestamibi net retention 1 min after tracer injection (P < 0.04). However, at 26 min, flow had an equivalent effect on the retention of both flow tracers (P < 0.4). The relationship between 125I-iodorotenone and 99mTc-sestamibi washout was complex and depended on elapsed time after isotope introduction and perfusion rate. Reflecting the favorable extraction and retention characteristics of 125I-iodorotenone, both its maximum myocardial uptake and its 26-min uptake were more closely related to flow than were those of 99mTc-sestamibi (P < 0.001 for both comparisons). The extraction and retention of 125I-iodorotenone were greater than those of 99mTc-sestamibi, making 125I-iodorotenone the superior flow tracer in the isolated rabbit heart.


Changes in the sugarcane metabolome with stem development. Are they related to sucrose accumulation?
Sucrose content increases with internode development down the stem of sugarcane. In an attempt to determine which other changes in metabolites may be linked to sucrose accumulation gas chromatography-mass spectrometry was used to obtain metabolic profiles from methanol/water extracts of four samples of different age down the stem of cultivar Q117. Extracts were derivatized with either N-methyl-N-(trimethylsilyl) trifluoracetamide (TMS) or N-methyl N-(tert-butyldimethylsilyl) trifluoroacetamide (TBS) separately in order to increase the number of metabolites that could be detected. This resulted in the measurement of 121 and 71 metabolites from the TMS and TBS derivatization, respectively. Fifty-five metabolites were identified using commercial and publicly available libraries. Statistical analysis of the metabolite profiles resulted in clustering of tissue types. Particular metabolites were correlated with the level of sucrose accumulation, which as expected increased down the stem. Metabolites, such as tricarboxylic acid cycle intermediates and amino acids, were more abundant in the M2 sample (meristem to internode 2) that was actively growing and decreased in an apparently coordinated developmentally programmed manner in more mature internodes down the stem. However, other metabolites such as trehalose and raffinose showed positive correlations with sucrose concentration. Here we discuss the technique used to measure metabolites in sugarcane and the changes in metabolite abundance down the sugarcane stem.


A DFT+U study on the contribution of 4f electrons to oxygen vacancy formation and migration in Ln-doped CeO2.
A rare earth doped form of ceria (CeO2) is of interest as a potential candidate for solid oxide fuel cells (SOFCs) because of its relatively high oxygen ion conductivity at temperatures below 600 °C. At the present time, computational chemistry has reached a certain maturity which allows the prediction of materials properties that are difficult to observe experimentally. However, understanding of the roles of dopants in the oxygen ion conduction in CeO2 is still incomplete for quantitatively reliable analysis due to the strong electron correlation of 4f electrons. In this study, density functional theory calculations with Hubbard U corrections are used to discuss ionic/covalent interactions in rare-earth-doped CeO2 and their consequences to oxygen ion conduction. This study suggests that the variable occupancy of empty 4f orbitals is important typically for early Ln elements to produce the covalent interactions that essentially affect the formation and migration of oxygen vacancies. This finding is important in understanding the factors responsible for oxygen ion diffusion in doped CeO2.


Alterations in NF-kappaB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-kappaB.
Stratified epithelium contains a mitotically active basal layer of cells that cease proliferating, then migrate outwards and undergo terminal differentiation. The control of this process, which is abnormal in cutaneous neoplasia and inflammation, is not well understood. In normal epidermis, NF-kappaB proteins were found to exist in the cytoplasm of basal cells and then to localize in the nuclei of suprabasal cells, suggesting a role for NF-kappaB in the switch from proliferation to growth arrest and differentiation. Functional blockade of NF-kappaB by expressing dominant-negative NF-kappaB inhibitory proteins in transgenic murine and human epidermis produced hyperplastic epithelium in vivo. Consistent with this, application of a pharmacologic inhibitor of NF-kappaB to intact skin induced epidermal hyperplasia. In contrast, overexpression of active p50 and p65 NF-kappaB subunits in transgenic epithelium produced hypoplasia and growth inhibition. These data suggest that spatially restricted NF-kappaB activation occurs in stratified epithelium and indicate that NF-kappaB activation in this tissue, in contrast to its role in other settings, is important for cellular growth inhibition.


Metformin selectively targets redox control of complex I energy transduction.
Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled.


Estimation of Apigenin, an Anxiolytic Constituent, in Turnera aphrodisiaca.
An HPTLC densitometric method has been developed to estimate apigenin in Turnera aphrodisiaca aerial and its segregated parts (leaves, stems, flowers and fruits) so that plant can be standardized on the basis of its bioactive marker. The apigenin content in methanol extract of T. aphrodisiaca aerial parts was found to be about fourteen times less than acid hydrolyzed methanol extract of the plant indicating the presence of most of apigenin in glycosidic form. Amongst different plant parts, flowers possessed maximum content of apigenin followed by leaves. The apigenin content was also determined in three marketed formulations of T. aphrodisiaca viz., NLK, DWSG and SBL. DWSG contained higher content of apigenin. Aerial parts of the plant were collected at bimonthly intervals over a period of one year in the months of January, March, May, July, September and November. The plant material collected in September showed maximum content of apigenin.


A two-label microfluorometric analysis of the expression of OKT5 and Leu 2a antigens on peripheral blood lymphocytes in patients with multiple sclerosis.
Four patients with relapsing-remitting multiple sclerosis (MS) and one control were evaluated serially over a 10-week interval. Peripheral blood lymphocyte (PBL) subsets were enumerated using a double labelling technique, OKT5 and anti-Leu 2a monoclonal antibodies, and FACS IV analysis. Results were correlated with clinically assessed disease activity. Two subsets were identified. Subset 1 is characterized by cells positive for Leu 2a and either weakly positive or negative for OKT5 . Subset 2 was positive for both. Subset 1 was constantly present in both patients and controls while subset 2 was variable in presence and in size. No associations between these subsets and disease activity were made in this preliminary study, however, no acute relapses occurred in this interval. It is postulated that the reason for the differences in results of studies attempting to correlate disease activity with PBL phenotypes as assessed by different monoclonal antibodies may be the result of the suppressor/cytotoxic cell subpopulation being nonhomogeneous for the expression of various cell surface antigens. The technique of multiple labelling of lymphocytes may be useful in defining subsets which correlate more closely with disease activity.


Histomorphometric Assessment of Cancellous and Cortical Bone Material Distribution in the Proximal Humerus of Normal and Osteoporotic Individuals: Significantly Reduced Bone Stock in the Metaphyseal and Subcapital Regions of Osteoporotic Individuals.
Osteoporosis is a systemic disorder predominantly affecting postmenopausal women but also men at an advanced age. Both genders may suffer from low-energy fractures of, for example, the proximal humerus when reduction of the bone stock or/and quality has occurred.The aim of the current study was to compare the amount of bone in typical fracture zones of the proximal humerus in osteoporotic and non-osteoporotic individuals.The amount of bone in the proximal humerus was determined histomorphometrically in frontal plane sections. The donor bones were allocated to normal and osteoporotic groups using the T-score from distal radius DXA measurements of the same extremities. The T-score evaluation was done according to WHO criteria. Regional thickness of the subchondral plate and the metaphyseal cortical bone were measured using interactive image analysis.At all measured locations the amount of cancellous bone was significantly lower in individuals from the osteoporotic group compared to the non-osteoporotic one. The osteoporotic group showed more significant differences between regions of the same bone than the non-osteoporotic group. In both groups the subchondral cancellous bone and the subchondral plate were least affected by bone loss. In contrast, the medial metaphyseal region in the osteoporotic group exhibited higher bone loss in comparison to the lateral side.This observation may explain prevailing fracture patterns, which frequently involve compression fractures and certainly has an influence on the stability of implants placed in this medial region. It should be considered when planning the anchoring of osteosynthesis materials in osteoporotic patients with fractures of the proximal humerus.


Scaling binary images with the telescoping template.
The importance of enlarging and reducing two-level images such as graphical and documentary matter by digital means continues to grow as more such images are digitally represented. A nonlinear scaling scheme is devised which exploits the simplicity of this binary nature, treating images logically instead of arithmetically; a convolution-like effect is achieved without a single addition or multiplication! This method yields high-fidelity digital scaling and meets the objectives of being fast, conducive to hardware realization, and void of special pre-encoding requirements.


Two energy gaps and Fermi-surface "arcs" in NbSe2.
Using angle-resolved photoemission spectroscopy, we report on the direct observation of the energy gap in 2H-NbSe2 caused by the charge-density waves (CDW). The gap opens in the regions of the momentum space connected by the CDW vectors, which implies a nesting mechanism of CDW formation. In remarkable analogy with the pseudogap in cuprates, the detected energy gap also exists in the normal state (T>T0) where it breaks the Fermi surface into "arcs," it is nonmonotonic as a function of temperature with a local minimum at the CDW transition temperature (T0), and it forestalls the superconducting gap by excluding the nested portions of the Fermi surface from participating in superconductivity.


Chemical Properties and Biological Activity of Bee Pollen.
Pollen, a remarkably versatile natural compound collected by bees for its abundant source of proteins and nutrients, represents a rich reservoir of diverse bioactive compounds with noteworthy chemical and therapeutic potential. Its extensive biological effects have been known and exploited since ancient times. Today, there is an increased interest in finding natural compounds against oxidative stress, a factor that contributes to various diseases. Recent research has unraveled a multitude of biological activities associated with bee pollen, ranging from antioxidant, anti-inflammatory, antimicrobial, and antifungal properties to potential antiviral and anticancer applications. Comprehending the extensive repertoire of biological properties across various pollen sources remains challenging. By investigating a spectrum of pollen types and their chemical composition, this review produces an updated analysis of the bioactive constituents and the therapeutic prospects they offer. This review emphasizes the necessity for further exploration and standardization of diverse pollen sources and bioactive compounds that could contribute to the development of innovative therapies.


[A small open reading frame of the Stalker retrotransposon reveals a high similarity to the second small frame of the MDG1 retrotransposon].
Sequence analysis of a 5' terminal fragment of stalker retrotransposon, about 1600 bp in length, revealed a number of motifs in the nucleotide sequences of the LTR and other untranslated regions that are common to retrotransposons 412 and MDG1. Taken together, experimental data and computer analysis of this sequence suggest that stalker falls into the gypsy group of retrotransposons and most closely resembles related retrotransposons 412 and MDG1. Stalker bears a small open reading frame (sORF) that shares 24 and 75% identical amino acid residues with the second sORFs of retrotransposons 412 and MDG1, respectively. Thus high similarity between the discovered sORF of stalker and the corresponding frame of MDG1 looks intriguing, since other regions of the sequences display little resemblance. Therefore, the evolutionary proximity of stalker to MDG1 cannot be conjectured solely on the basis of the mentioned similarity. The similarity may be explained by recombination of the two transposons, or, alternatively, the frame can retain its function in the genomes of stalker and MDG1 and lose it in 412.


Successful Withdrawal of Insulin Therapy After Post-Treatment Clearance of Hepatitis C Virus in a Man with Type 2 Diabetes.
BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with increased insulin resistance and risk of type 2 diabetes. Successful antiviral treatment can improve insulin resistance and allow a reduction in blood glucose-lowering treatment. There have been case reports of a reduced insulin requirement in this situation, although 1 case in which insulin was stopped exhibited a subsequent deterioration in glycemic control. CASE REPORT A 55-year-old Italian man was diagnosed with HCV infection in 2000 at the age of 39 years and with type 2 diabetes 6 years later. He was started on metformin but progressed to multiple daily insulin injections after 3 years. He was treated with pegylated interferon, ribavirin, and telaprevir over 12 months from early 2013, and achieved a sustained virologic response and normalization of hepatic function within 6 months of starting therapy. He was subsequently able to reduce his insulin doses from 0.56 to 0.44 U/kg/day over the next 2 years and, based on a random serum C-peptide of 1.73 nmol/L (fasting reference range 0.37-1.47 nmol/L) in the presence of serum glucose 7.9 mmol/L (143 mg/dL) and negative glutamic acid decarboxylase antibodies, he accelerated withdrawal and stopped insulin 6 months later. He is currently taking linagliptin 5 mg daily with good glycemic control. His body mass index and HbA1c have remained <25 kg/m² and <6.0% (<42 mmol/mol), respectively, throughout. CONCLUSIONS This case shows that complete withdrawal of long-term insulin therapy may be possible after HCV treatment has induced a sustained virologic response.


Increased cell death in rat blastocysts exposed to maternal diabetes in utero and to high glucose or tumor necrosis factor-alpha in vitro.
The morphogenetic function of the transient phase of cell death that occurs during blastocyst maturation is not known but it is thought that its regulation results from a delicate balance between survival and lethal signals in the uterine milieu. In this paper, we show that blastocysts from diabetic rats have a higher incidence of dead cells than control embryos. Differential lineage staining indicated that increased nuclear fragmentation occurred mainly in the inner cell mass. In addition, terminal transferase-mediated dUTP nick end labeling (TUNEL) demonstrated an increase in the incidence of non-fragmented DNA-damaged nuclei in these blastocysts. Analysis of the expression of clusterin, a gene associated with apoptosis, by quantitative reverse transcription-polymerase chain reaction detected an increase in the steady-state level of its transcripts in blastocysts from diabetic rats. In situ hybridization revealed that about half the cells identified as expressing clusterin mRNA exhibited signs of nuclear fragmentation. In vitro experiments demonstrated that high D-glucose increased nuclear fragmentation, TUNEL labeling and clusterin transcription. Tumor necrosis factor-alpha (TNF-alpha), a cytokine whose synthesis is up-regulated in the diabetic uterus, did not induce nuclear fragmentation nor clusterin expression but increased the incidence of TUNEL-positive nuclei. The data suggest that excessive cell death in the blastocyst, most probably resulting from the overstimulation of a basal suicidal program by such inducers as glucose and TNF-alpha, may be a contributing factor of the early embryopathy associated with maternal diabetes.


Depression augments activity-related pain in women but not in men with chronic musculoskeletal conditions.
The primary objective of the present study was to examine the role of sex as a moderator of the relation between depression and activity-related pain. The study sample consisted of 83 participants (42 women, 41 men) with musculoskeletal conditions. Participants were asked to lift a series of 18 canisters that varied in weight (2.9 kg, 3.4 kg and 3.9 kg) and distance from the body. Participants were asked to rate their pain while they lifted each canister and estimate the weight of the canisters. Consistent with previous research, the relations among depression, pain intensity and disability were stronger for women than for men. ANOVA revealed that depression was associated with more intense activity-related pain in women only. For both women and men, the intensity of pain increased with each trial, although the weight of the objects lifted remained constant. Neither sex nor depression had an effect on participants' weight estimates. The present discussion addresses the mechanisms through which depression may differentially affect pain in women and men. It also addresses the potential clinical implications of pain-augmenting effects of depression in women.


Regulation of energy consumption in cardiac muscle: analysis of isometric contractions.
The well-known linear relationship between oxygen consumption and force-length area or the force-time integral is analyzed here for isometric contractions. The analysis, which is based on a biochemical model that couples calcium kinetics with cross-bridge cycling, indicates that the change in the number of force-generating cross bridges with the change in the sarcomere length depends on the force generated by the cross bridges. This positive-feedback phenomenon is consistent with our reported cooperativity mechanism, whereby the affinity of the troponin for calcium and, hence, cross-bridge recruitment depends on the number of force-generating cross bridges. Moreover, it is demonstrated that a model that does not include a feedback mechanism cannot describe the dependence of energy consumption on the loading conditions. The cooperativity mechanism, which has been shown to determine the force-length relationship and the related Frank-Starling law, is shown here to provide the basis for the regulation of energy consumption in the cardiac muscle.


A meta-analytic review of prolonged exposure for posttraumatic stress disorder.
Two decades of research demonstrate the efficacy of exposure therapy for posttraumatic stress disorder (PTSD). The efficacy of prolonged exposure (PE), a specific exposure therapy program for PTSD that has been disseminated throughout the world, has been established in many controlled studies using different trauma populations. However, a meta-analysis of the effectiveness of PE for PTSD has not been conducted to date. The purpose of the current paper is to estimate the overall efficacy of PE for PTSD relative to adequate controls. We included all published randomized controlled trials of PE vs. control (wait-list or psychological placebo) for the treatment of PTSD in adolescents or adults. Treatments were classified as PE if they included multiple sessions of imaginal and in vivo exposure and were based on the manualized treatment developed by Foa, Rothbaum, Riggs, and Murdock (1991). Thirteen studies with a total sample size of 675 participants met the final inclusion criteria. The primary analyses showed a large effect for PE versus control on both primary (Hedges's g=1.08) and secondary (Hedges's g=0.77) outcome measures. Analyses also revealed medium to large effect sizes for PE at follow-up, both for primary (Hedges's g=0.68) and secondary (Hedges's g=0.41) outcome measures. There was no significant difference between PE and other active treatments (CPT, EMDR, CT, and SIT). Effect sizes were not moderated by time since trauma, publication year, dose, study quality, or type of trauma. The average PE-treated patient fared better than 86% of patients in control conditions at post-treatment on PTSD measures. PE is a highly effective treatment for PTSD, resulting in substantial treatment gains that are maintained over time.


Evidence for ontogenetically and morphologically distinct alternative reproductive tactics in the invasive Round Goby Neogobius melanostomus.
Alternative reproductive tactics are characterized by the occurrence of discrete alternative morphs that differ in behavioural, morphological and physiological traits within the same sex. Although much effort has been made to describe the behaviour, morphology and physiology of such alternative morphs, less effort has been invested investigating how much overlap there is in the characteristics of such morphs in natural populations. We studied random population samples of the invasive Round Goby Neogobius melanostomus from five different localities in the river Rhine system in the Netherlands. We found two morphologically and physiologically distinct male morphs which likely represent alternative reproductive tactics. Almost all mature males under 9.35 cm total length had a gonadosomatic index > 3%, suggestive of a sneaker tactic, while nearly all males above 9.35 cm has a gonadosomatic index of < 3%, suggestive of a parental tactic. Cheek size and eye diameter alone were sufficient to distinguish the two morphs. Gonads had a different relationship with size in the two morphs, indicating separate growth trajectories. The gonad mass of sneaker morphs would be ca. 7.5 times as high as the gonad mass of parental morphs of the same total length after extrapolation. Few (9%) intermediates were found, suggesting that the expression of alternative reproductive tactics is determined before the first breeding season. This contrasts with studies on other goby species, which show evidence of plastic tactics that can be affected by social circumstances. We conclude that it is possible to distinguish two alternative male morphs in the Dutch Round Goby population using morphological measurements alone. Although behavioural observations are needed to provide conclusive evidence, the difference in GSI between these morphs indicates that these morphs reflect alternative reproductive tactics.


Two-dimensional switchable blue phase gratings manufactured by nanosphere lithography.
Switchable two dimensional liquid crystal diffraction gratings are promising candidates in beam steering devices, multiplexers and holographic displays. For these areas of applications a high degree of integration in optical systems is much sought-after. In the context of diffraction gratings this means that the angle of diffraction should be rather high, which typically poses a problem as the fabrication of small grating periods is challenging. In this paper, we propose the use of nanosphere lithography (NSL) for the fabrication of two-dimensionally structured electrodes with a periodicity of a few micrometers. NSL is based on the self-assembly of micro- or nanometer sized spheres into monolayers. It allows for easy substrate structuring on wafer scale. The manufactured electrode is combined with a liquid crystalline polymer-stabilized blue phase, which facilitates sub-millisecond electrical switching of the diffraction efficiency at a diffraction angle of 21.4°.


Neurogenesis and sensorimotor gating: bridging a microphenotype and an endophenotype.
Human genetic data on psychiatric disorders repeatedly demonstrate the involvement of various genes that are associated with neural development and neurogenesis. Neurogenesis is a biological process that is critical in brain development and continues throughout life. Neurogenesis is a multi-step process starting from the division of neural stem cells/progenitor cells, leading to self-renewal and simultaneously to the production of lineage-committed cells, including neurons and glial cells. Minor defects in the neurogenesis process, such as production of fewer new neurons and malformation of neural circuits, could represent phenotypes of psychiatric disorders at molecular and cellular levels in animal models (here termed as "microphenotypes"). However, microphenotypes are not easily used as biomarkers. We have focused on a physiological condition, sensorimotor gating deficits, that can be scored by a prepulse inhibition (PPI) test. Impaired PPI is considered to be one of the compelling endophenotypes (biological markers) of mental disorders such as schizophrenia, autism, and other neurodevelopmental disorders. Because the neural circuit for PPI involves the hippocampus, a unique brain region where neurogenesis occurs postnatally, we hypothesize that an impairment of preadolescent neurogenesis is critical for the onset of sensorimotor gating defects. To test this hypothesis, we investigated a critical period of neurogenesis that can affect PPI. In this paradigm, we introduced an enriched environment to restore neurogenesis, thereby recovering PPI deficits in mice. We noted impairments in the maturation of newborn neurons in the hippocampal dentate gyrus (DG) and GABAergic neurons in the hippocampus, which could be considered as microphenotypes associated with PPI defects. More precise genetically controlled neurogenesis models (with precise time points or periods) are needed to be studied in further investigation to support our hypothesis.


Expanded biochemical analyses of human tear fluid: Polyvalent faces of the schirmer strip.
The tear film forms a protective barrier between the ocular surface and the external environment. Despite its small volume, recent advancements in preanalytical and analytical procedures have enabled its in-depth analysis using multiple approaches. However, the diversity of tear film collection methods and the lack of standardization in pre-analytical methods represent the main obstacles to reproducible results and comparison among different studies. In this study, we first improved the pre-analytical procedures for the extraction of various molecular entities from Schirmer strips (ScS). Subsequently, our investigation focused on analyzing the molecular variances that might occur between two primary tear collection methods: capillary tube (CT) and ScS. Additionally, we examined different parts of the ScS to underscore these variations, which could serve as crucial factors for developing a standardized, optimized protocol for sample processing. Our results show that the inclusion of surfactants in the extraction process enhanced both the yield of protein extraction and the number of proteins identified in ScS, by effectively lysing the cells and improving the solubility of several intracellular proteins. In addition to proteins, nucleic acids could also be recovered for gene expression analyses, particularly from the bulb region of the ScS which is placed in the cul-de-sac. Despite their diluted nature, extracts from ScS remain a suitable material for retrieving tear proteins such as IL-17A at levels as low as the fg/mL range, thanks to highly sensitive immunoassays. Collection methods can affect measured tear protein levels. Lactoferrin is found in higher percentages in capillary electrophoresis analysis of tears collected using ScS compared to tears collected by CT (39.6 ± 4.8% versus 31 ± 4.4%).


Identification and characterization of multiple Spidroin 1 genes encoding major ampullate silk proteins in Nephila clavipes.
Spider dragline silk is primarily composed of proteins called major ampullate spidroins (MaSps) that consist of a large repeat array flanked by nonrepetitive N- and C-terminal domains. Until recently, there has been little evidence for more than one gene encoding each of the two major spidroin silk proteins, MaSp1 and MaSp2. Here, we report the deduced N-terminal domain sequences for two distinct MaSp1 genes from Nephila clavipes (MaSp1A and MaSp1B) and for MaSp2. All three MaSp genes are co-expressed in the major ampullate gland. A search of the GenBank database also revealed two distinct MaSp1 C-terminal domain sequences. Sequencing confirmed that both MaSp1 genes are present in all seven Nephila clavipes spiders examined. The presence of nucleotide polymorphisms in these genes confirmed that MaSp1A and MaSp1B are distinct genetic loci and not merely alleles of the same gene. We experimentally determined the transcription start sites for all three MaSp genes and established preliminary pairing between the two MaSp1 N- and C-terminal domains. Phylogenetic analysis of these new sequences and other published MaSp N- and C-terminal domain sequences illustrated that duplications of MaSp genes may be widespread among spider species.


[A peculiarity in the humoral immunity of BALB/C mice with Rauscher leukemia].
There proved to be an increase in B-lymphocyte count (associated with increased synthesis of nonspecific immunoglobulins) in BALB/C mice highly sensitive to Rausher virus, after the administration of a relatively low dose of the virus. After the administration of the virus in combination with complete Freund's adjuvant in the spleen of mice, at the early periods of development of the disease, there were present normal cells synthesizing antibodies against the surface antigen of Rausher leukemia and leukemic cells with blocking antibodies adsorbed on their surface.


Blister Packaging Medication Increases Treatment Adherence in Psychiatric Patients.
To evaluate whether blister packing medications would improve prescription medication adherence in psychiatric patients. It was hypothesized that patients in the blister pack (BP) condition would be more adherent to their daily medications than those in the dispense as usual condition. This was a randomized trial involving up to 1 year of monthly follow-up assessments. Participants were recruited from an urban Veterans Affairs (VA) Medical Center in the Western United States. Inclusion criteria for participants included being diagnosed with a major affective disorder, posttraumatic stress disorder, schizophrenia, or a combination of these disorders; being 18 to 89 years of age; receiving prescription medications from the VA pharmacy; and being considered competent to manage their own medications. Of the 303 patients who consented to participate, 277 were randomized to 1 of the 2 study conditions, and 243 were retained in the study. The sample was 87% male, 47% white, with a mean age of 54.4 years. All medications prescribed and dispensed by the VA were either repackaged in monthly BPs or dispensed in standard pill vials. The primary hypothesis was supported. Patients in the BPs condition showed evidence of better adherence at 12-month follow-up, as well as larger increases in adherence from 1 month to 12 months. Psychiatric patients adhere better to prescription medication regimens when receiving their medications in BP.


SPSB1 promotes breast cancer recurrence by potentiating c-MET signaling.
Breast cancer mortality is principally due to tumor recurrence; however, the molecular mechanisms underlying this process are poorly understood. We now demonstrate that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregulated during mammary tumor recurrence and is both necessary and sufficient to promote tumor recurrence in genetically engineered mouse models. The recurrence-promoting effects of SPSB1 result from its ability to protect cells from apoptosis induced by HER2/neu pathway inhibition or chemotherapy. This, in turn, is attributable to SPSB1 potentiation of c-MET signaling, such that preexisting SPSB1-overexpressing tumor cells are selected for following HER2/neu downregulation. Consistent with this, SPSB1 expression is positively correlated with c-MET activity in human breast cancers and with an increased risk of relapse in patients with breast cancer in a manner that is dependent upon c-MET activity. Our findings define a novel pathway that contributes to breast cancer recurrence and provide the first evidence implicating SPSB proteins in cancer. The principal cause of death from breast cancer is recurrence. This study identifies SPSB1 as a critical mediator of breast cancer recurrence, suggests activation of the SPSB1-c-MET pathway as an important mechanism of therapeutic resistance in breast cancers, and emphasizes that pharmacologic targets for recurrence may be unique to this stage of tumor progression.


Soybean allergen detection methods--a comparison study.
Soybean containing products are widely consumed, thus reliable methods for detection of soy in foods are needed in order to make appropriate risk assessment studies to adequately protect soy allergic patients. Six methods were compared using eight food products with a declared content of soy: a direct sandwich ELISA based on polyclonal rabbit antibody (ab) to raw soy flakes, a commercial and an in-house competitive ELISA both based on ab to denatured, 'renatured' soy protein, an enzyme-allergosorbent test (EAST) inhibition based on two sera from soy allergic patients, histamine release (HR) using basophils passively sensitized with patient serum and a PCR method detecting soy DNA. Eight food products were selected as model foods to test the performance of the methods. There was an overall good agreement between the methods in terms of ranks of soy content but not the quantity. The sandwich ELISA aimed at native soy proteins had the lowest detection limit of 0.05 ppm, but only identified soy in 5/8 products, and generally in lower amounts compared to other methods. The competitive ELISA had a higher detection limit of 21 ppm, but seemed more successful in detecting processed soy. Only HR, EAST inhibition and PCR detected soy in all eight products. In spite of a general good correlation in terms of ranks of soy content, more than a single method may be necessary to confirm the presence of soy in foods.


Applications of Transmission Electron Microscopy in Phase Engineering of Nanomaterials.
Phase engineering of nanomaterials (PEN) is an emerging field that aims to tailor the physicochemical properties of nanomaterials by precisely manipulating their crystal phases. To advance PEN effectively, it is vital to possess the capability of characterizing the structures and compositions of nanomaterials with precision. Transmission electron microscopy (TEM) is a versatile tool that combines reciprocal-space diffraction, real-space imaging, and spectroscopic techniques, allowing for comprehensive characterization with exceptional resolution in the domains of time, space, momentum, and, increasingly, even energy. In this Review, we first introduce the fundamental mechanisms behind various TEM-related techniques, along with their respective application scopes and limitations. Subsequently, we review notable applications of TEM in PEN research, including applications in fields such as metallic nanostructures, carbon allotropes, low-dimensional materials, and nanoporous materials. Specifically, we underscore its efficacy in phase identification, composition and chemical state analysis, in situ observations of phase evolution, as well as the challenges encountered when dealing with beam-sensitive materials. Furthermore, we discuss the potential generation of artifacts during TEM imaging, particularly in scanning modes, and propose methods to minimize their occurrence. Finally, we offer our insights into the present state and future trends of this field, discussing emerging technologies including four-dimensional scanning TEM, three-dimensional atomic-resolution imaging, and electron microscopy automation while highlighting the significance and feasibility of these advancements.


Identifying Appropriate Delivery of and Referral to Pulmonary Rehabilitation in Uganda: A Survey Study of People Living with Chronic Respiratory Disease and Health Care Workers.
Pulmonary rehabilitation (PR) is a low cost, high impact intervention that ameliorates the disability associated with chronic respiratory diseases (CRD). PR is becoming increasingly recognized in low resource settings where the burden of CRD is rapidly increasing. To aid the implementation of PR in Uganda, we conducted a study to assess the attitudes and opinions towards PR among patients with CRD in Uganda and explore barriers faced by health care workers (HCWs) in referring to PR. A cross-sectional study comprising two survey populations: people living with CRD and HCWs regarded as potential PR referrers and PR deliverers. This exploratory study sought initial opinions and thoughts regarding PR, as well as baseline knowledge and potential barriers faced in the referral process. Overall, 30 HCWs (53% female, 43% doctors) and 51 adults with CRD (63% female) participated in the survey. Among those with CRD, the majority reported breathlessness as a major problem (86%) and breathlessness affected their ability to do paid and unpaid work (70%). Interest in PR was high amongst adults with CRD (92%) with preference for a hospital-based programme (67%) as opposed to community-based (16%) or home-based (17%). All HCWs considered PR important in lung disease management, but 77% do not refer patients due to a lack of information about PR. HCWs' free-text responses identified the need for training in PR, patient education and streamlining the referral process as key elements to develop successful PR referral services. To successfully set up a PR service for people with CRD in Uganda, there is a great need for appropriately tailored training and education of prospective referrers about CRD and PR programs. Educating patients about the benefits of PR as well as streamlining the referral process is critical in expanding PR services across Uganda to fulfill this unmet need.


Nondestructive imaging of plant-parasitic nematode development and host response to nematode pathogenesis.
The secluded lifestyle of endoparasitic plant nematodes hampers progress toward a comprehensive understanding of plant-nematode interactions. A novel technique that enables nondestructive, long-term observations of a wide range of live nematodes in planta is presented here. As proof of principle, Pratylenchus penetrans, Heterodera schachtii, and Meloidogyne chitwoodi were labeled fluorescently with PKH26 and used to infect Arabidopsis thaliana grown in microscopy rhizosphere chambers. Nematode behavior, development, and morphology were observed for the full duration of each parasite's life cycle by confocal microscopy for up to 27 days after inoculation. PKH26 accumulated in intestinal lipid droplets and had no negative effect on nematode infectivity. This technique enabled visualization of Meloidogyne gall formation, nematode oogenesis, and nematode morphological features, such as the metacorpus, vulva, spicules, and cuticle. Additionally, microscopy rhizosphere chambers were used to characterize plant organelle dynamics during M. chitwoodi infection. Peroxisome abundance strongly increased in early giant cells but showed a marked decrease at later stages of feeding site development, which suggests a modulation of plant peroxisomes by root-knot nematodes during the infection process. Taken together, this technique facilitates studies aimed at deciphering plant-nematode interactions at the cellular and subcellular level and enables unprecedented insights into nematode behavior in planta.


Improving health, improving lives: impact of the African Youth Alliance and new opportunities for programmes.
The African Youth Alliance (AYA) was a partnership to improve adolescent sexual and reproductive health, and prevent HIV/AIDS in Botswana, Ghana, Tanzania and Uganda. The AYA model was a comprehensive range of integrated interventions, implemented concurrently and at scale using a multi-sectoral approach. AYA was funded for five years (2000-2005) with $56.7 million from the Bill and Melinda Gates Foundation. Over 35,000,000 stakeholders were reached through media campaigns, almost 400,000 young people received Life Planning Skills training, and over 2,500,000 visits were made by young people to static clinics and outreach services. A post-test evaluation was conducted by John Snow Inc. (JSI) in 2006 and combined case-control and self-reported exposure design. Case-control design data were analyzed using Propensity Score Matching (PSM), and the Self-Reported Exposure design data were analyzed using PSM and Instrumental Variable (two-stage regression) (IV). The results show AYA's significant and positive treatment effects on sexual knowledge, attitudes, and behaviours. The research suggests a comprehensive, multi-component approach such as AYA's can be effective in improving some key ASRH variables.


Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65.
Adeno-associated viral vectors (AAVs) have demonstrated potential in applications for neurologic disorders, and the discovery that some AAVs can cross the blood-brain barrier (BBB) after intravenous injection has further expanded these opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid designed from in silico reconstruction of the viral evolutionary lineage, has previously demonstrated robust transduction capabilities after local delivery in various tissues such as liver, retina, or cochlea, compared with conventional AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. Although the efficacy of Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the striatum, Anc80L65's diffusion throughout the CNS was more extensive than AAV9 after i.c.v. infusion, leading to widespread EGFP expression in the cerebellum. These findings demonstrate that Anc80L65 is a highly efficient gene transfer vector for the murine CNS. Systemic injection of Anc80L65 leads to notable expression in the CNS that does not rely on a self-complementary genome. These data warrant further testing in larger animal models.


Physician preferences for extra-glycemic effects of type 2 diabetes treatments.
The purpose of this study was to quantify United States (US) and United Kingdom (UK) physicians' preferences for attributes of type 2 diabetes treatments. Samples of general practitioners (GPs) and endocrinologists in the US (n = 204) and the UK (n = 200) completed a discrete-choice experiment in which respondents chose between pairs of hypothetical type 2 diabetes treatments in a series of trade-off questions. The questions described hypothetical injectable treatments with differing levels of attributes, such as glucose control and treatment side effects. Relative importance of attributes was estimated by a multivariate regression model for limited dependent variables. These results were used to calculate how the predicted probability of choosing hypothetical type 2 diabetes treatments varies with changes in given attributes. The most important attributes to physicians were glucose control, risk of a fatal myocardial infarction (MI), and weight change. For US physicians, glucose control was about twice as important as gastrointestinal side effects, 5 times more important than changes in depression symptoms, and 20 times more important than liver monitoring. For UK physicians, reduction in MI risk was about 1.5 times more important than glucose control, 2.5 times more important than gastrointestinal side effects, and 10 times more important than liver-monitoring requirements. Preferences were similar among physicians in the US and the UK and among GPs and endocrinologists. Physicians valued type 2 diabetes treatments that go beyond glycemic control, although mitigating different complications and comorbidities was not equally as important.


The mechanism of bacterial infection by filamentous phages involves molecular interactions between TolA and phage protein 3 domains.
The early events in filamentous bacteriophage infection of gram-negative bacteria are mediated by the gene 3 protein (g3p) of the virus. This protein has a sophisticated domain organization consisting of two N-terminal domains and one C-terminal domain, separated by flexible linkers. The molecular interactions between these domains and the known bacterial coreceptor protein (TolA) were studied using a biosensor technique, and we report here on interactions of the viral coat protein with TolA, as well as on interactions between the TolA molecules. We detected an interaction between the pilus binding second domain (N2) of protein 3 and the bacterial TolA. This novel interaction was found to depend on the periplasmatic domain of TolA (TolAII). Furthermore, extensive interaction was detected between TolA molecules, demonstrating that bacterial TolA has the ability to interact functionally with itself during phage infection. The kinetics of g3p binding to TolA is also different from that of bacteriocins, since both N-terminal domains of g3p were found to interact with TolA. The multiple roles for each of the separate g3p and TolA domains imply a delicate interaction network during the phage infection process and a model for the infection mechanism is hypothesized.


HFA of the ESC Position paper on the management of LVAD supported patients for the non LVAD specialist healthcare provider Part 1: Introduction and at the non-hospital settings in the community.
The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.


Sulphation of proteins secreted by a human hepatoma-derived cell line. Sulphation of N-linked oligosaccharides on alpha 2HS-glycoprotein.
Several human glycoproteins, including alpha 1-antitrypsin, alpha 1-acid glycoprotein, transferrin, caeruloplasmin and alpha 2HS-glycoprotein, synthesized by the hepatoma-derived cell line HepG2 were observed to contain covalently linked sulphate. These proteins were estimated to contain about 0.1 mol of sulphate/mol of protein. The most abundant of the sulphated glycoproteins, alpha 2HS-glycoprotein, was analysed in detail. All of the sulphate on this protein was attached to N-linked oligosaccharides which contained sialic acid and resisted release by endoglycosidase H. Several independent analytical approaches established that approx. 10% of the molecules of alpha 2HS-glycoprotein contained sulphate. Our results suggest that a number of human plasma proteins contain small amounts of sulphate linked to oligosaccharides.


Modelling component evaporation and composition change of traffic-induced ultrafine particles during travel from street canyon to urban background.
We developed a model (CiTTy-Street-UFP) of traffic-related particle behaviour in a street canyon and in the nearby downwind urban background that accounts for aerosol dynamics and the variable vapour pressure of component organics. The model simulates the evolution and fate of traffic generated multicomponent ultrafine particles (UFP) composed of a non-volatile core and 17 Semi-Volatile Organic Compounds (SVOC, modelled as n-alkane proxies). A two-stage modelling approach is adopted: (1) a steady state simulation inside the street canyon is achieved, in which there exists a balance between traffic emissions, condensation/evaporation, deposition, coagulation and exchange with the air above roof-level; and (2) a continuing simulation of the above-roof air parcel advected to the nearby urban park during which evaporation is dominant. We evaluate the component evaporation and associated composition changes of multicomponent organic particles in realistic atmospheric conditions and compare our results with observations from London (UK) in a street canyon and an urban park. With plausible input conditions and parameter settings, the model can reproduce, with reasonable fidelity, size distributions in central London in 2007. The modelled nucleation-mode peak diameter, which is 23 nm in the steady-state street canyon, decreases to 9 nm in a travel time of just 120 s. All modelled SVOC in the sub-10 nm particle size range have evaporated leaving behind only non-volatile material, whereas modelled particle composition in the Aitken mode contains SVOC between C26H54 and C32H66. No data on particle composition are available in the study used for validation, or elsewhere. Measurements addressing in detail the size resolved composition of the traffic emitted UFP in the atmosphere are a high priority for future research. Such data would improve the representation of these particles in dispersion models and provide the data essential for model validation. Enhanced knowledge of the chemical composition of nucleation-mode particles from diesel engine exhaust is needed to predict both their atmospheric behaviour and their implications for human health.


Robust nanocoatings based on ionic silicones.
Two oppositely charged water-soluble oligosiloxanes with the same main chain were synthesized and used for the formation of multilayer nanocoatings. In spite of low molecular weight of the components, due to entropic reasons, linearly growing and robust films with a hydrophilic surface were formed for the first time. The multilayer films were found to be resistant to high temperature water treatment undergoing only reversible swelling and no surface recovery was observed after prolonged exposure to air indicating permanent water wettability of these silicone-based coatings. High flexibility of the silicone chains resulted in low glass transition temperature (ca. 27 °C) of both dry polyplexes and films as determined using calorimetry and spectroscopic ellipsometry, respectively. Moreover, the thin coating was applied on plasma-treated poly(dimethylsiloxane) preventing surface reconstruction in air and leading to long-lasting hydrophilization of the surface (water contact angles around 65°). Such water-borne systems may be used in common applications of silicones providing high flexibility and at the same time water wettability of the coatings.


A proteogenomic survey of the Medicago truncatula genome.
Peptide sequencing by computational assignment of tandem mass spectra to a database of putative protein sequences provides an independent approach to confirming or refuting protein predictions based on large-scale DNA and RNA sequencing efforts. This use of mass spectrometrically-derived sequence data for testing and refining predicted gene models has been termed proteogenomics. We report herein the application of proteogenomic methodology to a database of 10.9 million tandem mass spectra collected over a period of two years from proteolytically generated peptides isolated from the model legume Medicago truncatula. These spectra were searched against a database of predicted M. truncatula protein sequences generated from public databases, in silico gene model predictions, and a whole-genome six-frame translation. This search identified 78,647 distinct peptide sequences, and a comparison with the publicly available proteome from the recently published M. truncatula genome supported translation of 9,843 existing gene models and identified 1,568 novel peptides suggesting corrections or additions to the current annotations. Each supporting and novel peptide was independently validated using mRNA-derived deep sequencing coverage and an overall correlation of 93% between the two data types was observed. We have additionally highlighted examples of several aspects of structural annotation for which tandem MS provides unique evidence not easily obtainable through typical DNA or RNA sequencing. Proteogenomic analysis is a valuable and unique source of information for the structural annotation of genomes and should be included in such efforts to ensure that the genome models used by biologists mirror as accurately as possible what is present in the cell.