bluuebunny/crossref_metadata_2025 huggingface dataset:
P-A5 HIV Infected Cells Have Depolarized Membrane Potentials and Increased Intracellular Calcium Levels
Authors: Furler Robert
Published: April 2018

Introduction/Background:

Ion distribution between the extracellular, cytoplasmic, and organellar spaces creates membrane potentials which drive many of life's processes. This bioelectric membrane potential, driven by ion channel and pump activity, can be harnessed to allow or prevent entry of signaling mediators like Ca2+ into the cytoplasm. Several HIV proteins have been reported to function as ion channels or alter ion channel activity. This activity likely influences cell fate including activation and apoptosis.

Hypothesis:

HIV depolarizes the plasma membrane and alters intracellular calcium levels. Changing the polarization of the plasma membrane would alter the levels of HIV infection.

Methods:

HIV infected cells were identified using anti-Env antibody PG9-AF647. Membrane potential measurements were done by flow cytometry using the DiBAC4(3) dye as previously reported. Intracellular Ca2+ measurements were also done by flow cytometry using the Fluo-4 dye. Ionomycin and PMA were used to show the contrast in intracellular Ca2+ levels between infected and uninfected cells. To assess the effects of membrane potential changes on HIV replication, 200µM diazoxide was added to cells during infections.

Results:

HIV infected cells consistently had depolarized membrane potentials in both primary cells and cell lines. Additional depolarization increased infection. Membrane depolarization was accompanied by increased intracellular Ca2+. Ionomycin induced a drastic difference in Ca2+ flow between uninfected and HIV-infected cells. In uninfected cells, ionomycin induced an influx of Ca2+ while PMA had little effect. In contrast, both ionomycin and PMA induced a large efflux of Ca2+ from HIV infected cells.
P-C5 Broadly neutralizing nanobodies selected from dromedary immune libraries with subtype C SOSIP Env glycoproteins: Optimization and preclinical development
Authors: Kalusche Sarah , Lehmann Felix , Koch Kathrin , Klein Florian , Torres Jonathan , Stanfield Robyn , Ward Andrew , Wilson Ian , Dietrich Ursula
Published: April 2018

Nanobodies or VHH are the smallest naturally occurring antibody fragments derived from heavy chain only antibodies from Camelidae. Due to their physicochemical properties (high stability, high affinity and target specificity, extended CDR3 loops and their small size allowing to enter into protein cavities), nanobodies are very suited for preventive and therapeutic applications. We recently selected nanobodies with broad neutralizing capacity against primary HIV-1 strains of different subtypes from phage immune libraries generated from dromedaries immunized with HIV-1 subtype C gp140 SOSIP Env glycoproteins (Koch et al., 2017, in press). Two nanobodies with complementary neutralization pattern neutralized 19 out of 21 pseudoviruses in the standard TZM-bl assay. Epitope mapping data by competition ELISAs as well as negative-stain EM reconstructions with trimeric SOSIPs identified the CD4 binding site as the major target. A new selection performed on a next-generation optC SOSIP664 plus sCD4 with libraries generated at a late timepoint (7 months after the initial 7 weeks immunization cycle) identified 2 new nanobodies, which are currently being analyzed for neutralization. We further proved functionality of the nanobodies at acidic pH (as found in the vagina) and identified nanobody combinations resulting in increased breadth of neutralization in vitro. In view of preventive applications at vaginal sites of HIV-1 transmission, we are expressing the best nanobodies in a membrane-bound form and as a secreted version from lactobacilli (L. rhamnosus), which colonize the human vagina. Finally, nanobodies will be analyzed in a humanized mouse model of HIV-1 infection for their HIV-neutralizing capacity in vivo.
Measuring Medical Housestaff Teamwork Performance Using Multiple Direct Observation Instruments: Comparing Apples and Apples
Authors: Weingart Saul N. , Yaghi Omar , Wetherell Matthew , Sweeney Megan
Published: April 2018

Purpose

To examine the composition and concordance of existing instruments used to assess medical teams’ performance.

Method

A trained observer joined 20 internal medicine housestaff teams for morning work rounds at Tufts Medical Center, a 415-bed Boston teaching hospital, from October through December 2015. The observer rated each team’s performance using nine teamwork observation instruments that examined domains including team structure, leadership, situation monitoring, mutual support, and communication. Observations recorded on paper forms were stored electronically. Scores were normalized from 1 (low) to 5 (high) to account for different rating scales. Overall mean scores were calculated and graphed; weighted scores adjusted for the number of items in each teamwork domain. Teamwork scores were analyzed using t tests, pairwise correlations, and the Kruskal–Wallis statistic, and team performance was compared across instruments by domain.

Results

The nine tools incorporated five major domains, with 5 to 35 items per instrument, for a total of 161 items per observation session. In weighted and unweighted analyses, the overall teamwork performance score for a given team on a given day varied by instrument. While all of the tools identified the same low outlier, high performers on some instruments were low performers on others. Inconsistent scores for a given team across instruments persisted in domain-level analyses.

Conclusions

There was substantial variation in the rating of individual teams assessed concurrently by a single observer using multiple instruments. Because existing teamwork observation tools do not yield concordant assessments, researchers should create better tools for measuring teamwork performance.
Policy Change From the Centers for Medicare and Medicaid Services Provides an Opportunity to Improve Medical Student Education and Recruit Community Preceptors
Authors: Power David V. , Byerley Julie Story , Steiner Beat
Published: April 2018

As U.S. medical educators know, it has been exceedingly difficult over the past decade to train medical students to document in the electronic health record (EHR) yet remain compliant with Centers for Medicare and Medicaid Services (CMS) guidelines. Indeed, some institutions have interpreted the guidelines to prohibit all medical student documentation in the EHR. This has been particularly challenging since the Association of American Medical Colleges has recommended that all medical school graduates be entrusted with 13 specific professional activities, two of which directly require student use of the EHR. Furthermore, critical efforts by clerkship directors to recruit community physicians as preceptors of medical students have been significantly hampered by the medical students’ inability to document encounters. Therefore, the CMS policy transmittal Pub 100-04 Medicare Claims Processing Manual, released on February 2, 2018, which now explicitly allows appropriately supervised student documentation to be submitted for billing, is a welcome policy change. U.S. medical educators need to seize this opportunity, encourage their health systems to revise their internal precepting practices, and widely advertise to community preceptors that students can now add value in the clinical setting by assisting with documentation in the EHR.
The Development of Kyphosis and Lordosis in the Growing Spine
Authors: Gardner Adrian , Berryman Fiona , Pynsent Paul
Published: April 2018

Study Design.

A longitudinal cohort study.

Objective.

The aim of this study was to do the analysis of the development of kyphosis and lordosis in the growing spine.

Summary of Background Data.

Previous studies have measured kyphosis and lordosis in different ways with differing techniques. None of the previous literature has a truly longitudinal design and there is disagreement as to whether there exists a difference between the development of kyphosis and lordosis between males and females.

Methods.

Repeated measures using Integrated Shape Imaging System Integrated Shape Imaging System 2 surface topography over 5 years of a group of children aged 5 to 16 years without spinal deformity. Longitudinal analysis was performed using linear mixed effects modeling.

Results.

There were 638 measures in 194 children. Both kyphosis and lordosis increased with age in both males and females (P < 0.001 for kyphosis and P = 0.002 for lordosis). There was no statistical difference in the development of kyphosis between males and females (P = 0.149). However, there was a significant difference in lordosis between males and females (P < 0.001) with female lordosis larger than that seen in males. Kyphosis and lordosis increased in a nonlinear fashion with age.

Conclusion.

Kyphosis and lordosis increase as children age. Between males and females there is no difference in the increase in the size of kyphosis, but there is difference in the size of lordosis with females having greater lordosis versus males at the same age.

Level of Evidence: 2
A case–control study of risk factors for colorectal cancer in an African population
Authors: Katsidzira Leolin , Gangaidzo Innocent T , Makunike-Mutasa Rudo , Manyanga Tadios , Matsena-Zingoni Zvifadzo , Thomson Sandie , Matenga Jonathan A , Rusakaniko Simbarashe , Ramesar Raj
Published: April 2018

The interplay between hereditary and environmental factors in the causation of colorectal cancer in sub-Saharan Africa is poorly understood. We carried out a community based case–control study to identify the risk factors associated with colorectal cancer in Zimbabwe. We recruited 101 cases of colorectal cancer and 202 controls, matched for age, sex and domicile. Potential risk factors including family history, socioeconomic status, urbanization, diabetes mellitus and previous schistosomiasis were evaluated. Conditional logistic regression was used to estimate the odds ratios associated with the different factors. Cases were more likely to have a tertiary education (32.7 vs. 13.4%, P<0.001) and a higher income (18.8 vs. 6.9%, P=0.002). After multivariate analysis, diabetes mellitus [odds ratio (OR): 5.3; 95% confidence interval (CI): 1.4–19.9; P=0.012], previous urban domicile (OR: 2.8; 95% CI: 1.0–7.8; P=0.042), previous schistosomiasis (OR: 2.4; 95% CI: 1.4–4.2; P=0.001) and cancer in a first-degree relative (OR: 2.4; 95% CI: 1.2–4.8; P=0.018) were associated independently with colorectal cancer. Our findings suggest that family history, diabetes mellitus, previous schistosomiasis and approximation to a western lifestyle are the predominant associations with colorectal cancer in Africans. This offers opportunities for targeted prevention and hypothesis-driven research into the aetiology of colorectal cancer in this population.
Disseminated Granulomatous Perifollicular Dermatosis With Comedones: A Follicular Variant of Lichen Nitidus or a New Entity?
Authors: Deza Gustavo , Gallardo Fernando , Barranco Carlos , Marquès Laura , Pujol Ramon M.
Published: April 2018

The presence of acquired generalized keratotic follicular papules and comedones developing in adulthood constitute an uncommon clinical situation. Although this clinical presentation has been described in several noninflammatory, inflammatory, and neoplastic skin disorders, its association with an exclusive perifollicular epitheliod or granulomatous inflammatory reaction represents an exceedingly rare phenomenon. We report a case of a 57-year-old male patient presenting clinically numerous acquired disseminated follicular papules and comedones, showing isolated perifollicular sarcoid-like granulomatous inflammatory infiltrates at the histological examination. These lesions experienced a complete spontaneous resolution after several months. The possibility that this disseminated, epithelioid, granulomatous, perifollicular dermatosis may represent an isolated follicular variant of lichen nitidus or a previously nonreported skin disorder is discussed.
Attitudes Toward Interprofessional Education: Comparing Physical Therapist and Other Health Care Professions' Students
Authors: Smith Barbara S. , Anderson Kelly
Published: April 2018

Background and Purpose.

Interprofessional teams provide the potential of comprehensive and reliable care for patient/clients with complex problems. Interprofessional education (IPE) may change students' attitudes and knowledge necessary to maintain interprofessional (IP) teamwork after graduation. Learning experiences that include interaction with standardized patients enable students to increase their skills to become IP health care providers. This case study assessed the first-time experience of a College of Health Professions in using standardized patients for an IPE activity.

Case Description.

Interprofessional student teams, representing 178 students, were formed representing the following health professions education programs: physical therapist (PT), physician assistant (PA), communication sciences and disorders (CSD), dental hygiene (DH), nursing, medical laboratory science, and public health. Standardized patients interacted with the students. Students participated in a faculty facilitator–guided discussion related to each disciplines' professional roles and patient care goals. Each discipline had faculty representation. Students received feedback from standardized patients and faculty facilitators. A pre-post design was used with a mixed quantitative–qualitative methodology. Quantitative data were analyzed using 1-way analysis of variance. Qualitative data were evaluated using frequency data.

Outcomes.

Only PT, PA, CSD, and DH students participated in sufficient numbers for use in analyses. All groups improved their ratings on the postsurvey statements. Percentages of students whose ratings improved on the postevent survey were examined by department. Physical therapist and PA students showed similar percentages. These percentages of improvements were smaller than improvements of CSD and DH students. Qualitative analysis of open-ended questions revealed four themes: collaborating without judgment of others, learning about the roles and responsibilities of their profession, as well as those of other professions, learning about themselves, and communicating with different personalities.

Discussion and Conclusion.

Students' perceptions of themselves and of other health care professional students changed. Overall, this 4-hour IPE exercise had a positive influence on these students' attitudes toward working as a team member and in being an effective member of that team.
Student Debt in Professional Doctoral Health Care Disciplines
Authors: Pabian Patrick S. , King Kathleen P. , Tippett Steve
Published: April 2018

Introduction.

Higher education has been experiencing funding shortfalls in the past several years. While it is apparent that the financial burden has been impacting students in all fields in both undergraduate and graduate education, there is a potentially even greater impact to those earning professional doctoral degrees. With continuously rising costs of professional education, many concerns are arising in regard to the student debt that is being accumulated by students in these disciplines. Therefore, the objective of this research article is to examine the affordability of doctoral education in medicine, pharmacy, and physical therapy. The primary aim is to analyze the financial impact and economic burden of the degree attainment on graduates in their early careers with a secondary aim to assess the trends in historic physical therapy education costs.

Methodology.

This study utilized publicly available data from the US Bureau of Labor Statistics to identify salary trends in the professions with a cross comparison to economic frameworks defining the hardships due to loan repayment dollar amounts and structure to examine economic strain on early career providers in medicine, pharmacy, and physical therapy. To assess trends in physical therapy education, Consumer Price Index adjustments were made to professional data, outlining annual and total costs of physical therapy education.

Key Findings, Discussion, and Implications.

Student indebtedness and salary data suggest significant impact to all disciplines upon their entry into their given profession. However, the implications to entry-level and early career physical therapists are much more severe due to lower earning potential compared to the other disciplines.

Conclusion.

Students in professional doctoral health care disciplines of medicine, pharmacy, and physical therapy need to be cognizant of their borrowing patterns and institutional costs of their education to avoid possessing financial hardships upon their entry into their given field of practice. Physical therapy students, however, possess high potential for obtaining unmanageable debt due to the costs of education and earning potential early in their career.
Clinical Usefulness of 18F-FDG PET/CT for Staging Cancer of the External Auditory Canal
Authors: Toriihara Akira , Nakadate Masashi , Fujioka Tomoyuki , Oyama Jun , Tsutsumi Takeshi , Asakage Takahiro , Tsunoda Atsunobu , Tateishi Ukihide
Published: April 2018

Objective:

Our objective was to evaluate the clinical usefulness of positron emission tomography/computed tomography using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG-PET/CT) for staging cancer of the external auditory canal (EAC).

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Twenty-three patients (seven men, 16 women, mean age of 59.6-year-old) who underwent FDG-PET/CT and high-resolution CT within 1 month for staging cancer of the EAC between July 2006 and December 2014 were enrolled in this study.

Intervention:

FDG-PET/CT, high-resolution CT.

Main Outcome Measures:

Sensitivity, specificity, and accuracy for diagnosing nodal metastases.

Results:

Most primary tumors were FDG-avid and maximum standardized uptake values were 7.72 ± 3.04 and 9.06 ± 3.94 for the early (60 min) and delayed (120 min) phases of FDG-PET/CT, respectively. FDG-PET/CT was capable of detecting small nodal metastases (short axis <10 mm), and patient-based sensitivity, specificity, and accuracy of FDG-PET/CT for the N staging were 71.4, 81.3, and 78.3%, respectively. There were no patients with distant metastases in our cohort. Compared with the combination of clinical examination and conventional imaging methods, additional FDG-PET/CT resulted in a change in the surgical strategy in five patients (21.7%).

Conclusions:

Most primary cancers of the EAC are FDG-avid, and FDG-PET/CT is useful for detecting small nodal metastases, followed by the change in the surgical strategy.
Temporal Bone Histopathology in Cockayne Syndrome
Authors: Handzel Ophir , Nadol Joseph B.
Published: April 2018

Cockayne syndrome (CS) is a rare autosomal recessive syndrome resulting in defective DNA repair. Its features include cachectic dwarfism, hearing loss, skin hypersensitivity to sunlight, premature aging, and dementia. Presented is a right temporal bone of a patient who died at the age of 29 years. The clinical course was compatible with type 1 CS, the classical form. Homozygous missense variant in the ERCC6 gene (Excision Repair Cross-Complementation group 6) was found, compatible with CS complementation group B. Five years before his death he complained of tinnitus. An audiogram 3 and a 1/2 years before his death demonstrated a moderate symmetrical sensorineural hearing loss at 2 to 8 kHz. The speech reception threshold was 20 dB, and the word recognition score was 100% on the right.

Histopathology revealed a near normal population of inner hair cells except in the basal 5 mm of the cochlea, and mild loss of outer hair cells particularly at the base of the cochlea. Severe atrophy of the spiral ligament and atrophy of stria vascularis and spiral prominence was present. There was loss of Claudius cells, outer sulcus cells, and mesenchymal cells on the scala tympani side of the basilar membrane and loss of cellularity of the limbus. There was a moderate loss of Scarpa's and spiral ganglion neurons, with the most severe loss in the basal segment. The vestibular neuro-epithelium was nearly intact, with the exception of mild loss in the saccule. The vestibular perilymphatic, and to a lesser extent endolymphatic spaces, were filled with filamentous material and osteoid. The patient had better hearing and a larger complement of neurons compared with the few published case reports.

Neurodegenerative symptoms are likely attributed to the effect of intramitochondrial reactive oxygen species. The pathogenesis of hearing loss in CS may shed light on other causes of hearing loss, such as that induced by noise.
Bilateral Congenital Cholesteatoma
Authors: Lee Chang Ho , Kim Mi Kyung , Kim Hyoung-Mi , Won Cheongse , Shin Tae Hyun , Kim So Young
Published: April 2018

Objective:

To report the first large case series of extremely rare bilateral congenital cholesteatoma (CC).

Study Design:

A retrospective cohort study.

Setting:

University hospital otology referral clinic.

Patients:

Six hundred four children with surgically confirmed CC.

Main Outcome Measures:

The bilateral CCs were compared with the unilateral CCs.

Results:

The incidence of bilateral CC was 3.6% (22/615) per case or 1.8% (11/604) per child. Bilateral CC did not differ from unilateral CC regarding its demographics, and invasiveness by the proportion of advanced CC as 31.8% (7/22) versus 28.2% (167/594). But the invasiveness or location randomly differed between the ears, that advanced CC per child was higher as 45.4% (5/11). Bilateral exploration was attempted with a concern for hearing loss, which featured a combination of laser myringotomy to treat early CC and endaural laser-assisted single-stage inside-out cholesteatoma surgery to treat advanced CC. Bilateral exploration was difficult in three children with initially negative otoendoscopy. Among the seven advanced CC, proportion of anterior type was 71.4% (5/7), who all exhibited more than 20 dB HL, but two posterior type retained normal hearing. Therefore, bilateral advanced CCs of anterior origin showed poorest hearing outcome as bilateral more than 20 dB HL, which were in two children. Six second-look operations and one third-look operation were required to treat six residual CCs (30%) in four children (40%), including bilateral residual CC in two (20%); such reoperations were significantly more frequent than in unilateral CC.

Conclusion:

The diagnosis of bilateral CC required high index of suspicion from TBCT, and early bilateral exploration.
Perfluorocarbon Emulsions, Platelet Counts, and Inflammation
Authors: Spiess Bruce D.
Published: April 2018

Perfluorocarbon emulsions (PFC) are a class of lipid-coated micelle slurries wherein the active center of the micelle is a completely halogen/fluorine-substituted hydrocarbon capable of dissolving very large quantities of nonpolar gases. Due to their unique enhanced solubility for oxygen (O2) and nitrogen (N2), PFCs have been used in research as enhanced gas transport media for situations wherein the microcirculation is dysfunctional. In the early 1990s a PFC emulsion was approved for human use during coronary artery angioplasty and one is presently in use in Russia as well as other countries. The pharmaceutical class has had reported in the past associated with variable amounts of time-limited thrombocytopenia. Anxiety about cerebral embolism surfaced after a pivotal phase III trial leading to the cessation of all human research in the United States. At that time papers both published and submitted to the FDA opined (without proof) that the platelet count decrease might be caused by platelet white cell conjugates and/or platelet aggregates, thereby signaling a general inflammatory response to PFCs and a potential thrombosis risk. Although thrombocytopenia has been reported in response to PFC emulsion formulations, it is not ubiquitous and seems to be less associated with some formulations. As well, in some recent animal studies there is no evidence of platelet white cell adverse interactions. The mechanism for the reported thrombocytopenia is as yet not fully understood, and risk–benefit profiles will have to be carefully studied as contemporary human trials move forward.
Humphry Davy: a study in narcissism?
Authors: Cantor Geoffrey
Published: April 2018

Drawing on Jan Golinski's analysis of Humphry Davy's adoption of a variety of social roles, this paper seeks to ground Davy's social interactions by identifying his underlying psychological orientation. A close reading of Davy's own letters and the accounts of him given by his contemporaries suggest that many facets of his behaviour accord closely with those associated with a narcissistic personality, as described in the psychological literature. This perspective helps us understand better many aspects of Davy's life, including his fraught relationship with the Royal Society during and after his election to the presidency in 1820, and especially his conduct in 1816–1818, when he engaged in a vituperative priority dispute with George Stephenson over the invention of the miners' safety lamp. By viewing Davy as a narcissist we can unify apparently disparate aspects of his behaviour.
Are monkeys intuitive Aristotelians? Associations between target size and vertical target position in long-tailed macaques
Authors: Keupp Stefanie , Barbarroja Natàlia , Topolinski Sascha , Fischer Julia
Published: April 2018

Different hypotheses have been put forward to explain the interaction between size perception and spatial position. To explore the evolutionary roots of these phenomena, we tested long-tailed macaques' performance in a two-choice discrimination task on a touchscreen and contrasted two hypotheses. First, a hierarchy association in which large objects are associated with top positions, due to a link between power, dominance and importance with top position. Second, a naive Aristotelian association in which large objects are associated with bottom positions, due to the experience that larger objects are heavier and thus more likely to be found at the bottom. Irrespective of training regime (positively reinforcing the small (Touch-Small) or large (Touch-Large) stimulus), the monkeys had a bias to touch the bottom compared to the top location. Individuals in the Touch-Small group took significantly longer to acquire the task, but subsequently made fewer mistakes. When presented with two stimuli of equal medium size, the Touch-Large group had a clear bias to touch the lower stimulus, while the Touch-Small group touched both locations at equal rates. Our findings point to an innate bias towards larger stimuli and a natural preference for the lower position, while the extent of interaction between size and position depends on executive control requirements of a task.
Generalized transformations and coordinates for static spherically symmetric general relativity
Authors: Hill James M. , O'Leary Joseph
Published: April 2018

We examine a static, spherically symmetric solution of the empty space field equations of general relativity with a non-orthogonal line element which gives rise to an opportunity that does not occur in the standard derivations of the Schwarzschild solution. In these derivations, convenient coordinate transformations and dynamical assumptions inevitably lead to the Schwarzschild solution. By relaxing these conditions, a new solution possibility arises and the resulting formalism embraces the Schwarzschild solution as a special case. The new solution avoids the coordinate singularity associated with the Schwarzschild solution and is achieved by obtaining a more suitable coordinate chart. The solution embodies two arbitrary constants, one of which can be identified as the Newtonian gravitational potential using the weak field limit. The additional arbitrary constant gives rise to a situation that allows for generalizations of the Eddington–Finkelstein transformation and the Kruskal–Szekeres coordinates.
Computing diffusivities from particle models out of equilibrium
Authors: Embacher Peter , Dirr Nicolas , Zimmer Johannes , Reina Celia
Published: April 2018

A new method is proposed to numerically extract the diffusivity of a (typically nonlinear) diffusion equation from underlying stochastic particle systems. The proposed strategy requires the system to be in local equilibrium and have Gaussian fluctuations but it is otherwise allowed to undergo arbitrary out-of-equilibrium evolutions. This could be potentially relevant for particle data obtained from experimental applications. The key idea underlying the method is that finite, yet large, particle systems formally obey stochastic partial differential equations of gradient flow type satisfying a fluctuation–dissipation relation. The strategy is here applied to three classic particle models, namely independent random walkers, a zero-range process and a symmetric simple exclusion process in one space dimension, to allow the comparison with analytic solutions.
Dilatancy induced ductile–brittle transition of shear band in metallic glasses
Authors: Zeng F. , Jiang M. Q. , Dai L. H.
Published: April 2018

Dilatancy-generated structural disordering, an inherent feature of metallic glasses (MGs), has been widely accepted as the physical mechanism for the primary origin and structural evolution of shear banding, as well as the resultant shear failure. However, it remains a great challenge to determine, to what degree of dilatation, a shear banding will evolve into a runaway shear failure. In this work, usingin situacoustic emission monitoring, we probe the dilatancy evolution at the different stages of individual shear band in MGs that underwent severely plastic deformation by the controlled cutting technology. A scaling law is revealed that the dilatancy in a shear band is linearly related to its evolution degree. A transition from ductile-to-brittle shear bands is observed, where the formers dominate stable serrated flow, and the latter lead to a runaway instability (catastrophe failure) of serrated flow. To uncover the underlying mechanics, we develop a theoretical model of shear-band evolution dynamics taking into account an atomic-scale deformation process. Our theoretical results agree with the experimental observations, and demonstrate that the atomic-scale volume expansion arises from an intrinsic shear-band evolution dynamics. Importantly, the onset of the ductile–brittle transition of shear banding is controlled by a critical dilatation.
A geometric framework for dynamics with unilateral constraints and friction, illustrated by an example of self-organized locomotion
Authors: Ghosh Shankar , Merin A. P. , Bhattacharya S. , Nitsure Nitin
Published: April 2018

We present a geometric framework to deal with mechanical systems which have unilateral constraints, and are subject to damping/friction, which cannot be treated within usual classical mechanics. In this new framework, the dynamical evolution of the system takes place on a multidimensional curvilinear polyhedron, and energetics near the corners of the polyhedron leads to qualitative behaviour such as stable entrapment and bifurcation. We illustrate this by an experiment in which dumbbells, placed inside a tilted hollow cylindrical drum that rotates slowly around its axis, climb uphill by forming dynamically stable pairs, seemingly against the pull of gravity.
Topographic somatosensory imagery for real-time fMRI Brain-Computer Interfacing
Authors: Kaas Amanda , Goebel Rainer , Valente Giancarlo , Sorger Bettina
Published: April 2018

Real-time functional magnetic resonance imaging (fMRI) is a promising non-invasive method for brain computer interfaces (BCIs). BCIs translate brain activity into signals that allow communication with the outside world. Visual and motor imagery are often used as information-encoding strategies, but can be challenging if not grounded in recent experience in these modalities, e.g. in patients with locked-in-syndrome (LIS). In contrast, somatosensory imagery might constitute a more suitable information-encoding strategy as somatosensory function is often very robust. Somatosensory imagery has been shown to activate somatotopic cortex, but it has been unclear so far whether it can be reliably detected on a single-trial level and successfully classified according to specific somatosensory imagery content.

Using ultra-high field 7-T fMRI, we show reliable and high-accuracy single-trial decoding of left-foot vs. right-hand somatosensory imagery. Correspondingly, higher decoding accuracies were associated with greater spatial separation of hand and foot decoding-weight patterns in primary somatosensory cortex (S1). Exploiting these novel neuroscientific insights, we developed – and provide a proof of concept for – basic BCI communication by showing that binary (yes/no) answers encoded by somatosensory imagery can be decoded with high accuracy not only offline but also in real-time.

This study demonstrates that body part-specific somatosensory imagery differentially activates somatosensory cortex in a topographically specific manner; evidence which was surprisingly still lacking in the literature. It is also offers a promising novel somatosensory imagery based fMRI-BCI control strategy, with particularly high potential for visually and motor-impaired patients. The strategy could also be transferred to lower MRI field strengths and to mobile functional near-infrared spectroscopy. Finally, given that communication BCIs provide the BCI user with a form of feedback based on their brain signals and can thus be considered as a specific form of neurofeedback, and that repeated use of a BCI has been shown to enhance underlying representations, we expect that the current BCI could also offer an interesting new approach for somatosensory rehabilitation training in the context of stroke and phantom limb pain.
Two biological constants for accurate classification and evolution pattern analysis of Subgen.strobus and subgen. Pinus
Authors: zou Huabin
Published: April 2018

Currently, biological classification and determination of different categories are all based on empirical knowledge,which is obtained relying on morphological and molecular characters. For these methods they lacks of absolutely quantitative criteria ground on intrinsically scientific principles. In fact, accurate science classification must depend on the correct description of biology evolution rules.

In this article a new theoretical approach was proposed, in which two characteristic constants were gained from biological common heredity and variation information theory equation, when it is at the maximum information states, corresponding to symmetric and asymmetric variation states. They are common composition ratios, Pg =0.61, and Pg=0.70. By analyzing the common composition ratios of compounds among oleoresins, two pine subgenus:Subgen.Strobus (Sweet) Held and Subgen. Pinus could be integrated into one class, Genus pinus, excellently, when Pg = 0.61.

These two pine subgenus could be classified into two groups clearly,when Pg = 0.70.

The results is somewhat different from that achieved by means of classical classification relying on morphological characters. On the other hand, the evolution relationship of two subgenus was analyzed based on characteristic sequences of samples, it indicated that white pine origin from pinus tabuliformis. The two constants should be used as the classification constants of some biological categories of plants.
Careful deployment of oilseed rape crops with Rlm6 resistance gene against L. maculans is recommended to prevent the loss of efficacy of this resistance gene in French condiment mustard
Authors: Bousset L. , Ermel M. , Delourme R.
Published: April 2018

Breeding varieties for increased disease resistance is a major means to control epidemics. However, the deployment of resistance genes through space and time drives the genetic composition of the pathogen population, with predictable changes in pathotype frequencies. In France, Leptosphaeria maculans causes disease on Brassica napus oilseed rape crops but not on B. juncea condiment mustard. Prior to the deployment of winter B. napus varieties with Rlm6 resistance gene introduced from B. juncea, the aim of our study was to investigate if this deployment could impact disease control in condiment mustard. We assessed the presence of resistance genes against phoma stem canker in a set of current French B. juncea varieties and breeding lines. Rlm6 was detected in all the 12 condiment mustard varieties. Rlm5 was also detected in 8 varieties. No additional resistance genes were detected with the set of isolates used. Because frequency of isolates virulent on Rlm6 is very low, these results indicate that Rlm6 gene is a major component of disease control in the French B. juncea mustards tested. Using Rlm6 in oilseed rape varieties will very likely induce an increase in frequency of Rlm6 virulent isolates. This raises the acute concern of a wise deployment of oilseed rape around the condiment mustard growing area. Scientific knowledge on adaptation dynamics, spatial segregation of crops and cooperation between actors is currently available in order to mitigate the risk and advert negative consequences of the introduction of Rlm6 resistance gene in oilseed rape varieties.
Model testing for distinctive functional connectivity gradients with resting-state fMRI data
Authors: O’Rawe Jonathan F. , Ide Jaime S. , Leung Hoi-Chung
Published: April 2018

In accordance with the concept of topographic organization of neuroanatomical structures, there is an increased interest in estimating and delineating continuous changes in the functional connectivity patterns across neighboring voxels within a region of interest using resting-state fMRI data. Fundamental to this functional connectivity gradient analysis is the assumption that the functional organization is stable and uniform across the region of interest. To evaluate this assumption, we developed a model testing procedure to arbitrate between overlapping, shifted, or different topographic connectivity gradients across subdivisions of a structure. We tested the procedure using the striatum, a subcortical structure consisting of the caudate nucleus and putamen, in which an extensive literature, primarily from rodents and non-human primates, suggest to have a shared topographic organization of a single diagonal gradient. We found, across multiple resting state fMRI data samples of different spatial resolutions in humans, and one macaque resting state fMRI data sample, that the models with different functional connectivity gradients across the caudate and putamen was the preferred model. The model selection procedure was validated in control conditions of checkerboard subdivisions, demonstrating the expected overlapping gradient. More specifically, while we replicated the diagonal organization of the functional connectivity gradients in both the caudate and putamen, our analysis also revealed a medial-lateral organization within the caudate. Not surprisingly, performing the same analysis assuming a unitary gradient obfuscates the medial-lateral organization of the caudate, producing only a diagonal gradient. These findings demonstrate the importance of testing basic assumptions and evaluating interpretations across species. The significance of differential topographic gradients across the putamen and caudate and the medial-lateral gradient of the caudate in humans should be tested in future studies.
Balancing selection drives maintenance of genetic variation inDrosophilaantimicrobial peptides
Authors: Chapman Joanne R. , Hill Tom , Unckless Robert L.
Published: April 2018

Genes involved in immune defense against pathogens provide some of the most well-known examples of both directional and balancing selection. Antimicrobial peptides (AMPs) are innate immune effector genes, playing a key role in pathogen clearance in many species, includingDrosophila. Conflicting lines of evidence have suggested AMPs may be under directional, balancing or purifying selection. Here, we use a case-control gene approach to show that balancing selection is an important force shaping AMP diversity in two species ofDrosophila. InD. melanogaster, this is most clearly observed in ancestral African populations. Furthermore, the signature of balancing selection is even clearer once background selection has been accounted for. Balancing selection also acts on AMPs inD. mauritiana, an isolated island endemic separated fromD. melanogasterby about 4 million years of evolution. This suggests that balancing selection may be acting to maintain adaptive diversity in AMPs in insects as it does in other taxa.
word2brain
Authors: Nunes Abraham
Published: April 2018

Mapping brain functions to their underlying neural substrates is a central goal of cognitive neuroscience. Functional magnetic resonance imaging (fMRI) has proven indispensable in this endeavour. Recently, there has been growing interest in tackling this problem by mapping semantic concepts onto brain regions using repositories of images and text from the neuroimaging literature. However, no study has thus far approached this problem using (dense) vector representations of words. Using data from the Neurosynth database, we sought to develop a model that could (A) capture local correlations between words in text, as well as topics, (B) capture representation of distributed brain networks in relation to word embeddings, and (C) generate synthetic images given word inputs. We show that jointly embedding words and brain imaging data on a vector space can yield semantic representations that sensibly relate concepts across biological, psychological, and observational levels of analysis. Moreover, our proposed model makes no assumption about spatial orientation of fMRI voxels, which allows for embedding of distributed brain networks onto the semantic space. We demonstrate this capability by generating synthetic brain activation vectors from word inputs. Our model has the potential to advance neuroimaging meta-analysis as well as contextual word-embedding methods more broadly.
Robust Perfect Adaptation in Biomolecular Reaction Networks
Authors: Xiao Fangzhou , Doyle John C.
Published: April 2018

For control in biomolecular systems, the most basic objective of maintaining a small error in a target variable, say the expression level of some protein, is often difficult due to the presence of both large uncertainty of every type and intrinsic limitations on the controller’s implementation. This paper explores the limits of biochemically plausible controller design for the problem of robust perfect adaptation (RPA), biologists’ term for robust steady state tracking. It is well-known that for a large class of nonlinear systems, a system has RPA iff it has integral feedback control (IFC), which has been used extensively in real control systems to achieve RPA. However, we show that due to intrinsic physical limitations on the dynamics of chemical reaction networks (CRNs), cells cannot implement IFC directly in the concentration of a chemical species. This contrasts with electronic implementations, particularly digital, where it is trivial to implement IFC directly in a single state. Therefore, biomolecular systems have to achieve RPA by encoding the integral control variable into the network architecture of a CRN. We describe a general framework to implement RPA in CRNs and show that well-known network motifs that achieve RPA, such as (negative) integral feedback (IFB) and incoherent feedforward (IFF), are examples of such implementations. We also develop methods to solve the problem of designing integral feedback variables for unknown plants. This standard control notion is surprisingly nontrivial and relatively unstudied in biomolecular control. The methods developed here connect different existing fields and approaches on the problem of biomolecular control, and hold promise for systematic chemical reaction controller synthesis as well as analysis.
Metagenomic sequencing provides insights into the location of microbial detoxification in the gut of a small mammalian herbivore
Authors: Kohl Kevin D. , Oakeson Kelly F. , Orr Teri J. , Miller Aaron W. , Forbey Jennifer Sorensen , Phillips Caleb D. , Dale Colin , Weiss Robert B. , Dearing M. Denise
Published: April 2018

Microbial detoxification of plant defense compounds influences the use of certain plants as food sources by herbivores. The location of microbial detoxification along the gut could have profound influences on the distribution, metabolism, and tolerance to toxic compounds. Stephen’s woodrats (Neotoma stephensi) specialize on juniper, which is heavily defended by numerous defensive compounds, such as oxalate, phenolics, and monoterpenes. Woodrats maintain two gut chambers harboring dense microbial communities: a foregut chamber proximal to the major site of toxin absorption, and a cecal chamber in their hindgut. We performed several experiments to investigate the location of microbial detoxification in the woodrat gut. First, we measured levels of toxins across gut chambers. Compared to food material, oxalate concentrations were immediately lower in the foregut chamber, while concentrations of terpenes remain high in the foregut, and are lowest in the cecal chamber. We also conducted metagenomic sequencing of the foregut and cecal chambers to compare microbial functions. We found that the majority of genes associated with detoxification functions were more abundant in the cecal chamber. However, some genes associated with degradation of oxalate and phenolic compounds were more abundant in the foregut. Thus, it seems that microbial detoxification may take place in various chambers depending on the class of chemical compound. We hypothesize that the location of microbial detoxification could impact the tolerance of animals to these compounds, which may have ecological and evolutionary consequences.