Miracle-dz/UniFAR-FTUs huggingface dataset:
Breadth of Genetic Testing Selected by Patients at Risk of Hereditary Breast and Ovarian Cancer

Objective The aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued. Methods A single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories. Patients meeting guidelines for testing were offered testing at 3 levels: single gene/condition (Single), small panels with highly penetrant genes (Plus), and large panels with high and moderately penetrant genes (Next). Associations between personal or family-related factors and breadth of testing selected were investigated. Continuous and categorical variables were compared using Student t and χ2 tests, as appropriate. Joint classification tables were used to test for effect modification, and a log-binomial model was used to compute rate ratios (RR) with a threshold of P < 0.05 considered significant. Results We identified 253 patients who underwent genetic counseling for HBOC syndrome. Most patients were personally affected by cancer (63.6%), reported at least some college (79.2%), met the National Comprehensive Cancer Network guidelines for BRCA testing (94.5%), and opted to undergo genetic testing (94.1%). Most (84.9%) patients opted for panel testing. An increased likelihood of choosing Next-level testing was found to be associated with patients having any college experience (RR, 1.53; 95% confidence interval, 1.02–2.30), as well as being unaffected by cancer (RR, 1.30; 95% confidence interval, 1.03–1.64). Conclusions Clinical genetic counseling is a highly specialized service, which should be provided to patients at risk of hereditary cancer syndromes. Although some epidemiologic factors can predict a patient's preference for testing breadth, patients were sufficiently able to self-identify the level of testing they were comfortable with after receiving genetic counseling. Most practitioners do not have the time or expertise to provide the degree of counseling needed to enable and empower patients to choose the level of testing they are comfortable with. When available, referral to genetic counselors remains an important component of comprehensive care for women with a personal or family history of cancer suggestive of hereditary risk.
New prospects and strategies for drug target discovery in neurodegenerative disorders

SummaryThe future of neurodegenerative therapeutics development depends upon effective disease modification strategies centered on carefully investigated targets. Pharmaceutical research endeavors that probe for a much deeper understanding of disease pathogenesis, and explain how adaptive or compensatory mechanisms might be engaged to delay disease onset or progression, will produce the needed breakthroughs. Below, we discuss the prospects for new targets emerging out of the study of brain disease genes and their associated pathogenic pathways. We describe a general experimental paradigm that we are employing across several mouse models of neurodegenerative disease to elucidate molecular determinants of selective neuronal vulnerability. We outline key elements of our target discovery program and provide examples of how we integrate genomic technologies, neuroanatomical methods, and mouse genetics in the search for neurodegenerative disease targets.
Endoscopic injection therapy

Since the U.S. Food and Drug Administration approved dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of vesicoureteral reflux, endoscopic injection therapy using Deflux has become a popular alternative to open surgery and continuous antibiotic prophylaxis. Endoscopic correction with Deflux is minimally invasive, well tolerated, and provides cure rates approaching those of open surgery (i.e., approximately 80% in several studies). However, in recent years a less stringent approach to evaluating urinary tract infections (UTIs) and concerns about long-term efficacy and complications associated with endoscopic injection have limited the use of this therapy. In addition, there is little evidence supporting the efficacy of endoscopic injection therapy in preventing UTIs and vesicoureteral reflux-related renal scarring. In this report, we reviewed the current literature regarding endoscopic injection therapy and provided an updated overview of this topic.
Labelling Proteins with Carbon Nanodots

We present efficient labelling of several proteins with orange‐emissive carbon dots. N‐Hydroxysuccinimide was used to activate the carboxyl groups of carbon dots, which subsequently reacted with the lysine groups present on the protein. Labelling was confirmed by UV absorption spectroscopy, PAGE and fluorescence correlation spectroscopy. Protein‐conjugated carbon dots showed an enhancement in fluorescence lifetime and intensity owing to reduced intramolecular dynamic fluctuations. Single‐molecule fluorescence measurements showed reduced fluorescence fluctuations and higher photon budget after protein tagging. Our study opens up opportunities to use carbon dots as highly precise biolabelling probes.
RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells

ABSTRACT RhoH is a haematopoietic -specific, GTPase-deficient Rho GTPase that plays an essential role in T lymphocyte development and haematopoietic cell migration. RhoH is known to interact with ZAP70 in T cell receptor (TCR) signaling and antagonize Rac GTPase activity. To further elucidate the molecular mechanisms of RhoH in T cell function, we carried out in vivo biotinylation and mass spectrometry analysis to identify new RhoH-interacting proteins in Jurkat T cells. We indentified Kaiso by streptavidin capture and confirmed the interaction with RhoH by co-immunoprecipitation. Kaiso is a 95 kDa dual-specific Broad complex, Trantrak, Bric-a-brac/Pox virus, Zinc finger (POZ-ZF) transcription factor that has been shown to regulate both gene expression and p120 catenin-associated cell-cell adhesions. We further showed that RhoH, Kaiso and p120 catenin all co-localize at chemokine-induced actin-containing cell protrusion sites. Using RhoH knockdown we demonstrated that Kaiso localization depends on RhoH function. Similar to the effect of RhoH deficiency, Kaiso down-regulation led to altered cell migration and actin-polymerization in chemokine stimulated Jurkat cells. Interestingly, RhoH and Kaiso also co-localized to the nucleus in a time-dependent fashion after chemokine stimulation and with T cell receptor activation where RhoH is required for Kaiso localization. Based on these results and previous studies, we propose that extracellular microenvironment signals regulate RhoH and Kaiso to modulate actin-cytoskeleton structure and transcriptional activity during T cell migration.
Simulation and analysis of InP/GaInP nanowire Esaki diodes for photovoltaic device applications

In this thesis the WKB-approximation is used to simulate the tunneling current for an Esaki nanowire diode and the result is compared to data from Esaki nanowire diodes grown with MOVPE. The WKB-approximation with triangular potential barrier predicts a strong increase of the tunneling current as a function of the doping densities and at the highest doping levels it gives lower tunneling distances than more reliable drift-diffusion simulations and is thus overestimating the current. The voltage corresponding to the peak current was found to be much higher in the measured samples than in the simulations, and it is shown that an added contact resistance cannot explain this behaviour. Band tailing is suggested as a possible explanation for the difference in the voltage between simulations and experiments. The diode characteristics of the Esaki diode samples are also studied at larger voltages. It is shown that an exponential current law fits well with the diode current at the larger voltages and the resulting contact resistance is too small to significantly change the tunnel current due to its low magnitude. An ideality factor was calculated from the fittings to be larger than 2 indicating that the excess current of the Esaki diode may be due to trap tunneling. (Less)
MIDAS: Empowering 802.11ac Networks with Multiple-Input Distributed Antenna Systems

Next generation WLANs (802.11ac) are undergoing a major shift in their communication paradigm with the introduction of multi-user MIMO (MU-MIMO), transitioning from single-user to multi-user communications. We argue that the conventional AP deployment model of co-located antennas as well as their PHY and MAC mechanisms are not designed to realize the complete potential of MU-MIMO. We propose to leverage distributed antenna systems (DAS) to empower next generation 802.11ac networks. We highlight the multitude of benefits that DAS brings to MU-MIMO and 802.11ac in general. However, several challenges arise in the process of realizing these benefits in practice, where avoiding client modifications and making only minimal software modifications to APs is important to enable rapid adoption. Towards addressing these challenges, we present the design and implementation of MIDAS, the Multiple-Input Distributed Antenna System. MIDAS couples a DAS deployment of AP antennas with a suite of novel yet standards-compatible mechanisms at the PHY and MAC layers that best leverage the DAS deployment to maximize 802.11ac performance. Our WARP-based experimental evaluation demonstrates MIDAS's ability to significantly boost the performance of current 802.11ac design, demonstrating throughput gains over 802.11ac MU-MIMO for 100-200%, while remaining amenable to commercial adoption.
Abce1 orchestrates M-phase entry and cytoskeleton architecture in mouse oocyte

ATP-binding cassette E1 (ABCE1) is a member of the ATP-binding cassette transporters and essential for diverse biological events regulating abroad range of biological functions including viral infection, cell proliferation, anti-apoptosis, translation initiation and ribosome biogenesis. Here, we discovered that Abce1 also plays indispensable roles in mouse oocyte meiotic progression. In the present study, we examined the expression, localization, and function of Abce1 during mouse oocyte meiotic maturation. Immunostaining and confocal microscopy identified that Abce1 localized as small dots in nucleus in germinal vesicle stage. After germinal vesicle breakdown, it dispersedly localized around the whole spindle apparatus. During the anaphase and telophase stages, Abce1 was just like a cap to localize around the two pole region of spindle but not the midbody and chromosome. Knockdown of Abce1 by specific siRNA injection delayed the resumption of meiosis (GVBD) and affected the extrusion of first polar body. Moreover, the process of spindle assembly and chromosome alignment were severely impaired. Abce1-RNAi led to the dissociation of γ-tubulin and p-MAPK from spindle poles, thus caused mounts of spindle morphology abnormities and chromosome alignment defects, leading to high incidence of aneuploidy. Our findings refresh the knowledge of Abce1 function by exploring its role in oocyte meiotic resumption, spindle assembly and chromosome alignment.
Influence of fiber length, fiber content and alkali treatment on mechanical properties of natural fiber-reinforced epoxy composites

: The composites of epoxy resin and Coccinia indica fibers (CIF) were obtained. The raw fibers were initially treated with 5 % NaOH. Compression molding technique was used for preparing the composites with four different fiber lengths (10, 20, 30, 40 mm) and various fiber loadings (25, 30, 35, 40 wt %). The mechanical properties of the produced composites were investigated and their structure was analyzed by using scanning electron microscope (SEM). It was found, that the composite matrix reinforced with 30 mm fiber length at 35 wt % fiber loading exhibited the best mechanical properties.
Renewable Energy Perspective for Turkey Using Sustainability Indicators

AbstractEnergy indicators for sustainable development which were introduced by the International Atomic Energy Agency in 2005 were used in this study to determine a renewable energy perspective for Turkey. The decision making includes social, economic, and environmental factors which affect each other resulting in a multi-criteria decision making problem. The problem is modeled integrating the technique of Analytic Network Process and TOPSIS. Also a sensitivity analysis is performed to monitor the influence of criteria weights on the model results.
A method of gene expression data transfer from cell lines to cancer patients for machine-learning prediction of drug efficiency

ABSTRACT Personalized medicine implies that distinct treatment methods are prescribed to individual patients according several features that may be obtained from, e.g., gene expression profile. The majority of machine learning methods suffer from the deficiency of preceding cases, i.e. the gene expression data on patients combined with the confirmed outcome of known treatment methods. At the same time, there exist thousands of various cell lines that were treated with hundreds of anti-cancer drugs in order to check the ability of these drugs to stop the cell proliferation, and all these cell line cultures were profiled in terms of their gene expression. Here we present a new approach in machine learning, which can predict clinical efficiency of anti-cancer drugs for individual patients by transferring features obtained from the expression-based data from cell lines. The method was validated on three datasets for cancer-like diseases (chronic myeloid leukemia, as well as lung adenocarcinoma and renal carcinoma) treated with targeted drugs – kinase inhibitors, such as imatinib or sorafenib.
Central place foragers and moving stimuli: A hidden‐state model to discriminate the processes affecting movement

Human activities can influence the movement of organisms, either repelling or attracting individuals depending on whether they interfere with natural behavioural patterns or enhance access to food. To discern the processes affecting such interactions, an appropriate analytical approach must reflect the motivations driving behavioural decisions at multiple scales. In this study, we developed a modelling framework for the analysis of foraging trips by central place foragers. By recognising the distinction between movement phases at a larger scale and movement steps at a finer scale, our model can identify periods when animals are actively following moving attractors in their landscape. We applied the framework to GPS tracking data of northern fulmars Fulmarus glacialis, paired with contemporaneous fishing boat locations, to quantify the putative scavenging activity of these seabirds on discarded fish and offal. We estimated the rate and scale of interaction between individual birds and fishing boats and the interplay with other aspects of a foraging trip. The model classified periods when birds were heading out to sea, returning towards the colony or following the closest boat. The probability of switching towards a boat declined with distance and varied depending on the phase of the trip. The maximum distance at which a bird switched towards the closest boat was estimated around 35 km, suggesting the use of olfactory information to locate food. Individuals spent a quarter of a foraging trip, on average, following fishing boats, with marked heterogeneity among trips and individuals. Our approach can be used to characterise interactions between central place foragers and different anthropogenic or natural stimuli. The model identifies the processes influencing central place foraging at multiple scales, which can improve our understanding of the mechanisms underlying movement behaviour and characterise individual variation in interactions with a range of human activities that may attract or repel these species. Therefore, it can be adapted to explore the movement of other species that are subject to multiple dynamic drivers.
Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.
Genetic disruption of fractalkine signaling leads to enhanced loss of cochlear afferents following ototoxic or acoustic injury

Cochlear hair cells are vulnerable to a variety of insults like acoustic trauma and ototoxic drugs. Such injury can also lead to degeneration of spiral ganglion neurons (SGNs), but this occurs over a period of months to years. Neuronal survival is necessary for the proper function of cochlear prosthetics, therefore, it is of great interest to understand the mechanisms that regulate neuronal survival in deaf ears. We have recently demonstrated that selective hair cell ablation is sufficient to attract leukocytes into the spiral ganglion, and that fractalkine signaling plays a role in macrophage recruitment and in the survival of auditory neurons. Fractalkine (CX3CL1), a chemokine that regulates adhesion and migration of leukocytes is expressed by SGNs and signals to leukocytes via its receptor CX3CR1. The present study has extended the previous findings to more clinically relevant conditions of sensorineural hearing loss by examining the role of fractalkine signaling after aminoglycoside ototoxicity or acoustic trauma. Both aminoglycoside treatment and acoustic overstimulation led to the loss of hair cells as well as prolonged increase in the numbers of cochlear leukocytes. Lack of CX3CR1 did not affect macrophage recruitment after injury, but resulted in increased loss of SGNs and enhanced expression of the inflammatory cytokine interleukin‐1β, when compared to mice with intact CX3CR1. These data indicate that the dysregulation of macrophage response caused by the absence of CX3CR1 may contribute to inflammation‐mediated neuronal loss in the deafened ear, suggesting a key role for inflammation in the long‐term survival of target‐deprived afferent neurons.
Latino men who have sex with transgender women: the influence of heteronormativity, homonegativity and transphobia on gender and sexual scripts

Abstract Latino men who have sex with transgender women make up an overlooked sector of the population that requires more attention than is currently given in sexuality and gender studies, particularly in regard to their non-commercial, long-term sexual and romantic relationships with transgender women. Sixty-one sexual histories were selected for this qualitative analysis from a larger study on Latino male bisexuality in the New York City metropolitan area. Findings suggest that participants’ sexual and gender scripts with transgender women are strongly regulated by heteronormativity. Furthermore, homonegativity and transphobia often intersect in the lived experiences of men who have sex with transgender women, resulting in relationship conflicts over the control of transgender women’s bodies, sexual behaviours and gender performance both in public and in private. Findings also suggest that low relationship conflict is more common among men who have sex with transgender women who exhibit diverse sexual roles (being both insertive and receptive during anal sex), or transgress heteronormative scripts through dialogue of desires and/or by embracing transgender women as human beings and not as hyperfeminised objects of desire. Stigma reduction and alternatives to heteronormative interventions are needed to improve relationship dynamics and potentially positively impact on the sexual health and overall wellbeing of Latino men who have sex with transgender women and their transgender partners.
CYCLOPS reveals human transcriptional rhythms in health and disease

Significance Circadian rhythms influence most aspects of physiology and behavior. However, how do we apply this knowledge in medicine? Identifying molecular mechanisms in humans is challenging as existing large-scale datasets rarely include time of day. To address this problem, we combine understanding of periodic structure, evolutionary conservation, and unsupervised machine learning to order unordered human biopsy data along a periodic cycle. We show this works using ordered mouse and human data and that it gives consistent results when applied to populations on different continents. Then, we investigate molecular rhythms in normal human lung and liver and cancerous liver. Finally, we demonstrate proof of concept by finding the best time to administer a chemotherapeutic drug in an animal model. Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular basis of these rhythms has exploded in the last 20 years. However, most of these data are from model organisms, and translation to clinical practice has been limited. Here, we present an approach to identify molecular rhythms in humans from thousands of unordered expression measurements. Our algorithm, cyclic ordering by periodic structure (CYCLOPS), uses evolutionary conservation and machine learning to identify elliptical structure in high-dimensional data. From this structure, CYCLOPS estimates the phase of each sample. We validated CYCLOPS using temporally ordered mouse and human data and demonstrated its consistency on human data from two independent research sites. We used this approach to identify rhythmic transcripts in human liver and lung, including hundreds of drug targets and disease genes. Importantly, for many genes, the circadian variation in expression exceeded variation from genetic and other environmental factors. We also analyzed hepatocellular carcinoma samples and show these solid tumors maintain circadian function but with aberrant output. Finally, to show how this method can catalyze medical translation, we show that dosage time can temporally segregate efficacy from dose-limiting toxicity of streptozocin, a chemotherapeutic drug. In sum, these data show the power of CYCLOPS and temporal reconstruction in bridging basic circadian research and clinical medicine.