Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of Genetic Variation on Plasma Protein Levels in Older Adults Using a Multi-Analyte Panel

Proteins, widely studied as potential biomarkers, play important roles in numerous physiological functions and diseases. Genetic variation may modulate corresponding protein levels and point to the role of these variants in disease pathophysiology. Effects of individual single nucleotide polymorphisms (SNPs) within a gene were analyzed for corresponding plasma protein levels using genome-wide association study (GWAS) genotype data and proteomic panel data with 132 quality-controlled analytes from 521 Caucasian participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Linear regression analysis detected 112 significant (Bonferroni threshold p = 2.44×10−5) associations between 27 analytes and 112 SNPs. 107 out of these 112 associations were tested in the Indiana Memory and Aging Study (IMAS) cohort for replication and 50 associations were replicated at uncorrected p<0.05 in the same direction of effect as those in the ADNI. We identified multiple novel associations including the association of rs7517126 with plasma complement factor H-related protein 1 (CFHR1) level at p<1.46×10−60, accounting for 40 percent of total variation of the protein level. We serendipitously found the association of rs6677604 with the same protein at p<9.29×10−112. Although these two SNPs were not in the strong linkage disequilibrium, 61 percent of total variation of CFHR1 was accounted for by rs6677604 without additional variation by rs7517126 when both SNPs were tested together. 78 other SNP-protein associations in the ADNI sample exceeded genome-wide significance (5×10−8). Our results confirmed previously identified gene-protein associations for interleukin-6 receptor, chemokine CC-4, angiotensin-converting enzyme, and angiotensinogen, although the direction of effect was reversed in some cases. This study is among the first analyses of gene-protein product relationships integrating multiplex-panel proteomics and targeted genes extracted from a GWAS array. With intensive searches taking place for proteomic biomarkers for many diseases, the role of genetic variation takes on new importance and should be considered in interpretation of proteomic results.
A graph-based approach to skin mole matching incorporating template-normalized coordinates

Density of moles is a strong predictor of malignant melanoma. Some dermatologists advocate periodic full-body scan for high-risk patients. In current practice, physicians compare images taken at different time instances to recognize changes. There is an important clinical need to follow changes in the number of moles and their appearance (size, color, texture, shape) in images from two different times. In this paper, we propose a method for finding corresponding moles in patient's skin back images at different scanning times. At first, a template is defined for the human back to calculate the moles' normalized spatial coordinates. Next, matching moles across images is modeled as a graph matching problem and algebraic relations between nodes and edges in the graphs are induced in the matching cost function, which contains terms reflecting proximity regularization, angular agreement between mole pairs, and agreement between the moles' normalized coordinates calculated in the unwarped back template. We propose and discuss alternative approaches for evaluating the goodness of matching. We evaluate our method on a large set of synthetic data (hundreds of pairs) as well as 56 pairs of real dermatological images. Our proposed method compares favorably with the state-of-the-art.
Oscillations in I/O Monotone Systems Under Negative Feedback

Oscillatory behavior is a key property of many biological systems. The small-gain theorem (SGT) for input/output monotone systems provides a sufficient condition for global asymptotic stability of an equilibrium, and hence its violation is a necessary condition for the existence of periodic solutions. One advantage of the use of the monotone SGT technique is its robustness with respect to all perturbations that preserve monotonicity and stability properties of a very low-dimensional (in many interesting examples, just one-dimensional) model reduction. This robustness makes the technique useful in the analysis of molecular biological models in which there is large uncertainty regarding the values of kinetic and other parameters. However, verifying the conditions needed in order to apply the SGT is not always easy. This paper provides an approach to the verification of the needed properties and illustrates the approach through an application to a classical model of circadian oscillations, as a nontrivial "case study," and provides a theorem in the converse direction of predicting oscillations when the SGT conditions fail.
Use of N-butyl cyanoacrylate in implantation of a port-catheter system for hepatic arterial infusion chemotherapy with the fixed-catheter-tip method: is it necessary?

OBJECTIVE The purpose of our study was to evaluate the usefulness of N-butyl cyanoacrylate (NBCA) in addition to microcoils in the percutaneous implantation of a port-catheter system for repeated hepatic arterial infusion chemotherapy with the fixed-catheter-tip method. MATERIALS AND METHODS We retrospectively studied 166 consecutive patients with unresectable advanced liver cancer for whom a port-catheter system was percutaneously implanted with its tip fixed at the gastroduodenal artery with microcoils. In 107 patients, NBCA was also used for catheter tip fixation. We compared this group with a control cohort of 59 patients who did not receive NBCA. Outcomes, including rate of success in implantation, details of embolic agents for fixation, and occurrence of complications related to catheter placement that would prohibit continuation of chemotherapy if not corrected, were compared. RESULTS In all, port-catheter placement was successful. However, 38 complications occurred in 32 patients. Catheter dislocation occurred in nine. Hepatic artery obstruction or severe stenosis was seen in 10. Recanalization of a once-embolized gastroduodenal artery was found in two patients. The rate of dislocation did not differ significantly between patients in whom NBCA was and those in whom it was not used. However, hepatic artery obstruction appeared at a significantly higher rate, and recanalization of a gastroduodenal artery at a significantly lower rate, in patients in whom the catheter tip was fixed with NBCA. CONCLUSION The use of NBCA correlated with a higher rate of hepatic artery obstruction. The use of NBCA should not always be required in port-catheter implantation with the fixed-catheter-tip method.
2-Chloro-1,4-Dimethoxybenzene as a Novel Catalytic Cofactor for Oxidation of Anisyl Alcohol by Lignin Peroxidase

ABSTRACT 2-Chloro-1,4-dimethoxybenzene (2Cl-14DMB) is a natural compound produced de novo by several white rot fungi. This chloroaromatic metabolite was identified as a cofactor superior to veratryl alcohol (VA) in the oxidation of anisyl alcohol (AA) by lignin peroxidase (LiP). Our results reveal that good LiP substrates, such as VA and tryptophan, are comparatively poor cofactors in the oxidation of AA. Furthermore, we show that a good cofactor does not necessarily serve a role in protecting LiP against H2O2inactivation. 2Cl-14DMB was not a direct mediator of AA oxidation, since increasing AA concentrations did not inhibit the oxidation of 2Cl-14DMB at all. However, the high molar ratio of anisaldehyde formed to 2Cl-14DMB consumed, up to 13:1, indicates that a mechanism which recycles the cofactor is present.
Altered B-lymphocyte membrane architecture indicated by ganglioside accessibility in C3H/HeJ mice

We have analyzed both the total ganglioside composition and the surface accessibility of C3H/HeN B lymphocytes and C3H/HeJ B lymphocytes. Seventeen individual resorcinol-positive moieties were visualized by two-dimensional thin-layer chromatography of the purified gangliosides from both strains. Complete homology between strains was seen in the patterns of total gangliosides purified from the endotoxin-responsive and -hyporesponsive strains, with only minor differences in the relative concentrations of four gangliosides. In comparison, only 12 individual gangliosides were accessible to surface labeling following galactose oxidase treatment in these same strains, suggesting that some gangliosides are masked at the cell surface in both strains. However, labeling of the more polar components was greatly reduced in the endotoxin-hyporesponsive (C3H/HeJ) strain, suggesting that these gangliosides have decreased accessibility to galactose oxidase at the cell surface. Therefore, while the total ganglioside compositions of the two strains were nearly equivalent, there were dramatic differences in ganglioside surface accessibility. These findings indicate that an alteration in membrane structure that is associated with the endotoxin hyporesponsiveness observed in C3H/HeJ B lymphocytes exists.
Building Fast and Secure Web Services with OKWS

OKWS is a Web server specialized for secure and fast delivery of dynamic content. It provides Web developers with a small set of tools powerful enough to build complex Webbased systems. Despite its emphasis on security, OKWS shows performance improvements compared to popular systems: when servicing fully dynamic, non-disk-bound database workloads, OKWS's throughput and responsiveness exceed that of Apache 2 [3], Flash [42] and Haboob [76]. Experience with OKWS in a commercial deployment suggests it can reduce hardware and system management costs, while providing security guarantees absent in current systems. In the end, lessons gleaned from the OKWS project provide insight into how operating systems might better facilitate secure application design. Thesis Supervisor: M. Frans Kaashoek Title: Professor
YM500: a small RNA sequencing (smRNA-seq) database for microRNA research

MicroRNAs (miRNAs) are small RNAs ∼22 nt in length that are involved in the regulation of a variety of physiological and pathological processes. Advances in high-throughput small RNA sequencing (smRNA-seq), one of the next-generation sequencing applications, have reshaped the miRNA research landscape. In this study, we established an integrative database, the YM500 (http://ngs.ym.edu.tw/ym500/), containing analysis pipelines and analysis results for 609 human and mice smRNA-seq results, including public data from the Gene Expression Omnibus (GEO) and some private sources. YM500 collects analysis results for miRNA quantification, for isomiR identification (incl. RNA editing), for arm switching discovery, and, more importantly, for novel miRNA predictions. Wetlab validation on >100 miRNAs confirmed high correlation between miRNA profiling and RT-qPCR results (R = 0.84). This database allows researchers to search these four different types of analysis results via our interactive web interface. YM500 allows researchers to define the criteria of isomiRs, and also integrates the information of dbSNP to help researchers distinguish isomiRs from SNPs. A user-friendly interface is provided to integrate miRNA-related information and existing evidence from hundreds of sequencing datasets. The identified novel miRNAs and isomiRs hold the potential for both basic research and biotech applications.
Genetic manipulation of reptilian embryos: toward an understanding of cortical development and evolution

The mammalian neocortex is a remarkable structure that is characterized by tangential surface expansion and six-layered lamination. However, how the mammalian neocortex emerged during evolution remains elusive. Because all modern reptiles have a homolog of the neocortex at the dorsal pallium, developmental analyses of the reptilian cortex are valuable to explore the origin of the neocortex. However, reptilian cortical development and the underlying molecular mechanisms remain unclear, mainly due to technical difficulties with sample collection and embryonic manipulation. Here, we introduce a method of embryonic manipulations for the Madagascar ground gecko and Chinese softshell turtle. We established in ovo electroporation and an ex ovo culture system to address neural stem cell dynamics, neuronal differentiation and migration. Applications of these techniques illuminate the developmental mechanisms underlying reptilian corticogenesis, which provides significant insight into the evolutionary steps of different types of cortex and the origin of the mammalian neocortex.
Tumor suppressor Tsc1 is a new Hsp90 co‐chaperone that facilitates folding of kinase and non‐kinase clients

The tumor suppressors Tsc1 and Tsc2 form the tuberous sclerosis complex (TSC), a regulator of mTOR activity. Tsc1 stabilizes Tsc2; however, the precise mechanism involved remains elusive. The molecular chaperone heat‐shock protein 90 (Hsp90) is an essential component of the cellular homeostatic machinery in eukaryotes. Here, we show that Tsc1 is a new co‐chaperone for Hsp90 that inhibits its ATPase activity. The C‐terminal domain of Tsc1 (998–1,164 aa) forms a homodimer and binds to both protomers of the Hsp90 middle domain. This ensures inhibition of both subunits of the Hsp90 dimer and prevents the activating co‐chaperone Aha1 from binding the middle domain of Hsp90. Conversely, phosphorylation of Aha1‐Y223 increases its affinity for Hsp90 and displaces Tsc1, thereby providing a mechanism for equilibrium between binding of these two co‐chaperones to Hsp90. Our findings establish an active role for Tsc1 as a facilitator of Hsp90‐mediated folding of kinase and non‐kinase clients—including Tsc2—thereby preventing their ubiquitination and proteasomal degradation.
Dynamic right-sizing: a simulation study

Virtually all network applications requiring reliable end-to-end communication depend on TCP. Unfortunately, the performance of any stock TCP is abysmal over wide-area networks (WANs) and even over local-area networks (LANs) with very high-bandwidth links. Currently, network researchers manually optimize TCP buffer sizes to achieve acceptable performance over a given connection. Unfortunately, this manual optimization requires changes to the kernel on both end hosts involved in the network connection (changes that are only effective for connections between these two hosts). Furthermore, because two administrative domains must be coordinated to perform this optimization, this process can be tedious and time consuming. To address these problems, this paper illustrates the benefits of a new technique called dynamic right-sizing. This technique dynamically and automatically determines the best buffer size, and hence flow-control window size in TCP. Our simulation study shows that dynamic right-sizing can improve the performance of flows by two orders of magnitude over stock TCP implementations that have static flow-control windows.
Colloid cohydration and variable rate phenylephrine infusion effectively prevents postspinal hypotension in elective Cesarean deliveries

Background: Prevention of post-spinal hypotension in obstetric patients can be accomplished using intravenous fluid expansion and prophylactic use of sympathomimetic drugs. The affect of combination of colloids and phenylephrine infusion on maternal hemodynamics has not been widely studied and there is no consensus about the dosage required and time of starting its administration. Materials and Methods: This prospective, randomized, double-blind study enrolled 90 healthy term parturients undergoing elective Cesarean delivery under lumbar subarachnoid block (0.5% hyperbaric bupivacaine 10 mg with fentanyl 25 μg). Patients in Group A received prophylactic intravenous phenylephrine infusion (60 μg/minute) along with hydroxyl-ethyl-starch cohydration (6% HES 130/0.42;15 ml/kg) immediately after subarachnoid block. In Group B, patients received 6% HES cohydration and intermittent intravenous 50 μg boluses of phenylephrine. The efficacy of these in maintaining maternal SBP at 90-110% of baseline and neonatal well-being was evaluated. Results: In Group B, 75.5% of patients required rescue phenylephrine boluses to maintain SBP while maternal hemodynamics were well maintained in Group A and rescue drug was not needed. Reactive hypertension occurred in one patient (2.2%) and bradycardia in two patients (4.4%) in Group A. Six patients complained of nausea in Group B (13.3%) compared to one in Group A. All the newborns had normal Apgar scores and Umbilical arterial pH > 7.2. Conclusion: A combination of colloid cohydration and prophylactic phenylephrine infusion initiated at 60 μg/minute maintained maternal hemodynamics and neonatal well-being during Cesarean deliveries requiring minimum interventions by the anesthesiologist.
Injection force and dose accuracy of FlexTouch for the delivery of a new basal insulin

Objective: The aim of the paper is to determine the dose accuracy and injection force of FlexTouch (FT) filled with insulin degludec 100 U/ml, insulin degludec 200 U/ml and insulin degludec/insulin aspart 100 U/ml, SoloStar (SS) filled with insulin glargine 100 U/ml and KwikPen (KP) filled with insulin lispro mix 75/25 100 U/ml. Methods: Dose accuracy was measured at minimum, midpoint and maximum doses (FT 1, 2, 40, 80 and 160 U; SS 1, 40 and 80 U; KP 1, 30 and 60 U). Injection force was measured during the injection of the maximum dose. Results: All doses delivered from FT were within ISO limits (ISO 11608-1:2012) for degludec 100 U/ml, degludec 200 U/ml and degludec/aspart 100 U/ml, and the pens delivered insulin accurately and consistently at all doses tested. Similarly, all tested doses from KP filled with insulin lispro mix 75/25 100 U/ml were within ISO limits, while some doses from SS filled with insulin glargine 100 U/ml were outside ISO limits. FT had a significantly lower injection force than SS and KP (p < 0.05). Conclusions: FT filled with insulin degludec and insulin degludec/insulin aspart, delivered insulin accurately and consistently within ISO limitations at all doses tested; similarly, KP delivered insulin within ISO limitations at all doses tested and SS delivered most doses within ISO limitations. The significantly lower injection force of FT compared to SS and KP is an important feature that has the potential to make the injection process easier for people with diabetes.
Assessing Cancer Survivors’ Needs Using Web-Based Technology: A Pilot Study

Development of cancer survivor resources has been hampered by lack of knowledge regarding survivors’ needs. The main study aim was to pilot test a Web-based cancer survivor needs assessment survey. The second aim was to pilot three sampling approaches. This cross-sectional study was conducted at the Norris Cotton Cancer Center and nine community-based clinics serving urban and rural populations. Population-based and convenience sampling approaches were used to recruit 547 participants over 4 months. Participants completed a Web-based cancer survivor needs assessment survey. Respondents were mainly white (98%), married (71%) women (80%) with a college education (96%). Although most (66%) (n = 362) had been diagnosed with breast cancer, other cancer diagnoses were represented. Participants reported fatigue (47%), forgetfulness (39%), joint pain (34%), anxiety (31%), trouble sleeping (28%), peripheral neuropathy (27%), inflexibility (23%), and weight gain (23%). Survivors with nonbreast solid tumor malignancies reported more problems than those with breast or hematologic malignancies (P range = .037 to <.0001). Most survivors requested assistance for losing weight (74.2%), decreasing fatigue (50%), and improving flexibility (69.3%), sleep (68.5%), and memory (60.2%). Results supported that cancer survivors struggle with many enduring problems. Web-based technology will facilitate future exploration of unmet needs.
Degradation Mechanisms for GaN and GaAs High Speed Transistors

We present a review of reliability issues in AlGaN/GaN and AlGaAs/GaAs high electron mobility transistors (HEMTs) as well as Heterojunction Bipolar Transistors (HBTs) in the AlGaAs/GaAs materials systems. Because of the complex nature and multi-faceted operation modes of these devices, reliability studies must go beyond the typical Arrhenius accelerated life tests. We review the electric field driven degradation in devices with different gate metallization, device dimensions, electric field mitigation techniques (such as source field plate), and the effect of device fabrication processes for both DC and RF stress conditions. We summarize the degradation mechanisms that limit the lifetime of these devices. A variety of contact and surface degradation mechanisms have been reported, but differ in the two device technologies: For HEMTs, the layers are thin and relatively lightly doped compared to HBT structures and there is a metal Schottky gate that is directly on the semiconductor. By contrast, the HBT relies on pn junctions for current modulation and has only Ohmic contacts. This leads to different degradation mechanisms for the two types of devices.
Dosimetric and geometric evaluation of the use of deformable image registration in adaptive intensity-modulated radiotherapy for head-and-neck cancer

The aim of this study was to carry out geometric and dosimetric evaluation of the usefulness of a deformable image registration algorithm utilized for adaptive head-and-neck intensity-modulated radiotherapy. Data consisted of seven patients, each with a planning CT (pCT), a rescanning CT (ReCT) and a cone beam CT (CBCT). The CBCT was acquired on the same day (±1 d) as the ReCT (i.e. at Fraction 17, 18, 23, 24 or 29). The ReCT served as ground truth. A deformed CT (dCT) with structures was created by deforming the pCT to the CBCT. The geometrical comparison was based on the volumes of the deformed, and the manually delineated structures on the ReCT. Likewise, the center of mass shift (CMS) and the Dice similarity coefficient were determined. The dosimetric comparison was performed by recalculating the initial treatment plan on the dCT and the ReCT. Dose–volume histogram (DVH) points and a range of conformity measures were used for the evaluation. We found a significant difference in the median volume of the dCT relative to that of the ReCT. Median CMS values were ∼2–5 mm, except for the spinal cord, where the median CMS was 8 mm. Dosimetric evaluation of target structures revealed small differences, while larger differences were observed for organs at risk. The deformed structures cannot fully replace manually delineated structures. Based on both geometrical and dosimetrical measures, there is a tendency for the dCT to overestimate the need for replanning, compared with the ReCT.