gebhart/patrepeval huggingface dataset:
Alternative Splicing of SLC39A14 in Colorectal Cancer is Regulated by the Wnt Pathway (2010)

Alternative splicing is a crucial step in the generation of protein diversity and its misregulation is observed in many human cancer types. By analyzing 143 colorectal samples using exon arrays, SLC39A14, a divalent cation transporter, was identified as being aberrantly spliced in tumor samples. SLC39A14 contains two mutually exclusive exons 4A and 4B and the exon 4A/4B ratio was significantly altered in adenomas (p 3.6 10 10 ) and cancers (p 9.4 10 11 ), independent of microsatellite stability status. The findings were validated in independent exon array data sets and by quantitative real-time reverse-transcription PCR (qRT-PCR). Aberrant Wnt signaling is a hallmark of colorectal tumorigenesis and is characterized by nuclear -catenin. Experimental inactivation of Wnt signaling in DLD1 and Ls174T cells by knockdown of -catenin or overexpression of dominant negative TCFs (TCF1 and TCF4) altered the 4A/4B ratio, indicating that SLC39A14 splicing is regulated by the Wnt pathway. An altered 4A/4B ratio was also observed in gastric and lung cancer where Wnt signaling is also known to be aberrantly activated. The splicing factor SRSF1 and its regulator, the kinase SRPK1, were found to be deregulated upon Wnt inactivation in colorectal carcinoma cells. SRPK1 was also found up-regulated in both adenoma samples (p 1.5 10 5 ) and cancer samples (p 5 10 4 ). In silico splicing factor binding analysis predicted SRSF1 to bind predominantly to the cancer associated exon 4B, hence, it was hypothesized that SRPK1 activates SRSF1 through phosphorylation, followed by SRSF1 binding to exon 4B and regulation of SLC39A14 splicing. Indeed, siRNA-mediated knockdown of SRPK1 and SRSF1 in DLD1 and SW480 colorectal cancer cells led to a change in the 4A/4B isoform ratio, supporting a role of these factors in the regulation of SLC39A14 splicing. In conclusion, alternative splicing of SLC39A14 was identified in colorectal tumors and found to be regulated by the Wnt pathway, most likely through regulation of SRPK1 and SRSF1.
A neural mechanism of speed-accuracy tradeoff in macaque area LIP (2014)

Decision making often involves a tradeoff between speed and accuracy. Previous studies indicate that neural activity in the lateral intraparietal area (LIP) represents the gradual accumulation of evidence toward a threshold level, or evidence bound, which terminates the decision process. The level of this bound is hypothesized to mediate the speed-accuracy tradeoff. To test this, we recorded from LIP while monkeys performed a motion discrimination task in two speed-accuracy regimes. Surprisingly, the terminating threshold levels of neural activity were similar in both regimes. However, neurons recorded in the faster regime exhibited stronger evidence-independent activation from the beginning of decision formation, effectively reducing the evidence-dependent neural modulation needed for choice commitment. Our results suggest that control of speed vs accuracy may be exerted through changes in decision-related neural activity itself rather than through changes in the threshold applied to such neural activity to terminate a decision.
DNA statics and dynamics in nanoscale confinement (2005)

We present, along with theoretical scaling arguments, measurements of the equilibrium and dynamic properties of &#955; and T2 phage DNA molecules confined in quartz nanochannels. Such measurements serve a two-fold purpose: (1) we hope to assist in the design of future nanofluidic devices by quantifying the behavior of semiflexible polymers in confined environments and (2) we hope to test existing theories for confined semiflexible polymers.
Concordance between MRI fusion versus TRUS prostate biopsy and final pathology at radical prostatectomy: Data from the PURC. (2020)

354 Background: Studies suggest that MRI-fusion guided biopsies are superior to the transrectal ultrasound guided (TRUS) technique. Herein, we present the Pennsylvania Urologic Regional Collaborative (PURC) experience with MRI fusion biopsy. We aimed to calculate concordance rates between TRUS prostate needle biopsy versus MRI fusion biopsy and final pathology at the time of radical prostatectomy within our cohort. Methods: Within PURC, a prospective quality improvement collaborative of urology practices in Pennsylvania and New Jersey, we identified all men who underwent a TRUS or MRI fusion prostate needle biopsy followed by radical prostatectomy for the treatment of prostate cancer from 2015 to 2018. We analyzed International Society of Urological Pathology Grade Group (GG) scoring and calculated the concordance and upgrading rates at the time of biopsy versus final pathology at radical prostatectomy. To assess for differences between our rates, we performed a test of equal proportions and Pearson's chi-squared test (significance = p&lt;0.05). Results: We identified 1,437 men who underwent TRUS (n=1247) or MRI Fusion (n=196) biopsies followed by radical prostatectomy. Overall pathologic grading distribution at time of biopsy was: 35.8% (n=515) Grade Group (GG) 1, 28.5% (n=409) GG 2, 13.3% (n=191) GG 3, 11.5% (n=165) GG 4, and 10.9% (n=157) GG 5. Median number of cores at TRUS biopsy was 12 (IQR: 12,13). Median number of cores at MRI Fusion biopsy was 15 (IQR 13,18). Therefore, we inferred patients who underwent MRI Fusion biopsy also underwent standard TRUS biopsies at that time. On average, exact concordance rate between MRI Fusion biopsy and final pathology was 9.1% higher than concordance rate of TRUS biopsy (44.4% vs 35.3%, 95% CI: 1.6%-16.5%, p &lt; 0.01). The overall rate of upgrading on final pathology for MRI fusion biopsies was 5.7% lower than for TRUS biopsies, but this was not statistically significant (35.2% vs 40.9%, 95% CI: 1.5-13.0%, p=0.06). Conclusions: MRI fusion biopsies demonstrated higher concordance rates with final pathology at the time of radical prostatectomy than TRUS prostate biopsies alone.
Radioimmunodetection of colorectal cancer (1980)

This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131-I at a total dose of at least 1.0 muCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131-I-labelled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131-I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the appraent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.
Brain temperature changes coupled to sleep states persist during interleukin 1-enhanced sleep (1986)

The effects of human interleukin 1 (IL 1) on the architecture of rabbit sleep-wake cycles and brain temperature (Tbr) changes coupled to states of vigilance were examined. Cerebral intraventricular infusion of IL 1 induced increased slow-wave sleep (SWS), increased electroencephalographic slow-wave (0.5-4 Hz) amplitudes, and fever. Heat-inactivated IL 1 failed to elicit these responses. IL 1 also significantly inhibited rapid-eye-movement (REM) sleep; however, inactivated IL 1 also reduced REM sleep; thus some of the IL 1-induced REM reduction may be related to the infusion process. The duration and number of sleep cycles (REM-to-REM interval) were unaffected by IL 1. Similarly, Tbr changes that normally occur during the transition from one arousal state to another remained unchanged after IL 1 infusion, even though rabbits were simultaneously febrile. We conclude that IL 1 selectively enhances SWS while leaving sleep cycles and Tbr changes coupled to states of vigilance undisturbed.
Ultracompact fluorescence smartphone attachment using built-in optics for protoporphyrin-IX quantification in skin (2021)

Smartphone-based fluorescence imaging systems have the potential to provide convenient quantitative image guidance at the point of care. However, common approaches have required the addition of complex optical attachments, which reduce translation potential. In this study, a simple clip-on attachment appropriate for fluorescence imaging of protoporphyrin-IX (PpIX) in skin was designed using the built-in light source and ultrawide camera sensor of a smartphone. Software control for image acquisition and quantitative analysis was developed using the 10-bit video capability of the phone. Optical performance was characterized using PpIX in liquid tissue phantoms and endogenously produced PpIX in mice and human skin. The proposed system achieves a very compact form factor (<30 cm<sup>3</sup>) and can be readily fabricated using widely available low-cost materials. The limit of detection of PpIX in optical phantoms was <10 nM, with good signal linearity from 10 to 1000 nM (R<sup>2</sup> >0.99). Both murine and human skin imaging verified that in vivo PpIX fluorescence was detected within 1 hour of applying aminolevulinic acid (ALA) gel. This ultracompact handheld system for quantification of PpIX in skin is well-suited for dermatology clinical workflows. Due to its simplicity and form factor, the proposed system can be readily adapted for use with other smartphone devices and fluorescence imaging applications. Hardware design and software for the system is made freely available on GitHub (https://github.com/optmed/CompactFluorescenceCam).
Multiplexed optical loss based fiber optic sensor for displacement measurement (2005)

Continuous monitoring of soil movements is important to maintain civil structures. Fiber optic sensors can give the sensing solution for continuous displacement monitoring because they can be multiplexed with various sensors on one line of optical fiber, have the durability to harsh environments, and also are not affected by electro-magnetic effects. In this study, we work on the development of a multiplexed optical loss based fiber optic sensor for measuring displacements using the signal difference between the two reflected signals from a pair of optical connectors with various bending losses between them through an optical time domain reflectometer. We fabricate a multiplexed optical loss based fiber-optic sensor detecting linear displacements of 5 measuring positions of an object by setting these new 5 fiber-optic sensor probes on a single mode fiber simultaneously. We find that these sensors have a good capability to measure the displacements.
Origin of electroneutrality in living system (2021)

Abstract Identifying the first chemical transformations, from which life emerged is a central problem in the theories of life’s origins. These reactions would likely have been self-sustaining and self-reproductive before the advent of complex biochemical pathways found in modern organisms to synthesize lipid membranes, enzymes, or nucleic acids. Without lipid membranes and enzymes, exceedingly low concentrations of the organic intermediates of early metabolic cycles in protocells would have significantly hindered evolvability. To address this problem, we propose a mechanism, where a positive membrane potential elevates the concentration of the organic intermediates. In this mechanism, positively charged surfaces of protocell membranes due to accumulation of transition metals generate positive membrane potentials. We compute steady-state ion distributions and determine their stability in a protocell model to identify the key factors constraining achievable membrane potentials. We find that (i) violation of electroneutrality is necessary to induce nonzero membrane potentials; (ii) strategies that generate larger membrane potentials can destabilize ion distributions; and (iii) violation of electroneutrality enhances osmotic pressure and diminishes reaction efficiency, thereby driving the evolution of lipid membranes, specialized ion channels, and active transport systems. Significance The building blocks of life are constantly synthesized and broken down through concurrent cycles of chemical transformations. Tracing these reactions back 4 billion years to their origins has been a long-standing goal of evolutionary biology. The first metabolic cycles at the origin of life must have overcome several obstacles to spontaneously start and sustain their nonequilibrium states. Notably, maintaining the concentration of organic intermediates at high levels needed to support their continued operation and subsequent evolution would have been particularly challenging in primitive cells lacking evolutionarily tuned lipid membranes and enzymes. Here, we propose a mechanism, in which the concentration of organic intermediates could have been elevated to drive early metabolic cycles forward in primitive cells with ion-permeable porous membranes under prebiotic conditions and demonstrate its feasibility in a protocell model from first principles.
FoodLog: Multimedia Food Recording Platform and its Application (2019)

Most existing food recording tools rely on text-based recording, which makes it difficult for users to continuously record and is an unintuitive approach to understanding food content. Photo based recording is advantageous because it provides image-based input assistance and a quick understanding of food intake. Thus, we have constructed a multimedia food recording platform called FoodLog that helps users record their food intakes via photos through personalized image recognition. The number of food records uploaded by general public users exceeds 10 million as of July 2019. We discuss the technical framework and present various analyses of big data containing food records of general public users. We demonstrate that food intake trends have high correlation with the information trends of TV and social media. Based on the FoodLog platform, we collaborated with University Hospital, and we developed a new tool, FoodLog Athlete, that assists nutrition management and communication for sports dietitians and athletes. Thus, FoodLog is not only beneficial for healthcare purposes, but also for other applications, such as nutrition management for athletes.
OSTEOLYSIS WITH CEMENTLESS, SCREW THROUGH ACETABULAR COMPONENTS (2002)

Introduction: Osteolysis is a recognised complication in both cemented and cementless arthroplasty. This may be caused by macrophage mediated reaction to small particulate polyethylene debris. The effective joint space describes the area where polyethylene particles may travel, such as through holes in the cup, to cause a local osteolytic process.Methods: Twenty four cases of osteolysis (in twenty three patients) requiring revision were identified from patients on whom we had performed the primary arthroplasty. These cases were compared to an overall group of 560 primary hip arthroplasty cases performed during the same time and with the same implants.Results: The 24 index cases were revised for osteolysis. This represents 4.3% of the total group in this series of implants. Secondary loosening of the acetabular component was present in 7/24 with 13/24 cups being well fixed at the time of revision. All the cups with secondary loosening had evidence of bone ingrowth & had been undermined by the osteolytic pr...
WNK3 bypasses the tonicity requirement for K-Cl cotransporter activation via a phosphatase-dependent pathway (2006)

SLC12A cation/Cl- cotransporters are mutated in human disease, are targets of diuretics, and are collectively involved in the regulation of cell volume, neuronal excitability, and blood pressure. This gene family has two major branches with different physiological functions and inverse regulation: K-Cl cotransporters (KCC1-KCC4) mediate cellular Cl- efflux, are inhibited by phosphorylation, and are activated by dephosphorylation; Na-(K)-Cl cotransporters (NCC and NKCC1/2) mediate cellular Cl- influx and are activated by phosphorylation. A single kinase/phosphatase pathway is thought to coordinate the activities of these cotransporters in a given cell; however, the mechanisms involved are as yet unknown. We previously demonstrated that WNK3, a paralog of serine-threonine kinases mutated in hereditary hypertension, is coexpressed with several cation/Cl- cotransporters and regulates their activity. Here, we show that WNK3 completely prevents the cell swelling-induced activation of KCC1-KCC4 in Xenopus oocytes. In contrast, catalytically inactive WNK3 abolishes the cell shrinkage-induced inhibition of KCC1-KCC4, resulting in a >100-fold stimulation of K-Cl cotransport during conditions in which transport is normally inactive. This activation is completely abolished by calyculin A and cyclosporine A, inhibitors of protein phosphatase 1 and 2B, respectively. Wild-type WNK3 activates Na-(K)-Cl cotransporters by increasing their phosphorylation, and catalytically inactive kinase inhibits Na-(K)-Cl cotransporters by decreasing their phosphorylation, such that our data suggest that WNK3 is a crucial component of the kinase/phosphatase signaling pathway that coordinately regulates the Cl- influx and efflux branches of the SLC12A cotransporter family.
[Epidermal growth factor receptor (EGFR): therapeutic target in the treatment of lung adenocarcinoma]. (2005)

Revolution in biotechnology made possible to identify those gene errors, which via their encoded proteins (mostly kinase enzymes) are key players in tumor development, growth and progression, and could be considered as molecular targets in tumor diagnosis and therapy. Activity of EGFR (epidermal growth factor receptor), an outstanding representative of the regulatory cell surface receptors, can be inhibited by drugs proved for clinical use. In the past year many groups observed that those lung adenocarcinoma cells, which contain activating mutation in the tyrosine kinase domain of EGFR show remarkable sensitivity to anti-EGFR compounds. The basis of the effective therapy is the identification of the mutations. The clinical advantage of EGFR is an example from the coming age of tumor chemotherapy, when the presence of molecular targets will guide the therapeutic choice.
H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum (2020)

Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H<sub>2</sub>O<sub>2</sub> have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H<sub>2</sub>O<sub>2</sub> levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H<sub>2</sub>O<sub>2</sub> could participate in the patterning of the embryo. We find that perturbations of endogenous H<sub>2</sub>O<sub>2</sub> levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H<sub>2</sub>O<sub>2</sub> levels and taken up by cells with low H<sub>2</sub>O<sub>2</sub> levels where it leads to increased H<sub>2</sub>O<sub>2</sub> production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events.
Effects of Kindermusik training on infants’ rhythmic enculturation (2009)

Phillips-Silver and Trainor (2005) demonstrated a link between movement and the metrical interpretation of rhythm patterns in 7-month-old infants. Infants bounced on every second beat of a rhythmic pattern with no auditory accents later preferred to listen to an accented version of the pattern with accents every second beat (duple or march meter), whereas infants bounced on every third beat of the same rhythmic pattern preferred to listen to a version with accents every third beat (triple or waltz meter). The present study compared infants participating in Kindermusik classes with infants not participating in music classes. In Kindermusik classes infants receive enriched experience moving to music. Following Western musical norms, the majority of the music samples in the classes are in duple meter. During the preference test, Kindermusik infants listened longer overall, indicating heightened interest in musical rhythms. Both groups listened longer to the accented version that matched how they had been bounced, but only the Kindermusik group showed a stronger preference in the case of duple bouncing than in the case of triple bouncing. We conclude that musical classes for infants can accelerate the development of culture-specific metrical perception.
Energy-Efficient Adaptive Virtual MIMO Transmission in a Transmit-Side Correlated Wireless Sensor Network (2013)

In this paper, performances of two different virtual multiple-input multiple-output (MIMO) transmission schemes — spatial multiplexing (SM) and space-time block coding (STBC) — in a correlated wireless sensor network are analyzed. By utilizing a complex Wishart distribution, we investigate the statistical properties of a correlated virtual MIMO channel between the sensors and data collector that is used in the performance analysis of each MIMO transmission mode. Distributed sensors then transmit their data cooperatively to the data collector by choosing a proper transmission mode adaptively based on the channel conditions and spatial correlation among the sensors. Furthermore, after analyzing the energy efficiencies of SM and STBC, we propose a new energy efficient mode switching rule between SM and STBC. Finally, by analytically deriving the required transmit energy of the proposed adaptive transmission scheme, the manner in which the spatial correlation influences the energy consumption is shown. This suggests a cooperating node scheduling protocol that makes energy consumption less sensitive to the variation of the spatial correlation.
Novel inhibitory function of miR‐125b in melanogenesis (2013)

MicroRNAs are known to be the important regulators of skin physiology and considered as new therapeutic targets to treat skin diseases. In this study, miR-125b was identified as a potent regulator of steady-state melanogenesis. We found that the expression of miR-125b was inversely related to pigment levels. A miR-125b mimic decreased the expression of pigmentation-related gene and melanin content, implying that miR-125b functions to decrease pigmentation. Moreover, we observed that the reduction in miR-125b expression in pigmented cells was at least partially due to the hypermethylation of the MIR125B-1 promoter, and miR-125b expression was regulated by intracellular cAMP levels.