Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of the Akt Survival Pathway Contributes to TRAIL Resistance in Cancer Cells

The mechanism of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in cancer cells is not fully understood. Here, we show that the Akt survival pathway plays an important role in TRAIL resistance in human cancer cells. Specifically, we found that TRAIL treatment activates the Akt survival pathway and that inhibition of this pathway by the PI3K inhibitor LY294002 or knockdown of Akt sensitizes resistant cancer cells to TRAIL. Since Akt is negatively regulated by the tumor suppressor PTEN, we examined the TRAIL sensitivity in PTEN knockdown mouse prostate epithelial cells and found that PTEN−/− cells are more resistant than PTEN+/+ cells while the sensitivity of PTEN+/− cells fell in between. Further, we showed that overexpression of a mutant PTEN confers TRAIL resistance in PTEN+/+ cells, supporting a role of PTEN in TRAIL sensitivity. In TRAIL resistant breast T47D cells, overexpression of the mutant PTEN further increased their resistance to TRAIL. Taken together, our data indicate that inactivation of functional PTEN and the consequent activation of the Akt pathway prevents TRAIL-induced apoptosis, leading to TRAIL resistance. Therefore, our results suggest that TRAIL resistance can be overcome by targeting PTEN or the Akt survival pathway in cancer cells.
On Macroscopic Constitutive Relations and Microstructure Evolution in Multi-Scale Viscoplastic Composites

The determination of the effective or macroscopic properties of composite materials from the corresponding local properties of the constituent phases and the underlying sub-structure constitutes the fundamental problem in Mechanics of Composites. This problem is motivated from the remarkable physical observation that the constitutive properties of these materials appear to be homogeneous or uniform at the length scale of practical applications, despite the sharp variation of their local properties at the length scale of the heterogeneity and the fairly complex spatial distribution of their phases. This dissertation is concerned with the macroscopic mechanical properties of “multi-scale” viscoplastic composites, i.e., composite systems with viscoplastic constituents exhibiting heterogeneity at more than one, well-separated length-scales. Semicrystalline polymers, such as polyethylene, polypropylene, Nylon-6, etc., are prominent examples of two-scale systems, and constitute the largest class of polymers used in technological applications. At the larger lengthscale, a semi-crystalline polymer is an aggregate of a large number of randomly distributed grains that, at the smaller length scale, are made up of alternating layers of an amorphous and a crystalline phase, both of which exhibit nonlinear material behavior. During processing, these materials are often subjected to large deformations that may lead to highly anisotropic mechanical properties as a result of the evolution of the underlying sub-structure. Primarily motivated by applications to semi-crystalline polymers, this work develops general variational methods for the estimation of the effective behavior of multi-scale viscoplastic composites. This general theory is applied to several two-scale material systems with increasing degree of complexity and sophistication. The predictions and some important features of these methods are first investigated in the context of two-dimensional model problems. Then, the general variational methods are used to develop homogenization-based constitutive models for the macroscopic response and texture evolution of semicrystalline polymers under arbitrary finite-strain loading histories. Finally, the theory is specialized to twoscale polycrystals with granular structures at the meso-scale level and lamellar structures at the micro-scale level. In this context, we model the macroscopic instantaneous plastic anisotropy of -TiAl-based polysynthetically twinned crystals and the rolling textures of ( alpha+beta ) Ti alloys. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Mechanical Engineering & Applied Mechanics First Advisor Pedro Ponte Castaneda This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/193
A genetically encoded fluorescent sensor of ERK activity

The activity of the ERK has complex spatial and temporal dynamics that are important for the specificity of downstream effects. However, current biochemical techniques do not allow for the measurement of ERK signaling with fine spatiotemporal resolution. We developed a genetically encoded, FRET-based sensor of ERK activity (the extracellular signal-regulated kinase activity reporter, EKAR), optimized for signal-to-noise ratio and fluorescence lifetime imaging. EKAR selectively and reversibly reported ERK activation in HEK293 cells after epidermal growth factor stimulation. EKAR signals were correlated with ERK phosphorylation, required ERK activity, and did not report the activities of JNK or p38. EKAR reported ERK activation in the dendrites and nucleus of hippocampal pyramidal neurons in brain slices after theta-burst stimuli or trains of back-propagating action potentials. EKAR therefore permits the measurement of spatiotemporal ERK signaling dynamics in living cells, including in neuronal compartments in intact tissues.
Long-term persistence of transmitted HIV drug resistance in male genital tract secretions: implications for secondary transmission.

BACKGROUND Transmitted drug-resistant HIV slowly reverts in the blood to drug-sensitive virus. The environment of the male genital tract (MGT) may result in even slower rates of reversion to drug susceptibility. METHODS We measured the decay of resistance in longitudinally collected blood and semen samples from 5 individuals newly infected with HIV containing resistance mutations to nonnucleoside reverse-transcriptase inhibitors (NNRTIs). We also investigated the sexual transmission of HIV to and from these participants. RESULTS In 3 of the 5 individuals, NNRTI resistance persisted in blood and semen throughout follow-up (mean, 296 days after the estimated day of infection [EDI]). In the other 2 individuals, NNRTI resistance persisted in blood and semen for 871 and 1179 days after the EDI; however, even after NNRTI resistance had fully reverted in blood, it remained readily detectable in semen. Two transmission groups were identified among these participants--one as the recipient partner and the other as the source partner. CONCLUSIONS Transmitted drug-resistant HIV, which persists in blood for years, may revert to wild type even more slowly in the MGT. This prolonged persistence in the MGT may contribute to the high prevalence rates of transmitted drug resistance.
Measurement of ratios of fragmentation fractions for bottom hadrons in p(p)over-bar collisions at root s=1.96 TeV

This paper describes the first measurement of b-quark fragmentation fractions into bottom hadrons in Run II of the Tevatron Collider at Fermilab. The result is based on a 360 pb(-1) sample of data collected with the CDF II detector in p (p) over bar collisions at root s = 1.96 TeV. Semileptonic decays of (B) over bar (0), B-, and (B) over bar (0)(s) mesons, as well as Lambda(0)(b) baryons, are reconstructed. For an effective bottom hadron p(T) threshold of 7 GeV/c, the fragmentation fractions are measured to be f(u)/f(d)=1.054 +/- 0.018(stat)(-0.045)(+0.025)(sys)+/- 0.058(B), f(s)/(f(u)+f(d))=0.160 +/- 0.005(stat)(-0.010)(+0.011)(sys)(-0.034)(+0.057)(B), and f(Lambda b)/(f(u)+f(d))=0.281 +/- 0.012(stat)(-0.056)(+0.058)(sys)(-0.087)(+0.128)(B), where the uncertainty B is due to uncertainties on measured branching ratios. The value of f(s)/(f(u)+f(d)) agrees within one standard deviation with previous CDF measurements and the world average of this quantity, which is dominated by LEP measurements. However, the ratio f(Lambda b)/(f(u)+f(d)) is approximately twice the value previously measured at LEP. The approximately 2 sigma discrepancy is examined in terms of kinematic differences between the two production environments.
Perceptual asymmetry and youths’ responses to stress: Understanding vulnerability to depression

This research examined the hypothesis that reduced posterior right hemisphere activity interferes with the regulation of emotions and behaviour in response to stress, creating vulnerability to depression. Consistent with a diathesis–stress model, we predicted that youths with a reduced posterior right hemisphere bias in emotional processing would engage in less adaptive responses to stress, which would be associated with depressive symptoms in those who reported the recent experience of high, but not low, levels of stress. Participants were 510 4th through 8th graders who completed the Chimeric Faces Task and measures of responses to stress and depressive symptoms. Results supported the idea that responses to stress account for the association between reduced posterior right hemisphere activity and depressive symptoms in youths who report high, but not low, levels of stress. This study provides insight into one process through which reduced posterior right hemisphere activity may confer vulnerability to depressive symptoms, and implicates responses to stress as a target for intervention.
Lateralized auditory spatial perception and the contralaterality of cortical processing as studied with functional magnetic resonance imaging and magnetoencephalography

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were used to study the relationships between lateralized auditory perception in humans and the contralaterality of processing in auditory cortex. Subjects listened to rapidly presented streams of short FM‐sweep tone bursts to detect infrequent, slightly deviant tone bursts. The stimulus streams consisted of either monaural stimuli to one ear or the other or binaural stimuli with brief interaural onset delays. The onset delay gives the binaural sounds a lateralized auditory perception and is thought to be a key component of how our brains localize sounds in space. For the monaural stimuli, fMRI revealed a clear contralaterality in auditory cortex, with a contralaterality index (contralateral activity divided by the sum of contralateral and ipsilateral activity) of 67%. In contrast, the fMRI activations from the laterally perceived binaural stimuli indicated little or no contralaterality (index of 51%). The MEG recordings from the same subjects performing the same task converged qualitatively with the fMRI data, confirming a clear monaural contralaterality, with no contralaterality for the laterally perceived binaurals. However, the MEG monaural contralaterality (55%) was less than the fMRI and decreased across the several hundred millisecond poststimulus time period, going from 57% in the M50 latency range (20–70 ms) to 53% in the M200 range (170–250 ms). These data sets provide both quantification of the degree of contralaterality in the auditory pathways and insight into the locus and mechanism of the lateralized perception of spatially lateralized sounds. Hum. Brain Mapping 7:49–66, 1999. © 1999 Wiley‐Liss, Inc.
Effect of different milking intervals on the composition of cisternal and alveolar milk in dairy cows

Effects of six different milking intervals on the distribution of milk between cistern and alveoli were studied in a randomized, incomplete Latin Square experiment with four lactating Holstein cows. Cisternal and alveolar milk was measured by udder quarter at 4, 8, 12, 16, 20 and 24-h intervals with a 3-d interperiod of regular milking. Cisternal milk was evacuated using a cannula after injection of an oxytocin-receptor blocking agent, followed by an injection of oxytocin to remove the alveolar fraction. Milk samples from each fraction and quarter were collected for analysis. Cisternal and alveolar milk increased with milking interval and represented on average 30 and 70% of the milk stored in the udder, respectively. Fat content in alveolar milk remained constant during the first 16 h, increasing rapidly thereafter, reaching its maximum at 24 h (6·95%). Fat content in cisternal milk decreased with milking interval and reached its minimum at 24 h (0·96%). Total fat yield tended to increase for cisternal milk with longer milking intervals, but it increased markedly for alveolar milk, showing that fat globules did not pass freely from alveoli to cistern between milkings. Milk protein content was greater in rear quarters than in front quarters for both milk fractions. Milk protein content increased in the cisternal milk fraction and tended to increase in the alveolar milk fraction with longer milking intervals, but values did not differ between cisternal and alveolar fractions or between front and rear quarters. Total protein yield increased with milking interval in both fractions, indicating that casein micelles passed more freely than fat globules from the alveolar to the cisternal compartment. In conclusion, the short-term effects of milking intervals in milk composition were explained by the changes observed in alveolar and cisternal milk ratio.
Virtual endocast of Ignacius graybullianus (Paromomyidae, Primates) and brain evolution in early primates

Extant primates are distinctive among mammals in having relatively large brains. As stem primates, Paleogene plesiadapiforms provide direct information relevant to the earliest stages in the evolution of this characteristic. Here we describe a virtual endocast reconstructed from ultra high resolution X-ray computed tomography data for the paromomyid plesiadapiform Ignacius graybullianus (USNM 421608) from the early Eocene of Wyoming. This represents the most complete endocast known for a stem primate, allowing for an unprecedented study of both size and fine details of anatomy. Relative to fossil and extant euprimates, I. graybullianus had large olfactory lobes, but less caudal development of the cerebrum and a poorly demarcated temporal lobe, suggesting more emphasis on olfaction and a less well developed visual system. Although its brain was small compared to those of extant primates, the encephalization quotient of I. graybullianus is higher than that calculated for Paleocene Plesiadapis cookei and overlaps the lower portion of the range documented for fossil euprimates. Comparison to the basal gliroid Rhombomylus suggests that early primates exhibited some expansion of the cerebrum compared to their ancestors. The relatively small brain size of I. graybullianus, an arboreal frugivore, implies that neither arboreality nor frugivory was primarily responsible for the expanded brains of modern primates. However, the contrasts in features related to the visual system between I. graybullianus and fossil and extant euprimates suggest that improvements to these portions of the brain contributed to increases in brain size within Euprimates.
Increased Risk of Cerebral Hemorrhage in Chinese Male Heavy Drinkers with Mild Liver Disorder

Background: Epidemiological evidence suggests that heavy alcohol consumption increases the risk for either stroke or liver disease. The goal of this study was to determine whether heavy drinkers with mild liver disorder (MLD) are at risk of hemorrhagic stroke. Methods:All of the 524 patients recruited were males with a first-ever acute stroke and were consecutively admitted to the Tri-Service General Hospital between January 2000 and December 2001. The risk factors, liver function, stroke subtypes, and hemostatic factors were assessed among 68 patients defined as heavy drinker stroke (HDS) and 456 patients as nonheavy drinker stroke (NHDS). Results: HDS patients had a significantly higher incidence of hemorrhagic stroke than NHDS patients. HDS patients were also associated with significantly higher occurrence of cigarette smoking, hyperuricemia, liver dysfunction, and significantly lower platelet counts. HDS patients with MLD were more likely to have hemorrhagic stroke (76.5%) than HDS patients without MLD (33.3%) and NHDS patients with (40.3%) or without (26.7%) MLD. HDS patients with MLD also exhibited a significantly higher glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio (2.0 ± 1.2) and lower platelet number (185,000 ± 85,000 per µl) when compared with HDS patients without MLD (1.4 ± 0.5; 206,000 ± 59,000 per µl) and NHDS patients with (1.1 ± 1.0; 256,000 ± 97,000 per µl) or without (1.4 ± 0.7; 216,000 ± 68,000 per µl) MLD. Conclusions: HDS patients with MLD are at higher risk for hemorrhagic stroke in part due to the changes in hemostatic factors, although other factors may also contribute to hemorrhagic stroke.
Walking pace and handgrip strength: simple measures of fitness and mortality risk?

Department of Sport Science and Clinical Biomechanics, Research Unit for Exercise Epidemiology, Center of Research in Childhood Health, University of Southern Denmark, Odense, Denmark; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Sexual satisfaction in premarital relationships: Associations with satisfaction, love, commitment, and stability

This investigation focused on how sexual satisfaction is associated with relationship quality and stability in premarital couples. With data collected at multiple times over several years from a sample of heterosexual couples (who were all dating at Time 1), I examined how sexual satisfaction was associated with relationship satisfaction, love, commitment, and stability. At each wave of the study, sexual satisfaction was associated positively with relationship satisfaction, love, and commitment for both men and women. In addition, change in sexual satisfaction between Time 1 and Time 2 was associated with change over the same period in relationship satisfaction, love, and commitment. Furthermore, some evidence was found that sexual satisfaction was associated with relationship stability. Overall, sexual satisfaction had stronger links with relationship quality for men than for women.
Virtual Engineering Sciences Learning Lab: Giving STEM Education a Second Life

Engineering education in the 21st century faces multiple obstacles including limited accessibility of course resources due, in part, to the costs associated with acquiring and maintaining equipment and staffing laboratories. Another continuing challenge is the low level of participation of women and other groups historically underrepresented in STEM disciplines. As a partial remedy for these issues, we established a Virtual Engineering Sciences Learning Lab (VESLL) that provides interactive objects and learning activities, multimedia displays, and instant feedback procedures in a virtual environment to guide students through a series of key quantitative skills and concepts. Developed in the online virtual world Second Life™, VESLL is an interactive environment that supports STEM education, with potential to help reach women and other underrepresented groups. VESLL exposes students to various quantitative skills and concepts through visualization, collaborative games, and problem solving with realistic learning activities. Initial assessments have demonstrated high student interest in VESLL's potential as a supplementary instructional tool and show that student learning experiences were improved by use of VESLL. Ultimately, the VESLL project contributes to the ongoing body of evidence suggesting that online delivery of course content has remarkable potential when properly deployed by STEM educators.
Information weighted consensus-based cooperative space object tracking to overcome malfunctioned sensors and noisy links

With the rapid development of sensor technology, multiple sensors are often available in many engineering applications, such as space object tracking. How to effectively use multiple sensor information is the key to achieving accurate space object state information. In this paper, the information weighted consensus (IWC) strategy is deployed to solve the cooperative sensor tracking problem. In addition, the information theoretic method and the repeated consensus, are used to detect a malfunctioned sensor and overcome the problem of noisy links in the cooperative tracking scenario. The proposed algorithms are demonstrated by a typical space object tracking problem using multiple sensors. The results indicate that: 1) The proposed algorithms can obtain stable estimation results when there is malfunctioned node in the network, 2) can mitigate the effect of noisy links, and 3) achieves close performance to the result with perfect communication links and known malfunctioned node. The results will facilitate the application of using the information weighted consensus algorithm for real multiple sensor space object tracking scenarios.
Age‐related decrements in bone mineral density in women over 65

Age‐related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population‐based lists in four cities in the United States. Bone density in g/cm2 was measured by single‐photon absorptiometry (SPA) and dual x‐ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65–69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from ‐0.82% at the femoral neck and trochanter to ‐1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine.
Winning matches in Grand Slam men's singles: An analysis of player performance-related variables from 1991 to 2008

Abstract This study examines factors that lead to winning matches in men's singles Grand Slam tennis, and proposes guidelines for coaches and professional tennis players both in training and preparation for Grand Slam competitions. Using longitudinal data between 1991 and 2008 retrieved from the official website of the Association of Tennis Professionals, we analysed player performance over 9,144 matches in men's singles Grand Slam tournaments. To predict match outcome, 16 variables were classified into one of three categories: player skills and performance, player characteristics and match characteristics. The three categories were entered sequentially into a logistic regression model to predict the dependent variable: the chance of winning a men's singles Grand Slam match. The final altered model explains 79.4% of the variance (Nagelkerke's pseudo R 2) in match outcomes and correctly predicted 90.6% of cases. The importance of serving, receiving, and break points is further confirmed. The positive effect of stature diminishes when players are taller than 186 cm. We recommend more training in returning skills; to avoid overestimation of the positive impact of stature, left hand and professional experience; and that a male player begins his professional tennis career by participating in the US Open or Wimbledon.