Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer Discovery and Drug Development High Fidelity Patient-Derived Xenografts for Accelerating Prostate

Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed.We established a bank of transplantable patient-derived prostate cancer xenografts that capture the biologic and molecular heterogeneity currently confounding prognostication and therapy development. Xenografts preserved the histopathology, genome architecture, and global gene expression of donor tumors. Moreover, their aggressiveness matched patient observations, and their response to androgen withdrawal correlated with tumor subtype. The panel includes the first xenografts generated from needle biopsy tissue obtained at diagnosis. This advance was exploited to generate independent xenografts from different sites of a primary site, enabling functional dissection of tumor heterogeneity. Prolonged exposure of adenocarcinoma xenografts to androgenwithdrawal led to castration-resistant prostate cancer, including thefirst-in-fieldmodel of complete transdifferentiation into lethal neuroendocrine prostate cancer. Further analysis of thismodel supports the hypothesis that neuroendocrine prostate cancer can evolve directly from adenocarcinoma via an adaptive response and yielded a set of genes potentially involved in neuroendocrine transdifferentiation. We predict that these next-generation models will be transformative for advancing mechanistic understanding of disease progression, response to therapy, and personalized oncology. Cancer Res; 74(4); 1272–83. 2013 AACR.
Optimal step-size of a local voting protocol for differentiated consensuses achievement in a stochastic network with cost constraints

This paper deals with a “differentiated consensuses” problem in a distributed stochastic network system with priorities and cost constraints on system topology. The network is considered as a set of heterogeneous agents that process incoming tasks with different importance (priority) levels. The observations about neighbors' states are supposed to be obtained with random noise and delays and the topology could switch over time. Several consensus objectives are to be achieved. To maintain almost balanced load under cost constraints on network topology, i.e. approximate consensus for every priority class across the network, a new family of control protocols that use different step-size parameters for each task class is introduced. An instrument for choosing optimal step-sizes for the proposed control strategy is given. In addition, a numerical example that illustrates the proposed control strategy and the results of simulations are provided.
Attitude toward alternative therapy, compliance with standard treatment, and need for emotional support in patients with melanoma.

OBJECTIVE To examine the attitude of patients with melanoma toward alternative therapies, their compliance with standard treatment, social support received by them, and their ways of coping with illness. DESIGN Survey in a representative sample. SETTING University hospital; central melanoma clinic serving Tyrol region in Austria. PATIENTS Two hundred thirty-six consecutive patients with melanoma were approached in a 3-month-period, and 215 of them participated in the study. OUTCOME MEASURES Results of a self-developed questionnaire to record patients' interest in alternative therapies, the Hornheide Questionnaire to assess patients' distress and social support, and the Freiburg Questionnaire of Coping With Illness. RESULTS One hundred seventeen patients (54.4%) reported interest in nonconventional therapy. Thirty (14%) patients admitted actual use of such methods. The latter group more often suffered from advanced cancer (P < .001). Compared with uninterested patients, subjects interested in alternative therapy were younger (95% confidence intervals [CI] = 41.3-46.5 vs 48.7-56.7; P < .001), showed a more active coping style (95% CIs = 3.45-3.75 vs 2.91-3.50; P = .001) and a tendency toward religiousness and search for personal meaning in the disease (95% CIs = 2.56-2.85 vs 2.17-2.64; P < or = .08). Their faith in conventional medicine and ready compliance with physicians' suggestions were not less than those of uninterested patients (95% CIs = 4.26-4.46 vs 4.35- 4.64; P = .25). However, they believed that they were receiving less emotional support from their physicians (95% CIs = 0.95-1.74 vs 0.21-0.93; P = .04) and expressed interest in getting more such support (P = .04). CONCLUSIONS Patients with melanoma consider non-conventional therapies as supplementary to standard medical methods and as a way of avoiding passivity and coping with feelings of hopelessness. This does not lessen the need to educate patients about the lack of efficacy of unorthodox methods but stresses the importance of offering them adequate emotional support.
Neuropsychological effects of risperidone in children with pervasive developmental disorders: a blinded discontinuation study.

OBJECTIVE Little is known about the neuropsychological effects of risperidone in children with pervasive developmental disorders. METHOD Twenty-four children (aged 5-17 years) with pervasive developmental disorders and co-morbid disruptive behavior who responded favorably to open-label treatment with risperidone as part of a previously described controlled discontinuation study completed two different computerized attention tasks at baseline, weeks 4, 8, and 24 of open-label treatment, and, at 8 weeks after random assignment to either placebo or risperidone. The primary efficacy measures were response latencies to visually presented stimuli requiring two different types of attention-controlled processing, i.e., focused and divided attention. RESULTS About half of the clinical responders did not produce valid performance measures. These could be shown to be of younger mental age and less adaptive as measured by the Vineland Behavior Scales. For the valid task performers divided attention (serial search in working memory) was shown to regress in the placebo group (n = 7), while in the risperidone group (n = 7) there was further improvement. No such group difference was found for focused attention. CONCLUSIONS The study suggests a beneficial effect of risperidone after several months of treatment, enhancing divided attention in children with pervasive developmental disorders.
Comorbid substance use and age at onset of schizophrenia

Background Substance use may be a risk factor for the onset of schizophrenia. Aims To examine the association between substance use and age at onset in a UK, inner-city sample of people with recent-onset schizophrenia. Method The study sample consisted of 152 people recruited to the West London First-Episode Schizophrenia Study. Self-reported data on drug and alcohol use, as well as information on age at onset of psychosis, were collected. Mental state, cognition (IQ, memory and executive function) and social function were also assessed. Results In total, 60% of the participants were smokers, 27% reported a history of problems with alcohol use, 35% reported current substance use (not including alcohol), and 68% reported lifetime substance use (cannabis and psychostimulants were most commonly used). Cannabis use and gender had independent effects on age at onset of psychosis, after adjusting for alcohol misuse and use of other drugs. Conclusions The strong association between self-reported cannabis use and earlier onset of psychosis provides further evidence that schizophrenia may be precipitated by cannabis use and/or that the early onset of symptoms is a risk factor for cannabis use.
Ecological and evolutionary determinants for the adaptive radiation of the Madagascan vangas

Adaptive radiation is the rapid diversification of a single lineage into many species that inhabit a variety of environments or use a variety of resources and differ in traits required to exploit these. Why some lineages undergo adaptive radiation is not well-understood, but filling unoccupied ecological space appears to be a common feature. We construct a complete, dated, species-level phylogeny of the endemic Vangidae of Madagascar. This passerine bird radiation represents a classic, but poorly known, avian adaptive radiation. Our results reveal an initial rapid increase in evolutionary lineages and diversification in morphospace after colonizing Madagascar in the late Oligocene some 25 Mya. A subsequent key innovation involving unique bill morphology was associated with a second increase in diversification rates about 10 Mya. The volume of morphospace occupied by contemporary Madagascan vangas is in many aspects as large (shape variation)—or even larger (size variation)—as that of other better-known avian adaptive radiations, including the much younger Galapagos Darwin's finches and Hawaiian honeycreepers. Morphological space bears a close relationship to diet, substrate use, and foraging movements, and thus our results demonstrate the great extent of the evolutionary diversification of the Madagascan vangas.
T‐type Ca2+ channels encode prior neuronal activity as modulated recovery rates

T‐type Ca2+ channels give rise to low‐threshold inward currents that are central determinants of neuronal excitability. The availability of T‐type Ca2+ channels is strongly influenced by voltage‐dependent inactivation and recovery from inactivation. Here, we show that native and cloned T‐type Ca2+ channel subunits selectively encode specific aspects of prior membrane potential changes via a powerful modulation of the rates with which these channels recover from inactivation. Increasing the duration of subthreshold (−70 to −55 mV) conditioning depolarizations caused a pronounced slowing of subsequent recovery from inactivation of both cloned (Cav3.1–3.3) and native T‐type channels (thalamic neurones). The scaling of recovery rates with increasing duration of conditioning depolarizations could be well described by a power law function. Different T‐type channel isoforms exhibited overlapping but complementary ranges of recovery rates. Intriguingly, scaling of recovery rates was dramatically reduced in Cav3.2 and Cav3.3, but not Cav3.1 subunits, when mock action potentials were superimposed on conditioning depolarizations. Our results suggest that different T‐type channel subunits exhibit dramatic differences in scaling relationships, in addition to well‐described differences in other biophysical properties. Furthermore, the availability of T‐type channels is powerfully modulated over time, depending on the patterns of prior activity that these channels have encountered. These data provide a novel mechanism for cellular short‐term plasticity on the millisecond to second time scale that relies on biophysical properties of specific T‐type Ca2+ channel subunits.
Interface Traps in InAs Nanowire Tunnel FETs and MOSFETs—Part II: Comparative Analysis and Trap-Induced Variability

This paper extends the analysis of the companion paper by presenting a comparative analysis of the impact of interface traps on the I-V characteristics of InAs nanowire tunnel FETs or MOSFETs with a spatially random distribution of traps. The physical mechanisms behind the effects of traps in either tunnel FETs or MOSFETs are compared and, furthermore, traps are also investigated as a possible source of device variability. Our results show that, in MOSFETs, an aggressive oxide thickness scaling can effectively counteract the degradation of the subthreshold slope (SS) possibly produced by interface traps. Tunnel FETs are instead more vulnerable to traps, which are probably the main hindrance to the experimental realization of tunnel FETs with an SS better than 60 mV/decade.
Wireless smart shoe for gait analysis with automated thresholding using PSO

This paper proposes a novel decision system for segregation of five normal gait phases (stance, heel-off, swing 1, swing 2 and heel-strike) by using a real-time wireless smart shoe. The classification employs four force sensitive resistors (FSR) to measure the force underneath a foot together with an inertia measurement unit (IMU) that is attached at the back of the shoe. IMU gives the magnitude of acceleration and inclination angle of the foot with respect to the ground. Data acquisition is collected through XBee wireless network protocol in order to be processed serially by a computer. State transition theorem and threshold-based classification are used to distinguish gait phases according to received data, where the thresholds are optimized by particle swarm optimization. Video recording with real-time data and embedded interfacing is used to verify the output of the proposed state transition algorithm when tested in an indoor environment on a stationary treadmill. Experimentation and verification is conducted on a subject with a normal walking gait cycle.
Quantitative Analysis of Chiari-Like Malformation and Syringomyelia in the Griffon Bruxellois Dog

This study aimed to develop a system of quantitative analysis of canine Chiari-like malformation and syringomyelia on variable quality MRI. We made a series of measurements from magnetic resonance DICOM images from Griffon Bruxellois dogs with and without Chiari-like malformation and syringomyelia and identified several significant variables. We found that in the Griffon Bruxellois dog, Chiari-like malformation is characterized by an apparent shortening of the entire cranial base and possibly by increased proximity of the atlas to the occiput. As a compensatory change, there appears to be an increased height of the rostral cranial cavity with lengthening of the dorsal cranial vault and considerable reorganization of the brain parenchyma including ventral deviation of the olfactory bulbs and rostral invagination of the cerebellum under the occipital lobes.
Black-white differences in survival from late-stage prostate cancer.

OBJECTIVE To examine differences between African Americans (Blacks) and non-Hispanic Whites in risk of death after diagnosis of later-stage prostate cancer in a large sample of patients from US population-based cancer registries. The theory that Black patients with advanced cancer have a lower survival rate compared to their White counterparts, based on a single clinical trial, was tested with large samples of patients. METHODS The Cox proportional hazards regression model was used to compare survival rates among 24,136 non-Hispanic White, and 3,817 Black prostate cancer patients diagnosed between 1988 and 1997, whose cancer had spread beyond the prostate capsule, and who resided in 9 geographic areas covered by the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program of population-based cancer registries. Other analyses involved 5- and 10-year relative survival rates (RSRs) among non-Hispanic White and Black patients diagnosed with distant-stage prostate cancer from 1973 to 1994 (with almost all patients having had a chance to survive for at least 5 years). RESULTS The risk of death from prostate cancer was only slightly higher for Blacks than for Whites (adjusted hazard rate ratio = 1.05), when age, extent of disease, tumor grade, marital status, and surgery were included in the Cox proportional hazards regression model. Five- and 10-year RSRs were about 2%-22% higher for Blacks and Whites in strata defined by extent of disease, or among patients with distant stage cancer, but differences were small among married patients. CONCLUSIONS The findings do not indicate substantial Black-White differences in survival rates of later-stage prostate cancer patients, after adjusting for clinical characteristics and marital status.
Multicenter evaluation of a new enzyme immunoassay for detection of Clostridium difficile enterotoxin A

The Premier Clostridium difficile toxin A enzyme immunoassay (PTA EIA) (Meridian Diagnostics, Inc., Cincinnati, Ohio) for rapid diagnosis of antibiotic-associated colitis (AAC) was evaluated in a multicenter study. Stool samples from 421 patients suspected of having AAC were tested for toxin A by the PTA EIA and for toxin B by three tissue culture assays (TCA) employing WI-38 cells (New England Deaconess Hospital) in conventional tubes or foreskin fibroblasts (Children's Hospital) or Vero cells (Beth Israel Hospital) in microwells. The tubes and plates were examined at 24 and 48 h for cytotoxicity. Clinical criteria, repeat testing at another site, and culture of frozen stool samples for C. difficile were used to evaluate discrepant results. Of 504 samples, 66 were positive and 409 were negative by both tests. Eight samples had indeterminate PTA EIA results and were excluded from this analysis. Of 21 discrepancies, 9 were PTA EIA positive and TCA negative and 12 were PTA EIA negative TCA positive. Following resolution of the discrepancies, 11 of 12 PTA EIA-negative-TCA-positive and 5 of 9 PTA EIA-positive-TCA-negative samples were considered true positive for AAC. The sensitivity and specificity were, respectively, 86.6 and 99.0% for the PTA EIA and 93.9 and 99.8% for TCA. The predictive values of positive and negative tests were, respectively, 94.7 and 97.4% for the PTA EIA and 98.7 and 98.8% for TCA. We conclude that the PTA EIA is a rapid, simple EIA technique whose accuracy in detecting enterotoxin A approaches that of reference TCA methods for detection of cytotoxin B.
The (Biological or Cultural) Essence of Essentialism: Implications for Policy Support among Dominant and Subordinated Groups

Most research links (racial) essentialism to negative intergroup outcomes. We propose that this conclusion reflects both a narrow conceptual focus on biological/genetic essence and a narrow research focus from the perspective of racially dominant groups. We distinguished between beliefs in biological and cultural essences, and we investigated the implications of this distinction for support of social justice policies (e.g., affirmative action) among people with dominant (White) and subordinated (e.g., Black, Latino) racial identities in the United States. Whereas, endorsement of biological essentialism may have similarly negative implications for social justice policies across racial categories, we investigated the hypothesis that endorsement of cultural essentialism would have different implications across racial categories. In Studies 1a and 1b, we assessed the properties of a cultural essentialism measure we developed using two samples with different racial/ethnic compositions. In Study 2, we collected data from 170 participants using an online questionnaire to test the implications of essentialist beliefs for policy support. Consistent with previous research, we found that belief in biological essentialism was negatively related to policy support for participants from both dominant and subordinated categories. In contrast, the relationship between cultural essentialism and policy support varied across identity categories in the hypothesized way: negative for participants from the dominant category but positive for participants from subordinated categories. Results suggest that cultural essentialism may provide a way of identification that subordinated communities use to mobilize support for social justice.
Performance Bounds and Distance Spectra of Variable Length Codes in Turbo/Concatenated Systems

Variable length codes (VLCs), used in data compression, are very sensitive to error propagation in the presence of noisy channels. Addressing this problem with joint source-channel turbo techniques has been proposed in the literature and looks quite promising. But to date, most code-related conclusions are based on simulations. This paper states and proves several theoretical results about the robustness of prefix VLCs concatenated with linear error correcting codes (ECC), assuming a maximum likelihood decoder. Especially, an approximate and asymptotically tight distance spectrum of the concatenated code (VLC+ECC) is rigorously developed. Together with the union bound, it provides upper bounds on the symbol and frame/packet error rates.
Stochastic Funding of a Defined Contribution Pension Plan with Proportional Administrative Costs and Taxation under Mean-Variance Optimization Approach

This paper aim at studying a mean-variance portfolio selection problem with stochastic salary, proportional administrative costs and taxation in the accumulation phase of a defined contribution (DC) pension scheme. The fund process is subjected to taxation while the contribution of the pension plan member (PPM) is tax exempt. It is assumed that the flow of contributions of a PPM are invested into a market that is characterized by a cash account and a stock. The optimal portfolio processes and expected wealth for the PPM are established. The efficient and parabolic frontiers of a PPM portfolios in mean-variance are obtained. It was found that capital market line can be attained when initial fund and the contribution rate are zero. It was also found that the optimal portfolio process involved an inter-temporal hedging term that will offset any shocks to the stochastic salary of the PPM.
The Race to X-ray Microbeam and Nanobeam Science

X-ray microbeams are an emerging characterization tool with broad implications for science, ranging from materials structure and dynamics, to geophysics and environmental science, to biophysics and protein crystallography. We describe how submicrometer hard x-ray beams with the ability to penetrate tens to hundreds of micrometers into most materials and with the ability to determine local composition, chemistry, and (crystal) structure can characterize buried sample volumes and small samples in their natural or extreme environments. Beams less than 10 nanometers have already been demonstrated, and the practical limit for hard x-ray beam size, the limit to trace-element sensitivity, and the ultimate limitations associated with near-atomic structure determinations are the subject of ongoing research.
xPress

Although many older adults are active online, certain age-related disabilities, such as late-life vision impairment, make sustaining online participation difficult. Motivated by the need for accessible online spaces for people experiencing vision impairment in older adulthood, we developed xPress, a voice-based online blogging community. Through a 10-week deployment with seven older adults with acquired vision loss, we analyze how this type of online community enables connecting with peers, sharing experiences, and offering social support in new ways. The design of xPress also highlights the importance of human voice in accessible social platforms and reveals expectations around community participation. We discuss designing for age and disability through the lens of intersectionality and offer design considerations for similar voice-based online communities.