Miracle-dz/UniFAR-FTUs huggingface dataset:
Successful use of adjuvant raloxifene treatment in clozapine-resistant schizophrenia

This case report suggests a promising role for adjuvant raloxifene in premenopausal women with schizophrenia. Interestingly, estrogen has been postulated to have protective effects in young women also. For example, Cohen et al.[4] demonstrated that early menarche was found to predict later age-at-onset of psychosis in women. Also, early menarche was observed to be associated with better clinical outcome. [5] Given our observation that this patient maintained clinical improvement with 60 mg/day of raloxifene treatment (in contrast to 120 mg/day advocated for postmenopausal women), it is possible that premenopausal women might require lower dosage. In summary, this first time case report of striking clinical benefits of adjuvant raloxifene supports compelling need for further systematic studies in premenopausal women with schizophrenia.
Inhibiting clathrin-mediated endocytosis of the leucine-rich G protein-coupled receptor-5 diminishes cell fitness

The leucine-rich G protein-coupled receptor-5 (LGR5) is expressed in adult tissue stem cells of many epithelia, and its overexpression is negatively correlated with cancer prognosis. LGR5 potentiates WNT/β-catenin signaling through its unique constitutive internalization property that clears negative regulators of the WNT-receptor complex from the membrane. However, both the mechanism and physiological relevance of LGR5 internalization are unclear. Therefore, a natural product library was screened to discover LGR5 internalization inhibitors and gain mechanistic insight into LGR5 internalization. The plant lignan justicidin B blocked the constitutive internalization of LGR5. Justicidin B is structurally similar to more potent vacuolar-type H+-ATPase inhibitors, which all inhibited LGR5 internalization by blocking clathrin-mediated endocytosis. We then tested the physiological relevance of LGR5 internalization blockade in vivo. A LGR5-rainbow (LBOW) mouse line was engineered to express three different LGR5 isoforms along with unique fluorescent protein lineage reporters in the same mouse. In this manner, the effects of each isoform on cell fate can be simultaneously assessed through simple fluorescent imaging for each lineage reporter. LBOW mice express three different forms of LGR5, a wild-type form that constitutively internalizes and two mutant forms whose internalization properties have been compromised by genetic perturbations within the carboxyl-terminal tail. LBOW was activated in the intestinal epithelium, and a year-long lineage-tracing course revealed that genetic blockade of LGR5 internalization diminished cell fitness. Together these data provide proof-of-concept genetic evidence that blocking the clathrin-mediated endocytosis of LGR5 could be used to pharmacologically control cell behavior.
Extending Dylan's type system for better type inference and error detection

Whereas dynamic typing enables rapid prototyping and easy experimentation, static typing provides early error detection and better compile time optimization. Gradual typing [26] provides the best of both worlds. This paper shows how to define and implement gradual typing in Dylan, traditionally a dynamically typed language. Dylan poses several special challenges for gradual typing, such as multiple return values, variable-arity methods and generic functions (multiple dispatch). In this paper Dylan is extended with function types and parametric polymorphism. We implemented the type system and aunification-based type inference algorithm in the mainstream Dylan compiler. As case study we use the Dylan standard library (roughly 32000 lines of code), which witnesses that the implementation generates faster code with fewer errors. Some previously undiscovered errors in the Dylan library were revealed.
Multimodal music retrieval for large databases

We present a novel multi-modal access to large MP3 music databases. Retrieval can be fulfilled either in a content-based manner or by keywords. As input modalities, speech by natural language utterances or singing, and manual interaction by handwriting, typing or hardkeys are used. In order to achieve especially robust retrieval results and automatically suggest music to the user, contextual knowledge of the time, date, season, user emotion, and listening habits is integrated in the retrieval process. The system communicates with the user by speech or visual reactions. The concepts shown are especially designed for home and mobile access on tablet-PCs, PDAs, and similar PC solutions, The paper discusses the concept and a working prototype called Shangrila. An evaluation by a user study leads to an impression of the capabilities of the suggested approach to multimodal music retrieval.
UWFDM-988 Activation Analysis of the PULSAR-I Fusion Power Reactor

PULSAR-I is a 1000 MWe pulsed inductively-driven tokamak design. The reactor uses a helium-cooled SiC composite as a structural material and Li2O as a breeder. At shutdown, the blanket and shield activities are 693 and 77.9 MCi, respectively. The blanket activity drops by more than two orders of magnitude during the first hour following its replacement. The shield activity drops more slowly than the blanket’s. One year after shutdown, the shield activity drops to the same level as the blanket activity. The decay heat generated in the blanket drops from 17.3 MW at shutdown to only 1.14 × 10−3 MW within a week following shutdown. The total of 1.135 MW of decay heat is generated in the shield at shutdown. The shield’s decay heat drops by three orders of magnitude during the first day after shutdown. The biological hazard potentials produced in the blanket and shield at shutdown are 33.8 × 10 and 4.3 × 10 m air, respectively. The radwaste classification of the reactor structure is evaluated according to both the NRC 10CFR61 and Fetter waste disposal concentration limits. If the first wall and blanket are disposed of together, the waste package will qualify for Class C Low Level Waste (LLW) disposal. After 30 years of operation, the shield will qualify for disposal as Class A LLW. Assuming a 25 μSv/h limit for hands-on maintenance, only remote maintenance will be allowed at any location inside the containment.
Application of Bio-Based Wrinkled Surfaces as Cell Culture Scaffolds

Microscopic surface architectures that can be easily manufactured have been in demand as mechano-structural cues for tissue engineering. Microscopic surface reliefs synthesized by wrinkling were expected as cell culture scaffolds for cell proliferation, control of cellular alignment and differentiation, and spheroid generation. We previously developed bio-based wrinkled films prepared via lignification-mimetic reactions and drying. Although these films are expected as a candidate for cell culture scaffolds, stability and morphology of the wrinkled surfaces in aqueous buffer solutions were not explored. Here, we investigate the surface morphologies of the wrinkled films in phosphate-buffered saline, and their application to 3T3 cell culture. The wrinkled film prepared with the immersion treatment at 40 °C maintained its wrinkled structure in phosphate-buffered saline even after five days, although the wrinkles were broadened by hydration of the skin layer. Interestingly, higher cell numbers were observed in the 3T3 cell culture using the wrinkled film than using flat film with the same surface composition. In addition, the high biocompatibility of the wrinkled film was confirmed by in vivo experiments. These results strongly encourage application of the wrinkled film as a mechano-structural cue. Studies of the advanced applications for the wrinkled films are now in progress.
Soft robot with a novel variable friction design actuated by SMA and electromagnet

A novel variable friction mechanism is presented for a soft robot that can both move on a flat smooth surface and crawl on a steep smooth surface. First, the variable friction mechanism of the head and tail parts is presented, which can achieve three different frictions (low, medium and high) using SMA3 wire and an electromagnet. In addition, the lightweight and simple structures of both the body and steering parts are demonstrated. Second, according to the variable friction mechanism and the crawling locomotion sequence of the body, head and tail parts, the crawling performance is tested. When the head and tail parts switch between low and medium friction, the soft robot’s maximum inclined surface angles for climbing up and down are 6° and 12°, respectively; the corresponding values are 12° and 42°, respectively, when the head and tail parts switch between high and medium friction. Finally, the steering ability of the soft robot is confirmed to be due to the tunable high friction. In conclusion, a novel three-state switch mechanism using a shape memory alloy and an electromagnet for variable friction is presented, which can help the soft robot achieve crawl and steer.
The Diagnostic Conundrum and Liver Transplantation Outcome for Combined Hepatocellular‐Cholangiocarcinoma

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) is a rare primary liver malignancy with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) histological features. It is almost impossible to obtain an accurate, preoperative noninvasive diagnosis of cHCC‐CC with tumor markers or cross‐sectional abdominal imaging due to the mixed histological features. Despite these difficulties, accurate cHCC‐CC diagnosis remains an important goal with prognostic significance. In our study, we retrospectively reviewed the tumor markers: AFP and CA 19‐9, and cross‐sectional liver imaging, in light of liver explant findings, to identify and characterize cHCC‐CC features followed by liver transplantation (LT) outcome analysis. The results from this 12 patient cohort failed to identify characteristic features for cHCC‐CC. None of the imaging features helped to identify the cHCC‐CC tumor and they mimicked either HCC or CC, depending on the degree of glandular differentiation expressed histologically. In our cHCC‐CC LT recipients, the 1‐, 3‐ and 5‐year cumulative survival probabilities were 79%, 66% and 16%, respectively with a 5‐year survival comparable to or better than LT for intrahepatic CC but poorer than LT for HCC following the Milan criteria. Conceivably explained by its cholangiocarcinoma component the LT outcome for this rare and hard to diagnose tumor appears poor.
Characterization of SPATA5‐related encephalopathy in early childhood

Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole‐exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c. 989_991del (p.Thr330del) and c. 2130_2133del (p.Glu711Profs*21), and the third child had c.967T>A (p.Phe323Ile) and c.2146G>C (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6–12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike‐wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the SPATA5‐related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.
Efficient observability-based test generation by dynamic symbolic execution

Structural coverage metrics have been widely used to measure test suite adequacy as well as to generate test cases. In previous investigations, we have found that the fault-finding effectiveness of tests satisfying structural coverage criteria is highly dependent on program syntax - even if the faulty code is exercised, its effect may not be observable at the output. To address these problems, observability-based coverage metrics have been defined. Specifically, Observable MC/DC (OMC/DC) is a criterion that appears to be both more effective at detecting faults and more robust to program restructuring than MC/DC. Traditional counterexample-based test generation for OMC/DC, however, can be infeasible on large systems. In this study, we propose an incremental test generation approach that combines the notion of observability with dynamic symbolic execution. We evaluated the efficiency and effectiveness of our approach using seven systems from the avionics and medical device domains. Our results show that the incremental approach requires much lower generation time, while achieving even higher fault finding effectiveness compared with regular OMC/DC generation.
Navigating registers in placement for clock network minimization

The progress of VLSI technology is facing two limiting factors: power and variation. Minimizing clock network size can lead to reduced power consumption, less power supply noise, less number of clock buffers and therefore less vulnerability to variations. Previous works on clock network minimization are mostly focused on clock routing and the improvements are often limited by the input register placement. In this work, we propose to navigate registers in cell placement for further clock network size reduction. To solve the conflict between clock network minimization and traditional placement goals, we suggest the following techniques in a quadratic placement framework: (1) Manhattan ring based register guidance; (2) center of gravity constraints for registers; (3) pseudo pin and net; (4) register cluster contraction. These techniques work for both zero skew and prescribed skew designs in both wirelength driven and timing driven placement. Experimental results show that our method can reduce clock net wirelength by 16% -33% with no more than 0.5% increase on signal net wirelength compared with conventional approaches.
Stakeholder Perceptions of Climate Change in the Baltic Sea Region

The project “Developing Policies and Adaptation Strategies to Climate Change in the Baltic Sea Region” (AS­ TRA) assesses regional vulnerabilities to climate change and aims for developing adaptation options. To de­ termine whether the participating municipalities are prepared to climate change, this study investigates stake­ holder perspectives and knowledge in multiple case studies. Based on a qualitative survey, institutions perceived to be relevant as well as climate change impacts and exposure units were collected. Institutional failures are identified. While factors constraining adaptation are found more on the local level, enabling factors are seen at higher levels. Most importantly, climate change is not a priority issue on the municipal level. Respondents have difficulties in identifying concrete susceptibilities and response options, leaving the impression that many muni­ cipalities are not prepared to climate change. This is due to uncertainties, but also to missing frames of refer­ ence, indicating that many municipalities are at an early stage of awareness. Current priorities should be given to knowledge transfer and communication processes. The study further indicates that most actions happen on the mitigation part. This contradicts state-of-the art theory on adaptation such that the study gives impulses for future research.
Processing of Sentences With Intra-Sentential Code-Switching

Speakers of certain bilingual communities systematically produce utterances in which they switch from one language to another, suggesting that the two language systems systematically interact with each other in the production (and recognition) of these sentences. We have investigated this phenomenon in a formal or computational framework which consists of two grammatical systems and a mechanism for switching between the two systems. A variety of constraints apparent in these sentences are then explained in terms of constraints on the switching mechanism, especially, those on closed class items.
Spillovers from Wiring Schools with Broadband: The Critical Role of Children

Providing broadband to schools can be an effective way to foster household Internet adoption in neighboring areas. On the one hand, the infrastructure put into place to meet schools’ needs can also serve households. On the other hand, students get acquainted with the Internet at school and signal its usefulness to adults at home who, consequently, can be more likely to adopt it. In this paper, we model the roles that broadband use at school and Internet adoption in neighboring households play in the decision to adopt the Internet at home and measure their effects empirically. We use data from Portugal between 2006 and 2009 on household Internet penetration and on how much schools use broadband. We use two different sets of instruments for the schools’ broadband use to alleviate endogeneity concerns. Both approaches yield similar results. We find that broadband use at school leads to higher levels of Internet penetration in neighboring households. Broadband use in schools was responsible for a year-over-year increase of 3.5 percentage points on Internet penetration in households with children. Across our data set this effect accounts for about 17% of the increase in home Internet adoption. We also find evidence of regional spillovers in Internet adoption across households. These were roughly responsible for an increase of 2.1 percentage points in Internet penetration or 38% of the total increase in household Internet penetration between 2006 and 2009. These results show that wiring schools with broadband is an effective policy to lower the barriers for Internet adoption at home and as such contributes to accelerating the pace of broadband diffusion. This paper was accepted by Lorin Hitt, information systems .
Embodiment in data sculpture: a model of the physical visualization of information

Information is becoming pervasive in the contemporary society, and is increasingly saturating the visual senses and the cognitive efforts of the lay masses. As our attention for visual impulses and cognitive effort has become more competitive, new approaches are being pursued to convey information to people in memorable and intuitive ways. With human's inherent proficiency in comprehending the physical affordances present in the real world, some researchers and designers are investigating how meaningful insights can be conveyed by way of "sculpting" data. This paper proposes a domain model to establish the concept of data sculpture as a data-based physical artifact, possessing both artistic and functional qualities, that aims to augment a nearby audience's understanding of data insights and any socially relevant issues that underlie it. This paper also proposes a model of embodiment to capture and analyze the wide and multi-layered spectrum of existing data sculptures. In this model, the introduced concepts of metaphorical distances are used as a means to measure embodiment in data sculpture. The models provide groundwork for useful design principles for effective information communication of socially relevant, data-driven insights to a large, lay audience using data sculpture.
Nanoparticle Chemical Sensors: A Study on Optical Humidity Sensor Design

Chongson, Ross Bradley M.S.Ch.E Rose-Hulman Institute of Technology March 2018 Nanoparticle Chemical Sensors: A Study on Optical Humidity Sensor Design Thesis Advisor: Adam J. Nolte The need for sensors capable of operating in harsh environments such as those containing flammable, corrosive or reactive vapors is a niche which thin-film optical devices, with their robustness and ease of maintenance may effectively fill. Two such systems were developed using spin-coating techniques and evaluated for applicability as humidity sensors. The first is based on aggregated silica nanoparticles. The second is a polyelectrolyte multilayer film impregnated with silver nanoparticles which exhibited strong surface plasmon response. Ellipsometric experiments performed using a sealed test cell with constant humidity maintained using saturated salt solutions showed that the former responded strongly to changing humidity. The latter possessed interesting hysteresis behavior as analyzed in a climate-controlled glovebox via reflectometry, but proved insufficiently responsive to changing humidity. The silica nanoparticle substrate was found to be a simple, tunable sensor platform which may be viable for the detection of a wide variety of vapor-phase chemical species.
Hypersensitivity reactions associated with oxaliplatin and their clinical management

Introduction: Oxaliplatin, has become an integral part of the medical treatment of colorectal cancer and other malignancies. Increased use of the drug during the last decade, has led to increased occurrence of oxaliplatin-induced hypersensitivity reactions (HSRs), posing a significant challenge for clinicians. This article aims to review the existing literature regarding the incidence, clinical presentation, pathophysiology, risk factors and current management of oxaliplatin-induced HSRs. Areas covered: A systematic review of the English literature published in PubMed and Medline was undertaken. The clinical manifestations of HSRs were found to be variable and unpredictable. These reactions should be an important concern, as their potential life-threatening risks can force doctors to stop treatment and seek alternatives, which may be less effective, not as well tolerated and/or more expensive. There are a few strategies to prevent these reactions so that patients can still benefit from oxaliplatin. Such strategies include the use of premedication (steroid and antagonists of type I and II histamine receptors), prolonged infusion time and desensitization. Expert opinion: The presented management strategies as well as novel diagnostic tools including skin/intradermal tests and specific IgE have shown promising results. However, future research and validation are warranted in bigger clinical trials.
Aneuploidy in health, disease, and aging

Aneuploidy, an aberrant number of chromosomes, has been recognized as a feature of human malignancies for over a century, but compelling evidence for causality was largely lacking until mouse models for chromosome number instability were used. These in vivo studies have not only uncovered important new insights into the extremely complex aneuploidy–cancer relationship but also into the molecular mechanisms underlying proper and aberrant chromosome segregation. A series of diverse mouse models for the mitotic checkpoint protein BubR1 has provided evidence for a provocative novel link between aneuploidization and the development of age-related pathologies.