Miracle-dz/UniFAR-FTUs huggingface dataset:
The sample complexity of multi-reference alignment

The growing role of data-driven approaches to scientific discovery has unveiled a large class of models that involve latent transformations with a rigid algebraic constraint. Three-dimensional molecule reconstruction in Cryo-Electron Microscopy (cryo-EM) is a central problem in this class. Despite decades of algorithmic and software development, there is still little theoretical understanding of the sample complexity of this problem, that is, number of images required for 3-D reconstruction. Here we consider multi-reference alignment (MRA), a simple model that captures fundamental aspects of the statistical and algorithmic challenges arising in cryo-EM and related problems. In MRA, an unknown signal is subject to two types of corruption: a latent cyclic shift and the more traditional additive white noise. The goal is to recover the signal at a certain precision from independent samples. While at high signal-to-noise ratio (SNR), the number of observations needed to recover a generic signal is proportional to $1/\mathrm{SNR}$, we prove that it rises to a surprising $1/\mathrm{SNR}^3$ in the low SNR regime. This precise phenomenon was observed empirically more than twenty years ago for cryo-EM but has remained unexplained to date. Furthermore, our techniques can easily be extended to the heterogeneous MRA model where the samples come from a mixture of signals, as is often the case in applications such as cryo-EM, where molecules may have different conformations. This provides a first step towards a statistical theory for heterogeneous cryo-EM.
The potential effects of climate-change-associated temperature increases on the metabolic rate of a small Afrotropical bird

ABSTRACT Studies have only recently begun to underline the importance of including data on the physiological flexibility of a species when modelling its vulnerability to extinction from climate change. We investigated the effects of a 4°C increase in ambient temperature (Ta), similar to that predicted for southern Africa by the year 2080, on certain physiological variables of a 10–12 g passerine bird endemic to southern Africa, the Cape white-eye Zosterops virens. There was no significant difference in resting metabolism, body mass and intraperitoneal body temperature between birds housed indoors at 4°C above outside ambient temperature and those housed indoors at outside ambient temperature. We conclude that the physiological flexibility of Cape white-eyes will aid them in coping with the 4°C increase predicted for their range by 2080. Summary: The physiological flexibility of Cape white-eyes will aid them in coping with the 4°C increase predicted for their range by 2080.
Overexpression of homologous phytochrome genes in tomato: exploring the limits in photoperception

Transgenic tomato [Lycopersicon esculentum (=Solanum lycopersicum)] lines overexpressing tomato PHYA, PHYB1, or PHYB2, under control of the constitutive double-35S promoter from cauliflower mosaic virus (CaMV) have been generated to test the level of saturation in individual phytochrome-signalling pathways in tomato. Western blot analysis confirmed the elevated phytochrome protein levels in dark-grown seedlings of the respective PHY overexpressing (PHYOE) lines. Exposure to 4 h of red light resulted in a decrease in phytochrome A protein level in the PHYAOE lines, indicating that the chromophore availability is not limiting for assembly into holoprotein and that the excess of phytochrome A protein is also targeted for light-regulated destruction. The elongation and anthocyanin accumulation responses of plants grown under white light, red light, far-red light, and end-of-day far-red light were used for characterization of selected PHYOE lines. In addition, the anthocyanin accumulation response to different fluence rates of red light of 4-d-old dark-grown seedlings was studied. The elevated levels of phyA in the PHYAOE lines had little effect on seedling and adult plant phenotype. Both PHYAOE in the phyA mutant background and PHYB2OE in the double-mutant background rescued the mutant phenotype, proving that expression of the transgene results in biologically active phytochrome. The PHYB1OE lines showed mild effects on the inhibition of stem elongation and anthocyanin accumulation and little or no effect on the red light high irradiance response. By contrast, the PHYB2OE lines showed a strong inhibition of elongation, enhancement of anthocyanin accumulation, and a strong amplification of the red light high irradiance response.
Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer

Ovarian cancers, and possibly tumor-associated vasculature, express follicle-stimulating hormone receptors (FSHRs), a potential target for antitumor immunity. T cells expressing anti-FSHR receptors killed tumors expressing the FSHR in vitro and reduced tumor growth in mouse models. Adoptive transfer of T cells engineered to express chimeric immunoreceptors is an effective strategy to treat hematologic cancers; however, the use of this type of therapy for solid cancers, such as ovarian cancer, remains challenging because a safe and effective immunotherapeutic target has not yet been identified. Here, we constructed and evaluated a novel redirected T-cell–based immunotherapy targeting human follicle-stimulating hormone receptor (FSHR), a highly conserved molecule in vertebrate animals with expression limited to gonadal tissues, ovarian cancer, and cancer-associated vasculature. Receptor ligand–based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro. Similarly, the outgrowth of human ovarian cancer xenografts in immunodeficient mice was significantly inhibited by the adoptive transfer of FSHR-redirected T cells. Our experimental observations show that FSHR is a promising immunotherapeutic target for ovarian cancer and support further exploration of FSHR-targeted immune therapy approaches for patients with cancer. Cancer Immunol Res; 3(10); 1130–7. ©2015 AACR.
ConfGen: A Conformational Search Method for Efficient Generation of Bioactive Conformers

We describe the methodology, parametrization, and application of a conformational search method, called ConfGen, designed to efficiently generate bioactive conformers. We define efficiency as the ability to generate a bioactive conformation within a small total number of conformations using a reasonable amount of computer time. The method combines physics-based force field calculations with empirically derived heuristics designed to achieve efficient searching and prioritization of the ligand's conformational space. While many parameter settings are supported, four modes spanning a range of speed and quality trades-offs are defined and characterized. The validation set used to test the method is composed of ligands from 667 crystal structures covering a broad array of target and ligand classes. With the fastest mode, ConfGen uses an average of 0.5 s per ligand and generates only 14.3 conformers per ligand, at least one of which lies within 2.0 A root-mean-squared deviation of the crystal structure for 96% of the ligands. The most computationally intensive mode raises this recovery rate to 99%, while taking 8 s per ligand. Combining multiple search modes to "fill-in" holes in the conformation space or energy minimizing using an all-atom force field each lead to improvements in the recovery rates at higher resolutions. Overall, ConfGen is at least as good as competing programs at high resolution and demonstrates higher efficiency at resolutions sufficient for many downstream applications, such as pharmacophore modeling.
Real-time monitoring of antimicrobial use density to reduce antimicrobial resistance through the promotion of antimicrobial heterogeneity in a haematology/oncology unit.

BACKGROUND In haematology/oncology units, the frequent and heavy use of broad-spectrum antimicrobials can lead to outbreaks of antimicrobial resistance. Increasing antimicrobial heterogeneity might be a useful strategy for preventing such resistance. METHODS A real-time antimicrobial use density (AUD) monitoring system (RAMS) was developed to precisely assess antimicrobial heterogeneity. This study was prospectively conducted over a 39 month period and involved 970 patients. Patient-specific antimicrobial therapy with five carbapenems (meropenem, biapenem, panipenem/betamipron, imipenem/cilastatin and doripenem) and four non-carbapenems (piperacillin/tazobactam, ceftazidime, cefozopran and cefepime) was prescribed in the first 12 months. A first-line antimicrobial was selected from among nine antimicrobials according to a predetermined schedule for the next 15 months. AUD-based antimicrobial selection was implemented using the RAMS during the last 12 months. We compared our findings for the RAMS period with those for the other periods to determine the effects of RAMS-based AUD monitoring on antimicrobial resistance. RESULTS The mean absolute difference between the AUD values of carbapenems and non-carbapenems (AUD deviation) was 6.0% in the RAMS period (range 0.5%-15.8%) and antimicrobial heterogeneity (AUD deviation <10%) was achieved in 10 out of 12 months (83.3%). Furthermore, during the RAMS period, AUD deviation was significantly smaller and the frequency of outbreaks of antimicrobial-resistant strains other than Stenotrophomonas maltophilia was significantly decreased (from 7.9% to 3.5%; P < 0.01) compared with the other periods. CONCLUSIONS The longer period of stable antimicrobial heterogeneity achieved by the RAMS strengthened its preventive effects against antimicrobial resistance. Optimal antimicrobial heterogeneity based on real-time AUD monitoring could reduce the frequency of outbreaks of antimicrobial resistance.
Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

Background The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. Methodology Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. Principal Findings Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. Conclusions Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. Significance Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.
Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia: Swift or Sure? The Acceptable Rate of Neurovascular Mimics Among IV tPA–Treated Patients

# {#article-title-2} To the Editor: We congratulate Chernyshev et al.1 on their study concerning tissue plasminogen activator (tPA) safety in patients with stroke mimics (SM). In addition to its undeniable value, some methodologic issues are controversial. It is unclear how patients were allocated in neuroimaging-negative cerebral ischemia (NNCI) and SM subgroups. The NNCI group may include TIAs and patients in whom thrombolysis succeeded. The SM group may include patients who did not have a true stroke. This determination often requires advanced parenchymal and vascular examinations immediately after admission. Chernyshev et al. reported that CT scan was the only tool for tissue evaluation before tPA, yet early vascular studies were not mentioned. If the presence of an alternative diagnosis to stroke was the only difference between SM and NNCI definitions, the underrecognition of this alternative diagnosis could misclassify SM patients into the NNCI category. Misclassification of NNCI patients into the SM subgroup could also occur. Some strokes present with seizures, headache, confusional states, or other clinical pictures that resemble stroke-mimicking conditions. In these patients, a normal CT scan at baseline and early reperfusion may lead to a negative follow-up neuroimage. However, they do not have a SM. The reported SM rate of 14% is very high. We reviewed the frequency and outcome of SM among 199 …
Appropriateness of breast‐conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2

Although BRCA1 and BRCA2 were identified in 1994 and 1995, respectively, to the authors' knowledge the optimal management of women with BRCA‐associated breast carcinoma remains incompletely defined. The current study evaluates the appropriateness of breast‐conserving therapy (BCT) in women with BRCA mutations.
The Borders of "Europe": Autonomy of Migration, Tactics of Bordering

In recent years the borders of Europe have been perceived as being besieged by a staggering refugee and migration crisis. The contributors to The Borders of "Europe" see this crisis less as an incursion into Europe by external conflicts than as the result of migrants exercising their freedom of movement. Addressing the new technologies and technical forms European states use to curb, control, and constrain what contributors to the volume call the autonomy of migration, this book shows how the continent's amorphous borders present a premier site for the enactment and disputation of the very idea of Europe. They also outline how from Istanbul to London, Sweden to Mali, and Tunisia to Latvia, migrants are finding ways to subvert visa policies and asylum procedures while negotiating increasingly militarized and surveilled borders. Situating the migration crisis within a global frame and attending to migrant and refugee supporters as well as those who stoke nativist fears, this timely volume demonstrates how the enforcement of Europe’s borders is an important element of the worldwide regulation of human mobility. Contributors. Ruben Andersson, Nicholas De Genova, Dace Dzenovska, Evelina Gambino, Glenda Garelli, Charles Heller, Clara Lecadet, Souad Osseiran, Lorenzo Pezzani, Fiorenza Picozza, Stephan Scheel, Maurice Stierl, Laia Soto Bermant, Martina Tazzioli
KG‐135 Inhibits COX‐2 Expression by Blocking the Activation of JNK and AP‐1 in Phorbol Ester–Stimulated Human Breast Epithelial Cells

Abstract: Ginsenosides, ingredients of ginseng, have a wide array of pharmacologic effects. Especially, ginsenosides Rk1, Rg3, and Rg5 derived from heat‐processed ginseng have been shown to possess substantial anti‐tumor‐promoting effects. KG‐135 is a formulated complex that contains several antitumorigenic ginsenosides, such as Rk1, Rg3, Rg5, Rk2, Rk3, Rs3, Rs4, Rs5, Rs6, Rs7, etc. The present article was aimed at evaluating the chemopreventive as well as anti‐inflammatory effects of KG‐135 in the human breast epithelial cell line (MCF‐10A). One of the well‐recognized molecular targets for chemoprevention is cyclooxygenase‐2 (COX‐2) that is abnormally upregulated in many premalignant and malignant tissues and cells. In this study, we found that KG‐135 inhibited COX‐2 expression in MCF‐10A cells stimulated with a prototype tumor promotor 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Since the transcription factor activator protein‐1 (AP‐1) plays a role in tumor promotion and is also known to regulate COX‐2 induction, we attempted to determine the effect of KG‐135 on TPA‐induced activation of AP‐1. Cotreatment with KG‐135 resulted in a decrease in TPA‐induced DNA binding of AP‐1. In addition, KG‐135 inhibited TPA‐induced phosphorylation of c‐Jun N‐terminal kinases (JNK) that regulates COX‐2 expression in MCF‐10A cells. The JNK inhibitor SP600125 attenuated COX‐2 expression in TPA‐treated MCF‐10A cells. Taken together, the above findings suggest that KG‐135 inhibits TPA‐induced COX‐2 expression in MCF‐10A cells by blocking the JNK/AP‐1 signaling pathway.
Preinjury warfarin does not impact outcome in trauma patients.

OBJECTIVE The objective of this study was to determine whether the preinjury condition of anticoagulation had an adverse impact on patients sustaining injury. METHODS A retrospective analysis was performed for prospectively collected registry data from 1995-2000 from all accredited trauma centers in Pennsylvania. The registry was queried for all trauma patients who had anticoagulation therapy as a preinjury condition (PIC). This group served as our experimental cohort. A control cohort (not having warfarin therapy as a PIC) was developed using case-matching techniques for age, sex, Glasgow Coma Scale (GCS), Injury Severity Score (ISS), A Severity Characterization of Trauma (ASCOT) score, and in the head injured patients, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses. Head and non-head injured patients were evaluated separately. The cohorts were examined for 28-day mortality, intensive care unit length of stay (ICU-LOS), hospital length of stay (HOS-LOS), PICs, occurrences, discharge destinations, and functional status at discharge. Chi2 and Student's t test were used to evaluate the data; p values < 0.05 were considered significant. RESULTS Two thousand nine hundred forty-two patients were available for analysis. The prevalence of PICs was significantly greater in the warfarin group for both the head and non-head injured populations (p < 0.003 and p < 0.0001, respectively). The incidence of occurrences in the non-head injured population was statistically higher for the warfarin patients (p < 0.001), but showed no difference in the head injured group regardless of warfarin use (p = 0.15). Functional status at discharge demonstrated no clinically significant difference between the warfarin and non-warfarin groups in both head and non-head injured populations. There was no difference in discharge destination in the head injured population; however, in the non-head injured population a greater percentage of non-warfarin patients was discharged to home when compared with the warfarin patients. CONCLUSION Our data suggest that the PIC of anticoagulation with warfarin does not adversely impact mortality or LOS outcomes in both head and non-head injured patients. In non-head injured patients, however, the occurrence rates and discharge destination were different. More research needs to be done to determine whether this is related to anticoagulation or other reasons (i.e., number of PICs). These data should be used when weighing risk/benefit ratios of prescribing chronic anticoagulation.
Guiding the Application of Design Patterns Based on UML Models

Software design patterns are documented best practice solutions that can be applied to recurring problems. Although well documented, there are often opportunities to apply them which are overlooked by software designers. This can be the result of inexperience, the sheer complexity of the system, or the fact that design patterns do not always constitute intuitive designs. In this paper, we present a structured methodology for semi-automating the detection of areas within a UML design of a software system that are good candidates for the use of design patterns. This is achieved by the definition of detection rules formalized using the OCL and using a decision tree model. The approach is illustrated on an example GoF design pattern. A prototype tool was developed to show the feasibility of the approach in practical situations, and is used on a case study, producing encouraging results
VLSI Design of High-Throughput SISO-OFDM and MIMO-OFDM Baseband Transceivers for Wireless LAN Networks

This paper describes a VLSI design of highthroughput OFDM transceivers targeted to future wireless LAN systems. The optimum parameters composing a new packet OFDM frame are discussed by expanding the IEEE802.11a standard. The proposed system provides a maximum transfer rate of 600 Mbps by use of an 80-MHz occupied bandwidth and a MIMO technique. The SISO-OFDM and MIMO-OFDM transceivers have been designed according to the proposed OFDM format. A lowlatency and full-pipelined architecture enables a realtime processing of OFDM modulation/demodulation and MIMO detection. In the MIMO detection, the circuit structures of zero-forcing and MMSEV-BLAST algorithm in a 2 £ 2 MIMO conflguration are presented. The SISO-OFDM and MIMOOFDM transceivers have been implemented to a 90nm CMOS technology. It performed small implementation logic size and low power consumption after a real LSI evaluation. The circuit behavior of the OFDM transceivers has been verifled by using the FPGA prototyping platform that executes both digital and analog OFDM baseband transmissions.
Neural Belief Tracker: Data-Driven Dialogue State Tracking

One of the core components of modern spoken dialogue systems is the belief tracker, which estimates the user’s goal at every step of the dialogue. However, most current approaches have difficulty scaling to larger, more complex dialogue domains. This is due to their dependency on either: a) Spoken Language Understanding models that require large amounts of annotated training data; or b) hand-crafted lexicons for capturing some of the linguistic variation in users’ language. We propose a novel Neural Belief Tracking (NBT) framework which overcomes these problems by building on recent advances in representation learning. NBT models reason over pre-trained word vectors, learning to compose them into distributed representations of user utterances and dialogue context. Our evaluation on two datasets shows that this approach surpasses past limitations, matching the performance of state-of-the-art models which rely on hand-crafted semantic lexicons and outperforming them when such lexicons are not provided.
Emergence of Usutu virus, an African Mosquito-Borne Flavivirus of the Japanese Encephalitis Virus Group, Central Europe

During late summer 2001 in Austria, a series of deaths in several species of birds occurred, similar to the beginning of the West Nile virus (WNV) epidemic in the United States. We necropsied the dead birds and examined them by various methods; pathologic and immunohistologic investigations suggested a WNV infection. Subsequently, the virus was isolated, identified, partially sequenced, and subjected to phylogenetic analysis. The isolates exhibited 97% identity to Usutu virus (USUV), a mosquito-borne Flavivirus of the Japanese encephalitis virus group; USUV has never previously been observed outside Africa nor associated with fatal disease in animals or humans. If established in central Europe, this virus may have considerable effects on avian populations; whether USUV has the potential to cause severe human disease is unknown.