Miracle-dz/UniFAR-FTUs huggingface dataset:
Confidence in the curve: Establishing instantaneous cost mapping techniques using bilateral ankle exoskeletons.

Lower extremity robotic prostheses and exoskeletons can require tuning a large number of control parameters on a subject-specific basis to reduce users' metabolic power during locomotion. We refer to the functional relationship between control parameter configurations and users' metabolic power as the metabolic cost landscape. Standard practice for estimating a metabolic cost landscape, and thus identifying optimal parameter configurations, is to vary control parameters while measuring steady-state metabolic power during walking. This approach is time consuming, tedious, and inefficient. We have developed an instantaneous cost mapping analysis that allows for an estimate of the metabolic cost landscape without the explicit need for steady-state measurements. Here we present novel methods to quantify the confidence in an estimated metabolic cost landscape, allowing for an objective subject-specific comparison of protocols regardless of which metabolic analysis is used. We validated these techniques by estimating metabolic cost landscapes for healthy subjects walking with bilateral robotic ankle exoskeletons using a standard practice protocol and two innovative protocols that use an instantaneous cost mapping analysis. All cost landscapes were a function of the devices' actuation timing. Results showed that for this device a protocol using an instantaneous cost mapping analysis could accurately identify optimal parameter configurations in 20 min, where the standard practice protocol required 42 min. Additionally, using an instantaneous cost mapping analysis with the standard practice's parameter exploration significantly improved fit confidence. These methods could greatly improve real-time optimization of robotic assistive devices or studies focused on biomechanical manipulations of locomotion. NEW & NOTEWORTHY We are presenting novel subject-specific metabolic cost landscape confidence analyses. These confidence analyses can greatly improve experimental design, intersubject analysis, and the comparison of landscape mapping protocols. We validated these methods by mapping subject-specific metabolic cost landscapes using bilateral ankle exoskeletons and are presenting the first full study using instantaneous cost mapping techniques to optimally tune an assistive robotic device.
Exosome cofactor hMTR4 competes with export adaptor ALYREF to ensure balanced nuclear RNA pools for degradation and export

The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome‐mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap‐binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm. Together, our results indicate that the competition between hMTR4 and ALYREF determines exosome recruitment and functions in creating balanced nuclear RNA pools for degradation and export.
Physiology. Opsins: not just for eyes.

PhysiologyWhen researchers got their first glimpse of the sea urchin genome in 2006, they were surprised to find genes for opsins, light-sensitive proteins without which vision as we know it today would be impossible. Further work showed that sea urchin tube feet were loaded with photoreceptor cells that had been missed because they lack pigment typically associated with opsins. That work and other recent studies have driven home the fact that a wide variety of organisms don't need traditional eyes to make use of opsins, and that opsins can likely sense more than light. Last month, at the annual meeting of the Society for Integrative and Comparative Biology in San Francisco, researchers revealed the rich history and unexpectedly broad utility of these proteins.
BipedWalking control using offline and online optimization

The paper is aimed at an energetically efficient control method for biped walking. The walking cycle is composed of successive single-support phases and passive impacts. A parametric trajectory optimization method is implemented that finds symmetric, periodic, low torque walking gaits for a planar 5-link biped robot offline. The robot's configuration is then regulated by RHC (receding horizon control) with the same optimization criterion online. Only the geometric evolution of the robot's configuration is controlled, but not the temporal evolution. The effectiveness of the proposed method is evaluated using simulated walking control. The results show lower torques and more robustness from the proposed controller compared to a hand-tuned PD servo based walking controller.
Programmed necrosis and autophagy in immune function

It has long been known that apoptosis is vital to the generation and maintenance of proper adaptive immune function. An example is the essential requirement for apoptotic signaling during the generation of self‐tolerant lymphocytes: the apoptotic death of B and T cells with overt autoreactivity is essential to central tolerance. More recently, the contributions of additional processes including cellular autophagy and programmed necrosis have been implicated in controlling both innate and adaptive immune functions. Evidence has been provided to demonstrate that the death of cells following ligation of death receptors (DRs), a subfamily of cell surface molecules related to tumor necrosis factor receptor 1, is not exclusively the domain of caspase‐dependent apoptosis. In cells lacking the capacity to activate caspase‐8 following DR ligation, cell death instead occurs via programmed necrosis, or as it has been recently termed, ‘necroptosis’. This death process depends on RIP1 and RIP3, serine/threonine kinases that are recruited by DRs, and likely by other cellular signals including DNA damage and antigen receptor ligation. The generation of RIP1/RIP3 containing ‘necrosomes’ activates downstream necroptotic signaling that ultimately targets cellular energetic metabolism. Also related to cellular metabolic regulation, cellular autophagy has also been found to play unique and important roles in immunity. In this review, we describe the roles of necroptosis and autophagy in innate and adaptive immunity and speculate on the intriguing interplay between these two cellular processes.
The KSI tentacle manipulator

Robotic tentacles provide an interesting alternative to conventional rigid-link robotic arms; in certain situations, they may even be more capable. Kinetic Sciences Inc. has developed a hybrid electric-pneumatic tentacular robot called the KSI tentacle manipulator. It has variable compliance, can bend independently in two or more regions, and can extend to more than five times its contracted length. In total, the Tentacle has six degrees of freedom-or seven with the addition of a distal wrist-rotate joint. The Tentacle's unusual kinematics and inherent compliance demand new approaches to control. Three schemes are considered here: joystick-based teleoperation, inverse kinematics-based tendon length control, and machine vision-based fine position control. Under control, the Tentacle has broad potential in many applications, including teleoperated vacuuming and spray washing (for nuclear hot cell decontamination), general materials handling, agricultural harvesting, robotic refueling, and endoscopy.
Two cases of unilateral blindness following anaesthesia with vascular hypotension.

THE DAY HAS PASSED when the junior member of the hospital staff administered the anaesthetics. Anaesthesia has risen to its proper place as a specialty. With greater complexity of equipment has come the opportunity to help the surgeon more by improving the condition under which he operates. One of these aids is the use of drugs to reduce hkemorrhage. Pioneer work in the field of surgery under reduced blood pressure has been done in Britain. Griffith and Gillies' and others, in Edinburgh used spinal block, and Enderby2 and Shackleton3 and Rolleston4 used methonium compounds. Hexamethonium is the drug usually considered most reliable; the iodide is preferable to the bromide salt. In this technique the systolic blood pressure is reduced to, and maintained as far as possible, between 60 to 70 mm. of mercury. By tilting the patient, the vital circulation is maintained. The surgeon and the patient both benefit, the former by clearer vision and less delay catching bleeding points, and the latter by less shock from blood loss. So marked is the effect that Shackleton3 thus describes a thyroidectomy-"the thyroid resembled a demonstration of an anatomical dissection". One is tempted to wonder if Shylock might not have obtained his pound of flesh had he known about hexamethonium. All the exponents of the technique, in spite of enthusiasm, issue warnings that there are certain possible dangers. Shackleton3 lists these:
Text Processing Chains: Getting Help from Typed Applicative Systems

A processing chain must be the result of a discovery process that requires constant back and forth between theoretical description of the solution, software implementation, testing and refinement of the theoretical description in the light of the results of experimentation. This process is iterative. Some projects based on this philosophy have seen the light in the last years. However, they lack flexibility and formal foundations. The model we propose has strong logical foundations. It allows rapid prototyping and supports a maximal re-use and composition of existing modules
Identification of odorant‐binding proteins of the yellow fever mosquito Aedes aegypti: genome annotation and comparative analyses

The yellow fever mosquito Aedes aegypti is an important human health pest which vectors yellow fever and dengue viruses. Olfaction plays a crucial role in its attraction to hosts and although the molecular basis of this is not well understood it is likely that odorant‐binding proteins (OBPs) are involved in the first step of molecular recognition. Based on the OBPs of Drosophila melanogaster and Anopheles gambiae we have defined sequence motifs based on OBP conserved cysteine and developed an algorithm which has allowed us to identify 66 genes encoding putative OBPs from the genome sequence and expressed sequence tags (ESTs) of Ae. aegypti. We have also identified 11 new OBP genes for An. gambiae. We have examined all of the corresponding peptide sequences for the properties of OBPs. The predicted molecular weights fall within the expected range but the predicted isoeletric points are spread over a wider range than found previously. Comparative analyses of the 66 OBP sequences of Ae. aegypti with other dipteran species reveal some mosquito‐specific genes as well as conserved homologues. The genomic organisation of Ae. aegypti OBPs suggests that a rapid expansion of OBPs has occurred, probably by gene duplication. The analyses of OBP‐containing regions for microsynteny indicate a very high synteny between Ae. aegypti and An. gambiae.
Controlling elements in the mouse. V. Linkage tests with X-linked genes.

Previous studies have shown that the mouse X chromosomal locus, Xce , which causes non-random X chromosome inactivation, is closely linked to the Is( X ; 7)Ct X -autosome translocation. This has placed it either near Ta on one side of the breakpoint or near jp on the other. Linkage tests with Mo vbr and Ta now demonstrate that the locus in fact lies close to Ta . The data also provide genetic evidence which establish that the C3H/HeH X chromosome carries the Xce a allele of this gene and the JU/FaCt and C57BL/GoH X chromosomes carry the Xce b allele, and further suggest that the X -linked modification of the heterozygous phenotypes of X -linked genes observed by various other investigators are all attributable to differences at the Xce locus. Evidence of a maternal influence upon Mo vbr phenotypes is also presented. This appears to operate independently of the X -inactivation process, probably through an effect of differing levels of copper in the milk in early life upon the mutant coat colour in the young.
Regional Hyperthermia in Patients with Recurrent Genitourinary Cancer

During a 6-year period, 53 patients with advanced tumors of the genitourinary tract were treated in Phase I protocols with deep regional hyperthermia in combination with irradiation (83%) or in combination with chemotherapy (11%). Primary tumors included those of bladder in 22 patients (41%), prostate in 20 patients (37%), kidney in 9 patients (17%), and ureter testicle or adrenal in 3 patients (5%). The majority (77%) had prior definitive therapy and had experienced treatment failure, and 11 % had clinically important distant metastases. Treatment consisted of deep regional hyperthermia (mean of 4 sessions). In addition, 44 patients (83%) received irradiation (mean dose 39.2 Gy). The 1− and 3-year actuarial survival was 60% and 56%, respectively. Patients with carcinoma of the prostate had a 1− and 3-year survival of 82%. Complete response was observed in 7 patients (13%), partial response in 8 (15%), and nominal response in 13 (25%). Complete and partial response correlated well with histology of the tumor (adenocarcinoma), radiation dose (>50 Gy), primary site (prostate, kidney), and treatment (hyperthermiaradiotherapy combination), (p = 0.02). There was no such correlation between response and thermal dose (p = 0.13). The treatment tolerance was good in 79% of patients. Treatment toxicity was limited to acute side effects, including pain during hyperthermia (47%), tachycardia > 140/min (7%), and blister formation in the treated area (4%). Phase II studies in previously untreated patients with locally advanced tumors of bladder, prostate, and kidney are needed for evaluation of the role of deep regional hyperthermia in the management of these cancers.
Experimental rubella. Clinical and laboratory findings.

SINCE the initial observations of Gregg, 1 the adverse effects resulting from maternal rubella infection during the early part of pregnancy have been well recognized. Although rubella has been assumed to be of viral etiology, it was not until recently that the isolation of the virus in tissue culture and the detection of neutralizing antibody in patients was described. 2-4 With the availability of these methods, it has become possible to conduct detailed studies correlating the laboratory findings with the clinical course of experimentally produced disease. Studies of this type can provide a better understanding of the disease, and hence a more intelligent approach to the prophylaxis, and perhaps eventually the control of the disease. The present investigation describes the clinical and laboratory findings for young adults following experimental intranasal infection with tissue culture grown rubella virus. Materials and Methods This investigation was undertaken as part of three volunteer studies
Relationship between spatially restricted Krox‐20 gene expression in branchial neural crest and segmentation in the chick embryo hindbrain.

Previous studies have suggested that the rostrocaudal patterning of branchial arches in the vertebrate embryo derives from a coordinate segmental specification of gene expression in rhombomeres (r) and neural crest. However, expression of the Krox‐20 gene is restricted to neural crest cells migrating to the third branchial arch, apparently from r5, whereas this rhombomere contributes cells to both the second and third arches. We examined in the chick embryo how this spatially restricted expression is established. Expression occurs in precursors in both r5 and r6, and we show by cell labelling that both rhombomeres contribute to Krox‐20‐expressing neural crest, emigration occurring first from r6 and later caudally from r5. Krox‐20 transcripts are not detected in some precursors in rostral r5, presaging the lack of expression in cells migrating rostrally from this rhombomere. After transposition of r6 to the position of r4 or r5, many Krox‐20‐expressing cells migrate rostral to the otic vesicle, whereas when r5 is transplanted to the position of r4, only a small number of migrating cells express Krox‐20. These results indicate that, in the chick, Krox‐20 expression in branchial neural crest does not correlate with rhombomeric segmentation, and that there may be intrinsic differences in regulation between the r5 and r6 Krox‐20‐expressing populations.
Novel agents and treatment techniques to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix.

BACKGROUND Survival of patients with locally advanced carcinoma cervix (LACC) using the current standard of concurrent chemo-radiotherapy (CCRT) has reached a plateau over the last two decades. Loco-regional failure in first two years of treatment completion and distant metastasis in the subsequent years has put the survival curves at a halt. Strategies of induction and adjuvant chemotherapy have yielded little as has any advancement in techniques of delivery of radiation therapy. This article aims at discussing the current existing literature as well as promising novel strategies to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix. METHODS The review of English literature included phase I-III trials evaluating either a novel agent, novel application/modifications of an existing treatment regimen or an innovative treatment technique. The studies have been divided in to subsections with summary of most important findings at the end of each section. RESULTS Despite CCRT being the 'gold standard' treatment, several issues like optimum drug combination, schedule of drug delivery, combination with molecular targeted agents etc. remain undefined. Taxane, topoisomerase and gemcitabine based regimen needs to be further explored and compared with cisplatin based CCRT regimen. Several approaches like local delivery of cytotoxic agents, use of nano-medicine with CCRT are appearing on horizon with promises for the future. Therapies need to be designed based on the human papillomavirus titers of the patients and incorporation of radiosensitizers as an effective way of palliation with short course of radiotherapy may further enhance the radiotherapeutic outcomes. CONCLUSIONS The results of the studies with novel agents and treatment techniques appear promising. Further research in this arena including incorporation of cost-effectiveness analysis and quality of life issues in future trial designs are warranted.
Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes

The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d‐boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G1. We studied how d‐boxes determine APC/Cfzy/APC/Cfzr specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/Cfzy and APC/Cfzr; fzy has a KEN box and is degraded by APC/Cfzr only. We characterized the degradation of substrates with swapped d‐boxes. Cyclin B1 with KEN was degraded by APC/Cfzr only. Fzy with RXXL could be degraded by APC/Cfzy and APC/Cfzr. Interestingly, APC/Cfzy‐ but not APC/Cfzr‐specific degradation is highly dependent on the location of RXXL. We studied degradation of tagged substrates in real time and observed that APC/Cfzr is activated in early G1. These observations demonstrate how d‐box specificities of APC/Cfzy and APC/Cfzr, and the successive activation of APC/C by fzy and fzr, establish the temporal degradation pattern. Our observations can explain further why some endogenous RXXL substrates are degraded by APC/Cfzy, while others are restricted to APC/Cfzr.
A Candida albicans regulator of disseminated infection operates primarily as a repressor and governs cell surface remodeling

Virulence traits are often controlled by transcription regulators, i.e. sequence‐specific DNA‐binding proteins. The regulators that sustain microbial proliferation in the host typically work by promoting the expression of the genes that mediate such traits. Here, we report a singular example in the human fungal pathogen Candida albicans in which a transcription regulator functions by repressing the expression of virulence genes, yet its overall role is to promote virulence. We explain this apparent paradox by establishing that a major function of this protein, Zcf21p, is to set a default state of low expression of multiple cell wall components which include virulence determinants. These components comprise GPI‐anchored proteins, adhesins and enzymes that synthesize cell wall sugar decorations. Deletion or overexpression of ZCF21 results in cell wall structure modifications that influence recognition and elimination of the fungus by macrophages. By leveling off the expression of adhesins, ZCF21 also prevents C. albicans self‐aggregation. Balancing the expression of cell wall components – virulence determinants included – is, therefore, critical for C. albicans to assemble a cell surface configuration that is suitable to colonize mammalian tissues and evade immune surveillance.
Exercise aspects of obesity treatment.

The negative effect of obesity is significant in terms of U.S. health care dollars spent, totaling some $100 billion annually, or 5% to 10% of U.S. health care dollars. [1][1] An estimated 55% to 60% of adult Americans are overweight, defined as a body mass index (calculated as weight in kilograms
Toward a New Prevention of Suicide in Schizophrenia

Summary Suicide is the primary cause of death among schizophrenic patients; follow-up studies suggested that 10-13% of schizophrenic patients die by suicide. Preventive measures based on early recognition of risk factors and the establishment of drug treatment protocols are no doubt of great help but have not resulted in a significant reduction of the number of suicides among these patients. Schizophrenia is a chronic disorder affecting all aspects of the individual's life. Prevention should therefore be addressed to various areas. This paper overviews studies dealing with major fields of interest in the prevention of suicide among patients with schizophrenia. The authors focus on the role of pharmacological treatment, psychosocial interventions and psychotherapy, the struggle against stigmatisation and the role of GPs. Prevention of suicide among inpatients with schizophrenia is also analysed. It is concluded that those integrated strategies already in use and the implementation of less known interventions should constitute a more effective prevention of self-inflicted deaths among these patients.