Miracle-dz/UniFAR-FTUs huggingface dataset:
Medulla oblongata damage and cardiac autonomic dysfunction in Parkinson disease

Objective: To characterize medulla oblongata damage using diffusion tensor imaging (DTI) in Parkinson disease (PD) and correlate it with dysfunction of the cardiac sympathetic/vagal balance. Methods: Fifty-two patients with PD and 24 healthy controls were included in the study. All participants underwent clinical examination and 3T MRI using 3D T1-weighted imaging and DTI. DTI metrics were calculated within manually drawn regions of interest. Heart rate variability was evaluated using spectral analysis of the R–R cardiac interval during REM and slow-wave sleep based on continuous overnight electrocardiographic monitoring. Respiratory frequency was measured in 30-second contiguous epochs of REM and slow-wave sleep. The relationships between imaging and cardiac variables were calculated using partial correlations followed by the multiple comparisons permutation approach. Results: The changes in heart rate and respiratory frequency variability from slow-wave sleep to REM sleep in healthy controls were no longer detectable in patients with PD. There were significant increases in the mean (p = 0.006), axial (p = 0.006), and radial diffusivities (p = 0.005) in the medulla oblongata of patients with PD. In PD, diffusion changes were specifically correlated with a lower heart rate and respiratory frequency variability during REM sleep. Conclusions: This study provides evidence that medulla oblongata damage underlies cardiac sympathetic/vagal balance and respiratory dysfunction in patients with PD.
A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5'-monophosphate at 1.38 Å resolution.

Histidine triad nucleotide-binding protein 1 (HINT1) represents the most ancient and widespread branch of the histidine triad protein superfamily. HINT1 plays an important role in various biological processes and has been found in many species. Here, the structure of the human HINT1-adenosine 5'-monophosphate (AMP) complex at 1.38 Å resolution obtained from a new monoclinic crystal form is reported. The final structure has R(cryst) = 0.1207 (R(free) = 0.1615) and the model exhibits good stereochemical quality. Detailed analysis of the high-resolution data allowed the details of the protein structure to be updated in comparison to the previously published data.
Patterns of sexual dimorphism in the hominoid distal humerus.

Basic biomechanical principles predict that body size differences and differences in the positional behavior of primates should impact on the design of the locomotor skeleton. Allometric distortions in joint shape might be expected between sexes if the degree of body size dimorphism is substantial and/or if sex-specific differences exist in behavior. Nevertheless, there are few documented cases of sexual dimorphism in the limb joints of hominoids, despite substantial body size dimorphism and some reports of intersexual differences in positional behavior. This study re-examines sexual dimorphism in the hominoid distal humerus using coordinate data, and distinguishes explicitly between degree of dimorphism (i.e., the magnitude of intersexual differences) and pattern of dimorphism (i.e. , the nature of these differences). Using a variety of multivariate morphometric methods (e.g., canonical variates analysis of Mosimann shape variables; Euclidean Distance Matrix Analysis of both form and pattern difference matrices), we address the following issues: (1) do males and females of different species and subspecies (or ethnic groups for humans) maintain similar joint shapes? (2) are multiple patterns of dimorphism evident in this region of hominoids? (3) are differences and similarities in degree and pattern predicted by phylogenetic propinquity and positional behavior? For the most part, our results support earlier findings that sexual dimorphism in the shape of the anthropoid elbow is slight. Of the eight taxa considered here, only the western lowland gorillas exhibited significant differences in the shape of the distal humerus. Gorilla gorilla gorilla also displays a significantly different pattern of dimorphism from the orang-utan. Pattern differences between Andaman Islanders and both mountain gorillas and the orang-utan also approach statistical significance (P<0.06 and P<0.08, respectively). Overall, and despite marked differences in the degree of dimorphism, the knuckle-walking African apes are more similar in patterns of dimorphism to each other than to other taxa (e.g., gorillas are more similar to orang-utans in degree, but more similar to chimpanzees and bonobos in pattern). We could find no definitive "human pattern" in our results and suspect that this is because human upper limbs face less stringent mechanical constraints since they are relieved of locomotor stresses (but we cannot rule out the possibility of undocumented differences among our human groups in sex-specific, work-related activities). We anticipate finding additional pattern differences among anthropoids in articular dimorphism as we add other taxa to our sample (including fossil hominids), and examine other joint systems.
Performance Analysis and Optimization of Sparse Matrix-Vector Multiplication on Modern Multi- and Many-Core Processors

This paper presents a low-overhead optimizer for the ubiquitous sparse matrix-vector multiplication (SpMV) kernel. Architectural diversity among different processors together with structural diversity among different sparse matrices lead to bottleneck diversity. This justifies an SpMV optimizer that is both matrix- and architecture-adaptive through runtime specialization. To this direction, we present an approach that first identifies the performance bottlenecks of SpMV for a given sparse matrix on the target platform either through profiling or by matrix property inspection, and then selects suitable optimizations to tackle those bottlenecks. Our optimization pool is based on the widely used Compressed Sparse Row (CSR) sparse matrix storage format and has low preprocessing overheads, making our overall approach practical even in cases where fast decision making and optimization setup is required. We evaluate our optimizer on three x86-based computing platforms and demonstrate that it is able to distinguish and appropriately optimize SpMV for the majority of matrices in a representative test suite, leading to significant speedups over the CSR and Inspector-Executor CSR SpMV kernels available in the latest release of the Intel MKL library.
Inflation Forecast Targeting: A Monetary Policy Strategy without Shortcomings?

Abstract This paper provides a critical discussion of the benefits and shortcomings of the concept of inflation forecast targeting (IFT) which is becoming the dominating monetary policy strategy in theory and practice. The paper contains an analysis of the more practical and institutional aspects arising when following an inflation forecast targeting regime as well as a discussion of the theoretical reasoning behind it. The setting of an inflation target itself is a useful instrument to increase accountability. That is because the public can make judgements on how successful monetary policy has been. The concept of IFT also ensures that monetary policy is forward-looking. Nevertheless, this paper will argue that the theoretical reasoning behind IFT has limitations. The assumed monetary transmission process is too one-sided and the role of money is not incorporated adequately. Inflation forecast targeting does not necessarily ease the business of communication by focusing on inflation forecasts as the main communication vehicle. On the contrary, there are substantial difficulties in explaining the implications of conditional or unconditional forecasts. Forecasts as complementing devices are surely useful and important in monetary policy making. The discussion of transparency and credibility within an IFT regime neglects the fact that in the long term credibility relies on the degree of price stability achieved and not the publication of minutes.
Single dose recombinant erythropoietin versus moderate hypothermia for neonatal hypoxic ischemic encephalopathy in low resource settings

Abstract Objective: To determine the safety and efficacy of single dose systemic recombinant human erythropoietin (rEPO) in neonates with perinatal hypoxic Ischemic Encephalopathy (HIE), and its effect on serum brain-derived neurotrophic factor (BDNF) and neuron-specific enolase (NSE). Methods: Forty-five full-term neonates; 30 with perinatal HIE and 15 controls were studied. HIE neonates were randomized into three intervention groups (first 6 h of life): 10 received single subcutaneous 1500 U/kg rEPO at day-1, 10 subjected to hypothermia for 72 h and 10 received supportive care. BDNF and NSE measured during first 6 h and day 5 postnatal. Daily Thompson's score, MRI brain and neuromuscular function scale for survivors at 3 months of age were done. Results: Hypothermia group had best survival especially with stage-II Sarnat scale, followed by rEpo and supportive group. BDNF day-5 was significantly higher in each group compared to controls. MRI score and neuromuscular function score were non-significantly lower in the hypothermia group compared to rEPO. Conclusions: Therapeutic hypothermia was superior to single dose rEpo for neuro-protection in HIE especially in patients with stage-II Sarnat scale. Therapeutic effect of combined rEPO multiple dosing and modest hypothermia therapy should be studied.
Trib3 Is Elevated in Parkinson's Disease and Mediates Death in Parkinson's Disease Models

Parkinson's disease (PD) is characterized by the progressive loss of select neuronal populations, but the prodeath genes mediating the neurodegenerative processes remain to be fully elucidated. Trib3 (tribbles pseudokinase 3) is a stress-induced gene with proapoptotic activity that was previously described as highly activated at the transcriptional level in a 6-hydroxydopamine (6-OHDA) cellular model of PD. Here, we report that Trib3 immunostaining is elevated in dopaminergic neurons of the substantia nigra pars compacta (SNpc) of human PD patients. Trib3 protein is also upregulated in cellular models of PD, including neuronal PC12 cells and rat dopaminergic ventral midbrain neurons treated with 6-OHDA, 1-methyl-4-phenylpyridinium (MPP+), or α-synuclein fibrils (αSYN). In the toxin models, Trib3 induction is substantially mediated by the transcription factors CHOP and ATF4. Trib3 overexpression is sufficient to promote neuronal death; conversely, Trib3 knockdown protects neuronal PC12 cells as well as ventral midbrain dopaminergic neurons from 6-OHDA, MPP+, or αSYN. Mechanism studies revealed that Trib3 physically interacts with Parkin, a prosurvival protein whose loss of function is associated with PD. Elevated Trib3 reduces Parkin expression in cultured cells; and in the SNpc of PD patients, Parkin levels are reduced in a subset of dopaminergic neurons expressing high levels of Trib3. Loss of Parkin at least partially mediates the prodeath actions of Trib3 in that Parkin knockdown in cellular PD models abolishes the protective effect of Trib3 downregulation. Together, these findings identify Trib3 and its regulatory pathways as potential targets to suppress the progression of neuron death and degeneration in PD. SIGNIFICANCE STATEMENT Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Current treatments ameliorate symptoms, but not the underlying neuronal death. Understanding the core neurodegenerative processes in PD is a prerequisite for identifying new therapeutic targets and, ultimately, curing this disease. Here, we describe a novel pathway involving the proapoptotic protein Trib3 in neuronal death associated with PD. These findings are supported by data from multiple cellular models of PD and by immunostaining of postmortem PD brains. Upstream, Trib3 is induced by the transcription factors ATF4 and CHOP; and downstream, Trib3 interferes with the PD-associated prosurvival protein Parkin to mediate death. These findings establish this new pathway as a potential and promising therapeutic target for treatment of PD.
Topical cyclosporine a 0.05% eyedrops in the treatment of vernal keratoconjunctivitis - randomized placebo-controlled trial.

BACKGROUND Vernal keratoconjunctivitis (VKC) is a chronic, bilateral inflammation of the conjunctiva that mostly affects children and young adult males. Management of VKC is primarily aimed at reducing symptoms and preventing serious vision threatening sequelae. OBJECTIVES To assess the efficacy of topical cyclosporine A (CsA) 0.05% on the signs and symtomps in the management of VKC. MATERIAL AND METHODS This is a placebo-controlled, randomized prospective study. Sixty-two patients with VKC were included in this study. Patients were randomly assigned (1 : 1) to treatment with topical 0.05% CsA eyedrops or a placebo (artificial tears) for a period of 4 weeks, 4 times daily. Ocular signs and symptoms were in all patients scored at entry and at the end of 4 weeks. RESULTS When pre-treatment mean signs and symptoms scores were compared in both groups, there was no significant difference (p > 0.05). However, mean post-treatment scores as regards signs and symptoms were found to be lower in cyclosporine group than those in placebo group (p < 0.001). No side effects of the treatment with CsA 0.05% eyedrops were observed. CONCLUSIONS It was found that topical CsA 0.05% eyedrops were safe and effective in the treatment of patients with VKC.
Fusion of a tumour-associated antigen to HIV-1 Tat improves protein-based immunotherapy of cancer.

BACKGROUND The ultimate success of cancer vaccination is primarily dependent upon the generation of tumour-specific CTLs. Protein-based vaccination, while safe, poorly elicits such CTL responses. As fusion of an antigen to the HIV-1 Tat transduction domain was reported to increase MHC class I presentation and CTL responses in vitro, we tested the potency of this approach to augment tumour-directed responses. MATERIALS AND METHODS Human papillomavirus type 16 (HPV16) E7 proteins, fused (E7-Tat) or not (E7) to Tat carboxy-terminal region, were produced and studied in vitro and in vivo. RESULTS E7-Tat, not E7, penetrated the cell membrane and was transcriptionally active. In vitro, E7-Tat induced higher IFN-gamma production from E7-specific T-cells than E7. In C57BL/6 mice, E7-Tat mixed with Quil A generated enhanced prophylactic and therapeutic suppression of HPV16-positive C3 tumour outgrowth. Similar, but greatly enhanced E7-specific effector and helper T-cell responses were elicited following E7-Tat/Quil A rather than E7/Quil A vaccination. CONCLUSION This study offers a new strategy for improving subunit cancer vaccines.
Lateralisation of spatial processing and age

Studies assessing spatial ability suggest right hemisphere specialisation for coordinate spatial processing and left hemisphere specialisation for categorical spatial processing. With regard to healthy ageing, spatial abilities may be affected selectively, with right hemisphere based coordinate processes being more vulnerable to age-related decline, but previous research has been inconsistent. In the present study, age and hemispheric specialisation of categorical and coordinate spatial abilities were explored. Testing 56 right-handed younger and older participants clearly showed a left hemisphere advantage for the categorical task and a right hemisphere advantage for the coordinate spatial task, for both age groups combined. Older adults were slower to process information and make a spatial judgement; nevertheless, the neural specialisation underlying spatial abilities seems to have remained consistent with age.
Modeling dermatome selectivity of single-and multiple-current source spinal cord stimulation systems

A recently published computational modeling study of spinal cord stimulation (SCS) predicted that a multiple current source (MCS) system could generate a greater number of central points of stimulation in the dorsal column (DC) than a single current source (1CS) system. However, the clinical relevance of this finding has not been established. The objective of this work was to compare the dermatomal zone selectivity of MCS and 1CS systems. A finite element method (FEM) model was built with a representation of the spinal cord anatomy and a 2×8 paddle electrode array. Using a contact configuration with two aligned tripoles, the FEM model was used to solve for DC field potentials across incremental changes in current between the two cathodes, modeling the MCS and 1CS systems. The activation regions within the DC were determined by coupling the FEM output to a biophysical nerve fiber model, and coverage was mapped to dermatomal zones. Results showed marginal differences in activated dermatomal zones between 1CS and MCS systems. This indicates that a MCS system may not provide incremental therapeutic benefit as suggested in prior analysis.
A characterization of spectral abscissa and Perron-Frobenius theorem of positive linear functional differential equations

In this paper, we give a characterization of spectral abscissa of positive linear functional differential equations. Then the obtained result is applied to derive necessary and sufficient conditions for the exponential stability of positive linear functional differential equations. Finally, we give an extension of the classical Perron–Frobenius theorem to positive linear functional differential equations.
Reply to the “Letter to the Editor” by Morfeld et al.

Dear Editor, Morfeld et al. stated in the “Letter to the Editor” that the slicing technique (~80 nm) for TEM analysis reduces the size of particle agglomerates located in the treated tissue/compartment. We are aware of the fact that cutting very thin slices out of tissue with particles will lead in a lot of cases to only tangential cuts of the particles. Therefore, the real size of the particles will be bigger than measured. This is especially true the bigger the particles are. Consequently, the determination of agglomerate diameters based on TEM analysis would lead to a bias, resulting in lower average agglomerate diameters than originally existing. However, in our paper (Creutzenberg et al., 2012), TEM analysis was used to follow the temporal alteration of particle agglomerate diameters and to obtain information whether nanoscaled particle agglomerates tend to increase or to disintegrate. This question can be well investigated using TEM analysis. Though mean average diameters of originally existing agglomerates cannot be derived from this, we presented the results as measured under the conditions stated in the material and methods section. This will allow comparing these TEM analysis results to other publications (e.g. Schaudien et al., 2012).
Real-time implementation of stereo vision based on optimised normalised cross-correlation and propagated search range on a GPU

Due to the trade-offs between accuracy and speed, binocular stereo vision is still a challenging task in 3D computer vision research area. In this paper, an efficient stereo matching algorithm is implemented on a state-of-the-art GPU to achieve highly accurate disparity maps in real time for various autonomous vehicle applications. The proposed algorithm is developed from our previous paper, where the search range at row v is propagated from three estimated neighbourhood disparities located at row v + 1. In order to speed up the execution, the prevalent NCC algorithm is optimised by factorising the equation into five independent parts. The computations of hi, Hr, aj and ar are accelerated by using the integral images II, Ir, 12 and Ir2. The values of h and a are stored in static program storage for indexing during the stereo matching, which further reduces expensive calculations to help the system perform in real time. The main purpose of this work is to accelerate the processing speed by highly exploiting the parallel computing architectures (OpenMP and CUDA). The performance of the implementation on an NVIDIA GTX 970M GPU is compared with the performance of the implementations on an Intel Core i7-4720HQ CPU using both single thread and multiple threads. The experimental results illustrate that the GPU implementation yields 37 fps when processing the images (resolution: 1242 × 375) from the KITTI database, which is between two and nine times faster than the implementations on the CPU using a different number of threads.
Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan—a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity—can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors.
Validation of a novel method to determine non-invasively the rate of central aortic pressure changes

Introduction: One of the most sensitive indices of myocardial contractility is represented by the rate of increase of intraventricular pressure during isovolumetric contraction (dP/dt) and (dP/dtejc), which represents the rate of change of pressure during ejection. Today these parameters can be obtained only by invasive catheterization methods. We developed a novel technique that leads to the non-invasive reconstruction of the central aortic pressure. The technique is based on the concept of applying multiple successive occlusive pressures on the brachial artery from peak systole to diastole using an inflatable cuff and plotting the values against time intervals. The hypothesis is that the time intervals required for the aortic pressure wave to overcome a given occlusive brachial pressure applied by a sphyngomanometer on the arm are equal to time needed to reach the same pressure in the central aorta plus the propagation time to the brachial point, which is constant in the same patient throughout the measurements. Methods and results: We tested the hypothesis using an animal experiment. The new non-invasive device was mounted on the left forelimb of the animal. A Millar pressure transducer catheter was inserted to the aorta and the aorta pressure was recorded at time intervals of 1 ms. A second catheter was inserted into the coronary arteries and used to create controlled occlusion of the arteries using a balloon inflated to 10 atm. Measurements were obtained before the intervention was started, and throughout the sequence of repeated occlusions and deflations. At the end of the sequence, IV dobutamine was administered and results were monitored for 10 min while the heart rate and blood pressure were rising. Non-invasive dP/dtejc was reduced typically by 20% in response to balloon inflation. In long occlusion periods, stabilization and sometimes recovery of dP/dtejc is observed. By plotting dP/dtejc measured by the new non-invasive device versus catheter measurements a correlation factor of 0.843 was found. Conclusion: A newly developed method of non-invasive measurement of central dP/dt has been found to correlate to invasive measurements in an animal model.