Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo

Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target protein function(s). This approach has the advantage of being a model for therapeutic targeting. mAbs for use in mouse models can be obtained through immunization of gene-deficient mice with the autologous protein. Such mAbs react with both species-specific epitopes and epitopes conserved between species. mAbs against proteins involved in extracellular proteolysis, including plasminogen activators urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA), their inhibitor PAI-1, the uPA receptor (uPAR), two matrix metalloproteinases (MMP9 and MMP14), as well as the collagen internalization receptor uPARAP, have been developed. The inhibitory mAbs against uPA and uPAR block plasminogen activation and thereby hepatic fibrinolysis in vivo. Wound healing, another plasmin-dependent process, is delayed by an inhibitory mAb against uPA in the adult mouse. Thromboembolism can be inhibited by anti-PAI-1 mAbs in vivo. In conclusion, function-blocking mAbs are well-suited for targeted therapy in mouse models of different diseases, including cancer.
Assessment of Insulin Resistance with the Insulin Suppression Test and the Euglycemic Clamp

Insulin resistance was quantified with two different methods in 30 subjects with varying degrees of glucose tolerance. One method, the insulin suppression test, is performed by continuously infusing epinephrine, propranolol, insulin, and glucose. Epinephrine and propranolol suppress endogenous insulin release, and steady-state plasma levels of exogenous insulin and glucose are reached in all individuals. Because the steady-state insulin level is the same in all subjects, the height of the steady-state plasma glucose level provides a direct estimate of insulin resistance. The other method, the euglycemic clamp technique, produces a steady-state level of exogenous hyperinsulinemia by means of a primed and continuous insulin infusion. Glucose is also infused at a rate sufficient to prevent an insulin-induced fall in glucose concentration, and the amount of glucose required to maintain the basal plasma glucose level provides the estimate of insulin resistance. The results indicated that estimates of insulin resistance generated by the two methods were highly correlated (r = 0.93). Furthermore, both methods of assessing insulin resistance indicated that the greater the degree of glucose intolerance, the more severe the insulin resistance. These results serve to further emphasize the importance of insulin resistance in the pathogenesis of hyperglycemia in type II diabetes.
Epidemiological study of snoring from a random survey of 1075 participants

Snoring is a common complaint, the prevalence of which has been documented to be anything from 24% to 50% of males. Most studies have concentrated on male populations but there is an increasing number of females reporting that they snore. The aim of this study was to ascertain prevalence of snoring among males and females in order to extrapolate global figures for the UK population. From a suburban community 1075 men and women were invited to provide information about their snoring in a ‘snore survey’ questionnaire. From the results it was estimated that 43.75% of the middle aged (30 69 years) UK population snore and 41.5% of the UK adult population snore. The male to female ratio is approximately 2:1, with 29% of males and 12.5% females snoring. An approximate total 14.9 million adults snore with approximately 10.4 million males and 4.5 million females. Correspondence: Marianne J Davey MSc, BSSAA, 52 Albert Road North, Reigate, RH2 9EL UK email: marianne@britishsnoring.co.uk towards middle aged males with limited studies on other population groups. From a literature search of 15 articles, it was found that 58.3% (n=7) of 12 studies were confined to males only, 41.6% (n=5) of the studies being middle aged males, 25% (n=3) both males and females, one of which had an age range of 15 100 years, 8.3% (n=1) females, 8.3% (n=1) Table 2. Relationship between subjective self-reported snoring and the objectively-measured continuous snoring index (Stoohs RA et al 1998). Snoring index measured: 1 = never snore, 2 = rarely snore, 3 = occasionally snore, 4 = often snore, 5 = always snore. p u o r g t c e j b u S d n a x e d n I g n i r o n S d e t r o p e r f l e S g n i r o n s % g n i r o n s s u o u n i t n o C % x e d n i ) e m i t p e e l s l a t o t f o ( s t n e d u t S 5 5 1 = n 7 . 1 5 = 1 9 . 0 2 ± 3 . 0 2 9 . 0 3 = 2 5 . 2 2 ± 9 . 3 2 4 . 1 1 = 3 1 . 8 1 ± 7 . 3 2 4 . 3 = 4 2 . 0 3 ± 2 . 9 3 7 . 2 = 5 3 . 3 3 ± 7 . 5 4
Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.
How Does Information Technology Enable Innovation in Supply Chains?

The paper explores a mechanistic understanding of IT-enabled innovation in a context of supply chain. Based on the innovation dynamics perspective and resource-based view, it links IT resources for supply chain management and IT-enabled innovation via e-business capability with supply chain partners. A conceptual model is formulated to explain how and why IT can enable product and process innovations along the supply chain, and is empirically validated by the data from 676 manufacturing firms in six countries. It was found that IT resources for supply chain management are capable of achieving IT-enabled innovation through both upstream and downstream e-business capability to collaborate with suppliers and customers. The paper contributes to the literature of digitally enabled supply chain management and IT business value. It also allows important managerial implications to firms, especially those in manufacturing sector, about how to chase IT-enabled innovation in supply chains to overcome today’s depression.
Predictive Model of Outcome of Targeted Nodal Assessment in Colorectal Cancer

Background:Improvement in staging accuracy is the principal aim of targeted nodal assessment in colorectal carcinoma. Technical factors independently predictive of false negative (FN) sentinel lymph node (SLN) mapping should be identified to facilitate operative decision making. Purpose:To define independent predictors of FN SLN mapping and to develop a predictive model that could support surgical decisions. Patients and Methods:Data was analyzed from 2 completed prospective clinical trials involving 278 patients with colorectal carcinoma undergoing SLN mapping. Clinical outcome of interest was FN SLN(s), defined as one(s) with no apparent tumor cells in the presence of non-SLN metastases. To assess the independent predictive effect of a covariate for a nominal response (FN SLN), a logistic regression model was constructed and parameters estimated using maximum likelihood. A probabilistic Bayesian model was also trained and cross validated using 10-fold train-and-test sets to predict FN SLN mapping. Area under the curve (AUC) from receiver operating characteristics curves of these predictions was calculated to determine the predictive value of the model. Results:Number of SLNs (<3; P = 0.03) and tumor-replaced nodes (P < 0.01) independently predicted FN SLN. Cross validation of the model created with Bayesian Network Analysis effectively predicted FN SLN (area under the curve = 0.84–0.86). The positive and negative predictive values of the model are 83% and 97%, respectively. Conclusion:This study supports a minimum threshold of 3 nodes for targeted nodal assessment in colorectal cancer, and establishes sufficient basis to conclude that SLN mapping and biopsy cannot be justified in the presence of clinically apparent tumor-replaced nodes.
Primary and Secondary Stability of Implants in Postextraction and Healed Sites: A Randomized Controlled Clinical Trial.

PURPOSE This randomized clinical trial aimed to investigate the relationships between insertion torque, implant stability quotient (ISQ), and crestal bone loss (CBL) of implants placed in fresh or 12-week healed extraction sites. MATERIALS AND METHODS Forty patients were randomly assigned to one of two groups and had one implant placed immediately (test group, n = 20) or 12 weeks after extraction (control group, n = 20) at premolar or molar sites. For all implants, insertion torque and ISQ scores at insertion and loading were recorded. Patients were followed for up to 12 months. RESULTS Implant success was 100% in both groups. No differences were observed concerning both ISQ at insertion and ISQ at loading. A stronger correlation was detected between ISQ at insertion and insertion torque in the postextractive group (R = 0.83), than in the delayed group (R = 0.39), while ISQ at loading and insertion torque showed no correlation. CBL at 12 months was significantly different between test (0.68 ± 0.43 mm) and control (0.40 ± 0.26 mm, P = .02) groups. CONCLUSION Implant placement timing (immediate or delayed) may affect correlation between insertion torque and ISQ at insertion with ISQ at loading. While insertion torque influences ISQ at insertion, it does not affect ISQ at loading because of successful osseointegration. Postextraction and delayed implants seem to have similar ISQ at insertion and at loading, but different CBL after 12 months of follow-up because of postextraction bone remodeling.
Dense monocular reconstruction using surface normals

This paper presents an efficient framework for dense 3D scene reconstruction using input from a moving monocular camera. Visual SLAM (Simultaneous Localisation and Mapping) approaches based solely on geometric methods have proven to be quite capable of accurately tracking the pose of a moving camera and simultaneously building a map of the environment in real-time. However, most of them suffer from the 3D map being too sparse for practical use. The missing points in the generated map correspond mainly to areas lacking texture in the input images, and dense mapping systems often rely on hand-crafted priors like piecewise-planarity or piecewise-smooth depth. These priors do not always provide the required level of scene understanding to accurately fill the map. On the other hand, Convolutional Neural Networks (CNNs) have had great success in extracting high-level information from images and regressing pixel-wise surface normals, semantics, and even depth. In this work we leverage this high-level scene context learned by a deep CNN in the form of a surface normal prior. We show, in particular, that using the surface normal prior leads to better reconstructions than the weaker smoothness prior.
UvA-DARE ( Digital Academic Repository ) Bioenergetics , overcompensation , and the source-sink status of marine reserves

One of the hypothesized functions of marine protected areas (MPAs) is to serve as sources of biomass, with biomass spilling over from the reserve into neighbouring, harvested areas. We argue that the net larval flow (from or to the marine reserve) depends on between-area differences in the population-level biomass production rate, whereas the direction of adult flow depends on differences in the biomass standing stock. Hence, an important question is whether populationlevel biomass production increases (overcompensation) or decreases (undercompensation) with increased per capita mortality. We show that in a consumer–resource context, the source–sink status of an MPA may depend on the details of the individual-level bioenergetics, as well as on the dispersal rates of larvae and adults. We compare two classic bioenergetic models (net-production vs. gross-production allocation). The net-production model predicts that population-level reproduction may increase with mortality (overcompensation), whereas gross-production allocation always results in undercompensation. We show that models often implicitly assume gross-production allocation, thus potentially overestimating the capacity of MPAs to source unprotected areas. We briefly discuss results of two other models (a simplified, logistic model and a size-structured model), suggesting that the relation between overcompensation and the larval sink status of MPAs is
Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image‐guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA‐repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody‐based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. (Hepatology 2014;59:924–934)
The BTB domain of the nuclear matrix protein NRP/B is required for neurite outgrowth

The neuronal nuclear matrix protein, NRP/B, contains a BTB domain and kelch repeats and is expressed in primary neurons but not in primary glial cells. To examine the function of NRP/B in neurons, we analyzed the structure/function of the NRP/B-BTB domain and its role in neurite outgrowth. Based on three-dimensional modeling of NRP/B, we generated an NRP/B-BTB mutant containing three mutations in the conserved amino acids D47A, H60A and R61D that was termed BTB mutant A. BTB mutant A significantly reduced the dimerization of NRP/B compared to wild-type NRP/B. The NRP/B-BTB domain was required for nuclear localization and mediated the association of NRP/B with p110RB through the TR subdomain within the B pocket of p110RB. Overexpression of wild-type NRP/B and NRP/B-BTB domain significantly induced neurite outgrowth in PC12 cells and enhanced the G0-G1 cell population by ∼23% compared to the control cells, whereas NRP/B-BTB mutant A reduced neurite outgrowth by 70-80%, and inhibited NRP/B-p110RB association. Single cell microinjection of NRP/B-specific antibodies also blocked the neurite outgrowth of PC12 cells upon NGF stimulation. Interference of NRP/B expression by small interfering RNA (NRP/B-siRNA) inhibited neurite outgrowth and suppressed the NGF-induced outgrowth of neurites in PC12 cells. Additionally, p110RB phosphorylation at serine residue 795 was significantly reduced in PC12 cells treated with NRP/B siRNA compared to those treated with control GFP-siRNA, indicating that p110RB is a downstream target of NRP/B. Thus, the BTB domain of NRP/B regulates neurite outgrowth through its interaction with the TR subdomain within the B pocket of p110RB, and the conserved amino acids D47A, H60A and R61D within this domain of NRP/B are crucial residues for neurite extension in neuronal cells. These findings support a role for the BTB-domain of NRP/B as an important regulator of neuronal differentiation.
Oculomotor responses during partial and total sleep deprivation.

INTRODUCTION Oculomotor responses related to the pupil light reflex (PLR) and saccadic velocity may be sensitive to the effects of sleepiness and therefore could be used to evaluate an individual's fitness for duty. METHODS There were 12 normal subjects who completed an 8-d study. They were allowed 8 h in bed on the first three nights, 4 h in bed on the fourth night, and then were sleep deprived for the following 64 h. Approximately every 3 h, subjects performed a battery of tests which included a 45-s automated oculomotor test and a 40-min PC-based driving simulator task. Sleepiness was evaluated with a self-assessment instrument. Subjects were allowed 10 h of recovery sleep following sleep deprivation. RESULTS Oculomotor results for nine subjects showed a significant increase in latency to pupil constriction and a significant decrease in saccadic velocity with total, but not partial, sleep deprivation. The most robust changes during sleep deprivation occurred for saccadic velocity. A night of recovery sleep reversed the effects of total sleep deprivation on latency to pupil constriction and saccadic velocity. Subjective sleepiness and off-road accidents were found to significantly increase over the sleep deprivation period. A significant positive correlation between increasing latency to pupil constriction and increasing sleepiness and driving accidents, and a significant negative correlation between decreasing saccadic velocity and increasing sleepiness and driving accidents during sleep deprivation were found. CONCLUSION These findings suggest that oculomotor functions, particularly saccadic velocity, are feasible for assessing neurophysiological changes associated with and predictive of sleep deprivation-induced operational performance degradation.
Combined administration of the GPVI-Fc fusion protein Revacept with low-dose thrombolysis in the treatment of stroke

Background Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) remains the only approved medication for acute ischemic stroke, but incurs significant bleeding risks. Therefore, approaches to combine lower doses of thrombolytic therapy with other effective drugs aim at improving efficacy and reducing bleeding rates. We examined the safety and therapeutic effects of various dosings of rtPA, either alone or combined with glycoprotein VI-Fc fusion protein (GPVI-Fc, Revacept) on experimental stroke in mice. Methods and results The effect of filament-induced intracerebral thrombus formation and embolization was investigated after a one-hour occlusion of the middle cerebral artery. In accordance with previous studies, treatment with 10 mg/kg rtPA significantly improved functional outcome, cerebral infarct size and edema, but also resulted in markedly increased intracranial bleeding volumes. In contrast, low doses of rtPA (0.1 or 0.35 mg/kg body weight) did not change outcome parameters. However, addition of 1 mg/kg Revacept to 0.35 mg/kg rtPA led to improved reperfusion compared to rtPA alone. Moreover, these combined treatments resulted in improved grip strength, compared to the respective dose of rtPA alone. Infarct-surrounding edema improved after combined treatments, but not after respective single rtPA dosings. Intracranial bleeding volumes were below controls after all low-dose rtPA therapies, given either alone or combined with Revacept. Conclusions In contrast to using the equally effective full dose of rtPA, intracranial bleeding was not increased by low-dose rtPA combined with Revacept. Therefore, addition of Revacept to low-dose rtPA does not incur safety risks, but improves efficacy of treatment.
NOVA: QoE-driven optimization of DASH-based video delivery in networks

We consider the problem of optimizing video delivery for a network supporting video clients streaming stored video. Specifically, we consider the joint optimization of network resource allocation and video quality adaptation. Our objective is to fairly maximize video clients' Quality of Experience (QoE) realizing tradeoffs among the mean quality, temporal variability in quality, and fairness, incorporating user preferences on rebuffering and cost of video delivery. We present a simple asymptotically optimal online algorithm, NOVA, to solve the problem. NOVA is asynchronous, and using minimal communication, distributes the tasks of resource allocation to network controller, and quality adaptation to respective video clients. Video quality adaptation in NOVA is also optimal for standalone video clients, and is well suited for use in the DASH framework. Further, NOVA can be extended for use with more general QoE models, networks shared with other traffic loads and networks using fixed/legacy resource allocation.
Preserving quality of service guarantees in spite of flow aggregation

We investigate the preservation of quality of service guarantees to a flow of packets in the presence of flow aggregation. In flow aggregation, multiple flows, known as the constituent flows, are merged together resulting in a single aggregate flow. Packet schedulers located after the network point where the aggregation occurred are aware of the aggregate flow, but are unaware of its constituent flows. In spite of this, we show that quality of service may be guaranteed to the constituent flows provided the aggregation is performed fairly. Furthermore, contrary to intuition, the quality of service guarantees of a flow may be better under flow aggregation than in the case where no aggregation is performed.