A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins.

Proteasome subunit hRpn13 is partially proteolyzed in certain cancer cell types to generate hRpn13Pru by degradation of its UCHL5/Uch37-binding DEUBAD domain and retention of an intact proteasome- and ubiquitin-binding Pru domain. By using structure-guided virtual screening, we identify an hRpn13 binder (XL44) and solve its structure ligated to hRpn13 Pru by integrated X-ray crystallography and NMR to reveal its targeting mechanism. Surprisingly, hRpn13Pru is depleted in myeloma cells following treatment with XL44. TMT-MS experiments reveal a select group of off-targets, including PCNA clamp-associated factor PCLAF and ribonucleoside-diphosphate reductase subunit M2 (RRM2), that are similarly depleted by XL44 treatment. XL44 induces hRpn13-dependent apoptosis and also restricts cell viability by a PCLAF-dependent mechanism. A KEN box, but not ubiquitination, is required for XL44-induced depletion of PCLAF. Here, we show that XL44 induces ubiquitin-dependent loss of hRpn13Pru and ubiquitin-independent loss of select KEN box containing proteins.

Influence of the Type of Soft Segment on the Selected Properties of Polyurethane Materials for Biomedical Applications.

This work presents the synthesis and characterization of new TPUs obtained by melt polyaddition using 1,1'-methanediylbis(4-isocyanatocyclohexane) (HMDI, Desmodur W®), a new unconventional chain extender, i.e., (methanediyldibenze-ne-4,1-diyl)dimethanediol, and five types of soft segments differing in structure and molar masses. The structure of the obtained polymers was determined (by using the Fourier transform infrared spectroscopy and X-ray diffraction methods), and the physicochemical (reduced viscosity, density), optical (UV-VIS), processing (MFR) and thermal (DSC and TGA-FTIR) as well as surface, antibacterial and cytotoxic properties were determined. Based on the results obtained, it can be stated that the type of soft segment used significantly affects the properties of the obtained polymers. The most favorable properties for use in medicine were demonstrated by materials based on a polycarbonate soft segment.

Posturographic Standards for Optimal Control of Human Standing Posture.

Static posturography is a simple non-invasive technique commonly used in contemporary labs and clinics to quantify the central nervous system adaptive mechanisms involved in the control of posture and balance. Its diagnostic value, however, is quite limited due to the lack of posturographic standards for the stable posture. To solve this problem, in this research, we aimed to establish reference values for the stable human posture using our novel parameters of static posturography including the sway anteroposterior directional index (DIAP), the mediolateral directional index (DIML), the stability vector amplitude (SVamp), and the stability vector azimuth (SVaz). Towards this end, in a population of young (mean age 22 yrs), healthy able-bodied volunteers (50 males and 50 females), trajectories of postural sway, based upon the center-of-pressure (COP), were assessed. The experiment consisted of ten 60 s trials that were carried out 5 times while subjects were standing quietly on the force plate with eyes open (EO test) and 5 times with eyes closed (EC test). Results showed that in young healthy subjects, regardless of gender, the basic variables of COP remained at the following levels: SVamp = 9.2 ± 1.6 mm/s, SVaz = 0.9 ± 0.1 rad, and directional indices DIAP = 0.7 ± 0.05, DIML = 0.56 ± 0.06. Some of the measures were sensitive to visual input (EC trials), and showed a weak to moderate correlation with anthropometric features. These measures can be recommended as reference values that characterize the most stable erect posture.

Spinal tumours: recommendations of the Polish Society of Spine Surgery, the Polish Society of Oncology, the Polish Society of Neurosurgeons, the Polish Society of Oncologic Surgery, the Polish Society of Oncologic Radiotherapy, and the Polish Society of Orthopaedics and Traumatology.

PURPOSE: The purpose of these recommendations is to spread the available evidence for evaluating and managing spinal tumours among clinicians who encounter such entities. METHODS: The recommendations were developed by members of the Development Recommendations Group representing seven stakeholder scientific societies and organizations of specialists involved in various forms of care for patients with spinal tumours in Poland. The recommendations are based on data yielded from systematic reviews of the literature identified through electronic database searches. The strength of the recommendations was graded according to the North American Spine Society's grades of recommendation for summaries or reviews of studies. RESULTS: The recommendation group developed 89 level A-C recommendations and a supplementary list of institutions able to manage primary malignant spinal tumours, namely, spinal sarcomas, at the expert level. This list, further called an appendix, helps clinicians who encounter spinal tumours refer patients with suspected spinal sarcoma or chordoma for pathological diagnosis, surgery and radiosurgery. The list constitutes a basis of the network of expertise for the management of primary malignant spinal tumours and should be understood as a communication network of specialists involved in the care of primary spinal malignancies. CONCLUSION: The developed recommendations together with the national network of expertise should optimize the management of patients with spinal tumours, especially rare malignancies, and optimize their referral and allocation within the Polish national health service system.

New Segmented Poly(Thiourethane-Urethane)s Based on Poly(ε-Caprolactone)Diol Soft Segment: Synthesis and Characterization.

New segmented poly(thiourethane-urethane)s (SPTURs) were synthesized by the reaction of 1,1'-methanediylbis (4-isocyanatocyclohexane) (Desmodur W®, HMDI) and poly(ε-caprolactone)diol (PCL) and (methanediyldibenzene-4,1-diyl)dimethanethiol as nonconventional polymer chain extender. FTIR spectroscopy was used for the structural analysis of obtained polymers. The molecular weight distribution was examined by GPC chromatography. Based on the measured contact angles, free surface energy parameters were calculated. Thermal properties of polymers were examined by DSC and TGA, while viscoelastic properties were measured by DMTA. The tensile, adhesive and optical properties were also investigated for the obtained polymers. It was shown that SPTURs were transparent or partially transparent solids with high molar masses up to 84,300 Da. These polymers showed a good resistance to hydrolysis during incubation in Optylite® physiological saline over 8 weeks. Obtained polymers possessed a tensile strength of up to 43.26 MPa, hardness of up to 96.25/59.00 Sh A/D and adhesion to copper of 14.66 MPa. The surface properties of the obtained polymers show that all obtained SPTURs were hydrophilic (CAs for water between 64.07° and 73.12°) with calculated SFE up to 46.69 mN/m.

Synthesis and Characterization of New Polycarbonate-Based Poly(thiourethane-urethane)s.

The new segmented poly(thiourethane-urethane)s (PTURs) based on 1,1'-methanediylbis(4-isocyanatocyclohexane) (HMDI, Desmodur W®), polycarbonate diol (PCD, Desmophen C2200) and (methanediyldibenzene-4,1-diyl)dimethanethiol were synthesized by one-step melt polyaddition method. The obtained PTURs, with a content of 30-60 wt% of the hard segments (HS), were tested in which the influence of changes in the HS content on their properties was determined. The polymers were characterized by Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), thermal analysis (DSC, TGA) and thermomechanical analysis (DMTA). Additionally, tensile strength, optical (refractive index, UV-VIS and color) and surface properties of the obtained polymers (contact angle and surface free energy) and adhesion to copper were examined. FTIR analysis verified the supposed structure of the polymers obtained and showed a complete conversion of the isocyanate groups. TGA analysis confirmed the relatively good thermal stability of the polymers. On the other hand, after performing the DSC analysis, it was possible to state that the obtained materials were partially or completely amorphous, and the microphase separation decreased with increasing HS content in the polymer. Similar observations were made from the DMTA data. In addition, the hardness, tensile strength, modulus of elasticity, storage modulus, adhesion to copper, refractive index and total free surface energy increased with increasing HS content in the polymer.

Special Issue: Processing, Structure, Dynamics and Mechanical Properties of Polymeric Materials.

The current Special Issue entitled "Processing, structure, dynamics and mechanical properties of polymeric materials" brings together scientists working at universities, research institutes, laboratories and various industries to discuss cutting-edge research on processing new polymeric materials using standard and innovative machines and to understand the structure and properties of these materials [...].

Indium(II) Chloride as a Precursor in the Synthesis of Ternary (Ag-In-S) and Quaternary (Ag-In-Zn-S) Nanocrystals.

A new indium precursor, namely, indium(II) chloride, was tested as a precursor in the synthesis of ternary Ag-In-S and quaternary Ag-In-Zn-S nanocrystals. This new precursor, being in fact a dimer of Cl2In-InCl2 chemical structure, is significantly more reactive than InCl3, typically used in the preparation of these types of nanocrystals. This was evidenced by carrying out comparative syntheses under the same reaction conditions using these two indium precursors in combination with the same silver (AgNO3) and zinc (zinc stearate) precursors. In particular, the use of indium(II) chloride in combination with low concentrations of the zinc precursor yielded spherical-shaped (D = 3.7-6.2 nm) Ag-In-Zn-S nanocrystals, whereas for higher concentrations of this precursor, rodlike nanoparticles (L = 9-10 nm) were obtained. In all cases, the resulting nanocrystals were enriched in indium (In/Ag = 1.5-10.3). Enhanced indium precursor conversion and formation of anisotropic, longitudinal nanoparticles were closely related to the presence of thiocarboxylic acid type of ligands in the reaction mixture. These ligands were generated in situ and subsequently bound to surfacial In(III) cations in the growing nanocrystals. The use of the new precursor of enhanced reactivity facilitated precise tuning of the photoluminescence color of the resulting nanocrystals in the spectral range from ca. 730 to 530 nm with photoluminescence quantum yield (PLQY) varying from 20 to 40%. The fabricated Ag-In-S and Ag-In-Zn-S nanocrystals exhibited the longest, reported to date, photoluminescence lifetimes of ∼9.4 and ∼1.4 µs, respectively. It was also demonstrated for the first time that ternary (Ag-In-S) and quaternary (Ag-In-Zn-S) nanocrystals could be applied as efficient photocatalysts, active under visible light (green) illumination, in the reaction of aldehydes reduction to alcohols.

Modern Biodegradable Plastics-Processing and Properties Part II.

Four different plastics were tested: potato starch based plastic (TPS-P)-BIOPLAST GF 106/02; corn starch based plastic (TPS-C)-BioComp BF 01HP; polylactic acid (polylactide) plastic (PLA)-BioComp BF 7210 and low density polyethylene, trade name Malen E FABS 23-D022; as a petrochemical reference sample. Using the blown film extrusion method and various screw rotational speeds, films were obtained and tested, as a result of which the following were determined: breaking stress, strain at break, static and dynamic friction coefficient of film in longitudinal and transverse direction, puncture resistance and strain at break, color, brightness and gloss of film, surface roughness, barrier properties and microstructure. The biodegradable plastics tested are characterized by comparable or even better mechanical strength than petrochemical polyethylene for the range of film blowing processing parameters used here. The effect of the screw rotational speed on the mechanical characteristics of the films obtained was also demonstrated. With the increase in the screw rotational speed, the decrease of barrier properties was also observed. No correlation between roughness and permeability of gases and water vapor was shown. It was indicated that biodegradable plastics might be competitive for conventional petrochemical materials used in film blowing niche applications where cost, recyclability, optical and water vapor barrier properties are not critical.

New methods of posturographic data analysis may improve the diagnostic value of static posturography in multiple sclerosis.

BACKGROUND: Early and accurate diagnosis of multiple sclerosis (MS) is crucial for its effective treatment. In MS diagnostic, neuronal networks that control posture and movement are of particular importance, which performance can be assessed using static posturography. Unfortunately, most of the commercially available posturographic platforms are not equipped with the appropriate procedures. METHODS: To solve this problem, the postural sway trajectories have been recorded in 55 MS patients while standing quiet with eyes open (EO), and then with eyes closed (EC). The trajectories were analyzed using our novel methods of postural sway parametrization, including sway stability vector (SV), anteroposterior and mediolateral sway indices (DIAP and DIML). RESULTS: The results exhibited unique postural sway patterns that may be attributed to MS. Our novel parametrization methods of postural sway showed pathology specific increase of the postural sway velocity in EC tests. Additionally, we documented the abnormal alterations of the anteroposterior (AP) and the mediolateral (ML) sway indices that were also uniquely dependent on visual input. In EC tests, patients exhibited a characteristic pattern of sway increase in both AP and ML directions that correlated with the advance of the disease as measured by the EDSS Kurtzke scale and Functional System Scores. CONCLUSIONS: The applied in the present study our novel posturographic metrics give the assessment a diagnostic value. It allows us to recommend the static posturography test as a simple and safe supplementary clinical tool in the diagnosis of MS. In the assessment of MS pathology or the effects of its treatment, the impact of vision on the sway stability vector seems the most important factor.

Maturation of the postural control in adolescent girls: A 3-year follow-up study.

BACKGROUND: Stable posture is a manifestation of the appropriate functioning of the neuromuscular system that is essential for proper motor development and control. Balance and stability of the erect posture are shaped during the entire childhood to culminate in its full efficiency in adolescent subjects. METHODS: In this 3-year follow-up study, the process of the postural control maturation has been assessed in a group of 18 girls at the transition period between childhood to adolescence. Their balance and postural stability control were assessed using standard static posturography supplemented by two postural stability tests: the rising-on-toes (ROT), and the maximum forward lean (MFL), all performed with (EO) and without vision (EC). Balance control was analyzed with the sway vector (SV) and sway directional indices, whereas the anteroposterior trajectories of the center-of- pressure (COP) during forward-leaning and the raise-on-toes tests were used to determine changes in postural stability control. RESULTS: The study documented that stability control in girls aged 11-13 is shaped according to their own pace of development. Their postural sway was characterized by the lower COP velocity but very sensitive to visual input. The directional sway measures remained at the same level for the entire period of observation. MFL and ROT tests provided similar information on postural stability and its dependence on visual input. These tests allow for more thorough assessment of postural stability to compare with quiet stance testing. SIGNIFICANCE: Subtle changes in postural control in adolescents could be assessed based on the results of combined static and dynamic tests. In particular, the ROT test can be recommended for the assessment of postural stability.

Methods of investigation transformation kinetics of yttrium carbonate hydroxide in citric acid solution into yttrium citrate dihydrate.

A method of synthesis crystalline yttrium citrate dihydrate was proposed as a result of the transformation of the freshly precipitated basic yttrium carbonate phase in a citric acid solution. The synthesis time was determined on the basis of composition analysis, structure and thermogravimetric studies of samples taken during the synthesis. The research methods used have shown that in the initial stage of the synthesis, the processes of citric acid sorption on basic yttrium carbonate and transformation of amorphous yttrium carbonate hydroxide into crystalline yttrium hydroxide occurs. It is only after 72 h of synthesis that the crystalline yttrium citrate dihydrate is formed.•Synthesis crystalline yttrium citrate dehydrate.•The synthesis time 72 h.•Synthesis components: the freshly precipitated basic yttrium carbonate phase in a citric acid solution.

Modification of multiwalled carbon nanotubes with a ruthenium drug candidate-indazolium[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 ).

Functionalized carbon nanotubes are interesting, promising and unique delivery systems for anticancer drugs, which are now in the spotlight of nanomedicine. Connecting nanotubes with anticancer drugs or new compounds with anticancer properties aims at improving their stability, efficiency and reduces the toxic side effects of cancer treatment. In our research, we are interested in connecting functionalized MWCNTs-NH2 with [InH][trans-RuCl4(In)2], (KP1019) which is one of the most promising anticancer ruthenium(iii) drug candidates, known mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers. As a result of the amidation of MWCNTs (1), MWCNTs-NH2 (2) were obtained. Then, they were modified with [InH][RuCl4(In)2] (4) and the nanosystem [MWCNT-NH3+][RuCl4(In)2-] (3) was obtained. The characterization of the resulting products was performed using IR, Raman spectroscopy, thermal gravimetric, XRD, STEM-EDX, ESI-MS, ICP-MS, and XPS analyses. The cytotoxic activity has been tested on human lung carcinoma (A549), chronic myelogenous leukemia (K562) and human cervix carcinoma (HeLa) cells which showed the higher toxicity of the nanosystem than the ruthenium complex.

Step Response of Human Motor System as a Measure of Postural Stability in Children.

Postural sway is a product of the neuromuscular system that is commonly used in contemporary labs and clinics for the assessment of postural stability. In this study, we analyzed the transient responses of the neuromuscular system during the rise-on-toes (ROT) movement in eighteen 11 yrs old girls. Their center of pressure (COP) trajectories were recorded with standard force-platform during the transition from quiet stance to standing on toes. To assess the robustness of children's postural stability, we compared the ROT trajectories while the movement was performed with and without vision. Our results confirmed that the dynamic characteristics of the COP step response were significantly modified by visual feedback. In particular, the ROT test performed with eyes closed (EC) was characterized by a four-fold increase of COP chaotic oscillations at the target (tiptoe) position. This resulted in a substantial increase in the movement's index of difficulty (ID) thus to achieve adequate accuracy of the target-oriented movement the COP velocity was decreased accordingly. This inherent strategy of the brain controller allowed for precise positioning of the COP within the reduced size of the target. In conclusion, the dynamics of the ROT movement is always precisely adjusted to the stability of the upright posture, and thus, the dynamic characteristics of the COP step response are also sensitive measures of postural stability and the ROT can be recommended as a useful test for this assessment in the general population.

Polyethylene-Matrix Composites with Halloysite Nanotubes with Enhanced Physical/Thermal Properties.

The aim of the present work is to investigate the effect of halloysite nanotubes (HNT) on the mechanical properties of low-density polyethylene composites modified by maleic anhydride-grafted PE (PE-graft-MA). Polyethylene nanocomposites were prepared using an injection molding machine, Arburg Allrounder 320 C 500-170; the HNT content was varied at 0 wt %, 2 wt %, 4 wt % and 6 wt %, and the PE-graft-MA content was varied at 5 wt %. The composites were examined for their ultimate tensile stress, strain at ultimate stress, hardness, impact strength, melt flow rate, heat deflection temperature, Vicat softening temperature, crystallinity degree and phase transition temperature. It was found that the addition of halloysite nanotubes to low-density polyethylene (LDPE) led to an increased heat deflection temperature (HDT, up to 47 °C) and ultimate tensile strength (up to 16.00 MPa) while the Vicat softening temperature, strain at ultimate stress, impact strength and hardness of examined specimens slightly decreased. Processing properties of the materials specified by the melt flow rate (MFR) deteriorated almost twice. The results have demonstrated that the nanoparticles can reinforce enhance LDPE at low filler content without any considerable loss of its ductility, but only when halloysite nanotubes are superbly distributed in the polyethylene matrix.

Perspectives of UV nowcasting to monitor personal pro-health outdoor activities.

Nowcasting model for online monitoring of personal outdoor behaviour is proposed. It is envisaged that it will provide an effective e-tool used by smartphone users. The model could estimate maximum duration of safe (without erythema risk) outdoor activity. Moreover, there are options to estimate duration of sunbathing to get adequate amount of vitamin D3 and doses necessary for the antipsoriatic heliotherapy. The application requires information of starting time of sunbathing and the user's phototype. At the beginning the user will be informed of the approximate duration of sunbathing required to get the minimum erythemal dose, adequate amount of vitamin D3, and the dose necessary for the antipsoriatic heliotherapy. After every 20-min the application will recalculate the remaining duration of sunbathing based on the UVI measured in the preceding 20 min. If the estimate of remaining duration is <20 min the user will be informed that the deadline of sunbathing is approaching. Finally, a warning signal will be sent to stop sunbathing if the measured dose reaches the required dose. The proposed model is verified using the data collected at two measuring sites for the warm period of 2017 (1st April-30th September) in large Polish cities (Warsaw and Lodz). First instrument represents the UVI monitoring station. The information concerning sunbathing duration, which is sent to a remote user, is evaluated on the basis of the UVI measurements collected by the second measuring unit in a distance of ~7 km and 10 km for Warsaw and Lodz, respectively. The statistical analysis of the differences between sunbathing duration by nowcasting model and observation shows that the model provides reliable doses received by the users during outdoor activities in proximity (~10 km) to the UVI source site. Standard 24 h UVI forecast based on prognostic values of total ozone and cloudiness appears to only be valid for sunny days.

Trunk forward flexion mobility in reference to postural sway in women after delivery: A prospective longitudinal comparison between early pregnancy and 2- and 6-month postpartum follow-ups.

BACKGROUND: It has been documented that pregnancy-related increased connective tissue laxity may persist postpartum; however, it is still unclear for how long. This longitudinal study aimed to compare total trunk forward flexion mobility in women between their first trimester of pregnancy and at 2- and 6-month postpartum follow-ups. We also searched for a correlation between women's trunk flexibility and their postural stability in the sagittal plane. METHODS: Seventeen healthy women participated in the study. Data were collected at their 7-12 weeks gestation appointments and at 6-10 and 25-28 weeks postpartum. At each session, the women performed a finger floor distance test, and data were collected on their waist circumference and BMI. The women's center of foot pressure mean velocity in the anterior-posterior direction was computed from 30-s long quiet-standing trials on a stationary force plate. FINDINGS: Total trunk forward flexion mobility was significantly higher at 2 and 6 months postpartum compared to that in early pregnancy (P < 0.05). At 6 months postpartum, a moderate negative correlation between finger floor distance test values and their anterior-posterior center of foot pressure mean velocity was observed (r = -0.6, P < 0.05). INTERPRETATION: Increased total trunk flexibility may be present in women 6 months postpartum. During that period, women with higher trunk flexibility may be more likely to present higher anterior-posterior postural sway velocity in quiet standing.

Controlling sunbathing safety during the summer holidays - The solar UV campaign at Baltic Sea coast in 2015.

Information regarding the intensity of surface UV radiation, provided for the public, is frequently given in terms of a daily maximum UV Index (UVI), based on a prognostic model. The quality of the UV forecast depends on the accuracy of column amount of ozone and cloudiness prediction. Daily variability of UVI is needed to determine the risk of the UV overexposure during outdoor activities. Various methods of estimating the temporary UVI and the maximum duration of UV exposures (received a dose equal to minimal erythemal dose - MED), at the site of sunbathing, were compared. The UV indices were obtained during a field experiment at the Baltic Sea coast in the period from 13th to 24th July 2015. The following UVI calculation models were considered: UVI measurements by simple hand-held biometers (Silver Crest, Oregon Scientific, or more advanced Solarmeter 6.5), our smartphone models based on cloud cover observations at the site and the cloudless-sky UVI forecast (available for any site for all smartphone users) or measured UVI, and the 24h weather predictions by the ensemble set of 10 models (with various cloud parameterizations). The direct UV measurements, even by a simple biometer, provided useful UVI estimates. The smartphone applications yielded a good agreement with the UV measurements. The weather prediction models for cloudless-sky conditions could provide valuable information if almost cloudless-sky conditions (cloudless-sky or slightly scattered clouds) were observed at the sunbathing site.

Nigrostriatal interaction in the aging brain: new therapeutic target for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder of unclear etiology and pathogenesis. Research results gathered to date support the hypothesis that the motor symptoms of the disease result from the gradual loss of midbrain dopamine neurons residing in the substantia nigra pars compacta (SNpc). Recent discoveries, however, significantly expand this knowledge indicating that the primary source of the PD pathogenesis may be located both in the SNpc as well as in the GABAergic striatum. Newly discovered striatal neurogenesis - normally a lifelong process - determines the efficiency of nigrostriatal interaction. Deficient neurogenesis within the striatum followed by a decline in the GABAergic/dopaminergic interaction results in progressive disconnection of the dopaminergic input, which initiates a 'vicious circle' cascade of neuronal damage. Effects of both deficient striatal neurogenesis and age-related neurodegeneration within the striatum accumulate, resulting in a progressive decline in the control functions of the basal ganglia, loss of dopaminergic neurons, and occurrence of PD clinical symptoms. Functional and pharmacological control of these dynamic relationships may result in treatments that are more effective with fewer side-effects.