On the rapid in situ oxidation of two-dimensional V2CTz MXene in culture cell media and their cytotoxicity.

The plethora of emerging two-dimensional (2D) materials exhibit wide potential application in novel technologies and advanced devices. However, their stability in environmental conditions could be an issue, affecting their application possibilities and posing health risks. Moreover, their decomposed leftovers can also induce a negative influence on human health. In particular, transition metal carbides commonly referred to as MXenes are susceptible to environmental oxidation being decomposed toward transition metal oxides and carbide-derived carbon. In this study we focused on the oxidation-state-related in vitro cytotoxicity of delaminated V2CTz onto immortalized keratinocytes (HaCaT) and malignant melanoma (A375) human cell lines. Due to the fact, that the V2CTx MXenes are least stable from all known obtained MXenes up to date, the vanadium ones were a practical choice to visualize the oxidation-cytotoxic correlation keeping the standards of 24-48 h of cell culturing. We found that the oxidation of V2CTz highly increases their cytotoxicity toward human cells, which is also time and dose dependent. The identified mode of action relates to the cell cycle as well as cellular membrane disintegration through direct physicochemical interactions.

Magnetic properties of (Fe1-xMnx)2AlB2 and the impact of substitution on the magnetocaloric effect.

In this work, we investigate the magnetic structures of (Fe1-xMnx)2AlB2 solid-solution quaternaries in the x=0 to 1 range using x-ray and neutron diffraction, magnetization measurements, and mean-field theory calculations. While Fe2AlB2 and Mn2AlB2 are known to be ferromagnetic (FM) and antiferromagnetic (AFM), respectively, herein we focused on the magnetic structure of their solid solutions, which is not well understood. The FM ground state of Fe2AlB2 becomes a canted AFM at x≈0.2, with a monotonically diminishing FM component until x≈0.5. The FM transition temperature (TC) decreases linearly with increasing x. These changes in magnetic moments and structures are reflected in anomalous expansions of the lattice parameters, indicating a magnetoelastic coupling. Lastly, the magnetocaloric properties of the solid solutions were explored. For x=0.2 the isothermal entropy change is smaller by 30% than it is for Fe2AlB2, while the relative cooling power is larger by 6%, due to broadening of the temperature range of the transition.

The effect of hydrazine intercalation on the structure and capacitance of 2D titanium carbide (MXene).

Herein we show that hydrazine intercalation into 2D titanium carbide (Ti3C2-based MXene) results in changes in its surface chemistry by decreasing the amounts of fluorine, OH surface groups and intercalated water. It also creates a pillaring effect between Ti3C2Tx layers pre-opening the structure and improving the accessability to active sites. The hydrazine treated material has demonstrated a greatly improved capacitance of 250 F g(-1) in acidic electrolytes with an excellent cycling ability for electrodes as thick as 75 µm.

Mo2Ga2C: a new ternary nanolaminated carbide.

We report the discovery of a new hexagonal Mo2Ga2C phase, wherein two Ga layers ­ instead of one ­ are stacked in a simple hexagonal arrangement in between Mo2C layers. It is reasonable to assume this compound is the first of a larger family.

Synthesis and characterization of two-dimensional Nb4C3 (MXene).

We report on the synthesis of a phase-pure, 2-dimensional transition metal carbide Nb4C3, produced by immersing Nb4AlC3 powders in hydrofluoric acid. The structure of this, only second MXene with formula M4X3, was investigated with pair distribution function analysis. The resistivity of a cold-pressed disc was 0.0046 Ω m, rendering this MXene one of the most conductive to date.

Perturbed angular correlation studies of uniaxial compressive stressed zinc, titanium, rutile, Ti2AlN, and Nb2AlC.

We use the perturbed angular correlation method with (111)In-(111)Cd probe atoms to in situ study the changes in the electric field gradient at room temperature of polycrystalline Ti(2)AlN and Nb(2)AlC, titanium and zinc, and rutile samples, as a function of cyclic uniaxial compressive loads. The load dependence of the quadrupole coupling constant νQ was found to be large in titanium and zinc but small in Ti(2)AlN, Nb(2)AlC and rutile. Reversible and irreversible increases in the electric field gradient distribution widths were found under load and after releasing the load, respectively. Annihilation of dislocations, as well as elastic deformation, are considered to contribute to the reversible behavior. The irreversible response must be caused by a permanent increase in dislocation and point defect densities. The deformation induced broadening of the electric field gradient can be recovered by post-annealing of the deformed sample.

A phase 2 study of the combination of gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines with/without taxanes.

BACKGROUND AND OBJECTIVES: Many patients with relapsed metastatic breast cancer are pre-treated with taxanes and anthracyclines, which are usually given in the neoadjuvant/adjuvant setting or as first-line treatment for metastatic disease. The primary objective of this study was to determine the overall response rate for combination treatment with gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer who had relapsed after receiving one adjuvant/neoadjuvant or first-line metastatic chemotherapy regimen containing an anthracycline with/without a taxane. Secondary endpoints included duration of response, time to progression, one-year survival probability, and toxicity. DESIGN AND SETTING: A single-arm, open-label, phase 2 study conducted at 17 investigative sites in Egypt. PATIENTS AND METHODS: treatment consisted of gemcitabine (1250 mg/m2) on Days 1 and 8 and cisplatin (70 mg/m2) on Day 1 of each 21-day cycle. Treatment continued until disease progression or a maximum of 6 cycles. RESULTS: Of 144 patients all were evaluable for safety and 132 patients were evaluable for efficacy. The overall response rate was 33.3% and 45.5% of the patients with stable disease as their best response. The median time-to-progression was 5.1 months and the one-year survival probability was 73%. The most common grade 3/4 adverse events were nausea/vomiting (20.1%), neutropenia (19.4%), anemia (13.9%), asthenia (11.1%), diarrhea (9.7%), stomatitis (7.6%), leucopenia (7.6%), and thrombocytopenia (6.2%). twelve (8.3%) patients had serious adverse events. CONCLUSIONS: The results of this study indicate that gemcitabine and cisplatin were active and generally well tolerated in pretreated patients with locally advanced or metastatic breast cancer.

Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial.

The eLEcTRA trial compared efficacy and safety of letrozole combined with trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR) positive metastatic breast cancer (MBC). Patients were randomized to either letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as first-line treatment. Additional 35 patients with HER2 negative and HR positive tumors received letrozole alone (arm C). Median time to progression in arm A was 3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39% for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01-8.84) and 77% in arm C (odds ratio 5.34, 95% CI 1.83-15.58). The eLEcTRA trial showed that the combination of letrozole and trastuzumab is a safe and effective treatment option for patients with HER2 positive and HR positive MBC.

Electric field gradients at (111)In/(111)Cd probe atoms on A-sites in 211-MAX phases.

The method of perturbed angular correlation (PAC) was applied to selected MAX phases with 211 stoichiometry. Radioactive (111)In ions were implanted in order to measure the electric field gradients (EFG) in the key compounds Ti(2)InC and Zr(2)InC to determine the strength and symmetry of the EFG at the In-site. Further PAC studies in the In-free MAX phases Ti(2)AlN, Nb(2)AlC, Nb(2)AsC and Cr(2)GeC were performed to confirm that the In probes occupy the A-site as well. The strength of the EFG, with a quadrupole coupling constant ν(Q) between 250 and 300 MHz in these phases, is quite similar to the ones found in Ti(2)InC with ν(Q) = 292(1) MHz and in Zr(2)InC with ν(Q) = 344(1) MHz, respectively. Different annealing behavior was observed whereas in all cases a linear decrease of ν(Q) with increasing measuring temperatures was found. The experimental results are also in excellent agreement with those predicted by ab initio calculations using the APW+lo method implemented in the WIEN2k code. This study shows in an exceptional manner that (111)In → (111)Cd atoms are suitable probes to investigate the local surrounding at the A-site in 211-MAX phases.

Dynamic elastic hysteretic solids and dislocations.

Recently we showed that the quasistatic response of nonlinear mesoscopic elastic solids to stress can be explained by invoking the formation of dislocation-based incipient kink bands. In this Letter, using resonant ultrasound spectroscopy, we confirm that the dynamical behavior of these nonlinear elastic systems is due to the interaction of dislocations with the ultrasound waves, thus resolving a long-standing mystery.

Planning of the internal mammary field based on lymphoscintigraphy localization before postoperative radiotherapy of breast cancer.

BACKGROUND: Internal mammary irradiation is still an issue of great debate. Although treatment of internal mammary lymph nodes was routinely given in the majority of randomized trials, data in its value are still limited. The aim of this study is to determine the variability of position of the internal mammary lymph nodes using lymphoscintigraphy and to compare the dose of radiation that reaches these lymph nodes, the heart and lungs if only tangential fields are used. MATERIAL AND METHODS: This is a prospective study that included 30 breast cancer patients treated in the department of radiation oncology of the Egyptian National Cancer Institute, Cairo University, planned for postoperative radiotherapy. Lymphoscintigraphy was done for all patients for detection of the exact site of the internal mammary lymph nodes. Dose volume histogram (DVH) was done to measure the dose to the heart using CT planning. Two plans were done for each patient, the first with internal mammary field (plan I), and the second without but with contralateral crossing of the midline by 1cm (plan II). RESULTS: The mean percentage of the internal mammary lymph nodes included in the internal mammary field (plan I) was 70.03% while in plan II it was 3.05%. The mean dose percentage reaching the heart in plan I was 54.5% of total dose, while in plan II it was 9.16% of total dose with significant p value<0.001. The mean dose to the heart decreased as the heart volume increased, this significant difference between the 2 plans was maintained for the different heart volumes. Also, the radiation dose to the heart in plan I varied significantly (p: 0.001) between the right side vs the left side with a mean dose of 48.02% and 63.5%, respectively. The mean dose percentage reaching the lungs in plan I and plan II was 46.53% and 24.5% respectively, with significant p value<0.001. CONCLUSION: If irradiation of internal mammary chain is intended, then a direct internal mammary field should be used. The planning of internal mammary field should be adjusted according to lymphoscintigraphy so as to include most of the draining internal mammary lymph nodes. The risk of late cardiac and pulmonary complications will increase when using direct internal mammary field, but the risk of cardiac complications will be less in irradiation of right side internal mammary lymph nodes compared to that of irradiation of the left side.

Driving force and mechanism for spontaneous metal whisker formation.

The room temperature spontaneous growth of low melting point metal whiskers, such as Sn, poses a serious reliability problem in the semiconducting industry; a problem that has become acute with the introduction of Pb-free technology. To date, this 50+ year old problem has resisted interpretation. Herein we show that the driving force is essentially a reaction between oxygen and the sprouting metal. The resulting volume expansion creates a compressive stress that pushes the whiskers up. The model proposed explains our observations on In and Sn whiskers and many past observations. The solution is in principle simple: diffusion of oxygen into the metal must be prevented or slowed down. This was demonstrated by coating the active surfaces with a polymer coating.

Kinking nonlinear elastic solids, nanoindentations, and geology.

The physical mechanism responsible for nonlinear elastic, hysteretic, and discrete memory response of nonlinear mesoscopic elastic solids has to date not been identified. We show, by nanoindenting mica single crystals, that this response is most likely due to the formation of dissipative and fully reversible, dislocation-based kink bands. We further claim that solids with high c/a ratios, which per force are plastically anisotropic, should deform by kinking, provided they do not twin. These kinking nonlinear elastic solids include layered ternary carbides, nitrides, oxides, and semiconductors, graphite, and the layered phases, such as mica, present in nonlinear mesoscopic elastic solids.

Fully reversible, dislocation-based compressive deformation of Ti3SiC2 to 1 GPa.

Dislocation-based deformation in crystalline solids is almost always plastic. Here we show that polycrystalline samples of Ti3SiC2 loaded cyclically at room temperature, in compression, to stresses up to 1 GPa, fully recover on the removal of the load, while dissipating about 25% (0.7 MJ x m(-3)) of the mechanical energy. The stress-strain curves outline fully reversible, rate-independent, closed hysteresis loops that are strongly influenced by grain size, with the energy dissipated being significantly larger in the coarse-grained material. At temperatures greater than 1,000 degrees C, the loops are open, the response is strain-rate dependent, and cyclic hardening is observed. This hitherto unreported phenomenon is attributed to the reversible formation and annihilation of incipient kink bands at room-temperature deformation. At higher temperatures, the incipient kink bands dissociate and coalesce to form regular irreversible kink bands. The loss factor for Ti3SiC2 is higher than most woods, and comparable to polypropylene and nylon. The technological implications of having a stiff, lightweight machinable ceramic that can dissipate up to 25% of the mechanical energy per cycle are discussed.

Purine nucleotides modulate proliferation of brown fat preadipocytes.

The hypothesis that purine nucleotides and nucleosides affect brown fat preadipocyte proliferation was tested using isolated rat interscapular brown fat preadipocytes in culture. Daily addition of 100 microM adenosine triphosphate (ATP) (n = 4) to cultures enhanced the relative DNA content by 1.5-fold compared to control cultures (P < 0.05) measured using CyQUANT-GR fluorescence. Higher concentrations of ATP inhibited growth and 500 (n = 2) or 1000 microM ATP (n = 3) almost completely inhibited growth. ATP (100 microM) did not affect while 250-1000 microM ATP decreased protein content relative to control cultures. Adenosine (100 microM; n = 3) did not affect DNA or protein content, but 500 microM and 1000 microM adenosine suppressed brown adipocyte proliferation and inhibited protein synthesis. Cultured brown adipocytes quickly removed or degraded ATP in the culture media as determined by luciferin-luciferase bioluminescence, suggesting that the inhibitory effects of high ATP concentrations may result from its breakdown to adenosine. The results support the conclusion that ATP promotes and adenosine inhibits brown adipocyte proliferation.

Acute variceal hemorrhage: the persistent bleeder. A plea for management.

A group of 1910 patients with acutely bleeding esophagogastric varices were managed in the Kasr El Aini sclerotherapy project; 458 of the patients (24%) were lost to follow-up. The remaining patients were studied in five groups: group I (294/401 patients), rigid versus flexible sclerotherapy; group II (254/336 patients), intravariceal versus paravariceal sclerotherapy; group III (174/227 patients), timing of initial sclerotherapy and the optimum frequency of sclerotherapy sessions; group IV (80/99 patients), splenectomy devascularization operation alone versus combined surgery with sclerotherapy; group V (650/847 patients), management of failures of and recurrences after sclerotherapy. The mean period of follow-up was 72 months. Rigid sclerotherapy was significantly superior to flexible sclerotherapy for emergency control of acute bleeding but was associated with significantly more morbidity. Paravariceal injection achieved insignificantly better initial control of bleeding and had more morbidity than intravariceal injection, which obliterated the varices in a significantly larger proportion of patients. Emergency injection of the acute bleeder should be carried out soon after admission, with sclerotherapy sessions repeated every 2 weeks. Combined sclerotherapy with splenectomy and devascularization was significantly more effective for controlling bleeding than surgery alone. Surgery should be done without delay for continued bleeding after the second attempt of sclerotherapy and in patients who rebleed after their third sclerotherapy session. Survival, however, was not significantly improved by the different modalities of sclerotherapy.

Accelerated versus conventional fractionation in the postoperative irradiation of locally advanced head and neck cancer: influence of tumour proliferation.

Fifty-six patients with locally advanced head and neck squamous cell carcinoma were subjected to adjuvant radiotherapy after radical surgery with randomisation to either conventional fractionation (CF), comprising 50 Gy/25 F/5 weeks, or to accelerated hyperfractionation (AHF) to a dose of 42 Gy/30 F/11 days (3 F/day), a dose/F of 1.4 Gy and an interfraction interval of 4 h. The in vitro [3H]thymidine labelling index (TLI) was determined as an indicator of tumour proliferation. Early mucosal reactions were somewhat more severe after AHF than after CF and the peak was attained earlier. The actuarial 3-year complication rate was significantly lower in the AHF (64%) than in the CF group (87%). This is probably related to a smaller fraction size and a lower total dose. The overall 3-year disease-free survival amounted to 46 +/- 7%. Sex, the anatomical site, the nodal status, the performance status and TLI have been shown to be significant prognostic factors, but only the latter two proved to be independent covariates. Overall, the type of fractionation did not seem to influence survival. However, AHF seemed to offer higher survival probabilities in fast growing tumours and this attained a significant level for tumours with TLI > 10.4% (Tpot < 4.5 days). However, CF and AHF were associated with similar survival rates in slowly growing tumours. The relative effectiveness of the CF and AHF schedules is predictable on the basis of the linear-quadratic system. In the case of tumour response, a time factor has to be included assuming that accelerated repopulation of microscopic residues occurs from the outset.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological constriction of the lower oesophageal sphincter: a simple method of arresting variceal haemorrhage.

The effect of pharmacological constriction of the lower oesophageal sphincter (LOS) on oesophageal varices was investigated in an experimental study followed by a controlled clinical trial. In the experimental study intravariceal pressure was measured just above the LOS in 11 patients before and after constricting the LOS by intravenous pentagastrin. Intravariceal pressure fell from a mean of 23 (range 12-36) mmHg to 4 (range 0-7) mmHg (p less than 0.001). This marked pressure drop indicated the considerable compression of varices that occurred within the LOS. A prospective controlled clinical trial examined whether LOS constriction (effected by the longer acting metoclopramide) would compress varices sufficiently to arrest active variceal bleeding originating from the lowest 2 cm oesophagus--the area encircled by the LOS. Of 11 patients who received metoclopramide, 10 stopped bleeding compared with four of the 11 who received placebo (p less than 0.01). Pharmacological constriction of the LOS appears to offer a new and effective approach for arresting active bleeding from oesophageal varices.

Aetiology of recurrent aphthous ulcers (RAU).

A significant decrease in the pH of saliva has been detected in patients with recurrent aphthous ulcers (RAU). The decrease in pH was more prominent at night than between meals, and some persistent decrease was noticed even after recovery. The total proteins of saliva in RAU were also significantly decreased. These findings were similar to those observed in patients complaining of peptic ulcers, so it is recommended that patients with RAU should be treated with antacids as well as anticholinergic drugs, and that the possibility of concomitant peptic ulceration should also be investigated.