A SIMULTANEOUS ESTIMATION, VALIDATION AND FORCED DEGRADATION STUDIES OF 5-FLUOROURACIL AND TEGAFUR IN A PHARMACEUTICAL DOSAGE FORM USING REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD

Objective: The present study describes the stability indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous estimation of 5-fluorouracil and tegafur in pharmaceutical dosage forms.Method: 5-fluorouracil and tegafur the propose RP-HPLC method were developed by using Shimadzu Prominence-i LC-2030 HPLC system equipped with UV detector and chromatographic separation was carried on shim-pack gist c18 (250 × 4.6 mm, 5 μ) column at a flow rate of 1 ml/min and the run time was 10 min. The mobile phase consisted of methanol and water in the ratio of 50:50% v/v and elements were scanned using a UV detector at 271 nm.Result: The retention time of 5-fluorouracil and tegafur was found to be 2.74 and 3.66 min, respectively. A linearity response was observed in the concentration range of 13.4 μg/ml–31.3 μg/ml for 5-fluorouracil and 6 μg/ml–14 μg/ml for tegafur, respectively. Limit of detection and limit of quantification of 5-fluorouracil were 10.97 μg/ml and 33.26 μg/ml and for tegafur are 4.89 μg/ml and 14.83 μg/ml, respectively.Conclusion: The stability indicating that the method was developed by subjecting drugs to stress conditions such as acid and base hydrolysis, oxidation, photo and thermal degradation, and degraded products formed were resolved successfully from samples

Cryptography from Information Loss

© Marshall Ball, Elette Boyle, Akshay Degwekar, Apoorvaa Deshpande, Alon Rosen, Vinod. Reductions between problems, the mainstay of theoretical computer science, efficiently map an instance of one problem to an instance of another in such a way that solving the latter allows solving the former.1 The subject of this work is “lossy” reductions, where the reduction loses some information about the input instance. We show that such reductions, when they exist, have interesting and powerful consequences for lifting hardness into “useful” hardness, namely cryptography. Our first, conceptual, contribution is a definition of lossy reductions in the language of mutual information. Roughly speaking, our definition says that a reduction C is t-lossy if, for any distribution X over its inputs, the mutual information I(X; C(X)) ≤ t. Our treatment generalizes a variety of seemingly related but distinct notions such as worst-case to average-case reductions, randomized encodings (Ishai and Kushilevitz, FOCS 2000), homomorphic computations (Gentry, STOC 2009), and instance compression (Harnik and Naor, FOCS 2006). We then proceed to show several consequences of lossy reductions: 1. We say that a language L has an f-reduction to a language L0 for a Boolean function f if there is a (randomized) polynomial-time algorithm C that takes an m-tuple of strings X = (x1, . . ., xm), with each xi ∈ {0, 1}n, and outputs a string z such that with high probability, L0(z) = f(L(x1), L(x2), . . ., L(xm)) Suppose a language L has an f-reduction C to L0 that is t-lossy. Our first result is that one-way functions exist if L is worst-case hard and one of the following conditions holds: f is the OR function, t ≤ m/100, and L0 is the same as L f is the Majority function, and t ≤ m/100 f is the OR function, t ≤ O(m log n), and the reduction has no error This improves on the implications that follow from combining (Drucker, FOCS 2012) with (Ostrovsky and Wigderson, ISTCS 1993) that result in auxiliary-input one-way functions. 2. Our second result is about the stronger notion of t-compressing f-reductions – reductions that only output t bits. We show that if there is an average-case hard language L that has a t-compressing Majority reduction to some language for t = m/100, then there exist collision-resistant hash functions. This improves on the result of (Harnik and Naor, STOC 2006), whose starting point is a cryptographic primitive (namely, one-way functions) rather than average-case hardness, and whose assumption is a compressing OR-reduction of SAT (which is now known to be false unless the polynomial hierarchy collapses). Along the way, we define a non-standard one-sided notion of average-case hardness, which is the notion of hardness used in the second result above, that may be of independent interest

T-replete cord transplants give superior outcomes in high risk and relapsed/refractory paediatric myeloid malignancy

Stem cell transplant (SCT) outcomes in high-risk (HR) and relapsed/refractory (R/R) paediatric acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) have been poor historically. Cord blood allows T-cell replete transplant (TRCB), enabling enhanced graft-versus-leukaemia. We collected data from 367 consecutive patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for paediatric AML/MDS in the UK and Ireland between January 2014 and December 2021. Data was collected about patient's demographics, disease and its treatment including previous transplant, measurable residual disease (MRD) status at transplant, HLA-match, relapse, death, graft versus host disease (GvHD) and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6% and 5.1% respectively in the comparator group (all p <0.001). Within the TRCB cohort, Event Free Survival (EFS) was 64.1%, 50% in MRD positive patients and 79% in MRD negative (p= 0.009). To allow for the imbalance in baseline characteristics, a multivariable analysis was performed: the TRCB cohort had significantly improved EFS (0.57[0.35-0.91], p=0.019), time to relapse (0.46[0.26-0.81), p=0.008), and reduced chronic GVHD (HR 0.28 [95% CI 0.11-0.70]; p=0.007), with some evidence of improved Overall Survival (OS) (0.65[0.39-1.07], p = 0.088). The effect appeared similar regardless of MRD status, (interaction p-value= 0.29). CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy

Unsteady Dynamics of Shock-Wave Boundary-Layer Interactions

Shock-wave/turbulent boundary-layer interactions (SWTBLIs) are characterized by lowfrequency unsteadiness, amplified aerothermal loads, and a complex three-dimensional flowfield. Presence of a broad range of length and time-scales associated with compressible turbulence generates additional gasdynamic features that interact with different parts of the flowfield via feedback mechanisms. Determining the physics of such flows is of practical importance as they occur frequently in different components of a supersonic/hypersonic aircraft such as inlets operating in both on- and off-design conditions, exhaust nozzles, and control surfaces. SWTBLIs can cause massive flow separation which may trigger unstart by choking the flow in an inlet. On control surfaces, fatigue loading caused by low-frequency shock unsteadiness, coupled with high skin-friction and heat transfer at the surface, can result in failure of the structure. The objective of this study is twofold. The first aspect involves examining the causes of unsteadiness in SWTBLIs associated with two geometries – a backward facing step flow reattaching on to a ramp, and a highly confined duct flow. Signal processing and statistical techniques are performed on the results obtained from Delayed Detached-Eddy Simulations (DDES) and Implicit Large-Eddy Simulations (ILES). Dynamic Mode Decomposition (DMD) is used as a complement to this analysis, by obtaining a low-dimensional approximation of the flowfield and associating a discrete frequency value to individual modes. In case of the backward facing step, Fourier analysis of wall-pressure data brought out several energy dominant frequency bands such as separation bubble breathing, oscillations of the reattachment shock, shear-layer flapping, and shedding of vortices from the recirculation zone. The spectra of reattachment shock motion suggested a broadband nature of the oscillations, wherein separation bubble breathing affected the low-frequency motion and shear-layer flapping, and vortex shedding correlated well at higher frequencies. A similar exercise was carried out on the highly confined duct flow which featured separation on the floor and sidewalls. In addition to the low-frequency shock motions, the entire interaction exhibited a cohesive back-and-forth in the streamwise direction as well as a left-right motion along the span. Mode reconstruction using DMD was used in this case to recover complex secondary flows induced by the presence of sidewalls. For the final aspect of this study, a flow-control actuator was computationally modeled as a sinusoidally varying body-force function. Effects of high-frequency forcing at F+= 1.6 on the flowfield corresponding to a backward facing step flow reattaching on to a ramp were examined. Conditionally averaged profile of streamwise velocity fluctuations, based on reattachment shock position, was used for the formulation of spatial distribution of the actuator. The forcing did not change the mean and RMS profiles significantly, but affected the unsteadiness of the interaction significantly. The effects of forcing were localized to the recirculation zone and did not affect the evolution of the shear-layer. The acoustic disturbances propagating through the freestream and recirculation zone drove the motion of the reattachment shock, and did not alter the low-frequency dynamics of the interaction

Supersonic Flow Control of Swept Shock Wave/Turbulent Boundary Layer Interaction Using Plasma Actuators

The effect of plasma actuators on the physics of the swept shock-wave/boundary-layer interaction induced by a sharp fin is investigated in this study by means of Reynolds-averaged Navier-Stokes calculations, using the SU2 code developed at Stanford University. The present work focuses on a sharp-fin configuration placed in a Mach 5 flow, with a spatially developing turbulent boundary layer, at an angle of attack of 12 deg. At the streamwise location of the fin leading edge, the Reynolds numbers based on momentum thickness and boundary layer thickness for the undisturbed boundary layer case are around 5075 and 3.321 mm, respectively. The mean pressure distribution and heat transfer data at the wall for the case without any actuators were compared to experimental data. The plasma actuator is modeled semi-empirically as a heating source and magnetic bodyforce term, which is included in the energy and momentum equations respectively. The plasma actuator is placed within the boundary layer at a certain distance upstream of the mean separation line. A horse-shoe vortex is created as the streamlines encounter the disturbance, which decays some distance downstream. The heat addition due to actuator acts as a virtual fillet, which slows the compression and makes separation more gradual. The resulting time-averaged flow fields showed decreased intensity of the reflected shock wave, reduction in peak skin friction coefficient, and increase in the separation bubble length with plasma actuator control.

Applications of Atomic Force Microscopy in HIV-1 Research

Obtaining an understanding of the mechanism underlying the interrelations between the structure and function of HIV-1 is of pivotal importance. In previous decades, this mechanism was addressed extensively in a variety of studies using conventional approaches. More recently, atomic force microscopy, which is a relatively new technique with unique capabilities, has been utilized to study HIV-1 biology. Atomic force microscopy can generate high-resolution images at the nanometer-scale and analyze the mechanical properties of individual HIV-1 virions, virus components (e.g., capsids), and infected live cells under near-physiological environments. This review describes the working principles and various imaging and analysis modes of atomic force microscopy, and elaborates on its distinctive contributions to HIV-1 research in areas such as mechanobiology and the physics of infection

Free anteromedial thigh perforator flap: Complementing and completing the anterolateral thigh flap

Objective: Theobjective of this study was to determine the indications, utility, advantages and surgical approach for the anteromedial thigh (AMT) flap. Materials and Methods: We reviewed the records of the patients in whom the AMT flap was used for head and neck reconstruction. We use an anterior approach to harvest the anterolateral thigh (ALT) flap with a non-committal straight line incision. This preserves both ALT and AMT flap territories intact, and further decision is based on the intraoperative anatomy of perforator and pedicle. The ALT flap was usually used as the first choice when available and suitable. Results: Free AMT skin flaps were harvested in 24 patients. All flaps were used for the head and neck reconstruction. Two flaps had marginal flap necrosis. One flap was lost due to venous thrombosis. Discussion: The thigh is an excellent donor site as it has large available skin territory, expendable lateral circumflex femoral artery system and low donorsite morbidity. The ALT flap is the most commonly used flap for reconstruction of soft-tissue defects. However, it is characterised by variable vascular pedicle and perforator anatomy. The AMT flap is an excellent alternative when the ALT flap is not available due to variable perforator anatomy, injury to perforator, when an intermediate thickness is needed between distal and proximal thigh or a chimeric flap is needed. Conclusion: The AMT flap offers all the advantages of the ALT flap without increasing donor-site morbidity. The anterior non-committal approach keeps both the ALT and the AMT flap options viable

DUODENAL WEBS: AN EXPERIENCE WITH 18 PATIENTS

Aim: To describe the management and outcome of patients with duodenal webs, managed over a period of 12 ½ years in our unit.Methods: It is a retrospective case series of 18 patients with congenital duodenal webs, managed in our unit, between 1999 and 2011. The medical record of these patients was retrieved and analyzed for demographic details, clinical presentation, associated anomalies, and outcome. Results: The median age of presentation was 8 days (range 1 day to 1.5 years). Antenatal diagnosis was made in only 2 (11.1%) patients. The commonest presentation was bilious vomiting. Associated anomalies were present in 8/18 patients, common being malrotation of gut. Down’s syndrome was seen in 2 patients and congenital heart disease in 1 patient. One patient had double duodenal webs. There was a delay in presentation of more than 5 days of life in 11/18 (61%) patients. Three patients who presented beyond neonatal age group had fenestrated duodenal membranes causing partial obstruction. In addition, the diagnosis was missed in patients operated for malrotation elsewhere (n=2), imperforate anus (n=2) and esophageal atresia with tracheo-esophageal fistula (n=1). A lateral duodenotomy with excision of the obstructive membrane was done in all patients. A trans-anastomotic tube (TAT) for enteral feeding was used in 8 patients The mortality rate was 4/18 (22%); the main causes being sepsis, prematurity, very low birth weight and associated congenital anomalies. The mean hospital stay for the 14 survivors was 18 days. Total parental nutrition (TPN) was not given to any patient.Conclusions: Congenital duodenal webs are different as the diagnosis is often missed especially in case of perforated webs. Outcome depends upon the time of presentation and associated anomalies. The use of TAT feeding for nutritional support is an easy alternative to TPN