Advance Pricing Agreements in India: A Revolution in Taxation Law

Double taxation is one of the biggest challenges faced by multinational corporations, especially when the taxable transaction is between associated enterprises. The determination of transfer pricing becomes a bone of contention among the revenue authorities of different countries. One mechanism to counter this problem is to take recourse to „Advance Pricing Agreement‟ (APA). An APA is an arrangement entered into between revenue authority(s) and the taxpayer to determine the transfer pricing in advance. It has a plethora of advantages and procedural benefits over the conventional methods of determination of transfer pricing. APA, which was in existence in many countries for many years, was recently introduced in India. The aim of this paper is primarily to explore the Indian law on APA in the light of the situation prevalent in other countries, and to suggest measures to improve the same. This aim shall be achieved by firstly studying the concepts pertaining to transfer pricing and the problems associated with it, which has led to the emergence of APA. Thereafter, an overview of the Indian APA regime is provided. Further, in order to evaluate the merits and demerits of Indian APA, a comparative study with the law on APA in other countries has been presented, while simultaneously making certain suggestions to make the Indian APA system robust. In the last part of the paper, some suggestions apart from those which were made after analyzing the comparative law have been made. If India improves upon its APA regime by taking a cue from other countries, and by implementing measures such as the creation of safe harbours, better dispute settlement mechanism, easier documentation etc., then the APA will surely bring the much desired revolution in the taxation of multinational corporations

A Correlation of Tumor Budding and Tumor Stroma Ratio with Clinicopathological Factors in Oral Squamous Cell Carcinoma

Background: Squamous cell carcinoma is the most common carcinoma in the head and neck region. Both tumor budding and tumor stroma ratio are being studied in the recent years in various solid tumors for their role as a prognostic marker, however the studies in oral squamous cell carcinoma are limited. Methods: A total of 50 patients of oral squamous cell carcinoma proved histologically were included in the study over a period of 4 months (July 2022-October 2022). Tumor budding(TB) and Tumor stroma ratio (TSR) were evaluated on routine hematoxylin and eosin stained sections and these were correlated with clinicopathological parameters. Statistical analysis was done using Chi-square test and p value <.05 considered significant. Result: The mean age was 52.72 +_ 13.16 and M: F of 7.1:1. Most of the tumors were located on tongue (46%) followed by buccal mucosa (26%), gingivobuccal sulcus (12%) and retromolar trigone (8%). Palate and alveolus were the other sites involved constituting 4% each. Both TB and TSR were found to be significantly associated with grade of the tuumor, lymph node metastasis and size of the tumor. A highly significant correlation was also found between Tb and TSR with a p value <.001. Conclusion: Both TB and TSR can be easily evaluated on routine H&E sections and are highly reproducible and found to be reliable independent prognostic markers in OSCC. Thus, this simple and cost-effective method of prognostification which is currently lacking will help in identifying patients with poor prognosis and thus, individualise the treatment plan. Keywords: Tumor Budding, Oral squamous cell carcinoma, Tumor stroma ratio

Portunus: Re-imagining access control in distributed systems

TLS termination, which is essential to network and security infrastructure providers, is an extremely latency sensitive operation that benefits from access to sensitive key material close to the edge. However, increasing regulatory concerns prompt customers to demand sophisticated controls on where their keys may be accessed. While traditional access-control solutions rely on a highly available centralized process to enforce access, the round-trip latency and decreased fault tolerance make this approach unappealing. Furthermore, the desired level of customer control is at odds with customizing the distribution process for each key. To solve this dilemma, we have designed and implemented Portunus, a cryptographic storage and access control system built using a variant of public-key cryptography called attribute-based encryption (ABE). Using Portunus, TLS keys are protected using ABE under a policy chosen by the customer. Each server is issued unique ABE keys based on its attributes, allowing it to decrypt only the TLS keys for which it satisfies the policy. Thus, the encrypted keys can be stored at the edge, with access control enforced passively through ABE. If a server receives a TLS connection but is not authorized to decrypt the necessary TLS key, the request is forwarded directly to the nearest authorized server, further avoiding the need for a centralized coordinator. In comparison, a trivial instantiation of this system using standard public-key cryptography might wrap each TLS key with the key of every authorized data center. This strategy, however, multiplies the storage overhead by the number of data centers. We have deployed Portunus on Cloudflare\u27s global network of over 400 data centers. Our measurements indicate that we can handle millions of requests per second globally, making it one of the largest deployments of ABE

Experiences of frontline workers in Rajasthan and Himachal Pradesh during the Covid-19 pandemic

In the advent of COVID-19, frontline workers (FLWs) such as Accredited Social Health Activists (ASHAs), Auxiliary Nurse Midwives (ANMs) and Anganwadi Workers (AWWs) found themselves at the forefront of combating the pandemic. In addition to regular healthcare and nutrition delivery, their revised responsibilities included screening for COVID-19, contact tracing, communication of preventative measures, adapting nutrition-related programmes, and doorstep delivery of maternal and child health services. In this report, the Accountability Initiative (AI) at the Centre for Policy Research (CPR) highlights the oft-overlooked stories of government functionaries at the frontline of COVID-19 response since the advent of the initial lockdown. The overall objectives covered in this report are: 1. Understanding the evolving role of FLW workers during the pandemic and the impact of COVID work on their regular duties. 2. Gaining insight into the processes and best practices for training, implementation and supportive supervision

Characterization of Proteins Involved in Membrane Fusion- Atlastin and Munc18c

Membranes provide a barrier to cells and organelles, and allow the selective transport of molecules between compartments. Membrane fusion is essential for organelle biogenesis as well as trafficking of molecules between cellular compartments. Membrane fusion is also required for the formation of the branched network of tubules that make up the Endoplasmic Reticulum (ER). One protein implicated in ER fusion is Atlastin, a dynamin like GTPase. Mutations in Atlastin-1, among others, cause Hereditary Spastic Paraplegias (HSP), a group of neurological disorders that cause progressive weakness of lower extremities. We have shown that the C-terminal tail of atlastin is necessary for membrane fusion. The requirement of the C-terminal tail can be partially abrogated in an unstable lipid environment. This implies that the C-terminal tail of Atlastin plays a role in perturbing the lipid bilayer to allow membrane fusion. Understanding the molecular details of how Atlastin drives membrane fusion may help elucidate the pathogenesis of HSP. Intracellular fusion at the plasma membrane is SNARE mediated and regulated by Sec1p/Munc18 (SM) proteins. Increased rate of glucose transport into fat and muscles cells by translocation of glucose transporter GLUT4 in response to insulin is a SNARE regulated fusion process. Recent reports have linked Munc18c and Syntaxin4 with obesity and Type 2 diabetes. We characterized the function of Munc18c, an SM protein, in regulating GLUT-4 containing vesicle fusion with the plasma membrane. We have shown that Munc18c directly inhibits membrane fusion by interacting with its cognate SNARE complexes. Characterization of membrane fusion in a minimal system as the in vitro liposome fusion assay offers a powerful tool with which to finely dissect the mechanistic basis of SM protein function

A detailed analysis on spam emails and detection using Machine Learning algorithms

Spam Email is the unwanted junk and solicited email sent in bulk to the receivers, using botnets, spambots, or a network of infected computers. These spam emails can be phishing emails that trick users to get their sensitive information, download malware into the user devices or scam the users stealing confidential data. This paper shows a systematic analysis of spam and its types. It also details the procedure of how the spammers get the email addresses of the receivers. It analyses the problems with spamming. A detailed state of the art on spam filters and the factors that put an email into the spam or ham category is also explained. The paper also discusses spam filtering methods of Gmail, Yahoo, and Outlook. Finally, it brings out several solutions to detect spam using principles of Machine Learning and Data Minin

Munc18c inhibits Syntaxin 4/SNAP-23/VAMP2-mediated bilayer fusion <i>in vitro</i>.

<p><i>(A,B) VAMP2 and syntaxin 4/SNAP23 form a functional complex capable of fusing liposomes.</i> (A) Coomassie blue stained gels of the recombinant proteins used in this study. Shown are samples of the t- and v- proteoliposomes used for fusion assay (10 µl each), the cytoplasmic domain of VAMP2 (VAMP2-cyto, 5 µg) and 5 µg of purified Munc18c were separated by SDS-PAGE and stained with Coomassie Blue. (B) Fluorescently labelled donor VAMP2 liposomes, 5 µl, were pre-incubated at 4°C overnight with 45 µl of unlabelled acceptor syntaxin 4/SNAP23 liposomes (with the addition of 2 µl of A200 to correct for volume) and fusion between the two vesicle populations monitored by measuring NBD fluorescence at 520 nm every 2 min (filled circles). As a control fluorescence was monitored with the addition of 2 µl of VAMP2-cyto (open circles). The fluorescence was converted into rounds of fusion as outlined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004074#pone.0004074-Scott1" target="_blank">[16]</a>. Data shown is representative of over 6 experiments of this type. <i>(C) Munc18c added to v-SNARE and t-SNARE vesicles inhibits fusion in a dose dependant manner</i>. Munc18c, dialysed against glycerol free A200 buffer, was added directly to the fusion assay set up as outlined in panel A and the mixture incubated at 4°C overnight. Fusion between the two vesicle populations in the absence (filled circles) and presence of Munc18c at two different ratios to syntaxin4/SNAP23 (2∶1, filled triangles, 10∶1, filled squares) was monitored by measuring NBD fluorescence at 520 nm every 2 min. As a control, fluorescence was monitored in each population in the presence of 2 µl of VAMP2-cyto (open circles, open triangles and open squares respectively). The fluorescence was converted into rounds of fusion as outlined <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004074#pone.0004074-Scott1" target="_blank">[16]</a>. The experiment shown was repeated four times with quantitatively similar results. <i>(D) Munc18a does not inhibit fusion</i>. Unlabeled acceptor liposomes containing the syntaxin4/SNAP23 t-SNARE complex (20 µl) were mixed with labelled VAMP2 liposomes (2.8 µl) in a total reaction volume of 70 µl with or without Munc18a or Munc18c. The final concentration of t-SNAREs in the reaction was 3.7 µM protein and 1.6 µM VAMP2. Munc18a or Munc18c were added at 10 µM. SNARE liposome were preincubated with SM proteins for 3 h at 4°C prior to fusion at 37°C and fusion assayed as in <i>B</i>. <i>(E) Munc18c pre-incubated with t-SNAREs prior to reconstitution inhibits fusion facilitated by VAMP2 and syntaxin 4/SNAP23</i>. Equimolar amounts of Munc18c, dialysed against A200 buffer, and t-SNARE complex were mixed overnight at 4°C. As a control the same amount of t-SNARE was mixed overnight at 4°C with A200 buffer alone. OG was added to maintain the concentration at 1%. Reconstitution was then carried out as described and aliquots (10 µl) of t-SNARE vesicles analyzed by SDS-PAGE and Coomassie staining (left panel) the left hand panel. Fusion was monitored between vesicles containing t-SNAREs alone (filled circles) and t-SNAREs premixed with Munc18c (filled triangles) with v-SNARE vesicles. Data from a representative experiment is shown (right hand panel), repeated three times with quantitatively similar data. As a control, fusion was also monitored between vesicles containing t-SNAREs alone and v-SNARE vesicles in the presence of excess VAMP2-cyto (open squares). N.B. Lower quantities of input SNAREs were employed due to dilution of t-SNAREs with Munc18c during the reconstitution, hence the fusion rates in this experiment are lower than those in B and C. Note that the addition of Munc18c reduced fusion by the same amount as VAMP2-cyto in these experiments.</p