Half Life 2 Mobile

I was wondering if people had tried to port Half Life 1 to mobile phones, since phones now are generally much better and stronger and since Half Life 1 is an old game, I wonder if it is possible to port into mobile?

Background: Adapter chimeric antigen receptor (CAR) approaches have emerged has promising strategies to increase clinical safety of CAR T-cell therapy. In the UniCAR system, the safety switch is controlled via a target module (TM) which is characterized by a small-size and short half-life. The rapid clearance of these TMs from the blood allows a quick steering and self-limiting safety switch of UniCAR T-cells by TM dosing. This is mainly important during onset of therapy when tumor burden and the risk for severe side effects are high. For long-term UniCAR therapy, the continuous infusion of TMs may not be an optimal setting for the patients. Thus, in later stages of treatment, single infusions of TMs with an increased half-life might play an important role in long-term surveillance and eradication of residual tumor cells. Given this, we aimed to develop and characterize a novel TM with extended half-life targeting the tumor-associated carbohydrate sialyl-Tn (STn).

Half Life 2 Mobile

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Methods: The extended half-life TM is composed of the STn-specific single-chain variable fragment (scFv) and the UniCAR epitope, fused to the hinge region and Fc domain of a human immunoglobulin 4 (IgG4) antibody. Specific binding and functionality of the STn-IgG4 TM as well as pharmacokinetic features were assessed using in vitro and in vivo assays and compared to the already established small-sized STn TM.

Results: The novel STn-IgG4 TM efficiently activates and redirects UniCAR T-cells to STn-expressing tumors in a target-specific and TM-dependent manner, thereby promoting the secretion of proinflammatory cytokines and tumor cell lysis in vitro and in experimental mice. Moreover, PET-imaging results demonstrate the specific enrichment of the STn-IgG4 TM at the tumor site, while presenting a prolonged serum half-life compared to the short-lived STn TM.

Small therapeutic proteins are receiving increased interest as therapeutic drugs; however, their clinical success has been limited due to their rapid elimination. Here, we report a half-life extension strategy via strategy via red blood cell red blood cell (RBC) hitch-hiking. This manuscript details the development and characterization of novel anti-RBC single-domain antibodies (sdAbs), their genetic fusion to therapeutic antibody fragments (TAF) as bispecific fusion constructs, and their influence on TAF pharmacokinetics and biodistribution. Several sdAbs specific to the band 3 antigen were generated via phage-display technology. Binding affinity to RBCs was assessed via flow cytometry. Affinity maturation via random mutagenesis was carried out to improve the binding affinity of the sdAbs. Bi-specific constructs were generated by fusing the anti-RBC sdAbs with anti-tissue necrosis factor alpha (TNF-) TAF via the use of a glycine-serine flexible linker, and assessments for binding were performed via enzyme-linked immunosorbent assay and flow cytometry. Pharmacokinetics of anti-RBC sdAbs and fusion constructs were evaluated following intravenous bolus dosing in mice at a 1 mg/kg dose. Two RBC-binding sdAbs, RB12 and RE8, were developed. These two clones showed high binding affinity to human RBC with an estimated KD of 17.7 nM and 23.6 nM and low binding affinity to mouse RBC with an estimated KD of 335 nM and 528 nM for RB12 and RE8, respectively. Two derivative sdAbs, RMA1, and RMC1, with higher affinities against mouse RBC, were generated via affinity maturation (KD of 66.9 nM and 30.3 nM, respectively). Pharmacokinetic investigations in mice demonstrated prolonged circulation half-life of an anti-RBC-TNF- bispecific construct (75 h) compared to a non-RBC binding control (1.3 h). In summary, the developed anti-RBC sdAbs and fusion constructs have demonstrated high affinity in vitro, and sufficient half-life extension in vivo.

Fc-less bispecific T-cell engagers have reached the immuno-oncology market but necessitate continual infusion due to rapid clearance from the circulation. This work introduces a programmable serum half-life extension platform based on fusion of human albumin sequences engineered with either null (NB), wild type (WT) or high binding (HB) FcRn affinity combined with a bispecific T-cell engager. We demonstrate in a humanised FcRn/albumin double transgenic mouse model (AlbuMus) the ability to tune half-life based on the albumin sequence fused with a BiTE-like bispecific (anti-EGFR nanobody x anti-CD3 scFv) light T-cell engager (LiTE) construct [(t 0.6 h (Fc-less LiTE), t 19 hours (Albu-LiTE-NB), t 26 hours (Albu-LiTE-WT), t 37 hours (Albu-LiTE-HB)]. We show in vitro cognate target engagement, T-cell activation and discrimination in cellular cytotoxicity dependent on EGFR expression levels. Furthermore, greater growth inhibition of EGFR-positive BRAF mutated tumours was measured following a single dose of Albu-LiTE-HB construct compared to the Fc-less LiTE format and a full-length anti-EGFR monoclonal antibody in a new AlbuMus RAG1 knockout model introduced in this work. Programmable half-life extension facilitated by this albumin platform potentially offers long-lasting effects, better patient compliance and a method to tailor pharmacokinetics to maximise therapeutic efficacy and safety of immuno-oncology targeted biologics.

Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast, mouse, and human proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives than proteins without these features. The lengths of the disordered segments that affect protein half-life are compatible with the structure of the proteasome. Divergence in terminal and internal disordered segments in yeast proteins originating from gene duplication leads to significantly altered half-life. Many paralogs that are affected by such changes participate in signaling, where altered protein half-life will directly impact cellular processes and function. Thus, natural variation in the length and position of disordered segments may affect protein half-life and could serve as an underappreciated source of genetic variation with important phenotypic consequences.

Developers devote a lot of attention to the time immediately after an app is launched. How quickly is it growing? Will it go viral? How is it ranking in app stores? While that launch period is critical, managing apps well throughout their entire lifecycle means also paying special attention to what happens after an app peaks. Does it decline precipitously or manage to hold much of its audience for a long time?

We start by looking at the overall rate of decay for 26,176 apps that peaked in the first half of 2011, 2012, and 2013. (That allows enough time for decay even for apps peaking in 2013 and also controls for the time of year in which the app peaked.) The chart below shows what proportion of apps were at what percentage of their peak MAU in each of the first ten months after they peaked. Apps in the gray band fell below 25% of their peak MAU by the month indicated, apps in the orange band had fallen below 50% but were still above 25%, apps in the green band were below 75% but above 50%, and apps in the blue band were above 75% of their peak MAU in the month shown in the horizontal axis.

As shown in the chart, decay is fairly rapid in the first few months post peak. A quarter of apps fall below half of their peak MAU the month after peaking (see the top of the orange band in the chart). That percentage grows to 43% in the second month post peak. In the third month post peak, just over half (52%) of apps fall below half of their peak MAU. The fourth month post peak is a critical benchmark: From this point on, MAU decay continues, but at a much slower rate (note the flattening of the color bands after the 4th month).

The overall pattern of app user decay has been remarkably stable over the past three years, but there is variation based on app category, size, and operating system. The table below shows median app half-life for apps within each grouping. This corresponds to the month in which the top of the orange band and the bottom of the green band intersect at the 50% line in the previous chart.

Those first few months post peak are key since the rate of decay levels off after about four months. More than half (56%) of apps that manage to hold more than half of their peak users for the first four months after they peak are still holding on to more than half of them ten months post peak. That could have a sizeable revenue impact. For example, consider an app that peaks at 100,000 monthly average users and has average revenue per user per month of $2.50. Holding at least half of those users through month four means the app has a 56% chance of holding them for another six months and that translates into revenue of $750,000 (100,000 users* half of them remaining *$2.50 per user per month * 6 months).

Just as actuarial tables help insurance companies anticipate costs, understanding typical app decay patterns can help developers and those who fund them anticipate app revenue streams. For example, assuming similar development costs and average revenue per user per month, a game app would need to peak with many more active users than a news app to have the same profit potential since its life can be expected to be a lot shorter. And it pays to invest in growing MAU for any app to the highest peak possible since that is also likely to mean the app will enjoy a longer half-life.

Welcome to Half-Life Mobile, a recreation of Valve's huge hit game Half-Life from 1998 for your mobile devices! Half-Life, Named Game of the Year by over 50 publications, Valve's debut title blends action and adventure with award-winning technology to create a frighteningly realistic world where players must think to survive. Game pads and bluetooth controllers supported. Game is currently in Beta form, may not represent final release. ff782bc1db