The last new plug-in is Video Player. Image Line have been behind the times when it comes to video support, but they had their reasons: they are a small company and were concerned about keeping up with the proliferation of video codecs. So Video Player opens, plays and syncs to video, but doesn't render video. You can score against the video, but you'll have to render audio-only and use another program to put the two together as a single file. Video Player successfully opened both DV AVI and DVD file formats from my hard drive, so the likeliest suspects are covered. It is an optional plug-in, so if you need it you'll have to fork over more cash, but it only costs $35, so it won't break the bank if it is a must-have.
ImageLine FL Studio v5.0.0 XXL Producer Edition [Full version]FL Studio is the most complete virtual studio currently available. You will be creating wav, mp3 or midi songs or loops only minutes after launching it.FEATURES:* Internal 32 bit floating point mixing, up to 96kHz stereo.* Supports DirectSound and ASIO enabled sound cards for audio output.* Ability to function as a VSTi, DXi and a ReWire client.* Ability to host ReWire clients itself.* Realtime linear interpolation & sophisticated interpolation algorithms at rendering time.* Open architecture allowing third-party instruments (enhanced proprietary FL instruments standard, VSTi and DXi2) and effects (enhanced proprietary FL effects standard, VST, VST2 and DirectX).* A full set of high-precision mastering and special effects filters: reverb, compressor, procedural equalizer, distortion, phaser, flanger, bass boost, delay line and other.* Advanced sequencing methods allowing quick entering of realistic drum loops (step sequencing grid) and composing complex instrumentals (advanced piano roll, arpeggiator, keyboard tracking, real-time gate).* Unique note properties morphing ability (pitch, cutoff, resonance, panning).* Advanced mixer: 68 mixer tracks (64 insert and 4 send tracks) supporting up to 8 filters each; mixer tracks rerouting for creating of complex mixer chains; track recording with ASIO input support (for recording MIDI, vocals etc.); integrated procedural equalizer, volume and panning for each mixer track.* Integrated instruments: Sampler, TS404 (the popular bassline engine), 3xOSC (subsynth), Plucked! (plucked strings), MIDI Out, DX10 (FM synth), Scratcher (turntable emulator), WaveTraveller (wave bend synth), Wasp (demo), SimSynth Live (demo), and more.* Advanced playlist & full-featured audio tracks.* Live recording of control movements & integrated automation events editor.* Easy MIDI remote controlling of most parameters (VST plugins supported as well).* Procedural control over parameters by using special controller plugins.* Click removal & volume ramping to avoid pops.* Imports *.WAV, *.SYN (SimSynth 1 & 2), *.DS (DrumSynth) files, with effects applied.* Imports MIDI sequences and controller events.* Exports audio to 16Bit or 32Bit *.WAV file, *.MP3.* Can export MIDI notes & controller events to a standard MIDI file.
While being easy of access it's an 'all-in-one' audio environment that features multi-track-recording and arrangement, a variable pattern-length step-sequencer with an advanced song arrangement play-list, complete automation tracks, a 64+ track mixer with FX inserts, full VST plug-in support for generators and effects, great in-the-box synthesizers and effect plug-ins, like Poizone or Sytrus or the large and complete FX & sample bank provided. You can record wave from your audio interface or catch MIDI signals right from your favorite controllers and assign them to the VSTs controls. You can easily patch mixer tracks with each other, and almost everything is template-ed/preset-able. The default sampler & synthesizer plug-ins all provide arpegiator and glide functions, a cool delay and granularizer. Advanced audio features may be time-stretching (also known as warping) & beat slicing of samples, BPM detection for samples and so on. I don't really know what it is missing of 'bare features'. One thing that makes it different is just how the interface is. Needed to be acquired like any other, most intuitive, easy, fast and enjoyable once in it. Oh yeah, and the coolest & neatest interface on earth an audio software has is fully skin-able.
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Since most PPIs lack endogenous small molecule ligands, it is challenging to rationally design the associate PPI modulators. However, the hot-spots provide important structural information and a basis for the rational design of PPI modulators. At present, there are two design strategies for structure-based design PPI modulators. The first is based on the hot-spots structure. Through bioisosterism and de novo design, the novel small molecule modulators can be obtained.44 For example, during the development of VHL/HIF1α PPI inhibitors, Hyp564 was identified as a crucial amino acid. Through the de novo design targeting the Hyp546, the inhibitors were obtained.45,46 The second is peptidomimetic design which mainly rely on computer modeling and phage display to simulate the secondary structure of the key peptides in PPIs. Furthermore, small molecules were designed or binding peptides were synthesized based on the stable α-helix structure formed by the key peptides.47 The α-helix is the most common identified secondary structure in PPIs.48 At present, many PPI modulators have been successfully developed based on the α-helix structure, including c-Myc/Max,49 Bcl-2/Bax,50 and MDM2/p53.51
The virtual screening is based on professional application software to screen out hits from compound libraries. One big challenge in developing PPI modulators is to identify the disease-related and druggable PPIs among thousand of available ones. The virtual screening may be useful to locate the binding sites by analyzing the protein surface. It can be classified into both a structure-based approach and a ligand-based approach. The ligand-based approach aims to screen compounds that satisfy the built pharmacophore model. In contrast, the structure-based approach relies on the structural information of the target protein. The virtual screening was successfully applied in the development of PPI modulators including Ubc13/Uevl,52 MDM2/p53,53 and TCF/β-catenin.54
Up to date, the PPI modulators can be classified into three categories (Table 2). The first category is the small molecule modulators. Compare to the classic drug targets like enzymes or ion channels, the PPI interface is large, flat, and lacks a suitable size pocket which the small molecules can bind with. What is more, the PPI interface is usually hydrophobic. Therefore, a potent PPI modulator should cover a large surface area and make a large number of hydrophobic contacts. Such a modulator may face pharmacokinetic issues due to its large molecular weight and poor solubility.8 Therefore, the small molecule modulator is more suitable for the tight and narrow PPI interface.44 The second category is an antibody. When targeting a large PPI interface, an alternative other than small molecular compounds is needed to cover the large interface. Although monoclonal antibodies compete with PPIs, because of their large molecular weight, the application of monoclonal antibodies is limited to the extracellular targets. Up to date, the monoclonal antibodies have been successfully used in clinical treatment although they may trigger adverse reactions associated with the immune reactions. The third category is peptides. The peptides are designed based on the structure information of the hot-spots.64 The designed peptides retain the key roles when they bind to proteins, thereby forming a strong affinity with the proteins. Compared with small-molecule PPI modulators and monoclonal antibodies, the molecular weight of peptide is between the two. It has higher target specificity and affinity and is a potential PPI modulator. However, the peptide is susceptible to hydrolysis by various hydrolases in the body, which makes its half-life short.
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